bluuebunny/crossref_metadata_2025 huggingface dataset:
Microhabitat of Myotis leibii summer roosts at the southwestern periphery of their range
Authors: Kearny Valerie M. , Perry Roger W. , Risch Thomas S. , Rolland Virginie
Published: May 2023

Understanding microhabitat use is needed to make sound conservation decisions for at-risk, patchy-habitat specialists, such as rock-habitat specialists. Rock habitats offer unique microclimatic refugia for reptiles and mammals. Eastern small-footed bats ( Myotis leibii (Audubon and Bachman, 1842)) use rock roosts during the summer, but data on these summer roosts are lacking for this species classified as (critically) imperiled in several US states and Canadian provinces and globally endangered. Our goal was to characterize the structure and microclimate of Myotis leibii roosts at the southwestern periphery of their range. We predicted that Myotis leibii roost temperatures would be warmer and less variable than ambient temperatures and that solitary bats would use horizontal roosts cooler at night, whereas maternity group roosts would be vertical and warmer at night. During summers of 2019 and 2020, we recorded physical (e.g., width) and temperature attributes of 58  Myotis leibii roosts at 16 sites in the Ouachita Mountains. Crevice roosts of Myotis leibii had narrow dimensions like elsewhere in their range and roost temperatures (measured with iButtons) were warmer and more variable than ambient temperatures. Group roosts were larger and had more stable temperatures than solitary roosts. These findings may be useful for assessing population threats, monitoring roost suitability, identifying roost-rich areas that need protection, and even planning artificial roost structures where natural roosts are limited.
Factors affecting site selection by beavers colonizing streams in the upper Midwest region of the United States
Authors: Rugg David J. , Ribic Christine A. , Donner Deahn M. , Beck Albert J. , Wolcott Daniel M. , Reinecke Sue , Eklund Dan
Published: May 2023

Beaver management requires understanding beaver habitat preferences. Despite the American beaver ( Castor canadensis Kuhl, 1820) being relatively common in the upper Midwest region of the United States, there are no beaver habitat relationship models based on this area. We used 1735 colonization events from long-term monitoring data generated by the Chequamegon-Nicolet National Forest in northern Wisconsin, USA, to determine what geomorphological and biological factors were selected by beavers colonizing new sites. We developed and evaluated prediction performance for three colonization models: geomorphology factors only, geomorphology and vegetation factors, and a full colonization model based on geomorphology, vegetation, and availability of dispersing beavers. Overall, the geomorphology–vegetation–colonizer model was the best model, predicting actual colony locations better than the other two models. Spatially, the landscape open to beaver colonization was a mosaic of streams with suitable and unsuitable habitat. These models improve our understanding of how beaver site selection factors in the upper Midwest region differ from factors identified in the literature for the western and eastern United States. This information may be useful for land managers in this region seeking to spatially target resources for restoring northern forest landscapes such as the Chequamegon-Nicolet National Forest.
Ising Cosmology
Authors: Irges Nikos , Kalogirou Antonis , Koutroulis Fotis
Published: May 2023

Using arguments from holography we propose that the deviation of the cosmological spectral index $$n_S$$

n
S

of scalar fluctuations from unity may be controlled almost entirely by the critical exponent $$\eta $$
η
of the $$d=3$$

d
=
3

Ising model.
Content and Location Based Point-of-Interest Recommendation System Using HITS Algorithm
Authors: Vinodha R. , Parvathi R.
Published: May 2023

A study of geographic information has become a significant field of concentrate in software engineering because of the expansion of much information created by electronic gadgets fit together geographic data from people, like advanced mobile phones and GPS gadgets. Area facts allow a deeper understanding of users’ options and actions by bridging the gap between the physical and digital worlds. This expansion of wide geo-spatial datasets has inspired studies into novel recommender systems that aim to make users’ travels and social interactions easier. This huge amount of data generated by these devices has prompted an increase in the number of research activities and procedures aimed at breaking down and recovering useful data based on these large datasets. The aim of this challenge is to study GPS directions from a variety of people, as well as examine and apply computational strategies to recover useful data from those directions, useful data from GPS directions, including areas of interest and people’s proximity, and then create an instrument for information representation. This paper demonstrates how data mining techniques is used to recover valuable information from spatial data. As well as how such data can be useful in understanding people and areas within a district. Depending on the outcomes, we recommend a HITS (Hypertext Induced Topic Search) based POI recommendation calculation that can take into account the effect of social connections when recommending POIs to individual users.
Comprehensive standard system for generalized mixed module and its application to singularity theory
Authors: Teramoto Hiroshi , Nabeshima Katsusuke
Published: May 2023

The concept of standard basis for a module is generalized to that for a mixed module that can be written as sums of more than one modules over different rings. An algorithm to compute a standard basis for a mixed module is presented, along with a proof of its correctness and termination in finite steps. The algorithm is demonstrated in several examples appearing in computations of codimensions of divergent diagrams. A parametric extension of the standard basis (comprehensive standard system, CSS) for a mixed-module is also presented, along with a proof of its correctness and termination in finite steps and its computational algorithms. The algorithm is demonstrated in several examples in the classification of divergent diagrams including applications of Mather’s lemma and the complete transversal theorem.
On the harmonic evolute of time-like Hasimoto surfaces in Lorentz–Minkowski space
Authors: Khalifa Saad M.
Published: May 2023

The movement of a thin vortex in a thin viscous fluid by the motion of a curve propagating in Lorentz–Minkowski space [Formula: see text] is described by the vortex filament or smoke ring equation and can be viewed as a dynamical system on the space curves in [Formula: see text]. This paper investigates the harmonic evolute surfaces of time-like Hasimoto surfaces in [Formula: see text]. Also, we discuss the geometric properties of these surfaces, namely, we obtain the Gaussian and mean curvatures of the first and second fundamental forms. As a verification, we construct a concrete example for the meant surfaces to demonstrate our theoretical results.
Nanoparticles Surface Energy Effect on Mechanical Properties and Microscopic Deformation of 3D Heterogeneous Nanostructures
Authors: Bilal Khan Muhammad , Mustafa Azeem M. , Qasim Zafar Muhammad , Hussain Ghulam
Published: May 2023

Nanoparticle-contained graphene foam material has attracted many practical applications in recent years, which require an in-depth comprehension of the basic mechanics of these heterogenous materials. In this paper, the effect of nanoparticles surface energy on the mechanical properties of nanoparticle-filled graphene foam under uniaxial tension and compression is systematically studied by the coarse-grained molecular dynamics simulation method. The mechanical strength of these nanoparticle-filled graphene foam is directly influenced by tuning the nanoparticles surface energy. The varying peeling-off behaviors of graphene sheets influenced by the surface energy of nanoparticles are observed. The stress distribution under uniaxial compression and tension at different nanoparticles surface energy is also studied. The mechanical behavior of nanoparticle-filled graphene foam is directly dependent on nanoparticles surface energy. The results should be helpful not only to understand the micro mechanism of such nanomaterials, but also to the design of advanced composites and devices based on porous materials mixed with particles.
Simulation research on breakdown diagnosis based on least squares support vector machine optimized by simulated annealing genetic algorithm
Authors: Zhang Dawei , Li Weilin , Wang Chenggang , Li Jianhai
Published: May 2023

The application of support vector machine to the aircraft power supply system breakdown diagnosis is one of the research focuses in the tomorrow. Support vector machine (SVM) belongs a new type of machine learning technique, which uses structural hazard minimization rule to substitute for the conventional empirical hazard minimization according to great specimen. The powerful performance of the least squares support vector machine (LSSVM) needs to be reflected in the optimal selection of appropriate parameters, and the quality of parameters greatly affects the accuracy and efficiency of breakdown diagnosis. The traditional LSSVM parameters selection method is inefficient, the calculation is huge, and it takes expensive time to select the satisfactory solution. Aiming at the problem of parameters selection of LSSVM, the way of optimizing the parameters of LSSVM by apply simulated annealing genetic algorithm (SAGA) is proposed. SAGA uses the parallel sampling process of genetic algorithm to improve the time performance of optimization, and makes use of the simulated annealing algorithm to dominate the constriction of majorization to prevent precocity. On the one hand, genetic algorithm has strong ability to grasp the overall search process, on the other hand, simulated annealing algorithm is used to control the convergence of the algorithm to prevent premature phenomenon. The automatic optimal selection of LSSVM parameters is achieved. The Iris system classification and recognition in the UCI machine learning database and the breakdown diagnosis of the autopilot flight control box are used as experimental platforms to obtain data samples for simulation research. The simulation results show that LSSVM optimized by SAGA improves both the accuracy and efficiency of classification recognition. It not only effectively overcomes the problem of low efficiency caused by searching optimal parameters by experience, but also effectively improves the accuracy of classification recognition. The false alarm rate and redundant breakdowns are effectively reduced.
Increasing the Robustness of TERO-TRNGs Against Process Variation
Authors: Skubich Christian , Reichel Peter , Reichenbach Marc
Published: May 2023

The transition effect ring oscillator is a popular design for building entropy sources because it is compact, built from digital elements only, and is very well suited for FPGAs. However, it is known to be quite sensitive to process variation. Although the latter is useful for building physical unclonable functions, it is interfering with the application as an entropy source.

In this article, we investigate an approach to increase reliability. We show that adding a third stage eliminates much of the susceptibility to process variation and how a resulting gigahertz oscillation can be evaluated on an FPGA. The design is supported by physical and stochastic modeling. The physical model is validated using an experiment with dynamically reconfigurable look-up tables.
Fréchet Distance for Uncertain Curves
Authors: Buchin Kevin , Fan Chenglin , Löffler Maarten , Popov Aleksandr , Raichel Benjamin , Roeloffzen Marcel
Published: May 2023

In this article, we study a wide range of variants for computing the (discrete and continuous) Fréchet distance between uncertain curves. An uncertain curve is a sequence of
uncertainty regions,
where each region is a disk, a line segment, or a set of points. A
realisation
of a curve is a polyline connecting one point from each region. Given an uncertain curve and a second (certain or uncertain) curve, we seek to compute the lower and upper bound Fréchet distance, which are the minimum and maximum Fréchet distance for any realisations of the curves.

We prove that both problems are NP-hard for the Fréchet distance in several uncertainty models, and that the upper bound problem remains hard for the discrete Fréchet distance. In contrast, the lower bound (discrete [
5
] and continuous) Fréchet distance can be computed in polynomial time in some models. Furthermore, we show that computing the expected (discrete and continuous) Fréchet distance is #P-hard in some models.

On the positive side, we present an FPTAS in constant dimension for the lower bound problem when Δ/δ is polynomially bounded, where δ is the Fréchet distance and Δ bounds the diameter of the regions. We also show a near-linear-time 3-approximation for the decision problem on roughly δ-separated convex regions. Finally, we study the setting with Sakoe–Chiba time bands, where we restrict the alignment between the curves, and give polynomial-time algorithms for the upper bound and expected discrete and continuous Fréchet distance for uncertainty modelled as point sets.
ElectAnon: A Blockchain-based, Anonymous, Robust, and Scalable Ranked-choice Voting Protocol
Authors: Onur Ceyhun , Yurdakul Arda
Published: May 2023

Remote voting has become more critical in recent years, especially since the COVID-19 outbreak. Blockchain technology and its benefits such as decentralization, security, and transparency have given rise to proposals for blockchain-based voting systems. However, the traceability of blockchain transactions violates voter anonymity in existing proposals. Besides, transaction costs also need to be considered. Solutions that may cause repeated elections should be avoided for a low-cost scalable voting system. In this work, we propose ElectAnon, a blockchain-based, self-tallying, and ranked-choice voting protocol focusing on anonymity, robustness, and scalability. ElectAnon achieves anonymity by enabling voters to register with identity commitments and cast their votes via zero-knowledge proofs. Robustness is realized by removing the direct control of the authorities in the voting process by using timed-state machines. Each voter encodes the ballot into a single integer and blinds the vote off-chain while making the verification on-chain. This makes the protocol infinitely scalable in the number of voters. ElectAnon is also a solution for governance in Decentralized Autonomous Organizations (DAO): It includes a candidate proposal module and an algorithm-agnostic mechanism to plug-in different tallying methods easily. The
Merkle forest
extension is proposed for conducting even more trustless elections. ElectAnon is implemented with smart contracts based on Ethereum Virtual Machine (EVM) and a zero-knowledge gadget, Semaphore. The implementation also includes two different sophisticated tallying methods, Borda Count and Tideman. Experimental results show that a 40-voter and 10-candidate election can be implemented with the gas consumption reduced up to 89% compared to previous works. While other studies could not exceed a 25,000-voter setup, ElectAnon has been observed to run safely for 1,000,000 voters. The implementation can be found at
https://github.com/ceyonur/electanon
.
Effects of Varieties and Different Environments on Growth and Yield Performance of Shallot (Allium cepa var. aggregatum)
Authors: Yeshiwas Yebirzaf , Temsegen Zebyder , Wubie Mengistu , Wagnew Tadessu
Published: May 2023

Shallot (Allium cepa var. aggregatum) is one of the major cash crops produced in the Amhara region, including East Gojjam Zone, Ethiopia. However, the shallot is being out of production, and there are limited research efforts concerning the influence of the growing environment on shallot varieties. Thus, the objective of the study was to identify adaptable and high-yielding shallot varieties across different agroecologies/location in the East Gojjam Zone of Ethiopia. The experiment was conducted at three locations (Debre Markos, Wonka, and Yelam Gej) during 2019/20 and 2020/21 growing seasons. The study consists of four shallot varieties (Minjar, Huruta, Negelle, and local). The experiment was conducted in a randomized complete block design with three replications. Data on growth, yield, and yield component parameters were recorded and analyzed using SAS Computer Software version 9.0. The present results indicated that the highest plant height, leaf length, number of shoots per plant, number of bulblets per bulb, average bulb weight, total yield, and marketable yield per hectare were recorded from improved shallot varieties Minjar, Negelle, and Huruta. Thus, Minjar, Negelle, and Huruta were better performed for growth, yield, and yield components at all testing locations. Thus, Minjar, Negelle, and Huruta were found to be superior in yield and yield components at all testing locations and were thus suggested to be used by the growers in the study area. It would be advisable to evaluate the varieties in the participatory varietal trail for further dissemination of varieties to shallot growers in the study area.
Prolonged Disease Course of COVID-19 in a Patient with CTLA-4 Haploinsufficiency
Authors: Hoffman T. W. , Leavis H. L. , Smits B. M. , van der Veken L. T. , van Kessel D. A.
Published: May 2023

Patients with primary immunodeficiencies are especially vulnerable to developing severe coronavirus disease 2019 (COVID-19) after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important regulator of immune responses, and patients who suffer from CTLA4 haploinsufficiency have hyperactivation of effector T cells and infiltration of various organs. Overexpression of CTLA4 has been associated with a more severe disease course in patients with COVID-19, but there have only been a few reports on the disease course of COVID-19 in patients with CTLA4 haploinsufficiency. We report on a 33-year-old female with a history of immune thrombocytopenia, autoimmune haemolytic anaemia, granulomatous-lymphocytic interstitial lung disease, and common variable immunodeficiency who developed COVID-19. She was admitted and discharged from the hospital several times in the months thereafter and remained symptomatic and had a positive SARS-CoV-2 PCR for up to 137 days after the first symptoms. No SARS-CoV-2 antibodies were identified in the patients’ serum. The disease was finally controlled after repeated infusions of convalescent plasma and treatment of concurrent bacterial and fungal infections. Genetic analysis revealed a likely pathogenic variant in CTLA4, and CTLA4 expression on regulatory T-cells was low. This case illustrates that patients with primary immunodeficiencies who have a protracted disease course of COVID-19 could benefit from convalescent plasma therapy.
A Randomized Controlled Study of Robot-Assisted versus 3D Laparoscopic Radical Prostatectomy in Patients with Carcinoma Prostate
Authors: Kapoor Ketan Kumar , Kumar Anup
Published: May 2023

Background and Objectives. The objectives of this study are to report a single institute and single surgeon outcomes comparing 3D laparoscopic radical prostatectomy vs robotically assisted technique in the form of preoperative, intraoperative, or postoperative parameters. Materials and Methods. A prospective randomized comparative study was performed from 1st January 2020 to 30th June 2021. All patients included were diagnosed with localized/locally advanced ca prostate. 60 patients fulfilling the inclusion and exclusion criteria were randomized into 2 groups. Groups A and B included patients who underwent robot-assisted radical prostatectomy and 3D laparoscopic transperitoneal radical prostatectomy, respectively. Various demographic, intraoperative, postoperative, and follow-up parameters were collected. Outcomes were evaluated in the form of the trifecta (continence, potency, and BCR-free status) and pentafecta rates (trifecta with no perioperative complications and negative surgical margins) in between the two groups. Results. The mean operative time in Group A was 137.83 mins ± 17.27 compared to 148.20 mins ± 26.16 in Group B. Trifecta rates in Group A and Group B were 43.3%, 63.3%, and 76.6% and 40%, 53.3%, and 70% at 1, 3, and 6 months. Pentafecta rates in Group A and Group B were 36.6%, 53.3%, and 70% and 33.3%, 40%, and 53.3% at 1, 3, and 6 months. Complication rates were 10% in Group A and 13.3% in Group B, respectively. Only one patient in our study (Group B) had a positive surgical margin. Conclusions. We conclude from our comparative study, that both robot-assisted and 3D laparoscopic transperitoneal radical prostatectomy are feasible and efficacious treatment modalities for achieving acceptable trifecta and pentafecta rates in managing ca prostate with earlier continence and shorter urethrovesical anastomosis time in the robotic arm.
Effect of Multilayers CdS Nanocrystalline Thin Films on the Performance of Dye-Sensitized Solar Cells
Authors: Hussain Abdullah A. , Abdulelah Haider , Amteghy Ali H. , Dheyab Raed A. , Hamdan AlMulla Ban
Published: May 2023

Due to relatively low price and nontoxicity of photovoltaic (PV) systems, dye-sensitized solar cells (DSSCs) recently gained a lot of attention in terms of improving their performance and longevity. Because most of the major elements are impacted by their separate production and layering procedures, the substances in DSSCs are critical to achieving these goals. Methylene blue dye sensitizer-based solar cells were effectively constructed in this work, and DSSC performance was assessed. The morphologies of nanocrystalline CdS thin films were investigated by the FE-SEM machine, and then XRD patterns of 1 layer, 2 layers, and 3 layers of nanocrystalline CdS thin films were analyzed. The thicknesses of the prepared samples were about 391 nm, 457 nm, and 912 nm for 1, 2, and 3 layers of nanocrystalline CdS thin film, respectively. J-V characteristics of the multilayer CdS thin films have been studied under a 100 mW/cm2 sunlight source. The experimental results revealed that the highest power conversion efficiency of a 3 layer porous-nanowall CdS/MB device was about 0.47%.
Proteomic Characterization of Human Gut Habitual Bacteroides intestinalis against Common Intestinal Bile Acid Stress
Authors: Sun Zeyu , Wang Yu , Su Xiaoling , Yang Xue , Luo Qixia
Published: May 2023

Bacteroides intestinalis (B. intestinalis) is an abundant gastrointestinal commensal bacterium and is able to produce secondary bile acids (BAs) among other important metabolic functions. However, deoxycholic acid (DCA) is known to suppress Bacteroides, suggesting differential molecular impact of different BA species on Bacteroides. Among major human gastrointestinal BA components, we first demonstrated that DCA and chenodeoxycholic acid (CDCA) and their taurine-conjugated species at 1 mM showed significantly higher inhibitory effects on the growth of B. intestinalis than cholic acid (CA) and lithocholic acid (LCA) and their taurine-conjugated species. Then, high-throughput proteomic strategy was used to show that both TCDCA and TDCA caused more proteome-wide modulation than TCA and TLCA. In response to incremental BA toxicity, the main functional changes of B. intestinalis include enhanced protein synthesis, DNA integrity maintenance, and suppressed central metabolic activities. Importantly, key energy and BA metabolism enzymes of B. intestinalis were inhibited by TCDCA and TDCA. These findings provide a basis for future studies to explore how Bacteroides respond to bile stress and how BA composition modulate gut microbiome homeostasis.
Supplementary Figure from Association of Prostate-Specific Antigen Levels with Prostate Cancer Risk in a Multiethnic Population: Stability Over Time and Comparison with Polygenic Risk Score
Authors: Chou Alisha , Darst Burcu F. , Wilkens Lynne R. , Marchand Loïc Le , Lilja Hans , Conti David V. , Haiman Christopher A.
Published: May 2023

Supplementary Figure from Association of Prostate-Specific Antigen Levels with Prostate Cancer Risk in a Multiethnic Population: Stability Over Time and Comparison with Polygenic Risk Score
Supplementary Tables 1-4; Supplementary Figures 1-4 from Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk
Authors: Drummond Ann E. , Swain Christopher T.V. , Milne Roger L. , English Dallas R. , Brown Kristy A. , Skinner Tina L. , Lay Jannelle , van Roekel Eline H. , Moore Melissa M. , Gaunt Tom R. , Martin Richard M. , Lewis Sarah J. , Lynch Brigid M.
Published: May 2023

Supplementary Material and Methods includes search terms; excluded papers; study characteristics; risk of bias; forest plots; funnel plots. Supplementary Table 1: Search terms used for each component of the systematic review. Supplementary Table 2: Papers Excluded at Full Text Screen.* Supplementary Table 3A: Study characteristics of Mendelian randomisation studies. Supplementary Table 3B: Study characteristics of prospective cohort studies. Supplementary Table 4. Risk of Bias: Prospective Cohort Studies. Figure 1: Funnel plots. Figure 2: IGF-1 and breast cancer risk in models that adjust for IGFBP-3. Figure 3: IGF-1 and breast cancer risk by menopause status at blood draw. Figure 4: IGFBP-3 and breast cancer risk by menopause status at blood draw
Supplementary Data from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy
Authors: Ykema Berbel L.M. , Gini Andrea , Rigter Lisanne S. , Spaander Manon C.W. , Moons Leon M.G. , Bisseling Tanya M. , de Boer Jan Paul , Verbeek Wieke H.M. , Lugtenburg Pieternella J. , Janus Cecile P.M. , Petersen Eefke J. , Roesink Judith M. , van der Maazen Richard W.M. , Aleman Berthe M.P. , Meijer Gerrit A. , van Leeuwen Flora E. , Snaebjornsson Petur , Carvalho Beatriz , van Leerdam Monique E. , Lansdorp-Vogelaar Iris
Published: May 2023

Supplementary Data from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy
Supplementary Figure from Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study
Authors: Cross Temara , George Anthony , Attwood Kristopher , Zhang Yali , O'Connor Tracey L. , Barone Nancy , Hulme Karen , Ambrosone Christine B. , Yao Song , Hong Chi-Chen
Published: May 2023

Supplementary Figure from Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study
Data from Associations of Individual and Combined Physical Activity and Body Mass Index Groups with Proinflammatory Biomarkers among Colorectal Cancer Patients
Authors: Himbert Caroline , Warby Christy A. , Gigic Biljana , Ose Jennifer , Lin Tengda , Viskochil Richard , Peoples Anita R. , Ashworth Anjelica , Schrotz-King Petra , Scaife Courtney L. , Cohan Jessica N. , Jedrzkiewicz Jolanta , Schirmacher Peter , Grady William M. , Cohen Stacey A. , Krane Mukta , Figueiredo Jane C. , Toriola Adetunji T. , Siegel Erin M. , Shibata David , Round June L. , Huang Lyen C. , Li Christopher I. , Schneider Martin , Ulrich Alexis , Hardikar Sheetal , Ulrich Cornelia M.
Published: May 2023

AbstractBackground:
Physical activity and obesity are well-established factors of colorectal cancer risk and prognosis. Here, we investigate associations of individual and combined physical activity and body mass index (BMI) groups with proinflammatory biomarkers in colorectal cancer patients.
Methods:
Self-reported physical activity levels were classified as “active” (≥8.75 MET-hours/week) versus “inactive” (<8.75 MET-hours/week) in n = 579 stage I–IV colorectal cancer patients enrolled in the ColoCare Study. BMI [normal weight (≥18.5–<25 kg/m2), overweight (≥25–<30 kg/m2), and obese (≥30 kg/m2)] was abstracted from medical records. Patients were classified into four combinations of physical activity levels and BMI. Biomarkers [C-reactive protein (CRP), SAA, IL6, IL8, and TNFα] in presurgery serum samples were measured using the Mesoscale Discovery Platform. Regression models were used to compute relative percent differences in biomarker levels by physical activity and BMI groups.
Results:
“Inactive” patients had non-statistically significant higher IL6 levels compared with “active” patients (+36%, P = 0.10). “Obese” patients had 88% and 17% higher CRP and TNFα levels compared with “normal weight” patients (P = 0.03 and 0.02, respectively). Highest CRP levels were observed among “overweight or obese/inactive” compared with “normal weight/active” patients (P = 0.03).
Conclusions:
We provide evidence of associations between individual and combined physical activity and BMI groups with proinflammatory biomarkers. Although BMI was identified as the key driver of inflammation, biomarker levels were higher among “inactive” patients across BMI groups.
Impact:
This is the largest study in colorectal cancer patients investigating associations of energy balance components with inflammatory biomarkers. Our results suggest that physical activity may reduce obesity-induced inflammation in colorectal cancer patients and support the design of randomized controlled trials testing this hypothesis.
Data from Tumor Mutational Burden by Whole-Genome Sequencing in Resected NSCLC of Never Smokers
Authors: Ruel Louis-Jacques , Li Zhonglin , Gaudreault Nathalie , Henry Cyndi , Saavedra Armero Victoria , Boudreau Dominique K. , Zhang Tongwu , Landi Maria Teresa , Labbé Catherine , Couture Christian , Desmeules Patrice , Joubert Philippe , Bossé Yohan
Published: May 2023

AbstractBackground:
Data are scarce about tumor mutational burden (TMB) as a biomarker in never smokers with non–small cell lung cancer (NSCLC).
Methods:
TMB was assessed by whole-genome sequencing (WGS) and compared with in silico reduced whole-exome sequencing (WES) and targeted commercial next-generation sequencing (NGS) gene panels in 92 paired tumor-normal samples from never smokers who underwent NSCLC resection with curative intent. Analyses were performed to test for association with survival after surgery and to identify the optimal prognostic TMB cutoff.
Results:
Tumors of never smokers with NSCLC had low TMB scores (median 1.57 mutations/Mb; range, 0.13–17.94). A TMB cutoff of 1.70 mutations/Mb was associated with a 5-year overall survival of 58% in the high-TMB (42% of cases) compared with 86% in low-TMB patients (Wald P = 0.0029). TMB scores from WGS and WES were highly correlated (Spearman ρ = 0.93, P < 2.2e−16). TMB scores from NGS panels demonstrated high intraindividual fluctuations and identified high-TMB patients with 65% concordance in average compared with WGS.
Conclusions:
In resected NSCLC of never smokers, high TMB was associated with worse prognosis. WES provided a good estimate of TMB while targeted NGS panels seem to lack adequate depth and resolution in the setting of low mutation burden.
Impact:
TMB is a prognostic indicator of survival in resected NSCLC from individuals who never smoked. In this setting of low mutation counts, TMB can be accurately measured by WGS or WES, but not NGS panels.
Data from Validation of BD Onclarity HPV Assay on Vaginal Self-Samples versus Cervical Samples Using the VALHUDES Protocol
Authors: Latsuzbaia Ardashel , Vanden Broeck Davy , Van Keer Severien , Weyers Steven , Donders Gilbert , Doyen Jean , Tjalma Wiebren , De Sutter Philippe , Peeters Eliana , Vorsters Alex , Arbyn Marc
Published: May 2023

AbstractBackground:
In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples.
Methods:
Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31–49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation.
Results:
The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90–1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02–1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94–1.06) and 1.15 (95% CI, 1.05–1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79–1.04) and 1.03 (95% CI, 0.95–1.13), respectively for Qvintip.
Conclusions:
Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples.
Impact:
VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.
Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case–Control Study from the Ovarian Cancer Association Consortium
Authors: Gersekowski Kate , Ibiebele Torukiri I ,   for the Australian Ovarian Cancer Study Group, Doherty Jennifer A. , Harris Holly R. , Goodman Marc T. , Terry Kathryn L. , Wu Anna H. , Bandera Elisa V. , Qin Bo , Ong Jue-Sheng , Tyrer Jonathan P. , Dixon-Suen Suzanne C. , Modugno Francesmary , Risch Harvey A , Webb Penelope M.
Published: May 2023

Background:

Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown.

Methods:

We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status.

Results:

Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR.

Conclusions:

High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis.

Impact:

Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.
FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors
Authors: Duke Elizabeth S. , Bradford Diana , Marcovitz Michelle , Amatya Anup K. , Mishra-Kalyani Pallavi S. , Nguyen Emily , Price Lauren S.L. , Fourie Zirkelbach Jeanne , Li Yangbing , Bi Youwei , Kraft Jeffrey , Dorff Sarah E. , Scepura Barbara , Stephenson Maritsa , Ojofeitimi Idara , Nair Abhilasha , Han Yu , Tezak Zivana , Lemery Steven J. , Pazdur Richard , Larkins Erin , Singh Harpreet
Published: May 2023

On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval was based on data from Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), an international, non-randomized, multi-cohort clinical trial that included patients with advanced solid tumors harboring RET alterations. The overall response rate in 41 patients with locally advanced or metastatic RET fusion-positive solid tumors other than non–small cell lung cancer (NSCLC) or thyroid cancer was 44% [95% confidence interval (CI), 28%–60%], with median duration of response 24.5 months (95% CI, 9.2–not evaluable). Patients with 10 of 14 tumor types with a variety of fusion partners had objective responses, including patients with the following tumors: pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft-tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma. The recommendation for approval was supported by results from LIBRETTO-001 in patients with RET fusion-positive NSCLC and thyroid cancer, which formed the basis of prior approvals in these tumor types. The most common adverse reactions (>25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. This is the first tissue-agnostic approval of a RET-directed targeted therapy.
Fibronectin Contributes to a BRAF Inhibitor–driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2
Authors: Hicks Hannah M. , Pozdeyev Nikita , Sams Sharon B. , Pugazhenthi Umarani , Bales Elise S. , Hofmann Marie-Claude , McKenna Logan R. , Schweppe Rebecca E.
Published: May 2023

Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, patients with BRAF-mutant PTC currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress. Thus, we screened a panel of BRAF-mutant thyroid cancer cell lines to identify new therapeutic strategies. We showed that thyroid cancer cells resistant to BRAF inhibition (BRAFi) exhibit an increase in invasion and a proinvasive secretome in response to BRAFi. Using reverse-phase protein array (RPPA), we identified a nearly 2-fold increase in expression of the extracellular matrix protein, fibronectin, in response to BRAFi treatment, and a corresponding 1.8- to 3.0-fold increase in fibronectin secretion. Accordingly, the addition of exogenous fibronectin phenocopied the BRAFi-induced increase in invasion while depletion of fibronectin in resistant cells resulted in loss of increased invasion. We further showed that BRAFi-induced invasion can be blocked by inhibition of ERK1/2. In a BRAFi-resistant patient-derived xenograft model, we found that dual inhibition of BRAF and ERK1/2 slowed tumor growth and decreased circulating fibronectin. Using RNA sequencing, we identified EGR1 as a top downregulated gene in response to combined BRAF/ERK1/2 inhibition, and we further showed that EGR1 is necessary for a BRAFi-induced increase in invasion and for induction of fibronectin in response to BRAFi.

Implications:

Together, these data show that increased invasion represents a new mechanism of resistance to BRAF inhibition in thyroid cancer that can be targeted with an ERK1/2 inhibitor.
Supplementary Table S2 from Safety and clinical response to combined immunotherapy with autologous iNKT cells and PD-1+CD8+ T cells in patients failing first-line chemotherapy in stage IV pancreatic cancer
Authors: Wang Jing , Cheng Xiaobo , Jin Yanling , Xia Bili , Qin Ran , Zhang Wei , Hu Huiliang , Mao Xiaoting , Zhou Liting , Yan Jia , Zhang Xiaoyan , Xu Jianqing
Published: May 2023

Count of CD8+T cell and iNKT cell products in each course
Data from Safety and Clinical Response to Combined Immunotherapy with Autologous iNKT Cells and PD-1+CD8+ T Cells in Patients Failing First-line Chemotherapy in Stage IV Pancreatic Cancer
Authors: Wang Jing , Cheng Xiaobo , Jin Yanling , Xia Bili , Qin Ran , Zhang Wei , Hu Huiliang , Mao Xiaoting , Zhou Liting , Yan Jia , Zhang Xiaoyan , Xu Jianqing
Published: May 2023

Purpose:
A phase I clinical trial was conducted to assess the safety and feasibility of invariant natural killer T (iNKT) cells combined with PD-1+CD8+ T cells in patients with advanced pancreatic cancer and failing the first-line chemotherapy.
Patients and Methods:
Fifteen eligible patients were enrolled, of whom 9 received at least three cycles of treatment each. In total, 59 courses were administered.
Results:
Fever was the most common adverse event, peaking at about 2–4 hours after cell infusion and reverting within 24 hours without treatment in all patients. Influenza-like reactions such as headache, myalgia, and arthralgia were also observed in 4, 4, and 3 of the patients, respectively. In addition, vomiting and dizziness were prevalent, while abdominal pain, chest pain, rash, and stuffy nose were rare adverse events, each reported in 1 patient. Side effects above grade 2 were not observed. Two patients achieved partial regression, while 1 patient experienced disease progression assessed 4 weeks after the third course. Three patients are still alive at the time of writing and have progression-free survival longer than 12 months. The overall survival time has been extended to over 12 months in 6 of the 9 patients. No constant changes of CD4+ T, B, and NK cells were recorded except for elevated CD8+ T cells after the first course.
Conclusions:
The combination of autologous iNKT cells and PD-1+CD8+ T cells was a safe therapeutic strategy against advanced pancreatic cancer. The patients exhibited a potentially promising prolonged survival time. Further study appears warranted to evaluate the efficacy of these combined cell infusions in pancreatic cancer.
Trial registration:
This trial was included in the clinical trial which was registered in ClinicalTrials.gov (ID:NCT03093688) on March 15, 2017.
Significance:
There is an unmet need for novel, more effective, and tolerable therapies for pancreatic cancer. Here we present a phase I clinical trial employing iNKT cells combined with PD-1+CD8+ T cells in 9 patients with advanced pancreatic cancer and failing the first-line chemotherapy. The combined immunotherapy was shown to be feasible in the enrolled patients with limited side effects and optimistic clinical responses, which could bring opportunity of therapeutic advancement.
Duty and Love: Flora Lee's Resistance to Slavery in Revolutionary Marblehead
Authors: O'brien G. Patrick
Published: May 2023

This study explores the life of Flora Lee, an enslaved Massachusetts woman, who had her daughter spirited away from her during the Revolution. Lee's efforts to be reunited with her daughter in Nova Scotia, and to protect other vulnerable Black children, highlight enslaved women's resistance to their family's enslavement during the Revolutionary Era.
The LOSC Renvois as a Source of Untapped Jurisdiction
Authors: Georgoula Danae F.
Published: May 2023

This article aims to contribute to the discussion around the jurisdictional effects of the express renvois in the substantive rules of the United Nations Convention on the Law of the Sea (LOSC). Through the lens of pre-existing scholarship on the function of the renvois, it examines the function of this type of provision in the Convention and attempts to delineate the scope of jurisdiction granted through them. It is posited that this jurisdiction can be both broad and dynamic, but it has remained largely untapped by States and the judiciary. Prompted by this observation, the possible reasons behind this underutilisation are examined and finally, possible ways to use this mechanism to judicially address some of the contemporary challenges that the ocean is facing are outlined.
Rediscovery of Tomosomus Motschulsky, 1855 (Coleoptera: Anthicidae) with redescription of the genus, a new genus-rank synonym, and a key to species
Authors: TELNOV DMITRY , GUSAKOV ALEXEY A.
Published: May 2023

Tomosomus Motschulsky, 1855, an obscure incertae sedis genus of Anthicidae erroneously considered monotypic, was found to be congeneric with the tomoderine genus Holcopyge Champion, 1890. A new genus-rank synonym (Tomosomus Motschulsky = Holcopyge Champion syn. nov.) and two new combinations are proposed for the species hitherto attributed to Holcopyge. Tomosomus subtestaceus Motschulsky, 1855, the type of its genus, is redescribed from rediscovered type material and recently collected specimens. An annotated checklist, key to species and new records of Tomosomus are provided.
Comparative Analysis of NSQIP National Outcomes and Projected Outcomes versus Our Institutional Outcomes for Robotic Gastrectomy: The Future of Gastric Resection
Authors: Ross Sharona B. , Slavin Moran , Sucandy Iswanto , Crespo Kaitlyn L. , Syblis Cameron C. , Saravanan Sneha , Rosemurgy Alexander S.
Published: May 2023

Background

The robotic approach has vast applications in surgery; however, the utility of robotic gastrectomy has yet to be clearly defined. This study aimed to compare outcomes following robotic gastrectomy at our institution to the national patient-specific predicted outcomes data provided by the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP).

Methods

We prospectively studied 73 patients who underwent robotic gastrectomy under our care. ACS NSQIP outcomes after gastrectomy and predicted outcomes for our patients were compared with our actual outcomes utilizing students t test and chi-square analysis, where applicable. Data are presented as median (mean ± SD).

Results

Patients were 65 (66 ± 10.7) years old with a BMI of 26 (28 ± 6.5) kg/m2. 35 patients had gastric adenocarcinomas and 22 had gastrointestinal stromal tumors Operative duration was 245 (250 ± 114.7) minutes, estimated blood loss was 50 (83 ± 91.6) mL, and there were no conversions to ‘open’. 1% of patients experienced superficial surgical site infections compared to the NSQIP predicted rate of 10% ( P < .05). Length of stay (LOS) was 5 (6 ± 4.2) days vs NSQIP’s predicted LOS of 8 (8 ± 3.2) days ( P < .05). Three patients died during their postoperative hospital course (4%), due to multi-system organ failure and cardiac arrest. 1-year, 3-year, and 5-year estimated survival for patients with gastric adenocarcinoma was 76%, 63%, and 63%, respectively.

Discussion

Robotic gastrectomy yields salutary patient outcomes and optimal survival for varying gastric diseases, particularly gastric adenocarcinoma. Our patients experienced shorter hospital stays and reduced complications relative to patients in NSQIP and predicted outcome for our patients. Gastrectomy undertaken robotically is the future of gastric resection.