bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperspectral quantitative phase microscopy for decoupling refractive index and thickness of thin transparent samples
Authors: Joshi Himanshu , Surya Varun , Mishra Deepika , Mehta Dalip Singh
Published: September 2024

Quantitative phase microscopy (QPM) is a label-free imaging technique that has revolutionized transparent sample analysis. It offers precise insights into the sub-wavelength morphological composition of the sample by generating quantitative maps of optical path length delay. However, its potential for explicit study of the microscopic composition of the samples is limited by coupled information of refractive index (RI) and thickness. In this work, we present a technique that effectively decouples RI and thickness from the phase map, using high spectral resolution hyperspectral QPM in conjunction with the higher-order Cauchy dispersion equation. The effectiveness of the proposed approach is established through validation on a simulated phase object, where the recovered RI and thickness values agree well with the pre-assigned values. Further, the versatility of this technique is demonstrated through successful application to thin transparent industrial objects and biological samples, positioning it as a promising tool for decoupling RI and thickness with minimal assumptions for various transparent specimens.
Design, analysis and experimental characterization of MEMS based one hot-arm electrothermal actuator
Authors: Javaid Faraz , Bashir Uzair , Saleem Muhammad Mubasher , Arshad Adeel , Tiwana Mohsin Islam , Ali Osama
Published: September 2024

The focus of this study is to analyse the temperature, stress, and mechanical displacement distribution of a U-shaped one hot-arm Microelectromechanical System (MEMS) based electrothermal actuator using CoventorWare software. The actuator was fabricated using the commercially available SOIMUMPs process from Science. The Finite Element Method (FEM) simulation results were verified through the experimental characterization of fabricated structure at different actuation voltages and are found to be in good agreement. Furthermore, peak value of actuation voltage is measured before the failure of the electrothermal structure occurs.
Multiplayer game dynamics and their applications into simplicial complexes with memory effect
Authors: Cui Heng , Zhu Yuying , Xia Chengyi
Published: September 2024

We investigate the evolutionary dynamics of the multiplayer, snowdrift-like game based on memory effects, in which cooperators and defectors interact with another type of player named as exiter. To avoid being exploited by defectors, the conservative exiters tend to drop out of a game and merely share quite minor returns. Results on the well-mixed populations indicate that the existence of exiters is less conducive to cooperation. Whereas, in networks with simplicial complexes, the memory effect can effectively inhibit evolution of defection and promote cooperation. Other outcomes with respect to the evolution of exiters and defectors, including the co-existence of all three types of players in the network and the favor of exiter, can be obtained by tuning the payoff to exit and the proportion of 1-simplices and 2-simplices. The current results provide insight into how mutual cooperation emerges in real networked populations, influenced by the memory-based exit options.
Energy system models should consider evolving charging profiles
Authors: Belman Martínez Aaron , MacLean Heather L , Posen I Daniel
Published: September 2024

Abstract

Globally, sales of battery electric vehicles (BEVs) are surpassing records every year, and their growing charging needs will ultimately reshape power infrastructure planning practices. While studies have analyzed the impact of light-duty BEVs on the electricity sector, they have overlooked the prospective evolution in charging profiles. We developed a framework for analyzing passenger vehicle electrification futures accounting for the evolution in charging infrastructure, BEVs technical features, and socio-demographics. We soft-link a BEV charging profiles generator with an energy system optimization model to analyze a light-duty vehicle electrification scenario in the U.S. from 2020–2050. Compared to static charging profiles, common in prior work, evolving profiles lead to substantial differences in projected power plant installed capacity (up to ∼300 GW more solar PV) and activity (up to ∼460 TWh more solar PV generation). Hence, future studies should consider not only different charging profiles (e.g. day, night, uncontrolled) but also how these evolve over time.
Childhood anaesthesia and autism risk: population and murine study
Authors: Sun Mingyang , Fu Ningning , Li Ting , Miao Mengrong , Chen Wan-Ming , Wu Szu-Yuan , Zhang Jiaqiang
Published: September 2024

Early childhood exposure to general anaesthesia has been linked to potential changes in infant brain morphology and behaviour in preclinical studies, contributing to long-term behaviours associated with autism spectrum disorder. This study investigates the association between early childhood exposure to general anaesthesia and the risk of autism, using a population-based cohort study with matching for baseline characteristics and evaluates the effect of sevoflurane exposure on autism-like behaviour in mice, using the Taiwan Maternal and Child Health Database. Children aged 0–3 who received at least one exposure to general anaesthesia between 2004 and 2014 were matched 1:1 with children who were not exposed. Risk ratios and confidence intervals were used to assess the relationship between general anaesthesia and the occurrence of autism. Additionally, mice were exposed to sevoflurane for 2 h on postnatal days 5–7, and changes in behaviour related to autism were evaluated. Propensity score matching resulted in 7530 children in each group. The incidence rates (IRs) of autism were 11.26 and 6.05 per 100 000 person-years in the exposed and unexposed groups, respectively. The incidence ratio for autism following exposure to general anaesthesia was 1.86 (95% confidence interval, 1.34–2.59). In mice, sevoflurane exposure induced autism-like behaviours and led to the downregulation of high-risk autism genes, including ARID1B, GABRA5, GABRB3, GRIN2B, SHANK3 and SUV420H1. Early childhood exposure to general anaesthesia is associated with an increased risk of autism. Repeated exposure to sevoflurane in mice induces autism-like behaviours, suggesting a potential link between anaesthesia and the development of autism.
Optimization of bio-oil production parameters from the pyrolysis of elephant grass (Pennisetum purpureum) using response surface methodology
Authors: Ikpeseni Sunday C , Sada Samuel O , Efetobor Ufuoma J , Orugba Henry O , Ekpu Mathias , Owamah Hilary I , Chukwuneke Jeremiah L , Oyebisi Solomon , Onochie Uche P
Published: September 2024

The need to increase bio-oil yield from biomass and enhance its fuel properties has driven research into optimizing the pyrolysis process. This study investigated the influence of three key process parameters—temperature, heating rate, and nitrogen flow rate—on the pyrolysis of elephant grass (Pennisetum purpureum) in a fixed-bed reactor. Response surface methodology was used to study the impact of the aforementioned variables on bio-oil yield to improve its production efficiency. Proximate analysis of the biomass revealed 79.24 wt% volatile matter, 14.22 wt% fixed carbon, and 5.86% ash, with ultimate analysis showing 45.44% carbon, 5.59% hydrogen, and 40.95% oxygen. The high volatile matter content and favourable carbon and hydrogen percentages indicate that elephant grass is a viable energy source due to its potential for high bio-oil yield and energy content. The resulting bio-oil exhibited a higher heating value of 20.9 MJ/kg, indicating its suitability for various heating applications. A second-order regression model was developed for bio-oil yield, with optimal conditions identified as a temperature of 550°C, a heating rate of 17°C/min, and a nitrogen flow rate of 6 ml/min. The study achieved an optimal bio-oil yield of 59.03 wt%, and the model’s high R² value of 0.8683 from analysis of variance analysis confirmed its predictive accuracy. This research highlights elephant grass as a sustainable feedstock for bio-oil production, offering valuable insights into optimizing pyrolysis conditions to enhance bio-oil yield, thus advancing biofuel technology.
Multigraph reconstruction via nonlinear random walk
Authors: de Kemmeter Jean-François , Carletti Timoteo
Published: September 2024

Over the last few years, network science has proved to be useful in modelling a variety of complex systems, composed of a large number of interconnected units. The intricate pattern of interactions often allows the system to achieve complex tasks, such as synchronization or collective motions. In this regard, the interplay between network structure and dynamics has long been recognized as a cornerstone of network science. Among dynamical processes, random walks are undoubtedly among the most studied stochastic processes. While traditionally, the random walkers are assumed to be independent, this assumption breaks down if nodes are endowed with a finite carrying capacity, a feature shared by many real-life systems. Recently, a class of nonlinear diffusion processes accounting for the finite carrying capacities of the nodes was introduced. The stationary nodes densities were shown to be nonlinearly correlated with the nodes degrees, allowing to uncover the network structure by performing a few measurements of the stationary density at the level of a single arbitrary node and by solving an inverse problem. In this work, we extend this class of nonlinear diffusion processes to the case of multigraphs, in which links between nodes carry distinct attributes. Assuming the knowledge of the pattern of interactions associated with one type of links, we show how the degree distribution of the whole multigraph can be reconstructed. The effectiveness of the reconstruction algorithm is demonstrated through simulations on various multigraph topologies.
Flecainide toxicity with pill-in-pocket approach from accidental overdose: a case report
Authors: Oudih Mohamad Anas , Ginsburg Avraham , Hakim Mumin , Zou Fengwei , Guttenplan Nils
Published: September 2024

Background

The Pill-in-the-Pocket (PiP) approach may be used in highly selected patients to achieve acute pharmacological cardioversion into sinus rhythm. Flecainide toxicity is rarely reported, especially with patients who take flecainide as PiP, and only limited evidence exists in its management. We present a case of accidental flecainide overdose for a patient who is on PiP and the acute management strategy.

Case summary

A 78-year-old female with persistent atrial fibrillation (AF), previously underwent pulmonary vein isolation and maintained on verapamil 240 mg twice daily, presented to the electrophysiology clinic following a recent hospital admission for recurrent AF. Due to infrequent recurrent episodes of symptomatic AF, the patient preferred to avoid both repeat ablation and additional daily medications. After an initial trial on telemetric monitoring, a PiP approach with flecainide 300 mg was adopted. Unfortunately, palpitations and dyspnoea in the context of chronic obstructive pulmonary disease exacerbation led the patient to self-medicate with multiple doses of albuterol and flecainide. Twelve-lead electrocardiogram showed slow AF with a wide QRS complex. The patient received 1 g of calcium gluconate with a 180 mEq bolus of sodium bicarbonate 8.4% and was started on continuous sodium bicarbonate infusion at 150 mL/h. Over a 12 h period, the QRS complex narrowed down, and the rhythm returned to normal sinus rhythm with a QRS interval of 136 ms.

Discussion

The PiP strategy with flecainide is safe and effective. Reinforcement of medication dosing and frequency with patient read back is key to avoid accidental toxicity, which could be life-threatening. Treatment with sodium bicarbonate is quick and highly effective.
Transcatheter aortic valve replacement-in-transcatheter aortic valve replacement for high-risk anatomies: demonstrating the feasibility of index leaflet overhang in a first-in-human case report
Authors: De Ferrari Tommaso , Ancona Marco B , Romano Vittorio , Ferri Luca , Russo Filippo , Agricola Eustachio , Esposito Antonio , Montorfano Matteo
Published: September 2024

Background

Transcatheter aortic valve replacement (TAVR)-in-TAVR within index supra-annular transcatheter heart valves (THVs) and high-risk anatomy can compromise coronary perfusion and re-access.

Case summary

An 80-year-old male presented with acute heart failure caused by degeneration of an Evolut R THV, leading to severe aortic regurgitation. Aortic computed tomography imaging revealed a high-risk anatomy characterized by the index THV’s commissural plane being placed above the coronary ostia and a valve-to-aorta distance of less than 2 mm, resulting not eligible for redo-TAVR according to recent literature. The current case represents the first-in-human application of redo-TAVR with low SAPIEN 3 THV implantation within an Evolut R THV obtaining index leaflet overhang, preserving coronary perfusion and potential coronary re-engagement.

Discussion

Following in vitro study, this case demonstrates in vivo feasibility of redo-TAVR with low SAPIEN 3 THV implantation within an Evolut R THV obtaining index leaflet overhang.
Implementation of an EHR-integrated web-based depression assessment in primary care: PORTAL-Depression
Authors: Franco Melissa I , Staab Erin M , Zhu Mengqi , Deehan William , Moses John , Gibbons Robert , Vinci Lisa , Shah Sachin , Yohanna Daniel , Beckman Nancy , Laiteerapong Neda
Published: September 2024

Objectives

To integrate a computerized adaptive test for depression into the electronic health record (EHR) and establish systems for administering assessments in-clinic and via a patient portal to improve depression care.

Materials and Methods

This article reports the adoption, implementation, and maintenance of a health information technology (IT) quality improvement (QI) project, Patient Outcomes Reporting for Timely Assessment of Life with Depression (PORTAL-Depression). The project was conducted in a hospital-based primary care clinic that serves a medically underserved metropolitan community. A 30-month (July 2017-March 2021) QI project was designed to create an EHR-embedded system to administer adaptive depression assessments in-clinic and via a patient portal. A multi-disciplinary team integrated 5 major health IT innovations into the EHR: (1) use of a computerized adaptive test for depression assessment, (2) 2-way secure communication between cloud-based software and the EHR, (3) improved accessibility of depression assessment results, (4) enhanced awareness and documentation of positive depression results, and (5) sending assessments via the portal. Throughout the 30-month observational period, we collected administrative, survey, and outcome data.

Results

Attending and resident physicians who participated in the project were trained in depression assessment workflows through presentations at clinic meetings, self-guided online materials, and individual support. Developing stakeholder relationships, using an evaluative and iterative process, and ongoing training were key implementation strategies.

Conclusions

The PORTAL-Depression project was a complex and labor-intensive intervention. Despite quick adoption by the clinic, only certain aspects of the intervention were sustained in the long term due to financial and personnel constraints.
Development and validation of a deep learning algorithm for the prediction of serum creatinine in critically ill patients
Authors: Ghanbari Ghodsieh , Lam Jonathan Y , Shashikumar Supreeth P , Awdishu Linda , Singh Karandeep , Malhotra Atul , Nemati Shamim , Yousif Zaid
Published: September 2024

Objectives

Serum creatinine (SCr) is the primary biomarker for assessing kidney function; however, it may lag behind true kidney function, especially in instances of acute kidney injury (AKI). The objective of the work is to develop Nephrocast, a deep-learning model to predict next-day SCr in adult patients treated in the intensive care unit (ICU).

Materials and Methods

Nephrocast was trained and validated, temporally and prospectively, using electronic health record data of adult patients admitted to the ICU in the University of California San Diego Health (UCSDH) between January 1, 2016 and June 22, 2024. The model features consisted of demographics, comorbidities, vital signs and laboratory measurements, and medications. Model performance was evaluated by mean absolute error (MAE) and root-mean-square error (RMSE) and compared against the prediction day’s SCr as a reference.

Results

A total of 28 191 encounters met the eligibility criteria, corresponding to 105 718 patient-days. The median (interquartile range [IQR]) MAE and RMSE in the internal test set were 0.09 (0.085-0.09) mg/dL and 0.15 (0.146-0.152) mg/dL, respectively. In the prospective validation, the MAE and RMSE were 0.09 mg/dL and 0.14 mg/dL, respectively. The model’s performance was superior to the reference SCr.

Discussion and Conclusion

Our model demonstrated good performance in predicting next-day SCr by leveraging clinical data routinely collected in the ICU. The model could aid clinicians in in identifying high-risk patients for AKI, predicting AKI trajectory, and informing the dosing of renally eliminated drugs.
Magnification calibration of X-ray 3D microscopy using micro-line structures
Authors: Azuma Yasushi , Kumagai Kazuhiro , Kunishima Naoki , Ito Koichiro
Published: September 2024

X-ray microscopy using computed tomography is an excellent 3D imaging instrument. Three-dimensional X-ray microscopy (3DXRM) is a nondestructive imaging technique used to inspect internal and external structures in units of submicrometers or less. The 3DXRM, although attractive, is mostly used as an observation instrument and is limited as a measurement system in quantitative evaluation and quality control. Calibration is required for use in measurement systems such as coordinate measurement systems, and specific standard samples and evaluation procedures are needed. The certified values of the standard samples must ideally be traceable to the International System of Units (SI). In the 3DXRM measurement system, line structures (LSs) are fabricated as prototype standard samples to conduct magnification calibration. In this study, we evaluated the LS intervals using calibrated cross-sectional scanning electron microscopy (SEM). A comparison of the evaluation results between SEM and 3DXRM for the LS intervals provided the magnification calibration factor for 3DXRM and validated the LSs, whereby the interval methods and feasibility of constructing an SI traceability system were evaluated using the calibrated SEM. Consequently, a magnification calibration factor of 1.01 was obtained for 3DXRM based on the intervals of the LSs evaluated by SEM. A possible route for realizing SI-traceable magnification calibration of 3DXRM has been presented.
Latent profiles and predictors of barriers to care in Swiss children and adolescents with rare diseases
Authors: Wehrli Susanne , Baumgartner Matthias R , Dwyer Andrew A , Landolt Markus A
Published: September 2024

Objective

Children and adolescents with rare diseases face significant barriers when accessing healthcare. We aimed to assess and predict these barriers and investigate associations with health-related quality of life (HRQoL).

Method

We conducted a cross-sectional survey of Swiss parents (N = 189) of children with rare diseases including the Barriers to Care Questionnaire (BCQ), containing six barriers and the Pediatric Quality of Life Inventory (PedsQL). Latent profile analysis (LPA) was used to uncover distinct classes, which were compared using chi-square tests and Mann–Whitney U tests. Relevant medical and sociodemographic class predictors were identified using Elastic Net regression, followed by regression analysis to investigate their role in predicting barriers to care and examine the effects of these classes on HRQoL.

Results

Two distinct groups were identified, a higher barriers class (59%) and a lower barriers class (41%). In the higher barriers class, participants showed elevated scores across all subscales and specifically on pragmatics and expectations. More barriers to care were linked to a nonstable disease course (OR = 2.27, p = .002) and a diagnosis after the age of 3 months (OR = 2.17, p = .006). Individuals in the higher barriers class exhibited more psychological comorbidities (p = .044), congenital malformations/deformations/chromosomal abnormalities (p=.042), and medical misdiagnoses (p = .006). Children in the higher barriers class had significantly lower PedsQL scores compared to the lower barriers class (p <.05).

Conclusion

This study highlights the need for comprehensive assessment of barriers to pediatric care in rare diseases, offering potential entry points for targeted interventions.
Estimating racial disparities in emergency general surgery
Authors: Ben-Michael Eli , Feller Avi , Kelz Rachel , Keele Luke
Published: September 2024

Research documents that Black patients experience worse general surgery outcomes than White patients in the U.S. In this paper, we focus on an important but less-examined category: the surgical treatment of emergency general surgery (EGS) conditions, which refers to medical emergencies where the injury is internal, such as a burst appendix. Our goal is to assess racial disparities in outcomes after EGS treatment using administrative data. We also seek to understand the extent to which differences are attributable to patient-level risk factors vs. hospital-level factors, as well as to the decision to operate on EGS patients. To do so, we develop a class of linear weighting estimators that reweight White patients to have a similar distribution of baseline characteristics to Black patients. This framework nests many common approaches, including matching and linear regression, but offers important advantages over these methods in terms of controlling imbalance between groups, minimizing extrapolation, and reducing computation time. Applying this approach to the claims data, we find that disparities estimates that adjust for the admitting hospital are substantially smaller than estimates that adjust for patient baseline characteristics only, suggesting that hospital-specific factors are important drivers of racial disparities in EGS outcomes.
The transition state for coupled folding and binding of a disordered DNA binding domain resembles the unbound state
Authors: Kuravsky Mikhail , Kelly Conor , Redfield Christina , Shammas Sarah L
Published: September 2024

The basic zippers (bZIPs) are one of two large eukaryotic families of transcription factors whose DNA binding domains are disordered in isolation but fold into stable α-helices upon target DNA binding. Here, we systematically disrupt pre-existing helical propensity within the DNA binding region of the homodimeric bZIP domain of cAMP-response element binding protein (CREB) using Ala-Gly scanning and examine the impact on target binding kinetics. We find that the secondary structure of the transition state strongly resembles that of the unbound state. The residue closest to the dimerization domain is largely folded within both unbound and transition states; dimerization apparently propagates additional helical propensity into the basic region. The results are consistent with electrostatically-enhanced DNA binding, followed by rapid folding from the folded zipper outwards. Fly-casting theory suggests that protein disorder can accelerate binding. Interestingly however, we did not observe higher association rate constants for mutants with lower levels of residual structure in the unbound state.
Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks
Authors: Palermo Valentina , Malacaria Eva , Semproni Maurizio , Camerini Serena , Casella Marialuisa , Perdichizzi Benedetta , Valenzisi Pasquale , Sanchez Massimo , Marini Federica , Pellicioli Achille , Franchitto Annapaola , Pichierri Pietro
Published: September 2024

Replication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination (HR), a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for end resection and is instrumental in selecting the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases defines a complex regulatory layer essential for correct long-range end resection, connecting it to repair by HR. We establish that long-range end resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphorylation at Ser1141, together with dephosphorylation at the CDK1 site Ser1133, is needed for the proper metabolism of RAD51 foci and RAD51-dependent repair. Collectively, our findings suggest that regulation of WRN by multiple kinases functions as a molecular switch to allow timely execution of end resection and repair at replication-dependent DNA double-strand breaks.
Effective requesting method to detect fusion transcripts in chronic myelomonocytic leukemia RNA-seq
Authors: Rufflé Florence , Reboul Jérôme , Boureux Anthony , Guibert Benoit , Bessière Chloé , Silva Raissa , Jourdan Eric , Gaillard Jean-Baptiste , Boland Anne , Deleuze Jean-François , Sénamaud-Beaufort Catherine , Selimoglu-Buet Dorothée , Solary Eric , Gilbert Nicolas , Commes Thérèse
Published: September 2024

RNA sequencing technology combining short read and long read analysis can be used to detect chimeric RNAs in malignant cells. Here, we propose an integrated approach that uses k-mers to analyze indexed datasets. This approach is used to identify chimeric RNA in chronic myelomonocytic leukemia (CMML) cells, a myeloid malignancy that associates features of myelodysplastic and myeloproliferative neoplasms. In virtually every CMML patient, new generation sequencing identifies one or several somatic driver mutations, typically affecting epigenetic, splicing and signaling genes. In contrast, cytogenetic aberrations are currently detected in only one third of the cases. Nevertheless, chromosomal abnormalities contribute to patient stratification, some of them being associated with higher risk of poor outcome, e.g. through transformation into acute myeloid leukemia (AML). Our approach selects four chimeric RNAs that have been detected and validated in CMML cells. We further focus on NRIP1-MIR99AHG, as this fusion has also recently been detected in AML cells. We show that this fusion encodes three isoforms, including a novel one. Further studies will decipher the biological significance of such a fusion and its potential to improve disease stratification. Taken together, this report demonstrates the ability of a large-scale approach to detect chimeric RNAs in cancer cells.
Comparative analysis of single-cell pathway scoring methods and a novel approach
Authors: Wang Ruoqiao H , Thakar Juilee
Published: September 2024

Single-cell gene set analysis (scGSA) provides a useful approach for quantifying molecular functions and pathways in high-throughput transcriptomic data, facilitating the biological interpretation of complex human datasets. However, various factors such as gene set size, quality of the gene sets and the dropouts impact the performance of scGSA. To address these limitations, we present a single-cell Pathway Score (scPS) method to measure gene set activity at single-cell resolution. Furthermore, we benchmark our method with six other methods: AUCell, AddModuleScore, JASMINE, UCell, SCSE and ssGSEA. The comparison across all the methods using two different simulation approaches highlights the effect of cell count, gene set size, noise, condition-specific genes and zero imputation on their performance. The results of our study indicate that the scPS is comparable with other single-cell scoring methods and detects fewer false positives. Importantly, this work reveals critical variables in the scGSA.
Exploring the impact of sequence context on errors in SNP genotype calling with whole genome sequencing data using AI-based autoencoder approach
Authors: Kotlarz Krzysztof , Mielczarek Magda , Biecek Przemysław , Guldbrandtsen Bernt , Szyda Joanna
Published: September 2024

A critical step in the analysis of whole genome sequencing data is variant calling. Despite its importance, variant calling is prone to errors. Our study investigated the association between incorrect single nucleotide polymorphism (SNP) calls and variant quality metrics and nucleotide context. In our study, incorrect SNPs were defined in 20 Holstein–Friesian cows by comparing their SNPs genotypes identified by whole genome sequencing with the IlluminaNovaSeq6000 and the EuroGMD50K genotyping microarray. The dataset was divided into the correct SNP set (666 333 SNPs) and the incorrect SNP set (4 557 SNPs). The training dataset consisted of only the correct SNPs, while the test dataset contained a balanced mix of all the incorrectly and correctly called SNPs. An autoencoder was constructed to identify systematically incorrect SNPs that were marked as outliers by a one-class support vector machine and isolation forest algorithms. The results showed that 59.53% (±0.39%) of the incorrect SNPs had systematic patterns, with the remainder being random errors. The frequent occurrence of the CGC 3-mer was due to mislabelling a call for C. Incorrect T instead of A call was associated with the presence of T in the neighbouring downstream position. These errors may arise due to the fluorescence patterns of nucleotide labelling.
Multidisciplinary team approach for CKD-associated osteoporosis
Authors: Hansen Ditte , Jørgensen Hanne Skou , Andersen Thomas Levin , Ferreira Ana Carina , Ferreira Aníbal , de Jongh Renate , Keronen Satu , Kröger Heikki , Lafage-Proust Marie Hélène , Martola Leena , Poole Kenneth E S , Tong Xiaoyu , Evenepoel Pieter , Haarhaus Mathias
Published: September 2024

Chronic kidney disease–mineral and bone disorder (CKD-MBD) contributes substantially to the burden of cardiovascular disease and fractures in patients with CKD. An increasing arsenal of diagnostic tools, including bone turnover markers and bone imaging, is available to support clinicians in the management of CKD-associated osteoporosis. Although not mandatory, a bone biopsy remains useful in the diagnostic workup of complex cases. In this special report, the European Renal Osteodystrophy (EUROD) initiative introduces the concept of a kidney–bone multidisciplinary team (MDT) for the diagnosis and clinical management of challenging cases of CKD-associated osteoporosis. In 2021, the EUROD initiative launched virtual clinical-pathological case conferences to discuss challenging cases of patients with CKD-associated osteoporosis, in whom a bone biopsy was useful in the diagnostic workup. Out of these, we selected four representative cases and asked a kidney–bone MDT consisting of a nephrologist, an endocrinologist and a rheumatologist to provide comments on the diagnostic and therapeutic choices. These cases covered a broad spectrum of CKD-associated osteoporosis, including bone fracture in CKD G5D, post-transplant bone disease, disturbed bone mineralization, severely suppressed bone turnover and severe hyperparathyroidism. Comments from the MDT were, in most cases, complementary to each other and additive to the presented approach in the cases. The MDT approach may thus set the stage for improved diagnostics and tailored therapies in the field of CKD-associated osteoporosis. We demonstrate the clinical utility of a kidney-bone MDT for the management of patients with CKD-MBD and recommend their establishment at local, national, and international levels.
Actionable alterations in glioblastoma: Insights from the implementation of genomic profiling as the standard of care from 2016 to 2023
Authors: Fougner Vincent , Urup Thomas , Poulsen Hans Skovgaard , Grunnet Kirsten , Westmose Christina Yde , Melchior Linea Cecilie , Larsen Karen Bonde , Højgaard Martin , Spanggaard Iben , Belcaid Laila , Rohrberg Kristoffer Staal , Lassen Ulrik , Hasselbalch Benedikte , Nørøxe Dorte Schou
Published: September 2024

Background

In 2016, genomic profiling was implemented for patients with grade 4 primary brain tumors at Rigshospitalet, Denmark. The aim of this study was to discover actionable alterations and to match these with targeted therapies.

Methods

Between January 2016 and December 2023, 483 brain tumor patients were profiled. We retrieved clinical data and molecular data. Whole exome, whole genome, or panel sequencing, along with SNP array analyses, and RNA-seq were performed on resected primary tumor tissue. Alterations were classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) following the European Association of Neuro-Oncology (EANO) guideline on rational molecular testing.

Results

A total of 200 (41.4%) patients’ tumors harbored an alteration of interest according to the EANO guideline. Twenty (4.1%) patients had an ESCAT high-tier alteration (tier I or II), while 155 patients (32.1%) had an alteration corresponding to ESCAT IIIA. Thirty-five patients (7.2%) had an actionable alteration, and 15 (3.1%) received targeted therapy. The treated targets were BRAFV600E mutations, FGFR alterations, NTRK fusions, PDGFRA fusions, PTPRZ1-MET fusions, and TMB-high. The overall response rate was 20%, with a median duration of response of 12 months, and 47% achieved stable disease as the best response.

Conclusions

Genomic profiling uncovers alterations of interest in a substantial number of patients, but only a minority are considered by the Danish National Molecular Tumor Board to have actionable alterations, and even fewer receive targeted therapy. Nevertheless, factors, such as promising targets and the increasing availability of trials, may contribute to a future increase in the number of patients benefiting from targeted therapies based on genomic profiling.
(Digital) Things as Objects of Property Rights: What Can Crypto Learn From Comparative Law?
Authors: Held Amy
Published: September 2024

This review article engages critically with Christian von Bar’s proposed definition of things as objects of property rights and their proposed place as one category in a tripartite taxonomy of the objects of private law; both expounded as part of a broader aim of bringing together the property laws of the Member States of the European Union and the UK as part of a single picture. The article first contextualises these proposals against the background of the UNIDROIT Principles on Digital Assets and the ongoing debates in England and Wales as to the property status of cryptoassets such as bitcoin; then offers a primer for both common law and civilian law readers on the structure, content and objectives of the book. After setting out the proposed taxonomy and the core theses upon which it is premised, the article then evaluates von Bar’s proposals and illustrates how they can inform and guide the debates as international and domestic laws grapple with the challenges posed by new and novel objects of economic value. The book under review is an abridged version of the first two parts of Gemeineuropäisches Sachenrecht, originally published in German by CH Beck in 2015, which were translated into English by Jason Grant Allen and reworked into a standalone text published by OUP in 2023.
Tax and Public Revenue
Authors: Nakamba Pamela , Nyanga Maimbo , Simbeye Laban , Mulenga Mukuka S. , Shamabobo Yenda
Published: September 2024

This chapter on tax and public revenue is aimed at analysing the broad policy and administration framework for tax and public revenue that Zambia has undertaken in responding to the increasing need to raise more revenue while at the same time keeping up with the developments in both the domestic and global environment. Many studies have attempted to document Zambia’s revenue performance over time, but fewer have endeavoured to include a detailed evolution of Zambia’s revenue administration and management reforms and systems. The discussion in this chapter shows that Zambia has made significant progress in reforming revenue administration. Key among these reforms has been the development of taxpayer registration databases, use of high-integrity unique taxpayer identification number, and establishment of a semi-autonomous revenue authority. These reforms have resulted in considerable successes tax revenue mobilization. However, challenges such as how to tax the large informal sector still remain.
Capital Markets in Zambia
Authors: Mwenda Kenneth K.
Published: September 2024

This chapter is an exploratory study of Zambian capital markets. The chapter argues that the Lusaka Stock Exchange continues to play a limited role in the raising of capital in Zambia. The extent to which Zambian capital markets can be said to have served as a vehicle for attracting private capital and savings for portfolio investment is examined. An interdisciplinary study is provided, using a qualitative methodology. The chapter argues that many banks and financial institutions in Zambia have shown hesitancy to list on the Zambian capital market, thus, depriving the Lusaka Stock Exchange of the desired levels of liquidity. Pension funds and collective investment schemes are also said to have played a limited role in mobilizing private capital for investment on the Lusaka Stock Exchange. The chapter highlights the need to deepen the Zambian capital markets through increased volumes of trade and market capitalization. Policy interventions are thus spelt out for the integration of capital markets in the Southern and Eastern Africa regions through dual listings and multiple listings of securities as a way to stimulate the growth and development of the Zambian capital markets.
The Mining Industry and Local Content Policy in Zambia
Authors: Kragelund Peter
Published: September 2024

Local content policies (LCP) are often depicted as a useful policy tool for tackling the conundrum in many resource-rich economies of the Global South of great mineral wealth and pervasive inequality, poverty, and lack of structural transformation. Therefore, many African heads of state perceive LCPs to be an important tool in turning non-renewable commodities into broad-based development. This is also the case in Zambia where the Zambian government has worked hard to introduce LCPs. In spite of this, LCPs have not led to structural transformation. This chapter seeks to explain why. It argues that several interrelated factors account for this, including an inability among domestic firms to supply goods and services of a sufficient quality to the multinational mining corporations; LCPs characterized by too high hopes; too little attention to demand capacity and intersectoral in LCPs (and related policies); and inadequate finance to back the LCPs.
Public Revenue–Expenditure Nexus in Malawi
Authors: Bangara Bertha Chipo
Published: September 2024

Despite the impressive performance of domestic revenue mobilization over the years, the expenditure–revenue gap has continued to widen, leading to increased government deficits in Malawi. This chapter uses the Autoregressive Distributed Lag (ARDL) model and Cointegrating Vector Autoregression (VAR) to examine the asymmetries between government revenue and expenditure in Malawi. The results reveal that there exists a unidirectional causality between government revenue and expenditure, and that causality runs from government revenue to expenditure without feedback mechanism. The short-run results show that expenditure and revenue reinforce each other, indicating a significant long-run and short-run relationship. However, the lagged values of the short-run model for revenue show that increases in taxes have a negative impact on government spending, implying the absence of fiscal illusion. Therefore, the government should push for institutional separation of allocation and taxation functions, as there is strong evidence of causation between government revenues and expenditures.
The Impact of the Covid-19 Pandemic on the Malawian Economy
Authors: Ahiakpor Ferdinand , Bondzie Eric Amoo , Cantah William Godfred , Chavula Hopestone Kayiska
Published: September 2024

This study tries to assess the impact of the unexpected COVID-19 pandemic, and the various policy options adopted by different countries to mitigate its effect, on the Malawi economy. The study employs the structural macroeconometric model developed for developing countries by the Economic Commission for Africa. Among others, the results show that the Malawi economy has been severely affected by the pandemic, with GDP growth expected to be below its pre-pandemic projection levels, and with worsened fiscal deficits and debt levels. This calls for a comprehensive policy agenda that tackles the country’s vulnerabilities to generate a transformational and inclusive recovery process. There is a need for the government to enhance its domestic revenue mobilization efforts and public service delivery with fiscal and monetary policy measures that would create an enabling economic environment and strengthen the government’s long-term commitment to structural transformation and long-term growth of the economy.
Development Aid: Complementarity or Competition?
Authors: Chasukwa Michael , Banik Dan
Published: September 2024

This chapter examines whether and to what extent development aid provided by traditional and non-traditional donors competes with and/or complements the development agenda of recipient countries. We focus on aid narratives and the nature of projects supported by donors, the perceived levels of ‘interference’ in domestic politics, the extent of policy space available, and the actual modalities of aid delivery. Based on primary and secondary data collected in the period 2016–2021, we find that while traditional donors have, on numerous occasions, withdrawn or suspended their aid, China is yet to do so. Non-traditional donors such as China often focus on ‘orphan’ sectors that are typically neglected by Western actors, but which are nonetheless important for socio-economic development in Malawi. Despite some competition, the activities of traditional and non-traditional donors in Malawi complement each other.
India’s Civil–Military Relations
Authors: Mukherjee Anit
Published: September 2024

This chapter provides an overview of the state of civil-military relations in India. This is especially topical, as India is undertaking its most transformative post-Independence defence reforms by creating a post of Chief of Defence Staff (CDS), among other measures. What are the sources of continuity and change in India’s civil-military relations? How can India guard against politicization of the military while consolidating civilian control and military effectiveness? While answering these questions, this chapter makes three main arguments. First, India’s politicians have historically privileged civilian control over the military. This has had an adverse impact on the effectiveness of the military. Second, political control of the military has been exercised mainly through the civilian bureaucracy, leading to heartburn within the military and creating considerable discord between them. Third, the current government, led by Prime Minister Narendra Modi, is undertaking the most significant institutional transformation which could potentially overturn existing norms of civil-military relations. There is great promise in these measures, mainly of enhancing effectiveness and efficiency. However, there is also some peril—that of a politicization of the armed forces. Civil-military relations therefore require careful rewiring and constant monitoring.
Cultivating long-term well-being through transformative undergraduate education
Authors: White Holly C , Allen Debra M , Buffinton Keith , Humphrey Dana , Malpiede Marjorie , Miller Richard K , Volin John C
Published: September 2024

Despite the growing body of research suggesting certain pedagogical approaches that can support student well-being, higher education has not fully embraced these approaches and typically still does not view well-being as a high priority in comparison with other metrics such as retention or GPA. Here, we contend that universities must play an active role in supporting lifelong well-being in their student populations by expanding their definitions of student success and providing opportunities and programs that support elements related to well-being. We propose a student well-being nexus, which comprises a sense of belonging, agency, purpose, identity, civic engagement, and financial well-being. This article provides a perspective on the importance of each element to well-being and which pedagogical practices have been shown to support various dimensions of well-being in undergraduate education, such as service learning, undergraduate research, and mentoring. In addition, it showcases 6 exceptional initiatives from various universities that aim to support one or more of the student well-being nexus dimensions, which can serve as models for other universities. Finally, several guiding principles are outlined for higher education institutions to support the implementation of student well-being initiatives and transformational learning opportunities. These include assessment of initiatives, embedding initiatives into the curriculum, and avoidance of creating additional financial burdens for students. These efforts can promote well-being on college campuses and beyond graduation.
Forage conservation is a neglected nitrous oxide source
Authors: Yang Seongmin , Mahmood Maheen , Baral Rudra , Wu Hui , Almloff Marc , Stanton Lauren E , Min Doohong , Smiley Brenda K , Iiams J Chris , Yu Jisang , Im Jeongdae
Published: September 2024

Agricultural activities are the major anthropogenic source of nitrous oxide (N2O), an important greenhouse gas and ozone-depleting substance. However, the role of forage conservation as a potential source of N2O has rarely been studied. We investigated N2O production from the simulated silage of the three major crops—maize, alfalfa, and sorghum—used for silage in the United States, which comprises over 90% of the total silage production. Our findings revealed that a substantial N2O could be generated, potentially placing forage conservation as the third largest N2O source in the agricultural sector. Notably, the application of chlorate as an additive significantly reduced N2O production, but neither acetylene nor intermittent exposure to oxygen showed any impact. Overall, the results highlight that denitrifiers, rather than nitrifiers, are responsible for N2O production from silage, which was confirmed by molecular analyses. Our study reveals a previously unexplored source of N2O and provides a crucial mechanistic understanding for effective mitigation strategies.
A model of dyadic merging interactions explains human drivers’ behavior from control inputs to decisions
Authors: Siebinga Olger , Zgonnikov Arkady , Abbink David A
Published: September 2024

Safe and socially acceptable interactions with human-driven vehicles are a major challenge in automated driving. A good understanding of the underlying principles of such traffic interactions could help address this challenge. Particularly, accurate driver models could be used to inform automated vehicles in interactions. These interactions entail complex dynamic joint behaviors composed of individual driver contributions in terms of high-level decisions, safety margins, and low-level control inputs. Existing driver models typically focus on one of these aspects, limiting our understanding of the underlying principles of traffic interactions. Here, we present a Communication-Enabled Interaction model based on risk perception, that does not assume humans are rational and explicitly accounts for communication between drivers. Our model can explain and reproduce observed human interactions in a simplified merging scenario on all three levels. Thereby improving our understanding of the underlying mechanisms of human traffic interactions and posing a step towards interaction-aware automated driving.