bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities to Improve Symptom Control with Somatostatin Congeners in GEP-NETs: A Review of Key Issues
Authors: Anthony Lowell B. , O'Dorisio Thomas M.
Published: June 2021

Octreotide acetate (octreotide) is the most prescribed and most studied somatostatin congener, or analog, for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and carcinoid syndrome, the latter of which may be characterized by debilitating diarrhea and flushing. Approved in the U.S. more than 30 years ago, octreotide is widely used to control the symptoms of carcinoid syndrome and has been shown to demonstrate antiproliferative activity. The two formulations available in the U.S. include a subcutaneous immediate-release (IR) injection introduced in 1989 and a long-acting repeatable (LAR) intramuscular injection approved in 1999. Lanreotide depot (lanreotide), a more recent somatostatin congener, has been available in the U.S. since 2014.

Despite widespread use of octreotide LAR, several key challenges exist with the current depot-based treatment paradigm. Studies indicate that LAR formulations are associated with continued unmet patient needs, owing in part to a loss of bioactivity over time that may necessitate progressive supplemental treatment with IR octreotide to adequately control symptoms. Clinicians should understand the key differences in the pharmacokinetic profiles of the LAR and IR formulations that may contribute to bioactivity loss and somatostatin receptor desensitization. In addition, there is a need to re-evaluate the role of IR octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms.

The purpose of this review is to explore all these issues and to re-establish a rationale for the IR formulation, particularly with respect to novel use cases and its use during the COVID-19 pandemic.

Implications for Practice

There is a need to re-evaluate the role of immediate-release octreotide in combination with depot therapy to provide consistent bioavailability and better control of carcinoid syndrome symptoms.
Effect of dispensing rate on internal void formation in restorations built with sonically activated resin composite
Authors: Irmak Özgür , Demirel Gülbike , Orhan Ayşe Işıl , Orhan Kaan
Published: June 2021

Internal void formation in sonically activated resin composite (SonicFill 2, Kavo Kerr, Orange, CA, USA) applied at three different extrusion force magnitudes was evaluated. Forty SonicFill 2 composite compules were divided into four groups according to dispensing method and magnitude of extrusion force as follows: No sonic energy/manual dispensing (FM) (control), sonic energy with low extrusion force (F1), sonic energy with medium extrusion force (F3), and sonic energy with high extrusion force (F5) (n = 10). For F1, F3, and F5, sonic energy was delivered using a SonicFill handpiece. For the control, no sonic energy was applied. Composites were placed into the molds and polymerized. Micro‐computed tomography scanning for intrarestoration void assessment was performed and intrarestoration void rates (%) were calculated. Data were statistically analyzed (α = 0.05). Sonic energy yielded lower intrarestoration void rates than that of the control (10.58% ± 1.74%) (p < 0.05). Intrarestoration void rates between F1 (8.11% ± 0.99%) and F3 (7.00% ± 0.95%) were similar (p > 0.05), whereas F5 (5.14 ± 0.91%) led to significantly lower void rates compared to F1 and F3 (p < 0.05). The highest extrusion force (F5) setting of the SonicFill handpiece caused the lowest internal void rates in SonicFill 2 resin composite restorations compared to those of the medium (F3) and lowest (F1) settings.
From sample preparation to NMR‐based metabolic profiling in food commodities: The case of table olives
Authors: Beteinakis Stavros , Papachristodoulou Anastasia , Mikros Emmanuel , Halabalaki Maria
Published: June 2021

Introduction

Nuclear magnetic resonance (NMR)‐based metabolic profiling has been widely used in food and plant sciences. Despite its simplicity and inherent reproducibility, the determination of the appropriate pre‐processing procedures greatly affects the obtained metabolic profile.

Objectives

The current study represents a detailed guide of use for untargeted NMR‐based metabolic profiling of table olives (Olea europaea L.).

Methods

Greek Kalamon table olives from different geographical origins were selected as reference materials. Differently treated samples were extracted using different solvents and/or solvent systems. Chemical profiles were evaluated with high‐performance thin layer chromatography (HPTLC). Different deuterated solvents and sample concentrations were evaluated for the recording of optimal quality spectra.

Results

The methanol extract of freeze‐dried table olives was found to contain the most representative secondary metabolites, in higher concentrations, as well. The optimal deuterated solvent for the NMR analysis was methanol‐d4, while final sample concentration should be within the range of 10 to 15 mg/mL. Multivariate data analysis was also used to estimate and confirm the variation and clustering caused by different characteristics of the samples.

Conclusions

Results of the present study make evident the necessity for thorough planning and method development prior to any extensive metabolomic study based on NMR spectroscopy. Pre‐processing and sample preparation stages seemed to greatly affect the metabolic profile and spectral quality in the case of table olives, which by extrapolation could apply to other food commodities. Nevertheless, the nature of the samples must be fully described in general, in order to proceed to solid conclusions.
Exploring the lived experience of partners of women impacted by cervical cancer and the CervicalCheck screening failure in Ireland
Authors: D’Alton Paul , Craddock Fiona , Bergin Niamh , Lynch Julie
Published: June 2021

Key Points

The aim of the study was to explore partners’ experiences of cervical cancer and perspectives on the CervicalCheck controversy.

Seven male partners of women who were diagnosed with cervical cancer following a false‐negative screening result were interviewed between May and July 2020.

Thematic analysis was conducted on the data. Three superordinate themes were identified; the adverse impact of a cervical cancer diagnosis on partners; the unsatisfactory treatment of partners throughout the trajectory of cervical cancer diagnosis and treatment, and partners’ attitudes surrounding the CervicalCheck controversy.

The findings highlight the unique challenges experienced by the partners of women diagnosed with cervical cancer and the impact of the CervicalCheck screening failure on partners.

The findings also highlight the need for appropriate structures to be established within Ireland's health service to better support the informational and psychological needs of partners of women with cervical cancer.
Aromatic compounds that attract Meloidogyne species second‐stage juveniles in soil
Authors: Oka Yuji
Published: June 2021

BACKGROUND

Nematode attractants could serve in nematode control strategies by combining with chemical or biological nematicides or by interrupting the nematodes' host‐finding process. The attractiveness of some benzenoid aromatic compounds, mainly benzoic acids, alcohols, aldehydes and phenols, to second‐stage juveniles (J2) of four Meloidogyne species (M. hapla, M. incognita, M. javanica and M. marylandi) was evaluated by using trap tubes and balls filled with washed dune sand buried in nematode‐inoculated sand in Petri dishes.

RESULTS

Two‐methoxybenzaldehyde, 2‐methoxycinnamaldehyde, 2‐hydroxybenzoic acid (salicylic acid), 2‐hydroxy‐3‐methoxybenzaldehyde (o‐vanillin), 3‐methoxybenzoic acid, 4‐methoxybenzoic acid and trans‐cinnamic acid effectively attracted J2 of all or most of the four Meloidogyne species to trap tubes in a one‐compound assay. When nematodes were exposed to three different compounds simultaneously in the three‐compound assay, J2 of all Meloidogyne species were attracted mainly to 2‐methoxycinnamaldehyde, salicylic acid and 4‐methoxybenzoic acid. Exceptions were M. hapla J2, which were not attracted to salicylic acid. In the soil column assay, M. javanica and M. incognita J2 were attracted upward to 4‐methoxybenzoic acid in a trap ball located 4 or 8 cm above the inoculation point, whereas salicylic acid and 3‐methoxybenzoic acid demonstrated slight, if any attraction.

CONCLUSION

Although some of the tested compounds exist in root exudates, it is not clear whether they are involved in the nematode host‐searching process in nature. The attractants found in the study have potential for use in Meloidogyne species control, probably as a nematode trap constituent or as compounds that disrupt the nematodes' host‐finding process. © 2021 Society of Chemical Industry.
Role of red blood cell distribution width, as a prognostic indicator in COVID‐19: A systematic review and meta‐analysis
Authors: Sarkar Soumya , Kannan Sundara , Khanna Puneet , Singh Akhil Kant
Published: June 2021

The red blood cell distribution width (RDW), an indicator of anisocytosis has emerged as a potential tool for risk stratification of critically ill patients with sepsis. Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in this ongoing context of the Coronavirus Disease 2019 (COVID‐19) pandemic. The current systematic review and meta‐analysis aims to explore the utility of RDW in the prognosis of COVID‐19 patients. A comprehensive screening of electronic databases was performed up to 30th April 2021 after enrolling in PROSPERO (CRD42020206685). Observational studies or interventional studies, evaluating the impact of RDW in COVID‐19 outcomes (mortality and severity) are included in this meta‐analysis.Our search retrieved 25 studies, with a total of 18,392 and 3,446 COVID‐19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher RDW levels on admission in comparison to survivors and non‐severe patients (SMD = 0.46; 95%CI 0.31–0.71; I2 = 88% and SMD = 0.46; 95%CI 0.26–0.67; I2 = 60%, respectively). In a sub‐group analysis of 2,980 patients, RDW > 14.5 has been associated with increased risk of mortality (OR = 2.73; 95%CI 1.96–3.82; I2 = 56%). However, the evidences is of low quality. A higher level of RDW on admission in COVID‐19 patients is associated with increased morbidity and mortality. However, further studies regarding the cut‐off value of RDW are the need of the hour.
Probing an Interfacial Ionic Pairing‐Induced Molecular Dipole Effect in Ionovoltaic System
Authors: Yoon Sun Geun , Park Byoung Joon , Jin Huding , Lee Won Hyung , Han Junghyup , Cho Yong Hyun , Yook Hyunwoo , Han Jeong Woo , Kim Youn Sang
Published: June 2021

A surficial molecular dipole effect depending on ion‐molecular interactions has been crucial issues regarding to an interfacial potential, which can modulate solid electronic and electrochemical systems. Their properties near the interfacial region can be dictated by specific interactions between surface and adsorbates, but understandings of the corresponding details remain at interesting issues. Here, intuitive observations of an ionic pair formation‐induced interfacial potential shifts are presented with an ionovoltaic system, and corresponding output signal variations are analyzed in terms of the surficial dipole changes on self‐assembled monolayer. With aiding of photoelectron spectroscopies and density function theory simulation, the ionic pair formation‐induced potential shifts are revealed to strongly rely on a paired molecular structure and a binding affinity of the paired ionic moieties. Chemical contributions to the binding event are interrogated in terms of polarizability in each ionic group and consistent with chaotropic/kosmotropic character of the ionic groups. Based on these findings, the ionovoltaic output changes are theoretically correlated with an adsorption isotherm reflecting the molecular dipole effect, thereby demonstrating as an efficient interfacial molecular probing method under electrolyte interfacing conditions.
Characterization of phenotypic spectrum of fetal heterotaxy syndrome by combining ultrasound and magnetic resonance imaging
Authors: Seidl‐Mlczoch E. , Kasprian G. , Ba‐ssalamah A. , Stuempflen M. , Kitzmueller E. , Muin D. A. , Zimpfer D. , Prayer D. , Michel‐behnke I. , Ulm B.
Published: June 2021

Objective

Heterotaxy or isomerism of the atrial appendages is a congenital disorder with variable presentation, associated with both cardiac and non‐cardiac anomalies, which may have a serious impact on fetal outcome. The aim of this exploratory study was to assess the value of fetal magnetic resonance imaging (MRI), as a complementary tool to ultrasound, for describing the morphological spectrum encountered in heterotaxy.

Methods

This retrospective study included 27 fetuses that underwent fetal MRI following prenatal suspicion of heterotaxy on ultrasound from 1998 to 2019 in a tertiary referral center. Heterotaxy was classified as left atrial isomerism (LAI) or right atrial isomerism (RAI) based on fetal echocardiography (FE) examination. In addition to routine prenatal ultrasound, fetal MRI was offered routinely to enhance the diagnosis of non‐cardiac anomalies, which might have been missed on ultrasound. Prenatal findings on ultrasound, FE and MRI were reviewed systematically and compared with those of postnatal imaging and autopsy reports.

Results

Twenty‐seven fetuses with heterotaxy and cardiovascular pathology, of which 19 (70%) had LAI and eight (30%) had RAI, were included. Seven (7/19 (37%)) fetuses with LAI had normal intracardiac anatomy, whereas all fetuses with RAI had a cardiac malformation. All 27 fetuses had non‐cardiac anomalies on fetal MRI, including situs and splenic anomalies. In 12/19 (63%) fetuses with LAI, a specific abnormal configuration of the liver was observed on MRI. In three fetuses, fetal MRI revealed signs of total anomalous pulmonary venous connection obstruction. An abnormal bronchial tree pattern was suspected on prenatal MRI in 6/19 (32%) fetuses with LAI and 3/8 (38%) fetuses with RAI.

Conclusions

Visualization on MRI of non‐cardiac anomalies in fetuses with suspected heterotaxy is feasible and can assist the complex diagnosis of this condition, despite its limitations. This modality potentially enables differentiation of less severe cases from more complex ones, which may have a poorer prognosis. Fetal MRI can assist in prenatal counseling and planning postnatal management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
MRI characterization of hemodynamic patterns of human fetuses with cyanotic congenital heart disease
Authors: Sun L. , van Amerom J. F. P. , Marini D. , Portnoy S. , Lee F.‐T. , Saini B. S. , Lim J. M. , Aguet J. , Jaeggi E. , Kingdom J. C. , Macgowan C. K. , Miller S. P. , Huang G. , Seed M.
Published: June 2021

Objectives

To characterize, using magnetic resonance imaging (MRI), the distribution of blood flow and oxygen transport in human fetuses with subtypes of congenital heart disease (CHD) that present with neonatal cyanosis.

Methods

Blood flow was measured in the major vessels of 152 late‐gestation human fetuses with CHD and 40 gestational‐age‐matched normal fetuses, using cine phase‐contrast MRI. Oxygen saturation (SaO2) was measured in the major vessels of 57 fetuses with CHD and 40 controls.

Results

Compared with controls, we found lower combined ventricular output in fetuses with single‐ventricle physiology, with the lowest being observed in fetuses with severe forms of Ebstein's anomaly. Obstructive lesions of the left or right heart were associated with increased flow across the contralateral side. Pulmonary blood flow was reduced in fetuses with Ebstein's anomaly, while those with Ebstein's anomaly and tricuspid atresia had reduced umbilical flow. Flow in the superior vena cava was elevated in fetuses with transposition of the great arteries, normal in fetuses with hypoplastic left heart, tetralogy of Fallot or tricuspid atresia and reduced in fetuses with Ebstein's anomaly. Umbilical vein SaO2 was reduced in fetuses with hypoplastic left heart or tetralogy of Fallot. Ascending aorta and superior vena cava SaO2 were reduced in nearly all CHD subtypes.

Conclusions

Fetuses with cyanotic CHD exhibit profound changes in the distribution of blood flow and oxygen transport, which result in changes in cerebral, pulmonary and placental blood flow and oxygenation. These alterations of fetal circulatory physiology may influence the neonatal course and help account for abnormalities of prenatal growth and development that have been described in newborns with cyanotic CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Oestrogen responsive vulvovaginal lipoma in an intact Siberian Husky
Authors: Yoon Jin , Vinayak Arathi , Whitley Derick B. , Kiupel Matti
Published: June 2021

A 7‐year‐old, intact female, Siberian Husky was presented for a vulvovaginal tumour noted 6 months prior to presentation. The tumour had doubled with each oestrus cycle. Haematology and serum biochemistry, thoracic and abdominal imaging were unremarkable. The cytology of the tumour was most consistent with a lipoma. Due to increasing size and discomfort from the tumour, excision and ovariohysterectomy were elected by the owner. Histopathology revealed a lipoma with no smooth muscle. Immunohistochemical labelling for oestrogen receptors revealed strong nuclear expression in adipocytes within the tumour. Immunohistochemical labelling for progesterone receptors was negative. Based on these findings, the tumour was diagnosed as an oestrogen responsive lipoma. One‐year post surgery, the patient is doing well with no recurrence of the tumour noted on physical examination. In addition to hormone responsive smooth muscle tumours, hormone responsive lipomas should be considered as a differential diagnosis for tumours in the reproductive tract that grows during oestrus cycles.
The Image of Marshal Mannerheim, Moral Panic, and the Refashioning of the Nation in the 1990s
Authors: Tepora Tuomas
Published: June 2021

This chapter shows how the social and political changes in Finnish society in the early 1990s were reflected in the images of C. G. E. Mannerheim (1867–1951), the Marshal of Finland. By looking at the debate concerning the construction of the Museum of Contemporary Art right next to the Mannerheim equestrian statue in Helsinki, Tepora analyzes the public dispute as a moral panic that sprang from the 1990s recession, the collapse of the Soviet Union, and joining the European Union. Arguing for the study of nontotalitarian personality cults, Tepora shows how the opposing sides in the debate either rose to defend the conservative Mannerheim image as an unchanging emotional figure or recoded the figure to reflect their liberal and cosmopolitan perspectives.
The History of Experience: Afterword
Authors: Hoegaerts Josephine , Olsen Stephanie
Published: June 2021

This short thought piece focuses on the novel contributions the authors of Lived Nation make to the study of the nation, and to the new history of experience. It discusses the historiographical origins of the new history of experience, especially in its links to the history of emotions, and the boundaries of this exciting new historical approach. It further points to promising innovations as other subfields start to implement this approach, specifically in the history of childhood and youth, and the history of disability.
Temporalization of Experiencing: First-Hand Experience of the Nation in Mid-Nineteenth Century Finland
Authors: Kokko Heikki
Published: June 2021

Kokko tests and develops further Benedict Anderson’s thesis about “imagined communities” through analyzing the experiential change that the emerging of first-hand experience of the nation required at the individual level. The analysis of readers’ letters published in the Finnish-language press provides a rare history-from-below approach to the emerging experience of the nation. Besides focusing on the mid-1800s’ Finnish grass roots experience of the nation, the chapter draws attention to the form of belonging which existed prior to it. ‘Temporalization of Experiencing’ presents the first-hand experience of the nation as a social phenomenon. The chapter indicates that the absorbing of the experience of the nation was based on a transformation in the structures of experiencing that was linked to the modernization process.
National Belonging Through Signed and Spoken Languages: The Case of Finland-Swedish Deaf People in the Late Nineteenth and Early Twentieth Centuries
Authors: Lindberg Hanna
Published: June 2021

In the chapter, Lindberg analyzes the role of nationalism and language among the Finland-Swedish deaf people in the late nineteenth and early twentieth centuries in Finland. Although the deaf community in many cases defined itself as standing on the sidelines of national conflicts, Lindberg shows, by examining published letters by deaf persons belonging to the Swedish minority in Finland, how nationalism was incorporated into everyday experiences. Focusing on periods of language conflicts in Finnish society, Lindberg shows, furthermore, how the Swedish and Finnish languages were used to divide and spark conflict, while sign language united deaf people belonging to different linguistic groups in Finland.
Disentangling a deep learned volume formula
Authors: Craven Jessica , Jejjala Vishnu , Kar Arjun
Published: June 2021

Abstract

We present a simple phenomenological formula which approximates the hyperbolic volume of a knot using only a single evaluation of its Jones polynomial at a root of unity. The average error is just 2.86% on the first 1.7 million knots, which represents a large improvement over previous formulas of this kind. To find the approximation formula, we use layer-wise relevance propagation to reverse engineer a black box neural network which achieves a similar average error for the same approximation task when trained on 10% of the total dataset. The particular roots of unity which appear in our analysis cannot be written as e2πi/(k+2) with integer k; therefore, the relevant Jones polynomial evaluations are not given by unknot-normalized expectation values of Wilson loop operators in conventional SU(2) Chern-Simons theory with level k. Instead, they correspond to an analytic continuation of such expectation values to fractional level. We briefly review the continuation procedure and comment on the presence of certain Lefschetz thimbles, to which our approximation formula is sensitive, in the analytically continued Chern-Simons integration cycle.
Correction to: Effects of angiotensin II receptor blockers on serum levels of epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids in patients admitted to a cardiovascular center
Authors: Kato Yuka , Senda Asuna , Mukai Yuji , Yamashita Miki , Sasaoka Yuki , Hanada Minayo , Hongo Fuminori , Hirokami Mitsugu , Rane Anders , Inotsume Nobuo , Toda Takaki
Published: June 2021

A Correction to this paper has been published: 10.1007/s00228-021-03092-2
Dynamic Molecular Evolution of Mammalian Homeobox Genes: Duplication, Loss, Divergence and Gene Conversion Sculpt PRD Class Repertoires
Authors: Lewin Thomas D. , Royall Amy H. , Holland Peter W. H.
Published: June 2021

The majority of homeobox genes are highly conserved across animals, but the eutherian-specific ETCHbox genes, embryonically expressed and highly divergent duplicates ofCRX, are a notable exception. Here we compare the ETCHbox genes of 34 mammalian species, uncovering dynamic patterns of gene loss and tandem duplication, including the presence of a large tandem array ofLEUTXloci in the genome of the European rabbit (Oryctolagus cuniculus). Despite extensive gene gain and loss, all sampled species possess at least two ETCHbox genes, suggesting their collective role is indispensable. We find evidence for positive selection and show thatTPRX1andTPRX2have been the subject of repeated gene conversion across the Boreoeutheria, homogenising their sequences and preventing divergence, especially in the homeobox region. Together, these results are consistent with a model where mammalian ETCHbox genes are dynamic in evolution due to functional overlap, yet have collective indispensable roles.
Hyphal growth of Penicillium rubens in changing relative humidity
Authors: Ruijten Philip , Huinink Hendrik P. , Adan Olaf C. G.
Published: June 2021

When considering mold prevention strategies, the environmental conditions in which fungi grow need to be taken into consideration. This environment is often characterized by a time-dependent relative humidity, and porous substrate. Growth has mainly been investigated in steady-state experiments. Therefore, the goal of this study is to understand the hyphal growth of Penicillium rubens on porous gypsum, under dynamic humidity conditions. Spores of P. rubens were inoculated on porous gypsum containing nutrients, and placed in a small incubation chamber, allowing for microscopic hyphal observation. The relative humidity in this chamber varied multiple times between a high (close to 100%) and low value (35%, 55%, or 75%). The hyphae reacted to a lowered relative humidity by an immediate growth stop and dehydration. When the relative humidity was increased again, the hyphae re-hydrated and three responses were found: regrowing after approximately 4 h, after a time equal to the germination time, or no regrowth at all. No substantial regrowth was found for fluctuations faster than 4 h. This time-scale was found for multiple decreases in relative humidity, and has been reported for the first time.

Key points

• Hyphae restart growth after a characteristic time of approximately 4 h.

• Relative humidity fluctuations of 3 h can suppress hyphal growth.

• Hyphae do not regrow after a severe desiccation and short periods of high humidity.
Reduction of overtreatment without reduction of overdiagnosis in patients with differentiated thyroid cancer: mission impossible
Authors: Oblak Tjasa , Perhavec Andraz , Hocevar Marko , Peric Barbara
Published: June 2021

Purpose

Lateral neck nodal metastases are common in patients with differentiated thyroid cancer (DTC) and usually have an indolent nature. They may be detected via neck palpation or preoperative ultrasound (US) of the neck. We hypothesized that preoperative neck metastases detected with US did not affect regional recurrence or long-term survival.

Methods

A retrospective analysis of patients’ records treated for DTC at our institution between January 2006 and December 2016 was performed. Information about preoperative US of the neck, treatment, demographics, staging, and histopathology was obtained. The endpoints for the study were nodal recurrence and survival. Differences in survival were analyzed between three groups of patients divided by presence or lack of preoperative US and/or palpable cervical lymph nodes (PLN). Furthermore, the prognostic value of multiple variables was tested by univariate and multivariate analysis.

Results

There were 1108 patients with DTC, 221 males and 887 females. The median age was 48.3 years (range 3 to 86), the median time of observation was 68 months (range 0 to 142). Eight hundred sixty-two patients without PLN or preoperative US represented group 1, 112 patients with PLN were in group 2, and 134 patients without PLN and with preoperative US were in group 3. Only five patients had a regional recurrence, one died due to distant metastases. There was no statistically significant difference in survival between the groups (p = 0.841) and neck US was not significantly associated with overall survival neither in univariate nor in multivariate analysis.

Conclusion

In patients with DTC, the benefits of preoperative US of cervical lymph nodes are probably limited and “less is more” approach is advised.
Expression patterns of signalling molecules and transcription factors in the early rabbit embryo and their significance for modelling amniote axis formation
Authors: Plöger Ruben , Viebahn Christoph
Published: June 2021

The anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.
Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document
Authors: Massimi Luca , Peretta Paola , Erbetta Alessandra , Solari Alessandra , Farinotti Mariangela , Ciaramitaro Palma , Saletti Veronica , Caldarelli Massimo , Canheu Alexandre Casagrande , Celada Carlo , Chiapparini Luisa , Chieffo Daniela , Cinalli Giuseppe , Di Rocco Federico , Furlanetto Marika , Giordano Flavio , Jallo George , James Syril , Lanteri Paola , Lemarchand Christian , Messing-Jünger Martina , Parazzini Cecilia , Paternoster Giovanna , Piatelli Gianluca , Poca Maria. A. , Prabahkar Prab , Ricci Federica , Righini Andrea , Sala Francesco , Sahuquillo Juan , Stoodley Marcus , Talamonti Giuseppe , Thompson Dominic , Triulzi Fabio , Zucchelli Mino , Valentini Laura ,   International Experts - Jury of the Chiari & Syringomyelia Consensus Conference, “Milan, November 11–13, 2019”
Published: June 2021

Background

Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children.

Methods

A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale (“strongly disagree,” “disagree,” “agree,” “strongly agree”). Statements that were endorsed (“agree” or “strongly agree”) by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three).

Results

Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the “definition of radiological failure 24 month post-surgery.”

Conclusions

The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.
Sjögren’s syndrome: a systemic autoimmune disease
Authors: Negrini Simone , Emmi Giacomo , Greco Monica , Borro Matteo , Sardanelli Federica , Murdaca Giuseppe , Indiveri Francesco , Puppo Francesco
Published: June 2021

Sjögren’s syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren’s syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren’s syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren’s syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren’s syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren’s syndrome, starting from its pathogenesis to current therapeutic options.
Stories Told Together: Male Narratives of Non-Monogamous Bi+ and Heterosexual Men
Authors: Castro Aurelio
Published: June 2021

The stories we tell about our identities and sexual orientations shape how we perform gendered scripts and negotiate relationships with significant others. Previous literature inquired the styles and outcomes of consensual non-monogamous (CNM) relationships, but more research is need on how CNM men resist or abide to hegemonic models of masculinity. To understand how constructions of masculinity and conceptualizations of sexual orientation are embedded in CNMs, the study analysed the stories of non-monogamous Bi+ and heterosexual men. Following a critical narrative approach, the study inquired the diverse conceptualizations of masculinity, sexual orientation and relationship practices in the narratives of 20 non-monogamous Bi+ and heterosexual identified men. The semi-structured in-depth narrative interviews (105 min on average) were analyzed via Nvivo 12 and explored their stories of desire and the sense-making process of being sexually oriented to one or more genders and to one or more partner/s. Engaging in non-monogamy was signified as a relevant insight from their personal stories and/or from adopting new concepts of desire beyond the “love as a zero-sum game.” The latter theme was also shared by many heterosexual participants that, when negotiating a non-monogamous agreement, signified their attractions to more than one person as part of their personal identity. Finally, the paper discusses how non-monogamous spaces can offer a positive and safe space for bisexuals/Bi+ people to explore and reaffirm their identities, constantly challenged by biphobia, invisibility, and erasure. Experiences and stories of Italian cisgender Bi+ and heterosexual men cannot be generalized to the whole spectrum of masculinities within CNM spaces, and the study lacks how other gendered and sexual subjectivities construct masculinity. Diverse stories and construction of sexuality and gender can lead to similar relationship preferences and understanding how we signify them can greatly improve our understanding of intimacies.
Soil age and soil organic carbon content shape biochemical responses to multiple freeze–thaw events in soils along a postmining agricultural chronosequence
Authors: Rosinger Christoph , Bonkowski Michael
Published: June 2021

Freeze–thaw (FT) events exert a great physiological stress on the soil microbial community and thus significantly impact soil biogeochemical processes. Studies often show ambiguous and contradicting results, because a multitude of environmental factors affect biogeochemical responses to FT. Thus, a better understanding of the factors driving and regulating microbial responses to FT events is required. Soil chronosequences allow more focused comparisons among soils with initially similar start conditions. We therefore exposed four soils with contrasting organic carbon contents and opposing soil age (i.e., years after restoration) from a postmining agricultural chronosequence to three consecutive FT events and evaluated soil biochgeoemical responses after thawing. The major microbial biomass carbon losses occurred after the first FT event, while microbial biomass N decreased more steadily with subsequent FT cycles. This led to an immediate and lasting decoupling of microbial biomass carbon:nitrogen stoichiometry. After the first FT event, basal respiration and the metabolic quotient (i.e., respiration per microbial biomass unit) were above pre-freezing values and thereafter decreased with subsequent FT cycles, demonstrating initially high dissimilatory carbon losses and less and less microbial metabolic activity with each iterative FT cycle. As a consequence, dissolved organic carbon and total dissolved nitrogen increased in soil solution after the first FT event, while a substantial part of the liberated nitrogen was likely lost through gaseous emissions. Overall, high-carbon soils were more vulnerable to microbial biomass losses than low-carbon soils. Surprisingly, soil age explained more variation in soil chemical and microbial responses than soil organic carbon content. Further studies are needed to dissect the factors associated with soil age and its influence on soil biochemical responses to FT events.
Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients
Authors: Nteliopoulos Georgios , Page Karen , Hills Allison , Howarth Karen , Emmett Warren , Green Emma , Martinson Luke J. , Fernadez-Garcia Daniel , Hastings Robert , Guttery David S. , Kenny Laura , Stebbing Justin , Cleator Susan , Rehman Farah , Gleason Kelly L. T. , Sanela Andrijac , Ion Charlotte , Rushton Amelia J. , Rosenfeld Nitzan , Coombes R. Charles , Shaw Jacqueline A.
Published: June 2021

Purpose

There is growing interest in the application of circulating tumour DNA (ctDNA) as a sensitive tool for monitoring tumour evolution and guiding targeted therapy in patients with cancer. However, robust comparisons of different platform technologies are still required. Here we compared the InVisionSeq™ ctDNA Assay with the Oncomine™ Breast cfDNA Assay to assess their concordance and feasibility for the detection of mutations in plasma at low (< 0.5%) variant allele fraction (VAF).

Methods

Ninety-six plasma samples from 50 patients with estrogen receptor (ER)-positive metastatic breast cancer (mBC) were profiled using the InVision Assay. Results were compared to the Oncomine assay in 30 samples from 26 patients, where there was sufficient material and variants were covered by both assays. Longitudinal samples were analysed for 8 patients with endocrine resistance.

Results

We detected alterations in 59/96 samples from 34/50 patients analysed with the InVision assay, most frequently affectingESR1, PIK3CAandTP53. Complete or partial concordance was found in 28/30 samples analysed by both assays, and VAF values were highly correlated. Excellent concordance was found for most genes, and most discordant calls occurred at VAF < 1%. In longitudinal samples from progressing patients with endocrine resistance, we detected consistent alterations in sequential samples, most commonly inESR1andPIK3CA.

Conclusion

This study shows that both ultra-deep next-generation sequencing (NGS) technologies can detect genomic alternations even at low VAFs in plasma samples of mBC patients. The strong agreement of the technologies indicates sufficient reproducibility for clinical use as prognosic and predictive biomarker.
Anger Responses in Adolescents: Relationship with Punishment and Reward Sensitivity
Authors: Kreuze L. J. , de Jong P. J. , Bennik E. C. , Nauta M. H.
Published: June 2021

A substantial proportion of youth with anxiety disorders shows comorbid behavioral (anger) problems. Such comorbid profile is associated with low treatment effectiveness and negative (longterm) outcomes. This study was therefore designed to examine trait factors that may promote anger responding in adolescents. By presenting participants (N = 158, mean age = 15.7, 56% female) with a series of common anger-eliciting situations, we tested whether high reward sensitivity would be associated with anger via perceived non-reward, and high punishment sensitivity via perceived threat. In line with the hypotheses, an indirect effect of reward sensitivity on anger was found via perceived non-reward, and an indirect effect of punishment sensitivity on anger via perceived threat. The latter association also had an indirect effect via perceived non-reward. High punishment and reward sensitivity may thus set adolescents at risk for developing (comorbid) anger problems via heightened threat and non-reward perceptions.
Correction to: Barriers and Facilitators of Disclosing Domestic Violence to the UK Health Service
Authors: Heron Rebecca L. , Eisma Maarten C. , Browne Kevin
Published: June 2021

A correction to this paper has been published: https://doi.org/10.1007/s10896-021-00281-6
Guidelines and pitfalls of refraction microtremor surveys
Authors: Louie John N. , Pancha Aasha , Kissane B.
Published: June 2021

The geotechnical industry has widely adopted the refraction microtremor shear-wave velocity measurement technique, which is accepted by building authorities for evaluation of seismic site class around the world. Clark County and the City of Henderson, Nevada, populated their Earthquake Parcel Map with over 10,000 site measurements for building code enforcement, made over a 3-year period. 2D refraction microtremor analysis now allows engineers to image lateral shear-wave velocity variations and do passive subsurface imaging. Along with experience at a basic level, the ability to identify the “no energy area” and the “minimum-velocity envelope” on the slowness-frequency (p-f) image helps practitioners to assess the quality of their ReMi data and analysis. Guides for grading (p-f) image quality, and for estimating depth sensitivity, velocity-depth tradeoffs, and depth and velocity resolution also assist practitioners in deciding whether their refraction microtremor data will meet their investigation objectives. Commercial refraction microtremor surveys use linear arrays, and a new criterion of 2.2% minimum microtremor energy in the array direction allows users to assess the likelihood of correct results. Unfortunately, any useful and popular measurement technique can be abused. Practitioners must follow correct data collection, analysis, interpretation, and measurement procedures, or the results cannot be labeled “refraction microtremor” or “ReMi” results. We present some of the common mistakes and provide solutions with the objective of establishing a “best practices” template for getting consistent, reliable models from refraction microtremor measurements.
Leveraging Transmedia storytelling to engage tourists in the understanding of the destination’s local heritage
Authors: Dionisio Mara , Nisi Valentina
Published: June 2021

Transmedia Stories are becoming an increasingly important technique for the tourism industry. They are successful tools to engage, inspire and gather audiences online and offline. In this article, we describe the design, implementation and evaluation of Fragments of Laura, a bespoke Transmedia Storytelling (TS) experience designed to involve visitors in developing knowledge and awareness about the cultural and natural heritage of Madeira Island. Fragments of Laura (FoL) is composed of two interconnected components: a Location-Aware Multimedia Story, and a Hypermedia Platform populated with locally collected testimonies and interviews. Results from the extensive evaluation of Fragments of Laura, highlights the potential of interactive multimedia, TS in particular, in engaging tourists with the destination values and community. Our contribution is twofold, on one hand we extend on the state of the art of multimedia interactive storytelling, with the description of the Fragments of Laura TS artifact. On the other hand, results from FoL evaluation highlight how the artifact impacts on the tourism experience its implications for the design of future tourism driven TS experiences.
The dynamics of gene transcription with a periodic synthesis rate
Authors: Sun Qiwen , Jiao Feng , Yu Jianshe
Published: June 2021

The periodic transcription output is ubiquitously observed in an isogenic cell population. To understand mechanisms of cyclic behavior in transcription, we extend the gene activation process in the two-state model by assuming that the synthesis rate is periodic. We derive the analytical forms of the mean transcript level and the noise. The limits of them indicate that the mean level and the noise display periodic behaviors. Numerical examples strongly suggest that the transcription system with a periodic synthesis rate generates more noise than that with a constant rate but maintains transcription homeostasis in each period. It is also suggested that if the periodicity is not considered, the calculated noise may be greater than the real value.