bluuebunny/crossref_metadata_2025 huggingface dataset:
Semi-empirical model of galactic cosmic ray spectrum
Authors: Buchvarova M
Published: January 2024

The galactic cosmic rays are high-energy particles that reach us from all directions of the vast universe. Their transport in the interplanetary medium is well described by the transport equation, first derived by Parker in 1965. An approximate solution of the cosmic ray transport equation for 1 AU is used to construct a simplified, semi-empirical model of the cosmic ray spectrum. The model parameters are obtained by fitting the proton spectra of the PAMELA experiment. The values of the model parameters are presented for the period 2006-2014, which includes the solar minimum between cycles 23 and 24 and the maximum phase of cycle 24. Our analysis shows that the proposed semi-empirical model agrees approximately well with the force-field approximation to the cosmic ray transport equation.
The forward calorimeter of the ALICE experiment at CERN LHC
Authors: Simeonov Radoslav ,   the ALICE Collaboration
Published: January 2024

A new forward calorimeter (FoCal), covering the pseudorapidity range 3.4 ≤ η ≤ 5.8, is proposed in order to extend the physics reach of ALICE during the LHC Run 4. The FoCal comprises a high-granularity electromagnetic calorimeter with silicon pixel and pad readout as well as a hadronic calorimeter. FoCal gives access to the nuclear gluon densities down to Bjorken-x ∼ 10−6, where they are not constrained by other measurements and their evolution may be affected by non-linear effects of quantum chromodynamics. The hadronic subsystem of FoCal (FoCal-H) will be based on capillary copper tubes with scintillating fibers inside. A full-length prototype was assembled and it was exposed to a non-separated charged particle beam in the H2 SPS CERN beamline in November 2022. An energy scan from 60 to 350 GeV was performed and the reconstructed signals are processed in a custom developed ROOT based environment. The design of the 2022 prototype as well as the first results from the energy reconstruction are presented.
Study of the motivation for choosing physics as an elective course among 10th-grade students
Authors: Kotseva I. , Yaneva N.
Published: January 2024

The article presents the original results of a study of various parameters of motivation for choosing physics as an elective course among students in the 10th grade of High schools in Bulgaria. Since motivation is one of the main factors for taking certain actions, it also determines whether or not a student will choose physics as an elective course after the 10th grade. That is why it is very important to find out those motivational features that are a prerequisite for choosing the “Physics” profile in high school. One possible way to analyze these features is to look for statistically significant differences using the independent samples method. The instrument of measurement and the selection of the independent samples are described in the Methods of Research section, followed by the presentation of the Statistical analysis and the results and their interpretation in the Results and Discussion section.
Complex analysis of earthquake deformations using SAR images: Examples from Croatia and Greece
Authors: Dimova L , Raykova R
Published: January 2024

This study presents an assessment of the displacements of the Earth’s crust generated by two earthquakes: one in Croatia on 29th December 2020 and one in Greece on 3rd March 2021. The main data source is SAR satellite images from Sentinel-1A and B (ascending and descending orbits) in the form of images of the amplitude and phase signals. The data is processed via SNAP software package. The results are obtained applying the differential radar interferometry method (DInSAR). The Line of Sight (LoS) displacements are converted into vertical displacements and compared with modeled deformations of the Earth’s surface using rectangle finite source model proposed by Okada.
Methodology based on the Hu moment invariants for object comparison on radar satellite imagery
Authors: Gancheva Irina , Peneva Elisaveta
Published: January 2024

In this paper we present a methodology for comparing objects, identified on satellite images acquired by Synthetic Aperture Radar (SAR). The methodology describes object transformations mathematically and provides a quantitative estimate of the similarity of different shapes. To demonstrate its capabilities we examine a case study – we detect an underwater structure in the Western Black Sea, which becomes visible on radar imagery under favourable sea conditions. Our aim is to quantitatively describe if it changes over time and to determine on which dates the detections reveal the greatest similarity.

The suggested methodology is based on computation of the Hu moment invariants, or the image moments. They give a set of 7 invariants, which describe object transformations, such as translation, scale, rotation and reflection. The presented methodology can be applied in different contexts on satellite imagery for quantitative description of structure transformations.
Architectural gear ratio depends on actuator spacing in a physical model of pennate muscle
Authors: Sleboda David A , Roberts Thomas J , Azizi Emanuel
Published: January 2024

Pennate muscles are defined by the architectural arrangement of their muscle fibers, which run at an angle to the primary axis of muscle shortening. Pennation angles can vary dynamically over the course of individual contractions, influencing the speed and distance of muscle shortening. Despite their relevance to muscle performance, the physical mechanisms that drive dynamic changes in pennation angle remain poorly understood. Muscle fibers bulge radially as they shorten, a consequence of maintaining a constant internal fluid volume, and we hypothesized that radial interactions between tightly packed muscle fibers are essential to dynamic pennation angle changes. To explore this, we built physical models of pennate muscles in which the radial distance between fiber-like actuators could be experimentally altered. Models were built from pennate arrays of McKibben actuators, a type of pneumatic actuator that forcefully shortens and bulges radially when inflated with compressed air. Consistent with past studies of biological muscle and engineered pennate actuators, we found that the magnitude of pennation angle change during contraction varied with load. Importantly, however, we found that pennation angle changes were also strongly influenced by the radial distance between neighboring McKibben actuators. Increasing the radial distance between neighboring actuators reduced pennation angle change during contraction and effectively eliminated variable responses to load. Radial interactions between muscle fibers are rarely considered in theoretical and experimental analyses of pennate muscle; however, these findings suggest that radial interactions between fibers drive pennation angle changes and influence pennate muscle performance. Our results provide insight into the fundamental mechanism underlying dynamic pennation angle changes in biological muscle and highlight design considerations that can inform the development of engineered pennate arrays.
Hydrodynamic analysis of fin–fin interactions in two-manta-ray schooling in the vertical plane
Authors: Huang Zihao , Menzer Alec , Guo Jiacheng , Dong Haibo
Published: January 2024

This study investigates the interaction of a two-manta-ray school using computational fluid dynamics simulations. The baseline case consists of two in-phase undulating three-dimensional manta models arranged in a stacked configuration. Various vertical stacked and streamwise staggered configurations are studied by altering the locations of the top manta in the upstream and downstream directions. Additionally, phase differences between the two mantas are considered. Simulations are conducted using an in-house developed incompressible flow solver with an immersed boundary method. The results reveal that the follower will significantly benefit from the upstroke vortices (UVs) and downstroke vortices depending on its streamwise separation. We find that placing the top manta 0.5 body length (BL) downstream of the bottom manta optimizes its utilization of UVs from the bottom manta, facilitating the formation of leading-edge vortices (LEVs) on the top manta’s pectoral fins during the downstroke. This LEV strengthening mechanism, in turn, generates a forward suction force on the follower that results in a 72% higher cycle-averaged thrust than a solitary swimmer. This benefit harvested from UVs can be further improved by adjusting the phase of the top follower. By applying a phase difference of

π

/

3

to the top manta, the follower not only benefits from the UVs of the bottom manta but also leverages the auxiliary vortices during the upstroke, leading to stronger tip vortices and a more pronounced forward suction force. The newfound interaction observed in schooling studies offers significant insights that can aid in the development of robot formations inspired by manta rays.
Bridging the gap between the water-energy-food nexus and compound risks
Authors: Leah Jones-Crank J , Lu Jessie , Orlove Ben
Published: January 2024

The water-energy-food (WEF) nexus is a concept and approach to examine the interactions of water, energy, and food resources. Similarly, compound risks are a set of risk types that consider multiple connected factors that amplify risks. While both concepts are promoted as approaches to move beyond silos and address complex problems in environmental governance, there has been limited exploration of their overlap. Our study integrates these two approaches for more holistic assessment and management of resources in the context of climate risks. We examine the connections between the WEF nexus and compound risk in two ways. First, we review the literature to identify previous conceptual connections between the WEF nexus and compound risks. Second, we review seven case studies with WEF nexus interactions and compound risks to identify how the two approaches might be considered in practice. Our results demonstrate that there is limited, though not non-existent, integration of the two concepts in both the theoretical literature and in the case studies. The four of the seven cases that do show some level of connection in practice demonstrate opportunities for greater integration in the future, such as leveraging the water sector as a bridge to address WEF nexus and compound risk challenges together.
Focus on the future of water-limited agricultural landscapes
Authors: Peterson Caitlin A , Davis Kyle Frankel , E Dybala Kristen , Fernández Francisco J , Ghimire Rajan , Nidumolu Uday , Roche Rose
Published: January 2024

Water scarcity and related climate volatility are growing constraints on agricultural production landscapes around the world. While the adaptation options available are often dictated by system context, in many places broad-scale transformations are occurring in response to water-related pressures. We sought contributions from across regions, agricultural system types, and scientific disciplines to examine agricultural land use transitions driven by water scarcity, including the tradeoffs associated with alternative land uses; impacts on food production, environment, and society; innovations that can buffer risk; and considerations for planning and implementation. The research presented in this collection highlights the spectrum of policy and practice changes that are needed to facilitate beneficial land use transitions and system transformations, from quantifying risks, to evaluating multidimensional tradeoffs, to developing socio-technical policy bundles to maximize co-benefits.
Ionically annealed zwitterionic microgels for bioprinting of cartilaginous constructs
Authors: Surman František , Asadikorayem Maryam , Weber Patrick , Weber Daniel , Zenobi-Wong Marcy
Published: January 2024

Foreign body response (FBR) is a pervasive problem for biomaterials used in tissue engineering. Zwitterionic hydrogels have emerged as an effective solution to this problem, due to their ultra-low fouling properties, which enable them to effectively inhibit FBR in vivo. However, no versatile zwitterionic bioink that allows for high resolution extrusion bioprinting of tissue implants has thus far been reported. In this work, we introduce a simple, novel method for producing zwitterionic microgel bioink, using alginate methacrylate (AlgMA) as crosslinker and mechanical fragmentation as a microgel fabrication method. Photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) are mechanically fragmented through meshes with aperture diameters of 50 and 90 µm to produce microgel bioink. The bioinks made with both microgel sizes showed excellent rheological properties and were used for high-resolution printing of objects with overhanging features without requiring a support structure or support bath. The AlgMA crosslinker has a dual role, allowing for both primary photocrosslinking of the bulk hydrogel as well as secondary ionic crosslinking of produced microgels, to quickly stabilize the printed construct in a calcium bath and to produce a microporous scaffold. Scaffolds showed ∼20% porosity, and they supported viability and chondrogenesis of encapsulated human primary chondrocytes. Finally, a meniscus model was bioprinted, to demonstrate the bioink’s versatility at printing large, cell-laden constructs which are stable for further in vitro culture to promote cartilaginous tissue production. This easy and scalable strategy of producing zwitterionic microgel bioink for high resolution extrusion bioprinting allows for direct cell encapsulation in a microporous scaffold and has potential for in vivo biocompatibility due to the zwitterionic nature of the bioink.
Recent progress on degradation mechanism and antioxidation of low-dimensional black phosphorus
Authors: Fu Mingfu , Li Jiabao , Yang Wen , Zhang Yong , Yang Peizhi
Published: January 2024

Among the allotropes of phosphorus, black phosphorus (BP) is one of the most thermodynamically stable structures. Due to its unique physical and chemical properties, BP has shown considerable potential in many applications, such as field-effect transistors, energy storage and conversion, and photocatalysis. However, low-dimensional BP is easily corroded by oxygen and water owing to the large specific surface area and unbonded lone pair electrons on the surface, which reduces its chemical stability in the environment. As a result, different passivation approaches, relying on noncovalent bonding, covalent functionalization, and surface coordination, are employed to enhance the stability and performance of BP. In this review, the degradation mechanisms of BP are first analyzed for the material in both its ground state and excited state. Subsequently, the promising strategies for improving stability are overviewed. A comprehensive and in-depth understanding of the oxidation mechanisms and protection strategies of BP will provide guidance for the large-scale applications of BP and its derivatives.
Initial measurement of ultrafast charge exchange recombination spectroscopy on the EAST tokamak
Authors: JIANG 蒋 Jun 军 , LI 李 Yingying 颖颖 , CHEN 陈 Ran 冉 , FU 符 Jia 佳 , LYU 吕 Bo 波 , YU 余 Yi 羿 , XU 徐 Guosheng 国盛 , YE 叶 Minyou 民友
Published: January 2024

Ultrafast charge exchange recombination spectroscopy (UF-CXRS) has been developed on the EAST tokamak (Yingying Li et al 2019 Fusion Eng. Des. 146 522) to measure fast evolutions of ion temperature and toroidal velocity. Here, we report the preliminary diagnostic measurements after relative sensitivity calibration. The measurement results show a much higher temporal resolution compared with conventional CXRS, benefiting from the usage of a prism-coupled, high-dispersion volume-phase holographic transmission grating and a high quantum efficiency, high-gain detector array. Utilizing the UF-CXRS diagnostic, the fast evolutions of the ion temperature and rotation velocity during a set of high-frequency small-amplitude edge-localized modes (ELMs) are obtained on the EAST tokamak, which are then compared with the case of large-amplitude ELMs.
Metabolic Syndrome, Modifiable Lifestyle Factors, and Sleep-Disordered Breathing: The Hispanic Community Health Study
Authors: Richard Shannon L , Renn Brenna N , Tran Dieu-My T , Kim Jinyoung , Feng Du
Published: January 2024

Background

US Hispanics/Latinos are disproportionately susceptible to metabolic syndrome (MetS), attributed in part to systemic inequities related to health and lifestyle factors such as low physical activity (PA) levels, diet quality, alcohol use, tobacco use, and sleep disorder. Gender and heritage group differences are vastly understudied and need to be examined in this heterogeneous population.

Purpose

To examine the relationships between select health and lifestyle factors and MetS among Hispanic gender and heritage subgroups (Hypothesis 1) and determine whether gender and heritage moderate those relationships (Hypothesis 2).

Methods

Participants included 14,155 Hispanic Americans aged 18–76 (59% female, mean age 45.92 ± 13.97) from seven heritage subgroups. This secondary analysis of cross-sectional data from the observational Hispanic Community Health Study/Study of Latinos (HCHS/SOL) dataset used hierarchical multinomial logistic regression to test Hypothesis 1; the dependent variable, MetS, included three categories delineating absence of MetS and presence of MetS with or without related medication use. Hayes’ PROCESS macro tested Hypothesis 2.

Results

Low PA and sleep-disordered breathing (SDB) each had significant (p < .001) predictive value of MetS group membership, whereas both low and high alcohol use (p < .001) were associated with decreased MetS risk. Cigarette pack-years were not significantly associated with MetS outcomes. Gender moderated the association between MetS and alcohol use (p < .001), cigarette pack-years (p < .001), and SDB (p < .001) such that the effects on MetS were higher in females than males. The association between MetS and diet quality (p < .001) was stronger among males than in females.

Conclusions

Gender and heritage differences were prominent among study variables.
Comprehensive assessment of protein loop modeling programs on large-scale datasets: prediction accuracy and efficiency
Authors: Wang Tianyue , Wang Langcheng , Zhang Xujun , Shen Chao , Zhang Odin , Wang Jike , Wu Jialu , Jin Ruofan , Zhou Donghao , Chen Shicheng , Liu Liwei , Wang Xiaorui , Hsieh Chang-Yu , Chen Guangyong , Pan Peichen , Kang Yu , Hou Tingjun
Published: January 2024

Protein loops play a critical role in the dynamics of proteins and are essential for numerous biological functions, and various computational approaches to loop modeling have been proposed over the past decades. However, a comprehensive understanding of the strengths and weaknesses of each method is lacking. In this work, we constructed two high-quality datasets (i.e. the General dataset and the CASP dataset) and systematically evaluated the accuracy and efficiency of 13 commonly used loop modeling approaches from the perspective of loop lengths, protein classes and residue types. The results indicate that the knowledge-based method FREAD generally outperforms the other tested programs in most cases, but encountered challenges when predicting loops longer than 15 and 30 residues on the CASP and General datasets, respectively. The ab initio method Rosetta NGK demonstrated exceptional modeling accuracy for short loops with four to eight residues and achieved the highest success rate on the CASP dataset. The well-known AlphaFold2 and RoseTTAFold require more resources for better performance, but they exhibit promise for predicting loops longer than 16 and 30 residues in the CASP and General datasets. These observations can provide valuable insights for selecting suitable methods for specific loop modeling tasks and contribute to future advancements in the field.
Quantitative differences in volumetric calculations for radiation dosimetry in segmental Y90 treatment planning using hybrid angiography-CT compared with anatomic segmentation
Authors: Kwak Daniel H , Lionberg Alex , Patel Mikin , Nijhawan Karan , Martens Spencer , Yu Qian , Cao David , Youssef Salma , Ahmed Osman
Published: January 2024

Objective

To compare treatment volumes reconstructed from hybrid Angio-CT catheter-directed infusion imaging and Couinaud anatomic model as well as the implied differences in Y-90 radiation dosimetry.

Methods

Patients who underwent transarterial radioembolization (TARE) using Y-90 glass microspheres with pretreatment CT or MRI imaging as well as intraprocedural angiography-CT (Angio-CT) were analysed. Treatment volumes were delineated using both tumoural angiosomes (derived from Angio-CT) and Couinaud anatomic landmarks. Segmental and lobar treatment volumes were calculated via semi-automated contouring software. Volume and dose differences were compared by the two-tailed Student t test or Wilcoxon signed-rank test. Factors affecting volume and dose differences were assessed via simple and/or multiple variable linear regression analysis.

Results

From September 2018 to March 2021, 44 patients underwent 45 lobar treatments and 38 patients received 56 segmental treatments. All target liver lobes and all tumours were completely included within the field-of-view by Angio-CT. Tumour sizes ranged between 1.1 and 19.5 cm in diameter. Segmental volumes and treatment doses were significantly different between the Couinaud and Angio-CT volumetry methods (316 vs 404 mL, P < .0001 and 253 vs 212 Gy, P < .01, respectively). Watershed tumours were significantly correlated with underestimated volumes by the Couinaud anatomic model (P < .001). There was a significant linear relationship between tumour diameter and percent volume difference (R2 = 0.44, P < .0001). The Couinaud model overestimated volumes for large tumours that exhibited central hypovascularity/necrosis and for superselected peripheral tumours.

Conclusions

Angio-CT may confer advantages over the Couinaud anatomic model and enable more accurate, personalized dosimetry for TARE.

Advances in knowledge

Angio-CT may confer advantages over traditional cross-sectional and cone-beam CT imaging for selective internal radiation therapy planning.
Does CT overestimate extra-pancreatic perineural invasion in patients with pancreatic ductal adenocarcinoma following neoadjuvant chemoradiation therapy?
Authors: Noda Yoshifumi , Pisuchpen Nisanard , Parakh Anushri , Srinivas-Rao Shravya , Kinowaki Yuko , Mino-Kenudson Mari , Kambadakone Avinash R
Published: January 2024

Objectives

To evaluate the diagnostic performance of CT in the assessment of extra-pancreatic perineural invasion (EPNI) in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

This retrospective study included 123 patients (66 men; median age, 66 years) with PDAC who underwent radical surgery and pancreatic protocol CT for assessing surgical resectability between September 2011 and March 2019. Among the 123 patients, 97 patients had received neoadjuvant chemoradiation therapy (CRT). Two radiologists reviewed the CT images for evidence of EPNI using a 5-point scale (5 = definitely present, 4 = probably present, 3 = equivocally present, 2 = probably absent, and 1 = definitely absent). Diagnostic performance for assessing EPNI was evaluated with receiver operating characteristic (ROC) curve analysis.

Results

The sensitivity, specificity, and area under the ROC curve for assessing EPNI were 98%, 30%, and 0.62 in all patients; 97%, 22%, and 0.59 in patients with neoadjuvant CRT; and 100%, 100%, and 1.00 in patients without neoadjuvant CRT, respectively. False-positive assessment of EPNI occurred in 23% of patients (n = 28/123), and 100% of these (n = 28/28) had received neoadjuvant CRT. There was moderate to substantial agreement between the readers (ĸ = 0.49–0.62).

Conclusion

Pancreatic protocol CT has better diagnostic performance for determination of EPNI in treatment naïve patients with PDAC and overestimation of EPNI is likely in patients who have received preoperative CRT.

Advances in Knowledge

Pancreatic protocol CT has better diagnostic performance for the detection of EPNI in treatment naïve patients compared to patients receiving neoadjuvant CRT.
AI in imaging: the regulatory landscape
Authors: Hill Derek L G
Published: January 2024

Artificial intelligence (AI) methods have been applied to medical imaging for several decades, but in the last few years, the number of publications and the number of AI-enabled medical devices coming on the market have significantly increased. While some AI-enabled approaches are proving very valuable, systematic reviews of the AI imaging field identify significant weaknesses in a significant proportion of the literature. Medical device regulators have recently become more proactive in publishing guidance documents and recognizing standards that will require that the development and validation of AI-enabled medical devices need to be more rigorous than required for tradition “rule-based” software. In particular, developers are required to better identify and mitigate risks (such as bias) that arise in AI-enabled devices, and to ensure that the devices are validated in a realistic clinical setting to ensure their output is clinically meaningful. While this evolving regulatory landscape will mean that device developers will take longer to bring novel AI-based medical imaging devices to market, such additional rigour is necessary to address existing weaknesses in the field and ensure that patients and healthcare professionals can trust AI-enabled devices. There would also be benefits in the academic community taking into account this regulatory framework, to improve the quality of the literature and make it easier for academically developed AI tools to make the transition to medical devices that impact healthcare.
Are Welsh primary schools Sunproofed? Results of a national survey, part 1: scoping the landscape of sun safety policies in Wales
Authors: Peconi Julie , Lanyon Kirsty , Tod Daniel , Driscoll Timothy , Prathap Swetha , Watkins Alan , Abbott Rachel A
Published: January 2024

Background

Schools with formal sun safety polices generally show better sun safety practices than schools without.

Objectives

To understand the extent to which Welsh primary schools have sun safety policies; to identify the key characteristics of policies; to assess whether policy adoption varies by school characteristics; and to consider what support schools need to develop sun safety policies.

Methods

An online multiple-choice survey on sun safety was distributed to all 1241 primary schools in Wales.

Results

In total, 471 (38.0%) schools responded. Of these, 183 (39.0%) reported having a formal sun safety policy. Welsh medium schools (P = 0.036) and schools in North Wales (P = 0.008) were more likely to report having a policy. Schools with a higher percentage of pupils receiving free school meals (P = 0.046) and with lower attendance rates (P = 0.008) were less likely to report having a sun safety policy. The primary reasons for schools not having a policy included being ‘not aware of the need’ (34.6%); ‘need assistance with policy or procedure development’ (30.3%); and ‘not got around to it just yet’ (26.8%).

Conclusions

With less than half of schools reporting a sun safety policy and variation in the presence/absence of a policy by school characteristics, our survey revealed inconsistency in formal sun safety provision in Welsh schools. The findings also suggest that schools are unaware of the importance of sun safety and need support to develop and implement policies. This snapshot of the current situation in primary schools in Wales provides a basis upon which the comprehensiveness, effectiveness and implementation of sun safety policies can be further evaluated.
Real-world outcomes of children treated with dupilumab for moderate-to-severe atopic dermatitis: a single-centre retrospective observational UK study
Authors: Hosseini-Ashrafi Mozhgan , Clayton Tim H , Herring Michelle , Herety Nichola , Arkwright Peter D
Published: January 2024

Background

Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 6 months.

Objectives

The aim of this study was to examine real-world outcomes and safety of dupilumab in British children with moderate-to-severe AD attending a tertiary referral paediatric centre.

Methods

Skin and quality of life scores, adverse events and discontinuation rates were assessed. Patients aged ≤ 18 years with moderate-to-severe AD were included if they had skin scores recorded at baseline and at least one follow-up visit. Efficacy and safety were assessed using descriptive statistics.

Results

In this retrospective observational survey, 72 children/teenagers, with a median age of 14 years (range 7–18) were included. Oral systemic immunosuppressants had failed to control AD in 88% of children recruited. All patients commenced on dupilumab had pretreatment eczema skin scores consistent with moderate-to-severe disease, with a median Eczema Area and Severity Index (EASI) score of 25 [interquartile range (IQR) 20–31]. EASI scores decreased by a median of 94% (IQR 82–100) and remained consistently low over 10–52 months of the study, with a median EASI score at final follow-up of 2 (IQR 0–6). Of the 72 children, 8 (11%) were able to discontinue dupilumab as they were in remission. Nineteen (26%) experienced adverse events, most commonly conjunctivitis (12 patients; 17%). Eight (11%) discontinued dupilumab (six with ongoing inflammatory skin flares, one with severe allergic conjunctivitis, one with intercurrent Wilson disease).

Conclusions

Dupilumab was highly effective in treating most children with moderate-to-severe AD with good safety outcomes in the real world. However, 10% of children may need alternative therapy because of drug ineffectiveness or side-effects.
Circulating Tumor Cells: From Basic to Translational Research
Authors: Cortés-Hernández Luis Enrique , Eslami-S Zahra , Pantel Klaus , Alix-Panabières Catherine
Published: January 2024

Background

Metastasis is the leading cause of cancer-related deaths. Most studies have focused on the primary tumor or on overt metastatic lesions, leaving a significant knowledge gap concerning blood-borne cancer cell dissemination, a major step in the metastatic cascade. Circulating tumor cells (CTCs) in the blood of patients with solid cancer can now be enumerated and investigated at the molecular level, giving unexpected information on the biology of the metastatic cascade.

Content

Here, we reviewed recent advances in basic and translational/clinical research on CTCs as key elements in the metastatic cascade.

Findings from translational studies on CTCs have elucidated the complexity of the metastatic process. Fully understanding this process will open new potential avenues for cancer therapeutic and diagnostic strategies to propose precision medicine to all cancer patients.
Detection of Multiple HPV Types in Liquid Biopsies of Cervical Neoplasia
Authors: Herbst Johanna , Vohl Vanessa , Krajina Maroje , Leffers Markus , Kropidlowski Jolanthe , Prieske Katharina , Jaeger Anna , Oliveira Ferrer Leticia , Schmalfeldt Barbara , Goy Yvonne , Burandt Eike , Pantel Klaus , Vollmert Caren , Sartori Alexander , Woelber Linn , Effenberger Katharina , Wikman Harriet
Published: January 2024

Background

More than 95% of cervical cancers and their precancerous lesions are caused by human papillomavirus (HPV). Cell-free (cf) HPV DNA detection in blood samples may serve as a monitoring tool for cervical cancer.

Methods

In our methodological study, an HPV panel for simultaneous detection of 24 types using mass spectrometry-based analysis was developed for liquid biopsy approaches and tested on HPV positive cell lines, plasmid controls, and cervical high-grade squamous intraepithelial lesions (HSIL) in positive smear samples (n = 52). It was validated in cfDNA blood samples (n = 40) of cervical cancer patients.

Results

The HPV panel showed proficient results in cell lines and viral plasmids with a limit of detection of 1 IU (international units)/µL for HPV16/18 and 10GE/µL for HPV11/31/33/39/45/51/52/58/59 and a specificity of 100% for the tested HPV types. In cervical smear samples, HPV DNA was detected with a sensitivity of 98.14%. The overall agreement between the new HPV panel and clinical records was 97.2% (κ = 0.84). In cervical cancer cfDNA, 26/40 (65.0%) tested positive for any HPV type, with most infections due to hrHPV (24/26). HPV positive samples were found in all FIGO stages, with the highest positivity ratio in FIGO III and IV. Even the lowest stage, FIGO I, had 12/23 (52.2%) patients with a positive HPV plasma status.

Conclusions

This proof-of-concept paper shows that the described assay produces reliable results for detecting HPV types in a multiplex mass spectrometry-based assay in cervical smear and cfDNA with high specificity and sensitivity in both cohorts. The assay shows potential for liquid biopsy-based applications in monitoring cervical cancer progression.
Critical Factors in the Analytical Work Flow of Circulating Tumor DNA-Based Molecular Profiling
Authors: van der Leest Paul , Schuuring Ed
Published: January 2024

Background

Liquid biopsy testing, especially molecular tumor profiling of circulating tumor DNA (ctDNA) in cell-free plasma, has received increasing interest in recent years as it serves as a reliable alternative for the detection of tumor-specific aberrations to guide treatment decision-making in oncology. Many (commercially available) applications have been developed, however, broad divergences in (pre)analytical work flows and lack of universally applied guidelines impede routine clinical implementation. In this review, critical factors in the blood-based ctDNA liquid biopsy work flow are evaluated.

Content

In the preanalytical phase, several aspects (e.g., blood collection tubes [BCTs], plasma processing, and extraction method) affect the quantity and quality of the circulating cell-free DNA (ccfDNA) applicable for subsequent molecular analyses and should meet certain standards to be applied in diagnostic work flows. Analytical considerations, such as analytical input and choice of assay, might vary based on the clinical application (i.e., screening, primary diagnosis, minimal residual disease [MRD], response monitoring, and resistance identification). In addition to practical procedures, variant interpretation and reporting ctDNA results should be harmonized. Collaborative efforts in (inter)national consortia and societies are essential for the establishment of standard operating procedures (SOPs) in attempts to standardize the plasma-based ctDNA analysis work flow.

Development of universally applicable guidelines regarding the critical factors in liquid biopsy testing are necessary to pave the way to clinical implementation for routine diagnostics.
Screening for Colorectal Cancer: The Role of Clinical Laboratories
Authors: Toth Joseph F , Trivedi Mehul , Gupta Samir
Published: January 2024

Background

Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality. Screening can result in reductions in incidence and mortality, but there are many challenges to uptake and follow-up.

Content

Here, we will review the changing epidemiology of CRC, including increasing trends for early and later onset CRC; evidence to support current and emerging screening strategies, including noninvasive stool and blood-based tests; key challenges to ensuring uptake and high-quality screening; and the critical role that clinical laboratories can have in supporting health system and public health efforts to reduce the burden of CRC on the population.

Clinical laboratories have the opportunity to play a seminal role in optimizing early detection and prevention of CRC.
Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction
Authors: Temtem Margarida , Mendonça Maria Isabel , Gomes Serrão Marco , Santos Marina , Sá Débora , Sousa Francisco , Soares Carolina , Rodrigues Ricardo , Henriques Eva , Freitas Sónia , Borges Sofia , Rodrigues Mariana , Guerra Graça , Drumond Freitas António , Sousa Ana Célia , Palma dos Reis Roberto
Published: January 2024

Aims

Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2).

Methods and results

In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events’ predictive and discriminative ability through Harrell’s C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories.

Conclusion

In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.
Severe acute kidney injury related to haemolysis after pulsed field ablation for atrial fibrillation
Authors: Venier Sandrine , Vaxelaire Nathan , Jacon Peggy , Carabelli Adrien , Desbiolles Antoine , Garban Frederic , Defaye Pascal
Published: January 2024

Aims

Pulsed field ablation (PFA) has been proposed as a novel alternative to radiofrequency (RF) and cryoablation in the treatment of atrial fibrillation (AF). Following the occurrence of two cases of acute kidney injury (AKI) secondary to haemolysis after a PFA procedure, we evaluated haemolysis in a cohort of consecutive patients.

Methods and results

Two cases of AKI occurred in last May and June 2023. AKI was secondary to acute and severe haemolysis after a PFA procedure. From June 2023, a total of 68 consecutive patients (64.3 ± 10.5 years) undergoing AF ablation with PFA were enrolled in the study. All patients had a blood sample the day after the procedure for the assessment of haemolysis indicators. The pentaspline PFA catheter was used with a total number of median applications of 64 (54; 76). Nineteen patients (28%) showed significantly depleted haptoglobin levels (<0.04 g/L). A significant inverse correlation was found between the plasma level of haptoglobin and the total number of applications. Two groups were compared: the haemolysis+ group (haptoglobin < 0.04 g/L) vs. the haemolysis− group. The total number of applications was significantly higher in the haemolysis+ group vs the haemolysis - group respectively 75 (62; 127) vs 62 (54; 71) P = 0.011. More than 70 applications seem to have better sensitivity and specificity to predict haemolysis.

Conclusion

Intravascular haemolysis can occur after certain procedures of PFA. Acute kidney injury is a phenomenon that appears to be very rare after a PFA procedure. However, caution must be exercised in the number of applications to avoid severe haemolysis.
Q-BioLiP: A Comprehensive Resource for Quaternary Structure-based Protein–ligand Interactions
Authors: Wei Hong , Wang Wenkai , Peng Zhenling , Yang Jianyi
Published: January 2024

Since its establishment in 2013, BioLiP has become one of the widely used resources for protein–ligand interactions. Nevertheless, several known issues occurred with it over the past decade. For example, the protein–ligand interactions are represented in the form of single chain-based tertiary structures, which may be inappropriate as many interactions involve multiple protein chains (known as quaternary structures). We sought to address these issues, resulting in Q-BioLiP, a comprehensive resource for quaternary structure-based protein–ligand interactions. The major features of Q-BioLiP include: (1) representing protein structures in the form of quaternary structures rather than single chain-based tertiary structures; (2) pairing DNA/RNA chains properly rather than separation; (3) providing both experimental and predicted binding affinities; (4) retaining both biologically relevant and irrelevant interactions to alleviate the wrong justification of ligands’ biological relevance; and (5) developing a new quaternary structure-based algorithm for the modelling of protein–ligand complex structure. With these new features, Q-BioLiP is expected to be a valuable resource for studying biomolecule interactions, including protein–small molecule interaction, protein–metal ion interaction, protein–peptide interaction, protein–protein interaction, protein–DNA/RNA interaction, and RNA–small molecule interaction. Q-BioLiP is freely available at https://yanglab.qd.sdu.edu.cn/Q-BioLiP/.
Projective Transformations of Convex Bodies and Volume Product
Authors: Balacheff Florent , Solanes Gil , Tzanev Kroum
Published: January 2024

In this paper, we study certain variational aspects of the volume product functional restricted to the space of small projective deformations of a fixed convex body. In doing so, we provide a short proof of a theorem by Klartag: a strong version of the slicing conjecture implies the non-symmetric Mahler conjecture. We also exhibit an interesting family of critical convex bodies in dimension $2$ containing saddle points for this functional.
The performance of artificial intelligence chatbot large language models to address skeletal biology and bone health queries
Authors: Cung Michelle , Sosa Branden , Yang He S , McDonald Michelle M , Matthews Brya G , Vlug Annegreet G , Imel Erik A , Wein Marc N , Stein Emily Margaret , Greenblatt Matthew B
Published: January 2024

Artificial intelligence (AI) chatbots utilizing large language models (LLMs) have recently garnered significant interest due to their ability to generate humanlike responses to user inquiries in an interactive dialog format. While these models are being increasingly utilized to obtain medical information by patients, scientific and medical providers, and trainees to address biomedical questions, their performance may vary from field to field. The opportunities and risks these chatbots pose to the widespread understanding of skeletal health and science are unknown. Here we assess the performance of 3 high-profile LLM chatbots, Chat Generative Pre-Trained Transformer (ChatGPT) 4.0, BingAI, and Bard, to address 30 questions in 3 categories: basic and translational skeletal biology, clinical practitioner management of skeletal disorders, and patient queries to assess the accuracy and quality of the responses. Thirty questions in each of these categories were posed, and responses were independently graded for their degree of accuracy by four reviewers. While each of the chatbots was often able to provide relevant information about skeletal disorders, the quality and relevance of these responses varied widely, and ChatGPT 4.0 had the highest overall median score in each of the categories. Each of these chatbots displayed distinct limitations that included inconsistent, incomplete, or irrelevant responses, inappropriate utilization of lay sources in a professional context, a failure to take patient demographics or clinical context into account when providing recommendations, and an inability to consistently identify areas of uncertainty in the relevant literature. Careful consideration of both the opportunities and risks of current AI chatbots is needed to formulate guidelines for best practices for their use as source of information about skeletal health and biology.
Rapid bone microarchitecture decline in older men with high bone turnover—the prospective STRAMBO study
Authors: Szulc Pawel , Whittier Danielle E , Boyd Steven K , Chapurlat Roland
Published: January 2024

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60–87 yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8 yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: −0.94 vs –0.31% yr−1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8 yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%–215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).