bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Insights on Global Journeys of Adaptive Wheat Genes that Brought Us to Modern Wheat
Authors: Sehgal Deepmala , Dixon Laura , Pequeno Diego , Hyles Jessica , Lacey Indi , Crossa Jose , Bentley Alison , Dreisigacker Susanne
Published: November 2023

Since its first cultivation, hexaploid wheat has evolved, allowing for its widespread cultivation and contributing to global food security. The identification of adaptive genes, such as vernalization and photoperiod response genes, has played a crucial role in optimizing wheat production, being instrumental in fine-tuning flowering and reproductive cycles in response to changing climates and evolving agricultural practices. While these adaptive genes have expanded the range of variation suitable for adaptation, further research is needed to understand their mechanisms, dissect the pathways involved, and expedite their implementation in breeding programs. By analyzing data across different environments and over time, Meta-QTL analysis can help identify novel genomic regions and facilitate the discovery of new candidate genes. This chapter reports on two previously unknown Meta-QTL regions, highlighting the potential for further exploration in this field. Moving forward, it will be increasingly important to expand our understanding of how genetic regions influence not only flowering time but also other developmental traits and their responses to environmental factors. Advances in gene-based modeling hold promise for describing growth and development processes using QTL and other genomic loci analysis. Integrating these findings into process-based crop models can provide valuable insights for future research. Overall, the study of adaptive genes and their impact on wheat production represents a vital area of research that continues to contribute to global food security.
Genome Sequences from Diploids and Wild Relatives of Wheat for Comparative Genomics and Alien Introgressions
Authors: Schoen Adam , Saripalli Gautam , Hosseinirad Seyedali , Sharma Parva Kumar , Kajla Anmol , Yadav Inderjit Singh , Tiwari Vijay
Published: November 2023

Bread wheat is an important food source worldwide, contributing ~20% of the caloric intake per person worldwide. Due to a domestication bottleneck and highly selective breeding for key traits, modern wheat cultivars have a narrow genetic base. Wheat production faces several challenges due to both abiotic and biotic stresses as well as changing climatic conditions and genetic improvement of wheat is generally considered to be the most sustainable approach to develop climate resilient cultivars with improved yield and end-use traits. Since wheat cultivars and landraces have been explored extensively to identify novel genes and alleles, one way to overcome these pitfalls is by looking into the proverbial treasure trove of genomic diversity that is present in wheat’s wild relatives. These wild relatives hold reservoirs of genes that can confer broad-spectrum resistance to pathogens, increase yield, provide additional nutrition, and improve dough quality. Genetic approaches and techniques have existed to introgress wild chromatin to bread wheat, as well as trace introgressions present in the germplasm for over 7 decades. However with the availability of NGS technologies, it is now easier to detect and efficiently integrate the genetic diversity that lies within wheat’s gene pools into breeding programs and research. This chapter provides a concise explanation of current technologies that have allowed for the progression of genomic research into wheat’s primary, secondary, and tertiary gene pools, as well as past technologies that are still in use today. Furthermore, we explore resources that are publicly available that allow for insight into genes and genomes of wheat and its wild relatives, and the application and execution of these genes in research and breeding. This chapter will give an up-to-date summary of information related with genomic resources and reference assemblies available for wheat’s wild relatives and their applications in wheat breeding and genetics.
Wheat Data Integration and FAIRification: IWGSC, GrainGenes, Ensembl and Other Data Repositories
Authors: Alaux Michael , Dyer Sarah , Sen Taner Z.
Published: November 2023

Wheat data integration and FAIRification are key to tackling the challenge of wheat improvement. The data repositories presented in this chapter play a central role in generating knowledge and allow data exchange and reuse. These repositories rely on international initiatives such as (i) the International Wheat Genome Sequencing Consortium (IWGSC), which delivers common genomics resources such as reference sequences, communal Web-based seminars and (ii) the Wheat Information System (WheatIS) of the Wheat Initiative (http://www.wheatis.org), which improves the interoperability and findability of the wheat data across the repositories.
Structural and Functional Annotation of the Wheat Genome
Authors: Choulet Frédéric , Wang Xi , Spannagl Manuel , Swarbreck David , Rimbert Hélène , Leroy Philippe , Lasserre-Zuber Pauline , Papon Nathan
Published: November 2023

Wheat genome sequencing has passed through major steps in a decade, starting from the sequencing of large contiguous sequences obtained from chromosome-specific BAC libraries, to reach high-quality genome assemblies of a dozen of bread wheat varieties and wild relatives. While access to an assembled genome sequence is crucial for research, the resource that is mainly used by the community is not the sequence itself, but rather the annotated features, i.e., genes and transposable elements. In this chapter, we describe the work performed to predict the repertoire of 107 k high-confidence genes and 4 million TE copies in the hexaploid wheat genome (cultivar CHINESE SPRING; IWGSC RefSeq) and the procedures established to transfer the annotation through the different releases of genome assembly. Limitations and implications for building a wheat pangenome are discussed, as well as the possibilities for future improvements of structural annotation, and opportunities offered by novel approaches for functional annotation.
Genome Sequence-Based Features of Wheat Genetic Diversity
Authors: Zhang Xueyong , Appels Rudi
Published: November 2023

Common wheat is a hexaploid species crop that is widely recognized as an important staple food crop. The establishment of a gold standard reference genome sequences of the well-studied CHINESE SPRING, and its progenitors (including Triticum turgidum ssp. dicoccoides accession Zavitan, Triticum durum accession Svevo, Triticum urartu, Aegilops tauschii), in the last 5 years has dramatically promoted our understanding of wheat genome diversity and evolution through the resequencing of collections of wheat and its progenitors. In this chapter, we review progress in the analysis and interpretation of genome‑based studies of wheat focusing on geographic genome differentiation, interspecies gene flow, haplotype blocks, and gene diversity in breeding. We also consider approaches for efficiently discovering and integrating the genes and genome variations, hidden in Genebank collections, into wheat breeding programs.
Ancient Wheat Genomes Illuminate Domestication, Dispersal, and Diversity
Authors: Iob Alice , Scott Michael F. , Botigué Laura
Published: November 2023

Ancient DNA (aDNA) promises to revolutionise our understanding of crop evolution. Wheat has been a major crop for millennia and has a particularly interesting history of domestication, dispersal, and hybridisation, summarised briefly here. We review how the fledgling field of wheat archaeogenomics has already contributed to our understanding of this complex history, revealing the diversity of wheat in ancient sites, both in terms of species and genetic composition. Congruently, ancient genomics has identified introgression events from wild relatives during wheat domestication and dispersal. We discuss the analysis of degraded aDNA in the context of large, polyploid wheat genomes and how environmental effects on preservation may limit aDNA availability in wheat. Despite these challenges, wheat archaeogenomics holds great potential for answering open questions regarding the evolution of this crop, namely its domestication, the different dispersal routes of the early domestic forms and the diversity of ancient agricultural practices. Not only will this research enhance our understanding of human history, but it will also contribute valuable knowledge about ancient selective pressures and agriculture, thus aiding in addressing present and future agricultural challenges.
Gene Flow Between Tetraploid and Hexaploid Wheat for Breeding Innovation
Authors: Mazzucotelli Elisabetta , Mastrangelo Anna Maria , Desiderio Francesca , Barabaschi Delfina , Maccaferri Marco , Tuberosa Roberto , Cattivelli Luigi
Published: November 2023

Durum and bread wheat are two related species with different ploidy levels but a high similarity between the common A and B genomes. This feature, which allows a continuous gene flow between the two species, can be exploited in breeding programs to improve key traits in both crops. Therefore, durum wheat, despite covering only 5% of cultivated wheat worldwide, also represents an asset for the genetic improvement of bread wheat. Tetraploid wheat, with a very large availability of wild and domesticated accessions, durum landraces, and cultivars, offers a large gene reservoir to increase the genetic diversity of A and B genomes in bread wheat. Moreover, thanks to the possibility of crossing durum wheat with Aegilops tauschii, synthetic hexaploid lines are generated which show a much larger genetic diversity also in the D genome compared to common wheat. The genome sequences of wild emmer, durum, and bread wheat provide power tools for gene cloning and comparative genomics that will also facilitate the shuttling of genes between tetraploid and hexaploid wheats.
Gravitoelectric dynamical tides at second post-Newtonian order
Authors: Mandal Manoj K. , Mastrolia Pierpaolo , Silva Hector O. , Patil Raj , Steinhoff Jan
Published: November 2023

Abstract

We present a gravitoelectric quadrupolar dynamical tidal-interaction Hamiltonian for a compact binary system, that is valid to second order in the post-Newtonian expansion. Our derivation uses the diagrammatic effective field theory approach, and involves Feynman integrals up to two loops, evaluated with the dimensional regularization scheme. We also derive the effective Hamiltonian for adiabatic tides, obtained by taking the appropriate limit of the dynamical effective Hamiltonian, and we check its validity by verifying the complete Poincaré algebra. In the adiabatic limit, we also calculate two gauge-invariant observables, namely, the binding energy for a circular orbit and the scattering angle in a hyperbolic scattering. Our results are important for developing accurate gravitational waveform models for neutron-star binaries for present and future gravitational-wave observatories.
Personalisierte Therapie des Phäochromozytoms
Authors: Schlegel Nicolas , Meir Michael , Reibetanz Joachim , Markus Christian , Wiegering Armin , Fassnacht Martin
Published: November 2023

Hintergrund

Das Phäochromozytom ist eine seltene, aber schwerwiegende Erkrankung der Nebennieren. Ziel dieser Arbeit ist die Darstellung und Diskussion aktueller Entwicklungen zum diagnostischen und therapeutischen Vorgehen beim Phäochromozytom.

Material und Methoden

Es wurde ein narrativer Übersichtsartikel auf Basis der aktuellsten Literatur erstellt.

Ergebnisse und Diskussion

Der Anteil von Phäochromozytomen als Tumoren adrenalen Ursprungs liegt bei etwa 5 % der zufällig entdeckten Nebennierentumoren. Die klassische symptomatische Triade aus Kopfschmerzen, Schwitzen und Palpitationen tritt nur bei etwa 20 % der Patientinnen und Patienten auf, während fast alle Patientinnen und Patienten mindestens eines dieser Symptome aufweisen. Die Diagnostik umfasst im ersten Schritt den biochemischen Nachweis der freien Plasmametanephrine oder alternativ fraktionierter Metanephrine im 24-h-Sammelurin. Erst im zweiten Schritt erfolgt ein Schnittbildverfahren (Computer- oder Magnetresonanztomographie) zur Lokalisationsdiagnostik. Eine funktionelle Bildgebung ist ebenfalls sinnvoll, um eine Metastasierung präoperativ zu erkennen. Eine genetische Testung sollte immer im Verlauf der Behandlung angeboten werden, da 30–40 % der Phäochromozytome mit genetischen Veränderungen assoziiert sind. Das Dogma der präoperativen α‑Blockade wird durch aktuelle Daten zunehmend infrage gestellt und in den letzten Jahren kontrovers diskutiert. Die minimal-invasive Entfernung des Nebennierentumors ist Standard, wobei transabdominelle und retroperitoneoskopische laparoskopische Verfahren als gleichwertig anzusehen sind. Die Wahl des minimal-invasiven Verfahrens hängt von der Expertise und Erfahrung des Operateurs/der Operateurin ab und sollte in erster Linie daran angepasst werden. Postoperativ ist eine individualisierte und regelmäßige Nachsorge wichtig.
Mechanical properties of ply-lam cross-laminated timbers fabricated with lumber and plywood
Authors: Yang Seungmin , Lee Hyunjae , Choi Gyuwoong , Kang Seoggoo
Published: November 2023

The mechanical properties of four ply-lam cross-laminated timbers (CLTs) containing a plywood layer were compared with those of glued laminated timber (GLT) and CLT. The bending, out-of-plane shear, and compression strengths were highest in the GLT, followed by the ply-lam CLTs and CLT. The modulus of elasticity (MOE) values for the three studied ply-lam CLT samples were 1–2.5 GPa higher than GLT; however, the modulus of rupture (MOR) of all ply-lam CLTs was 7.3–18.8 MPa lower than GLT. The length of the plywood product is 2,440 mm, and longitudinal bonding is required to manufacture ply-lam CLTs of length > 3 m. The prediction of bending capabilities by shear analogy was compared with the bending properties when joints were included. The performances of all the pilot-scale ply-lam CLT samples exceeded the predicted bending performance standards for MOE (10 GPa) and MOR (30 MPa) All samples exceeded 10 GPa and 30 MPa, based on projected and experimental data.
Nierenerkrankungen bei Diabetes mellitus Typ 2
Authors: Kellerer Monika , Wanner Christoph
Published: November 2023

Hintergrund

Nationale und internationale Fachgesellschaften publizieren Leitlinien zur Diagnostik und Verlaufsbeobachtung einer chronischen Nierenerkrankung bei Menschen mit Diabetes mellitus Typ 2. Über die Kongruenz und Implementierung dieser Publikationen im klinischen Alltag wird jedoch selten berichtet.

Ziel der Arbeit

Diese Arbeit bietet einen Überblick über die Empfehlungen als Ausdruck des globalen Wissensstands und eruiert deren Umsetzung im deutschen Praxisalltag. Dazu wurde eine repräsentative Befragung erhoben.

Material und Methoden

Aktuelle Leitlinien wurden in Bezug auf Kongruenz der folgenden Aspekte verglichen: diagnostische Parameter, Testfrequenz und Empfehlungen zur nephrologischen Mitbetreuung. Die Ergebnisse wurden im nächsten Schritt mit den Antworten aus der Befragung verglichen. So war es möglich, die Umsetzung im deutschen Praxisalltag einzuschätzen.

Ergebnisse

Laut Empfehlungen sollten die geschätzte glomeruläre Filtrationsrate (eGFR) und das Albumin-Kreatinin-Verhältnis im Urin mindestens 1‑mal pro Jahr bei allen Menschen mit Diabetes mellitus Typ 2 bestimmt werden. Bei höhergradiger Niereninsuffizienz (ab Kidney-Disease:Improving-Global-Outcomes[KDIGO]-Stadium 3b mit eGFR < 45 ml/min/1,73 m2) bzw. Albuminurie (ab Stadium A2) sind eine häufigere Bestimmung sowie die nephrologische Mitbetreuung empfehlenswert; hier werden jedoch unterschiedliche Schwellenwerte und Frequenzen empfohlen. In der Auswertung der Fragebögen wurde die jährliche Bestimmung der eGFR in 96,5 % aller Fragebögen positiv beantwortet, die Bestimmung der Albuminurie in 77,2 %. Eine eGFR-getriggerte nephrologische Mitbetreuung wird von 19,6 % der nichtnephrologischen Praxen umgesetzt; die Albuminurie-getriggerte Mitbetreuung erfolgt in der Mehrzahl der Fälle.

Schlussfolgerungen

Die Messung der eGFR ist als Standard in Deutschland etabliert. Verbesserungspotenzial ergibt sich bei Albuminuriemessung, Häufigkeit der Testung und Zeitpunkt der nephrologischen Konsultation. Die interdisziplinäre Zusammenarbeit wird von allen Leitlinien betont.
Kinderneurologische Untersuchung
Authors: Bonfert Michaela V. , Wagner Johanna , Jung Eva L. , Grosse Leonie , Lieftüchter Victoria , Gerstl Lucia , Heinen Florian
Published: November 2023

Im Alltag von Klinik und Praxis ist der neurologische Status eines Kindes wegweisend: für die differenzialdiagnostische Einordnung bei akuten oder chronischen Fragestellungen ebenso wie für die Beurteilung des Entwicklungsstandes. Die kinderneurologische Untersuchung entspricht einem hochinformativen, ganzheitlichen Zugang zum Kind als Person, seiner klinischen Fragestellungen und nichtorganspezifischen Entwicklung. Im Folgenden wird die alltagspraktische Umsetzung einer situations- und kontextgerechten Untersuchung mit 6 neurologischen Dimensionen vorgestellt. Zu Standardisierung der Untersuchung und Dokumentation der Befunde eignen sich die innovativen, visualisierenden Werkzeuge NeuroMap und Complexity Signature. Mit dieser Strukturierung wird die ärztliche Kompetenz in Untersuchung, Beurteilung und Entscheidungsfindung gestärkt, hohe Qualität in der Versorgung generiert, Orientierung zu Zeit- und Strukturplanungen gegeben sowie der Dialog zwischen Allgemein- und Neuropädiatrie betont.
The apex of the deep cartilage is a stable landmark to position the femoral tunnel during remnant‐preserving anterior cruciate ligament reconstruction
Authors: Zhang Keying , Meng Qingyang , Zhang Jingwei , Gao Yitian , Yang Yuping , Liu Ping , Wang Cheng , Ma Yong , Shi Weili
Published: November 2023

Purpose

The aim of this retrospective cohort study was to investigate whether the apex of the deep cartilage (ADC) could help surgeons position the femoral tunnel accurately in remnant‐preserving anterior cruciate ligament (ACL) reconstruction (ACLR).

Methods

In the current retrospective cohort study, a total of 134 patients who underwent ACLR between 2016 and 2020 were included. The femoral tunnel position was located using ADC as the landmark. The patients were divided into two groups: the remnant‐preserving group (RP group, n = 68) underwent remnant‐preserving ACLR, and the nonremnant group (NRP group, n = 66) underwent traditional ACLR with remnant removal. Postoperatively, the femoral tunnel position was evaluated on 3D‐CT. The length from the ADC to the shallow cartilage margin (L) and to the centre of the femoral tunnel (l) and the length from the centre of the femoral tunnel to a low cartilage ratio in the direction from high to low (H) were measured.

Results

The l/L values of the RP and NRP groups were both 0.4 ± 0.1 after rounding (n.s.), and the H values were 9.3 ± 1.6 mm and 9.3 ± 1.7 mm, respectively (n.s.). There was no significant difference in l/L or H between the two groups. The estimation plot also showed high consistency of H and l/L of the two groups. The inter‐ and intraobserver reliability of I, L, l/L, and H were almost perfect.

Conclusions

The apex of the deep cartilage is a good landmark for positioning the femoral tunnel in remnant‐preserving ACL reconstruction.

Level of evidence

Level III.
The lowest singlet states of hexatriene revisited
Authors: Guareschi Riccardo , Angeli Celestino
Published: November 2023

The two lowest excited singlet states of trans-hexatriene and cis-hexatriene are studied by multireference perturbation theory approaches (NEVPT2 and CASPT2) in their quasi-degenerate version (QD-NEVPT2 and MS-CASPT2). For these states, we report spectroscopic properties such as the vertical and adiabatic excitation energies, some features of the topology of the potential energy surfaces (PES), and the emission energies. The theoretical vertical excitation energies for the $${2{\hspace{0.05cm}}{^1\textrm{A}_g^-}}$$

2

1

A
g
-

and $${1{\hspace{0.05cm}}{^1\textrm{B}_u^+}}$$

1

1

B
u
+

states of trans-hexatriene are found to be almost degenerate, with a value, $$\simeq$$
≃
5.5–5.6 eV, higher than that normally accepted in the literature, 5.2 eV and 5.1 eV, respectively. The $${2{\hspace{0.05cm}}{^1\textrm{A}_1}}$$

2

1

A
1

and $${1{\hspace{0.05cm}}{^1\textrm{B}_2}}$$

1

1

B
2

states of cis-hexatriene are also almost degenerate and are estimated to be at $$\simeq$$
≃
5.4–5.5 and $$\simeq$$
≃
5.5 eV, respectively, again higher than the accepted values. The adiabatic excitation energies to the $${2{\hspace{0.05cm}}{^1\textrm{A}_g^-}}$$

2

1

A
g
-

and $${2{\hspace{0.05cm}}{^1\textrm{A}_1}}$$

2

1

A
1

states can be observed experimentally (in particular for the cis isomer), and our results are in excellent agreement with the experimental values. On the contrary, the vertical excitation energies for these states are not directly observable in the experimental spectra and the “experimental” values are obtained by educated guesses. We show that the hypotheses underlying these guesses are not entirely grounded.
Polyharmonic surfaces in 3-dimensional homogeneous spaces
Authors: Montaldo S.  , Oniciuc C.  , Ratto A. 
Published: November 2023

In the first part of this paper we shall classify proper triharmonic isoparametric surfaces in 3-dimensional homogeneous spaces (Bianchi-Cartan-Vranceanu spaces, shortly BCV-spaces). We shall also prove that triharmonic Hopf cylinders are necessarily CMC. In the last section we shall determine a complete classification of CMC r-harmonic Hopf cylinders in BCV-spaces, $$r \ge 3$$

r
≥
3

. This result ensures the existence, for suitable values of r, of an ample family of new examples of r-harmonic surfaces in BCV-spaces.
Deeplasia: deep learning for bone age assessment validated on skeletal dysplasias
Authors: Rassmann Sebastian , Keller Alexandra , Skaf Kyra , Hustinx Alexander , Gausche Ruth , Ibarra-Arrelano Miguel A. , Hsieh Tzung-Chien , Madajieu Yolande E. D. , Nöthen Markus M. , Pfäffle Roland , Attenberger Ulrike I. , Born Mark , Mohnike Klaus , Krawitz Peter M. , Javanmardi Behnam
Published: November 2023

Background

Skeletal dysplasias collectively affect a large number of patients worldwide. Most of these disorders cause growth anomalies. Hence, evaluating skeletal maturity via the determination of bone age (BA) is a useful tool. Moreover, consecutive BA measurements are crucial for monitoring the growth of patients with such disorders, especially for timing hormonal treatment or orthopedic interventions. However, manual BA assessment is time-consuming and suffers from high intra- and inter-rater variability. This is further exacerbated by genetic disorders causing severe skeletal malformations. While numerous approaches to automate BA assessment have been proposed, few are validated for BA assessment on children with skeletal dysplasias.

Objective

We present Deeplasia, an open-source prior-free deep-learning approach designed for BA assessment specifically validated on patients with skeletal dysplasias.

Materials and methods

We trained multiple convolutional neural network models under various conditions and selected three to build a precise model ensemble. We utilized the public BA dataset from the Radiological Society of North America (RSNA) consisting of training, validation, and test subsets containing 12,611, 1,425, and 200 hand and wrist radiographs, respectively. For testing the performance of our model ensemble on dysplastic hands, we retrospectively collected 568 radiographs from 189 patients with molecularly confirmed diagnoses of seven different genetic bone disorders including achondroplasia and hypochondroplasia. A subset of the dysplastic cohort (149 images) was used to estimate the test–retest precision of our model ensemble on longitudinal data.

Results

The mean absolute difference of Deeplasia for the RSNA test set (based on the average of six different reference ratings) and dysplastic set (based on the average of two different reference ratings) were 3.87 and 5.84 months, respectively. The test–retest precision of Deeplasia on longitudinal data (2.74 months) is estimated to be similar to a human expert.

Conclusion

We demonstrated that Deeplasia is competent in assessing the age and monitoring the development of both normal and dysplastic bones.

Graphical Abstract
Mitigating SUV uncertainties using total body PET imaging
Authors: Smith Charlotte L. C. , Zwezerijnen Gerben J. C. , den Hollander Marijke E. , Weijland Jolijn , Yaqub Maqsood , Boellaard Ronald
Published: November 2023

Purpose

Standardised uptake values (SUV) are commonly used to quantify 18F-FDG lesion uptake. However, SUVs may suffer from several uncertainties and errors. Long-axial field-of-view (LAFOV) PET/CT systems might enable image-based quality control (QC) by deriving 18F-FDG activity and weight from total body (TB) 18F-FDG PET images. In this study, we aimed to develop these image-based QC to reduce errors and mitigate SUV uncertainties.

Methods

Twenty-five out of 81 patient scans from a LAFOV PET/CT system were used to determine regression fits for deriving of image-derived activity and weight. Thereafter, the regression fits were applied to 56 independent 18F-FDG PET scans from the same scanner to determine if injected activity and weight could be obtained accurately from TB and half-body (HB) scans. Additionally, we studied the impact of image-based values on the precision of liver SUVmean and lesion SUVpeak. Finally, 20 scans were acquired from a short-axial field-of-view (SAFOV) PET/CT system to determine if the regression fits also applied to HB scans from a SAFOV system.

Results

Both TB and HB 18F-FDG activity and weight significantly predicted reported injected activity (r = 0.999; r = 0.984) and weight (r = 0.999; r = 0.987), respectively. After applying the regression fits, 18F-FDG activity and weight were accurately derived within 4.8% and 3.2% from TB scans and within 4.9% and 3.1% from HB, respectively. Image-derived values also mitigated liver and lesion SUV variability compared with reported values. Moreover, 18F-FDG activity and weight obtained from a SAFOV scanner were derived within 6.7% and 4.5%, respectively.

Conclusion

18F-FDG activity and weight can be derived accurately from TB and HB scans, and image-derived values improved SUV precision and corrected for lesion SUV errors. Therefore, image-derived values should be included as QC to generate a more reliable and reproducible quantitative uptake measurement.
The Role of the Inframammary Fold (IMF) in Aesthetic and Reconstructive Surgery: A Critical Analysis and Surgical Solution
Authors: Hudson Donald A
Published: November 2023

Introduction

The inframammary fold (IMF) is a critical structure in breast aesthetics and is affected by various types of breast surgery. The ideal IMF has a semi-elliptical shape, which may become attenuated with age and descends in macromastia. The aim of this study was to analyse the IMF and retain/restore its shape with sutures.

Methods

A retrospective study was conducted on breast surgeries performed over a four-year period (2019–2022). The morphometry of the IMF was evaluated preoperatively while the patients were standing. In cases where the IMF was symmetrical, sutures were used to reinforce it during surgery. When the loss of the semi-elliptical shape was clinically indicated, the IMF was mobilized, repositioned, and then sutured into place.

Results

The study included 56 patients: 43 undergoing immediate breast reconstruction, and 13 undergoing bilateral breast reductions. In over two thirds of the patients, the lateral IMF was inferiorly displaced compared to the medial IMF.

Conclusion

It is recommended to reinforce the IMF in all patients undergoing breast surgery. Where the IMF has an elliptical shape preoperatively, it is reinforced. Where IMF is inferiorly displaced, mobilization and superior advancement of the IMF, followed by suture reinforcement, are necessary. This approach results in a well-defined IMF with improved breast aesthetics.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Relative bioavailability of fedratinib through various alternative oral administration methods in healthy adults
Authors: Chen Yizhe , Wyatt David , Attanasio Massimo , Thomas Mark , Thomas Michael , He Bing , Nishii Rina , Liu Liangang , Shan Vivian , Xue Yongjun , Carayannopoulos Leonidas N. , Ogasawara Ken , Krishna Gopal
Published: November 2023

Fedratinib is an oral Janus kinase 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis; however, some patients have difficulty with oral dosing. This randomized, phase 1, open-label, 2-part crossover study evaluated the relative bioavailability, safety, tolerability, taste, and palatability of fedratinib resulting from various alternative oral administration methods in healthy adults. Participants could receive fedratinib 400 mg orally as intact capsules along with a nutritional supplement; as contents of capsules dispersed in a nutritional supplement, delivered via nasogastric tube; or as a divided dose of 200 mg orally twice daily as intact capsules with a nutritional supplement. Fifty-eight participants received treatment. Total exposure to fedratinib was similar after oral administration of intact capsules or when dispersed in a nutritional supplement (area under the plasma concentration–time curve from time 0 to the time of the last quantifiable concentration geometric mean ratio [AUC0–t GMR] [90% CI], 1.007 [0.929–1.092]). Total exposure to fedratinib was slightly reduced following nasogastric administration (AUC0–t GMR 0.850 [0.802–0.901]) and as a divided dose (AUC0–t GMR 0.836 [0.789–0.886]). No new safety signals were identified for fedratinib, and most participants found the taste and palatability acceptable when dispersed in a nutritional supplement. Overall, results suggest no clinically meaningful differences in total exposure to fedratinib between the tested oral administration methods. These findings may facilitate administration of fedratinib to patients who are intolerant of swallowing the capsule dosage form. (ClinicalTrials.gov: NCT05051553).
Imaging of alert patients after non-self-inflicted strangulation: MRI is superior to CT
Authors: Ruder Thomas D , Gonzenbach Alexandra , Heimer Jakob , Arneberg Leonie , Klukowska-Rötzler Jolanta , Blunier Simone , Exadaktylos Aristomenis K , Zech Wolf-Dieter , Wagner Franca
Published: November 2023

Objective

To assess the accuracy of CT and MRI reports of alert patients presenting after non-self-inflicted strangulation (NSIS) and evaluate the appropriateness of these imaging modalities in NSIS.

Material and methods

The study was a retrospective analysis of patient characteristics and strangulation details, with a comparison of original radiology reports (ORR) to expert read-outs (EXR) of CT and MRI studies of all NSIS cases seen from 2008 to 2020 at a single centre.

Results

The study included 116 patients (71% women, p < .001, χ2), with an average age of 33.8 years, mostly presenting after manual strangulation (97%). Most had experienced intimate partner violence (74% of women, p < .001, χ2) or assault by unknown offender (88% of men, p < 0.002 χ2). Overall, 132 imaging studies (67 CT, 51% and 65 MRI, 49%) were reviewed. Potentially dangerous injuries were present in 7%, minor injuries in 22%, and no injuries in 71% of patients. Sensitivity and specificity of ORR were 78% and 97% for MRI and 30% and 98% for CT. Discrepancies between ORR and EXR occurred in 18% of all patients, or 62% of injured patients, with a substantial number of unreported injuries on CT.

Conclusions

The results indicate that MRI is more appropriate than CT for alert patients presenting after non-self-inflicted strangulation and underline the need for radiologists with specialist knowledge to report these cases in order to add value to both patient care and potential future medico-legal investigations.

Clinical relevance statement

MRI should be preferred over CT for the investigation of strangulation related injuries in alert patients because MRI has a higher accuracy than CT and does not expose this usually young patient population to ionizing radiation.

Key Points

• Patients presenting after strangulation are often young women with a history of intimate partner violence while men typically present after assault by an unknown offender.

• Expert read-outs of CT and MRI revealed potentially dangerous injuries in one of 14 patients.

• MRI has a significantly higher sensitivity than CT and appears to be more appropriate for the diagnostic workup of alert patients after strangulation.
Performance of artificial intelligence in 7533 consecutive prevalent screening mammograms from the BreastScreen Australia program
Authors: Waugh John , Evans Jill , Miocevic Miranda , Lockie Darren , Aminzadeh Parisa , Lynch Anne , Bell Robin J.
Published: November 2023

Objectives

To assess the performance of an artificial intelligence (AI) algorithm in the Australian mammography screening program which routinely uses two independent readers with arbitration of discordant results.

Methods

A total of 7533 prevalent round mammograms from 2017 were available for analysis. The AI program classified mammograms into deciles on the basis of breast cancer (BC) risk. BC diagnoses, including invasive BC (IBC) and ductal carcinoma in situ (DCIS), included those from the prevalent round, interval cancers, and cancers identified in the subsequent screening round two years later. Performance was assessed by sensitivity, specificity, positive and negative predictive values, and the proportion of women recalled by the radiologists and identified as higher risk by AI.

Results

Radiologists identified 54 women with IBC and 13 with DCIS with a recall rate of 9.7%. In contrast, 51 of 54 of the IBCs and 12/13 cases of DCIS were within the higher AI score group (score 10), a recall equivalent of 10.6% (a difference of 0.9% (CI −0.03 to 1.89%, p = 0.06). When IBCs were identified in the 2017 round, interval cancers classified as false negatives or with minimal signs in 2017, and cancers from the 2019 round were combined, the radiologists identified 54/67 and 59/67 were in the highest risk AI category (sensitivity 80.6% and 88.06 % respectively, a difference that was not different statistically).

Conclusions

As the performance of AI was comparable to that of expert radiologists, future AI roles in screening could include replacing one reader and supporting arbitration, reducing workload and false positive results.

Clinical relevance statement

AI analysis of consecutive prevalent screening mammograms from the Australian BreastScreen program demonstrated the algorithm’s ability to match the cancer detection of experienced radiologists, additionally identifying five interval cancers (false negatives), and the majority of the false positive recalls.

Key Points

• The AI program was almost as sensitive as the radiologists in terms of identifying prevalent lesions (51/54 for invasive breast cancer, 63/67 when including ductal carcinoma in situ).

• If selected interval cancers and cancers identified in the subsequent screening round were included, the AI program identified more cancers than the radiologists (59/67 compared with 54/67, sensitivity 88.06 % and 80.6% respectively p = 0.24).

• The high negative predictive value of a score of 1–9 would indicate a role for AI as a triage tool to reduce the recall rate (specifically false positives).
High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy
Authors: Haj-Yehia Elias , Mincu Raluca I. , Korste Sebastian , Lampe Lena , Margraf Simone M. , Michel Lars , Mahabadi Amir A. , Ferdinandy Péter , Rassaf Tienush , Totzeck Matthias
Published: November 2023

Background

Cancer therapy-related cardiovascular toxicity (CTR-CVT) from immune checkpoint inhibitor (ICI) therapy is still incompletely characterized, and patients with pre-existing cardiovascular disease represent a particularly high-risk cohort. Valid parameters for risk stratification of these patients are missing. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict mortality and adverse events in other cardiovascular cohorts. The present study aims to examine the predictive capacity of NLR for risk stratification of patients particularly vulnerable for CTR-CVT under ICI therapy.

Methods

We performed an analysis of 88 cancer patients (69 ± 11 years, 25% female) with pre-existing cardiovascular disease under ICI therapy from the prospective Essen Cardio-Oncology Registry (ECoR). NLR was assessed at patient enrollment and the population was divided through receiver operator characteristic (ROC) curve analysis in patients with low (< 4.57) and high (≥ 4.57) NLR. Endpoint was the whole spectrum of CTR-CVT, according to the European guidelines on cardio-oncology. The median follow-up was 357 days (interquartile range (IQR): 150–509 days).

Results

We observed 4 cases of myocarditis, 17 cases of vascular toxicity, 3 cases of arterial hypertension, 22 cases of arrhythmia or QTc prolongation and 17 cases of cardiovascular dysfunction. NLR was associated with overall CTR-CVT by univariable Cox regression (hazard ratio (HR): 1.443; 95% confidence interval (CI) 1.082–1.925; p = 0.013). However, this association was attenuated after adjusting for further confounders.

Conclusion

NLR is moderately associated with CTR-CVT in cancer patients with pre-existing cardiovascular disease under ICI therapy. Surveillance of NLR during ICI therapy might be an effective and economically biomarker for risk stratification in these high-risk patients.

Graphical abstract
Transcranial direct current stimulation combined with a brief intervention for smoking cessation: a randomized double-blind clinical trial
Authors: Palm Ulrich , Obergfell Mark , Rabenstein Andrea , Björklund Jonas , Koller Gabi , Padberg Frank , Rüther Tobias
Published: November 2023

Non-invasive brain stimulation methods are currently being evaluated for treatment of addictive disorders. Some evidence indicates that modulating left and right prefrontal brain activity by transcranial direct current stimulation (tDCS) can reduce craving and relapse rates in tobacco addiction. Therefore, this study investigated the effects of active and sham tDCS as an add-on treatment to a standardized brief intervention for smoking cessation. This randomized, double-blind study included 36 participants (22 women and 14 men) with nicotine dependence according to ICD-10 criteria. At five visits on alternate days, participants underwent a 20-min active or sham tDCS over the left dorsolateral prefrontal cortex and subsequently participated in a 10-min brief intervention for smoking cessation. Patients were followed up after 3 months. On each treatment day and at follow-up, abstinence was assessed as the smoking status nonsmoker and craving was assessed with the German version of the Questionnaire on Smoking Urges. At each visit, the number of cigarettes smoked per day was recorded and carbon monoxide in expired air and cotinine in saliva were measured. At follow-up, a study-specific questionnaire was used to assess tobacco use. All 36 participants completed the treatment sessions, but one participant in each group was lost to follow-up. Abstinence rates were not significantly different between the groups at any of the study visits, but craving was significantly lower in the active group at tDCS session 5 compared with session 1. tDCS combined with a brief intervention may support smoking cessation, but studies need to evaluate whether longer and more intensive treatment can achieve significant, sustainable effects.
On Maximizing Sums of Non-monotone Submodular and Linear Functions
Authors: Qi Benjamin
Published: November 2023

We study the problem of () as defined by Bodek and Feldman (Maximizing sums of non-monotone submodular and linear functions: understanding the unconstrained case, arXiv:2204.03412, 2022): given query access to a non-negative submodular function $$f:2^{{\mathcal {N}}}\rightarrow {\mathbb {R}}_{\ge 0}$$

f
:

2
N

→

R

≥
0

and a linear function $$\ell :2^{{\mathcal {N}}}\rightarrow {\mathbb {R}}$$

ℓ
:

2
N

→
R

over the same ground set $${\mathcal {N}}$$
N
, output a set $$T\subseteq {\mathcal {N}}$$

T
⊆
N

approximately maximizing the sum $$f(T)+\ell (T)$$

f
(
T
)
+
ℓ
(
T
)

. An algorithm is said to provide an $$(\alpha ,\beta )$$

(
α
,
β
)

-approximation for if it outputs a set T such that $${\mathbb {E}}[f(T)+\ell (T)]\ge \max _{S\subseteq {\mathcal {N}}}[\alpha \cdot f(S)+\beta \cdot \ell (S)]$$

E

[
f

(
T
)

+
ℓ

(
T
)

]

≥

max

S
⊆
N

[
α
·
f

(
S
)

+
β
·
ℓ

(
S
)

]

. We also consider the setting where S and T are constrained to be independent in a given matroid, which we refer to as  Constrained (). The special case of with monotone f has been extensively studied (Sviridenko et al. in Math Oper Res 42(4):1197–1218, 2017; Feldman in Algorithmica 83(3):853–878, 2021; Harshaw et al., in: International conference on machine learning, PMLR, 2634–2643, 2019), whereas we are aware of only one prior work that studies with non-monotone f (Lu et al. in Optimization 1–27, 2023), and that work constrains $$\ell $$
ℓ
to be non-positive. In this work, we provide improved $$(\alpha ,\beta )$$

(
α
,
β
)

-approximation algorithms for both and with non-monotone f. Specifically, we are the first to provide nontrivial $$(\alpha ,\beta )$$

(
α
,
β
)

-approximations for where the sign of $$\ell $$
ℓ
is unconstrained, and the $$\alpha $$
α
we obtain for improves over (Bodek and Feldman in Maximizing sums of non-monotone submodular and linear functions: understanding the unconstrained case, arXiv:2204.03412, 2022) for all $$\beta \in (0,1)$$

β
∈
(
0
,
1
)

. We also prove new inapproximability results for and , as well as 0.478-inapproximability for maximizing a submodular function where S and T are subject to a cardinality constraint, improving a 0.491-inapproximability result due to Oveis Gharan and Vondrak (in: Proceedings of the twenty-second annual ACM-SIAM symposium on discrete algorithms, SIAM, pp 1098–1116, 2011).
A versatile implicit computational framework for continuum-kinematics-inspired peridynamics
Authors: Firooz S. , Javili A. , Steinmann P.
Published: November 2023

Continuum-kinematics-inspired peridynamics (CPD) has been recently proposed as a novel reformulation of peridynamics that is characterized by one-, two- and three-neighbor interactions. CPD is geometrically exact and thermodynamically consistent and does not suffer from zero-energy modes, displacement oscillations or material interpenetration. In this manuscript, for the first time, we develop a computational framework furnished with automatic differentiation for the implementation of CPD. Thereby, otherwise tedious analytical differentiation is automatized by employing hyper-dual numbers (HDN). This differentiation method does not suffer from round-off errors, subtractive cancellation errors or truncation errors and is thereby highly stable with superb accuracy being insensitive to perturbation values. The computational framework provided here is compact and model-independent, thus once the framework is implemented, any other material model can be incorporated via modifying the potential energy solely. Finally, to illustrate the versatility of our proposed framework, various potential energies are considered and the corresponding material response is examined for different scenarios.
Complement dysregulation associated with a genetic variant in factor H-related protein 5 in atypical hemolytic uremic syndrome
Authors: Aradottir Sigridur Sunna , Kristoffersson Ann-Charlotte , Linnér Erik , Karpman Diana
Published: November 2023

Background

Atypical hemolytic uremic syndrome (aHUS) can be associated with mutations, deletions, or hybrid genes in factor H-related (FHR) proteins.

Methods

A child with aHUS was investigated. Genetics was assessed by Sanger and next generation sequencing. Serum FHR5 was evaluated by immunoblotting, ELISA, and by induction of rabbit red blood cell hemolysis in the presence/absence of recombinant human rFHR5. Mutagenesis was performed in HEK cells.

Results

A heterozygous genetic variant in factor H-related protein 5 (CFHR5), M514R, was found in the child, who also had a homozygous deletion of CFHR3/CFHR1, and antibodies to factor H, as well as low levels of C3. Patient serum exhibited low levels of FHR5. In the presence of rabbit red blood cells, patient serum induced hemolysis which decreased when rFHR5 was added at physiological concentrations. Similar results were obtained using serum from the father, bearing the CFHR5 variant without factor H antibodies. Patient FHR5 formed normal dimers. The CFHR5 M514R variant was expressed in HEK cells and minimal secretion was detected whereas the protein level was elevated in cell lysates.

Conclusions

Decreased secretion of the product of the mutant allele could explain the low FHR5 levels in patient serum. Reduced hemolysis when rFHR5 was added to serum suggests a regulatory role regarding complement activation on red blood cells. As such, low levels of FHR5, as demonstrated in the patient, may contribute to complement activation.

Graphical abstract
Evolutionary algorithm with a regression model for multiobjective minimization of systemic risk in financial systems
Authors: Michalak Krzysztof
Published: November 2023

This paper addresses a problem of systemic risk minimization in which the optimization algorithm has to simultaneously minimize the number of companies affected by a wave of bankruptcies simulated on a graph as well as the level of reserves the companies keep to avoid going bankrupt. A MOEA/D-NN algorithm (where NN stands for a neural network) is proposed, which optimizes parameters of a machine learning model (a neural network) used in turn to determine the level of reserves the companies keep, based on several attributes describing each node in the graph. In the experiments, the proposed MOEA/D-NN algorithm was found to outperform comparison methods: evolutionary algorithms optimizing the level of reserves for all companies and a method based on the training of neural networks on a dataset previously collected by an evolutionary algorithm solving “training” instances of the optimization problem. The neural networks optimized by MOEA/D-NN were also tested on problem instances based on REDS graphs generated using varying values ofR,E, andSparameters and were found to be applicable to these instances for certain ranges of parameters. TheRparameter controlling the possibility of generating long-distance connections was found to have a bigger impact on the performance of the optimized neural networks than the other two parameters.