bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the profiles of CB1 cannabinoid receptor signalling bias using joint kinetic modelling
Authors: Zhu Xiao , Finlay David B. , Glass Michelle , Duffull Stephen B.
Published: April 2020

Background and Purpose

Biased agonism describes the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor. Signalling is affected by rapid agonist‐induced receptor internalisation. Hence, the conventional use of equilibrium models may not be optimal, because (i) receptor numbers vary with time and, in addition, (ii) some pathways may show non‐monotonic profiles over time.

Experimental Approach

Data were available from internalisation, cAMP inhibition and phosphorylation of ERK (pERK) of the cannabinoid‐1 (CB1) receptor using a concentration series of six CB1 ligands (CP55,940, WIN55,212‐2, anandamide, 2‐arachidonylglycerol, Δ9‐tetrahydrocannabinol and BAY59,3074). The joint kinetic model of CB1 signalling was developed to simultaneously describe the time‐dependent activities in three signalling pathways. Based on the insights from the kinetic model, fingerprint profiles of CB1 ligand bias were constructed and visualised.

Key Results

A joint kinetic model was able to capture the signalling profiles across all pathways for the CB1 receptor simultaneously for a system that was not at equilibrium. WIN55,212‐2 had a similar pattern as 2‐arachidonylglycerol (reference). The other agonists displayed bias towards internalisation compared to cAMP inhibition. However, only Δ9‐tetrahydrocannabinol and BAY59,3074 demonstrated bias in the pERK–cAMP pathway comparison. Furthermore, all the agonists exhibited little preference between internalisation and pERK.

Conclusion and Implications

This is the first joint kinetic assessment of biased agonism at a GPCR (e.g. CB1 receptor) under non‐equilibrium conditions. Kinetic modelling is a natural method to handle time‐varying data when traditional equilibria are not present and enables quantification of ligand bias.
Key role of macrophages in tolerance induction via T regulatory type 1 (Tr1) cells
Authors: Mfarrej B , Jofra T , Morsiani C , Gagliani N , Fousteri G , Battaglia M
Published: April 2020

T regulatory type 1 (Tr1) cells are a class of regulatory T cells (Tregs) participating in peripheral tolerance, hence the rationale behind their testing in clinical trials in different disease settings. One of their applications is tolerance induction to allogeneic islets for long-term diabetes-free survival. Currently the cellular and molecular mechanisms that promote Tr1-cell induction in vivo remain poorly understood. We employed a mouse model of transplant tolerance where treatment with granulocyte colony-stimulating factor (G-CSF)/rapamycin induces permanent engraftment of allogeneic pancreatic islets in C57BL/6 mice via Tr1 cells. The innate composition of graft and spleen cells in tolerant mice was analyzed by flow cytometry. Graft phagocytic cells were co-cultured with CD4+ T cells in vitro to test their ability to induce Tr1-cell induction. Graft phagocytic cells were depleted in vivo at different time-points during G-CSF/rapamycin treatment, to identify their role in Tr1-cell induction and consequently in graft survival. In the spleen, the site of Tr1-cell induction, no differences in the frequencies of macrophages or dendritic cells (DC) were observed. In the graft, the site of antigen uptake, a high proportion of macrophages and not DC was detected in tolerant but not in rejecting mice. Graft-infiltrating macrophages of G-CSF/rapamycin-treated mice had an M2 phenotype, characterized by higher CD206 expression and interleukin (IL)-10 production, whereas splenic macrophages only had an increased CD206 expression. Graft-infiltrating cells from G-CSF/rapamycin-treated mice-induced Tr1-cell expansion in vitro. Furthermore, Tr1-cell induction was perturbed upon in-vivo depletion of phagocytic cells, early and not late during treatment, leading to graft loss suggesting that macrophages play a key role in tolerance induction mediated by Tr1 cells. Taken together, in this mouse model of Tr1-cell induced tolerance to allogeneic islets, M2 macrophages infiltrating the graft upon G-CSF/rapamycin treatment are key for Tr1-cell induction. This work provides mechanistic insight into pharmacologically induced Tr1-cell expansion in vivo in this stringent model of allogeneic transplantation.
Guillain‐Barré syndrome: Novel treatment by complement inhibition
Authors: Misawa Sonoko , Suichi Tomoki
Published: April 2020

Guillain‐Barré syndrome (GBS) is an immune‐mediated polyneuropathy that can cause acute flaccid tetraparesis and respiratory failure. Intravenous immunoglobulin and plasmapheresis were established as a standard of care, but 20% to 30% of patients require mechanical ventilation during the acute phase and up to 20% of patients cannot walk independently even 1 year after the onset. As the pathophysiology of GBS has been elucidated, complement activation draws attention as a key treatment point. In acute motor axonal neuropathy, anti‐ganglioside antibody deposition and resulting complement activation lead to nerve conduction failure and eventually axonal degeneration. In acute inflammatory demyelinating polyneuropathy, although the process has not been clearly revealed, autopsied specimens showed that terminal complement complex rimmed the surface of the Schwann cells. Eculizumab is an antibody to the complement protein C5 and can potently inhibit complement activation. In a murine model with anti‐ganglioside antibody–mediated neuropathy, eculizumab can avert respiratory failure and motor neuropathy. A randomized controlled phase II trial showed that eculizumab might be effective also for GBS patients. Inhibition of complement activation can be a new therapeutic option in the near future.
Kosaki overgrowth syndrome: A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications
Authors: Foster Alison , Chalot Basile , Antoniadi Thalia , Schaefer Elise , Keelagher Rebecca , Ryan Gavin , Thomas Quentin , Philippe Christophe , Bruel Ange‐Line , Sorlin Arthur , Thauvin‐Robinet Christel , Bardou Marc , Luu Maxime , Quenardelle Veronique , Wolff Valerie , Woodley Jessica , Vabres Pierre , Lim Derek , Igbokwe Rebecca , Joseph Annie , Walker Harriet , Jester Andrea , Ellenbogen Jonathan , Johnson Diana , Rooke Bethanie , Moss Celia , Cole Trevor , Faivre Laurence
Published: April 2020

Heterozygous activating variants in platelet‐derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long‐term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS‐like disorders and suggest vascular imaging is indicated in these patients.
The Suppression of Inferences From Counterfactual Conditionals
Authors: Espino Orlando , Byrne Ruth M. J.
Published: April 2020

We examine two competing effects of beliefs on conditional inferences. The suppression effect occurs for conditionals, for example, “if she watered the plants they bloomed,” when beliefs about additional background conditions, for example, “if the sun shone they bloomed” decrease the frequency of inferences such as modus tollens (from “the plants did not bloom” to “therefore she did not water them”). In contrast, the counterfactual elevation effect occurs for counterfactual conditionals, for example, “if she had watered the plants they would have bloomed,” when beliefs about the known or presupposed facts, “she did not water the plants and they did not bloom” increase the frequency of inferences such as modus tollens. We report six experiments that show that beliefs about additional conditions take precedence over beliefs about presupposed facts for counterfactuals. The modus tollens inference is suppressed for counterfactuals that contain additional conditions (Experiments 1a and 1b). The denial of the antecedent inference (from “she did not water the plants” to “therefore they did not bloom”) is suppressed for counterfactuals that contain alternatives (Experiments 2a and 2b). We report a new “switched‐suppression” effect for conditionals with negated components, for example, “if she had not watered the plants they would not have bloomed”: modus tollens is suppressed by alternatives and denial of the antecedent by additional conditions, rather than vice versa (Experiments 3a and 3b). We discuss the implications of the results for alternative theories of conditional reasoning.
Targeted next generation sequencing (NGS) to classify melanocytic neoplasms
Authors: Zarabi Samaneh K. , Azzato Elizabeth M. , Tu Zheng Jin , Ni Ying , Billings Steven D. , Arbesman Josh , Funchain Pauline , Gastman Brian , Farkas Daniel H. , Ko Jennifer S.
Published: April 2020

This study piloted a pan‐solid‐tumor next generation sequence (NGS)‐based laboratory developed test as a diagnostic aid in melanocytic tumors. 31 cases (4 “epithelioid” nevi, 5 blue nevi variants, 7 Spitz tumors [3 benign and 4 malignant] and 15 melanomas) were evaluated. All tumors [median diameter 7 mm (range 4‐15 mm); median thickness 2.25 mm (range 0.25‐12 mm)] yielded satisfactory results. The number of small nucleotide variants/tumor was significantly different between melanoma (median 18/tumor, range 4‐71) and all other lesions (median 8/tumor, range 3‐17) (P < 0.004) and malignant (median 16/tumor, range 4‐71) vs benign lesions (median 7/tumor, range 3‐14) (P = 0.01). BRAF, MET, NTRK1, and ROS fusions only occurred in benign Spitz tumors; EML4 fusion, BRAF, MAP2K1 and TERT mutations occurred in malignant Spitz tumors and/or melanoma. Amplifications and NRAS and NF1 mutations only occurred in melanoma. Most melanomas contained >1 pathogenic alteration. Developed NGS‐based criteria correctly classified all malignant lesions in this series. 10/12 cases showed concordance with FISH; consensus diagnosis agreed with NGS classification in FISH‐non‐concordant cases. This pilot study suggests that NGS may be an effective diagnostic adjunct comparable to FISH, but further studies with larger numbers of cases are needed.
Night‐time is the right time? Late‐night drinking and assaults in Finnish public and private settings
Authors: Mäkelä Pia , Warpenius Katariina
Published: April 2020

Introduction and Aims

The risk of alcohol‐related injuries and violence increases in late‐night settings. We analysed temporal patterns of drinking and assaults and present an event‐level analysis of connections between night‐time drinking, estimated blood alcohol level, location and drinkers' age and sex.

Design and Methods

Main data source is a Finnish general population (aged 18–69 years) survey carried out in 2016 (n = 1962), including event‐level data on drinking occasions in the previous 7 days (n = 1891). Statistical analyses consisted of tabulations and logistic regression analyses.

Results

Finns' drinking peaked around 8–9 pm on most days, with the greatest peaks on Fridays and Saturdays. The main pattern was similar for drinking occasions occurring in home surroundings and in licensed premises, but a larger proportion of the latter occurred in later hours of the day. Assaults had a similar weekday distribution, but the peak occurred several hours later, around 3–5 am. One explanation is that the mean estimated blood alcohol concentration strongly increased as the ending time of the drinking occasion extended later into the night, and the proportion of late‐night drinking was higher in licensed premises than home surroundings.

Discussion and Conclusions

Peaks for assaults in public places temporally coincide with the late closing times of licensed premises and with high estimated blood alcohol concentrations among drinkers. The results underline a need to reduce harm from intoxication, which in public places could include restricted opening hours, increased law enforcement, improved responsible beverage service practices and other interventions to better manage aggression.
Rezidivierende mukokutane Infektionen durch PVL‐positive Staphylococcus aureus‐Stämme: Eine Herausforderung im klinischen Alltag
Authors: Balakirski Galina , Hischebeth Gunnar , Altengarten Julia , Exner Daniel , Bieber Thomas , Dohmen Jonas , Engelhart Steffen
Published: April 2020

Hintergrund

Rezidivierende mukokutane Infektionen durch PVL‐positive Staphylococcus (S.) aureus‐Stämme stellen in Deutschland ein zunehmendes Problem dar. In den letzten Jahren wurden Ausbrüche in Kindertagesstätten und Kommunen beschrieben. Dennoch liegen zurzeit keine diagnostischen Algorithmen oder Therapieempfehlungen für die entsprechenden Infektionen in Deutschland vor.

Methode

Eine Literaturrecherche in der Datenbank PubMed/MEDLINE erfolgte mit dem Ziel, einen diagnostischen und therapeutischen Algorithmus zu erarbeiten. Zudem wurden nationale und internationale Empfehlungen berücksichtigt.

Ergebnisse

Panton‐Valentine Leukozidin (PVL) ist ein porenbildendes Protein, das von bestimmten S. aureus‐Stämmen produziert wird. Sowohl Methicillin‐sensible (MSSA) als auch Methicillin‐resistente S. aureus (MRSA)‐Stämme können das für die PVL‐Produktion verantwortliche Gen lukS‐lukF besitzen. Das klinische Bild der durch einen PVL‐positiven S. aureus verursachten Infektionen erstreckt sich von einzelnen rezidivierenden Abszessen bis hin zu einer ausgedehnten Furunkulose. Bei etwa 40 % der Patienten kommt es zu Rezidiven der Beschwerden trotz einer konsequenten Behandlung der Erstinfektion. Die Therapie variiert je nach klinischem Bild der jeweiligen Infektion. Zudem wird in der Literatur eine Screeninguntersuchung der Patienten und ihrer engen Kontaktpersonen sowie eine bakterielle Dekolonisation der Betroffenen empfohlen.

Schlussfolgerungen

Diese Arbeit fokussiert auf die Pathogenese und Risikofaktoren der rezidivierenden mukokutanen Infektionen durch PVL‐positive S. aureus‐Stämme und versucht einen diagnostischen und therapeutischen Algorithmus zur optimalen Patientenversorgung vorzuschlagen.
Sexuell übertragbare Koinfektionen bei Patienten mit anogenitalen Warzen – eine retrospektive Analyse von 196 Patienten
Authors: Mueller Simon M. , Menzi Sheryl , Kind André B. , Blaich Annette , Bayer Michael , Navarini Alexander , Itin Peter , Brandt Oliver
Published: April 2020

Hintergrund und Ziele

Anogenitale Warzen (AGW) werden vorwiegend durch Niedrigrisiko‐Typen des humanen Papillomavirus (HPV) verursacht. Obgleich sie die häufigste sexuell übertragbare Virusinfektion darstellen, ist über Koinfektionen mit anderen sexuell übertragbaren Infektionen (sexual transmitted infections, STI) bei den betroffenen Patienten wenig bekannt. Ziel unserer Studie war es, die Rate der Koinfektionen mit STI bei Patienten mit AGW zu ermitteln, STI‐Koinfektionen zu spezifizieren und für jede STI die number needed to screen (NNS) zu berechnen.

Methoden

In einer retrospektiven Querschnittsstudie wurden die Datensätze von AGW‐Patienten auswertet, die zwischen 2008–2016 in unserer Klinik behandelt wurden.

Ergebnisse

142/196 (72 %) Patienten waren in unterschiedlicher Weise auf Infektionen mit HIV, HBV, HCV, Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium und HSV untersucht worden. Die STI‐Koinfektionsrate bei allen getesteten Patienten betrug 24,6 %, was einer NNS von 4,1 zum Nachweis einer STI entspricht. Interessanterweise unterschied sich die Koinfektionsrate zwischen heterosexuellen Männern, homosexuellen Männern und Frauen nicht signifikant. Die NNS für Syphilis betrug 8,4, für HIV 14,0, für HCV 28,5 und für HBV 39,0. Die NNS bei asymptomatischen Patienten, die auf HSV, Chlamydia trachomatis und Mycoplasma genitalium getestet wurden, betrug 1,4, 5,3 bzw. 12,0.

Schlussfolgerung

Aufgrund der hohen Prävalenz von STI‐Koinfektionen sollten AGW‐Patienten stets auf das Vorhandensein weiterer STI untersucht werden.
Linear patterns of the skin and their dermatoses
Authors: Senner Sonja , Eicher Laurie , Nasifoglu Suzan , Wollenberg Andreas
Published: April 2020

Knowledge about the linear patterns of the skin is a key competence of dermatologists. Four major groups of linear patterns can be distinguished: Langer lines, dermatomes, Blaschko lines and exogenous patterns. Langer lines run in the direction of the underlying collagen fibers (least skin tension) and play an important diagnostic role for some exanthematous skin diseases. In the thoracodorsal region, the distribution of the Langer lines gives rise to what is referred to as a ’Christmas tree pattern’. A dermatome is an area of skin that is supplied by a single spinal nerve. Disorders with a neuronal origin follow this pattern of distribution. The lines of Blaschko delineate the lines of migration of epidermal cells during embryogenesis. Exogenous linear patterns are caused by external factors.

The present CME article will highlight important skin disorders that primarily present in the form of one of the aforementioned patterns. In addition, we will also address skin conditions that may secondarily follow with these patterns (or distinctly not do so) as the result of various mechanisms such as the Koebner phenomenon, reverse Koebner phenomenon, and Wolf’s isotopic response.
Efficacy and safety of insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26‐week, open‐label, multicentre study: The LixiLan JP‐O2 randomized clinical trial
Authors: Terauchi Yasuo , Nakama Takahiro , Spranger Robert , Amano Atsushi , Inoue Takahiro , Niemoeller Elisabeth
Published: April 2020

Aims

To assess efficacy and safety of 26‐week treatment with insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi) compared with insulin glargine U100 (iGlar) in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs).

Materials and Methods

This phase 3, multicentre, open‐label, 1:1 randomized, parallel‐group study compared efficacy of iGlarLixi and iGlar in patients with T2DM, HbA1c of ≥7.5% to ≤9.5% and fasting plasma glucose ≤10.0 mmol/L (180 mg/dL). The primary endpoint was change in HbA1c from baseline to week 26.

Results

Patients were randomized to iGlarLixi (n = 260) or iGlar (n = 261) (mean age 59.7 years, baseline BMI 26.04 kg/m2, and HbA1c 8.04% [64.4 mmol/mol]). HbA1c reduction was significantly greater with iGlarLixi (−1.40% [−15.3 mmol/mol]) than with iGlar (−0.76% [−8.3 mmol/mol]). Significantly more iGlarLixi patients reached HbA1c <7% at week 26 (71.5% vs 38.5%, P < .0001), with significantly lower weight gain (LS mean difference −1.06 kg, P < .0001). Documented symptomatic hypoglycemia (plasma glucose ≤3.9 mmol/L [70 mg/dL]) was recorded in 14.2% of patients with iGlarLixi and 12.3% with iGlar. No severe hypoglycemia was reported in either group. Other than the expected gastrointestinal issues associated with glucagon‐like peptide 1 receptor agonists, we found no major difference in the incidence of TEAEs.

Conclusions

HbA1c reduction was significantly greater with iGlarLixi than with iGlar; significantly more patients achieved HbA1c <7%, with no additional risk of hypoglycemia and without weight gain. iGlarLixi (1:1) provided an effective treatment option for Japanese patients with T2DM inadequately controlled on OADs.

Clinical Trial Number: NCT02752828
Systemic immune‐inflammation index (SII) predicted clinical outcome in patients with coronary artery disease
Authors: Yang Ya‐Ling , Wu Cheng‐Hsueh , Hsu Pai‐Feng , Chen Su‐Chan , Huang Shao‐Sung , Chan Wan Leong , Lin Shing‐Jong , Chou Chia‐Yu , Chen Jaw‐Wen , Pan Ju‐Pin , Charng Min‐Ji , Chen Ying‐Hwa , Wu Tao‐Cheng , Lu Tse‐Min , Huang Po‐Hsun , Cheng Hao‐Min , Huang Chin‐Chou , Sung Shih‐Hsien , Lin Yenn‐Jiang , Leu Hsin‐Bang
Published: April 2020

Background

This study examines the predictive value of a novel systemic immune‐inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients.

Methods

A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long‐term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure.

Results

An optimal SII cut‐off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43‐2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09‐1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28‐2.99), MACE (HR: 1.65; 95% CI: 1.36‐2.01) and total major events (HR: 1.53; 95% CI: 1.32‐1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C‐index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05).

Conclusions

SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.
Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease
Authors: Giannini Edoardo G. , De Maria Costanza , Crespi Mattia , Demarzo Maria Giulia , Fazio Valentina , Grasso Alessandro , Torre Francesco , Bodini Giorgia , Marabotto Elisa , Furnari Manuele
Published: April 2020

Background

In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct‐acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA‐induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure.

Material and methods

Sixty‐three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated.

Results

Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6‐96.7), 83.3% (66.3‐92.7) and 80.7% (67.1‐89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria.

Conclusions

In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.
Establishment of the novel bivalve body plan through modification of early developmental events in mollusks
Authors: Wada Hiroshi , Phuangphong Supanat , Hashimoto Naoki , Nagai Kiyohito
Published: April 2020

Mollusks have a wide variety of body plans, which develop through conserved early embryogenesis, namely spiral embryonic development and trochophore larvae. Although the comparative study of mollusks has attracted the interest of evolutionary developmental biology researchers, less attention has been paid to bivalves. In this review, we focused on the evolutionary process from single‐shell ancestors to bivalves, which possess bilaterally separated shells. Our study tracing the lineage of shell field cells in bivalves did not support the old hypothesis that shell plate morphology is due to modification of the spiral cleavage pattern. Rather, we suggest that modification of the shell field induction process is the key to understanding the evolution of shell morphology. The novel body plan of bivalves cannot be established solely via separating shell plates, but rather requires the formation of additional organs, such as adductor muscles. The evolutionary biology of bivalves offers a unique view on how multiple organs evolve in a coordinated manner to establish a novel body plan.
The making of the defensive caste: Physiology, development, and evolution of the soldier differentiation in termites
Authors: Miura Toru , Maekawa Kiyoto
Published: April 2020

Termites (Blattodea, Termitoidea, or Isoptera) constitute one of the major lineages of eusocial insects. In termite societies, multiple types of functional individuals, that is, castes, perform divisions of labors to coordinate social behaviors. Among other castes, the soldier caste is distinctive since it is sterile and exclusively specialized into defensive behavior with largely modified morphological features. Therefore, many of the previous studies have been focused on soldiers, in terms of ecology, behavior, and evolution as well as developmental and physiological mechanisms. This article overviews the accumulation of studies especially focusing on the developmental and physiological mechanisms underlying the soldier differentiation in termites. Furthermore, the evolutionary trajectories that have led the acquisition of soldier caste and have diversified the soldier characteristics in association with the social evolution are discussed.
Joint Physical Custody and Adolescents’ Life Satisfaction in 37 North American and European Countries
Authors: Steinbach Anja , Augustijn Lara , Corkadi Gerrit
Published: April 2020

Joint physical custody, a parental care arrangement in which a child lives with each parent about equally after separation or divorce, is an increasingly common phenomenon in many Western countries. Although attention from family scholars, practitioners, and law professionals is growing, there are hardly any numbers on the prevalence of joint physical custody (JPC). Moreover, studies using large‐scale representative data on the effects of JPC for children’s well‐being are still rare. The data for this study come from Health Behaviour in School‐Aged Children (HBSC), a representative cross‐national survey of adolescents in 37 European and North American countries that was conducted in 2002, 2006, and 2010 and included information on students at the ages of 11, 13, and 15 years (N = 92,886). First, results revealed that symmetrical JPC after family dissolution is still very rare in the majority of countries (5% or less), but reaches 10–20% in some countries. Second, adolescents’ life satisfaction in nonintact families is higher in symmetric JPC arrangements than in asymmetric care arrangements. However, after controlling for children and family characteristics, the differences disappear. Thus, it is not the symmetric JPC arrangement that induces adolescents’ higher life satisfaction, but rather the children and family characteristics that are associated with the choice of such a custody arrangement by separated or divorced parents.
Mechanical and fracture properties of aluminium cylinders manufactured by orbital friction stir welding
Authors: Aliha M.R.M. , Ghoreishi S.M.N. , Imani D.M. , Fotoohi Y. , Berto F.
Published: April 2020

Butt welding of AA6063 aluminium cylindrical shells was performed using the orbital friction stir welding (FSW) method. Tool rotation speed and orbital speed (i.e., traverse speed of rotating cylinder during welding) were considered as variable, and the strength and the mechanical properties including tensile strength, microhardness, mode I fracture energy and mode I crack growth behaviour of manufactured cylinders were investigated experimentally. A novel and subsized test specimen was designed and manufactured for fracture testing of specimens extracted from both base metal and weld zone region of cylinders. The initial precrack was introduced along (i) the tool penetration through the pipe thickness (i.e., T‐direction) and (ii) along the tool travelling direction (i.e., L‐direction). It was found that the crack growth resistance and fracture energy values of FSW samples are greater than the corresponding values of base aluminium material along both “L”‐ and “T”‐directions. Also, the fracture resistance value in T‐direction was higher than the L‐direction for the whole tested FSW samples with different welding speeds.
Influence of fishes on macroinvertebrate communities and insect emergence production in intermittent stream refuges
Authors: Bonjour Sophia M. , Whiles Matt R. , Gido Keith B.
Published: April 2020

Drying intermittent stream networks often have permanent water refuges that are important for recolonisation. These habitats may be hotspots for interactions between fishes and invertebrates as they become isolated, but densities and diversity of fishes in these refuges can be highly variable across time and space.

Insect emergence from streams provides energy and nutrient subsidies to riparian habitats. The magnitude of such subsidies may be influenced by in‐stream predators such as fishes.

We examined whether benthic macroinvertebrate communities, emerging adult insects, and algal biomass in permanent grassland stream pools differed among sites with naturally varying densities of fishes. We also manipulated fish densities in a mesocosm experiment to address how fishes might affect colonisation during recovery from hydrologic disturbance.

Fish biomass had a negative impact on invertebrate abundance, but not biomass or taxa richness, in natural pools. Total fish biomass was not correlated with total insect emergence in natural pools, but orangethroat darter (Etheostoma spectabile) biomass was inversely correlated with emerging Chironomidae biomass and individual midge body size. The interaction in our models between predatory fish biomass and date suggested that fishes may also delay insect emergence from natural pools, altering the timing of aquatic–terrestrial subsidies.

There was an increase over time in algal biomass (chlorophyll‐a) in mesocosms, but this did not differ among fish density treatments. Regardless, fish presence in mesocosms reduced the abundance of colonising insects and total invertebrate biomass. Mesocosm invertebrate communities in treatments without fishes were characterised by more Chironomidae, Culicidae, and Corduliidae.

Results suggest that fishes influence invertebrates in habitats that represent important refuges during hydrologic disturbance, hot spots for subsidy exports to riparian food webs, and source areas for colonists during recovery from hydrologic disturbance. Fish effects in these systems include decreasing invertebrate abundance, shifting community structure, and altering patterns of invertebrate emergence and colonisation.
Cyclopoids feed selectively on free‐living stages of parasites
Authors: Mironova Ekaterina , Gopko Mikhail , Pasternak Anna , Mikheev Viktor , Taskinen Jouni
Published: April 2020

Many aquatic organisms can consume parasite larvae, thus hampering parasite transmission; however, information about feeding on them in the presence of an alternative prey remains scarce. When having a food choice, predators may decrease parasite consumption, therefore, it is important to assess the role of parasites in the diet of predators in natural communities with different types of prey available. Our study aims to test whether common freshwater cyclopoids feed on trematode free‐living stages (cercariae) when an alternative food source is present.

We experimentally studied ingestion rates of cyclopoids Macrocyclops distinctus fed with cercariae of trematode Diplostomum pseudospathaceum, a common and harmful parasite of freshwater fishes, and ciliates Paramecium caudatum (an alternative prey, known as suitable food for copepods). First, the feeding response of cyclopoids to different densities of each prey was studied. Then, feeding selectivity in the mixtures of cercariae and ciliates was tested.

Feeding rates of cyclopoids increased with prey densities (both ciliates and cercariae) but almost stopped growing at high prey densities, which indicated saturation (Holling type II functional response). In most cases, cyclopoids consumed cercariae at higher rates than ciliates. Maximum ingestion rates estimated from the obtained curves were 37 cercariae ind−1 hr−1 and 17 ciliate ind−1 hr−1.

When exposed to prey mixtures, cyclopoids fed on cercariae selectively. When cercariae were offered to cyclopoids at concentrations exceeding the saturation level, the ingestion of ciliates remained constantly low at all ciliate densities. In contrast, the ingestion of cercariae increased with rising cercariae densities even when ciliates were presented ad libitum, decreasing only at very high prey densities. Possible reasons of such feeding preferences are discussed.

Our study demonstrated that cyclopoids may prefer to feed on cercariae when there is an alternative food choice and can ingest cercariae at high rates. These experimental results could be extended to natural communities, suggesting that cyclopoids can reduce the transmission of parasites and contribute to the incorporation of parasite production in food webs of lentic ecosystems.
Spatiotemporal Analysis of Extracted Groundwater Volumes Estimated from Electricity Consumption
Authors: Chu Hone‐Jay , Lin Cheng‐Wei , Burbey Thomas J. , Ali Muhammad Zeeshan
Published: April 2020

Land subsidence caused by groundwater overexploitation is a serious global problem. The acquisition of spatiotemporal pumping rates and volumes is a first step for water managers to develop a strategic plan for mitigating land subsidence. This study investigates an empirical formulation to estimate the monthly maximum pumped volume over a 10‐year period based on electric power consumption data. A spatiotemporal variability analysis of monthly pumped volume is developed to provide an improved understanding of seasonal pumping patterns and the role of irrigation type. The analysis of regional pumped volume provides an approximation of the spatiotemporal patterns of the variations in pumped volume. Results show the effects of climate, seasonal changes in pumping from irrigation, and the local differences in pumping caused to crop types. A seasonal pumped volume peak occurs annually, with the highest and least pumped volumes occurring in March (highest peak) and September (lowest peak), respectively. However, the majority of the historical maximum pumped volumes have occurred during the last few years. Extracted volumes continue to increase in some locations. The analysis reveals increasing trends in pumping, thereby possibly providing the locations where increased effective stresses may lead to land subsidence.
Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials
Authors: Tosetto Alberto , Neff Anne , Lentz Steven R. , Santagostino Elena , Nemes Laszlo , Sathar Jameela , Meijer Karina , Chowdary Pratima , Shen Chunduo , Landorph Andrea , Hampton Kingsley
Published: April 2020

Introduction

Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half‐life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A.

Aim

Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials.

Methods

Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII <1%) received perioperative turoctocog alfa pegol treatment planned to achieve FVIII activity levels >80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0‐11 years) undergoing minor surgeries received 20‐75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5).

Results

pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1‐6. No safety concerns or inhibitors were identified. Forty‐five minor surgeries in 23 children were performed without complications.

Conclusion

Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A.
Long‐term analysis of the benefit of prophylaxis for adult patients with severe or moderate haemophilia A
Authors: Miesbach Wolfgang , Kittler Sabine , Bauhofer Artur , Königs Christoph , Becker Thomas , Nemes László , Staus Alexander , Schüttrumpf Jörg
Published: April 2020

Introduction

Prophylaxis with factor VIII (FVIII) concentrates in children with haemophilia A (HA) is current standard of care. The benefit of prophylactic treatment for adult HA patients is not commonly accepted.

Aim

To investigate the benefit of prophylaxis over on‐demand treatment in adult and elderly patients with severe or non‐severe HA in a real‐life setting.

Methods

Data from 163 patients comprising 1202 patient‐years were evaluated for 7.5 (±5.3) years. The effects on the annual bleeding rate (ABR, including spontaneous and traumatic bleeds) of treatment with a plasma‐derived FVIII concentrate, the patient's age and disease severity were investigated. The effect of changing the treatment from on demand to continuous prophylaxis on the patients’ ABRs was further analysed.

Results

Prophylaxis had the greatest effect on the ABRs of patients of any age with severe or non‐severe HA. The difference in ABR of all patients treated on demand (median 31.4; interquartile range (IQR) 27.6; N = 83) compared with those treated prophylactically (median 1.3; IQR 3.6; N = 122) was statistically significant (P < .05), even for patients with non‐severe HA (median 8.4; IQR 15.5; N = 11) vs median 1.5; IQR 4.2 (N = 17), P < .05). Patients, aged up to 88 years, switching from on demand to continuous prophylaxis showed the lowest median ABR (1.1; N = 51) after their regimen change.

Conclusion

Any (even low‐frequency) prophylaxis results in lower ABR than on‐demand treatment. Patients switching to prophylaxis benefitted the most, irrespective of age or HA severity. Prophylactic treatment—even tertiary—is the regimen of choice for patients of any age, including elderly patients, with severe or non‐severe HA.
Osmophobia and Odor‐Triggered Headaches in Children and Adolescents: Prevalence, Associated Factors, and Importance in the Diagnosis of Migraine
Authors: Albanês Oliveira Bernardo Albérico , Lys Medeiros Fabiola , Sampaio Rocha‐Filho Pedro Augusto
Published: April 2020

Objective

The objectives of this study are to study osmophobia and odor‐triggered headaches among headache pediatric patients.

Background

Achieving the correct diagnosis for headaches in younger children can be challenging. The presence of osmophobia could constitute a helpful piece of information for making the correct diagnosis of headaches among adults.

Methods

This was a cross‐sectional study. Children and adolescents with headaches who were seen consecutively at a pediatric outpatient service and had at least 1 headache attack over the previous 12 months were included. We used a semi‐structured questionnaire, Pediatric Migraine Disability Assessment, State‐Trait Anxiety Inventory, and Children’s Depression Inventory.

Results

About 300 patients were included; 253 had migraine, 47 had a tension‐type headache; 137 had osmophobia during headaches (135 were migraineurs). “Osmophobia during headaches” for diagnosing migraine: Sensitivity: 54.4% (95% CI: 48.2%‐60.5%); specificity: 95.8% (95% CI: 85.8%‐98.8%); positive predictive value (PPV): 98.5% (95% CI: 94.8%‐99.6%); negative predictive value (NPV): 28.5% (95% CI: 22.0%‐36.0%). Osmophobia was associated with higher intensity (OR: 2.90; 95% CI: 1.63, 5.15; P < .001) and duration of the headache (OR: 5.73; 95% CI: 2.29, 14.3; P < .001) and with vomiting (OR: 3.56; 95% CI: 1.83, 6.96; P < .001) (logistic regression). There were 62 patients (all of them migraineurs) with odor‐triggered headaches: sensitivity for diagnosing migraine: 24.9% (95% CI: 19.9%‐30.6%); specificity: 100% (95% CI: 92.4%‐100%), PPV: 100% (95% CI: 94.8%‐100%), NPV: 20% (95% CI: 16%‐26.0%). Odor‐triggered headaches were associated with higher intensity (OR: 3.47; 95% CI: 1.64, 7.35; P = .001) and duration of the headache (OR: 3.28; 95% CI: 1.37, 7.86; P = .001), vomiting (OR: 2.37; 95% CI: 1.19, 4.74; P = .014), and phonophobia (OR: 2.40; 95% CI: 1.08, 5.32; P = .031) (logistic regression). Osmophobia was associated with higher‐impact migraine (OR: 4.65; 95% CI: 1.30, 16.6; P = .018) and emergency care (OR: 4.65; 95% CI: 1.81, 12.0; P = .001) (logistic regression).

Conclusions

Osmophobia and odors as triggers for headaches are useful in diagnosing migraine and are markers for the severity of migraine in the pediatric population.
Cold‐batter mincing of hot‐boned and crust‐freeze‐air‐chilled ham muscle reduced fat content in protein gels
Authors: Lee Hong Chul , Wonderly Morgan P. , Pokharel Siroj , Strasburg Gale M. , Marks Bradley P. , Fernando Raymond H. , Kang Iksoon
Published: April 2020

The purpose of this study was to generate low‐fat hot dog using a combination of hot‐boning/crust‐freeze‐air‐chilling (HB‐CFAC) and cold‐batter mincing technologies. After slaughter, pork hams were subjected to hot boning (HB)/CFACor chill‐boning (CB)/CFAC prior to 9 min mincing including 3 min pre‐mincing. Control gels were prepared with ham, back fat and common ingredients while low‐fat gels were prepared with ham, water and common ingredients. The pH values of HB muscle and cooked gels were significantly higher than those of CB muscle and cooked gels. The fat and moisture contents of control gels were higher and lower, respectively, than those of low‐fat gels, regardless of HB or CB. The protein functionality and gel‐forming ability of HB muscle were superior to those of the CB muscle. These results indicate that fat can be reduced with no textural quality loss when HB‐CFAC muscle was cold‐batter minced presumably due to improved protein functionality and gel‐forming ability.
Gliadin/amidated pectin core–shell nanoparticles for stabilisation of Pickering emulsion
Authors: Jiang Yang , Zhu Yuzhu , Li Feng , Li Dapeng , Huang Qingrong
Published: April 2020

Over the past decade, edible colloidal particle‐stabilised Pickering emulsions have regained research interest. However, little information is available regarding the application of amidated pectin in stabilising Pickering emulsions. In this work, a ‘two‐step’ method was used to synthesise gliadin/pectin composite colloidal particles. The effects of pectin type, particle ratio, particle amount and oil fraction on the formation and stability of the resulting Pickering emulsion were systematically investigated by particle size and microscopy. The results showed that the particles formed after the addition of amidated pectin could better stabilise the o/w Pickering emulsion with a concentration of 2%, lower than that of the gliadin colloid particles. Confocal laser scanning microscopy (CLSM) revealed the cross‐sectional structure and the attachment of protein particles to the external interface. These results may provide reference for the selection of shell materials for Pickering colloidal particles (especially gliadin) in the future.
The effects of leader‐member exchange and employee learning on perceived employability
Authors: Park Yongho
Published: April 2020

In today’s rapidly changing society, the critical issues for organizations are how to attract individuals with high‐level employability and what role to play in maintaining and enhancing that employability. This study primarily aimed to investigate the effects of leader‐member exchange and employee learning on perceived employability. The literature review showed that leader‐member exchange is about the mutual relationship between the leader and members of an organization, and that employee learning consists in the individual employees’ continuing learning behaviours. The data for this study were collected from 257 South Korean insurance company employees. The study findings demonstrated that leader‐member exchange has a significant positive influence on the one dimension of perceived employability: corporate sense. Employee learning, on the contrary, was shown to have statistically significant positive effects on all the five dimensions of employability. Conclusions were drawn, and the implications and limitations of the study are discussed.