bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring repeatability of dynamic contrast-enhanced MRI biomarkers improves evaluation of biological response to radiotherapy in lung cancer
Authors: Sridharan Nivetha , Salem Ahmed , Little Ross A. , Tariq Maira , Cheung Susan , Dubec Michael J. , Faivre-Finn Corinne , Parker Geoffrey J. M. , Porta Nuria , O’Connor James P. B.
Published: August 2024

Objectives

To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response.

Materials and methods

A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (K
trans), extravascular extracellular space volume fraction (v
e) and plasma volume fraction (v
p) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation.

Results

Fourteen patients (mean age, 67 years +/− 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for v
p, which was 42.44%. Cohort-level changes were significant for K
trans and v
e (p < 0.001) and tumour volume (p = 0.002). K
trans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in v
e despite the cohort-level change.

Conclusion

Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies.

Clinical relevance statement

Dynamic contrast-enhanced magnetic resonance imaging biomarkers K
trans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics.

Key Points

Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility.

Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable.

Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.
Pattern-based forecasting enhances the prediction skill of European heatwaves into the sub-seasonal range
Authors: Rouges Emmanuel , Ferranti Laura , Kantz Holger , Pappenberger Florian
Published: August 2024

The prediction of European heatwaves at the subseasonal range is of key importance to mitigate their impact. This study builds on previous work which identifies five main European heatwave types based on their atmospheric circulation patterns (CPs). These CPs are potential predictors of heatwaves, as these patterns are connected with a high probability of 2-meter temperature exceeding the 90th percentile. Therefore, the aim of this study is to use these patterns to construct a pattern-based forecast method. The skill of this method to forecast extreme warm temperatures is then assessed and compared with the direct grid-point based forecast (using the direct 2-meter temperature forecast of the model). The extended (or subseasonal) range reforecast data from the European Centre for Medium-Range Weather Forecasts (ECMWF) is used for the skill evaluation. Firstly, the skill of the extended range model is assessed in predicting CPs. The pattern-based methodology is then compared with the direct prediction of extreme warm temperatures. The results show that the pattern-based methodology has a low skill at the short to medium range compared to the direct method, however it maintains skill for longer lead times, extending the forecast skill horizon significantly by up to six days over key heatwave regions. This improvement is localized over regions with the highest conditional probability of extreme warm temperatures. Furthermore, the prediction skill of 4-day periods of high temperatures using CPs lasting at least five days is also assessed. A similar improvement in forecast skill horizon is observed but the improvement is more modest and even more localized. This methodology provides skilful forecast at longer lead times to the end of the medium range and into the subseasonal range, which would be beneficial for early warnings of European heatwaves and therefore support the timely implementation of mitigation plans.
Short-term complication rates of open reduction and plate fixation and intramedullary nailing in the treatment of humeral shaft fractures: a propensity score matched analysis
Authors: Whitaker Sarah , Cole Sarah , O’Neill Conor , Satalich James , Schmidt R. Cole , Vanderbeck Jennifer
Published: August 2024

Introduction

This is a retrospective cohort study designed to compare short-term postoperative complication rates between closed humeral shaft fractures treated by open reduction and internal fixation (ORIF) versus intramedullary nailing (IMN), as well as secondary independent risk factors for adverse outcomes.

Materials and methods

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried using CPT codes to identify patients that underwent an open reduction and plate fixation or intramedullary nailing procedure for a closed humeral shaft fracture from 2010 to 2021. Cohorts were matched using propensity scores to account for demographic differences and rates of complications were compared between the two groups.

Results

From the database, a total of 4,222 patients were identified who met inclusion criteria, with 3,326 and 896 undergoing ORIF and IMN respectively. After propensity score matching, 866 of the nearest-neighbor matches were included in each cohort for a total of 1,732 patients in the final analysis. The rate of any adverse event (AAE) was significantly higher in the ORIF cohort (16.3%) than the IMN cohort (12.1%, p = 0.01). The ORIF group had higher rates of postoperative transfusion (p = 0.002), return to OR (p = 0.005), and surgical site infection (SSI, p = 0.03). After multivariate analysis, ASA class 4, increasing age, increasing operative time, and history of bleeding disorder were found to increase the risk of AAE in both ORIF and IMN patients.

Conclusions

While prior studies have claimed higher complication rates in IMN patients, this study found a significantly higher short-term risk of AAE in ORIF patients when compared in matched cohorts. However, individual 30-day complication rates do not differ significantly between procedures, and both have been shown to be safe and effective tools in the management of humeral shaft fractures.
Risk factors for developing intra-abdominal abscess following appendicectomy for acute appendicitis: a retrospective cohort study
Authors: Mao B P , Collins G , Ayeni F E , Vagg D J
Published: August 2024

Background

Laparoscopic appendicectomy is commonly performed in Australia for treatment of acute appendicitis. Intra-abdominal abscess (IAA) is a potential complication following appendicectomy for acute appendicitis. Risk factors for developing post-operative IAA remain controversial and poorly defined. Laparoscopic washout may be performed for patients who develop complication(s) including IAA. The aim of this study was to define risk factors for both the development of IAA and identify patients who may require laparoscopic washout following appendicectomy.

Methods

Data were obtained from 423 patients who underwent laparoscopic appendicectomy over a five-year period (2012–2017). Clinical (fever, haemodynamics, examination findings), biochemical (white cell count, neutrophil count, C-reactive protein, bilirubin, albumin), radiological (CT free fluid), and operative factors (inflammation, suppuration, free-fluid, perforation, histopathology) collected in the pre-, peri-, and post-operative period(s) were analysed.

Results

23 (5.4%) patients developed post-operative IAA. Duration of intravenous antibiotics was significantly longer in patients who developed IAA and in those who required laparoscopic washout (p < 0.0001). C-reactive protein (CRP) on admission (p < 0.05) and appendiceal perforation (p = 0.0005) were significantly higher in patients who either developed IAA or needed laparoscopic washout. No clinical or radiological finding predicted either the development of IAA or need for laparoscopic washout.

Conclusion

Elevated CRP on admission may predict the development of post-operative IAA formation or the need for laparoscopic washout post-appendicectomy. Prolonged post-operative antibiotic use appears independent of the development of IAA as well as the need for laparoscopic washout. These data highlight the need for clear guidelines on peri-operative antibiotic use following appendicectomy.
Lowering platelet-count threshold for transfusion in preterm neonates decreases the number of transfusions without increasing severe hemorrhage events
Authors: Billion Elodie , Ghattas Souad , Jarreau Pierre-Henri , Irmesi Roberta , Ndoudi Likoho Bellaure , Patkai Juliana , Zana-Taieb Elodie , Torchin Heloise
Published: August 2024

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm3. We conducted a before–after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm3 during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm3) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm3). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events.

Conclusions: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events.

What is Known:• A recent randomized trial suggested that restrictive platelet-count thresholds for platelet transfusion could be beneficial for preterm neonates.

What is New:• On lowering the platelet-count threshold for transfusion from 50,000 to 25,000/mm3, the number of transfusions significantly decreased without increasing severe hemorrhage events in a neonatal intensive care unit.
The Allen–Cahn equation with weakly critical random initial datum
Authors: Gabriel Simon , Rosati Tommaso , Zygouras Nikos
Published: August 2024

This work considers the two-dimensional Allen–Cahn equation $$\begin{aligned} \partial _t u = \frac{1}{2}\Delta u + \mathfrak {m}\, u -u^3, \quad u(0,x)= \eta (x), \qquad \forall (t,x) \in [0, \infty ) \times {\textbf {R}}^{2}, \end{aligned}$$

∂
t

u
=

1
2

Δ
u
+
m

u
-

u
3

,

u

(
0
,
x
)

=
η

(
x
)

,

∀

(
t
,
x
)

∈

[
0
,
∞
)

×

R

2

,

where the initial condition $$ \eta $$
η
is a two-dimensional white noise, which lies in the scaling critical space of initial data to the equation. In a weak coupling scaling, we establish a Gaussian limit with nontrivial size of fluctuations, thus casting the nonlinearity as marginally relevant. The result builds on a precise analysis of the Wild expansion of the solution and an understanding of the underlying stochastic and combinatorial structure. This gives rise to a representation for the limiting variance in terms of Butcher series associated to the solution of an ordinary differential equation.
The effect of ATLS/PHTLS spinal motion restriction protocol on the incidence of spinal cord injury, a nationwide database study
Authors: Kraai Tijmen W. , Groen Sylvester R. , Nawijn Femke , Panneman Martien J.M. , Hogervorst Mike , Brinke Joost G. Ten , Goslings J. Carel
Published: August 2024

Purpose

To study trends in incidence and outcome of patients with traumatic spinal cord injury (TSCI) in the Netherlands before, during and after implementation of the Advanced Trauma Life Support (ATLS®) and Pre-Hospital Trauma Life Support (PHTLS®)- Spinal Motion Restriction(SMR) protocol.

Methods

In an observational database we studied national hospital admission and emergency department databases to analyse incidence rates and outcome of traumatic spinal cord injury and spinal fractures in the emergency department and in admittances in The Netherlands between 1986 and 2021.

Results

A significant increase of 39% in TSCI in admitted patients with spinal fractures over the past 35 years (p < 0.001). This increase was especially prevalent in cervical spinal fractures (132%), while thoracic and lumbosacral spinal fractures showed a decrease in accompanied TSCI (64% and 88% respectively). The overall increase in spinal fractures was not significant. The duration of hospital admission decreased for spinal fractures without TSCI and with TSCI (66% and 56% respectively).

Conclusion

Since implementation of the SMR-protocol was aiming to limit TSCI in patients who suffered a spinal fracture, the increase in TSCI is an unexpected finding. Exact explanation for this increase is unclear and the contribution of the SMR-protocol is not fully understood due to confounders in the used datasets. Either way, the scientific evidence supporting this costly time- and labor-intensive SMR-protocol remains debated, along with evidence contradicting it. Therefore it stresses the need for clear, evidencebased reasoning for spinal immobilization according to ATLS, as this is currently lacking.
EPR at 80: Carotenoid Radical Cation Detection
Authors: Focsan A. Ligia , Kispert Lowell D.
Published: August 2024

Electron Paramagnetic Resonance (EPR) has proven to be a powerful research tool in the study of carotenoid radicals providing detailed information on their structure, stability, and biological functions. Previously published simultaneous electrochemical and EPR (SEEPR) and high-field/high-frequency (HFEPR) experiments in vitro performed by Kispert’s group and in collaboration with National High Magnetic Field Laboratory (NHMFL) for the HFEPR measurements, were extremely helpful in elucidating the structure of the carotenoid radical cation and obtaining EPR parameters for carotenoids that were further used in the literature for comparison with parameters obtained for in vivo experiments.
The effect of laser therapy for the treatment of dentin hypersensitivity on surface roughness and bacterial adhesion
Authors: Parlar Oz Ozge , Karagozoglu İrem , Kocer Ipek , Demırkol Nermin , Zer Yasemin
Published: August 2024

The aim of the study was to measure the degree of dentine surface roughness caused by five distinct lasers used to treat dentine hypersensitivity, as well as to evaluate the subsequent bacterial colonization on these irradiated surfaces. Sixty human maxillary premolar teeth without caries or restoration which were extracted for periodontal reasons were used in this study. Five different types of lasers were applied to the root dentin surface. Tested samples were divided into six groups of 10 samples each; control, diode (810 nm), diode (980 nm), Nd: YAG, Er: YAG, and Er, Cr: YSGG laser groups. The arithmetic mean of the surface roughness values (Ra) and the average roughness over a measurement area (Sa) were measured pre- and post-application using any of the laser types. Swab samples were then collected from the dentin surface. Following a 24-hour incubation period at 37 °C, the colony forming units were counted using a stereoscope. The results demonstrated a statistically significant difference in the surface roughness values pre- and post-application (Ra and Sa, respectively) in the Er, Cr: YSGG laser group (p = 0.037,p = 0.007). No significant difference was observed in the other groups (p > 0.05). There was no statistically significant difference in the number of bacterial colonies observed between the test and control groups. Diode and Nd: YAG lasers showed either a decrease or no change in surface roughness; however, the hard tissue lasers (Er: YAG, Er, Cr: YSGG) showed an increase. The Er: YAG and Nd: YAG laser groups exhibited decreased bacterial adhesion compared to the other groups.
Time value of informal care of people with alzheimer’s disease in Spain: a population-based analysis
Authors: C Vilaplana-Prieto , J Oliva-Moreno
Published: August 2024

The aims of this paper are to estimate the monetary value of informal care for people with Alzheimer’s disease (AD) in Spain, to compare results with those obtained in 2008 and to analyse the main determinants of the time of the value of informal care. The Survey on Disabilities, Autonomy and Dependency carried out in Spain in 2020/21 was used to obtain information about disabled individuals with AD and their informal caregivers. Assessment of informal care time was carried out using two alternative approaches: the replacement method, and the contingent valuation method (willingness to pay & willingness to accept). The number of people with AD residing in Spanish households and receiving informal care rose to more than 200,000, representing an increase of 43% compared with 2008. The average number of hours of informal care per week ranged from 86 to 101 h, with an estimated value of between €31,584 - €37,019 per year per caregiver (willingness to accept) or €71,653 - €83,984 per year (replacement). The annual total number of caregiving hours ranged between 896 and 1,061 million hours, representing between 0.52 and 0.62 of GDP in 2021 (willingness to accept) or 1.19–1.40 of GDP (replacement). The level of care needs plays a central role in explaining heterogeneity in estimates. These results should be taken into account by decision-makers for long-term care planning in the coming years.
Robust ROI Detection in Whole Slide Images Guided by Pathologists’ Viewing Patterns
Authors: Ghezloo Fatemeh , Chang Oliver H. , Knezevich Stevan R. , Shaw Kristin C. , Thigpen Kia Gianni , Reisch Lisa M. , Shapiro Linda G. , Elmore Joann G.
Published: August 2024

Deep learning techniques offer improvements in computer-aided diagnosis systems. However, acquiring image domain annotations is challenging due to the knowledge and commitment required of expert pathologists. Pathologists often identify regions in whole slide images with diagnostic relevance rather than examining the entire slide, with a positive correlation between the time spent on these critical image regions and diagnostic accuracy. In this paper, a heatmap is generated to represent pathologists’ viewing patterns during diagnosis and used to guide a deep learning architecture during training. The proposed system outperforms traditional approaches based on color and texture image characteristics, integrating pathologists’ domain expertise to enhance region of interest detection without needing individual case annotations. Evaluating our best model, a U-Net model with a pre-trained ResNet-18 encoder, on a skin biopsy whole slide image dataset for melanoma diagnosis, shows its potential in detecting regions of interest, surpassing conventional methods with an increase of 20%, 11%, 22%, and 12% in precision, recall, F1-score, and Intersection over Union, respectively. In a clinical evaluation, three dermatopathologists agreed on the model’s effectiveness in replicating pathologists’ diagnostic viewing behavior and accurately identifying critical regions. Finally, our study demonstrates that incorporating heatmaps as supplementary signals can enhance the performance of computer-aided diagnosis systems. Without the availability of eye tracking data, identifying precise focus areas is challenging, but our approach shows promise in assisting pathologists in improving diagnostic accuracy and efficiency, streamlining annotation processes, and aiding the training of new pathologists.
Image-Based Computational Fluid Dynamics to Compare Two Repair Techniques for Mitral Valve Prolapse
Authors: Bennati Lorenzo , Puppini Giovanni , Giambruno Vincenzo , Luciani Giovanni Battista , Vergara Christian
Published: August 2024

Objective 

The treatment of mitral valve prolapse involves two distinct repair techniques: chordal replacement (Neochordae technique) and leaflet resection (Resection technique). However, there is still a debate in the literature about which is the optimal one. In this context, we performed an image-based computational fluid dynamic study to evaluate blood dynamics in the two surgical techniques.

Methods 

We considered a healthy subject (H) and two patients (N and R) who underwent surgery for prolapse of the posterior leaflet and were operated with the Neochordae and Resection technique, respectively. Computational Fluid Dynamics (CFD) was employed with prescribed motion of the entire left heart coming from cine-MRI images, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method for managing valve dynamics. We created three different virtual scenarios where the operated mitral valves were inserted in the same left heart geometry of the healthy subject to study the differences attributed only to the two techniques.

Results 

We compared the three scenarios by quantitatively analyzing ventricular velocity patterns and pressures, transition to turbulence, and the ventricle ability to prevent thrombi formation. From these results, we found that the operative techniques affected the ventricular blood dynamics in different ways, with variations attributed to the reduced mobility of the Resection posterior leaflet. Specifically, the Resection technique resulted in turbulent forces, related with the risk of hemolysis formation, up to 640 Pa, while the other two scenarios exhibited a maximum of 240 Pa. Moreover, in correspondence of the ventricular apex, the Resection technique reduced the areas with low velocity to 15%, whereas the healthy case and the Neochordae case maintained these areas at 30 and 48%, respectively. Our findings suggest that the Neochordae technique developed a more physiological flow with respect to the Resection technique.

Conclusion

Resection technique gives rise to a different direction of the mitral jet during diastole increasing the ability to washout the ventricular apex preventing from thrombi formation, but at the same time it promotes turbulence formation that is associated with ventricular effort and risk of hemolysis.
Evidence generalization-based discounting method: assigning unreliable information to partial ignorance
Authors: Hu Qiying , Zhou Qianli , Li Zhen , Deng Yong , Cheong Kang Hao
Published: August 2024

Conflict management is an important topic when dealing with unreliable sources information fusion in Dempster–Shafer theory. Discounting unreliable bodies of evidence has proven to be effective to decrease conflict. Based on the generalization of belief functions, a new generalization-based discounting method is proposed. When resolving conflicts with the same degree, our method can realize less information loss in comparison with other discounting methods. By simulating the process of resolving conflicts of randomly generated bodies of evidence, using entropy measurements and binary conflict as evaluation index, we show our method’s rationality and superiority. Finally, the hyperparameters of the conflict metrics are generated and generalization-based discounting is applied to classify real-world datasets. The improved classification performance further illustrates the usefulness of the method.
Multiplex antibiotic susceptibility testing of urinary tract infections using an electrochemical lab-on-a-chip
Authors: Crane Benjamin , Iles Alex , Banks Craig E. , Rashid Mamun , Linton Patricia E. , Shaw Kirsty J.
Published: August 2024

Urinary tract infections (UTIs) represent the most prevalent type of outpatient infection, with significant adverse health and economic burdens. Current culture-based antibiotic susceptibility testing can take up to 72 h resulting in ineffective prescription of broad-spectrum antibiotics, poor clinical outcomes and development of further antibiotic resistance. We report an electrochemical lab-on-a-chip (LOC) for testing samples against seven clinically-relevant antibiotics. The LOC contained eight chambers, each housing an antibiotic-loaded hydrogel (cephalexin, ceftriaxone, colistin, gentamicin, piperacillin, trimethoprim, vancomycin) or antibiotic-free control, alongside a resazurin bulk-modified screen-printed electrode for electrochemical detection of metabolically active bacteria using differential pulse voltammetry. Antibiotic susceptibility in simulated UTI samples or donated human urine with either Escherichia coli or Klebsiella pneumoniae could be established within 85 min. Incorporating electrochemical detection onto a LOC provides an inexpensive, simple method for the sensitive determination of antibiotic susceptibility that is significantly faster than using a culture-based approach.
Can Good Information Prevent Misconduct? The Role of Organizational Epistemic Virtues for Ethical Behavior
Authors: Meyer Marco , Li Tong
Published: August 2024

This study explores epistemic virtue as a new lens to scrutinize organizational behavior. Organizational epistemic virtues are the qualities of organizations that support the creation, sharing, and retaining of knowledge. We study how well organizations handle information and if that can prevent organizational misconduct. We propose a theoretical framework to link epistemic virtue to the prevention of misconduct and test this model using data from 822 U.S. companies. These companies are scored on six epistemic virtues by analyzing over one million online employee reviews using natural language processing. We focus on the epistemic virtues of curiosity, epistemic beneficence, epistemic justice, epistemic integration, humility, and open-mindedness. We find that companies with these virtues engage in less corporate misconduct, measured in terms of the number of penalties imposed by government agencies. We also give practitioners a framework to assess the epistemic virtues of organizations.
Advances in the molecular biology of the solitary fibrous tumor and potential impact on clinical applications
Authors: Ren Chongmin , D’Amato Gina , Hornicek Francis J. , Tao Hao , Duan Zhenfeng
Published: August 2024

Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm. The current classification has merged SFT and hemangiopericytoma (HPC) into the same tumor entity, while the risk stratification models have been developed to compensate for clinical prediction. Typically, slow-growing and asymptomatic, SFT can occur in various anatomical sites, most commonly in the pleura. Histologically, SFT consists of spindle to oval cells with minimal patterned growth, surrounded by stromal collagen and unique vascular patterns. Molecularly, SFT is defined by the fusion of NGFI-A-binding protein 2 (NAB2) and signal transducer and activator of transcription 6 (STAT6) genes as NAB2-STAT6. This fusion transforms NAB2 into a transcriptional activator, activating early growth response 1 (EGR1) and contributing to SFT pathogenesis and development. There are several fusion variants of NAB2-STAT6 in tumor tissues, with the most frequent ones being NAB2ex4-STAT6ex2 and NAB2ex6-STAT6ex16/ex17. Diagnostic methods play a crucial role in SFT clinical practice and basic research, including RT-PCR, next-generation sequencing (NGS), FISH, immunohistochemistry (IHC), and Western blot analysis, each with distinct capabilities and limitations. Traditional treatment strategies of SFT encompass surgical resection, radiation therapy, and chemotherapy, while emerging management regimes include antiangiogenic agents, immunotherapy, RNA-targeting technologies, and potential targeted drugs. This review provides an update on SFT's clinical and molecular aspects, diagnostic methods, and potential therapies.
Improving Teacher Health and Well-Being: Mixed Methods Outcomes Evaluation of the Be Well Care Well Program
Authors: Moreland Angela , Schnake Kerrie , Lessard Laura , Davies Faraday , Prowell Katelyn , Hubel Grace S.
Published: August 2024

Early Care and Education (ECE) providers earn low wages, have limited access to employer sponsored health insurance, and are at higher risk for poor health (Lessard, 2020). Evidence shows that poor ECE teacher physical and mental health is associated with decreased ability to provide quality care for young children (Esquivel et al., 2016). One potential way to improve ECE teacher health is through workplace wellness interventions. Through longitudinal surveys and qualitative interviews with ECE providers, we found that, over the course of a year, ECE providers who participated in Be Well Care Well (BWCW), a 12-month wellness program designed specifically for ECEproviders, improved significantly on measures of personal strength and resilience, worker stress, job satisfaction, motivation towards health, and engagement in physical activity, which was supported by interviews conducted by a subset of teachers. Providers’ physical activity was specifically associated with the amount of time they reported engaging in components of the BWCW intervention. Compelling data was also gathered about the experience of children in the care of ECE providers who participated in BWCW. Findings show that after participating in BWCW, teachers’ interactions with the children in their care proactively facilitate healthy social and emotional development. This provides initial evidence that BWCW is a promising approach for improving the lives of ECE providers and the quality of care they provide to young children.
Treating heart failure by targeting the vagus nerve
Authors: Gentile Francesco , Orlando Giulia , Montuoro Sabrina , Ferrari Chen Yu Fu , Macefield Vaughan , Passino Claudio , Giannoni Alberto , Emdin Michele
Published: August 2024

Increased sympathetic and reduced parasympathetic nerve activity is associated with disease progression and poor outcomes in patients with chronic heart failure. The demonstration that markers of autonomic imbalance and vagal dysfunction, such as reduced heart rate variability and baroreflex sensitivity, hold prognostic value in patients with chronic heart failure despite modern therapies encourages the research for neuromodulation strategies targeting the vagus nerve. However, the approaches tested so far have yielded inconclusive results. This review aims to summarize the current knowledge about the role of the parasympathetic nervous system in chronic heart failure, describing the pathophysiological background, the methods of assessment, and the rationale, limits, and future perspectives of parasympathetic stimulation either by drugs or bioelectronic devices.
DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans
Authors: Azizoglu Zehra Busra , Babayeva Royala , Haskologlu Zehra Sule , Acar Mustafa Burak , Ayaz-Guner Serife , Okus Fatma Zehra , Alsavaf Mohammad Bilal , Can Salim , Basaran Kemal Erdem , Canatan Mehmed Fatih , Ozcan Alper , Erkmen Hasret , Leblebici Can Berk , Yilmaz Ebru , Karakukcu Musa , Kose Mehmet , Canoz Ozlem , Özen Ahmet , Karakoc-Aydiner Elif , Ceylaner Serdar , Gümüş Gülsüm , Per Huseyin , Gumus Hakan , Canatan Halit , Ozcan Servet , Dogu Figen , Ikinciogullari Aydan , Unal Ekrem , Baris Safa , Eken Ahmet
Published: August 2024

Loss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown. Mutations were identified by whole exome sequencing. T-cell immunophenotyping, proliferation, migration, cytokine signaling, survival, and NK cell cytotoxicity were studied via flow cytometry-based assays, confocal microscopy, and real-time qPCR. CD4+ T cell proteome was analyzed by mass spectrometry. p.R351* and p.R322*variants led to a significant reduction in the DIAPH1 mRNA and protein levels. DIAPH1-deficient T cells showed proliferation, activation, as well as TCR-mediated signaling defects. DIAPH1-deficient PBMCs also displayed impaired transwell migration, defective STAT5 phosphorylation in response to IL-2, IL-7 and IL-15. In vitro generation/expansion of Treg cells from naïve T cells was significantly reduced. shRNA-mediated silencing of DIAPH1 in Jurkat cells reduced DIAPH1 protein level and inhibited T cell proliferation and IL-2/STAT5 axis. Additionally, NK cells from patients had diminished cytotoxic activity, function and IL-2/STAT5 axis. Lastly, DIAPH1-deficient patients’ peripheral blood contained dramatically reduced numbers of all helper ILC subsets. DIAPH1 deficiency results in major functional defects in T, NK cells and helper ILCs underlining the critical role of formin DIAPH1 in the biology of those cell subsets.

Graphical Abstract
Semaglutide treatment of hypothalamic obesity – a real-life data study
Authors: Svendstrup Mathilde , Rasmussen Aase Krogh , Kistorp Caroline , Klose Marianne , Andreassen Mikkel
Published: August 2024

Purpose

Patients with tumors involving the hypothalamic region are at high risk of developing morbid obesity due to disturbances in the appetite regulative nuclei in hypothalamus. We evaluated the effect of the Glucagon-like peptide 1 (GLP-1) analogue semaglutide in patients with hypothalamic obesity.

Methods

We recorded weight changes from real-time data before and after treatment with semaglutide in patients with hypothalamic obesity from our outpatient clinic at the Department of Endocrinology at Rigshospitalet, from September 2020 to November 2023.

Results

A total of 26 patients were included in this study (15 females, median age at initiation of semaglutide was 52 (range 18–65) years). Body mass index (BMI) at initial diagnosis was median 25 (range 20–38) kg/m2 while BMI at initiation of semaglutide was median 38 (range 28–58) kg/m2. All but one patient lost weight during semaglutide treatment with a mean weight loss of 13.4 kg (95% CI 10.3–16.5 kg, p = < 0.001) after 12 months corresponding to a loss in BMI of 4.4 kg/m2 (95% CI 3.4–5.4 kg/m2, p = < 0.001) with a median dosage of semaglutide of 1.6 (range 0.5–2.5) mg. Fifteen patients (58%) lost more than 10% and two patients (8%) lost more than 20% of initial body weight, respectively.

Conclusion

Treatment with semaglutide shows promising results in reducing body weight in patients with acquired hypothalamic obesity. Whether the weight reduction remains stable after long time follow-up needs further investigation.
Real effects of capitalized research and development expenditures: a leading indicator for future innovation performance?
Authors: Herb Wolfgang , Lotze Maria , Schultze Wolfgang , Sandner Philipp
Published: August 2024

This paper analyzes the relationship between capitalized Research and Development (R&D) expenditures under IFRS and innovation performance measured by patent data. Under IFRS, development expenditures are capitalized when the success of an R&D investment is highly likely. Hence, such capitalization could be a leading indicator for future innovation performance. We analyze this question based on a hand-collected sample of R&D capitalization data under IFRS and patent data from the European Patent Office’s Worldwide Patent Statistical Database. We find that the capitalization rate of R&D is positively related to future patent applications and citations as measures of future innovation performance. We also find a positive association with measures of future financial performance. The results imply that the rate of R&D capitalization is informative and can be considered a leading indicator for future innovation performance.
Adapting and Validating a Survey to Assess Host Communities Support for Migration
Authors: Botello Jhon G. , Palacio Katherine , Frydenlund Erika , Llinás Humberto , Padilla Jose J.
Published: August 2024

Migration presents challenges to receiving communities, as it tests their ability to respond to unexpected expenditures and social stresses. Evaluating the local impact of rapid and substantial migration flows is difficult due to the absence of a validated instrument for assessing community support for migration. Our study adapted and validated a Support for Migration Assessment survey (SMA) based on Social Exchange Theory (SET). The validation of the SMA contributes in two significant ways. First, it establishes an instrument that enables the assessment of support for migration (SFM) by considering community-level factors: trust in institutions (TII), overall community satisfaction (OCS), and perceived negative impact on infrastructure (INF). Second, the SMA extends SET to the context of migration to assess support by a receiving community. We recruited 333 survey participants between January and July 2022 using proportional stratified random sampling to measure locals’ perceptions toward the Venezuelan migrant population in Barranquilla, Colombia. The internal consistency of the factors was calculated with Cronbach’s alpha (α) and omega coefficient (ω), resulting in α = 0.88, ω = 0.89 for TII; α = 0.90, ω = 0.92 for OCS; α = 0.87, ω = 0.88 for INF; and α = 0.84, ω = 0.86 for SFM. After conducting exploratory and confirmatory factor analysis, construct validity was confirmed based on the model’s goodness of fit (CFI = 0.939, TLI = 0.935, RMSEA = 0.062, SRMR = 0.076). The adapted survey demonstrates adequacy in assessing perceived community support for migration.
How to Distinguish Non-Inflammatory from Inflammatory Pain in RA?
Authors: Khot Sharmila , Tackley George , Choy Ernest
Published: August 2024

Purpose of the Review

Managing non-inflammatory pain in rheumatoid arthritis (RA) can be a huge burden for the rheumatologist. Pain that persists despite optimal RA treatment is extremely challenging for patient and physician alike. Here, we outline the latest research relevant to distinguishing non-inflammatory from inflammatory RA pain and review the current understanding of its neurobiology and management.

Recent Findings

Nociplastic pain is a recently introduced term by the international pain community. Its definition encompasses the non-inflammatory pain of RA and describes pain that is not driven by inflamed joints or compromised nerves, but that is instead driven by a functional reorganisation of the central nervous system (CNS).

Insights from all areas of nociplastic pain research, including fibromyalgia, support a personalised pain management approach for non-inflammatory pain of RA, with evidence-based guidelines favouring use of non-pharmacological interventions. Future developments include novel CNS targeting pharmacotherapeutic approaches to treat nociplastic pain.
Odontological, pathological and contextual patterns of the Late Glacial human tooth assemblage from Level E at Balma Guilanyà (south-eastern Pyrenees, Iberian Peninsula)
Authors: Arenas del Amo Sergio , López José López , Martínez-Moreno Jorge , Torcal Rafael Mora
Published: August 2024

Balma Guilanyà shelter (north-eastern Iberian Peninsula, Spain) contains a stratigraphic sequence spanning the Late Upper Palaeolithic to early Holocene. During excavations from 1992 to 2008, seventeen human teeth, and several cranial and postcranial bones were unearthed from the layer E (Late Glacial). In this contribution, we report new unpublished dental remains, which add to the previously dental assemblage from level E at Balma Guilanyà. The purpose of this article is to provide an updated description of the morphology of this material, as well as an analysis of the MNI, age at death, and the presence of several pathologies, approaching it from a holistic vision of the teeth assemblage from the Late Glacial. This review has made it possible to diagnose a dens invaginatus, the persistence of a deciduous upper central incisor (possibly caused by a mesiodens), teeth with cavities, deep occlusal pits conducive to cariogenesis, an atypical lower second molar and several molars with fused roots. This pattern of dental anomalies attributed to a single individual (Individual III) is not usual among hunter-gatherers who lived 13,000 years ago. Likewise, the presence of enamel hypoplasia in several teeth allows us to discuss this aetiology. These new identifiers derived from the review of the dental assemblage from Balma Guilanyà can help extend our knowledge of dental pathologies and stress markers in Late Glacial Homo sapiens populations in Western Europe. Additionally, an accumulation of teeth attributed to two individuals found in a confined area of the excavation was examined. Potential scenarios were assessed regarding the arrangement of this grouping, which presents challenges in attributing its formation to post-depositional or natural processes. This pattern would have the potential to elucidate behavioural funerary practices among late glacial hunter-gatherer populations.
On the influence of conventional and automated market makers on market quality in cryptoeconomic systems
Authors: Kirste Daniel , Poddey Alexander , Kannengießer Niclas , Sunyaev Ali
Published: August 2024

Decentralized exchanges (DEXs) have become an alternative to centralized exchanges (CEXs) for trading assets in the form of tokens in cryptoeconomic system markets. The emergence of DEXs is strongly driven by their potential to tackle challenges for market quality originating from CEXs by design, such as opaque market-making strategies and centralization of power. However, it remains unclear to what extent DEXs can enhance market quality compared to CEXs. A core reason for this is the lack of an analysis concept for investigating influences of market makers, including automated market makers (AMMs) used in DEXs and conventional market makers used in CEXs, on market quality in cryptoeconomic systems. To better understand influences of market makers on market quality in cryptoeconomic systems, we developed an analysis concept based on our formal price model grounded in established concepts of market microstructure. We demonstrate the usefulness of the analysis concept by examining conventional market makers on CEXs (i.e., Binance and Coinbase) and automated market makers (AMMs) on DEXs (i.e., Uniswap v2 and Uniswap v3). The main purpose of this work is to support the analysis of influences of different market makers on market quality in cryptoeconomic systems. This is useful to better understand how cryptoeconomic systems can ensure high market quality and safeguard market participants, when issuing tokens.
A two-step procedure for damage detection in beam structures with incomplete mode shapes
Authors: Modesti Martina , Gentilini Cristina , Palermo Antonio , Reynders Edwin , Lombaert Geert
Published: August 2024

In this work, we present a two-step procedure for damage identification in beam structures exploiting modal curvature changes. The reconstruction of modal curvatures requires the knowledge of several mode shape components along the analyzed beam. This requirement is practically unachievable when mode shapes are identified via vibration-based monitoring using a limited number of accelerometers. To overcome this limitation, in the first step of the proposed procedure, we perform a mode shape expansion employing a reduced subset of measured modal components. The remaining measured components are used as control parameters to formulate a first hypothesis on damage location and extent. For this purpose, the expansion procedure is performed considering a number of possible damage scenarios, consisting of a location and a severity (loss of stiffness) of the damage. Using the Total modal assurance criterion (TMAC), we select the expanded modes with the highest degree of correspondence with the measured control components. These expanded modes are thus associated with a first guess of the damage location and severity. In the next step, this initial damage identification is verified through the computation of a modal curvature-based damage index. If the curvature-based damage identification confirms the previous identification, the damage location and extent are determined. The procedure can be easily extended to identify multiple simultaneously damaged elements. The approach is numerically validated using a benchmark beam modeled via finite elements, investigating the influence of different parameters such as noise, position of the control components and beam discretization on the identification success rate. Finally, the procedure is tested on two experimental specimens: a steel beam, with three different damage configurations and a concrete beam progressively damaged with multiple damage locations.
An inertial extragradient method for solving strongly pseudomonotone equilibrium problems in Hilbert spaces
Authors: Le Thi Thanh Hai , Duong Viet Thong , Phan Tu Vuong
Published: August 2024

In this work, we propose an inertial extragradient method for solving strongly pseudomonotone equilibrium problems utilizing a novel self-adaptive stepsize approach. We establish the R-linear convergence rate of the proposed method without prior knowledge of the Lipschitz-type constants associated with the bifunction. We also discuss the application of the obtained results to variational inequality problems involving strongly pseudomonotone and Lipschitz continuous mapping. Numerical examples are presented to illustrate the efficiency of the proposed method.
Compensation mechanics application of NPR anchor cable to large deformation tunnel in soft rock
Authors: Li Yong , Huo Shusen , He Manchao , Tao Zhigang
Published: August 2024

NPR anchor cable is a new type of support material with negative Poisson's ratio effect, which is widely used in mine support because of its superb compensating mechanical effect. In order to study more deeply the support effect of NPR anchor cable in soft rock large deformation tunnel, indoor test, numerical simulation and field monitoring were used to study the strong weathering carbonaceous slate tunnel in Min County. The study shows that NPR anchor cable has extraordinary compensating mechanical behavior for soft rock large deformation tunnel, which can control the deformation of tunnel surrounding rock below 300 mm and keep the constant resistance value around 350 kN, which has obvious effect on the control of broken rock. To provide a basis for other research on support for large deformation tunnels in soft rock.