bluuebunny/crossref_metadata_2025 huggingface dataset:
A Compact MIMO T Slot Microstrip Antenna Design for K-band Applications
Authors: Nishandhi S , Kavitha K , Gayathri M
Published: April 2023

In this paper, two compact T-Slot Microstrip antennas have been proposed, designed, and presented using design equations. Each antenna design has the same dimensions and characteristics. High-frequency structure simulator has been used for the proposed design and output has been verified. FR-4 Substrate which is having 1.6mm thickness is used to mount the prototype. The patch operates for 25.75 GHz resonant frequencies and T-Shaped slot has been designed for K-Band applications. In this work, 50 x 40 mm2 measurements is used. The antenna designed is having perfect radiation patterns with good VSWR, Return loss, and Radiation efficient achieved.
Design and Performance prediction of Liquid based Tunable Cylindrical Dielectric Resonator Antenna
Authors: Dhanush R , Kumar Kunde Santhosh , Madhan M Ganesh
Published: April 2023

In this paper, we report a liquid-based tunable Cylindrical Dielectric Resonator Antenna (CDRA), whose resonance is varied by loading the cavity installed in the CDRA with different volumes of liquid. The tunability of the CDRA is investigated by loading the cavity with two different types of liquids, one with lower permittivity (i.e.) oil and the other with higher permittivity (i.e.) water. CDRA loaded with oil is found to be tunable over a small frequency range of 32MHz (5.76GHz to 5.728GHz), whereas the change in water volume in the cavity provides a wide tuning range of 452MHz (5.76GHz to 5.308GHz). Further, the antenna gain is found to be almost constant, around 5.1 dB, for oil-based CDRA. In a water-filled cavity, the gain is observed to reduce by 1dB as the volume is increased from 0 to 100%.
Reduction of Near-End and Far - End Crosstalk in Microwave and Millimetre Wave Band of Parallel Transmission Lines using Meander Shaped DMS
Authors: Gobinath A , Kumar N Suresh , Rajeswari P
Published: April 2023

This research proposes a unique design that makes use of a defective microstrip topology to decrease electromagnetic coupling between parallel high speed interconnects. The performance of this new microstrip construction with defects is evaluated using near-end crosstalk and far-end crosstalk. Serpentine shaped defected microstrip is introduced in one parallel of high speed interconnects and its performance is also compared the existing structure. In this research, the proposed defected microstrip structure (DMS) is simulated and compared with a conventional microstrip structure using Ansoft HFSS software which employs the Finite Element Method (FEM). Simulation results indicate that the DMS design effectively reduces crosstalk in comparison to the previous structure. It reduces more than 5dB near end crosstalk and more than 3dB far end crosstalk compared to conventional model.
Analysis of Three-Stage LNA Architecture for CMOS RF Front End
Authors: Sathya R , Ambulker Sunanda
Published: April 2023

Wireless communication continues to lead the world. The term “wireless” significantly influences everything from telephone to satellite communication. Recent years have seen the need for appropriately built Low Noise Amplifiers (LNAs) in receiver front end because of the modem wireless communication in broadcast and microwave radio. In this paper a high performance LNA for the radio frequency range is presented. To achieve high gain a three stage LNA with each stage as Cascode stage is considered here. The simulation shows that the presented LNA has a gain of 26.12 dB and a Noise Figure (NF) of 2.6 dB. The achieved output and input returns losses are -8.4 dB and -11.6 dB respectively.
A Deep Learning approach to 3D Viewing of MRI/CT images in Augmented Reality
Authors: Paul Dewanshi , Patel Ankit Kumar , Rohith G
Published: April 2023

CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) are both used to diagnose internal damage and deformities of the organs. These are 3D data so doctors diagnose these scans by splitting them into many 2D slices and analyse each slices for detecting disease. This is a hard and time-consuming task to accomplish. Experts are enough trained to analyse this data for interpreting insights. But when they try to explain vulnerable situations to their patients, these scans are not very readable and understandable for them. Thus, it scares them a lot when they are asked to take these scans for diagnosis. Thus, an approach is given to viewing these scans in AR (augmented reality), making them available to view via their smartphones. The idea is to build an application that can take CT and MRI scans as input from “.stl” files and help to view them in AR with plane detection for mesh to be rendered and placed properly. This also reduces the task of storing these scans in bulk. Instead, one can just send data to their patients and store it as records on their phones. Whenever necessary, one can visualise it on the spot.
LSTM and GRU based Accurate Water Quality Prediction for Smart Aquaculture
Authors: Rahul Gandh D , Rasheed Abdul Haq K P , Harigovindan V P , Bhide Amrtha
Published: April 2023

The fast and precise water quality prediction in smart aquaculture can assist the farmers in taking corrective actions before the ecological environment deteriorates. However, the empirical methods take high computation time and provide low accuracy in water quality prediction due to the non-linear and dynamic nature of water quality parameters. This research work proposes long short-term memory (LSTM) and gated recurrent unit (GRU) deep learning recurrent neural network (DL-RNN) models for aquaculture water quality prediction (A-WQP). This work also presents an extensive study about the impact of hyper-parameters (hp) on the performance of the proposed DL-RNN models using two different water quality datasets. The experimental evaluations show that for the optimal sets of hyper-parameters, the proposed DL models offer superior prediction accuracy and computation efficiency.
Machine learning and IoT-based smart farming for enhancing the crop yield
Authors: Sundaresan S. , Daniel Johnson S. , Mani Bharathy V. , Mohan Pavan Kumar P. , Surendar M.
Published: April 2023

The lack of favourable atmospheric conditions leads to the loss of many crops each year. In India alone, over 11 billion dollars are lost. By combining IoT and machine learning technologies, this team has created a system that integrates agriculture’s three primary operations: crop selection, autonomous watering, and fertiliser suggestion. The following crops—Apple, Rice, Maize, Grape, Banana, Orange, Cotton, and Coffee—were considered in the study. Three systems are covered in the paper: The crop recommendation system employs machine learning to examine factors including nitrogen (N), phosphorous (P), potassium (K), pH, and weather before recommending a crop. The crop type and the current levels of soil nutrients are the two main determinants on which the fertiliser recommendation method bases its recommendation. When employing an automatic irrigation system, the crop is irrigated automatically while taking current soil moisture levels and weather forecasts into consideration. This paper attempted to implement the mentioned systems. The paper discusses the successes of the crop recommendation system, the automatic watering system, and the fertiliser recommendation system. In this paper, we report the results of simulations of the mentioned systems.
A study on flow field characteristics of a self-propelled robot fish approaching static obstacles based on artificial lateral line
Authors: Xie Ou , Sun Zhaoguang , Shen Can
Published: April 2023

To perceive the static obstacles in still water, the flow field characteristics of a self-propelled robot fish approaching static obstacles were studied based on artificial lateral line (ALL). The pressure distribution on the fish body surface was calculated with different separation between the robot fish and the obstacle boundary, obstacle size and undulating frequency. Subsequently, an ALL system was established and five obstacle perception models were studied to analyze the perceptual characteristics of the ALL. Finally, the experiments were conducted to further reveal the effects of obstacles and motion parameters on the body surface pressure of robot fish. The results indicate that the obstacles have a significant effect on the pressure distribution of the surface of the fish body. Namely the parameters of separation, obstacle size and undulating frequency will affect the peak value of the amplitude envelope of the pressure signals. The obstacle size and distance between the obstacles can be predicted using the time parameters of the amplitude envelope of the pressure signals. Moreover, the self-propelled robot fish with a medium undulating frequency approach to the large obstacles with small separation has better perceptual performance. The findings could offer some insight into understanding the perception of complex underwater environment based on ALL.
Winter cold extremes over the eastern North America: Pacific origins of interannual-to-decadal variability
Authors: Ge Yao , Luo Dehai
Published: April 2023

Winter cold extreme events have been observed to frequently take place over North America mainly over its east side, which show significant interannual and decadal variability and cause huge economic losses in the United States. However, it is unclear what leads to the interannual-decadal variability of winter cold extremes over the eastern North America. In this study, we indicate that the decadal variability of winter cold extremes over the eastern North America, whose period is shortened in the recent decades, is mainly tied to Pacific decadal oscillation (PDO), whereas their interannual variability is mainly regulated by Victoria mode (VM). A positive PDO promotes cold extremes in the lower latitudes of the eastern North America mainly owing to the presence of positive Pacific North American (PNA+) patterns, whereas a positive VM is favorable for intense cold extremes in the higher latitudes of the eastern North America mainly due to the occurrence of negative North Pacific oscillation (NPO−) patterns. Thus, the positive VM and PDO combine to significantly contribute to the interannual-to-decadal variability of winter cold extremes over the eastern North America through changes in the winter NPO− and PNA+ patterns due to the variations of meridional background potential vorticity gradient and basic zonal winds. These new findings can help us understand what are the origins of the interannual-decadal variability of winter cold extremes over the eastern North America.
Frobenius monoidal functors from (co)Hopf adjunctions
Authors: Yadav Harshit
Published: April 2023

Let

U
:

C

→

D

U:\mathcal {C}\rightarrow \mathcal {D}

be a strong monoidal functor between abelian monoidal categories admitting a right adjoint

R
R

, such that

R
R

is exact, faithful and the adjunction

U
⊣
R

U\dashv R

is coHopf. Building on the work of Balan [Appl. Categ. Structures 25 (2017), pp. 747–774], we show that

R
R

is separable (resp., special) Frobenius monoidal if and only if

R
(

1

D

)

R(\mathbb {1}_{\mathcal {D}})

is a separable (resp., special) Frobenius algebra in

C

\mathcal {C}

. If further,

C

,

D

\mathcal {C},\mathcal {D}

are pivotal (resp., ribbon) categories and

U
U

is a pivotal (resp., braided pivotal) functor, then

R
R

is a pivotal (resp., ribbon) functor if and only if

R
(

1

D

)

R(\mathbb {1}_{\mathcal {D}})

is a symmetric Frobenius algebra in

C

\mathcal {C}

. As an application, we construct Frobenius monoidal functors going into the Drinfeld center

Z

(

C

)

\mathcal {Z}(\mathcal {C})

, thereby producing Frobenius algebras in it.
Relatively quasimöbius mappings in Banach spaces
Authors: Zhou Qingshan , Li Liulan , Ponnusamy Saminathan , He Yuehui
Published: April 2023

In this paper, we explore relatively quasimöbius invariance of

φ
\varphi

-uniform domains and natural domains. Firstly, we prove that the control function of relatively quasimöbius mappings can be chosen in a power form. Applying this observation and a deformed cross–ratio introduced by Bonk and Kleiner, we next show that relatively quasimöbius mappings are coarsely bilipschitz in the distance ratio metric. Combined with the assumption that the mapping is coarsely bilipschitz in the quasihyperbolic metric, we establish relatively quasimöbius invariance of

φ
\varphi

-uniform domains and natural domains. As a by-product, we also obtain a similar result for uniform domains which provides a new method to answer a question posed by Väisälä.
An arithmetic analysis of closed surfaces
Authors: Harrison-Trainor Matthew , Melnikov Alexander
Published: April 2023

From a computability-theoretic standpoint, we consider the following problem: Given a closed surface, as a topological space, how hard is it to recover an atlas? We prove that every computable Polish space homeomorphic to a closed surface admits an arithmetic atlas, and indeed an arithmetic triangulation. This is as simple as one could reasonably hope for; essentially, the locally Euclidean structure of a surface can be recovered from the topological structure in a first-order way, i.e., without reference to curves or homeomorphisms or other higher-order objects.

It follows that given two computable presentations of the same closed surface, there is an arithmetic homeomorphism between them. Moreover, the homeomorphism problem for closed surfaces, presented as topological spaces, is arithmetic. From the algorithmic and definability-theoretic standpoint, this improves Kline’s conjecture proved by Bing in the 1940s. We also consider

R

2

\mathbb {R}^2

and the closed unit ball.
Morse theory for group presentations
Authors: Fernández Ximena
Published: April 2023

We introduce a novel combinatorial method to study

Q

∗
∗

Q^{**}

-transformations of group presentations or, equivalently, 3-deformations of CW-complexes of dimension 2. Our procedure is based on a refinement of discrete Morse theory that gives a Whitehead simple homotopy equivalence from a regular CW-complex to the simplified Morse CW-complex, with an explicit description of the attaching maps and bounds on the dimension of the complexes involved in the deformation. We apply this technique to show that some known potential counterexamples to the Andrews–Curtis conjecture do satisfy the conjecture.
Ploidy variation in Rhododendron subsection Maddenia and its implications for conservation
Authors: Hu Ling , Tate Jennifer A , Gardiner Susan E , MacKay Marion
Published: April 2023

Polyploidy, which is common in plants, can confound taxon recognition and hence conservation assessments. In the taxonomically complex genus Rhododendron, 25 % of the over 1,300 taxa are considered under threat and 27 % Near Threatened or Data Deficient, with their taxonomy needing to be resolved urgently. Although ploidy levels of Rhododendron taxa range from diploid (2x) to dodecaploid (12x) according to previous reports, the extent of polyploidy across the genus has not been examined. We first summarized the taxonomic distribution of polyploids in the genus based on the literature. Then as a case study, we estimated ploidy levels of 47 taxa in subsection Maddenia (subgenus Rhododendron, section Rhododendron) using flow cytometry, together with verification of meiotic chromosome counts for representative taxa. The summary of reported ploidy in Rhododendron indicates that polyploidy is most common in subgenera Pentanthera and Rhododendron. In subsection Maddenia, all examined taxa are diploids except for the R. maddenii complex that shows a high ploidy variation (2–8x, 12x). We investigated ploidy level of 12 taxa in subsection Maddenia for the first time, and estimated genome sizes of two Rhododendron species. Knowledge of ploidy levels will inform phylogenetic analysis of unresolved species complexes. Overall, our study of subsection Maddenia provides a model for examining multiple issues including taxonomic complexity, ploidy variation and geographic distribution in relation to biodiversity conservation.
Key issues when considering adopting a skin cancer diagnostic tool that uses artificial intelligence
Authors: Kelly Laura , Coote Laura , Dinnes Jacqueline , Fleming Colin , Holmes Hayden , Matin Rubeta N
Published: April 2023

Image-based skin cancer diagnostic technologies utilizing artificial intelligence (AI) are increasing in popularity in dermatology. The World Health Organization has cautioned against overestimating the benefits of AI at the expense of core investment and strategies required to achieve universal health coverage. In the UK, the National Health Service has a fixed budget, and expenditure decisions regarding new AI technologies need to be fully justified. Health economic evaluations can be challenging, but such evaluations can also help to elucidate the factors that determine suitability of a new AI diagnostic tool beyond its immediate costs and purported benefits.
Accuracy and reliability of automated three-dimensional facial landmarking in medical and biological studies. A systematic review
Authors: Al-baker Bodore , Alkalaly Abdullah , Ayoub Ashraf , Ju Xiangyang , Mossey Peter
Published: April 2023

Background

3D facial landmarking is becoming a fundamental part of clinical and biological applications. Manual landmarking is time consuming and prone to cumulative errors, so attempts have been made to automate 3D facial landmarking. However, data in the literature are sparse.

Objectives

The objectives of this study are to investigate current evidence for the accuracy and reliability of various 3D facial automated landmarking methods used in medical and biological studies and evaluate their performance against the manual annotation method.

Search methods

Electronic and manual searches of the literature were performed in April 2021.

Selection criteria

Only studies that were published in English and evaluated the accuracy of automated landmarking algorithms in 3D facial images for medical or biological settings were included.

Data collection and analysis

Two authors independently screened the articles for eligibility. The QUADAS-2 tool was used for the quality analysis of the included studies. Due to the heterogeneity of the selected studies, a meta-analysis was not possible, so a narrative synthesis of the findings was performed.

Results

From 1002 identified records, after applying the inclusion and exclusion criteria, 14 articles were ultimately selected, read, and critically analysed. Different algorithms were used for the automated 3D landmarking of various numbers of facial landmarks ranging from 10 to 29 landmarks. The average difference between the manual and automated methods ranged from 0.67 to 4.73 mm, and the best performance was achieved using deep learning models. Poor study design and inadequate reporting were found in the implementation of the reference standards and population selection for the intended studies, which could have led to overfitting of the tested algorithm.

Limitations

This systematic review was limited by the quality of the included studies and uncovered several methodological limitations evident in the corresponding literature

Conclusion and implications

Compared to manual landmarking, automated Landmark localization of individual facial landmarks reported in the literature is not accurate enough to allow their use for clinical purposes. This result indicates that automatic facial landmarking is still developing, and further studies are required to develop a system that could match or exceed the performance of the current gold standard.

Registration

PROSPERO: CRD42021241531.
Listening to Human Rights: Class Conflict in Hanns Eisler’s Deutsche Sinfonie
Authors: Marcus Kenneth H
Published: April 2023

In what began as a piece against the Nazi concentration camps, the composer Hanns Eisler and his collaborator, the poet and playwright Bertolt Brecht, created the eleven-movement, twelve-tone Deutsche Sinfonie, Op. 50 (1935–1958) to communicate political ideas. They soon expanded it to articulate what they saw as the very roots of fascism: militarism and capitalism. To explain the problems of class conflict in Europe, Eisler and Brecht focused on two groups that were central to Marxist–Leninist ideology: peasants and industrial workers. In two movements, the Peasant Cantata (Bauernkantate) and Workers Cantata (Arbeiterkantate), they portrayed long-standing injustices that peasants and industrial workers endured in the twentieth century. Eisler thus viewed the Deutsche Sinfonie, his largest and most ambitious work, as a way of explaining the arc of modern German history—from the late nineteenth century through to the 1940s—and how the Nazis came to power. The article further argues that the Deutsche Sinfonie can be analysed in relation to the discourse on human rights, drawing on the work of Martha Nussbaum, Micheline Ishay and other human rights theorists and historians, as a contribution to what Mark Philip Bradley calls the ‘global human rights imagination’. The article explains the vital role that the Peasant Cantata and Workers Cantata had in the overall conception of the work and how human rights issues were at the core of that musical idea. To place the Deutsche Sinfonie in historical and cultural context, this interdisciplinary analysis integrates methodologies of both cultural history and musicology.
In-Depth Assessment of Endoscopic Remission in Inflammatory Bowel Disease Treated by Anti-TNF or Vedolizumab
Authors: Loly Jean-Philippe , Vieujean Sophie , Reenaers Catherine , Van Kemseke Catherine , Seidel, ScD Laurence , Louis Edouard , Somja Joan
Published: April 2023

Background and aims

Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor–treated patients.

Methods

We screened patients with Crohn’s disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded.

Results

Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline.

Conclusion

Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor– and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.
Comparison of time series clustering methods for identifying novel subphenotypes of patients with infection
Authors: Bhavani Sivasubramanium V , Xiong Li , Pius Abish , Semler Matthew , Qian Edward T , Verhoef Philip A , Robichaux Chad , Coopersmith Craig M , Churpek Matthew M
Published: April 2023

Objective

Severe infection can lead to organ dysfunction and sepsis. Identifying subphenotypes of infected patients is essential for personalized management. It is unknown how different time series clustering algorithms compare in identifying these subphenotypes.

Materials and Methods

Patients with suspected infection admitted between 2014 and 2019 to 4 hospitals in Emory healthcare were included, split into separate training and validation cohorts. Dynamic time warping (DTW) was applied to vital signs from the first 8 h of hospitalization, and hierarchical clustering (DTW-HC) and partition around medoids (DTW-PAM) were used to cluster patients into subphenotypes. DTW-HC, DTW-PAM, and a previously published group-based trajectory model (GBTM) were evaluated for agreement in subphenotype clusters, trajectory patterns, and subphenotype associations with clinical outcomes and treatment responses.

Results

There were 12 473 patients in training and 8256 patients in validation cohorts. DTW-HC, DTW-PAM, and GBTM models resulted in 4 consistent vitals trajectory patterns with significant agreement in clustering (71–80% agreement, P < .001): group A was hyperthermic, tachycardic, tachypneic, and hypotensive. Group B was hyperthermic, tachycardic, tachypneic, and hypertensive. Groups C and D had lower temperatures, heart rates, and respiratory rates, with group C normotensive and group D hypotensive. Group A had higher odds ratio of 30-day inpatient mortality (P < .01) and group D had significant mortality benefit from balanced crystalloids compared to saline (P < .01) in all 3 models.

Discussion

DTW- and GBTM-based clustering algorithms applied to vital signs in infected patients identified consistent subphenotypes with distinct clinical outcomes and treatment responses.

Conclusion

Time series clustering with distinct computational approaches demonstrate similar performance and significant agreement in the resulting subphenotypes.
Optimization of backpropagation neural network models for reliability forecasting using the boxing match algorithm: electro-mechanical case
Authors: Tanhaeean M , Ghaderi S F , Sheikhalishahi M
Published: April 2023

Presenting a robust intelligent model capable of making accurate reliability forecasts has been an attractive topic to most industries. This study mainly aims to develop an approach by utilizing backpropagation neural network (BPNN) to predict the reliability of engineering systems, such as industrial robot systems and turbochargers, with reasonable computing speed and high accuracy. Boxing match algorithm (BMA), as an evolutionary metaheuristic algorithm with a new weight update strategy, is proposed to bring about performance improvements of the ANN in reliability forecast. Consequently, the hybrid model of BMA-BPNN has been provided to gain a significant level of accuracy in optimizing the weight and bias of BPNN using three sets of function approximation data to benchmark the proposed approach’s performance. Then, the BMA is utilized to improve reliability forecasting accuracy in engineering problems. The obtained results reveal that the presented algorithm delivers exceptional performance in function approximation, and its performance in forecasting engineering systems’ reliability is about 20% better than further compared algorithms. Similarly, rapid convergence rate, reasonable computing time, and well-performing are additional characteristics of the presented algorithm. Given the BMA-BPNN characteristics and the acquired findings, we can conclude that the proposed algorithm can be applicable in forecasting engineering problems’ reliability.
Reference genome of the long-jawed orb-weaver, Tetragnatha versicolor (Araneae: Tetragnathidae)
Authors: Adams Seira A , Graham Natalie R , Holmquist Anna J , Sheffer Monica M , Steigerwald Emma C , Sahasrabudhe Ruta , Nguyen Oanh , Beraut Eric , Fairbairn Colin , Sacco Samuel , Seligmann William , Escalona Merly , Shaffer H Bradley , Toffelmier Erin , Gillespie Rosemary G
Published: April 2023

Climate-driven changes in hydrological regimes are of global importance and are particularly significant in riparian ecosystems. Riparian ecosystems in California provide refuge to many native and vulnerable species within a xeric landscape. California Tetragnatha spiders play a key role in riparian ecosystems, serving as a link between terrestrial and aquatic elements. Their tight reliance on water paired with the widespread distributions of many species make them ideal candidates to better understand the relative role of waterways versus geographic distance in shaping the population structure of riparian species. To assist in better understanding population structure, we constructed a reference genome assembly for Tetragnatha versicolor using long-read sequencing, scaffolded with proximity ligation Omni-C data. The near-chromosome-level assembly is comprised of 174 scaffolds spanning 1.06 Gb pairs, with a scaffold N50 of 64.1 Mb pairs and BUSCO completeness of 97.6%. This reference genome will facilitate future study of T. versicolor population structure associated with the rapidly changing environment of California.
Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study
Authors: Cantini Luca , Paoloni Francesco , Pecci Federica , Spagnolo Francesco , Genova Carlo , Tanda Enrica Teresa , Aerts Sophie , Rebuzzi Sara Elena , Fornarini Giuseppe , Zoratto Federica , Fancelli Sara , Lupi Alessio , Della Corte Carminia Maria , Parisi Alessandro , Bennati Chiara , Ortega Cinzia , Atzori Francesco , Piovano Pier Luigi , Orciuolo Corrado , De Tursi Michele , Ghidini Michele , Botticelli Andrea , Scagnoli Simone , Belluomini Lorenzo , Leporati Rita , Veccia Antonello , Di Giacomo Anna Maria , Festino Lucia , Cortinovis Diego , Acquati Mirko , Filetti Marco , Giusti Raffaele , Tucci Marco , Sergi Maria Chiara , Garutti Mattia , Puglisi Fabio , Manglaviti Sara , Citarella Fabrizio , Santoni Matteo , Rijavec Erika , Lo Russo Giuseppe , Santini Daniele , Addeo Alfredo , Antonuzzo Lorenzo , Indini Alice , Rocchi Marco Bruno Luigi , Cortellini Alessio , Grossi Francesco , Ascierto Paolo Antonio , Aerts Joachim G J V , Berardi Rossana
Published: April 2023

Background

Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods

Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described.

Results

A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront).

Conclusions

Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.
Clonal hematopoiesis in older patients with breast cancer receiving chemotherapy
Authors: Mayerhofer Christina , Sedrak Mina S , Hopkins Judith O , Li Tianyu , Tayob Nabihah , Faggen Meredith G , Sinclair Natalie F , Chen Wendy Y , Parsons Heather A , Mayer Erica L , Lange Paulina B , Basta Ameer S , Perilla-Glen Adriana , Lederman Ruth I , Wong Andrew R , Tiwari Abhay , McAllister Sandra S , Mittendorf Elizabeth A , Gibson Christopher J , Burstein Harold J , Kim Annette S , Freedman Rachel A , Miller Peter G
Published: April 2023

Background

The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints.

Methods

We examined serial samples from 40 older women with triple-negative or hormone receptor–positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks).

Results

CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02).

Conclusions

Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies.

Trial Registration

ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.
Studying root–environment interactions in structured microdevices
Authors: Kaiser Christian-Frederic , Perilli Alessia , Grossmann Guido , Meroz Yasmine
Published: April 2023

When interacting with the environment, plant roots integrate sensory information over space and time in order to respond appropriately under non-uniform conditions. The complexity and dynamic properties of soil across spatial and temporal scales pose a significant technical challenge for research into the mechanisms that drive metabolism, growth, and development in roots, as well as on inter-organismal networks in the rhizosphere. Synthetic environments, combining microscopic access and manipulation capabilities with soil-like heterogeneity, are needed to elucidate the intriguing antagonism that characterizes subsurface ecosystems. Microdevices have provided opportunities for innovative approaches to observe, analyse, and manipulate plant roots and advanced our understanding of their development, physiology, and interactions with the environment. Initially conceived as perfusion platforms for root cultivation under hydroponic conditions, microdevice design has, in recent years, increasingly shifted to better reflect the complex growth conditions in soil. Heterogeneous micro-environments have been created through co-cultivation with microbes, laminar flow-based local stimulation, and physical obstacles and constraints. As such, structured microdevices provide an experimental entry point into the complex network behaviour of soil communities.
Continuous Monitoring of the Environment of Electron Microscopes
Authors: Ouyang Hsiu-Yi
Published: April 2023

Electron microscopes (EMs) are very sensitive to external disturbances, like acoustic noise, vibrations, and magnetic fields, which can significantly decrease their precision and compromise the resolution of images. It is, therefore, crucial to survey the room environment carefully before these instruments are installed, and to continue to monitor the surroundings when they are in use, since subsequent or transient changes to conditions can lead to ongoing problems. This is particularly important for EMs used for quality control in semiconductor production, as perturbed images make it hard to detect faults, and ultimately affect the yield and performance of semiconductor products. Fortunately, there are now dedicated systems designed especially for continuous monitoring of the environment surrounding sensitive equipment. Although the technologies used for this application have been on the market for some time, new solutions that provide uninterrupted and automatic logging of various environmental parameters will be a gamechanger for electron beam (EB) instrument applications.
When, where, and how many planets end up in first-order resonances?
Authors: Huang Shuo , Ormel Chris W
Published: April 2023

The theory of Type I migration has been widely used in many studies. Transiting multiplanet systems offer us the opportunity to examine the consistency between observation and theory, especially for those systems harbouring planets in Mean Motion Resonance (MMR). The displacement these resonant pairs show from exact commensurability provides us with information on their migration and eccentricity-damping histories. Here, we adopt a probabilistic approach, characterized by two distributions – appropriate for either the resonant or non-resonant planets – to fit the observed planet period ratio distribution. With the Markov chain Monte Carlo (MCMC) method, we find that ${\approx }15{{\ \rm per\ cent}}$ of exoplanets are in first-order (j + 1: j) MMRs, the ratio of eccentricity-to-semimajor axis damping is too high to allow overstable librations, and that the results are by-and-large consistent with Type-I migration theory. In addition, our modelling finds that a small fraction of resonant pairs is captured into resonance during migration, implying late planet formation (gas-poor). Most of the resonant pairs park themselves at the migration barrier, indicating early planet formation (gas-rich). Furthermore, after improving the criterion on two-body resonant trapping, we obtain an upper limit of the disc surface density at the time the planets are locked in resonance.
SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions
Authors: Taylor Cherish A , Grant Stephanie M , Jursa Thomas , Melkote Ashvini , Fulthorpe Rebecca , Aschner Michael , Smith Donald R , Gonzales Rueben A , Mukhopadhyay Somshuvra
Published: April 2023

Loss-of-function mutations in SLC30A10 induce hereditary manganese (Mn)-induced neuromotor disease in humans. We previously identified SLC30A10 to be a critical Mn efflux transporter that controls physiological brain Mn levels by mediating hepatic and intestinal Mn excretion in adolescence/adulthood. Our studies also revealed that in adulthood, SLC30A10 in the brain regulates brain Mn levels when Mn excretion capacity is overwhelmed (e.g. after Mn exposure). But, the functional role of brain SLC30A10 under physiological conditions is unknown. We hypothesized that, under physiological conditions, brain SLC30A10 may modulate brain Mn levels and Mn neurotoxicity in early postnatal life because body Mn excretion capacity is reduced in this developmental stage. We discovered that Mn levels of pan-neuronal/glial Slc30a10 knockout mice were elevated in specific brain regions (thalamus) during specific stages of early postnatal development (postnatal day 21), but not in adulthood. Furthermore, adolescent or adult pan-neuronal/glial Slc30a10 knockouts exhibited neuromotor deficits. The neuromotor dysfunction of adult pan-neuronal/glial Slc30a10 knockouts was associated with a profound reduction in evoked striatal dopamine release without dopaminergic neurodegeneration or changes in striatal tissue dopamine levels. Put together, our results identify a critical physiological function of brain SLC30A10—SLC30A10 in the brain regulates Mn levels in specific brain regions and periods of early postnatal life, which protects against lasting deficits in neuromotor function and dopaminergic neurotransmission. These findings further suggest that a deficit in dopamine release may be a likely cause of early-life Mn-induced motor disease.
Government funding incentives and study program capacities in public universities: theory and evidence
Authors: Dyrstad Jan Morten , Sohlman Mia Marie Wallgren , Teigen Tor Henrik
Published: April 2023

Objectives aimed at increasing higher education productivity, for instance, measured by credits per student, have stimulated the use of performance-based funding (PBF) by higher education institutions (HEIs). On theoretical grounds, PBF is expected to speed-up study program capacity adjustments through (re)allocations of study places. We conclude from analyses of Norwegian data that study places are adjusted efficiently if there are binding capacity restrictions at the institution level, or competition for students. Strengthened PBF does not affect long-run adjustments. Instead, admissions seem to adjust to secure full enrollment. The results provide an explanation of why very few positive effects of PBF in higher education are found in the literature. Given continued use of PBF to enhance productivity, a likely policy implication is to impose tighter restrictions on the total number of study places allocated to HEIs, or to change the price structure of the PBF model.
Factors Associated With Enrollment into Inpatient Coronavirus Disease 2019 Randomized Controlled Trials: A Cross-sectional Analysis
Authors: Kaczynski Matthew , Benitez Gregorio , Mylona Evangelia K , Tran Quynh-Lam , Atalla Eleftheria , Tsikala-Vafea Maria , Kalagara Saisanjana , Shehadeh Fadi , Mylonakis Eleftherios
Published: April 2023

Background

Clinical trials for coronavirus disease 2019 (COVID-19) have struggled to achieve diverse patient enrollment, despite underrepresented groups bearing the largest burden of the disease and, presumably, being most in need of the treatments under investigation.

Methods

To assess the willingness of patients to enroll into inpatient COVID-19 clinical trials when invited, we conducted a cross-sectional analysis of adults hospitalized with COVID-19 who were approached regarding enrollment. Associations between patient and temporal factors and enrollment were assessed by multivariable logistic regression analysis.

Results

A total of 926 patients were included in this analysis. Overall, Hispanic/Latinx ethnicity was associated with a nearly half-fold decrease in the likelihood to enroll (adjusted odds ratio [aOR], 0.60 [95% confidence interval {CI}, .41–.88]). Greater baseline disease severity (aOR, 1.09 [95% CI, 1.02–1.17]), age 40–64 years (aOR, 1.83 [95% CI, 1.03–3.25]), and age ≥65 years (aOR, 1.92 [95% CI, 1.08–3.42]) were each independently associated with higher likelihood to enroll. Over the course of the pandemic, patients were less likely to enroll during the summer 2021 wave in COVID-19–related hospitalizations (aOR, 0.14 [95% CI, .10–.19]) compared with patients from the first wave in winter 2020.

Conclusions

The decision to enroll into clinical trials is multifactorial. Amid a pandemic disproportionately affecting vulnerable groups, Hispanic/Latinx patients were less likely to participate when invited, whereas older adults were more likely. Future recruitment strategies must consider the nuanced perceptions and needs of diverse patient populations to ensure equitable trial participation that advances the quality of healthcare for all.
Petition and response as social process: Royal power, justice and the people in late medieval Castile (
c
.1474–1504)
Authors: Israeli Yanay
Published: April 2023

This article analyses the petition and response process in late medieval Castile, focusing on petitions of grievance submitted to the Royal Council during the reign of Isabel I and Fernando II (r.1474–1504). Studies published in recent decades have revised our understanding of petitionary practices and their significance to systems of governance in medieval and early modern Europe. One persistent gap in this scholarship, however, concerns the ‘aftermath’ of petitioning — that is, the occurrences that followed the grant of petitions and the issuance of royal decrees in response. Drawing on the rich documentation that has survived from late fifteenth- and early sixteenth-century Castile, this article highlights the importance of studying the local spaces of interactions where beneficiaries of royal decrees tried to bring them into effect through acts of claims-making. The evidence from Castile is mobilized to illuminate the forms of negotiation and contestation that informed the presentations of ‘letters of justice’ issued by the Royal Council, the mechanisms used by the royal authority to enforce its commands, and the ways that factors such as speed, publicity and violence shaped the meanings petitioning assumed in different contexts of dispute. The analysis of petitioning bears implications for understanding royal power in the Castilian monarchy, drawing attention to a pattern of intensifying communications between the central royal government and non-elites. As they petitioned the Royal Council, thousands of Castilians sought empowerment in local disputes. At the same time, mass participation in the petitioning process played a major role in legitimizing royal power and furthering its embeddedness in the localities.
Point mutations in the catalytic domain disrupt cellulose synthase (CESA6) vesicle trafficking and protein dynamics
Authors: Huang Lei , Zhang Weiwei , Li Xiaohui , Staiger Christopher J , Zhang Chunhua
Published: April 2023

Cellulose, the main component of the plant cell wall, is synthesized by the multimeric cellulose synthase (CESA) complex (CSC). In plant cells, CSCs are assembled in the endoplasmic reticulum or Golgi and transported through the endomembrane system to the plasma membrane (PM). However, how CESA catalytic activity or conserved motifs around the catalytic core influence vesicle trafficking or protein dynamics is not well understood. Here, we used yellow fluorescent protein (YFP)-tagged AtCESA6 and created 18 mutants in key motifs of the catalytic domain to analyze how they affected seedling growth, cellulose biosynthesis, complex formation, and CSC dynamics and trafficking in Arabidopsis thaliana. Seedling growth and cellulose content were reduced by nearly all mutations. Moreover, mutations in most conserved motifs slowed CSC movement in the PM as well as delivery of CSCs to the PM. Interestingly, mutations in the DDG and QXXRW motifs affected YFP-CESA6 abundance in the Golgi. These mutations also perturbed post-Golgi trafficking of CSCs. The 18 mutations were divided into 2 groups based on their phenotypes; we propose that Group I mutations cause CSC trafficking defects, whereas Group II mutations, especially in the QXXRW motif, affect protein folding and/or CSC rosette formation. Collectively, our results demonstrate that the CESA6 catalytic domain is essential for cellulose biosynthesis as well as CSC formation, protein folding and dynamics, and vesicle trafficking.
Indirect Costs of Financial Distress
Authors: Custódio Cláudia , Ferreira Miguel A , Garcia-Appendini Emilia
Published: April 2023

We estimate the indirect costs of financial distress due to lost sales by exploiting real estate (RE) shocks and cross-supplier variation in RE assets and leverage. We show that for the same client buying from different suppliers, the client’s purchases from distressed suppliers decline by an additional 13% following a drop in local RE prices. The effect is more pronounced in more competitive industries, manufacturing, durable goods, less-specific goods, and when the costs of switching suppliers are low. Our results suggest that clients reduce their exposure to suppliers in financial distress.