bluuebunny/crossref_metadata_2025 huggingface dataset:
Phyto‐pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID‐19, based on its promising immunomodulatory, anti‐coagulant and anti‐viral property
Authors: Palit Partha , Mukhopadhyay Aparna , Chattopadhyay Debprasad
Published: April 2021

Coronavirus disease 2019 (COVID‐19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus‐2 (SARS‐CoV‐2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID‐19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune‐cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon‐stimulated gene 15, for the management of COVID‐19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to −1,350.61 kcal/mol and a full fitness score of −8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS‐CoV‐2 replication. We propose in‐depth pre‐clinical and clinical review studies of silymarin for the development of anti‐COVID‐19 lead, based on its clinical manifestations of COVID‐19 and multifaceted bioactivities.
Polypharmacy in clozapine‐treated patients
Authors: Lam Y. W. Francis
Published: April 2021

Clozapine has been the primary atypical antipsychotic agent used for managing patients with treatment‐resistant schizophrenia. Despite clozapine's efficacy, its usefulness is limited by the occurrence of significant side effects, including neutropenia and agranulocytosis in 1% to 2% of treated patients. Other side effects are also often reported with long‐term use, including metabolic effects such as weight gain, obesity, diabetes, hypertension, and dyslipidemia; cardiopulmonary effects such as tachycardia and pneumonia; and patient complaints of hypersalivation. The occurrence of one or more of these side effects might necessitate the initiation of concurrent medications for pharmacological management, and the potential of drug‐drug interaction.
Kinematic processes contributing to the intensification of anomalously strong North Atlantic jets
Authors: Winters Andrew C.
Published: April 2021

Anomalously strong North Atlantic jets, defined in this study as jets with wind speeds exceeding 100 m·s−1, are notable due to their potential to induce high‐impact weather. This study examines the kinematic processes that contribute to the intensification of anomalously strong North Atlantic jets, as well as the variability in those processes across a large number of events. Anomalously strong jets are objectively identified during September–May 1979–2018 within the Climate Forecast System Reanalysis and composited to reveal the synoptic‐scale flow evolution associated with jet intensification. The analysis demonstrates that anomalously strong North Atlantic jets are most frequent during the winter compared with the fall and spring, and that their development is preceded by low‐level warm‐air advection, poleward moisture advection, and moist ascent within the warm conveyor belt of a surface cyclone beneath the equatorward jet‐entrance region. A diagnosis of the irrotational and nondivergent components of the ageostrophic wind within the near‐jet environment reveals that both wind components facilitate jet intensification via their nonnegligible contributions to negative potential vorticity (PV) advection and PV frontogenesis in the vicinity of the dynamic tropopause. Weather Research and Forecasting (WRF) model simulations of a jet event from December 2013 with and without latent heating further suggest that the ageostrophic wind field within the near‐jet environment is substantially modulated by latent heating. The foregoing results indicate that a diagnosis of jet intensification during anomalously strong jet events is dependent on an accurate representation of the cumulative effects of latent heating within the near‐jet environment.
Robotic single‐site versus multiport radical hysterectomy in early stage cervical cancer: An analysis of 62 cases from a single institution
Authors: Jang Tae‐Kyu , Chung Hyewon , Kwon Sang‐Hoon , Shin So‐Jin , Cho Chi‐Heum
Published: April 2021

Background

This study aimed to compare the surgical outcomes and cost of robotic single‐site radical hysterectomy (RSSRH) versus robotic multiport radical hysterectomy (RMPRH) with pelvic lymph node dissection in early stage cervical cancer.

Methods

Sixty‐two patients with early stage cervical cancer were recruited between November 2011 and July 2017 and underwent RSSRH (20 patients) and RMPRH (42 patients) for early stage cervical cancer using the da Vinci Si Surgical System (Intuitive Surgical).

Results

There were no significant difference between the two groups in most of parameters. However, postoperative hospital discharge and total hospital costs for RSSRH were significantly shorter than RMPRH (both p < 0.001). However, lymph node retrieval of RMPRH was significantly higher than RSSRH in (18.0 vs. 9.5, respectively; p < 0.001).

Conclusions

RSSRH has comparable surgical outcomes to the RMPRH method. RSSRH could be considered a surgical option in a well‐selected patient group.
Development and in vivo assessment of a novel MRI‐compatible headframe system for the ovine animal model
Authors: Trovatelli Marco , Brizzola Stefano , Zani Davide Danilo , Castellano Antonella , Mangili Paola , Riva Marco , Woolley Max , Johnson Dave , Rodriguez y Baena Ferdinando , Bello Lorenzo , Falini Andrea , Secoli Riccardo
Published: April 2021

Background

The brain of sheep has primarily been used in neuroscience as an animal model because of its similarity to the human brain, in particular if compared to other models such as the lissencephalic rodent brain. Their brain size also makes sheep an ideal model for the development of neurosurgical techniques using conventional clinical CT/MRI scanners and stereotactic systems for neurosurgery.

Methods

In this study, we present the design and validation of a new CT/MRI compatible head frame for the ovine model and software, with its assessment under two real clinical scenarios.

Results

Ex‐vivo and in vivo trial results report an average linear displacement of the ovine head frame during conventional surgical procedures of 0.81 mm for ex‐vivo trials and 0.68 mm for in vivo tests, respectively.

Conclusions

These trial results demonstrate the robustness of the head frame system and its suitability to be employed within a real clinical setting.
Controlled Aggregation Enhances Immunomodulatory Potential of Mesenchymal Stromal Cell Aggregates
Authors: Xie Angela W. , Zacharias Nicholas A. , Binder Bernard Y. K. , Murphy William L.
Published: April 2021

Human mesenchymal stromal cells (MSCs) are promising candidates for cell therapy due to their ease of isolation and expansion and their ability to secrete antiapoptotic, pro-angiogenic, and immunomodulatory factors. Three-dimensional (3D) aggregation “self-activates” MSCs to augment their pro-angiogenic and immunomodulatory potential, but the microenvironmental features and culture parameters that promote optimal MSC immunomodulatory function in 3D aggregates are poorly understood. Here, we generated MSC aggregates via three distinct methods and compared them with regard to their (a) aggregate structure and (b) immunomodulatory phenotype under resting conditions and in response to inflammatory stimulus. Methods associated with fast aggregation kinetics formed aggregates with higher cell packing density and reduced extracellular matrix (ECM) synthesis compared to those with slow aggregation kinetics. While all three methods of 3D aggregation enhanced MSC expression of immunomodulatory factors compared to two-dimensional culture, different aggregation methods modulated cells' temporal expression of these factors. A Design of Experiments approach, in which aggregate size and aggregation kinetics were systematically covaried, identified a significant effect of both parameters on MSCs' ability to regulate immune cells. Compared to small aggregates formed with fast kinetics, large aggregates with slow assembly kinetics were more effective at T-cell suppression and macrophage polarization toward anti-inflammatory phenotypes. Thus, culture parameters including aggregation method, kinetics, and aggregate size influence both the structural properties of aggregates and their paracrine immunomodulatory function. These findings underscore the utility of engineering strategies to control properties of 3D MSC aggregates, which may identify new avenues for optimizing the immunomodulatory function of MSC-based cell therapies.
Waste to energy in Kathmandu Nepal—A way toward achieving sustainable development goals
Authors: Lohani Sunil Prasad , Keitsch Martina , Shakya Siddhartha , Fulford David
Published: April 2021

The Sustainable Development Goals (SDG) explicitly focus on responsible use of resources, production, and consumption, which comprises sensible waste management includes SDG 3, 7, 11, and 12. Yet, gaps between policies and current waste management practices are prevailing globally as well as nationally. This article discusses waste management (WM) in Kathmandu Metropolitan City (KMC) with a focus on cleaner technology. Waste management has always been an issue in KMC with almost all wastes being dumped directly to a landfill site. The article aims to points out challenge with current waste management based on literature‐ and document reviews. Further, it introduces and analyses technologies to convert waste into energy and evaluates the applicability of the Asian Develop Bank recommendations for waste management in KMC and suggests strategies toward aligning KMC waste management with Nepal's SDG agenda. Findings indicate that Kathmandu has huge potential for implementing waste to energy technologies, and anaerobic digestion seems one of the most promising technologies. Yet, the city lacks a proper waste treatment infrastructure and would benefit from a systematic alignment of technology, policy, and environmental possibilities and challenges in both analysis, planning, and design.
Precisely Encoded Barcodes through the Structure‐Fluorescence Combinational Strategy: A Flexible, Robust, and Versatile Multiplexed Biodetection Platform with Ultrahigh Encoding Capacities
Authors: Wang Yao , Chen Cang , He Jing , Cao Yimei , Fang Xiaoxia , Chi Xiaomei , Yi Jingwei , Wu Jiancong , Guo Qingsheng , Masoomi Hajar , Wu Chongzhao , Ye Jian , Gu Hongchen , Xu Hong
Published: April 2021

With the rapid development of suspension array technology, microbeads‐based barcodes as the core element with sufficient encoding capacity are urgently required for high‐throughput multiplexed detection. Here, a novel structure‐fluorescence combinational encoding strategy is proposed for the first time to establish a barcode library with ultrahigh encoding capacities. Based on the never revealed transformability of the structural parameters (e.g., porosity and matrix component) of mesoporous microbeads into scattering signals in flow cytometry, the enlargement of codes number has been successfully realized in combination with two other fluorescent elements of fluorescein isothiocyanate isomer I (FITC) and quantum dots (QDs). The barcodes are constructed with precise architectures including FITC encapsulated within mesopores and magnetic nanoparticles as well as QDs immobilized on the outer surface to achieve the ultrahigh encoding level of 300 accompanied with superparamagnetism. To the best of knowledge, it is the highest record of single excitation laser‐based encoding capacity up to now. Moreover, a ten‐plexed tumor markers bioassay based on the tailored‐designed barcodes has been evaluated to confirm their feasibility and effectiveness, and the results indicate that the barcodes platform is a promising and robust tool for practical multiplexed biodetection.
A Self‐Ordered Nanostructured Transparent Electrode of High Structural Quality and Corresponding Functional Performance
Authors: Döhler Dirk , Triana Andrés , Büttner Pascal , Scheler Florian , Goerlitzer Eric S.A. , Harrer Johannes , Vasileva Anna , Metwalli Ezzeldin , Gruber Wolfgang , Unruh Tobias , Manshina Alina , Vogel Nicolas , Bachmann Julien , Mínguez‐Bacho Ignacio
Published: April 2021

The preparation of a highly ordered nanostructured transparent electrode based on a combination of nanosphere lithography and anodization is presented. The size of perfectly ordered pore domains is improved by an order of magnitude with respect to the state of the art. The concomitantly reduced density of defect pores increases the fraction of pores that are in good electrical contact with the underlying transparent conductive substrate. This improvement in structural quality translates directly and linearly into an improved performance of energy conversion devices built from such electrodes in a linear manner.
The Optimization Design of Sound Arrester for the Dry Type Air Core Smoothing Reactor Based on the Multi‐Physical Field Coupling Method
Authors: Yuan Fating , Yang Shouwei , Qin Shihong , Tang Bo , Lv Kai , Han Shanshan , Ding Can , Huang Li
Published: April 2021

In this paper, according to the parameters of the dry type air core smoothing reactor, the stress‐sound field and fluid‐temperature field coupling simulation model is established, the detailed temperature field and sound field distribution are obtained, and the influence law of sound arrester on the sound pressure level and temperature rise are analyzed. It can be found that the temperature rise of encapsulation coils are significantly increased when adding the sound arrester, and the reasons are given by analyzing the fluid velocity in the air ducts. Meanwhile, the optimization design method about sound arrester is proposed based on the orthogonal experiment design and finite element method. The influence curve and contribution rate of sound arrester on the pressure level and temperature rise are analyzed, and the optimal structural parameters of the sound arrester are obtained. The results show that the optimization method can significantly reduce the temperature rise and sound pressure level simultaneously, and improving the operational reliability of the smoothing reactor. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Adaptive Iteration Methods for Blind Carrier Frequency Estimation in Multi‐UserOFDMASystems
Authors: Cheng Nan‐Hung , Wang Yi‐Fan , Chen Yung‐Fang , Tseng Shu‐Ming
Published: April 2021

Subspace‐based blind carrier frequency offset (CFO) estimation algorithms in orthogonal frequency division multiple access (OFDMA) systems have been developed in the literature. However, the algorithms have some restrictions or require high computational complexity. In this paper, we propose simple iteration schemes to reduce complexity with an adaptive manner and present a time‐variant CFO adaptive estimation method. In the first part of the proposed algorithm, with initial rough estimated CFOs, it employs iterative methods to obtain CFO estimates. And the second part is to use proposed adaptive process to obtain the updated CFO estimation and track the parameters' time‐variations. The simulation results demonstrate the efficacy of the proposed iteration and adaptive schemes and the mean squared errors are near to the Cramer‐Rao bounds. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Comparison of food‐animal veterinarians’ and producers’ perceptions of producer‐centered communication following on‐farm interactions
Authors: DeGroot Antonia , Coe Jason B. , Kelton David , Miltenburg Cynthia , Wichtel Jeffrey , Duffield Todd
Published: April 2021

Background: Human medicine has demonstrated that a patient‐centered physician‐patient relationship is more effective than the traditional physician‐centered model. Objectives were to explore food‐animal veterinarians’ and producers’ perceptions of producer‐centered communication (VPPC and PPPC), during on‐farm interactions and examine associated factors.

Methods: A cross‐sectional sample of food‐animal veterinarians and their clients were recruited in Ontario, Canada. Immediately following on‐farm veterinarian‐producer interactions, the producer and veterinarian independently completed a questionnaire assessing PPC. Symmetry of paired responses between veterinarians and producers was examined. Employing listwise deletion, independent mixed linear regression models were developed to determine factors associated with PPPC and VPPC, respectively.

Results: Two hundred and three paired veterinarian and producer survey responses were analysed. Significant asymmetry (p‐value < 0.05) was observed, with veterinarians assessing PPC lower than producers. Based on data from 32 veterinarians and 159 producers, the only factor associated with PPPC was veterinarian burnout (PPPC decreased with burnout). Based on data from 32 veterinarians and 155 producers, factors positively associated with VPPC included veterinarian compassion satisfaction (VPPC increased with compassion satisfaction), length of interaction (VPPC increased with length of interaction) and producers identifying as female (VPPC higher with female producers).

Conclusion: Producer's positive PPPC is encouraging, yet veterinarians should be aware that mental health parameters may impact producers’ and their own perceptions of PPC. Further examining veterinarians’ delivery of PPC is important for food‐animal practice.
Hightech mit Blick auf Mensch und Planet
Authors: Bergner Ute
Published: April 2021

Die Herausforderung der Zukunft besteht darin, mit unseren Ressourcen, die außer der Sonnenenergie auf unserem Erdball begrenzt sind, achtsam umzugehen. Hier gilt es, kluge Ansätze und Leitplanken für jeden Menschen in jeder Lebenslage zu finden, richtige und nachhaltige Entscheidungen zu treffen. Kreislaufwirtschaft, abgeleitet von den Erhaltungssätzen der Physik, ist ein wesentlicher Denk‐ und Handlungsansatz, den sich jeder zu eigen machen sollte. In diesem Artikel werden aus den verschiedensten Perspektiven Denk‐ und Handlungsansätze sowie erfolgreiche Lösungsbeispiele dargestellt.
Oesophageal dysmotility in a dog following surgical correction of an oesophageal perforation
Authors: Phillips Victoria , Allerton Fergus , Robinson Will
Published: April 2021

A 9‐year‐old, male neutered Jack Russell terrier, weighing 6.7 kg, required general anaesthesia for retrieval of an oesophageal foreign body (OFB) of 7 days' duration. Removal of the osseous foreign body with oesophagoscopy was successful but revealed severe oesophageal necrosis with two full thickness tears of the caudal thoracic oesophagus prompting surgical intervention. Bilateral thoracotomy was performed, and the oesophageal lesions were successfully apposed. A gastrostomy tube was placed to provide nutrition until oral feeding resumed. Fourteen days post‐operatively the dog began to regurgitate with increasing frequency. Oesophagoscopy was repeated and revealed healing of the oesophageal lesions. Thoracic radiography was also normal. A fluoroscopic barium swallow study was performed 24 days post‐operatively which revealed severe oesophageal dysmotility of the caudal thoracic oesophagus. To the authors’ knowledge, this is the first report of severe oesophageal dysmotility as a delayed, post‐operative complication of oesophageal surgery following complete perforation by an osseous OFB.
Persistent hypotension resolved by neostigmine administration in a dog in which atracurium was used
Authors: Vettorato Enzo
Published: April 2021

A dog with a large abdominal mass underwent coeliotomy. Before surgery, the dog was anaemic, hypoalbuminaemic and had a grade III out of VI left sided holosystolic heart murmur; no signs related to heart failure were detected on thoracic radiographs. After intramuscular administration of methadone, anaesthesia was induced intravenously (IV) with fentanyl and propofol and maintained with isoflurane in oxygen. Lungs were mechanically ventilated using a volume‐controlled setting. To manage ventilation asynchrony, atracurium was administered IV. Concurrent hypotension did not respond to lowering the isoflurane concentration, crystalloid and colloid boluses administration, and dobutamine infusion. Surgery lasted 40 minutes, and the mass was easily removed. At end of surgery, neostigmine was administered IV slowly, and a progressive improvement of arterial blood pressure was recorded. The animal was then allowed to breathe spontaneously, and isoflurane was discontinued. Recovery from general anaesthesia was uneventful.
Dopamine and dobutamine may be ineffective at managing hypotension in anaesthetised koalas (Phascolarctos cinereus)
Authors: Cumming Scott H. , Martinez‐Taboada Fernando
Published: April 2021

Managing hypotension during anaesthesia is a common challenge in all species for which there are numerous approaches. To the authors’ knowledge, managing hypotension in the anaesthetised koala has never been described. This case report details two separate koalas, anaesthetised for different reasons, who developed hypotension under anaesthesia. In one koala, hypotension was managed primarily through the administration of inotropic infusions. Hypotension in the other koala was managed primarily through the administration of an infusion of phenylephrine. The phenylephrine successfully improved the mean arterial pressure, while the inotropes appeared to be completely ineffective.
Forelimb amputation and long‐term follow‐up in a White Dorper ram
Authors: Bonow Mariana Oliveira , Veado Henrique Caetano , Borges José Renato Junqueira , Soto‐Blanco Benito , Câmara Antonio Carlos Lopes
Published: April 2021

This paper aimed to report a successful forelimb amputation and long‐term follow‐up in a White Dorper ram. An 8‐month‐old 45.5 kg White Dorper ram was found standing on the exposed metacarpal bone of the right forelimb. Detailed clinical examination and radiographic evaluation confirmed metacarpophalangeal avulsion. Limb amputation was performed by radiocarpal disarticulation. Postoperative complications included wound infection and dehiscence. Fifteen days post‐surgery, the necrotic accessory carpal bone was retrieved during wound cleaning. After this, the stump healed rapidly by secondary intention within 30 days. During this recovery time, the ram showed good adaptation to walking on three legs, and the owner gave up buying the prosthesis. The ram returned to the flock fully adapted 45 days after surgery. We emphasize that documenting more limb amputations in livestock is critical to obtain conclusions about the prognosis, life expectancy and expected quality of life.
MRI findings of ependymoma in a 12‐month‐old cat
Authors: Indzhova Viktoriya , Erles Kerstin , Brocal Josep
Published: April 2021

A 12‐month‐old domestic shorthair cat was presented for a progressive 2‐week history of behavioural changes, difficulties in jumping, falling, leaning towards the right side and right‐sided head tilt. Neurological examination revealed a right‐sided head tilt, leaning to the right and vestibular ataxia. Hopping was reduced on the right thoracic and right pelvic limbs. The rest of the neurological and the physical examinations were unremarkable. The neuroanatomic localisation was consistent with a right central vestibular lesion. On MRI an intraventricular mass, causing mass effect was identified in the fourth ventricle. In T1‐weighted post‐contrast images, the lesion showed peripheral ring contrast enhancement, causing obstructive hydrocephalus and ventriculomegaly, creating a similar appearance to that previously described in feline infectious peritonitis. The mass was found to be ependymoma on the histopathological examination.
Urothelial cell carcinoma with widespread local and distant metastasis and associated osseous metaplasia in a dog
Authors: Butler Thomas , Schiavo Luca , Hughes Katherine , Dobson Jane , Giuliano Antonio
Published: April 2021

A 9‐year‐old female neutered husky‐cross dog was referred for investigation of sanguinous vaginal discharge and a painful inguinal mass. On clinical and ultrasound examination, a pedunculated ‘cauliflower‐like’ mass was found originating from the vulva with plaque‐like masses at the bladder trigone, extending into the bladder neck and the proximal urethra. Bilateral medial iliac lymphadenopathy and a firm, erythematous and painful inguinal dermal thickening measuring 70 mm x 50 mm were also found. During recovery following sedation, the patient developed uncontrollable status epilepticus and was euthanized. Post‐mortem examination confirmed the presence of a highly infiltrative urothelial cell carcinoma with widespread local and distant metastases to the medial iliac lymph nodes, lungs, inguinal skin and pelvic musculature. Osseous metaplasia in association with small neoplastic aggregates was noted on histopathology within the pelvic musculature.
Matrix element regression with deep neural networks — Breaking the CPU barrier
Authors: Bury F. , Delaere C.
Published: April 2021

Abstract

The Matrix Element Method (MEM) is a powerful method to extract information from measured events at collider experiments. Compared to multivariate techniques built on large sets of experimental data, the MEM does not rely on an examples-based learning phase but directly exploits our knowledge of the physics processes. This comes at a price, both in term of complexity and computing time since the required multi-dimensional integral of a rapidly varying function needs to be evaluated for every event and physics process considered. This can be mitigated by optimizing the integration, as is done in the MoMEMta package, but the computing time remains a concern, and often makes the use of the MEM in full-scale analysis unpractical or impossible. We investigate in this paper the use of a Deep Neural Network (DNN) built by regression of the MEM integral as an ansatz for analysis, especially in the search for new physics.
Characterization of t-affine differences and related forms
Authors: Olbryś Andrzej
Published: April 2021

In the present paper we are concerned with the problem of characterization of maps which can be expressed as an affine difference i.e. a map of the form $$\begin{aligned} tf(x)+(1-t)f(y)-f(tx+(1-t)y), \end{aligned}$$

t
f
(
x
)
+
(
1
-
t
)
f
(
y
)
-
f
(
t
x
+
(
1
-
t
)
y
)
,

where $$t\in (0,1)$$

t
∈
(
0
,
1
)

is a given number. We give a general solution of the functional equation associated with this problem.
Flowering phenology in alpine grassland strongly responds to shifts in snowmelt but weakly to summer drought
Authors: Vorkauf Maria , Kahmen Ansgar , Körner Christian , Hiltbrunner Erika
Published: April 2021

Alpine plants complete their seasonal phenological cycle during two to three snow-free months. Under climate change, snowmelt advances and the risk of summer droughts increases. Yet, photoperiodism may prevent alpine plants from benefiting from an earlier start of the growing season. To identify the drivers of flowering phenology in the seven main species of an alpine grassland, we experimentally shifted the snowmelt date through snow manipulations, and excluded precipitation during summer. With “time-to-event” models, we analysed the beginning of main flowering with respect to temperature sums, time after snowmelt, and calendar day (photoperiod). We identified two phenology types: four species tracking snowmelt dates directly or with a certain lag set by temperature sums, including the dominant sedge Carex curvula, Anthoxanthum alpinum Helictotrichon versicolor, and Trifolium alpinum, and three species tracking photoperiod: Geum montanum, Leontodon helveticus and Potentilla aurea. Photoperiodism did not act as daylength threshold but rather modulated the thermal sums at flowering. Hence, photoperiod delayed flowering after earlier snowmelt. The grass A. alpinum was the only one of seven species that clearly responded to drought by earlier and longer flowering. The remarkably high importance of snowmelt dates for both phenology types suggests an earlier onset of flowering in a warmer climate, particularly for non-photoperiod-sensitive species, with an increasing risk for freezing damages and potential disruptions of biotic interactions in the most frequent type of alpine grassland across the Alps. Consequentially, the distinct microclimate and species-specific responses to photoperiod challenge temperature-only based projections of climate warming effects on alpine plant species.
Extension of Boley’s continuum mechanics-based successive approximation method to two-layer rectangular beams
Authors: Gahleitner Johannes , Irschik Hans
Published: April 2021

An extension of Boley’s continuum mechanics-based successive approximation method is presented for rectangular beams composed of two isotropic linear elastic layers. The solution is cast into the form of tables, in complete analogy to the tables originally presented by Boley and Tolins for single-layer strips. The first column in these tables corresponds to the classical Bernoulli–Euler theory of beams. The further columns represent comparatively fast converging correction terms of an increasing refinement. Our two-layer formulation automatically satisfies the stress continuity conditions at the interface of the two layers. Enforcing displacement continuity at the interface between the layers, we derive results that do satisfy the equilibrium field equations, the stress continuity conditions at the interface and the stress boundary conditions at the upper and lower edges. When converged, the field constitutive relations and the displacement continuity at the interface between the two layers are also satisfied. We present a compact formulation, which allows writing down the results for more than the three successive steps considered by Boley and Tolins. The elasticity solutions presented subsequently can be used as novel analytic benchmarks for comparison with refined structural mechanics beam theories. Interior solutions for beams with a finite axial extent can be obtained by assigning approximate boundary conditions at the lateral ends. Comparisons to finite element computations for a clamped–clamped beam give strong evidence for the correctness of our analytic results.
Bootstrap joint prediction regions for sequences of missing values in spatio-temporal datasets
Authors: Parrella Maria Lucia , Albano Giuseppina , Perna Cira , La Rocca Michele
Published: April 2021

Missing data reconstruction is a critical step in the analysis and mining of spatio-temporal data. However, few studies comprehensively consider missing data patterns, sample selection and spatio-temporal relationships. To take into account the uncertainty in the point forecast, some prediction intervals may be of interest. In particular, for (possibly long) missing sequences of consecutive time points, joint prediction regions are desirable. In this paper we propose a bootstrap resampling scheme to construct joint prediction regions that approximately contain missing paths of a time components in a spatio-temporal framework, with global probability $$1-\alpha $$

1
-
α

. In many applications, considering the coverage of the whole missing sample-path might appear too restrictive. To perceive more informative inference, we also derive smaller joint prediction regions that only contain all elements of missing paths up to a small number k of them with probability $$1-\alpha $$

1
-
α

. A simulation experiment is performed to validate the empirical performance of the proposed joint bootstrap prediction and to compare it with some alternative procedures based on a simple nominal coverage correction, loosely inspired by the Bonferroni approach, which are expected to work well standard scenarios.
Bayesian sparse convex clustering via global-local shrinkage priors
Authors: Shimamura Kaito , Kawano Shuichi
Published: April 2021

Sparse convex clustering is to group observations and conduct variable selection simultaneously in the framework of convex clustering. Although a weighted$$L_1$$L1norm is usually employed for the regularization term in sparse convex clustering, its use increases the dependence on the data and reduces the estimation accuracy if the sample size is not sufficient. To tackle these problems, this paper proposes a Bayesian sparse convex clustering method based on the ideas of Bayesian lasso and global-local shrinkage priors. We introduce Gibbs sampling algorithms for our method using scale mixtures of normal distributions. The effectiveness of the proposed methods is shown in simulation studies and a real data analysis.
“Metalloestrogenic” effects of cadmium downstream of G protein-coupled estrogen receptor and mitogen-activated protein kinase pathways in human uterine fibroid cells
Authors: Yu Linda , Liu Jingli , Yan Yitang , Burwell Alanna , Castro Lysandra , Shi Min , Dixon Darlene
Published: April 2021

Cadmium (Cd) is a toxic metal reported to act as an estrogen “mimic” in the rat uterus and in vitro. We have reported that Cd stimulates proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM; fibroid) cells through nongenomic signaling involving the G protein-coupled estrogen receptor (GPER), with activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (pMAPK44/42). In this study, we explored Cd-induced mechanisms downstream of MAPK and whether Cd could stimulate phosphorylation of Histone H3 at serine 10 (H3Ser10ph) through activated Aurora B kinase (pAurora B), a kinase important in activation of histone H3 at serine 10 during mitosis, and if this occurs via Fork head box M1 (FOXM1) and cyclin D1 immediately downstream of MAPK. We found that Cd increased proliferating cell nuclear antigen (PCNA) and H3Ser10ph expression by immunofluorescence, and that H3ser10ph and pAurora B were coexpressed along the metaphase plate in ht-UtLM cells. In addition, Cd-exposed cells showed higher expression of pMAPK44/42, FOXM1, pAurora B, H3ser10ph, and Cyclin D1 by western blotting. Immunoprecipitation and proximity ligation assays further indicated an association between FOXM1 and Cyclin D1 in Cd-exposed cells. These effects were attenuated by MAPK kinase (MEK1/2) inhibitor. In summary, Cd-induced proliferation of ht-UtLM cells occurred through activation of Histone H3 and Aurora B via FOXM1/Cyclin D1 interactions downstream of MAPK. This provides a molecular mechanism of how Cd acts as an “estrogen mimic” resulting in mitosis in hormonally responsive cells.
Asymptotic Symmetries in the BV-BFV Formalism
Authors: Rejzner Kasia , Schiavina Michele
Published: April 2021

We show how to derive asymptotic charges for field theories on manifolds with “asymptotic” boundary, using the BV-BFV formalism. We also prove that the conservation of said charges follows naturally from the vanishing of the BFV boundary action, and show how this construction generalises Noether’s procedure. Using the BV-BFV viewpoint, we resolve the controversy present in the literature, regarding the status of large gauge transformation as symmetries of the asymptotic structure. We show that even though the symplectic structure at the asymptotic boundary is not preserved under these transformations, the failure is governed by the corner data, in agreement with the BV-BFV philosophy. We analyse in detail the case of electrodynamics and the interacting scalar field, for which we present a new type of duality to a sourced two-form model.
Epidemiology of Tumor-Induced Osteomalacia in Denmark
Authors: Abrahamsen Bo , Smith Christopher D. , Minisola Salvatore
Published: April 2021

Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to phosphaturic mesenchymal tumors. Because the incidence and prevalence of TIO is unknown, we conducted an observational cohort study using national Danish health registers for the period 2008 to 2018 to obtain such information. The study also aimed to describe the demographics of the TIO population and the prognosis. The operational definition was based on hypophosphatemia or adult osteomalacia diagnoses, combined with prescriptions used in the initial management and procedures consistent with advanced imaging used for locating tumors. The incidence of TIO in Denmark was found to be below 0.13 per 100,000 person years for the total population of the country and 0.10 per 100,000 in adult-onset disease. The prevalence of TIO was estimated to be no more than 0.70 per 100,000 persons for the total population and 0.43 per 100,000 in adults. In 2018, there were a maximum of nine new cases of TIO in Danish adults. Mortality was low but few patients fulfilled the protocol cure criterion during the observation period. TIO has no ICD-10 code and limitations to the study include lack of information on serum biochemistry and on the use of phosphate supplements. Strengths include the use of long-term longitudinal, national hospital and prescription data from a country with universal healthcare. Given the very small patient population with TIO and the known delay to diagnosis and cure, management of patients with suspected TIO should be centralized.
An experimental assessment of social tolerance and den ecology in a high-density octopus population
Authors: O’Brien Duncan A. , Taylor Michelle L. , Masonjones Heather D. , Boersch-Supan Philipp H. , O’Shea Owen R.
Published: April 2021

Long held notions of the universally asocial octopus are being challenged due to the identification of high-density and interacting octopus populations in Australia, Indonesia, Japan and the deep sea. This study experimentally assessed the social tolerance and presence of potential prey items of Caribbean reef octopus, Octopus briareus, in a tropical marine lake (25°21′40″N, 76°30′40″W) on the island of Eleuthera, The Bahamas, by deploying artificial dens in multi-den groups or ‘units’ in the months of May and June 2019. Fifteen octopus were observed occupying dens (n = 100), resulting in 13 den units being occupied (n = 40). Two examples of adjacent occupation within a single den unit were identified but with zero examples of cohabitation/den sharing. Ecological models showed den and den unit occupation was predicted to increase with depth and differ between sites. Octopus also displayed no preference for isolated or communal units but preferred isolated dens over dens adjacent to others. Additionally, 47 % of occupied dens contained bivalve or crustacean items with no epifauna on their interior surface. The lack of epifauna suggests that these items have been recently ‘cleaned’ by occupying octopus and so represent likely prey. This study presents evidence of possible antisocial den use by O. briareus, a modification of the default ‘asocial’ ignoring of conspecifics typically attributed to octopus. This is likely in response to the high population density and may imply behavioural plasticity, making this system appropriate for further scrutiny as a research location on the influence of large, insular environments on marine species.
Synchronized broadcast spawning by six invertebrates (Echinodermata and Mollusca) in the north-western Red Sea
Authors: Webb Alice E. , Engelen Aschwin H. , Bouwmeester Jessica , van Dijk Inge , Geerken Esmee , Lattaud Julie , Engelen Dario , de Bakker Bernadette S. , de Bakker Didier M.
Published: April 2021

On the evenings of June 11 and 12, 2019, 5 and 6 days before full moon, broadcast spawning by four echinoderm species and two mollusc species was observed on the Marsa Shagra reef, Egypt (25° 14′ 44.2" N, 34° 47′ 49.0" E). Water temperature was 28 °C and the invertebrates were observed at 2–8 m depth. The sightings included a single basket star Astroboa nuda (Lyman 1874), 2 large Tectus dentatus (Forskal 1775) sea snails, 14 individuals of the Leiaster cf. leachi (Gray 1840) sea star and 1 Mithrodia clavigera (Lamarck 1816) sea star, 3 Pearsonothuria graeffei (Semper 1868) sea cucumbers, and 2 giant clams, Tridacna maxima (Röding 1798). The observations presented here provide relevant information on broadcast spawning of non-coral invertebrate taxa in the Red Sea, where spawning is considerably less well documented than in other tropical geographical regions such as the Indo-Pacific and Caribbean.
Bruton’s tyrosine kinase: an emerging targeted therapy in myeloid cells within the tumor microenvironment
Authors: Good Logan , Benner Brooke , Carson William E.
Published: April 2021

Bruton’s tyrosine kinase (BTK) is a non-receptor kinase belonging to the Tec family of kinases. The role of BTK in B cell receptor signaling is well defined and is known to play a key role in the proliferation and survival of malignant B cells. Moreover, BTK has been found to be expressed in cells of the myeloid lineage. BTK has been shown to contribute to a variety of cellular pathways in myeloid cells including signaling in the NLRP3 inflammasome, receptor activation of nuclear factor-κβ and inflammation, chemokine receptor activation affecting migration, and phagocytosis. Myeloid cells are crucial components of the tumor microenvironment and suppressive myeloid cells contribute to cancer progression, highlighting a potential role for BTK inhibition in the treatment of malignancy. The increased interest in BTK inhibition in cancer has resulted in many preclinical studies that are testing the efficacy of using single-agent BTK inhibitors. Moreover, the ability of tumor cells to develop resistance to single-agent checkpoint inhibitors has resulted in clinical studies utilizing BTK inhibitors in combination with these agents to improve clinical responses. Furthermore, BTK regulates the immune response in microbial and viral infections through B cells and myeloid cells such as monocytes and macrophages. In this review, we describe the role that BTK plays in supporting suppressive myeloid cells, including myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), while also discussing the anticancer effects of BTK inhibition and briefly describe the role of BTK signaling and BTK inhibition in microbial and viral infections.
Mixture models as a method for comparative sociality: social networks and demographic change in resident killer whales
Authors: Ellis Samuel , Franks Daniel W. , Weiss Michael N. , Cant Michael A. , Domenici Paolo , Balcomb Kenneth C. , Ellifrit David K. , Croft Darren P.
Published: April 2021

In studies of social behaviour, social bonds are usually inferred from rates of interaction or association. This approach has revealed many important insights into the proximate formation and ultimate function of animal social structures. However, it remains challenging to compare social structure between systems or time-points because extrinsic factors, such as sampling methodology, can also influence the observed rate of association. As a consequence of these methodological challenges, it is difficult to analyse how patterns of social association change with demographic processes, such as the death of key social partners. Here we develop and illustrate the use of binomial mixture models to quantitatively compare patterns of social association between networks. We then use this method to investigate how patterns of social preferences in killer whales respond to demographic change. Resident killer whales are bisexually philopatric, and both sexes stay in close association with their mother in adulthood. We show that mothers and daughters show reduced social association after the birth of the daughter’s first offspring, but not after the birth of an offspring to the mother. We also show that whales whose mother is dead associate more with their opposite sex siblings and with their grandmother than whales whose mother is alive. Our work demonstrates the utility of using mixture models to compare social preferences between networks and between species. We also highlight other potential uses of this method such as to identify strong social bonds in animal populations.

Significance statement

Comparing patters of social associations between systems, or between the same systems at different times, is challenging due to the confounding effects of sampling and methodological differences. Here we present a method to allow social associations to be robustly classified and then compared between networks using binomial mixture models. We illustrate this method by showing how killer whales change their patterns of social association in response to the birth of calves and the death of their mother. We show that after the birth of her calf, females associate less with their mother. We also show that whales’ whose mother is dead associate more with their opposite sex siblings and grandmothers than whales’ whose mother is alive. This clearly demonstrates how this method can be used to examine fine scale temporal processes in animal social systems.
Size is not everything: differing activity and foraging patterns between the sexes in a monomorphic mammal
Authors: Lodberg-Holm Hanna Kavli , Steyaert S.M.J.G. , Reinhardt S. , Rosell F.
Published: April 2021

Animals balance foraging with other activities, and activity patterns may differ between sexes due to differing physical requirements and reproductive investments. Sex-specific behavioural differences are common in sexually dimorphic mammals, but have received limited research attention in monomorphic mammals where the sexes are similar in body size. Eurasian beavers (Castor fiber) are obligate monogamous and monomorphic mammals and a good model species to study sex-specific differences. As females increase energy expenditure during reproduction, we hypothesized differing seasonal activity budgets, circadian activity rhythms and foraging patterns between male and reproducing female beavers. To test this hypothesis, we equipped adult beavers with VHF transmitters (N=41; 16 female, 25 male) and observed them throughout their active period at night from spring to late summer. Occurrence of their main activities (foraging, travelling and being in lodge) and use of food items (trees/shrubs, aquatic vegetation and herbs/grasses) were modelled to investigate sex-specific seasonal activity budgets and circadian activity rhythms. The sexes did not differ in time spent foraging across the season or night, but during spring, females resided more in the lodge and travelled less. Males and females both foraged on aquatic vegetation during spring, but females used this food source also during late summer, whereas males mostly foraged on trees/shrubs throughout the year. We conclude that seasonal activity budgets and foraging differ subtly between the sexes, which may relate to different energy budgets associated with reproduction and nutritional requirements. Such subtle seasonal behavioural adaptions may be vital for survival and reproduction of monomorphic species.

Significance statement

Activity budgets and foraging patterns of animals are key to their survival and may differ between males and females with different body sizes and physical requirements. In monomorphic species, where males and females have similar body sizes, fewer differences are expected, but may still be pronounced during certain times of the year. We modelled sex-specific seasonal activity budgets and circadian activity rhythms and use of food items in a monomorphic mammal, the Eurasian beaver. By treating season and time of day as a continuous variable rather than modelling differences within distinct predefined periods, we identified subtle sex-specific seasonal trends in activity budgets and use of food items.