bluuebunny/crossref_metadata_2025 huggingface dataset:
HER4 is a high‐affinity dimerization partner for all EGFR/HER/ErbB family proteins
Authors: Singh Pradeep Kumar , Kim Soyeon , Smith Adam W.
Published: September 2024

Human epidermal growth factor receptors (HER)—also known as EGFR or ErbB receptors—are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time‐resolved fluorescence technique called pulsed interleaved excitation fluorescence cross‐correlation spectroscopy (PIE‐FCCS). PIE‐FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single‐cell protein expression levels and diffusion coefficients. Our PIE‐FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4‐specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands.
BracketMaker: Visualization and optimization of chemical protein synthesis
Authors: Evangelista Judah L. , Kay Michael S.
Published: September 2024

Chemical protein synthesis (CPS), in which custom peptide segments of ~20–60 aa are produced by solid‐phase peptide synthesis and then stitched together through sequential ligation reactions, is an increasingly popular technique. The workflow of CPS is often depicted with a “bracket” style diagram detailing the starting segments and the order of all ligation, desulfurization, and/or deprotection steps to obtain the product protein. Brackets are invaluable tools for comparing multiple possible synthetic approaches and serve as blueprints throughout a synthesis. Drawing CPS brackets by hand or in standard graphics software, however, is a painstaking and error‐prone process. Furthermore, the CPS field lacks a standard bracket format, making side‐by‐side comparisons difficult. To address these problems, we developed BracketMaker, an open‐source Python program with built‐in graphic user interface (GUI) for the rapid creation and analysis of CPS brackets. BracketMaker contains a custom graphics engine which converts a text string (a protein sequence annotated with reaction steps, introduced herein as a standardized format for brackets) into a high‐quality vector or PNG image. To aid with new syntheses, BracketMaker's “AutoBracket” tool automatically performs retrosynthetic analysis on a set of segments to draft and rank all possible ligation orders using standard native chemical ligation, protection, and desulfurization techniques. AutoBracket, in conjunction with an improved version of our previously reported Automated Ligator (Aligator) program, provides a pipeline to rapidly develop synthesis plans for a given protein sequence. We demonstrate the application of both programs to develop a blueprint for 65 proteins of the minimal Escherichia coli ribosome.
Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi‐enzyme colocalization and environment
Authors: Kaushik Shivansh , Hung Ta I , Chang Chia‐en A.
Published: September 2024

Millions of years of evolution have optimized many biosynthetic pathways by use of multi‐step catalysis. In addition, multi‐step metabolic pathways are commonly found in and on membrane‐bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast–ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl‐CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol‐O‐acetyltransferase. Arranging two enzymes with the smallest inter‐enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter‐enzyme distances. When the off‐target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi‐enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems.
Developing and evaluating the extended epistemic vigilance framework
Authors: Bielik Tom , Krell Moritz
Published: September 2024

In science education, epistemic vigilance plays a key role in the development of students' critical thinking by supporting students' abilities to evaluate the expertise level of the source and to evaluate the claim itself, using rigorous scientific standards and appropriate argumentation heuristics. Based on previous studies, which suggested two aspects of epistemic vigilance—reflecting the source of information and the claim that is made—we developed the Extended Epistemic Vigilance Framework (EEVF) that includes an additional aspect of evaluating the receiver. In an empirical exploratory pilot study, we evaluated the reliability and validity of an EEVF‐based category system and investigated to what extent the EEVF can be used to characterize changes in biology graduate students' epistemic vigilance after participating in a critical thinking course. Results show that the EEVF‐based category system includes reliable and valid categories for identifying students' epistemic vigilance. A statistically significant increase with a small effect size was found in students' epistemic vigilance regarding the reliability of the source and the references used to support the claim following their participation in the critical thinking course. However, a statistically significant decrease with a small effect size was found regarding the awareness of the aspects of the one‐sidedness of the claim, the context of the claim, and cognitive biases and socioemotional influences on the receiver. In general, these findings indicate that the EEVF offers an improved framework to analyze students' epistemic vigilance more comprehensively.
Intraocular malignant nerve sheath tumour in a brown eyed labrador retriever
Authors: Salter Lauren , Scurrell Emma , Mignan Thomas
Published: September 2024

A 6‐year‐old, male, neutered, brown eyed labrador retriever was presented with an intraocular pale pink mass in the left eye. Enucleation of the globe was performed, and the mass was submitted for histopathology. Histology and immunohistochemistry confirmed the mass as a malignant nerve sheath tumour. There was no evidence of mass recurrence, and general and neurological examination remained normal at 9‐month follow‐up. While the majority of intraocular neoplasms are benign, a malignant neoplasm must be considered in all cases of intraocular mass. Differentiation between benign and malignant intraocular neoplasms is challenging and often requires enucleation with histopathology to confirm diagnosis. Tumour staging should be considered in the event of a malignant nerve sheath tumour. Finally, uveal malignant nerve sheath tumour should not only be considered in blue eyed dogs, but also in brown eyed dogs as in the present case.
Investigation of micropolar dusty fluid flow in a rotational frame with magnetic field: A meshless radial basis function pseudospectral approach
Authors: Himanshu  , Bhatia Gurpreet Singh , Chandrawat Rajesh Kumar
Published: September 2024

Rotational flow has numerous applications across a wide range of fields, including industrial processes for mixing, pumping, and processing materials, geophysical fluid dynamics for studying the Earth's atmosphere and oceans, aerospace engineering for designing and testing aircraft and spacecraft, medical imaging for creating detailed images of the human body, and environmental engineering for studying the transport of pollutants in water and air. In rotational flow, pumping power is an important parameter that measures the amount of energy required to maintain the flow of the fluid in a rotating frame. It is significant because the presence of the Coriolis force and other rotational effects can substantially alter the fluid dynamics, making it difficult to maintain a steady flow. The present study deals with the flow of micropolar dusty fluid in a rotating frame under the influence of the magnetic field, applied transversely to the flow in a horizontal channel. The fluid is induced to flow between two parallel plates by the movement of the upper plate and a constant pressure gradient. A meshless radial basis function pseudospectral approach is employed to derive a set of partial differential equations that determine the primary and secondary velocity profiles of the fluid, as well as the particle and microrotation velocities and temperature distribution. The pumping power required to sustain the flow in the absence of a pressure gradient is also calculated based on these velocity profiles. The findings provide valuable insights into the behavior of micropolar dusty fluids in a rotational channel and can potentially inform the design of industrial processes involving such fluids.
Flow around a slender body with sharp edges
Authors: Núñez Manuel
Published: September 2024

The behavior of harmonic functions near corners of the domain boundary has a universal character that may be applied to the study of the flow around slender bodies with sharp edges. Depending of the energy of the potential function near the tip of the corner, this may yield a fast rotating flow or a vortex in its vicinity. For internal angles, such as occur in grooves of the body, a stagnation region or an eddy may occur. Lateral forces are also affected by the presence of corners, yielding configurations that resemble either a circulation lift or a vortex lift.
Mosco Convergence of Gradient Forms with Non-Convex Interaction Potential
Authors: Grothaus Martin , Wittmann Simon
Published: September 2024

This article provides a new approach to address Mosco convergence of gradient-type Dirichlet forms, $${\mathcal {E}}^N$$

E

N

on $$L^2(E,\mu _N)$$

L
2

(
E
,

μ
N

)

for $$N\in {\mathbb {N}}$$

N
∈
N

, in the framework of converging Hilbert spaces by K. Kuwae and T. Shioya. The basic assumption is weak measure convergence of the family $${(\mu _N)}_{N}$$

(

μ
N

)

N

on the state space E—either a separable Hilbert space or a locally convex topological vector space. Apart from that, the conditions on $${(\mu _N)}_{N}$$

(

μ
N

)

N

try to impose as little restrictions as possible. The problem has fully been solved if the family $${(\mu _N)}_{N}$$

(

μ
N

)

N

contain only log-concave measures, due to Ambrosio et al. (Probab Theory Relat. Fields 145:517–564, 2009). However, for a large class of convergence problems the assumption of log-concavity fails. The article suggests a way to overcome this hindrance, as it presents a new approach. Combining the theory of Dirichlet forms with methods from numerical analysis we find abstract criteria for Mosco convergence of standard gradient forms with varying reference measures. These include cases in which the measures are not log-concave. To demonstrate the accessibility of our abstract theory we discuss a first application, generalizing an approximation result by Bounebache and Zambotti (J Theor Probab 27:168–201, 2014).
Enhanced Dissipation for Two-Dimensional Hamiltonian Flows
Authors: Bruè Elia , Coti Zelati Michele , Marconi Elio
Published: September 2024

Let $$H\in C^1\cap W^{2,p}$$

H
∈

C
1

∩

W

2
,
p

be an autonomous, non-constant Hamiltonian on a compact 2-dimensional manifold, generating an incompressible velocity field $$b=\nabla ^\perp H$$

b
=

∇
⊥

H

. We give sharp upper bounds on the enhanced dissipation rate of b in terms of the properties of the period T(h) of the closed orbit $$\{H=h\}$$

{
H
=
h
}

. Specifically, if $$0<\nu \ll 1$$

0
<
ν
≪
1

is the diffusion coefficient, the enhanced dissipation rate can be at most $$O(\nu ^{1/3})$$

O
(

ν

1
/
3

)

in general, the bound improves when H has isolated, non-degenerate elliptic points. Our result provides the better bound $$O(\nu ^{1/2})$$

O
(

ν

1
/
2

)

for the standard cellular flow given by $$H_{\textsf{c}}(x)=\sin x_1 \sin x_2$$

H
c

(
x
)

=
sin

x
1

sin

x
2

, for which we can also prove a new upper bound on its mixing rate and a lower bound on its enhanced dissipation rate. The proofs are based on the use of action-angle coordinates and on the existence of a good invariant domain for the regular Lagrangian flow generated by b.
Uniform Positivity of the Lyapunov Exponent for Monotone Potentials Generated by the Doubling Map
Authors: Zhang Zhenghe
Published: September 2024

We show that for any doubling map generated $$C^1$$

C
1

monotone potential with derivative uniformly bounded away from zero and infinity, the Lyapunov exponent of the associated Schrödinger operators is bounded below by $$\log {\lambda }-C$$

log
λ
-
C

for all energies, where C depends only on the potential. In particular, it answers an open question [D, Problem 5] raised by D. Damanik.
Juveniles of a biparental cichlid fish compensate lack of parental protection by improved shoaling performance
Authors: Zacke Maren Annika , Thünken Timo
Published: September 2024

Parental brood care greatly affects offspring’s fitness, but the specific effects of care on the collective behaviour of independent offspring are less well understood. It has been suggested that the loss of care induces increased sibling cooperation to compensate parental contributions. However, the empirical evidence is ambiguous. Here, we examined how the loss of early parental care affects the collective behaviour, i.e. shoaling performance of independent juveniles in a genetically heterogeneous lab-population of the biparental cichlid fish Pelvicachromis pulcher. Applying a split-clutch design, we reared in- and outbred offspring with or without parents. In the experiment, we examined shoal density (inter-individual distance) in relation to body size of the shoaling fish. Dense shoaling reduces predation risk and small fish may benefit strongest because they are particularly vulnerable to predation by gape-limited predators. Juveniles reared without parents formed denser shoals and they adjusted shoaling behaviour depending on own body size compared to juveniles reared with parents; especially smaller fish formed dense shoals. Inbreeding did not significantly affect shoaling performance. This indicates that juveniles compensate missing parental care by adjusting their shoaling behaviour depending on own vulnerability. Our study contributes to the understanding of the co-evolution of brood care and sibling cooperation.
Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial
Authors: Yang Shenmiao , Huang Haiwen , Zhou Keshu , Zhao Xielan , Han Yanqiu , Li Lindong , Wang Yujie , Liu Xiaofeng , Li Jianyong
Published: September 2024

Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor approved in the United States and Europe for chronic lymphocytic leukemia (CLL) based on phase 3 trials with limited representation of Asian populations. This phase 1/2 trial evaluates acalabrutinib in Chinese adults with relapsed/refractory (R/R) CLL receiving acalabrutinib 100 mg twice daily in 28-day cycles until disease progression or treatment discontinuation due to adverse events (AEs) presenting substantial clinical risk. The primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). A total of 60 patients from 20 sites in China received acalabrutinib (median age 62 years; median 1 prior therapy line; 21.7% with del(17p) and/or TP53 mutation; 51.7% with unmutated IGHV). Median total treatment duration was 19.4 months (range 0.6–28.2) with 53 patients (88.3%) receiving acalabrutinib at data cutoff; median study follow-up was 20.2 months. BICR-assessed ORR was 85.0% (95% CI, 73.4–92.9). Median duration of response, progression-free survival (PFS), and overall survival (OS) were not reached. Estimated 12-month and 18-month PFS rates were 91.5% (95% CI, 80.9–96.4) and 78.8% (95% CI, 60.9–89.2); OS rates were both 96.7% (95% CI, 87.3–99.2). AEs of grade ≥ 3 occurred in 25 patients (41.7%), most commonly decreased neutrophil count (13.3%, n = 8), pneumonia (6.7%, n = 4), and upper respiratory tract infection (6.7%, n = 4). AEs led to treatment discontinuation in 2 patients (paraneoplastic pemphigus; rectal neoplasm). This study demonstrated high ORR in acalabrutinib-treated Chinese patients with R/R CLL with no unexpected safety concerns. This trial is registered on ClinicalTrials.gov (NCT03932331).
Optimizing climate model selection in regional studies using an adaptive weather type based framework: a case study for extreme heat in Belgium
Authors: Serras Fien , Vandelanotte Kobe , Borgers Ruben , Van Schaeybroeck Bert , Termonia Piet , Demuzere Matthias , van Lipzig Nicole P. M.
Published: September 2024

Selecting climate model projections is a common practice for regional and local studies. This process often relies on local rather than synoptic variables. Even when synoptic weather types are considered, these are not related to the variable or climate impact driver of interest. Therefore, most selection procedures may not sufficiently account for atmospheric dynamics and climate change impact uncertainties. This study outlines a selection methodology that addresses both these shortcomings. Our methodology first optimizes the Lamb Weather Type classification for the variable and region of interest. In the next step, the representation of the historical synoptic dynamics in Global Climate Models (GCMs) is evaluated and accordingly, low-performing models are excluded. In the last step, indices are introduced that quantify the climate change signals related to the impact of interest. Using these indices, a scoring method results in assessing the suitability of GCMs. To illustrate the applicability of the methodology, a case study of extreme heat in Belgium was carried out. This framework offers a comprehensive method for selecting relevant climate projections, applicable in model ensemble-based research for various climate variables and impact drivers.
The effect of vitamin D supplementation on markers of insulin resistance in women with polycystic ovarian syndrome: a systematic review
Authors: Kohlhoff Georgia , Kirwan Richard , Mushtaq Sohail
Published: September 2024

Background

Insulin resistance (IR) is a common pathology in women with polycystic ovarian syndrome (PCOS) involved in increased rates of cardiometabolic disease such as diabetes and cardiovascular disease. Low serum vitamin D is often associated with insulin resistance but there is no consensus on whether vitamin D supplementation can ameliorate markers of IR in PCOS.

Objectives

We assessed evidence on the effects of vitamin D supplementation (≥ 1000 IU/day), without the use of additional supplements or other pharmacological treatments known to affect IR, on markers of IR and glycemic control in women with PCOS.

Design

A systematic search was conducted using PubMed, Medline and Web of Science databases from January 2000 up to November 2023. Randomized controlled trials that assessed the effects of vitamin D supplementation in women with PCOS, on fasting glucose, fasting insulin, glycated haemoglobin (HbA1c) or homeostatic model assessment for insulin resistance (HOMA-IR) were included.

Results

9 studies were identified. Study populations ranged from 28 to 180 participants, with mean ages ranging from 22 to 30 years. Daily vitamin D doses ranged from 1714-12,000 IU. Of the included studies, 3 reported statistically significant reductions in fasting glucose, 2 reported reductions in fasting insulin, 2 reported reductions in HOMA-IR, none reported reductions in HbA1c and 5 reported no differences in any of the relevant outcomes.

Conclusions

In conclusion, in RCTs of vitamin D supplementation in women with PCOS, the majority of studies do not report statistically significant improvements in fasting glucose, fasting insulin, HbA1c or HOMA-IR. However, as a minority of studies report some statistically significant results, further investigation may be warranted.

Registry

PROSPERO ID: CRD42023486144
Mood disorders and suicide: pilot study on postmortem toxicologic evidence and adherence to psychiatric therapy by determining blood levels of medications
Authors: Tambuzzi Stefano , Travaini Guido , Gambini Orsola , Collini Federica , Ginepro Lorenzo , Attanasio Francesco , Fregna Lorenzo , Zucca Federica , Di Candia Domenico , Amadeo Alida , Colombo Cristina , Battistini Alessio , Cattaneo Cristina
Published: September 2024

Suicide is one of the leading causes of death today, and among all mental illness, mood disorders account for one of the main risk factors. It is well known and proven that suicides are very common among people undergoing treatment and prescribed psychiatric medication. So far, however, there have only been a few studies dealing with this particular phenomenon. For this reason, autopsy patients who died by suicide, suffered from a mood disorder, and were known to be taking psychiatric medication at the time of death were selected for this study. The blood and urine samples taken during the autopsy underwent toxicological analysis and the results were compared with the prescribed therapy. A total of 22 people were included in the study: 12 presenting with depression and 10 with bipolar disorder. The toxicological analysis revealed that only 6 cases (27%) showed a qualitative match with the prescribed medication. In 5 cases (22.7%) the medication was only partially complied with and in 11 cases (50%) it was not complied with at all. Furthermore, even when medication was present, the value was often below the therapeutic range. Overall, more than 70% of the test subjects adhered to their medication only partially or not at all. Since treatment adherence is considered as a key factor in reducing the risk of suicide, this inevitably raises relevant clinical and forensic questions. Against this background, prospective monitoring of post-mortem medication levels in suicidal individuals and synergistic collaboration between clinicians and forensic pathologists could help to evaluate the effectiveness of specific medical interventions, highlight existing critical problems and develop new approaches to suicide prevention.
The management of retrorectal tumors – a single-center analysis of 21 cases and overview of the literature
Authors: Fechner K. , Bittorf B. , Langheinrich M. , Weber K. , Brunner M. , Grützmann R. , Matzel K. E.
Published: September 2024

Aim

Retrorectal tumors are rare and heterogeneous. They are often asymptomatic or present with nonspecific symptoms, making management challenging. This study examines the diagnosis and treatment of retrorectal tumors.

Methods

Between 2002 and 2022, 21 patients with retrorectal tumors were treated in our department. We analyzed patient characteristics, diagnosis and treatment modalities retrospectively. Additionally, a literature review (2002–2023, “retrorectal tumors” and “presacral tumors”, 20 or more cases included) was performed.

Results

Of the 21 patients (median age 54 years, 62% female), 17 patients (81%) suffered from benign lesions and 4 (19%) from malignant lesions. Symptoms were mostly nonspecific, with pain being the most common (11/21 (52%)). Diagnosis was incidental in eight cases. Magnetic resonance imaging was performed in 20 (95%) and biopsy was obtained in 10 (48%). Twenty patients underwent surgery, mostly via a posterior approach (14/20 (70%)). At a mean follow-up of 42 months (median 10 months, range 1–166 months), the local recurrence rate was 19%. There was no mortality. Our Pubmed search identified 39 publications.

Conclusion

Our data confirms the significant heterogeneity of retrorectal tumors, which poses a challenge to management, especially considering the often nonspecific symptoms. Regarding diagnosis and treatment, our data highlights the importance of MRI and surgical resection. In particular a malignancy rate of almost 20% warrants a surgical resection in case of the findings of a retrorectal tumour. A local recurrence rate of 19% supports the need for follow up.
A methodology for gene level omics-WAS integration identifies genes influencing traits associated with cardiovascular risks: the Long Life Family Study
Authors: Acharya Sandeep , Liao Shu , Jung Wooseok J. , Kang Yu S. , Moghaddam Vaha Akbary , Feitosa Mary F. , Wojczynski Mary K. , Lin Shiow , Anema Jason A. , Schwander Karen , Connell Jeff O. , Province Michael A. , Brent Michael R.
Published: September 2024

The Long Life Family Study (LLFS) enrolled 4953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8 × 10–7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein–Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genes FCER1A, MS4A2, GATA2, HDC, and HRH4 in atherosclerosis risks. Our findings also suggest that lower expression of ATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest that ENPP3 may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform (https://nf-co.re/omicsgenetraitassociation).
Graph network-based human movement prediction for socially-aware robot navigation in shared workspaces
Authors: Dik Casper , Emmanouilidis Christos , Duqueroie Bertrand
Published: September 2024

Methods for socially-aware robot path planning are increasingly needed as robots and humans increasingly coexist in shared industrial spaces. The practice of clearly separated zones for humans and robots in shop floors is transitioning towards spaces where both humans and robot operate, often collaboratively. To allow for safer and more efficient manufacturing operations in shared workspaces, mobile robot fleet path planning needs to predict human movement. Accounting for the spatiotemporal nature of the problem, the present work introduces a spatiotemporal graph neural network approach that uses graph convolution and gated recurrent units, together with an attention mechanism to capture the spatial and temporal dependencies in the data and predict human occupancy based on past observations. The obtained results indicate that the graph network-based approach is suitable for short-term predictions but the rising uncertainty beyond short-term would limit its applicability. Furthermore, the addition of learnable edge weights, a feature exclusive to graph neural networks, enhances the predictive capabilities of the model. Adding workspace context-specific embeddings to graph nodes has additionally been explored, bringing modest performance improvements. Further research is needed to extend the predictive capabilities beyond the range of scenarios captured through the original training, and towards establishing standardised benchmarks for testing human motion prediction in industrial environments.
Does the coronal deformity angular ratio affect bracing outcome in adolescent idiopathic scoliosis?
Authors: Ragborg Lærke C. , Thornberg David , Johnson Megan , McIntosh Amy , Sucato Daniel , Gehrchen Martin , Dahl Benny , Ohrt-Nissen Søren
Published: September 2024

Purpose

To examine if coronal deformity angular ratio (C-DAR) serves as a predictor for progression to surgical magnitude in patients with Adolescent Idiopathic Scoliosis (AIS) treated with thoracolumbar sacral orthosis (TLSO).

Methods

Patients with AIS, prescribed a full-time TLSO, Cobb angle 20–40°, Risser 0–2, who wore the brace ≥ 12.9 h and reached skeletal maturity/surgery were included retrospectively. C-DAR was defined as the Cobb angle divided by the number of vertebrae in the curve, yielding a larger value in short curves. The association between C-DAR and the risk of progression to surgical magnitude (> 45°) was assessed. Secondly, we evaluated the association between pre-treatment Cobb angle and in-brace correction on the risk of progression to > 45°.

Results

We included 165 patients with a mean Cobb angle of 30 ± 6°. Of these, 46/165 (28%) progressed ≥ 6° and 26/165 (16%) reached surgical magnitude at the end of treatment. C-DAR was a significant predictor for risk of progression to surgical magnitude with an OR of 1.9 (CI 1.2–2.9) per unit increase in C-DAR. A threshold value of 5.15 was established and demonstrated an OR 5.9 (CI 2.1–17.9) for curve progression to a surgical magnitude. Likewise, pre-treatment Cobb angle showed a significant OR 1.3(CI 1.2–1.4) per degree increase in Cobb, whereas in-brace % correction showed OR 0.96 (CI 0.93–0.98).

Conclusion

C-DAR is an independent predictor for progression to a surgical magnitude in AIS patients treated with bracing. Patients with a higher C-DAR should be counseled to help set realistic expectations regarding the likelihood of curve progression despite compliance with brace wear.
Puberty changes the natural history of idiopathic scoliosis: three prediction models for future radiographic curve severity from 1563 consecutive patients
Authors: Negrini Stefano , Yaskina Maryna , Donzelli Sabrina , Negrini Alberto , Rebagliati Giulia , Cordani Claudio , Zaina Fabio , Parent Eric C.
Published: September 2024

Purpose

Understanding idiopathic scoliosis (IS) natural history during growth is essential for shared decision-making between patients and physicians. We developed a retrospective model with the largest available sample in the literature and we aimed to investigate if using three peri-pubertal growth periods provides better prediction than a unique model.

Methods

Secondary analysis of a previous study on IS natural history data from radiographs before and at the first consult. Three groups: BEFORE (age 6–10), AT (age 11-Risser 2) and AFTER (from Risser 3) the pubertal growth spurt. Available predictors: Cobb angle, curve type, sex, observation time, and Risser score. We used linear mixed-effects models to predict future Cobb angles in each group. We internally validated prediction accuracy with over 100 patients per group (3 to 5-fold cross-validation).

Results

We included 1563 participants (275 BEFORE, 316 AFTER, 782 females and 190 males AT). Curves increased over time mostly in AT, importantly in BEFORE, but also in AFTER. All models performed better than the general one. In BEFORE, 74.2% of the predictions were within ± 5o, 71.8% in AFTER, 68.2% in AT females, and 60.4% in males. The predictors (baseline curve, observation time also squared and cubic, and Risser score) were similar in all the models, with sex influencing only AFTER.

Conclusion

IS curve severities increase differently during growth with puberty stages. Model accuracy increases when tailored by growth spurt periods. Our models may help patients and clinicians share decisions, identify the risk of progression and inform treatment planning.
Where has hydrogeologic science been, and where is it going? Research trends in hydrogeology publishing over the past 60 years
Authors: Christenson Catherine , Cardiff Michael
Published: September 2024

Quantifying historical research trends in the field of hydrogeology is not only generally informative for hydrogeologists but is essential for fostering interdisciplinary collaboration and assessing the relationship between academic study and societal interests in hydrogeologic issues. To address this, a topic model was applied to over 37,000 academic abstracts published in over 20 journals between 1963–2022 in the field of hydrogeology to study the evolution of topic trends through time. Model results were fed into the popular large-language model ChatGPT to assign topic names, representing an unsupervised method. The results indicate that, historically, popular topics related to methodological development and analytical and numerical models analytical and numerical methods in groundwater flow modeling and well hydraulics have given way to topics related to more increasingly complex models (groundwater monitoring and uncertainty estimation and groundwater modeling calibration and simulation) as data and computational capability becomes increasingly available. An insight into the period of boom-and-bust in contaminant hydrogeology is reflected by a shift in focus from topics related to assessment and characterization of contaminant sources toward topics related to degradation and remediation methods. Topics of emerging prevalence (sustainable groundwater resource management, catchment hydrology and runoff processes) in the current period reflect an increasing focus on treating the surface-water/groundwater system as a single system. In addition, results suggest that topic distribution within the field of hydrogeology has become more varied as time has progressed.
Barriers to creating value with cognitive accessibility features in digital services
Authors: Kärpänen Terhi
Published: September 2024

Digital services should be designed so that as many people as possible can use them. Designing digital services to be cognitively accessible brings value to the user if the user can use the digital service and understands its content. The benefits of cognitive accessibility, e.g., better customer experience or better usability in digital services, have been studied from the perspective of both users and organisations. Despite the benefits, there can be barriers to designing and implementing usable and understandable digital services. This paper aims to identify service providers’ perceptions of barriers to designing cognitively accessible digital services. When the barriers are understood, entrepreneurs can be supported to design digital services that generate value for customers. To better understand the barriers, qualitative research with semi-structured in-depth interviews was conducted with Finnish entrepreneurs. The results revealed different kinds of barriers to designing and implementing cognitively accessible digital services.
Local climate at breeding colonies influences pre-breeding arrival in a long-distance migrant
Authors: Lopez-Ricaurte Lina , Hernández-Pliego Jesús , García-Silveira Daniel , Bermejo-Bermejo Ana , Casado Susana , Cecere Jacopo G. , de la Puente Javier , Garcés-Toledano Fernando , Martínez-Dalmau Juan , Morganti Michelangelo , Ortega Alfredo , Rodríguez-Moreno Beatriz , Rubolini Diego , Sarà Maurizio , Bustamante Javier
Published: September 2024

The annual cycles of long-distance migrant species are synchronized with the local climatic conditions at their breeding areas, as they impact the availability of food resources. A timely arrival of individuals to the breeding grounds is crucial for achieving high fitness. Variation in factors influencing timing, including climate, may thus impact the life history of individuals. We studied between-individual variation in migration timing, in particular how local breeding climate influences arrival time and how early-arriving individuals achieve a timely arrival. We tracked individual Lesser Kestrel (Falco naumanni) with GPS tags across a gradient of latitude (37°–42° N) and longitude (6.5° W–16.5° E). Arrival time was influenced by the breeding latitude, the breeding longitude, and the local temperature, without any apparent influence of sex. The time of arrival at the breeding grounds was 6 days later for every degree increase in latitude and 2 days later for every degree increase in longitude. Lesser Kestrels from southwestern colonies achieve earlier arrival than conspecifics breeding at northeastern colonies, mostly due to earlier departure from their non-breeding grounds. While we found some effects of travel speed and stopover duration on arrival date, the latter was primarily influenced by food abundance and wind conditions en route. The large effect of departure date from West Africa on arrival date, relative to the more moderate influence of stopover duration close to breeding colonies, supports the idea that geographically uneven climate change may negatively affect fitness via ecological mismatches in the breeding area.
Exploring the implicit meanings of ‘cultural diversity’: a critical conceptual analysis of commonly used approaches in medical education
Authors: Zanting Albertine , Frambach Janneke M. , Meershoek Agnes , Krumeich Anja
Published: September 2024

Existing approaches to cultural diversity in medical education may be implicitly based on different conceptualisations of culture. Research has demonstrated that such interpretations matter to practices and people concerned. We therefore sought to identify the different conceptualisations espoused by these approaches and investigated their implications for education. We critically reviewed 52 articles from eight top medical education journals and subjected these to a conceptual analysis. Via open coding, we looked for references to approaches, their objectives, implicit notions of culture, and to implementation practices. We iteratively developed themes from the collected findings. We identified several approaches to cultural diversity teaching that used four different ways to conceptualise cultural diversity: culture as ‘fixed patient characteristic’, as ‘multiple fixed characteristics’, as ‘dynamic outcome impacting social interactions’, and as ‘power dynamics’. We discussed the assumptions underlying these different notions, and reflected upon limitations and implications for educational practice. The notion of ‘cultural diversity’ challenges learners’ communication skills, touches upon inherent inequalities and impacts how the field constructs knowledge. This study adds insights into how inherent inequalities in biomedical knowledge construction are rooted in methodological, ontological, and epistemological principles. Although these insights carry laborious implications for educational implementation, educators can learn from first initiatives, such as: standardly include information on patients’ multiple identities and lived experiences in case descriptions, stimulate more reflection on teachers’ and students’ own values and hierarchical position, acknowledge Western epistemological hegemony, explicitly include literature from diverse sources, and monitor diversity-integrated topics in the curriculum.
Cosmic strings and gravitational waves
Authors: Sousa Lara
Published: September 2024

Cosmic string networks are expected to generate a characteristic stochastic gravitational wave background that may be within the reach of current and upcoming gravitational wave detectors. A detection of this spectrum would provide invaluable information about the physics of the early universe, as it would allow us to probe the sequence of phase transitions that happened in the distant past. Here, I review the emission of gravitational waves by Nambu–Goto cosmic strings—thin cosmic strings that couple strongly to gravity only—and by superconducting strings—strings that carry electromagnetic currents. A comparison between the stochastic gravitational wave background predicted in these two very distinct string-forming scenarios reveals that this spectrum may have signatures that may allows us to discriminate between them observationally. The stochastic gravitational wave background generated by cosmic string networks may then enable us to uncover not only the energy-scale of the string-forming phase transition, but the underlying particle physics scenario as well.
UAV Routing for Enhancing the Performance of a Classifier-in-the-loop
Authors: Kumar Deepak Prakash , Rajbhandari Pranav , McGuire Loy , Darbha Swaroop , Sofge Donald
Published: September 2024

Some human-machine systems are designed so that machines (robots) gather and deliver data to remotely located operators (humans) through an interface to aid them in classification. The performance of a human as a (binary) classifier-in-the-loop is characterized by probabilities of correctly classifying objects (or points of interest) as a true target or a false target. These two probabilities depend on the time spent collecting information at a point of interest (POI), known as dwell time. The information gain associated with collecting information at a POI is then a function of dwell time and discounted by the revisit time, i.e., the duration between consecutive revisits to the same POI, to ensure that the vehicle covers all POIs in a timely manner. The objective of the routing problem for classification is to route the vehicles optimally, which is a discrete problem, and determine the optimal dwell time at each POI, which is a continuous optimization problem, to maximize the total discounted information gain while visiting every POI at least once. Due to the coupled discrete and continuous problem, which makes the problem hard to solve, we make a simplifying assumption that the information gain is discounted exponentially by the revisit time; this assumption enables one to decouple the problem of routing with the problem of determining optimal dwell time at each POI for a single vehicle problem. For the multi-vehicle problem, since the problem involves task partitioning between vehicles in addition to routing and dwell time computation, we provide a fast heuristic to obtain high-quality feasible solutions.
Flexible Superconducting Wiring for Integration with Low-Temperature Detector and Readout Fabrication
Authors: O’Neil Galen , Swetz Daniel , Doriese Randy , Schmidt Dan , Vale Leila , Weber Joel , Singh Robinjeet , Keller Mark , Vissers Michael , Morgan Kelsey , Mates John , Roy Avirup , Ullom Joel
Published: September 2024

We present a method of creating high-density superconducting flexible wiring on flexible thin silicon substrates. The flexible wiring, called SOI flex, is created by depositing superconducting wiring on a silicon-on-insulator (SOI) wafer, selectively etching away the thicker silicon section handle layer, and bending the thinner silicon device layer. We show measurements of superconducting transition temperature and critical current for Mo, Nb, and Al on SOI flex. We discuss the expected advantages of SOI flex for low-temperature detector applications, as well as the role of stress and strain in bent silicon and niobium.
Fabrication of sol-gel derived homogeneously doped Er3+/Yb3+:SiO2 microspheres using laser melting
Authors: Chen Jie , Ma Jianxing , Black Charles M. , Shao Yuchen , Lei Jincheng , Xiao Hai , Peng Fei
Published: September 2024

Silica microspheres have been demonstrated as the optical micro-cavity for laser generation based on whispering-gallery modes (WGM). They can achieve a high-quality factor (Q) within a tiny volume. Traditionally, complex processes are needed to process a coating containing photoluminescent elements, with enough thickness and uniformity, for laser generation. We developed a novel sol-gel fabrication method of Er3+/Yb3+doped silica microspheres with a homogeneous doping concentration over the entire microsphere volume. The sol-gel precursors were doped with 1–2 mol% Er3+ and/or Yb3+. The viscosity of the precursor was controlled at around 4000 cP, and gel fibers can be conveniently drawn from the precursor. After firing at 1000 °C for 1 h, transparent fibers with diameters of 40–180 µm were obtained. The fiber tips were quickly melted into microspheres using a CO2 laser. The diameters of microspheres were determined by the fiber diameter and laser parameters, such as laser power and irradiation time duration. Typically, the microspheres had diameters between 90 to 160 µm. The emission spectrum under 357 nm and 527 nm excitation showed characteristic Er3+ emission peaks, that match the literature well. The UV-VIS spectra confirm the photoluminescence results and showed both Er3+ and Yb3+ characteristic absorptions. The optical behaviors of the microspheres indicate that the Er3+ and Yb3+ were well dispersed in the silica matrix and the microspheres had typical optical activities of Er3+/Yb3+ glasses.

Graphical Abstract
Patches, Patchworks, and Epsilon Terms: A Neo-Carnapian Account of Theoretical Terms in Science
Authors: De Benedetto Matteo , La Rosa Elio
Published: September 2024

In the last decades, scientific laws and concepts have been increasingly conceptualized as a patchwork of contextual and indeterminate entities. These patchwork constructions are sometimes claimed to be incompatible with traditional views of scientific theories and concepts, but it is difficult to assess such claims due to the informal character of these approaches. In this paper, we will show that patchwork approaches pose a new problem of theoretical terms. Specifically, we will demonstrate how a toy example of a patchwork structure might trivialize Carnap’s semantics for theoretical terms based upon epsilon calculus. However, as we will see, this new problem of theoretical terms can be given a neo-Carnapian solution, by generalizing Carnap’s account of theoretical terms in such a way that it applies also to patchwork constructions. Our neo-Carnapian approach to theoretical terms will also demonstrate that the analytic/synthetic distinction is meaningful even for patchwork structures.