bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontal fibrosing alopecia – review of recent case reports and case series in PubMed
Authors: Valesky Eva Maria , Maier Manuela Denise , Kippenberger Stefan , Kaufmann Roland , Meissner Markus
Published: August 2018

Background

In his initial publication of frontal fibrosing alopecia (FFA) in 1994, Steven Kossard included six postmenopausal women. A type of cicatricial alopecia, FFA is clinically characterized by frontotemporal hairline recession and loss of eyebrows. In recent years, there has been an increasing number of case reports of FFA in both premenopausal women and men.

Study objective

Review and analysis of the literature on FFA with regard to epidemiology, associated disorders, disease presentation, diagnosis and treatment.

Methods and material

We conducted a Pubmed database search for case reports and case series on FFA. Overall, we reviewed and analyzed data from 68 articles, including 932 patients. Apart from epidemiological data such as age, gender or ethnicity, we also assessed other aspects such as predilection sites, associated skin lesions, comorbidities, drugs and treatment response as well as the diagnostic significance of autoantibodies.

Results

While we were able to confirm and more accurately define some of the data published in the literature, we were unable to reproduce certain assumptions that had previously been made. The high coincidence of FFA and thyroid disease we found in our analysis is particularly significant.

Conclusions

The present study provides the most comprehensive review to date of published cases of FFA.
Frontal fibrosierende Alopezie – Review aktueller Fallbeispiele und Fallserien in PubMed
Authors: Valesky Eva Maria , Maier Manuela Denise , Kippenberger Stefan , Kaufmann Roland , Meissner Markus
Published: August 2018

Hintergrund

In der 1994 erschienen Erstpublikation zur frontal fibrosierenden Alopezie (FFA) fasste Steven Kossard sechs Patientinnen, die sich allesamt in der Postmenopause befanden, zusammen. Bei der FFA handelt es sich um eine vernarbende Alopezie, die durch die klinischen Kriterien der frontotemporalen Haarlinienregression und den Verlust der Augenbrauen gekennzeichnet ist. In letzten Jahren wurden zunehmend Fallberichte zur Manifestation in der Prämenopause und bei männlichen Patienten publiziert.

Ziel der Arbeit

Zusammenfassung und Analyse der verfügbaren Literatur in Pubmed zur FFA bezüglich der Epidemiologie, der Begleiterkrankungen, der Krankheitspräsentation, Diagnostik und Therapie.

Material und Methoden

Die Datenbank Pubmed wurde nach Fallberichten und Fallserien zur FFA durchsucht. Insgesamt wurden 68 Artikel mit insgesamt 932 Patientenfällen eingeschlossen, analysiert und die patientengebundenen Daten ausgewertet. Neben den epidemiologischen Häufigkeiten wie Alter, Geschlecht oder Ethnie wurden zusätzliche Aspekte zu Prädilektionsstellen, assoziierten Hautveränderungen, Begleiterkrankungen, Medikationen und Therapieansprechen sowie die diagnostische Relevanz von Autoantikörpern erfasst.

Ergebnisse

Teilweise konnten die in Fallserien und Einzelfallberichten publizierten Erkenntnisse bestätigt und besser differenziert werden, wohingegen einzelne Annahmen nicht reproduziert werden konnten. Von besonderer Relevanz ist die in unserer Analyse ermittelte hohe Koinzidenz der FFA mit Schilddrüsenerkrankungen.

Schlussfolgerungen

Die vorliegende Arbeit präsentiert, die bislang umfangreichste Zusammenfassung der in der Literatur zur FFA publizierten Patientenfälle.
Lebensqualität und Behandlungsziele bei Psoriasis aus Patientensicht: Ergebnisse eines österreichweiten Querschnitt‐Survey
Authors: Wolf Peter , Weger Wolfgang , Legat Franz , Painsi Clemens , Saxinger Werner , Müllegger Robert , Sator Paul , Ratzinger Gudrun , Selhofer Sylvia , Richter Leo , Salmhofer Wolfgang , Lange‐Asschenfeldt Bernhard , Trautinger Franz , Mlynek Alexander , Strohal Robert , Augustin Matthias , Quehenberger Franz
Published: August 2018

Hintergrund

Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschränkung ihrer Lebensqualität konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt.

Patienten und Methodik

Wir führten einen bundesweiten Querschnitt‐Survey in Österreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualität und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit überwiegend tertiären Versorgungsaufgaben durch.

Ergebnisse

70,2 % der 1184 befragten Patienten berichtete über eine eingeschränkte Lebensqualität (DLQI 2–5: 29,4 %; 6–10: 19,3 %; 11–15: 11,5 %; 16–20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Fälle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewünschten Ausmaß erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear­man‐Rangkorrelation; p = 1.1e‐45), dem Ausmaß des psoriatischen Körperoberflächenbefalls (p = 3.2e‐11) und Kopfhautbefalls (p = 3.2e‐11) sowie Schmerzen (p = 2.3e‐22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant höheren Patientenzufriedenheit verbunden (Wilcoxon‐Test, p = 2.0e‐16).

Schlussfolgerungen

Die Lebensqualität der meisten österreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeinträchtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.
Nichtmelanozytäre Hauttumoren – von der aktinischen Keratose bis zum Plattenepithelkarzinom
Authors: Schmitz Lutz , Oster‐Schmidt Claus , Stockfleth Eggert
Published: August 2018

Aktinische Keratosen sind als intraepitheliale Proliferation atypischer Keratinozyten definiert und können in ein invasives Plattenepithelkarzinom übergehen, welches sich in der Folge zu einer potenziell lebensbedrohlichen Krankheit entwickeln kann. Die Inzidenz von AK hat in den letzten Jahrzehnten aufgrund eines veränderten Freizeitverhaltens der Bevölkerung und des demographischen Wandels in den Industrienationen deutlich zugenommen. Derzeit wissen wir jedoch nicht, ob und wann eine AK in einen invasiven Tumor übergeht, sodass die konsequente Behandlung der Feldkanzerisierung ein wichtiger Bestandteil zur Vermeidung eines möglichen Progresses darstellt. Neben einem breiten Armamentarium an interventionellen und medikamentösen Therapieoptionen kommt dabei der primären Prävention insbesondere durch konsequenten Sonnenschutz eine entscheidende Bedeutung zu. Weitergehend wären klinische, histomorphologische oder molekularbiologische Klassifikationen wünschenswert, die eine zuverlässige Risikostratifizierung der Patienten ermöglichen würden. Damit ließe sich, auch unter sozioökonomischen Gesichtspunkten, eine Über‐ bzw. Untertherapie der steigenden Patientenzahlen zukünftig vermeiden und individualisierte, bedarfsadaptierte Therapiekonzepte erstellen.
Individual‐based models forecast the spread and inform the management of an emerging riverine invader
Authors: Messager Mathis L. , Olden Julian D.
Published: August 2018

Aim

Mounting ecological impacts of invasive species on freshwater ecosystems are among the greatest challenges confronting ecologists and decision‐makers in conserving biodiversity and ecosystem function. Tools to slow the proliferation of aquatic invasive species are still needed to guide the allocation of limited resources more effectively and efficiently once a species is already established. Here we develop mechanistic models to recreate the invasion history of the rusty crayfish Faxonius rusticus in the John Day River (JDR) basin, forecast its future distribution, and evaluate the management efficiency of, and trade‐offs among, population control actions.

Location

John Day River Basin, Oregon.

Methods

The spread and control of rusty crayfish in the JDR was simulated with a spatially explicit individual‐based model (SEIBM) whereby the life history of each crayfish in the population is modelled in response to environmental conditions that vary across space and time. The model was calibrated by comparing modelled rusty crayfish spread throughout the JDR to known occurrences according to three comprehensive surveys.

Results

Our model accurately reproduced historical rusty crayfish distribution data for 2005, 2010, and 2016 with a specificity and sensitivity of ~80%. Leveraging this realistic model of the spread of rusty crayfish, we show that rapid management actions to the initial invasion would have resulted in an opportunity to slow the spread of rusty crayfish. We instead predict that rusty crayfish will reach the mainstem of the Columbia River by 2025, at which our model predicts that the crayfish population will number on the order of 108 individuals over more than 1100 km of river throughout the watershed and progress into critical salmon spawning habitat.

Main conclusion

This study demonstrates that SEIBMs can provide unique insight into the future distribution of aquatic invasive species and concretely support decision‐makers in choosing an optimal control strategy.
Molecular imaging within the lower gastrointestinal tract: From feasibility to future
Authors: Rath Timo , Kiesslich Ralf , Neurath Markus F. , Atreya Raja
Published: August 2018

Molecular imaging is based on the labelling of defined molecular targets through the utilization of fluorescently linked probes and their subsequent detection with high‐resolution endoscopic devices, thereby enabling visualization of single molecules including receptors. Whereas early studies have used molecular imaging for improved visualization and detection of early dysplasia and cancer as well as for assessing intestinal inflammation and inflammation‐associated cancer within the gastrointestinal (GI) tract, more recent studies have impressively demonstrated that molecular imaging can also be used to characterize and visualize the molecular fingerprint of cancer and inflammation in vivo and in real time. With this, molecular imaging can be used to guide expression‐tailored individualized therapy. With the rapid expansion and diversification of the repertoire of biological agents utilized in inflammatory bowel disease and cancer, this approach is gaining increasing attention. Within this review, we first summarize the technical components commonly used for molecular imaging and then review preclinical and clinical studies and evolving clinical applications on molecular imaging within the lower GI tract. Molecular imaging has the potential to significantly change endoscopic diagnosis and subsequent targeted therapy of gastrointestinal cancer and chronic gastrointestinal diseases.
Endoscopic diagnosis of cystic lesions of the pancreas
Authors: Kamata Ken , Kitano Masayuki
Published: August 2018

Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS‐guided fine‐needle aspiration cytology and EUS‐guided fine needle‐based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non‐mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast‐enhanced harmonic EUS (CH‐EUS), as an add‐on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH‐EUS has a sensitivity of 60–100% and a specificity of 75–92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta‐analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.
Divided disasters: examining the impacts of the conflict–disaster nexus for distanced crises in the Philippines
Authors: Field Jessica
Published: August 2018

‘Divided disasters’ are conflicts and natural hazard‐induced disasters that occur simultaneously, but in different locations within the same national boundaries. They will place pressure on the same national governance structures, will draw on the same international and national humanitarian resources, and therefore can mutually reinforce the challenges and risks faced by affected populations. Yet, as this paper argues, the impacts do not originate in the direct interaction of these two variables. Rather, they derive, in part, from the management of humanitarian responses to them—namely, through the reprioritisation of attention and the redeployment of resources as driven by the imperatives of ‘the good project'. Using a case study of the Philippines, and the parallel emergencies of Typhoon Haiyan (one of the strongest tropical cyclones on record) and the spike in violence in Mindanao in 2013, this paper explores the organisational motivators of humanitarian responses to divided disasters, and assesses their implications for affected populations.
Liraglutide treatment improves postprandial lipid metabolism and cardiometabolic risk factors in humans with adequately controlled type 2 diabetes: A single‐centre randomized controlled study
Authors: Matikainen Niina , Söderlund Sanni , Björnson Elias , Pietiläinen Kirsi , Hakkarainen Antti , Lundbom Nina , Taskinen Marja‐Riitta , Borén Jan
Published: August 2018

Aims

Patients with type 2 diabetes and non‐alcoholic fatty liver disease (NAFLD) exhibit considerable residual risk for cardiovascular disease (CVD). There is, therefore, increasing interest in targeting postprandial lipid metabolism and remnant cholesterol. Treatment with the glucagon‐like peptide 1 (GLP‐1) analogue liraglutide reduces CVD risk by mechanisms that remain unexplained in part. Here we investigated the effects of liraglutide intervention on ectopic fat depots, hepatic lipogenesis and fat oxidation, postprandial lipid metabolism and glycaemia in humans with type 2 diabetes.

Methods

The effect of liraglutide was investigated in 22 patients with adequately controlled type 2 diabetes. Patients were randomly allocated, in a single‐blind fashion, to either liraglutide 1.8 mg or placebo once daily for 16 weeks. Because liraglutide is known to promote weight loss, the study included dietary counselling to achieve similar weight loss in the liraglutide and placebo groups. Cardiometabolic responses to a high‐fat mixed meal were measured before and at the end of the liraglutide intervention.

Results

Weight loss at Week 16 was similar between the groups: −2.4 kg (−2.5%) in the liraglutide group and −2.1 kg (−2.2%) in the placebo group. HBA1c improved by 6.4 mmol/mol (0.6%) in the liraglutide group (P = 0.005). Liver fat decreased in both groups, by 31% in the liraglutide group and by 18% in the placebo group, but there were no significant changes in the rate of hepatic de novo lipogenesis or β‐hydroxybutyrate levels, a marker of fat oxidation. We observed significant postprandial decreases in triglycerides only in plasma, chylomicrons and VLDL, and remnant particle cholesterol after treatment in the liraglutide group. Fasting and postprandial apoCIII concentrations decreased after liraglutide intervention and these changes were closely related to reduced glycaemia. In relative importance analysis, approximately half of the changes in postprandial lipids were explained by reductions in apoCIII concentrations, whereas less than 10% of the variation in postprandial lipids was explained by reductions in weight, glycaemic control, liver fat or postprandial insulin responses.

Conclusions

Intervention with liraglutide for 16 weeks produces multiple improvements in cardiometabolic risk factors that were not seen in the placebo group, despite similar weight loss. Of particular importance was a marked reduction in postprandial atherogenic remnant particles. The underlying mechanism may be improved glycaemic control, which leads to reduced expression of apoCIII, a key regulator of hypertriglyceridaemia in hyperglycaemic patients.
Endogenous glucagon‐like peptide‐1 system response is impaired during ST‐elevation myocardial infarction in type 2 diabetes patients
Authors: Elbaz‐Greener Gabby , Bloch Olga , Kumets Ilya , Blatt Alex , Rapoport Micha J.
Published: August 2018

We previously demonstrated increased glucagon‐like peptide‐1 (GLP‐1) secretion during acute ST elevation myocardial infarction (STEMI) in non‐diabetic (ND) patients. Whether the endogenous GLP‐1 system response is different in patients with type 2 diabetes (T2D) during STEMI is unknown. Patients with STEMI (20 ND, 13 T2D) and 3 control groups (non‐STEMI [14 ND, 13 T2D], stable angina pectoris [SAP] [8 ND, 10 T2D] patients and healthy subjects) (n = 25) were studied. Plasma levels of total and active GLP‐1 and soluble dipeptidyl peptidase‐4 (sDPP4) were estimated by enzyme‐linked immunosorbent assay on admission and at 24 and 48 hours after percutaneous coronary intervention in all patients. Sharply elevated levels of total and active GLP‐1 were found in ND STEMI patients at 24 h (P < 0.05 and P < 0.005, respectively), but not in T2D STEMI patients. All patients demonstrated decreased sDPP4 levels compared with healthy controls (P < 0.0005) accompanied by increased active/total GLP‐1 ratio regardless of their ischemic state. These data demonstrate that T2D patients fail to further upregulate their endogenous GLP‐1 system during STEMI. This may underlie their worse cardiovascular outcome.
Influence of baseline modified Rheumatic Disease Comorbidity Index (mRDCI) on drug survival and effectiveness of biological treatment in patients affected with Rheumatoid arthritis, Spondyloarthritis and Psoriatic arthritis in real‐world settings
Authors: Iannone Florenzo , Salaffi Fausto , Fornaro Marco , Di Carlo Marco , Gentileschi Stefano , Cantarini Luca , Lopalco Giuseppe
Published: August 2018

Aim

To assess the impact of baseline modified Rheumatic Disease Comorbidity Index (mRDCI) a simple comorbidity count, on overall survival of treatments with biological drugs in patients affected with Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) and Psoriatic Arthritis (PsA) in real‐world settings.

Methods

Patients (nr. 635) with RA (nr. 214), SpA (nr. 213) and PsA (nr. 208) starting a first biological drug were retrospectively analysed. mRDCI was scored at baseline, and disease characteristics were recorded at entry and at last observation. Drug retention was analysed using Kaplan‐Meier curves. Cox regression models were used to estimate the association of baseline mRDCI with drug discontinuation and clinical outcomes, the achievement of clinical remission based on 28 joint‐Disease Activity Score (DAS28) <2.6 for RA and PsA, and on Ankylosing Spondylitis‐C‐reactive protein Disease Activity Score (ASDAS‐CRP) <1.3 for SpA.

Results

Baseline mRDCI significantly correlated with the number of biological drug switches (rho 0.26). Persistence on biologic therapy was significantly higher in patients with mRDCI=0 (96.4%), than in those with mRDCI ≥2 (83.9%). Patients without comorbidities showed significantly higher drug survival rate in PsA (P = 0.0001) or SpA (P = 0.02), but not in RA. mRDCI was also found to be a predictor of definitive drug discontinuation (HR: 1.53) and of failure to achieve remission in RA (HR: 0.66) or PsA (HR: 0.77), and in SpA (HR: 0.43).

Conclusions

This study provided evidence that baseline mRDCI negatively impacts the persistence on biologic treatments and clinical outcomes in patients with RA, SpA and PsA in real‐life settings.
High levels of circulating cell‐free DNA are a biomarker of active SLE
Authors: Xu Yalan , Song Yijun , Chang Jiazhen , Zhou Xiya , Qi Qingwei , Tian Xinping , Li Mengtao , Zeng Xiaofeng , Xu Mengnan , Zhang Wenjuan , Cram David S , Liu Juntao
Published: August 2018

Background

High levels of circulating cell‐free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE).

Materials and methods

Comparative groups comprised 22 nonpregnant and 36 pregnant women with SLE (test groups) and 60 nonpregnant and 199 pregnant women with no history of SLE (control groups). The levels of cfDNA in plasma were quantitated by a fluorometric dsDNA assay.

Results

Compared to controls, the median levels of cfDNA were significantly higher in nonpregnant SLE patients (7.38 ng/mL vs 4.6 ng/mL, P = 0.033) and in pregnant SLE patients (7.65 ng/mL vs 5.25 ng/mL, P = 0.003). Based on SLE disease activity index (SLEDAI) scores, the median cfDNA levels were significantly higher in patients with active disease (4 < SLEDAI < 15) compared with patients with inactive disease (SLEDAI < 4) (13.58 ng/mL vs 6.72 ng/mL, P = 0.01). While there was a trend of increased cfDNA levels with higher SLEDAI scores (R2 = 0.3, P < 0.001), we found no association of increased cfDNA levels with nephritis, skin manifestations, multiorgan inflammations or with other inflammatory markers such as decreased C3 and C4 levels or increased anti‐ds DNA antibodies.

Conclusions

Our results suggest that in addition to classical SLE serological markers, measurement of circulating plasma cfDNA levels has potential as a useful biomarker for assessing SLE disease activity in patients and monitoring treatment.
Co-operation in Social Dilemmas Through Position Uncertainty
Authors: Gallice Andrea , Monzón Ignacio
Published: August 2018

We present a natural environment that sustains full co-operation in one-shot social dilemmas among a finite number of self-interested agents. Players sequentially decide whether to contribute to a public good. They do not know their position in the sequence, but observe the actions of some predecessors. Since agents realise that their own action may be observed, they have an incentive to contribute in order to induce potential successors to also do so. Full contribution can then emerge in equilibrium. The same environment leads to full co-operation in the prisoners’ dilemma.
Country and gender differences in the motivation of dental students—An international comparison
Authors: Haslach Sandra D. , Aytepe Zeynep , Kokkari Anne , Azrak Birgül , Ehlers Vicky , Herz Marco M. , Jerg‐Bretzke Lucia , Geibel Margrit‐Ann
Published: August 2018

Purpose

The objective of this study, conducted in Germany, Finland and Turkey, was to identify whether motivations to study dentistry varied by country, gender or year of study.

Methods

The multicentre pilot study was conducted in English language in 2014. Participants (n = 469 dental students) were either in the first or last year of study. The response rate was 91%.

Results

The sample comprised 63% females and 37% males, reflecting the common gender distribution in dental education. A total of 236 first year students (50.3%) and 233 final year students (49.7%) took part in the study. The participants were aged 21‐25 years and of 15 different nationalities, mostly from Turkey, Germany and Finland. Considering who motivated them most to become a dentist, the most common answer was “self‐motivated” (49.5%). 23.4% of the students stated having been motivated by a “family member or friend, who is a dentist,” while 24.3% said they had been motivated by a “family member or friend, who is not a dentist.” —Very few students (2.8%) recorded having been motivated by a “high school or college counsellor.” Motivations for choosing dentistry as a career included “ability to help people,” “self‐employment,” “income potential,” “working with hands” and “status and prestige,” all of which were rated as highly important. “Time management” and “career variety” were rated as moderately important. Significant statistical differences were observed by country and gender. For the German students, a dental relative was significantly more often relevant than for the Finnish and Turkish students, who were more often influenced by family members or friends not working in the dental field. “Time management” seemed to be significantly more important to female than to male students.

Conclusion

In line with a feminisation of the workforce in dentistry, a well‐structured working environment and well‐thought‐out time management may play an increased role in future work force planning (Gender dentistry: International vergleichende Studie zu Karrierewahl und Spezialisierungswünschen von Zahnmedizinstudenten. Ulm: Universität Ulm).
Immune surveillance by autoreactive CD4‐positive helper T cells is a common phenomenon in patients with acute myeloid leukemia
Authors: Lam Tin Sing , van de Meent Marian , Marijt Erik W. A. , Falkenburg J. H. Frederik , Jedema Inge
Published: August 2018

Objectives

The importance of autologous T‐cell responses in immune surveillance against acute myeloid leukemia (AML) remains unclear. Therefore, we investigated the presence and functional reactivity of autoreactive T‐cell responses against autologous AML blasts.

Methods

T cells purified from PB samples harvested from patients during first complete remission were stimulated with autologous AML material harvested at diagnosis. After 12‐14 days of coculture, the T cells were restimulated with autologous AML cells, and leukemia‐reactive T‐cell clones were isolated based on their expression of the activation marker CD137.

Results

We demonstrated that AML‐induced autoreactivity was predominantly mediated by CD4 T cells. These autoreactive T cells showed abundant cytokine production, coincided by modest cytotoxic activity. Upon coculture, the autoreactive T cells were able to increase the immunogenicity of the AML blasts. Interestingly, similar AML‐directed reactivity was observed using HLA‐identical responder T cells from healthy donors.

Conclusions

We demonstrated that the presence of AML‐directed autoreactive T cells is a common phenomenon which appears to be part of the general T‐cell repertoire also in healthy individuals. This autoreactive AML‐directed T‐cell response may directly contribute to anti‐AML immune surveillance especially in the situation of minimal residual disease, but furthermore the immune‐modulatory effect on the AML phenotype may pave the way for other immunological interventions.
Second‐line treatment for acute graft‐versus‐host disease with mesenchymal stromal cells: A decision model
Authors: Thielen Frederick W. , Blommestein Hedwig M. , Oosten Liesbeth E.M. , Calkoen Friso G. , Lankester Arjan C. , Zwaginga Jaap J. , Le Blanc Katarina , Redondo Alba , Sánchez‐Guijo Fermin , Algeri Mattia , Locatelli Franco , Fibbe Wim E. , Uyl‐de Groot Carin A.
Published: August 2018

Objective

No standard second‐line treatment exists for acute graft‐versus‐host disease steroid‐refractory (SR‐aGvHD), and long‐term outcomes remain poor. Mesenchymal stromal cells (MSCs) have been evaluated as treatment, but no disease model (DM) exists that integrates and extrapolates currently available evidence. The aim of this study was to develop such a DM to describe the natural history of SR‐aGvHD and to predict long‐term outcomes.

Method

The DM was developed in collaboration with experts in haematology‐oncology. Subsequently, a model simulation was run. Input parameters for transition and survival estimates were informed by published data of clinical trials on MSC treatment for SR‐aGvHD. Parametric distributions were used to estimate long‐term survival rates after MSCs.

Results

The newly developed DM is a cohort model that consists of eight health states. For the model simulation, we obtained data on 327 patients from 14 published phase II trials. Due to limited evidence, DM structure was simplified and several assumptions had to be made. Median overall survival was 3.2 years for complete response and 0.5 years for no complete response.

Conclusion

The DM provides a comprehensive overview on the second‐line treatment pathway for aGvHD and enables long‐term predictions that can be used to perform a cost‐effectiveness analysis comparing any treatment for SR‐aGvHD.
The elusive and heterogeneous pattern of type 2M von Willebrand disease: A diagnostic challenge
Authors: Casonato Alessandra , Galletta Eva , Daidone Viviana
Published: August 2018

Type 2M is a very heterogeneous form of von Willebrand disease (VWD) associated with impaired platelet and von Willebrand factor (VWF) interactions not due to a lack of large VWF multimers.

Objectives

To investigate type 2M heterogeneity and to establish the most appropriate diagnostic flowchart.

Methods

Hemostatic and genetic VWF analyses were performed in 14 type 2M VWD patients carrying the p.G1324S, p.R1374H, p.R1374C, p.A1344_A1350del, or p.F1293L mutations.

Results

PFA‐100 was always significantly prolonged, and ristocetin‐induced platelet aggregation (RIPA) and VWF ristocetin cofactor (VWF:RCo) greatly reduced or absent. Plasma VWF antigen (VWF:Ag) was reduced except in the p.G1324S patient, while platelet VWF:Ag was normal or near normal except in the p.R1374C patients. The ratio of collagen binding (VWF:CB) to VWF:Ag was normal or near normal except in patients carrying the p.R1374H and p.A1344_A1350del mutations, whose large VWF multimers were slightly reduced. Multimer patterns were normal or lacking in large oligomers, or with larger than normal VWF components.

Conclusions

Only PFA100, RIPA and VWF:RCo were always abnormal. We thus propose a minimal diagnostic test battery: RIPA (demonstrating the defective VWF‐platelet interaction), VWF:Ag (exploring VWF synthesis), and VWF:CB and its ratio (to explore multimer patterns). Other tests would only serve for confirmation, if necessary.
Adaptive threshold hunting reveals differences in interhemispheric inhibition between young and older adults
Authors: Mooney Ronan A. , Cirillo John , Byblow Winston D.
Published: August 2018

Interhemispheric inhibition between bilateral motor cortices is important for the performance of unimanual activities and may be compromised with advancing age. Conventionally, interhemispheric inhibition is assessed using paired‐pulse transcranial magnetic stimulation (TMS) with constant conditioning and test stimulation parameters. Adaptive threshold hunting TMS, whereby a target motor‐evoked potential amplitude is maintained in the presence of the conditioning, may provide an alternative means of assessment. Furthermore, interhemispheric inhibition may suppress late indirect‐waves more so than early indirect‐waves which can be preferentially elicited using anterior–posterior (AP) and posterior–anterior (PA) induced currents, respectively. The aim of this study was to assess age‐related effects on interhemispheric inhibition using both conventional and threshold hunting techniques with PA‐ and AP‐induced current. In 15 young and 15 older adults, short (10 ms) and long (40 ms) interval interhemispheric inhibition was examined in the nondominant extensor carpi radialis muscle at rest and during voluntary extension of the contralateral wrist. With the conventional technique, there were no age‐related differences in short‐interval interhemispheric inhibition. With threshold hunting and AP‐induced current, young adults exhibited greater short‐interval interhemispheric inhibition during contralateral activation compared with rest and compared with older adults. Furthermore, long‐interval interhemispheric inhibition was greater in older adults compared with young for both conventional and threshold hunting techniques. Age‐related differences in interhemispheric inhibition are evident with threshold hunting using PA‐ and AP‐induced current.
Analytical solution of the one‐dimensional nonlinear Richards equation based on special hydraulic functions and the variational principle
Authors: Su L. , Wang Q. , Qin X. , Shan Y. , Zhou B. , Wang J.
Published: August 2018

A simple analytical solution of a one‐dimensional transient and nonlinear Richards equation is of great importance for estimating the hydraulic properties of soil and for precision irrigation. We developed simple approximate solutions in explicit and implicit forms for equations describing one‐dimensional, constant‐water‐head horizontal absorption and vertical infiltration for a special case of an exponential water‐retention curve and power‐law hydraulic conductivity, respectively, based on least‐action and variational principles. The profile of the soil water content (SWC) depended on the soil hydraulic parameter n associated with the pore‐size distribution, and the new solutions could be applied to most soils for 3.5 ≤ n ≤ 24.5. A comparison with numerical solutions calculated by an implicit‐difference scheme indicated that the approximate solution in explicit form accurately estimated the special hydraulic‐function parameters for calculating the SWC profile, cumulative infiltration, infiltration rate and wetting‐front distance in horizontal‐absorption experiments. An approximate solution in implicit form was also obtained with Nth order Taylor‐series expansions for an equation describing one‐dimensional, constant‐water‐head vertical infiltration. A large N was used to simulate SWC for soils with a large n, but this did not influence estimates of cumulative infiltration. The relation between infiltration rate and the inverse wetting‐front depth was not strictly linear for vertical infiltration, and the implicit method could be used to describe this nonlinear relation.

Highlights

A simple solution of the Richards equation is important to research soil water infiltration.

Least‐action and variational principles were used to analyse soil water content distribution.

Analytical solutions of a nonlinear Richards equation by special hydraulic functions were proposed.

A method was proposed to predict the infiltration and estimate soil hydraulic parameters.
Coupling effects of surface charges, adsorbed counterions and particle‐size distribution on soil water infiltration and transport
Authors: Gong Y. , Tian R. , Li H.
Published: August 2018

Soil pores are the channels for water transport. The surface charges, the non‐classic polarizabilities and concentrations of the adsorbed counterions in a soil determine soil particle interaction forces that affect soil pore status. Particle‐size distribution is another important factor that affects soil pore status. Therefore, surface charges, adsorbed counterions and particle‐size distribution would probably be coupled in soil water transport. In this study, two soils with different surface charge densities, different adsorbed counterions and different particle‐size distributions were used to study their coupling effects on soil water movement. The results showed that these factors were strongly coupled in soil water movement. When the soil electric field strength was strong (depending on surface charges, adsorbed counterion polarizabilities and concentrations), the net interaction forces of soil particles was repulsive, thus soil aggregates could be broken. The degree of aggregate breakdown coupled with particle‐size distribution determined soil water movement. For this case we found that (i) increasing attractive forces of soil particles could greatly improve soil water movement and (ii) water movement was slow when the soil had large clay or small silt or sand contents. When the soil electric field was weak, the net interaction force of soil particles was attractive, thus aggregates could not be broken. For this case we found that (i) further increasing the attractive forces of soil particles could not improve soil water movement and (ii) water movement was fast when the soil had large clay or small silt or sand contents.

Highlights

Coupling effects of particle size and particle interactions on soil water movement are not clear.

Large clay contents can decrease or increase soil water movement depending on soil particle interaction forces.

Fast water movement occurred in soil with strongly polarized cations and large clay content.

Particle interaction forces and particle‐size distribution were strongly coupled in soil water movement.
Fertilizer type and organic amendments affect gross N dynamics in a Chinese Chernozem
Authors: Li G. , Meng F. , Zhu P. , Lu C. , Yu W. , Müller C.
Published: August 2018

The effects of partial substitution of synthetic fertilizer N (NPK) with equal quantities of maize (Zea mays L.) stover N (50 kg ha−1, NPKS) or cattle manure N (115 N kg ha−1, NPKM) were investigated after 23 years with respect to maize yield, biomass N uptake, residual soil N and gross soil N dynamics in a fertile Chernozem soil. Maize yields were not different among these three treatments: maize biomass N uptake followed the order NPKM≈NPK > NPKS, whereas total N in soil was significantly larger under NPKM. A 15N tracing method was used to explain differences in gross N dynamics of labile and recalcitrant organic N pools and total N in soil. The results showed that NPKS and NPKM compared with NPK increased gross N mineralization by 2.8 and 1.3 times, respectively. The NPKS decreased the gross rate of N nitrification by 14%, whereas NPKM increased it by 47% compared with NPK. The NPKS stimulated microbial competition for NH4+, whereas NPKM increased NO3− immobilization compared with NPK. Our results suggested that acceleration of the soil N cycle under NPKS provided the most likely reason for the small total N stock in soil. In contrast, large organic N input and considerable immobilization of NO3− to a recalcitrant pool was probably the reason for the large total N stock under NPKM.

Highlights

How do fertilizer regimes affect gross N dynamics and soil N stock in a Chernozem soil?

Changes in NH4+, NO3− and 15N enrichment were simulated by a two‐pool model.

Mineralization of recalcitrant organic N was the main source for NH4+.

Large organic N input and considerable immobilization of NO3− to a recalcitrant pool probably resulted in large total N stock under NPKM.
Co‐evolution of exploration‐exploitation strategy and weak‐strong ties portfolios: A longitudinal case study
Authors: Wu Jiebing , Wang Xiaoyan , Guo Bin
Published: August 2018

This paper explores the interactive relationship between exploration‐exploitation strategy and alliance portfolios evolution, through examining underlying motivations of the evolution of alliance portfolios along with firm strategy change. Based on a 20‐year longitudinal case analysis on a leading Chinese pharmaceutical manufacturer, we establish a three‐stage process model: (1) stage 1: under turbulent environment and with the consequent reduction in profitability, the firm implements exploration strategy and forms weak alliance portfolio; (2) stage 2: the firm transforms its strategy from exploration to exploitation and forms strong alliance portfolio; and (3) stage 3: as this single business firm transforms into a multibusiness firm, it tends to make a balance between exploration and exploitation strategy and form weak‐strong alliance portfolio. Based on this process model, this study reveals the diverse motivations of alliance portfolios evolution along with firm strategy change, the interplay mechanisms between exploration‐exploitation strategy and weak‐strong ties portfolios, and the portfolio effects across businesses within a firm.
Identification of key determinants in Porphyromonas gingivalis host‐cell invasion assays
Authors: Al‐Taweel Firas B. H. , Al‐Magsoosi Mohanad J. N. , Douglas Charles W. I. , Whawell Simon A.
Published: August 2018

The periodontal pathogen Porphyromonas gingivalis can invade host cells, a virulence trait which may contribute to the persistence of infection at subgingival sites. Whilst the antibiotic protection assay has been commonly employed to investigate and quantify P. gingivalis invasion, data obtained have varied widely and a thorough investigation of the factors influencing this is lacking. We investigated the role of a number of bacterial and host‐cell factors and report that the growth phase of P. gingivalis, source (laboratory strain vs. clinical strain), host‐cell identity (cell line vs. primary), host‐cell lysis method, and host‐cell passage number had no significant effect on bacterial invasion. However, incubation time, host‐cell seeding density, method of quantification (viable count vs. DNA), and whether host cells were plated or in suspension, were shown to influence invasion. Also, cells isolated by rapid adhesion to fibronectin exhibited higher levels of P. gingivalis invasion, possibly as a result of increased levels of active α5β1 integrin. Interestingly, this may represent a population of cells with stem cell‐like properties. This study provides important new information by identifying the most important factors that influence P. gingivalis invasion assays and may help to explain variations in the levels previously reported.
Resilience of seed production to a severe El Niño‐induced drought across functional groups and dispersal types
Authors: O'Brien Michael J. , Peréz‐Aviles Daniel , Powers Jennifer S.
Published: August 2018

More frequent and severe El Niño Southern Oscillations (ENSO) are causing episodic periods of decreased rainfall. Although the effects of these ENSO‐induced droughts on tree growth and mortality have been well studied, the impacts on other demographic rates such as reproduction are less well known. We use a four‐year seed rain dataset encompassing the most severe ENSO‐induced drought in more than 30 years to assess the resilience (i.e., resistance and recovery) of the seed composition and abundance of three forest types in a tropical dry forest. We found that forest types showed distinct differences in the timing, duration, and intensity of drought during the ENSO event, which likely mediated seed composition shifts and resilience. Drought‐deciduous species were particularly sensitive to the drought with overall poor resilience of seed production, whereby seed abundance of this functional group failed to recover to predrought levels even two years after the drought. Liana and wind‐dispersed species were able to maintain seed production both during and after drought, suggesting that ENSO events promote early successional species or species with a colonization strategy. Combined, these results suggest that ENSO‐induced drought mediates the establishment of functional groups and dispersal types suited for early successional conditions with more open canopies and reduced competition among plants. The effects of the ENSO‐induced drought on seed composition and abundance were still evident two years after the event suggesting the recovery of seed production requires multiple years that may lead to shifts in forest composition and structure in the long term, with potential consequences for higher trophic levels like frugivores.
Royal Geographical Society (with IBG) Medals and Awards celebration 2018
Authors: Crane Nicholas , Larner Wendy , Macklin Mark , Malhi Yadvinder , Rose Paul , Vira Bhaskar
Published: August 2018

The Royal Geographical Society (with IBG) annual Medals and Awards recognise achievements in researching, communicating and teaching a wide range of geographical knowledge. The speeches and citations are a record of the 2018 celebration, with contributions from Professors Wendy Larner, Mark Macklin, Yadvinder Malhi, Bhaskar Vira, and Paul Rose. The speeches include comments on: the importance of geography for solving the most pressing of societal challenges; inspiring others through teaching, public engagement and leadership; interdisciplinarity and the pursuit of common intellectual agendas; fostering environmentally, economically and socially just futures; interconnections and exploration of the ecological world; and the value of field science.
JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities
Authors: Kang Changkeun , Saso Kayoko , Ota Kazushige , Kawazu Masahito , Ueda Takeshi , Okada Hitoshi
Published: August 2018

Obesity is a serious global health issue; however, the roles of genetics and epigenetics in the onset and progression of obesity are still not completely understood. The aim of this study was to determine the role of Kdm4b, which belongs to a subfamily of histone demethylases, in adipogenesis and fat metabolism in vivo. We established conditional Kdm4b knockout mice. Inactivation of Kdm4b in adipocytes (K4bKO) induced profound obesity in mice on a high fat diet (HFD). The HFD‐fed K4bKO mice exhibited an increased volume of fat mass and higher expression levels of adipogenesis‐related genes. In contrast, the genes involved in energy expenditure and mitochondrial functions were down‐regulated. Supporting these findings, the energy expenditure of Kdm4b‐deficient cells was markedly decreased. In addition, progression of glucose intolerance and hepatic steatosis with hepatocellular damages was observed. These data indicate that Kdm4b is a critical regulator of systemic metabolism via enhancing energy expenditure in adipocytes.
Teaching & Learning Tips 11: Teaching a procedure
Authors: Ojevwe Cindy , Rana Jasmine , Burgin Susan
Published: August 2018

Challenge: Balancing patient‐centered clinical care with learner‐centered teaching in a clinical setting becomes particularly challenging when it comes to teaching procedures to trainees (e.g. biopsies, excisions, etc.). How can procedures be taught in a way that reinforces repetition and mastery without compromising patient safety, care, and comfort?
Health‐related quality of life in patients with cutaneous T‐cell lymphoma?
Authors: Holahan Heather M. , Farah Ronda S. , Fitz Sara , Mott Sarah L. , Ferguson Nkanyezi N. , McKillip Julie , Link Brian , Liu Vincent
Published: August 2018

Background

Little is currently known about health‐related quality of life (HRQoL) of patients with cutaneous T‐cell lymphoma (CTCL), a condition characterized by chronic, pruritic, visible lesions, features which may be uniquely influential.

Objective

The aim of this study was to establish baseline HRQoL data for patients with CTCL and identify its influencing factors.

Methods

Prospective, nonblinded survey design utilizing questionnaires including panels of QoL indices obtained from 105 patients with mycosis fungoides, Sezary syndrome, and CD30+ lymphoproliferative disorder. Chart review correlated QoL with year of disease onset/diagnosis, type/stage of disease, current/past therapies, and medical/psychiatric diagnoses.

Results

Psychiatric condition was significantly associated with symptoms (P < 0.01), emotions (P < 0.01), and functioning (P < 0.03) subscales along with overall composite measure (P < 0.01). High‐grade systemic therapy (OR = 5.28) showed greater increase in odds of a lower health state than low grade (OR = 1.54). The number of medical comorbidities was significantly related to itching (P < 0.01). Increased age was a protective factor with respect to the emotions (P < 0.01), functioning (P < 0.01), and overall composite (P < 0.01) but not predictive of symptoms. Lower income was associated with higher bother on the symptoms subscale.

Conclusions

HRQoL in CTCL appears related to a number of factors, including presence of a psychiatric condition, use of systemic (particularly high grade) therapy, number of medical comorbidities, and income.