bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcome of patients with metastatic melanoma of unknown primary in the era of novel therapy
Authors: Verver Danielle , Grünhagen Dirk J. , van Akkooi Alexander C. J. , Aarts Maureen J. B. , van den Berkmortel Franchette W. P. J. , van den Eertwegh Alfonsus J. M. , de Groot Jan Willem B. , Boers-Sonderen Marye J. , Haanen John B. A. G. , Hospers Geke A. P. , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn S. , Suijkerbuijk Karijn P. M. , Tije Albert J.ten , Vreugdenhil Gerard , Verhoef Cornelis , van der Veldt Astrid A. M.
Published: March 2021

Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), and it is unclear whether these patients benefit equally from novel therapies. In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and/or targeted therapy. OS was estimated using the Kaplan–Meier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnosis with poorer performance status, higher LDH, and central nervous system metastases. In crude analysis, median OS of cMKP or MUP patients was 12 months (interquartile range [IQR] 5 – 44) and 14 months (IQR 5 – not reached), respectively (P = 0.278). In adjusted analysis, OS in MUP patients was superior (hazard rate 0.70, 95% confidence interval 0.58–0.85; P < 0.001). As compared to patients with advanced and metastatic cMKP, MUP patients have superior survival in adjusted analysis, but usually present with poorer prognostic characteristics. In crude analysis, OS was comparable indicating that patients with MUP benefit at least equally from treatment with novel therapies.
Can a simple fall cause a rotator cuff tear? Literature review and biomechanical considerations
Authors: Nyffeler Richard W. , Schenk Nicholas , Bissig Philipp
Published: March 2021

Purpose

A simple fall on the shoulder is often referred to as minor trauma that cannot cause a tendon tear but at best reveal a pre-existing rotator cuff pathology. We wanted to know whether this statement was true. The purpose of our study was therefore to summarize the causes of acute rotator cuff tears reported in the literature and provide a biomechanical explanation for tendon tears diagnosed after a fall.

Method

We searched PubMed and included studies reporting rotator cuff tears occurring due to a trauma. The number of cases, the tendons involved, the age of the patients, and the nature of trauma were summarized. In addition, we noted any information provided by the authors on the pathogenesis of acute tendon ruptures.

Results

Sixty-seven articles with a total of 4061 traumatic rotator cuff tears met the inclusion criteria. A simple fall was the most common cause (725 cases) and the supraspinatus tendon was most frequently affected. The postulated pathomechanism is a sudden stretch of the tendon-muscle unit while contracting (eccentric loading).

Conclusion

A simple fall can cause an acute rotator cuff tear and fall-related tears are not restricted to young individuals. They can affect patients of any age. The stresses occurring within the rotator cuff during an attempt to cushion a fall may locally exceed the tensile strength of the tendon fibers and cause a partial or full-thickness tear.
Pneumothorax detection in chest radiographs: optimizing artificial intelligence system for accuracy and confounding bias reduction using in-image annotations in algorithm training
Authors: Rueckel Johannes , Huemmer Christian , Fieselmann Andreas , Ghesu Florin-Cristian , Mansoor Awais , Schachtner Balthasar , Wesp Philipp , Trappmann Lena , Munawwar Basel , Ricke Jens , Ingrisch Michael , Sabel Bastian O.
Published: March 2021

Objectives

Diagnostic accuracy of artificial intelligence (AI) pneumothorax (PTX) detection in chest radiographs (CXR) is limited by the noisy annotation quality of public training data and confounding thoracic tubes (TT). We hypothesize that in-image annotations of the dehiscent visceral pleura for algorithm training boosts algorithm’s performance and suppresses confounders.

Methods

Our single-center evaluation cohort of 3062 supine CXRs includes 760 PTX-positive cases with radiological annotations of PTX size and inserted TTs. Three step-by-step improved algorithms (differing in algorithm architecture, training data from public datasets/clinical sites, and in-image annotations included in algorithm training) were characterized by area under the receiver operating characteristics (AUROC) in detailed subgroup analyses and referenced to the well-established “CheXNet” algorithm.

Results

Performances of established algorithms exclusively trained on publicly available data without in-image annotations are limited to AUROCs of 0.778 and strongly biased towards TTs that can completely eliminate algorithm’s discriminative power in individual subgroups. Contrarily, our final “algorithm 2” which was trained on a lower number of images but additionally with in-image annotations of the dehiscent pleura achieved an overall AUROC of 0.877 for unilateral PTX detection with a significantly reduced TT-related confounding bias.

Conclusions

We demonstrated strong limitations of an established PTX-detecting AI algorithm that can be significantly reduced by designing an AI system capable of learning to both classify and localize PTX. Our results are aimed at drawing attention to the necessity of high-quality in-image localization in training data to reduce the risks of unintentionally biasing the training process of pathology-detecting AI algorithms.

Key Points

• Established pneumothorax-detecting artificial intelligence algorithms trained on public training data are strongly limited and biased by confounding thoracic tubes.

• We used high-quality in-image annotated training data to effectively boost algorithm performance and suppress the impact of confounding thoracic tubes.

• Based on our results, we hypothesize that even hidden confounders might be effectively addressed by in-image annotations of pathology-related image features.
Percutaneous transforaminal endoscopic discectomy in a nine-year-old patient with sciatica: case report, technical note and overview of the literature
Authors: Gadjradj P. S. , Harhangi B. S.
Published: March 2021

Percutaneous transforaminal endoscopic discectomy (PTED) is an alternative procedure to open microdiscectomy (OM) to treat sciatica caused by lumbar disk herniation. Even though robust evidence comparing PTED with OM is lacking, PTED is becoming increasingly popular to treat spinal disorders. In this technical report, the surgical technique and outcomes of PTED in a 9-year-old patient are described. Furthermore, an overview of the literature on full-endoscopic techniques to treat sciatica is given, showing that PTED is feasible, safe and effective to treat lumbar disk herniation in the pediatric population.
Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study
Authors: Bahls Martin , Leitzmann Michael F. , Karch André , Teumer Alexander , Dörr Marcus , Felix Stephan B. , Meisinger Christa , Baumeister Sebastian E. , Baurecht Hansjörg
Published: March 2021

Aims

Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke.

Methods and results

We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke.

Conclusions

These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased.

Graphic abstract
Vaginal treatment with lactic acid gel delays relapses in recurrent urinary tract infections: results from an open, multicentre observational study
Authors: Diebold Ruth , Schopf Bettina , Stammer Holger , Mendling Werner
Published: March 2021

Purpose

The main objective of this open, prospective, multicentre, observational study is to investigate the relapse rate and tolerability of lactic acid gels in adult female patients with recurrent urinary tract infections during routine practice.

Methods

Data were collected from patients undergoing intermittent short courses of intravaginal treatment with lactic acid gel for prevention of recurrent urinary tract infections. The observation period for individual patients was 4 months, aimed at covering four short courses of intravaginal treatment. Data on UTI relapses, tolerability, handling and satisfaction with the treatment were collected via patient diaries and physician assessments and comprised any adverse events (AEs).

Results

In total, 72 patients were treated. During the last 12 months prior to the study, patients had on average 4.0 UTIs. In the 4 months after commencing treatment, 63.5% of patients had no recurrence of UTI symptoms. Overall efficacy was rated by physicians as ‘excellent/good’ for 96.7% of patients. The patients’ overall acceptance of local treatment was high with 94.1% being ‘(very) satisfied’. Similarly, handling was rated as ‘(very) easy’ by 94.2% of patients. The tolerability was assessed as ‘highly tolerable/tolerable’ by over 98% of patients and physicians alike. Safety analyses reported six AEs of mild intensity, all of which had resolved by the end of the study.

Conclusion

Treatment with lactic acid gel may increase resilience against uropathogens, possibly preventing the need for antibiotic prevention of recurrent urinary tract infections. Treatment was positively assessed by the patients. The physician assessments corroborate these findings.

Trial registration number and date of registration

DRKS00016760, 18.02.2019.
Self-organizing mappings on the flag manifold with applications to hyper-spectral image data analysis
Authors: Ma Xiaofeng , Kirby Michael , Peterson Chris
Published: March 2021

A flag is a nested sequence of vector spaces. The type of the flag encodes the sequence of dimensions of the vector spaces making up the flag. A flag manifold is a manifold whose points parameterize all flags of a fixed type in a fixed vector space. This paper provides the mathematical framework necessary for implementing self-organizing mappings on flag manifolds. Flags arise implicitly in many data analysis contexts including wavelet, Fourier, and singular value decompositions. The proposed geometric framework in this paper enables the computation of distances between flags, the computation of geodesics between flags, and the ability to move one flag a prescribed distance in the direction of another flag. Using these operations as building blocks, we implement the SOM algorithm on a flag manifold. The basic algorithm is applied to the problem of parameterizing a set of flags of a fixed type.
Rock Stress Measurements for Unlined Pressure Tunnels: A True Triaxial Laboratory Experiment to Investigate the Ability of a Simplified Hydraulic Jacking Test to Assess Fracture Normal Stress
Authors: Ødegaard Henki , Nilsen Bjørn
Published: March 2021

To avoid hydraulic failure of unlined pressure tunnels, knowledge of minimum principal stress is needed. Such knowledge is only obtainable from in situ measurements, which are often time-consuming and relatively costly, effectively limiting the number of measurements typically performed. In an effort to enable more stress measurements, the authors propose a simplified and cost-effective stress measuring method; the Rapid Step-Rate Test (RSRT), which is based on existing hydraulic testing methods. To investigate the ability of this test to measure fracture normal stresses in field-like conditions, a true triaxial laboratory test rig has been developed. Hydraulic jacking experiments performed on four granite specimens, each containing a fracture, have been performed. Interpretation of pressure-, flow- and acoustic emission (AE) data has been used to interpret fracture behaviour and to assess fracture normal stresses. Our experimental data suggest that the proposed test method, to a satisfactory degree of reliability, can measure the magnitude of fracture normal stress. In addition, a clear correlation has been found between fracture closure and sudden increase in AE rate, suggesting that AE monitoring during testing can serve as a useful addition to the test. The rapid step-rate test is also considered relevant for field-scale measurements, with only minor adaptions. Our findings suggest that the RSRT can represent a way to get closer to the ideal of performing more testing along the entire length of pressure tunnel, and not only at key locations, which requires interpolation of stress data with varying degree of validity.
A Step Towards Optimization of the qNMR Workflow: Proficiency Testing Exercise at an GxP-Accredited Laboratory
Authors: Monakhova Yulia B. , Diehl Bernd W. K.
Published: March 2021

Quantitative nuclear magnetic resonance (qNMR) is considered as a powerful tool for multicomponent mixture analysis as well as for the purity determination of single compounds. Special attention is currently paid to the training of operators and study directors involved in qNMR testing. To assure that only qualified personnel are used for sample preparation at our GxP-accredited laboratory, weighing test was proposed. Sixteen participants performed six-fold weighing of the binary mixture of dibutylated hydroxytoluene (BHT) and 1,2,4,5-tetrachloro-3-nitrobenzene (TCNB). To evaluate the quality of data analysis, all spectra were evaluated manually by a qNMR expert and using in-house developed automated routine. The results revealed that mean values are comparable and both evaluation approaches are free of systematic error. However, automated evaluation resulted in an approximately 20% increase in precision. The same findings were revealed for qNMR analysis of 32 compounds used in pharmaceutical industry. Weighing test by six-fold determination in binary mixtures and automated qNMR methodology can be recommended as efficient tools for evaluating staff proficiency. The automated qNMR method significantly increases throughput and precision of qNMR for routine measurements and extends application scope of qNMR.
Differences in the expression of caveolin-1 isoforms in cancer-associated and normal fibroblasts of patients with oral squamous cell carcinoma
Authors: Kaya S. , Wiesmann Nadine , Goldschmitt J. , Krüger M. , Al-Nawas B. , Heider J.
Published: March 2021

Objectives

For many years, tumor development has been viewed as a cell-autonomous process; however, today we know that the tumor microenvironment (TME) and especially cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression. Caveolin-1 (Cav-1) is a scaffolding protein which is involved in several cancer-associated processes as important component of the caveolae. Our goal was to shed light on the expression of the two different isoforms of Cav-1 in normal fibroblasts (NFs) and CAFs of patients with oral squamous cell carcinoma (OSCC).

Materials and methods

Fibroblasts from normal mucosa and CAFs were isolated and propagated in vitro. Gene expression of the different Cav-1 isoforms was assessed via quantitative real-time PCR (qPCR) and supplemented by protein expression analysis.

Results

We could show that the Cav-1β isoform is more highly expressed in NFs and CAFs compared to Cav-1α. Furthermore, the different Cav-1 isoforms tended to be differently expressed in different tumor stages. However, this trend could not be seen consistently, which is in line with the ambiguous role of Cav-1 in tumor progression described in literature. Western blotting furthermore revealed that NFs and CAFs might differ in the oligomerization profile of the Cav-1 protein.

Conclusion

These differences in expression of Cav-1 between NFs and CAFs of patients with OSCC confirm that the protein might play a role in tumor progression and is of interest for further analyses.

Clinical relevance

Our findings support a possible role of the two isoforms of Cav-1 in the malignant transformation of OSCC.
Correction to: Genome-wide association study identifies new loci for albuminuria in the Japanese population
Authors: Okuda Hiroshi , Okamoto Koji , Abe Michiaki , Ishizawa Kota , Makino Satoshi , Tanabe Osamu , Sugawara Junichi , Hozawa Atsushi , Tanno Kozo , Sasaki Makoto , Tamiya Gen , Yamamoto Masayuki , Ito Sadayoshi , Ishii Tadashi
Published: March 2021

A correction to this paper has been published: https://doi.org/10.1007/s10157-021-02053-4
Precise point positioning with GPS and Galileo broadcast ephemerides
Authors: Carlin Luca , Hauschild André , Montenbruck Oliver
Published: March 2021

For more than 20 years, precise point positioning (PPP) has been a well-established technique for carrier phase-based navigation. Traditionally, it relies on precise orbit and clock products to achieve accuracies in the order of centimeters. With the modernization of legacy GNSS constellations and the introduction of new systems such as Galileo, a continued reduction in the signal-in-space range error (SISRE) can be observed. Supported by this fact, we analyze the feasibility and performance of PPP with broadcast ephemerides and observations of Galileo and GPS. Two different functional models for compensation of SISREs are assessed: process noise in the ambiguity states and the explicit estimation of a SISRE state for each channel. Tests performed with permanent reference stations show that the position can be estimated in kinematic conditions with an average three-dimensional (3D) root mean square (RMS) error of 29 cm for Galileo and 63 cm for GPS. Dual-constellation solutions can further improve the accuracy to 25 cm. Compared to standard algorithms without SISRE compensation, the proposed PPP approaches offer a 40% performance improvement for Galileo and 70% for GPS when working with broadcast ephemerides. An additional test with observations taken on a boat ride yielded 3D RMS accuracy of 39 cm for Galileo, 41 cm for GPS, and 27 cm for dual-constellation processing compared to a real-time kinematic reference solution. Compared to the use of process noise in the phase ambiguity estimation, the explicit estimation of SISRE states yields a slightly improved robustness and accuracy at the expense of increased algorithmic complexity. Overall, the test results demonstrate that the application of broadcast ephemerides in a PPP model is feasible with modern GNSS constellations and able to reach accuracies in the order of few decimeters when using proper SISRE compensation techniques.
Central Asian wild tulip conservation requires a regional approach, especially in the face of climate change
Authors: Wilson Brett , Dolotbakov Aibek , Burgess Benjamin J. , Clubbe Colin , Lazkov Georgy , Shalpykov Kaiyrkul , Ganybaeva Myskalai , Sultangaziev Ormon , Brockington Samuel F.
Published: March 2021

Tulips (Tulipa spp.) are one of the most widely appreciated plants worldwide, nevertheless species taxonomy and biogeography are often poorly understood. Most wild tulips inhabit the mountains of Central Asia, a recognised biodiversity hotspot, and a centre of tulip diversity. Despite the presence of several country-level endemic Tulipa species, most taxa span the borders of several nations. With no globally Red Listed tulip taxa from this region national level conservation assessments are an important resource. Nonetheless, threats posed to tulips are still inadequately understood, especially climate change, and given the trans-national nature of most species, distributional information is restricted and often misleading. Here we collate 330 species records from the Global Biodiversity Information Facility with 85 newly collected records, to undertake species distribution modelling (MaxEnt) for ten native Central Asian species. This work showed that regional level models provide a much more comprehensive understanding of species’ extinction risks, proportions of habitat in different countries, and limitations in protected area coverage. Furthermore, our climate modelling, the first of its kind for tulips, suggests that climate change will have a significant negative impact on the range size of all species; including those that are currently widespread. We therefore add climate change to the list of threats affecting tulip populations in Central Asia, which already includes livestock overgrazing, urbanisation, wild collection, and mining. Overall, our work shows that although national information is important, a regional approach is crucial not just for tulip conservation efforts, but likely for Central Asian plant conservation in general.
Conservation genetics of the yellow-bellied toad (Bombina variegata): population structure, genetic diversity and landscape effects in an endangered amphibian
Authors: Pröhl Heike , Auffarth Jana , Bergmann Tjard , Buschmann Holger , Balkenhol Niko
Published: March 2021

Revealing patterns of genetic diversity and barriers for gene flow are key points for successful conservation in endangered species. Methods based on molecular markers are also often used to delineate conservation units such as evolutionary significant units and management units. Here we combine phylo-geographic analyses (based onmtDNA) with population and landscape genetic analyses (based on microsatellites) for the endangered yellow-bellied toadBombina variegataover a wide distribution range in Germany. Our analyses show that two genetic clusters are present in the study area, a northern and a southern/central one, but that these clusters are not deeply divergent. The genetic data suggest high fragmentation among toad occurrences and consequently low genetic diversity. Genetic diversity and genetic connectivity showed a negative relationship with road densities and urban areas surrounding toad occurrences, indicating that these landscape features act as barriers to gene flow. To preserve a maximum of genetic diversity, we recommend considering both genetic clusters as management units, and to increase gene flow among toad occurrences with the aim of restoring and protecting functional meta-populations within each of the clusters. Several isolated populations with especially low genetic diversity and signs of inbreeding need particular short-term conservation attention to avoid extinction. We also recommend to allow natural gene flow between both clusters but not to use individuals from one cluster for translocation or reintroduction into the other. Our results underscore the utility of molecular tools for species conservation, highlight outcomes of habitat fragmentation onto the genetic structure of an endangered amphibian and reveal particularly threatened populations in need for urgent conservation efforts.
Contact Versus Education: An Explorative Comparison Between the Contact and Education Strategy Considering Albinism Related Stigma in Tanzanian High Schools
Authors: De Groot T. M. M. , Meurs P. , Jacquet W. , Peters R. M. H.
Published: March 2021

Albinism in Tanzania causes fierce health-related stigma. Little research has focused on the impact of stigma reduction strategies aiming to reduce albinism related stigma. Therefore, this research assessed the impact of two short video interventions among high school students in Tanzania on their attitude towards people with albinism: a contact intervention (n = 95) and an education intervention (n = 97). A mixed method design was used. Directly before and after the interventions impact was measured among all participants through the Albinism Social Distance Scale for Adolescents (ASDS-A), knowledge items, and entertainment items. After these measurements focus group discussions were conducted, 16 in total (n = 80). Both interventions caused a significant increase in the levels of correct knowledge about albinism. The education intervention entailed a significant positive change in attitude measured through the ASDS-A, whereas the contact intervention did not have a significant effect. In terms of entertainment value, the respondents were more enthusiastic about the contact intervention. The study suggests that education interventions on their own can be a successful tool in decreasing albinism related stigma. Additionally, qualitative findings show many positive outcomes for the contact intervention. Therefore, we would recommend using a combination of these two interventions, which has also proved successful in the past. However, more research on the effect of a combination of the two strategies is recommended.
Wild Animals and Duties of Assistance
Authors: Jalagania Beka
Published: March 2021

Is there a moral requirement to assist wild animals suffering due to natural causes? According to the laissez-faire intuition, although we may have special duties to assist wild animals, there are no general requirements to care for them. If this view is right, then our positive duties toward wild animals can be only special, grounded in special circumstances. In this article I present the contribution argument which employs the thought that the receipt of benefits from wild animals is one such kind of special circumstance. If this argument is correct, then the circle of moral agents required to assist some wild animals is significantly widened.
Probabilistic Modelling for Incorporating Uncertainty in Least Cost Path Results: a Postdictive Roman Road Case Study
Authors: Lewis Joseph
Published: March 2021

The movement of past peoples in the landscape has been studied extensively through the use of least cost path (LCP) analysis. Although methodological issues of applying LCP analysis in archaeology have frequently been discussed, the effect of DEM error on LCP results has not been fully assessed. Due to this, the reliability of the LCP result is undermined, jeopardising how well the method can confidently be used to model past movement. To strengthen the reliability of LCP results, this research proposes the use of Monte Carlo simulation as a method for incorporating and propagating the effects of error on LCP results. Focusing on vertical error, random error fields are calculated and incorporated into the documented and reproducible LCP modelling process using the R packageleastcostpath. By graphically communicating the impact of vertical error using probabilistic LCPs, uncertainty in the results can be taken into account when interpreting LCPs. The method is applied to a Roman road case study, finding that the incorporation of vertical error results in the identification of multiple ‘least cost’ routes within the landscape. Furthermore, the deviation between the roman road and the probabilistic LCP suggests that the location of the roman road was influenced by additional factors other than minimising energy expenditure. This research finds that the probabilistic LCP derived using Monte Carlo simulation is a viable method for the graphical communication of the uncertainty caused by error within the input data used within the LCP modelling process. Therefore, it is recommended that probabilistic LCPs become the default approach when modelling movement using input data that contains errors.
Modelling inelastic Granular Media Using Dynamical Density Functional Theory
Authors: Goddard B. D. , Hurst T. D. , Ocone R.
Published: March 2021

We construct a new mesoscopic model for granular media using Dynamical Density Functional Theory (DDFT). The model includes both a collision operator to incorporate inelasticity and the Helmholtz free energy functional to account for external potentials, interparticle interactions and volume exclusion. We use statistical data from event-driven microscopic simulations to determine the parameters not given analytically by the closure relations used to derive the DDFT. We numerically demonstrate the crucial effects of each term and approximations in the DDFT, and the importance of including an accurately parametrised pair correlation function.
Corporate governance and IPO underpricing: evidence from the italian market
Authors: Teti Emanuele , Montefusco Ilaria
Published: March 2021

This paper aims to analyse the impact of firms’ corporate governance characteristics on the degree of first-day returns (i.e., underpricing) in the Italian initial public offering (IPO) market. In particular, this work investigates the impacts of the characteristics of boards of directors (BoDs) and ownership structure on the underpricing of newly offered shares. By studying a sample of 128 Italian IPOs between 2000 and 2016, it is concluded that corporate governance characteristics affect the degree of first-day returns following a company’s IPO. More specifically, the size of the BoD negatively affects underpricing, while the ownership of institutional investors and board members has a positive effect on the degree of underpricing. Conversely, no significant evidence is found with regard to board independence, the number of female directors in the boardroom, the implementation of stock option plans and ownership concentration.
Osteoblast role in the pathogenesis of rheumatoid arthritis
Authors: Berardi S. , Corrado A. , Maruotti N. , Cici D. , Cantatore F. P.
Published: March 2021

In the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, osteoarthritis, osteoporosis, alterations in osteoblast growth, differentiation and activity play a role. In particular, in rheumatoid arthritis bone homeostasis is perturbed: in addition to stimulating the pathologic bone resorption process performed by osteoclasts in course of rheumatoid arthritis, proinflammatory cytokines (such as Tumor Necrosis factor-α, Interleukin-1) can also inhibit osteoblast differentiation and function, resulting in net bone loss. Mouse models of rheumatoid arthritis showed that complete resolution of inflammation (with maximal reduction in the expression of pro-inflammatory factors) is crucial for bone healing, performed by osteoblasts activity. In fact, abnormal activity of factors and systems involved in osteoblast function in these patients has been described. A better understanding of the pathogenic mechanisms involved in osteoblast dysregulation could contribute to explain the generalized and focal articular bone loss found in rheumatoid arthritis. Nevertheless, these aspects have not been frequently and directly evaluated in studies. This review article is focused on analysis of the current knowledge about the role of osteoblast dysregulation occurring in rheumatoid arthritis: a better knowledge of these mechanisms could contribute to the realization of new therapeutic strategies.
EDXRF for screening micronutrients in lentil and sorghum biofortification breeding programs
Authors: Guild Georgia E. , Stangoulis James C. R.
Published: March 2021

Background and aims

This study explores the use of energy dispersive x-ray fluorescence (EDXRF) for screening micronutrient concentrations in lentil and sorghum grain for biofortification breeding programs.

Methods

Lentil and sorghum seed was provided from biofortification breeding programs and analysed with inductively coupled plasma mass spectrometry (ICP-MS) to determine the reference concentration levels of Ca, Mn, Fe, Cu and Zn. A subset of these samples was used to establish the EDXRF calibration and another subset used for validation of the method.

Results

The results show the EDXRF analyses of the lentil and sorghum are not significantly different to the reference ICP-MS for all elements analysed, except for Mn with %RSD of replicate analysis < 5 % for lentil analysis and < 10 % for sorghum.

Conclusions

EDXRF analysis enables rapid and accurate analysis of Ca, Mn, Fe, Cu and Zn in lentil and sorghum.
The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency
Authors: Smith Heather , Romero Beverly , Flood Emuella , Boney Anne
Published: March 2021

Purpose

Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic disorder characterized by a deficiency of the sucrase-isomaltase (SI) enzyme complex within the brush border membrane of the small intestine. Mutations in the SI gene result in abnormal synthesis and/or incorrect transport of the SI enzyme. Patients with CSID generally have reduced sucrase activity, but levels of isomaltase activity range from absent to almost normal. This study sought to better understand the experience of patients with CSID prior to, during, and after their diagnosis and its subsequent treatment with sacrosidase.

Methods

This was a cross-sectional interview study conducted in conjunction with a longitudinal, observational study of US patients prescribed and taking sacrosidase for at least three consecutive months as treatment for CSID. The observational study included both children and adults.

Results

This qualitative interview study explored the experiences of 43 adult and pediatric patients (n = 8 adults and n = 35 children/adolescents) with CSID pre-, during, and post-diagnosis. Findings suggest that a CSID diagnosis is particularly problematic given the disparate range of more commonly understood gastrointestinal (GI) disorders. After diagnosis and treatment with sacrosidase, participants reported considerable improvement in symptoms and health-related quality of life (HRQL), yet symptoms persist that continue to affect daily life, indicating areas of potential unmet need.

Conclusion

Educating clinicians about CSID may help improve the overall diagnosis experience. As this research is the first of its kind in CSID, additional research, qualitative and quantitative, will be important to furthering the understanding of HRQL impact and unmet need experienced by this population and identifying ways to best meet those needs.
Weighing the costs: the epistemic dilemma of no-platforming
Authors: Peters Uwe , Nottelmann Nikolaj
Published: March 2021

‘No-platforming’—the practice of denying someone the opportunity to express their opinion at certain venues because of the perceived abhorrent or misguided nature of their view(s)—is a hot topic. Several philosophers have advanced epistemic reasons for using the policy in certain cases. Here we introduce epistemic considerations against no-platforming that are relevant for the reflection on the cases at issue. We then contend that three recent epistemic arguments in favor of no-platforming fail to factor these considerations in and, as a result, offer neither a conclusive justification nor strong epistemic support for no-platforming in any of the relevant cases. Moreover, we argue that, taken together, our epistemic considerations against no-platforming and the three arguments for the policy suggest that no-platforming poses an epistemic dilemma (i.e., a difficult choice situation involving two equally undesirable options). While advocates and opponents of no-platforming alike have so far overlooked this dilemma, it should be addressed not only to prevent that actual no-platforming decisions create more epistemic harm than good, but also to put us into a better position to justify the policy when it is indeed warranted.
Riparian populations of minnesota reed canarygrass (Phalaris arundinacea) are most likely native, based on SNPs (DArTseqLD)
Authors: Noyszewski Andrzej K. , Anderson Neil O. , Smith Alan G. , Kilian Andrzej , Dalbotten Diana , Ito Emi , Timm Anne , Pellerin Holly , Kubátová Barbora , Kávová Tereza , Januš Vojtěch , Čurn Vladislav , Edwards Keith R. , Bastlová Daša , Květ Jan
Published: March 2021

The native vs. exotic status of reed canarygrass (RCG), a major invasive species of Minnesota wetlands, is unknown. The aim of this study was to investigate this native vs. exotic status to enhance its management. Genetic comparison of wild RCG populations from six Minnesota and six Czech Republic rivers was performed. A total of 2521 polymorphic SNP markers (single nucleotide polymorphisms) were used to evaluate 478 RCG samples across all collections. In the PCoA, all (n = 256) tested extant wild, riparian RCG genotypes from six Minnesota Rivers and six Czech Republic Rivers were genetically distinct, although some SNPs were common in both populations since they are the same species. DAPC analysis also resulted in the formation of two primary clusters separating the Minnesota Rivers and Czech Republic Rivers riparian samples, with little overlap; STRUCTURE analysis also supported this clustering with k = 4 groups as it separated the Czech Republic Rivers populations into three groups, along with Minnesota Rivers. The uniformity of PCoA, DAPC, STRUCTURE, and Evanno results indicates the distinct separation of Minnesota Rivers and Czech Republic Rivers populations. Portions of the genome (specific SNPs) are preserved or in common across continents, as indicated by STRUCTURE similarities. Nonetheless, overall significant SNP differences between the continents indicate that the Minnesota riparian populations are distinct enough from the European (Czech) collections to be delineated as native N. American RCG. PCoA of all the Minnesota RCG collections clustered Minnesota Rivers, Herbarium, Extant Herbarium, Research Field and Native Field collections together. STRUCTURE analysis (k = 2; Evanno) divided these Minnesota collections from the Commercial Field and Cultivars collections. There are two genetically distinct groups of RCG in Minnesota and since the Minnesota Rivers, the Research Field, the Native Field and pre-1930 herbaria collections clustered together, they are most likely native N. American types. Analysis of molecular variance (AMOVA) indicated that the genetic variation was more significant within, rather than among, the RCG populations. Native, historic herbaria types cluster together with all wild RCG river populations in Minnesota, all of which were distinct from those in Central Europe, suggesting native RCG type persistence in N. America. Also, cultivated forage types of RCG are distinct from wild RCG Minnesota river populations. The SNP genetic data shows that riparian Minnesota RCG populations are native. These data will facilitate future management strategies to control RCG as a native, but invasive, species.
Can a Bodily Theorist of Pain Speak Mandarin?
Authors: Nie Chenwei
Published: March 2021

According to a bodily view of pain, pains are objects which are located in body parts. This bodily view is supported by the locative locutions for pain in English, such as that “I have a pain in my back.” Recently, Liu and Klein (Analysis, 80(2), 262–272, 2020) carry out a cross-linguistic analysis, and they claim that (1) Mandarin has no locative locutions for pain and (2) the absence of locative locutions for pain puts the bodily view at risk. This paper rejects both claims. Regarding the philosophical claim, I argue that a language without locative locutions for pain only poses a limited challenge to the bodily view. Regarding the empirical claim, I identify the possible factors which might have misled Liu and Klein about the locative locutions for pain in Mandarin, and argue that Mandarin has a wide range of locative locutions for pain by conducting a corpus analysis. I conclude that compared to English, Mandarin lends no less, if not more, support to the bodily view of pain.
Plasmonic Coupler and Multiplexer/Demultiplexer Based on Nano-Groove-Arrays
Authors: Udupi Aparna , Madhava Sathish Kumar
Published: March 2021

A novel plasmonic unidirectional coupler and its extension to a multiplexer/demultiplexer are proposed and simulated. The proposed structure can be etched adjacent to metal-insulator-metal (MIM) waveguides which can result in considerable reduction in footprint of optical signal processing systems. Simulated results show very good agreement with design. Extinction ratio (ER) of more than 11 dB was achieved for both the coupler as well as the multiplexer/demultiplexer. Crosstalk as well as full width at half maximum (FWHM) was also highly acceptable for the multiplexer/demultiplexer. The proposed structures have an additional attractive feature of being amenable to integration with other relevant functionalities as demonstrated in the results.
Hoffa’s fat pad thickness: a measurement method with sagittal MRI sequences
Authors: Ricatti Giovanni , Veronese Nicola , Gangai Ilaria , Paparella Mariateresa , Testini Valentina , Guglielmi Giuseppe
Published: March 2021

Background

Hoffa’s fat pad is a structure located within the fibrous joint capsule of the knee joint, but outside the synovial cavity. It plays an important biomechanical and metabolic role in knee joint, reducing the impact of forces generated by loading and producing cytokines. Changes in its size can induce modifications in the knee homeostasis. However, a great variability exists regarding its measurements. This work aims to evaluate the reliability of a measurement method of Hoffa’s fat pad dimensions through MRI.

Methods

3T sagittal IW 2D TSE fat-suppressed MRI sequences, taken from the OAI (Osteoarthritis initiative) database, of 191 male and female patients, aged between 40 and 80 years, were analysed; a manual measurement of the thickness of Hoffa’s fat pad of each subject was then performed by two different readers. The interobserver reliability and intraobserver reliability of the measurements were described by coefficient of variation (CV), Pearson correlation and Bland–Altman plots.

Results

All statistical analyses have shown that not significant intra- or interobservers differences were evident (intraobserver CV % for the first observer was 2.17% for the right knee and 2.24% for the left knee, while for the second observer 2.31% for the right knee and 2.24% for the left knee; linear correlation was for the first observer r = 0.96 for the right knee and r = 0.96 for the left knee, while for the second observer r = 0.97 for the right knee and r = 0.96 for the left knee; in addition, the interobserver CV % was 1.25% for the right knee and 1.21% for the left knee and a high interobserver linear correlation was found: r = 0.97 for the right knee and r = 0.96 for the left knee).

All results suggest that this manual measurement method of Hoffa’s fat pad thickness can be performed with satisfactory intra- and interobserver reliability.

Conclusions

Hoffa’s fat pad thickness can be measured, using sagittal MRI images, with this manual method that represents, for his high reliability, an effective means for the study of this anatomical structure.
Quo vadis? Historical distribution and impact of climate change on the worldwide distribution of the Australasian fungus Clathrus archeri (Phallales, Basidiomycota)
Authors: Pietras Marcin , Kolanowska Marta , Selosse Marc-André
Published: March 2021

Clathrus archeri is a fungus native to Australia and New Zealand that has started to expand into Europe, and it is considered a potentially invasive species. In this study, we examine the historical occurrence, current geographical range and potential future changes in the distribution of C. archeri using worldwide distribution data. Ecological modelling was used to assess the locations of the potential climatic niches of C. archeri within both its native and introduced ranges in the past, present and future. Our study clearly shows that the coverage of suitable habitats of this fungus has decreased since the last glacial maximum, and anthropogenic climate changes are accelerating the process of niche loss. The highest rate of C. archeri range contraction is expected in Australia, where the fungus should be considered a threatened species in the future. Highly valuable habitats will be available in Tasmania and New Zealand. However, a significant expansion rate of C. archeri will still probably be observed in Europe, where the climatic conditions preferred by the fungus will allow its quick expansion northeast into the continent.
Improved strategies to efficiently isolate thermophilic, thermotolerant, and heat-resistant fungi from compost and soil
Authors: Witfeld Frederick , Begerow Dominik , Guerreiro Marco Alexandre
Published: March 2021

Thermophilic, thermotolerant and heat-resistant fungi developed different physiological traits, enabling them to sustain or even flourish under elevated temperatures, which are life-hostile for most other eukaryotes. With the growing demand of heat-stable molecules in biotechnology and industry, the awareness of heat-adapted fungi as a promising source of respective enzymes and biomolecules is still increasing. The aim of this study was to test two different strategies for the efficient isolation and identification of distinctly heat-adapted fungi from easily accessible substrates and locations. Eight compost piles and ten soil sites were sampled in combination with different culture-dependent approaches to describe suitable strategies for the isolation and selection of thermophilous fungi. Additionally, an approach with a heat-shock treatment, but without elevated temperature incubation led to the isolation of heat-resistant mesophilic species. The cultures were identified based on morphology, DNA barcodes, and microsatellite fingerprinting. In total, 191 obtained isolates were assigned to 31 fungal species, from which half are truly thermophilic or thermotolerant, while the other half are heat-resistant fungi. A numerous amount of heat-adapted fungi was isolated from both compost and soil samples, indicating the suitability of the used approaches and that the richness and availability of those organisms in such environments are substantially high.
Overlooked nitrogen-cycling microorganisms in biological wastewater treatment
Authors: Xu Shaoyi , Wu Xiaolong , Lu Huijie
Published: March 2021

Nitrogen-cycling microorganisms play key roles at the intersection of microbiology and wastewater engineering. In addition to the well-studied ammonia oxidizing bacteria, nitrite oxidizing bacteria, heterotrophic denitrifiers, and anammox bacteria, there are some other N-cycling microorganisms that are less abundant but functionally important in wastewater nitrogen removal. These microbes include, but not limited to ammonia oxidizing archaea (AOA), complete ammonia oxidation (comammox) bacteria, dissimilatory nitrate reduction to ammonia (DNRA) bacteria, and nitrate/nitrite-dependent anaerobic methane oxidizing (NOx-DAMO) microorganisms. In the past decade, the development of high-throughput molecular technologies has enabled the detection, quantification, and characterization of these minor populations. The aim of this review is therefore to synthesize the current knowledge on the distribution, ecological niche, and kinetic properties of these “overlooked” N-cycling microbes at wastewater treatment plants. Their potential applications in novel wastewater nitrogen removal processes are also discussed. A comprehensive understanding of these overlooked N-cycling microbes from microbiology, ecology, and engineering perspectives will facilitate the design and operation of more efficient and sustainable biological nitrogen removal processes.