bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Productivity and Patient Complexity of Academic Rhinologists: An Analysis of Medicare Metrics
Authors: Warn Michael J. , Torabi Sina J. , Bitner Benjamin F. , Chan Daniella , Nguyen Theodore V. , Kuan Edward C.
Published: April 2024

Introduction

Current data regarding reimbursement trends in Medicare services and the complexity of patients treated as physicians' progress in their academic career are conflicting. In otolaryngology, there are no data examining these metrics.

Methods

Medicare services, reimbursement, and patient complexity risk scores (based on hierarchical condition category coding) of US rhinology fellowship‐trained faculty were stratified and compared by rank and years in practice.

Results

A cohort of 209 rhinologists were included. Full professors were reimbursed more per service than assistant professors ($791.53 [$491.69–1052.46] vs. $590.34 [$429.91–853.07] p = 0.045) and had lower risk scores (1.37 [1.26–1.52] vs. 1.49 [1.29–1.68], p = 0.013). Full professors had similar risk scores to associate professors (1.47 [1.25–1.64], p = 0.14). Full professors ($791.53 [$491.69–1,052.46], p < 0.001), associate professors ($706.85 [$473.48–941.15], p < 0.001), and assistant professors ($590.34 [$429.91–853.07], p < 0.001) were all reimbursed more per service than non‐ranked faculty ($326.08 [$223.37–482.36]). As a cohort, significant declines in risk scores occurred within the 10th–14th year of practice (p = 0.032) and after the 20th year (p = 0.038). Years in practice were inversely correlated with risk score (R = −0.358, p < 0.001).

Conclusion

Full professors were reimbursed more per service and treated less comorbid Medicare patients than junior academic colleagues. Patient comorbidity was correlated negatively with years in practice, with significant drops in mid and late career. Rhinologists employed at academic institutions had greater total reimbursement and reimbursement per service than non‐ranked faculty.

Level of Evidence

N/A Laryngoscope, 134:3960–3964, 2024
Evaluation of Balance with Computerized Dynamic Posturography in Children with Otitis Media
Authors: Kaplan Büşra , Altın Büşra , Akyol Mehmet Umut , Aksoy Songül
Published: April 2024

Background

Otitis media with effusion (OME) frequently leads to vestibular symptoms in children. However, young children face difficulty expressing their symptoms due to their limited language abilities.

Methods

The balance of study and patient group evaluated with computer dynamic posturography, single‐leg stance test with eyes closed and regular Head Impulse Test. The study group was assessed once again after the insertion of a ventilation tube two months later.

Results

In the Sensory Organization Test, the scores for conditions 5, 6, and composite equilibrium of the preoperative patient group were notably lower compared with both the control and postoperative patient groups (p < 0.05). Additionally, a significant correlation was found between single‐leg stance test with eyes closed results and conditions 5, 6, and composite equilibrium scores.

Conclusion

The impact of OME on the vestibular system is negative. This effect can be objectively assessed using Computer Dynamic Posturography and following tube insertion, there is a notable improvement in vestibular function. Furthermore, the single‐leg stance (SLS) test with eyes closed has shown its reliability in assessing balance disorders, notably in children with OME.

Level of Evidence

2 Laryngoscope, 134:4126–4133, 2024
Composite Hydrogel Containing Collagen‐Modified Polylactic Acid‐Hydroxylactic Acid Copolymer Microspheres Loaded with Tetramethylpyrazine Promotes Articular Cartilage Repair
Authors: Pan Yalan , Li Bin , Sun Xiaoxian , Tu Pengcheng , Guo Yang , Zhao Zitong , Wu Mao , Wang Yun , Wang Zhifang , Ma Yong
Published: April 2024

Articular cartilage defects pose a significant challenge due to the limited self‐healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of the polylactic acid‐glycolic acid (PLGA) and collagen‐surface modified polylactic acid‐glycolic acid (CPLGA) microspheres loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. CPLGA microspheres are prepared by Steglich reaction and characterized. They evaluated the effect of TMP‐loaded microspheres on HUVECs (Human Umbilical Vein Endothelial Cells) and examined the compatibility of blank microspheres with BMSCs (Bone marrow mesenchymal stromal cells) and their potential to promote cartilage differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen‐induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP‐loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere‐composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation.
Geometric and analytic results for Einstein solitons
Authors: Agila Enrique F. L. , Gomes José N. V.
Published: April 2024

We compute a lower bound for the scalar curvature of a gradient Einstein soliton under a certain assumption on its potential function. We establish an asymptotic behavior of the potential function on a noncompact gradient shrinking Einstein soliton. As a result, we obtain the finiteness of its fundamental group and its weighted volume. We also prove some geometric and analytic results for constructing gradient Einstein solitons that are realized as warped metrics, and we give a few explicit examples.
Opicapone to Treat Early Wearing‐off in Parkinson's Disease Patients: The Korean ADOPTION Trial
Authors: Lee Jee‐Young , Ma Hyeo‐il , Ferreira Joaquim J. , Rocha José‐Francisco , Sung Young Hee , Song In‐Uk , Ahn Tae‐Beom , Kwon Do Young , Cheon Sang‐Myung , Kim Jong‐Min , Lee Chong Sik , Lee Phil Hyu , Park Jeong‐Ho , Lee Jae‐Hyeok , Park Mee Young , Kim Sang Jin , Baik Jong Sam , Choi Seong‐Min , Shin Hae‐Won , Lee Ho‐Won , Kang Suk Yun , Jeon Beomseok
Published: April 2024

Background

Increasing levodopa (L‐dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol‐O‐methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing‐off symptoms in Parkinson's disease (PD) patients.

Objectives

To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing‐off in PD patients.

Methods

ADOPTION was a randomized, parallel‐group, open‐label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L‐dopa 100 mg (n = 81) (added to current L‐dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society‐Unified Parkinson's Disease Rating Scale and 8‐item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change.

Results

The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L‐dopa 100 mg (−62.1 vs. −16.7 minutes; P = 0.0015). Opicapone‐treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L‐dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied.

Conclusions

Opicapone 50 mg was more effective than an additional 100 mg L‐dopa dose at decreasing off time in patients with PD and early wearing‐off.
Technical note: Radiological clinical equivalence for phantom materials in carbon ion therapy
Authors: Taylor Paige A. , Mirandola Alfredo , Ciocca Mario , Hartzell Shannon , Vai Alessandro , Alvarez Paola , Howell Rebecca M. , Koay Eugene J. , Peeler Christopher R. , Peterson Christine B. , Kry Stephen F.
Published: April 2024

Purpose

As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam.

Methods

Eight materials were tested for radiological material‐equivalence in a carbon ion beam. The materials were computed tomography (CT)‐scanned to obtain Hounsfield unit (HU) values, then irradiated in a monoenergetic carbon ion beam to determine relative linear stopping power (RLSP). The corresponding HU and RLSP for each phantom material were compared to clinical carbon ion calibration curves. For absorbed dose comparison, ion chamber measurements were made in the center of a carbon ion spread‐out Bragg peak (SOBP) in water and in the phantom material, evaluating whether the material perturbed the absorbed dose measurement beyond what was predicted by the HU‐RLSP relationship.

Results

Polyethylene, solid water (Gammex and Sun Nuclear), Blue Water (Standard Imaging), and Techtron HPV had measured RLSP values that agreed within ±4.2% of RLSP values predicted by the clinical calibration curve. Measured RLSP for acrylic was 7.2% different from predicted. The agreement for balsa wood and cork varied between samples. Ion chamber measurements in the phantom materials were within 0.1% of ion chamber measurements in water for most materials (solid water, Blue Water, polyethylene, and acrylic), and within 1.9% for the rest of the materials (balsa wood, cork, and Techtron HPV).

Conclusions

Several phantom materials (Blue Water, polyethylene, solid water [Gammex and Sun Nuclear], and Techtron HPV) are suitable for heterogeneous phantom measurements for carbon ion therapy. Low density materials should be carefully characterized due to inconsistencies between samples.
A noise robust image reconstruction using slice aware cycle interpolator network for parallel imaging in MRI
Authors: Kim Jeewon , Lee Wonil , Kang Beomgu , Seo Hyunseok , Park HyunWook
Published: April 2024

Background

Reducing Magnetic resonance imaging (MRI) scan time has been an important issue for clinical applications. In order to reduce MRI scan time, imaging acceleration was made possible by undersampling k‐space data. This is achieved by leveraging additional spatial information from multiple, independent receiver coils, thereby reducing the number of sampled k‐space lines.

Purpose

The aim of this study is to develop a deep‐learning method for parallel imaging with a reduced number of auto‐calibration signals (ACS) lines in noisy environments.

Methods

A cycle interpolator network is developed for robust reconstruction of parallel MRI with a small number of ACS lines in noisy environments. The network estimates missing (unsampled) lines of each coil data, and these estimated missing lines are then utilized to re‐estimate the sampled k‐space lines. In addition, a slice aware reconstruction technique is developed for noise‐robust reconstruction while reducing the number of ACS lines. We conducted an evaluation study using retrospectively subsampled data obtained from three healthy volunteers at 3T MRI, involving three different slice thicknesses (1.5, 3.0, and 4.5 mm) and three different image contrasts (T1w, T2w, and FLAIR).

Results

Despite the challenges posed by substantial noise in cases with a limited number of ACS lines and thinner slices, the slice aware cycle interpolator network reconstructs the enhanced parallel images. It outperforms RAKI, effectively eliminating aliasing artifacts. Moreover, the proposed network outperforms GRAPPA and demonstrates the ability to successfully reconstruct brain images even under severe noisy conditions.

Conclusions

The slice aware cycle interpolator network has the potential to improve reconstruction accuracy for a reduced number of ACS lines in noisy environments.
Small proteins, great promises: Geographic bioprospecting of Bowman–Birk protease inhibitors and domestication side‐effects in African cowpea (Vigna unguiculata L.)
Authors: Panzeri Davide , Toini Elisa , Vertemara Jacopo , Silvestri Giuseppe , Bunea Victor Vladut , Zecca Giovanni , Nissim Werther Guidi , Wagensommer Robert Philipp , Zampella Giuseppe , Labra Massimo , Grassi Fabrizio
Published: April 2024

Societal Impact Statement

The legume crop cowpea is grown worldwide, but 90% of the world's total share is produced in Africa. It is a promising species due to its resilience properties, balance of macro and micronutrients and presence of health‐promoting bioactive compounds. In African countries, cowpea has a crucial role in guaranteeing food security as a subsistence crop for families and commercial income for small farmers. The discovery of compounds with high nutraceutical value and bioactive properties supports socio‐economic policies to improve health and nutrition, especially in low‐ and middle‐income countries. In turn, this encourages biodiversity protection and crop enhancement programmes.

Bowman–Birk protease inhibitors (BBIs) are a restricted group of small proteins in plants mainly involved in defence mechanisms against pests. BBIs are demonstrated to be active components capable of reducing the viabilities of different cancer cell lines. BBI bioactivity is directly linked to the inhibition capacity, but the variability and the efficiency against the physiological targets of different BBI isoforms remain still unexplored.

We analysed the natural genetic diversity of two main genes encoding BBI trypsin‐trypsin (BBI‐TT) and trypsin‐chymotrypsin (BBI‐TC) in wild and domesticated cowpea samples mainly spread in Sub‐Saharan Africa. We analysed DNA sequences and respective amino acidic isoforms/isoproteins to explore signs of natural selection and haplotype relationships. Moreover, we calculated the binding energy between BBIs and their biological targets to identify which are the most efficient inhibitors and their geographical locations.

We found a high level of haplotype diversity for both genes, almost exclusively in wild accessions and detected positive and negative selection signals in the amino acid sequences. Furthermore, in the wild diversity pool, some BBI‐TT and BBI‐TC mature proteins were potentially better interactors with the physiological targets.

The long interaction between plant‐pathogen has selected new and useful isoforms in wild lineages that have allowed the chances of survival of the species to improve. On the other hand, the domestication process has produced an intense bottleneck leaving only poorly efficient BBI variants. In addition to providing information on the natural diversity and evolution of BBIs, our work discusses the potential applications in agriculture and human health.
Hybrid Approach for Modeling Memristive Elements
Authors: Abgaryan Karine Karlenovna , Morozov Alexander Yurievich , Reviznikov Dmitry Leonidovich
Published: April 2024

Typically, changes in the conductive properties of resistive random‐access memory elements happen due to the movement of ions in an ultra‐thin dielectric layer under the influence of an electric field. In the case of oxides, they often talk about the movement of oxygen vacancies and the formation/destruction of conducting filaments. Such processes are often described by dynamic systems in which the state parameter corresponds to the position of the boundary between regions with low and high concentrations of oxygen vacancies. In this case, the dependence of the current (or resistance) on the state parameter and the voltage applied to the element can be quite complex. In this regard, the work proposes an approach that uses neural networks to approximate the dependence of the current on the state parameter and voltage. Thus, a hybrid model is obtained in which the state parameter is determined using a dynamic system that takes into account the basic physical characteristics of the elements, and the model is finely tuned to the experimental data at the neural network level. A hybrid model for a memristor based on hafnium oxide (HfO2), as well as on nanocomposite (Co–Fe–B)m(LiNbO3)100−m, has been successfully constructed.
Vertical Cross‐Alignments of 2D Semiconductors with Steered Internal Electric Field for Urea Electrooxidation via Balancing Intermediates Adsorption
Authors: Du Hanxiao , Hu Huashuai , Wang Xunlu , Ran Nian , Chen Wei , Zhu Hongbo , Zhou Yin , Yang Minghui , Wang Jiacheng , Liu Jianjun
Published: April 2024

Single‐component electrocatalysts generally lead to unbalanced adsorption of OH− and urea during urea oxidation reaction (UOR), thus obtaining low activity and selectivity especially when oxygen evolution reaction (OER) competes at high potentials (>1.5 V). Herein, a cross‐alignment strategy of in situ vertically growing Ni(OH)2 nanosheets on 2D semiconductor g‐C3N4 is reported to form a hetero‐structured electrocatalyst. Various spectroscopy measurements including in situ experiments indicate the existence of enhanced internal electric field at the interfaces of vertical Ni(OH)2 and g‐C3N4 nanosheets, favorable for balancing adsorption of reaction intermediates. This heterojunction electrocatalyst shows high‐selectivity UOR compared to pure Ni(OH)2, even at high potentials (>1.5 V) and large current density. The computational results show the vertical heterojunction could steer the internal electric field to increase the adsorption of urea, thus efficiently avoiding poisoning of strongly adsorbed OH− on active sites. A membrane electrode assembly (MEA)‐based electrolyzer with the heterojunction anode could operate at an industrial‐level current density of 200 mA cm−2. This work paves an avenue for designing high‐performance electrocatalysts by vertical cross‐alignments of active components.
Post‐quantum attack resilience blockchain‐assisted data authentication protocol for smart healthcare system
Authors: Soni Lacchita , Chandra Harish , Gupta Daya Sagar
Published: April 2024

The smart healthcare system (SHS), a significant medical domain underpinning the Internet of Things (IoT), which collects and analyzes health data from many sources to provide better medical treatment. The smart healthcare system is a combination of hardware and software used in the medical care field, providing remote diagnosis and treatment via a patient‐based health data‐sharing system. To increase security, a large variety of authenticated techniques have been developed over the past several decades, most of which are based on conventional number‐theoretic assumptions such as discrete logarithms and integer factorization problems. However, Shor's method is capable of solving number‐theory‐based problems. As a result, Shor's technique might be used to resolve challenging number theory problems on a quantum computer effectively. Therefore, this article presents blockchain‐based healthcare record solutions with lattice RLWE‐based key exchange protocol using a smart card. Blockchain applications may correctly detect errors, including those that are risky, in the medical industry. It can also improve the efficiency, security, and transparency of transferring medical data throughout the healthcare protocol. The formal security of this protocol is shown under the ROM (random oracle model), and the informal security is also given in this article against well‐known attacks. The presented protocol outperforms related earlier mechanisms in terms of communication and computational cost overheads, according to the performance study.
Insight of Jeffrey flow over a stretching Riga plate with activation energy and viscous dissipation: Melting heat transfer regime
Authors: Javed Mubashar
Published: April 2024

Present article highlights the significance of Arrhenius activation energy along with viscous dissipation in Jeffrey fluid over a Riga plate. Riga plate is basically an actuator made up of array of magnets and electrodes scaled on a plane surface to tackle the weaker electrical conductivity during fluid flow. In order to ensure the novelty, a reliable melting heat surface condition has been incorporated on nonlinear stretching Riga plate of variable thickness to reconnoiter features of heat transfer. Moreover, stagnation point has been retained in this study. Adequate transformations are employed in order to attain system of nonlinear ordinary differential equations. A well known semi analytical technique (Homotopy analysis method) is utilized to obtain series solutions of prevailing dimensionless equations. Influence of several apposite parameters on velocity, thermal and concentration distributions is analyzed graphically. Physical evaluation and graphical sketch is presented for drag force coefficient and rate of heat transfer. Analysis of velocity as well as associated boundary layer thickness gives the growing up impact for the strength of modified Hartmann number. Enhancement of dimensionless reaction rate and endothermic/exothermic reaction parameter results in increment for heat flux over stretching Riga plate. Increase in thermal distribution takes place for higher Eckert number while thermal boundary layer thickness depicts opposite trend in this case. Concentration boundary layer thickness enhances while concentration profile declines for higher Schmidt number. Velocity distribution is found to be incremented for intense melting process. Higher dimensionless activation energy parameter is analyzed to be responsible for growing up concentration field.
Donor Selection for Adults and Pediatrics
Authors: Ayuk Francis , Balduzzi Adriana , Worel Nina
Published: April 2024

It is known that multiple factors impact transplantation outcome; the heaviest ones are disease-related (disease refractoriness, phase, clonal abnormalities, etc. in malignancies and disease type and associated rejection risk in nonmalignant diseases) and patient-related (age, comorbidities, infectious diseases/colonization, etc.). Moreover, donor-related issues and stem cell source may influence the extent of disease control and transplant-related mortality.
Conditioning
Authors: Shimoni Avichai , Radici Vera , Nagler Arnon
Published: April 2024

Hematopoietic cell transplantation (HCT) is a potentially curative therapeutic procedure in a broad range of malignant and nonmalignant hematological disorders. Conditioning is the preparative regimen that is administered to patients undergoing HCT before the infusion of stem cell (SC) grafts. The selection of an optimal conditioning regimen is critical for transplantation success.
Mobilization and Collection of HSCs in Children
Authors: Witt Volker , Pichler Herbert , Ahrens Norbert
Published: April 2024

Pediatric hematopoietic stem cell (HSC) products are crucial components of hematopoietic cell transplantation (HCT) in children. This chapter provides an overview of the techniques and considerations involved in pediatric bone marrow (BM) collection and in stem cell apheresis. It covers patient selection, pre-procedure preparation, apheresis procedures, and post-procedure care. Additionally, specific considerations related to pediatric patients, such as ethical considerations, vascular access, and volume management, are discussed. This chapter will focus on the technical, physiological, and ethical problems in the field of HSC collection from children to ensure safe and efficient procedures.
Procurement and Management of Cord Blood Unit for Allogeneic Transplantation
Authors: Querol Sergio , Rocha Vanderson , Ruggeri Annalisa
Published: April 2024

Umbilical cord blood (UCB) cells for allogeneic use are collected and stored in more than 160 public CB banks worldwide. More than 800,000 CB units (CBUs) are available for allogeneic transplantation through the WMDA’s Search & Match Service global database. In this chapter, we will describe the key procedures for cord blood collection, processing, banking, and recommendations on how to choose a single or double UCB unit for transplantation.
Clinically Relevant Drug Interactions in HCT
Authors: Bauters Tiene , Dadkhah Adrin
Published: April 2024

Patients undergoing HCT receive polymedication which carries the potential to result in drug interactions. To avoid unexpected outcomes, attention to drug interactions is crucial, especially when drugs with a narrow therapeutic index or inherent toxicity profile are involved.
Ocular and Oral Complications
Authors: Steven Philipp , Mays Jacqueline W. , Hashmi Shahrukh K.
Published: April 2024

The craniofacial complex includes the eyes and mouth, and each site has its own set of GVHD- and non-GVHD-related late effects which, if left untreated, can lead to permanent disability.
Skin, Hair, and Musculoskeletal Complications
Authors: Ayuk Francis , Savani Bipin N.
Published: April 2024

Nearly every recipient of an allo-HCT will at some stage develop complications involving the skin and hair. These complications can be grouped into drug-related toxicities and allergies, graft-versus-host disease, infections, and malignant conditions.
Cellular Therapy with Engineered T Cells, Efficacy, and Side Effects: Gene Editing/Gene Therapy
Authors: Bonini Chiara , Cavazzana Marina , Ciceri Fabio , Fehse Boris , Hudecek Michael
Published: April 2024

The cellular basis of cancer immune surveillance, already hypothesized in ancient times, was only proven with the advent of HCT. Indeed, the discovery of the nature of GVHD and its antileukemic effects (Weiden et al. 1979) was followed by the first successful attempts of adoptive immunotherapy using donor leukocytes (Kolb et al. 1990). To address the significant GVHD risk associated with allogeneic T cells, several approaches of T-cell manipulation were developed and tested (Table 60.1). Some of these strategies rely on the genetic manipulation of T cells. First, suicide gene therapy approaches were established to promote GVL and immune reconstitution while controlling GVHD. More recently, strategies based on the genetic transfer of tumor-specific T-cell receptors (TCRs) or chimeric antigen receptors (CARs) were developed to improve antitumor efficiency of T cells. This chapter provides an overview of this vastly evolving area.
Regulatory Aspects of ATMP Versus Minimally Manipulated Immune Cells
Authors: Chabannon Christian , Dolstra Harry
Published: April 2024

In 2023, three categories of therapeutic products obtained through the collection and subsequent engineering of hematopoietic cells exist and are valuable to patients treated for neoplastic diseases as well as a variety of nonneoplastic disorders: blood cell transfusions, stem and immune cell transplants, and cellular therapy medicinal products. The procurement and nature of various blood products and transfusion practices are described elsewhere in this handbook. In this chapter, we focus on hematopoietic cellular therapies as currently defined and managed in the FACT-JACIE International Standards for Hematopoietic Cellular Therapies (nowadays in version 8). Over the last two decades, major changes have occurred in the EU regulatory framework (as well as in other parts of the world, notably in the USA) that result in the coexistence of two categories of hematopoietic cellular therapies. Innovative and industry-manufactured somatic cell therapy or gene therapy medicinal products have entered the field at an accelerating pace since the last edition of this handbook. Some of them are distributed worldwide on a large scale, and a few of these medicinal products already complete or compete with traditional hematopoietic cell transplantation practices. We here update the description of organizational consequences of this historical transition for academic facilities and the new opportunities as well as challenges these advances are bringing to patients and healthcare practitioners, including strong needs for educational initiatives.
Overweight and Obese Patients
Authors: Langebrake Claudia
Published: April 2024

Overweight and obesity are associated with physiological changes that can influence the pharmacokinetics of drugs. This has consequences for the dosage of drugs. Currently, for example, there are international recommendations for antibiotics and chemotherapies (with the exception of high-dose regimens) for dosing in overweight and obese patients. Unfortunately, data for conditioning regimens prior to hematopoietic stem cell tranplantation in terms of pharmacokinetic and/or clinical data is still quite limited. Therefore, future studies should focus on the pharmacokinetics and pharmacodynamics of specific conditioning regimens while more consistent and biologically relevant definitions of obesity should be utilized.
Feasibility and Experiences of HCT in Resource-Constrained Settings
Authors: Srivastava Alok , Duarte Fernando Barroso , Faulkner Lawrence
Published: April 2024

Even though hematopoietic cell transplant (HCT) has been in vogue for more than six decades as a curative therapy for many hematological disorders, with increasing trends in all parts of the world (Fig. 69.1), the density of HCT services is low and access to existing services remain an unmet need in the resource-constrained settings (RCSs) of low- and middle-income countries (LMICs) (Niederwieser et al. 2022). The silver lining though is that within these limitations, there are several examples of high-quality HCT services functioning in several countries, some with full national/international accreditation showing that even in those circumstances this is possible (Damodar et al. 2021). The goal of this chapter will be to discuss how good HCT services may be established and sustained in RCSs (Pasquini et al. 2019; Faulkner et al. 2021).
Acute Lymphoblastic Leukaemia in Children and Adolescents
Authors: Peters Christina , Locatelli Franco , Bader Peter
Published: April 2024

Acute lymphoblastic leukaemia (ALL) is the most common cancer in children; approximately 60% of ALL cases occur in children and adolescents under the age of 20. Allogeneic haematopoietic cell transplantation (HCT) has become the most commonly used cellular immunotherapy and the standard of care for children with ALL who are either at high risk of relapse or have previously relapsed. HCT is a successful therapeutic option and a significant proportion of patients achieve long-term survival. The most common cause of treatment failure is relapse after allogeneic HCT. The risk of relapse after transplantation is influenced by several factors, including remission status at transplantation, conditioning regimen and donor type. Strategies to reduce the risk of relapse include reduction of pretransplant minimal residual disease (MRD), replacement of toxic pretransplant chemotherapy with bispecific antibodies, replacement of HCT with chimeric antigen receptor (CAR) T-cell therapy, improved transplantation strategies for specific groups, including infants, adolescents and young adults (AYA), and innovative prophylaxis and treatments for acute and chronic graft-versus-host disease. In addition, therapeutic drug monitoring with dose adjustment of some drugs, including busulfan, and novel radiation techniques may allow a more personalised approach.
Allogeneic Hematopoietic Cell Transplantation in Pediatric MDS Including Refractory Cytopenia of Childhood and in Juvenile Myelomonocytic Leukemia
Authors: Niemeyer Charlotte M. , Strahm Brigitte
Published: April 2024

Pediatric MDS can be associated with germline predisposition, related to cytotoxic or immunmodulatory therapy, or occurs as de novo disease. SCT strategy is primarily dependent on blast count, karyotype, molecular abberrations, and BM cellularity. Juvenile myelomonocytic leukemia is a very heterogenous disease, not all children require SCT. Risk factors for relapse following SCT include age, HbF level, presence of secondary mutations and DNA methylation class.
Poems Syndrome and Disease Produced by Other Monoclonal IGs
Authors: Cook Gordon , Rovira Montserrat
Published: April 2024

POEMS syndrome (acronym of: polyradiculoneuropathy, organomegaly, endocrinopathies, monoclonal protein and dermopathy/§skin) is a rare multisystemic disease due to an underlying plasma cell neoplasm. The pathogenesis of the syndrome is not well understood. Other names of the POEMS syndrome that are less frequently used are osteosclerotic myeloma, Takatsuki syndrome, or Crow-Fukase syndrome.
Histocompatibility
Authors: Spierings Eric , Madrigal Alejandro , Fleischhauer Katharina
Published: April 2024

Human leukocyte antigen (HLA) molecules are the most important histocompatibility antigens, due to their genetic polymorphism and their key role in peptide antigen presentation and T-cell alloreactivity. While full matching for the most relevant HLA loci had been regarded as a prerequisite for successful transplantation until recently, the introduction of posttransplant cyclophosphamide (PTCy) as immune prophylaxis has also allowed successful transplantation across multiple HLA mismatches, thus also enabling access to transplantation for patients without a fully compatible donor. The rules governing high-risk/nonpermissive HLA mismatches, identified in the past as immunopeptidome overlaps, expression levels, and predicted indirectly recognized HLA epitopes (PIRCHEs), will have to be redefined in the PTCy area to further improve patient outcomes.
Institutional Norms and the Cost of Doing Politics
Authors: Sawer Marian , Maley Maria
Published: April 2024

Women entering non-traditional workplaces commonly experience hostility in the form of sexual harassment. The parliamentary workplace has additional features that make reform difficult, despite feminist standard-setting in transnational bodies. Difficulties include applying employment law to MPs who are not employees in any real sense themselves but have almost complete power over their staff. Adversarial traditions normalise aggressive conduct rather than a respectful workplace and also make it likely that any complaint will be weaponised politically. Many are silenced by fear that to complain will damage their party as well as their own career. Another obstacle to reform has been the tradition of parliamentary privilege, the right of parliaments to regulate their own affairs free from external interference. This has held back the introduction of professional employment standards, on the grounds that the best form of accountability for parliamentarians is at the ballot box.
Citizens’ data afterlives: Practices of dataset inclusion in machine learning for public welfare
Authors: Ratner Helene Friis , Thylstrup Nanna Bonde
Published: April 2024

Public sector adoption of AI techniques in welfare systems recasts historic national data as resource for machine learning. In this paper, we examine how the use of register data for development of predictive models produces new ‘afterlives’ for citizen data. First, we document a Danish research project’s practical efforts to develop an algorithmic decision-support model for social workers to classify children’s risk of maltreatment. Second, we outline the tensions emerging from project members’ negotiations about which datasets to include. Third, we identify three types of afterlives for citizen data in machine learning projects: (1) data afterlives for training and testing the algorithm, acting as ‘ground truth’ for inferring futures, (2) data afterlives for validating the algorithmic model, acting as markers of robustness, and (3) data afterlives for improving the model’s fairness, valuated for reasons of data ethics. We conclude by discussing how, on one hand, these afterlives engender new ethical relations between state and citizens; and how they, on the other hand, also articulate an alternative view on the value of datasets, posing interesting contrasts between machine learning projects developed within the context of the Danish welfare state and mainstream corporate AI discourses of the bigger, the better.
Identification of β-aspartic semialdehyde and homocysteine as major reaction products of riboflavin-sensitized photooxidation of peptide-bound methionine
Authors: Krax Raphaela , Menneking Kira , Sajapin Johann , Hellwig Michael
Published: April 2024

Methionine is an essential amino acid for mammals and it is limiting for monogastric animals. It can be oxidized easily by UV light. This could influence the bioaccessibility and bioavailability of methionine. In this work, the photosensitized degradation of peptide-bound methionine in the presence of riboflavin was investigated in a model system. Capillary electrophoresis was employed to analyze the time course of the degradation. The products were identified by liquid chromatography coupled to mass spectrometry (LC–MS/MS). Benzoyl methionine was degraded by 50% during UV irradiation in the presence of riboflavin after 5.0 min with 10 mol% riboflavin and 6.4 min with 3 mol% riboflavin. Homocysteine (16–20 mol%) and β-aspartic semialdehyde (ca. 30 mol%) were found as major degradation products next to methionine sulfoxide (ca. 25 mol%). A smaller molar ratio of riboflavin led to a higher formation of aspartic semialdehyde. The formation of homocysteine was paralleled by the formation of formaldehyde. Furthermore, the experiment was transferred to small peptides, which showed the analogous degradation products of peptide-bound methionine.
Persistence of heterodimensional cycles
Authors: Li Dongchen , Turaev Dmitry
Published: April 2024

A heterodimensional cycle is an invariant set of a dynamical system consisting of two hyperbolic periodic orbits with different dimensions of their unstable manifolds and a pair of orbits that connect them. For systems which are at least $C^{2}$

C
2

, we show that bifurcations of a coindex-1 heterodimensional cycle within a generic 2-parameter family create robust heterodimensional dynamics, i.e., a pair of non-trivial hyperbolic basic sets with different numbers of positive Lyapunov exponents, such that the unstable manifold of each of the sets intersects the stable manifold of the second set and these intersections persist for an open set of parameter values. We also give a solution to the so-called local stabilization problem of coindex-1 heterodimensional cycles in any regularity class $r=2,\ldots ,\infty ,\omega $
r
=
2
,
…
,
∞
,
ω
. The results are based on the observation that arithmetic properties of moduli of topological conjugacy of systems with heterodimensional cycles determine the emergence of Bonatti-Díaz blenders.
To house or oust: Honey bee (Apis mellifera) colonies can evaluate and evict drones of low quality
Authors: Gilchrist Izaak R. , Nixon Jonathan M. , Shultz Riley R. , Ginzel Matthew D. , Harpur Brock A.
Published: April 2024

Across the animal kingdom, males advertise their quality to potential mates. Males of low reproductive quality, such as those that are sick, may be excluded from mating. In eusocial species, there is some evidence that reproductive females gauge the quality of their mates. However, males often spend much more time with non-reproductive females when being raised or when returning from unsuccessful mating flights. Do non-reproductive workers evaluate the quality of male reproductives? Here we address this question using male honey bees (Apis mellifera), called drones, as a model. We generated immune-challenged drones by injecting them with lipopolysaccharide and tested: 1) do workers evict immune-challenged drones from their colony, 2) do cuticular hydrocarbon (CHC) profiles, body size, or mass change when drones are immune-challenged, and 3) are these changes used by workers to exclude low quality males from the colony? We found that an immune challenge causes changes in CHC profiles of drones and reduces their body mass. Workers selectively evict small and immune-challenged drones who, themselves, do not self-evict. This work demonstrates that some eusocial males undergo an additional layer of scrutiny prior to mating mediated by the non-reproductive worker caste.

Significance statement

Males of some species must advertise their quality to mates but, in the case of eusocial species, must they also advertise their quality to nestmates? By manipulating honey bee male quality, we found that small and immune-challenged drones are evicted from colonies overnight. Workers may not use a drone’s cuticular hydrocarbon profile to make this assessment. This is a new example of social immunity expressed against adult males and an example of worker involvement in reproductive decisions.
Image-based biomarkers for engineering neuroblastoma patient-specific computational models
Authors: Hervas-Raluy Silvia , Sainz-DeMena Diego , Gomez-Benito Maria Jose , García-Aznar Jose Manuel
Published: April 2024

Childhood cancer is a devastating disease that requires continued research and improved treatment options to increase survival rates and quality of life for those affected. The response to cancer treatment can vary significantly among patients, highlighting the need for a deeper understanding of the underlying mechanisms involved in tumour growth and recovery to improve diagnostic and treatment strategies. Patient-specific models have emerged as a promising alternative to tackle the challenges in tumour mechanics through individualised simulation. In this study, we present a methodology to develop subject-specific tumour models, which incorporate the initial distribution of cell density, tumour vasculature, and tumour geometry obtained from clinical MRI imaging data. Tumour mechanics is simulated through the Finite Element method, coupling the dynamics of tumour growth and remodelling and the mechano-transport of oxygen and chemotherapy. These models enable a new application of tumour mechanics, namely predicting changes in tumour size and shape resulting from chemotherapeutic interventions for individual patients. Although the specific context of application in this work is neuroblastoma, the proposed methodologies can be extended to other solid tumours. Given the difficulty for treating paediatric solid tumours like neuroblastoma, this work includes two patients with different prognosis, who received chemotherapy treatment. The results obtained from the simulation are compared with the actual tumour size and shape from patients. Overall, the simulations provided clinically useful information to evaluate the effectiveness of the chemotherapy treatment in each case. These results suggest that the biomechanical model could be a valuable tool for personalised medicine in solid tumours.
Handling of long-term storage in multi-horizon stochastic programs
Authors: Kaut Michal
Published: April 2024

This paper introduces a method for incorporating long-term storage into the multi-horizon modelling paradigm, thereby expanding the scope of problems that this approach can address. The implementation presented here is based on the HyOpt optimization model, but the underlying concepts are designed to be adaptable to other models that utilize the multi-horizon approach. We demonstrate the effects of several formulations on a case study that explores the electrification of an offshore installation using wind turbines and a hydrogen-based energy storage system. The findings suggest that the formulations offer a realistic modelling of storage capacity, without compromising the advantages of the multi-horizon approach.
Teaching through their eyes: effects on optometry teachers’ adaptivity and students’ learning when teachers see students’ gaze
Authors: Korteland Robert-Jan , Kok Ellen , Hulshof Casper , van Gog Tamara
Published: April 2024

Adaptive teacher support fosters effective learning in one-to-one teaching sessions, which are a common way of learning complex visual tasks in the health sciences. Adaptive support is tailored to student needs, and this is difficult in complex visual tasks as visual problem-solving processes are covert and thus cannot be directly observed by the teacher. Eye-tracking apparatus can measure covert processes and make them visible in gaze displays: visualizations of where a student looks while executing a task. We investigate whether live dynamic gaze displays help teachers in being more adaptive to students’ needs when teaching optical coherence tomography interpretation in one-to-one teaching sessions and whether this fosters learning. Forty-nine students and 10 teachers participated in a one-to-one teaching session in clinical optometry. In the control condition, teachers saw the learning task of the student and could discuss it with them, whereas in the gaze-display condition, teachers could additionally see where the student looked. After the 15-minute teaching session, a test was administered to examine achievement. Furthermore, students filled in the ‘questionnaire on teacher support adaptivity’, and teachers rated how adaptive their support was. Bayesian analyses provide some initial evidence that students did not experience support to be more adaptive in the gaze-display condition versus the control condition, nor were their post-test scores higher. Teachers rated their provided support as being more adaptive in the gaze-display versus the control condition. Further research could investigate if live dynamic gaze displays impact adaptive teaching when used over longer periods or with more teacher training.
Adapted Beamforming: A Robust and Flexible Approach for Removing Various Types of Artifacts from TMS–EEG Data
Authors: Metsomaa Johanna , Song Yufei , Mutanen Tuomas P. , Gordon Pedro C. , Ziemann Ulf , Zrenner Christoph , Hernandez-Pavon Julio C.
Published: April 2024

Electroencephalogram (EEG) recorded as response to transcranial magnetic stimulation (TMS) can be highly informative of cortical reactivity and connectivity. Reliable EEG interpretation requires artifact removal as the TMS-evoked EEG can contain high-amplitude artifacts. Several methods have been proposed to uncover clean neuronal EEG responses. In practice, determining which method to select for different types of artifacts is often difficult. Here, we used a unified data cleaning framework based on beamforming to improve the algorithm selection and adaptation to the recorded signals. Beamforming properties are well understood, so they can be used to yield customized methods for EEG cleaning based on prior knowledge of the artifacts and the data. The beamforming implementations also cover, but are not limited to, the popular TMS–EEG cleaning methods: independent component analysis (ICA), signal-space projection (SSP), signal-space-projection-source-informed-reconstruction method (SSP–SIR), the source-estimate-utilizing noise-discarding algorithm (SOUND), data-driven Wiener filter (DDWiener), and the multiple-source approach. In addition to these established methods, beamforming provides a flexible way to derive novel artifact suppression algorithms by considering the properties of the recorded data. With simulated and measured TMS–EEG data, we show how to adapt the beamforming-based cleaning to different data and artifact types, namely TMS-evoked muscle artifacts, ocular artifacts, TMS-related peripheral responses, and channel noise. Importantly, beamforming implementations are fast to execute: We demonstrate how the SOUND algorithm becomes orders of magnitudes faster via beamforming. Overall, the beamforming-based spatial filtering framework can greatly enhance the selection, adaptability, and speed of EEG artifact removal.