bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of a Deep Learning–Based Contrast-Boosting Algorithm to Low-Dose Computed Tomography Pulmonary Angiography With Reduced Iodine Load
Authors: Park Minsu , Hwang Minhee , Lee Ji Won , Kim Kun-Il , Ahn Chulkyun , Suh Young Ju , Jeong Yeon Joo
Published: October 2024

Objective

The aim of this study was to assess the effectiveness of a deep learning–based image contrast-boosting algorithm by enhancing the image quality of low-dose computed tomography pulmonary angiography at reduced iodine load.

Methods

This study included 179 patients who underwent low-dose computed tomography pulmonary angiography with a reduced iodine load using 64 mL of a 1:1 mixture of contrast medium from January 1 to June 30, 2023. For single-energy computed tomography, the noise index was set at 15.4 to maintain a CTDIvol of <2 mGy at 80 kVp, and for dual-energy computed tomography, fast kV-switching between 80 and 140 kVp was employed with a fixed tube current of 145 mA. Images were reconstructed by 50% adaptive statistical iterative reconstruction (AR50) and a commercially available deep learning image reconstruction (TrueFidelity) package at a high strength level (TFH). In addition, AR50 images were further processed using a deep learning–based contrast-boosting algorithm (AR50-CB). Quantitative and qualitative image qualities and numbers of involved vessels with thrombus at each pulmonary artery level were compared in the 3 image types using the Friedman test and Wilcoxon signed rank test.

Results

Five hundred thirty-seven reconstructed image datasets of 179 patients were analyzed. Quantitative image analysis showed AR50-CB (30.8 ± 10.0 and 28.1 ± 9.6, respectively) had significantly higher signal-to-noise ratio and contrast-to-noise ratio values than AR50 (20.2 ± 6.2 and 17.8 ± 6.2, respectively) (P < 0.001) or TFH (28.3 ± 8.3 and 24.9 ± 8.1, respectively) (P < 0.001). Qualitative image analysis showed that contrast enhancement and noise scores of AR50-CB were significantly greater than those of AR50 (P < 0.001) and that AR50-CB enhancement scores were significantly higher than TFH enhancement scores (P < 0.001). The number of subsegmental pulmonary arteries affected by thrombus detected was significantly greater for AR50-CB (30 for AR50, 30 for TFH, and 55 for AR50-CB, P < 0.001).

Conclusions

The use of a deep learning–based contrast-boosting algorithm improved image quality in terms of signal-to-noise ratio and contrast-to-noise ratio values and the detection of thrombi in subsegmental pulmonary arteries.
Clinical Outcomes and Applicability of Serratus Anterior Muscle Flap With Split Thickness Skin Graft in Thin Resurfacing Reconstructive Surgeries
Authors: Ha Yooseok , Kim Youn Hwan
Published: October 2024

This retrospective study evaluates the efficacy of the serratus anterior muscle (SAm) free flap combined with a split thickness skin graft (STSG) for thin resurfacing in reconstructive surgery, presenting an alternative to pure skin perforator flaps. It analyzes 14 SAm free flap procedures performed between January 2015 and December 2023. The study cohort comprised 5 women and 9 men, aged 31–80 years, addressing defects caused by infection, malignancy, burn, and trauma, located in various body parts.

The study involves harvesting the SAm flap while focusing on anatomical features such as the distinct direction of muscle fibers and the surface location of the vascular pedicle for efficient dissection. It emphasizes the anatomical advantages of the SAm flap, such as robust vascular supply, controlled flap thickness, and preservation of the long thoracic nerve, making it suitable for a range of surgical needs. Complications included STSG loss, partial necrosis, and infection, all managed effectively. Postoperative shoulder function assessment showed no significant impairment.

Results demonstrated the successful application of the SAm flap in all cases, with an average flap dimension of 38.21 cm2 and pedicle length of 7.3 cm. The average operation time was 122.1 minutes. The study underscores the SAm flap's adaptability, versatility, and minimal donor site morbidity.

It concludes that the SAm flap, in conjunction with STSG, is a viable alternative for thin resurfacing in reconstructive surgery. However, limitations such as the small sample size and procedural variability suggest the need for further research to fully establish the flap's potential in diverse surgical contexts.
One-Stage Surgical Resection and Functional Reconstruction for Upper Limb Soft Tissue Sarcoma
Authors: Gatto Arianna , Cavalli Erica M. , Stucchi Sara , Giacomini Giorgio , Belingheri Michael , Radaelli Stefano , Gronchi Alessandro , Marchesi Andrea
Published: October 2024

Background

Currently, the gold standard of treatment for extremity soft tissue sarcoma (STS) is limb-sparing surgery. When the upper extremity is involved, the functional outcome is frequently poor. A 1-step resection and functional reconstruction would be advisable to obtain a fast recovery. Our study aims at retrospectively analyzing our case series of immediate nerves and tendons reconstructions of the upper limb after STS resection, while combining a review of the literature.

Methods

A retrospective review was conducted on a consecutive series of patients who underwent an immediate functional reconstruction after STS resection of the upper limb between 2015 and 2022 among the IRCCS Foundation “Istituto Nazionale dei Tumori.” The Disabilities of the Arm, Shoulder and Hand (DASH) score was considered the primary outcome. The obtained DASH scores were compared through groups that underwent different reconstructive procedures. The literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) criteria among 3 databases (PubMed, EMBASE, and Cochrane) using the search parameters “(((upper extremity) OR (upper limb)) AND (functional reconstruction) AND (soft tissue sarcoma).”

Results

Between 2015 and 2022, 52 patients required a functional reconstruction. The mean follow-up time was 49.63 months. The DASH score analysis reported a mean value of 44.1 ± 26.7. A statistically significant difference was found between groups who underwent different reconstruction techniques, whereas no difference was found regarding exposure to neoadjuvant radiation therapy. The literature review reported few articles focusing on immediate functional reconstruction after STS resection, and only 6 articles were included in the review.

Conclusions

Our review aimed at reporting our case series of immediate functional reconstructions after STS of the upper extremity, which is currently the most substantial one reported in literature to set an effective baseline for further studies in the field.
Assessing the Readability of Online English and Spanish Resources for Polydactyly and Syndactyly
Authors: Shin Ashley , Paidisetty Praneet S. , Chivukula Surya , Wang Leonard Kuan-Pei , Chen Wendy
Published: October 2024

Introduction

Online patient education materials (PEMs) that are difficult to read disproportionately affect patients with low health literacy and educational attainment. Patients may not be fully informed or empowered to engage meaningfully with providers and advocate for their goals. We aim to assess the readability of online PEMs regarding polydactyly and syndactyly.

Methods

Google was used to query “polydactyly” and “syndactyly” in English and Spanish. The first 50 results were categorized into institutional (government, medical school, teaching hospital), noninstitutional (private practice, blog), and academic (journal articles, book chapters). Readability scores were generated using the Simple Measure of Gobbledygook and Spanish Simple Measure of Gobbledygook scales.

Results

All polydactyly PEMs and >95% of syndactyly PEMs exceeded the National Institutes of Health recommended 6th-grade reading level. Altogether, English PEMs had an average reading level of a university freshman and Spanish PEMs had an average reading level of nearly a high school sophomore. For both diagnoses, English PEMs were harder to read than Spanish PEMs overall and when compared across the 3 categories between the 2 languages. Generally, noninstitutional PEMs were more difficult to read than their institutional counterparts.

Conclusions

To improve patient education, health literacy, and language equity, online resources for polydactyly and syndactyly should be written at the 6th-grade level. Currently, these PEMs are too advanced, which can make accessing, understanding, and pursuing healthcare decisions more challenging. Understanding health conditions and information is crucial to empower patients, regardless of literacy.
The Role of Tissue Expansion Before Baclofen Pump Insertion in the Pediatric Population
Authors: Atkinson Connor , Rawicki Barry , Low Nelson
Published: October 2024

Background

Tissue expansion is a well-established technique for soft tissue reconstruction in the pediatric population. We present a case series of this technique to create a safe pocket for baclofen pump insertion to minimize risk of complications including pump migration, extrusion, wound dehiscence and infection.

Methods

A case series of 3 pediatric patients undergoing tissue expansion prior to baclofen pump insertion at a single center in Melbourne. The expansion procedure was performed by senior surgeon N Low in all cases, and patients followed up 6 months after expander-pump exchange. The study was conducted over a 4-year period 2019 to 2023.

Results

We suffered 2 minor complications with the tissue expansion process including cellulitis and pump deflation. Neither complication precluded further tissue expansion nor led to premature removal of the expander. All patients proceeded to safely complete expander-pump exchange. One patient suffered a small (6 mL) abdominal seroma associated with pump insertion, which required no intervention. All patients have had a successful outcome 6 months after pump insertion.

Conclusions

We describe a reliable and reproducible approach in creating a safe abdominal wall pocket to better accommodate baclofen pump insertion. Our series has overcome the imbalance between device size and abdominal wall pocket, now offering an alternative approach to achieve the safe delivery of intrathecal baclofen in the pediatric population.
Archetypal Analysis of Kidney Allograft Biopsies Using Next-generation Sequencing Technology
Authors: Cortes Garcia Esteban , Giarraputo Alessia , Racapé Maud , Goutaudier Valentin , Ursule-Dufait Cindy , de la Grange Pierre , Letourneur Franck , Raynaud Marc , Couderau Clément , Mezine Fariza , Dagobert Jessie , Bestard Oriol , Moreso Francesc , Villard Jean , Halleck Fabian , Giral Magali , Brouard Sophie , Danger Richard , Gourraud Pierre-Antoine , Rabant Marion , Couzi Lionel , Le Quintrec Moglie , Kamar Nassim , Morelon Emmanuel , Vrtovsnik François , Taupin Jean-Luc , Snanoudj Renaud , Legendre Christophe , Anglicheau Dany , Budde Klemens , Lefaucheur Carmen , Loupy Alexandre , Aubert Olivier
Published: October 2024

Background.

In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes.

Methods.

We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers. Differentially expressed genes were determined for 11 Banff lesions. An ElasticNet model was used for feature selection, and 4 machine learning classifiers were trained to predict the probability of presence of the lesions. NGS-based classifiers were used in an unsupervised archetypal analysis to different archetypes. The association of the archetypes with allograft survival was assessed using the iBox risk prediction score.

Results.

The ElasticNet feature selection reduced the number of the genes from a range of 859–10 830 to a range of 52–867 genes. NGS-based classifiers demonstrated robust performances (precision-recall area under the curves 0.708–0.980) in predicting the Banff lesions. Archetypal analysis revealed 8 distinct phenotypes, each characterized by distinct clinical, immunological, and histological features. Although the archetypes confirmed the well-defined Banff rejection phenotypes for T cell–mediated rejection and antibody-mediated rejection, equivocal histologic antibody-mediated rejection, and borderline diagnoses were reclassified into different archetypes based on their molecular signatures. The 8 NGS-based archetypes displayed distinct allograft survival profiles with incremental graft loss rates between archetypes, ranging from 90% to 56% rates 7 y after evaluation (P < 0.0001).

Conclusions.

Using molecular phenotyping, 8 archetypes were identified. These NGS-based archetypes might improve disease characterization, reclassify ambiguous Banff diagnoses, and enable patient-specific risk stratification.
Normothermic Ex Vivo Perfusion Before Transplantation of the Kidney (NEXT-Kidney): A Single-center, Nonrandomized Feasibility Study
Authors: Hameed Ahmer M. , Wang Zane , Yoon Peter , Boroumand Farzaneh , Singla Animesh , Roberston Paul , Gaspi Renan , Zhang Chris , Laurence Jerome , Nahm Christopher , Yao Jinna , Yuen Lawrence , Lee Taina , Teixeira-Pinto Armando , Hawthorne Wayne J. , Rogers Natasha M. , Wong Germaine , Pleass Henry C.
Published: October 2024

Background.

There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys.

Methods.

In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP.

Results.

Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); one kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P = 0.046) was observed. There were no differences in the eGFR slopes between the two groups over time (P = 0.254).

Conclusions.

NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.
Unravelling a diversity of cellular structures and aggregation dynamics during the early development of
Myxococcus xanthus
Authors: Rivera-Yoshida Natsuko , Arzola Alejandro V. , Benítez Mariana
Published: October 2024

Aggregation underlies the collective dynamics of a diversity of organisms, enabling the formation of complex structures and emergent behaviours on interaction with the environment. Cellular aggregation constitutes one of the routes to collective motility and multicellular development.
Myxococcus xanthus
, a social bacterium, is a valuable model for studying the aggregative path to multicellularity, a major transition in the evolutionary history of life. While the collective developmental behaviour of
M. xanthus
has been largely studied in high cellular densities, there is a lack of understanding at low-density conditions that can be ecologically relevant. In this work, we study the early stages of emergent collective behaviour of
M. xanthus
under nutrient-poor and low-density conditions, uncovering the formation of diverse cellular structures with different shapes and sizes, ranging from individual cells to networks comprising thousands of cells. We study their motility patterns and their prevalence along development and discuss their cross-scale role on the population’s exploratory dynamics. This work contributes to understanding key, yet largely understudied, aspects in the early stages of multicellular development in myxobacteria, shedding light on the dynamics underlying aggregative processes in this and other taxa and study systems.
Weighting of sensory cues reflect changing patterns of visual investment during ecological divergence in
Heliconius
butterflies
Authors: Borrero José , Mogollon Perez Elisa , Wright Daniel Shane , Lozano-Urrego Daniela , Rueda-Muñoz Geraldine , Pardo-Diaz Carolina , Salazar Camilo , Montgomery Stephen H. , Merrill Richard M.
Published: October 2024

Integrating information across sensory modalities enables animals to orchestrate a wide range of complex behaviours. The relative importance placed on one sensory modality over another reflects the reliability of cues in a particular environment and corresponding differences in neural investment. As populations diverge across environmental gradients, the reliability of sensory cues may shift, favouring divergence in neural investment and the weight given to different sensory modalities. During their divergence across closed-forest and forest-edge habitats, closely related butterflies
Heliconius cydno
and
Heliconius melpomene
evolved distinct brain morphologies, with the former investing more in vision. Quantitative genetic analyses suggest that selection drove these changes, but their behavioural consequences remain uncertain. We hypothesized that divergent neural investment may alter sensory weighting. We trained individuals in an associative learning experiment using multimodal colour and odour cues. When positively rewarded stimuli were presented in conflict, i.e. pairing positively trained colour with negatively trained odour and
vice versa
,
H. cydno
favoured visual cues more strongly than
H. melpomene
. Hence, differences in sensory weighting may evolve early during divergence and are predicted by patterns of neural investment. These findings, alongside other examples, imply that differences in sensory weighting stem from divergent investment as adaptations to local sensory environments.
Uncertainties in exposure predictions arising from point measurements of carbon dioxide in classroom environments
Authors: Vouriot Carolanne V. M. , van Reeuwijk Maarten , Burridge Henry C.
Published: October 2024

Predictions of airborne infection risk can be made based on the fraction of rebreathed air inferred from point measurements of carbon dioxide (CO

⁣
2

). We investigate the extent to which environmental factors, particularly spatial variations due to the ventilation provision, affect the uncertainty in these predictions. Spatial variations are expected to be especially problematic in naturally ventilated spaces, which include the majority of classrooms in the UK. An idealized classroom, broadly representative of the physics of (buoyancy-driven) displacement ventilation, is examined using computational fluid dynamics, with different ventilation configurations. Passive tracers are used to model both the CO

⁣
2

generated by all 32 occupants and the breath of a single infectious individual (located in nine different regions). The distribution of infected breath is shown to depend strongly on the distance from the release location but is also affected by the pattern of the ventilating flow, including the presence of stagnating regions. However, far-field exposure predictions based on single point measurements of CO

⁣
2

within the breathing zone are shown to rarely differ from the actual exposure to infected breath by more than a factor of two—we argue this uncertainty is small compared with other uncertainties inherent in modelling airborne infection risk.
Energy barriers govern catheter herniation during endovascular procedures: a 2.5D vascular flow model analysis
Authors: Qiu Michael Y. , Suskin Charles B. , Zayed Mohamed A. , Genin Guy M. , Osbun Joshua W.
Published: October 2024

Endovascular procedures rely on navigating guidewires, catheters and other devices through tortuous vasculature to treat disease. A critical challenge in these procedures is catheter herniation, in which the device deviates from its intended path, often irrecoverably. To elucidate the mechanics of herniation, we developed a physical flow model of the aortic arch that enables direct measurement of device curvature during experimentally simulated neuroendovascular procedures conducted from an upper arterial access. Combined with measurements of initial, unstressed device shapes and flexural rigidities, the method enables the experimental estimation of the device bending energies during these simulated procedures. Characteristic energy profiles revealed distinct stages in both herniation and successful navigation, governed by the interplay between device properties and vascular anatomy. A deterministic progression from successful navigation to herniation was identified, with catheter systems following paths determined by measurable energy barriers. Increasing guidewire stiffness or decreasing catheter stiffness reduced the energy barrier for successful navigation while increasing that for herniation. This framework enables the prediction of endovascular herniation risk and offers unique insight into improved device design and clinical decision-making.
A brain-wide solute transport model of the glymphatic system
Authors: Quirk Keelin , Boster Kimberly A. S. , Tithof Jeffrey , Kelley Douglas H.
Published: October 2024

Brain waste is largely cleared via diffusion and advection in cerebrospinal fluid (CSF). CSF flows through a pathway referred to as the glymphatic system, which is also being targeted for delivering drugs to the brain. Despite the importance of solute transport, no brain-wide models for predicting clearance and delivery through perivascular pathways and adjacent parenchyma existed. We devised such a model by upgrading an existing model of CSF flow in the mouse brain to additionally solve advection–diffusion equations, thereby estimating solute transport. We simulated steady-state transport of 3 kDa dextran injected proximal to the perivascular space (PVS) of the middle cerebral artery, mimicking
in vivo
experiments. We performed a sensitivity analysis of 11 biological properties of PVSs and brain parenchyma by repeatedly simulating solute transport with varying parameter values. Parameter combinations that led to a large total pressure gradient, poor CSF perfusion or a steep solute gradient were deemed unrealistic. Solute concentrations in parenchyma were most sensitive to changes in pial PVS size, as this parameter linearly affects volume flow rates. We also found that realistic transport requires both highly permeable penetrating PVSs and high-resistance parenchyma. This study highlights the potential of brain-wide models to provide insights into solute transport processes.
Subtle frequency matching reveals resonant phenomenon in the flight of Odonata
Authors: Aracheloff C. , Garrouste R. , Nel A. , Godoy-Diana R. , Thiria B.
Published: October 2024

In this work, we investigate the connection between the flight flapping frequency and the intrinsic wing properties in Odonata (dragonflies and damselflies). For such large flying insect species, it has been noted that the wingbeat frequency is significantly lower than the structural resonance of the wing itself. However, the structural resonance mechanism is often evoked in the literature for flying and swimming animals as a means to increase locomotion performance. Here, we show that the flight of Odonata is based on a nonlinear mechanism that strongly depends on the wingbeat amplitude. For large flapping amplitudes (as observed in natural flight), the resonant frequency of the wings decreases with respect to its value at low amplitudes to eventually match the wingbeat frequency used in flight. By means of this nonlinear resonance, Odonata keep a strong wing stiffness while benefiting from a passive energy-saving mechanism based on the dynamic softening of the wing.
Dysregulation of locus-specific repetitive elements in TCGA pan-cancers
Authors: Wang Chao , Liang Chun
Published: October 2024

Understanding the role of repetitive elements (REs) in cancer development is crucial for identifying novel biomarkers and therapeutic targets. This study investigated the locus-specific dysregulation of REs, including differential expression and methylation of REs, across 12 TCGA cancer types stratified by their genomic context (i.e., genic and intergenic REs). We found uniquely dysregulated genic REs co-regulated with their corresponding transcripts and associated with distinct biological functions in different cancer types. Uniquely dysregulated intergenic REs were identified in each cancer type and used to cluster different sample types. Recurrently dysregulated REs were identified in several cancer types, with genes associated with up-regulated genic REs involved in cell cycle processes and those associated with down-regulated REs involved in the extracellular matrix. Interestingly, 4 out of 5 REs consistently down-regulated in all 12 cancer types were located in the intronic region of the TMEM252, a recently discovered tumor suppressor gene. TMEM252 expression was also down-regulated in 10 of 12 cancer types, suggesting its potential importance across a wide range of cancer types. With the corresponding DNA methylation array data, we found a higher prevalence of hypo-methylated REs in most cancer types (10 out of 12). Despite the slight overlaps between differentially expressed REs and differentially methylated REs, we showed that methylation of locus-specific REs negatively correlates with their expression in some cancer types.
Paracrine regulations of IFN-γ secreting CD4+T cells by lumican and biglycan are protective in allergic contact dermatitis
Authors: Maiti George , Frikeche Jihane , Loomis Cynthia , Chakravarti Shukti
Published: October 2024

The extracellular matrix (ECM) is known to regulate innate immune cells but its role in T cell functions is poorly understood. Here, we show a protective role for ECM proteoglycans, lumican and biglycan in hapten-induced contact dermatitis that is achieved through limiting proinflammatory CD4+T cells. Lumican and biglycan-null mice develop significant inflammation with greater numbers of CD4+T cells in hapten-challenged ear pinnae, while their draining lymph nodes show increased T-bet-STAT1 signaling, Th1 commitment, and IFN-γ secreting CD4+T cell proliferation. Wild type mouse lymph node fibroblastic reticular cells secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells.In vitro, lumican and biglycan co-localize with LFA-1 on T cell surfaces, and all three proteoglycans suppress LFA-1 mediated T cell activation. Overall, this study elucidates a novel paracrine regulation of Th1 cells by ECM proteoglycans to limit inflammation and tissue damage.
A school-based cluster-randomized pragmatic trial to control dental caries using minimally invasive interventions
Authors: Ruff Ryan Richard , Gawande Aditi Ashish , Xu Qianhui , Barry Godín Tamarinda J.
Published: October 2024

Background

Evidence-based non-surgical interventions to halt the progression of dental caries, the most prevalent noncommunicable disease in the world, include atraumatic restorative treatment (ART) and silver diamine fluoride (SDF). Data are needed on their effectiveness when used in school caries prevention programs.

Methods

In this school-based, cluster-randomized pragmatic trial conducted from February 1, 2018 to June 1, 2023, 48 primary schools in New York City were randomly assigned to receive either silver diamine fluoride or atraumatic restorations for untreated caries on any mesial, occlusal, distal, buccal, and lingual surface of permanent molars, premolars, and primary molars. All children then received fluoride varnish. Children were treated by either dental hygienists, pediatric dentists, or medical nurses (SDF group only). Dental caries was diagnosed as any lesion scoring either 5 or 6 on the ICDAS scale. The primary outcome was the caries control rate.

Results

A total of 7418 children were enrolled in the trial, of which 1668 (861 in the SDF group, 807 in the ART group) presented with treatable dental caries and completed at least one follow-up observation. The total surface-level failure in the SDF group was 38.3%, compared to 45.5% in the ART group. There were 2167 failures observed in SDF participants over 1372 person-years, compared to 2116 ART failures over 1291 person-years, yielding an incidence rate ratio of 0.96 (95% CI = 0.86, 1.03). At the subject level, 45.5% of SDF recipients experienced at least one surface failure, compared to 53.3% of ART recipients. There were no significant differences in the risk of recurrent surface failure between treatments (HR = 0.92, 95% CI = 0.82, 1.04).

Conclusions

In this four-year pragmatic trial of school-based utilization of minimally invasive interventions for dental caries, similar control rates were observed in children receiving either SDF or ART. These results support the use of secondary preventive therapies for school dental programs.

Author roles

RRR conceptualization, formal analysis, methodology, funding acquisition, supervision, writing-original draft; AG: formal analysis; QX: formal analysis; TJBG: data curation, investigation.
Impact of Remote Monitoring on Clinical Outcomes in Defibrillator Patients During the COVID-19 Pandemic: An Interrupted Time Series Analysis
Authors: Chand Sandeep , Torres Barbara , Vickers David , Whitten Tara A , Mardell Andrew , Sumner Glen
Published: October 2024

Background

Remote monitoring (RM) has become the standard of care in many Cardiac Implantable Electronic Device (CIED) clinics across North America and Europe. Some clinics are even adopting an alert-based, RM-only strategy for select patients. However, it remains unclear whether RM, compared to usual non-remote care, impacts the total number of CIED clinic visits, emergency department visits, hospitalizations, and all-cause mortality. Because such outcomes and their relationship to RM may be magnified in the presence of a global COVID-19 pandemic, we aimed to perform an interrupted time series analysis to observe trends in these outcomes in response to the declaration of the COVID-19 pandemic in patients with implantable cardioverter-defibrillators (ICD).

Methods

In this retrospective study, we utilized existing electronic provincial databases maintained by Alberta Health Services (AHS) and Alberta Health (AH) to determine CIED visits, emergency room visits, cardiovascular (CV) hospitalizations, and all-cause mortality. We performed Interrupted Time Series (ITS) analysis to compare outcome trends in ICD-patients with and without RM in Alberta, both during the COVID-19 pandemic and the pre-pandemic period. We defined the time-period of the pandemic as March 17, 2020, to July 17, 2021. Pre-pandemic was defined as March 17, 2018, to March 16, 2020. We compared best model fits using the Akaike Information Criterion (AIC), selecting the model with the lowest AIC for each outcome. The best-fitting models were plotted. Outcomes between RM and non-RM groups were compared using regression models, with differences reported using 95% confidence intervals.

Results

The CIED population consisted of 6,183 ICD patients from March 17, 2018, to July 17, 2021. Of these, 2,989 (48.3%) had access to RM. Our study found that access to virtual consultations sharply increased at the onset of the pandemic in both cohorts, though this trend was significantly higher in the RM group. Conversely, a sharp decline in in-person visits was observed for RM patients. Compared to those without RM, patients with RM showed no significant differences in all-cause mortality, hospitalizations, or emergency room visits, and these trends were not impacted by the COVID-19 pandemic.

Conclusion

In ICD patients with and without RM, the number of virtual consultations increased while in-person visits decreased during the pandemic. However, no significant changes in the trends of cardiovascular hospitalizations, emergency room visits, or all-cause mortality were observed in either group during this period. This suggests that RM did not significantly impact key health outcomes for ICD-patients during the pandemic in Alberta.
A distinctive PI(4,5)P2compartment forms during entosis and related engulfment processes
Authors: Durgan Joanne , Sloan Katherine , Domart Marie-Charlotte , Collinson Lucy M , Florey Oliver
Published: October 2024

Entosis is a form of cell cannibalism prevalent in human tumours. During entosis, one live and viable epithelial cell is completely internalised by another, then housed inside a large, single-membrane, endolysosomal vacuole in the host cytosol. The composition and maturation of this specialised, macroendocytic compartment has not been fully defined, but ultimately, the inner cell is killed and digested by host lysosomes. Here, we investigate the molecular characteristics and maturation profile of the entotic vacuole. Like phagosomes and macropinosomes, this vacuole undergoes a series of phospholipid modifications, but its maturation profile bears distinctive dynamics. While PI(4,5)P2is lost rapidly during phagosome maturation, entosis yields an unusual, intracellular PI(4,5)P2-positive compartment, that can persist for hours, suggesting vacuole maturation is uncoupled from membrane scission. Loss of PI(4,5)P2is eventually triggered, a requisite step for lysosomal killing of the internalised cell. More broadly, PI(4,5)P2-positive vacuoles also form during T-cell engulfment by thymic nurse cells, dependent on ROCK activity, suggesting this distinctive compartment represents a shared feature of entosis-like cell engulfments.
Executive control can query hidden human memories
Authors: Zhao Chong , Fukuda Keisuke , Woodman Geoffrey F.
Published: October 2024

When we try to retrieve a representation from visual long-term memory there is a chance that we will fail to recall seeing it even though the memory is stored in our brain. Here we show that although mechanisms of explicit memory retrieval are sometimes unable to retrieve stored memories, that mechanisms of executive control can quickly query memory and determine if a representation is stored therein. Our findings suggest that the representations stored in human memory that cannot be accessed explicitly at that moment are nonetheless directly accessible by the brain’s higher level control mechanisms.
Hierarchical emergence of opponent coding in auditory belt cortex
Authors: Johnson Jeffrey S. , Niwa Mamiko , O’Connor Kevin N. , Malone Brian J. , Sutter Mitchell L.
Published: October 2024

We recorded from neurons in primary auditory cortex (A1) and middle-lateral belt area (ML) while rhesus macaques either discriminated amplitude-modulated noise (AM) from unmodulated noise or passively heard the same stimuli. We used several post-hoc pooling models to investigate the ability of auditory cortex to leverage population coding for AM detection. We find that pooled-response AM detection is better in the active condition than the passive condition, and better using rate-based coding than synchrony-based coding. Neurons can be segregated into two classes based on whether they increase (INC) or decrease (DEC) their firing rate in response to increasing modulation depth. In these samples, A1 had relatively fewer DEC neurons (26%) than ML (45%). When responses were pooled without segregating these classes, AM detection using rate-based coding was much better in A1 than in ML, but when pooling only INC neurons, AM detection in ML approached that found in A1. Pooling only DEC neurons resulted in impaired AM detection in both areas. To investigate the role of DEC neurons, we devised two pooling methods that opposed DEC and INC neurons – a direct subtractive method and a two-pool push-pull opponent method. Only the push-pull opponent method resulted in superior AM detection relative to indiscriminate pooling. In the active condition, the opponent method was superior to pooling only INC neurons during the late portion of the response in ML. These results suggest that the increasing prevalence of the DEC response type in ML can be leveraged by appropriate methods to improve AM detection.
Searching for heavy neutral leptons through exotic Higgs decays at the ILC
Authors: Thor Simon , Ishino Masaya , Tian Junping
Published: October 2024

In this study we investigate the feasibility of detecting heavy neutral leptons (Nd) through exotic Higgs decays at the proposed International Linear Collider (ILC), specifically in the channel of e+e−→qqH with H→νNd→νlW→νlqq. Analyses based on full detector simulations of the ILD are performed at the center-of-mass energy of 250 GeV for two different beam polarization schemes with a total integrated luminosity of 2  ab−1. A range of heavy neutral lepton masses between the Z boson and Higgs boson masses are studied. The 2σ significance reach for the joint branching ratio of BR(H→νNd)·BR(Nd→lW) is about 0.1%, nearly independent of the heavy neutral lepton masses, while the 5σ discovery is possible at a branching ratio of 0.3%. Interpreting these results in terms of constraints on the mixing parameters |ϵid|2 between SM neutrinos and the heavy neutral lepton, it is expected to have a factor of 10 improvement from current constraints.

Published by the American Physical Society
2024
Flowerlike Spreading of Micellar Films during Emulsion Drop Evaporation
Authors: Dong Teng , Kotsi Kristo , Xu Teke , Kobayashi Takeshi , Moriarty Alexander , Angeli Panagiota , McRobbie Ian , Striolo Alberto
Published: October 2024

We investigated the film spreading during the evaporation of submillimeter oil-in-water emulsion droplets on a solid surface, and observed a novel phenomenon where the film follows a two-layer spreading. In combination with the instability at the film front, the spreading front acquires a flowerlike pattern. The emergence of the two-layer structure is attributed to micelles within the oil film that yield an oscillating disjoining pressure. By considering both the slipping condition and the disjoining pressure, a scaling analysis is carried out that agrees well with the observed film spreading dynamics. The film spreading follows Tanner’s law initially, while it becomes faster at a later stage, where the film radius follows r∼t1/2 for weak slip and r∼t3/8 for strong slip conditions.

Published by the American Physical Society
2024
Discovering dynamics and parameters of nonlinear oscillatory and chaotic systems from partial observations
Authors: Stepaniants George , Hastewell Alasdair D. , Skinner Dominic J. , Totz Jan F. , Dunkel Jörn
Published: October 2024

Despite rapid progress in data acquisition techniques, many complex physical, chemical, and biological systems remain only partially observable, thus posing the challenge to identify valid theoretical models and estimate their parameters from an incomplete set of experimentally accessible time series. Here, we combine sensitivity methods and ranked-choice model selection to construct an automated hidden dynamics inference framework that can discover predictive nonlinear dynamical models for both observable and latent variables from noise-corrupted incomplete data in oscillatory and chaotic systems. After validating the framework for prototypical FitzHugh-Nagumo oscillations, we demonstrate its applicability to experimental data from squid neuron activity measurements and Belousov-Zhabotinsky reactions, as well as to the Lorenz system in the chaotic regime.

Published by the American Physical Society
2024
Human transforming growth factor β type I receptor in complex with kinase inhibitor SB505124
Authors: Rodriguez Buitrago Jhon A. , Landström Maréne , Wolf-Watz Magnus
Published: October 2024

The crystal structure of the intracellular domain of transforming growth factor β type I receptor (TβR1) in complex with the competitive inhibitor SB505124 is presented. The study provides insights into the structure and function of TβR1 in complex with SB505124, and as such offers molecular-level understanding of the inhibition of this critical signalling pathway. The potential of SB505124 as an avenue for therapy in cancer treatment is discussed on basis of the results.
Structure and stability of an apo thermophilic esterase that hydrolyzes polyhydroxybutyrate
Authors: Thomas Gwendell M. , Quirk Stephen , Lieberman Raquel L.
Published: October 2024

Pollution from plastics is a global problem that threatens the biosphere for a host of reasons, including the time scale that it takes for most plastics to degrade. Biodegradation is an ideal solution for remediating bioplastic waste as it does not require the high temperatures necessary for thermal degradation and does not introduce additional pollutants into the environment. Numerous organisms can scavenge for bioplastics, such as polylactic acid (PLA) or poly-(R)-hydroxybutyrate (PHB), which they can use as an energy source. Recently, a promiscuous PHBase from the thermophilic soil bacterium Lihuaxuella thermophila (LtPHBase) was identified. LtPHBase can accommodate many substrates, including PHB granules and films and PHB block copolymers, as well as the unrelated polymers polylactic acid (PLA) and polycaprolactone (PCL). LtPHBase uses the expected Ser–His–Asp catalytic triad for hydrolysis at an optimal enzyme activity near 70°C. Here, the 1.75 Å resolution crystal structure of apo LtPHBase is presented and its chemical stability is profiled. Knowledge of its substrate preferences was extended to different-sized PHB granules. It is shown that LtPHBase is highly resistant to unfolding, with barriers typical for thermophilic enzymes, and shows a preference for low-molecular-mass PHB granules. These insights have implications for the long-term potential of LtPHBase as an industrial PHB hydrolase and shed light on the evolutionary role that this enzyme plays in bacterial metabolism.
A structural model of customer experience in rural tourism
Authors: Hangui Shin-Ichi
Published: October 2024

Purpose

The purpose of this study is to explore the diversification of agricultural management for development in rural tourism. Excellent service has been standardized in response to society becoming more service-oriented. However, the structure of customer evaluations of services in rural tourism and their association with customer satisfaction and customer delight remain under-investigated.

Design/methodology/approach

This study used survey data from the general consumer population in Japan and used SERVPERF to measure service quality post-service, focusing on rural tourism experiences. The author analyzed the mechanisms of service quality leading to customer satisfaction and value co-creation, and value co-creation leading to customer delight and the effects of customer delight compared with those of customer satisfaction, using structural equation modeling.

Findings

Enhancing services strongly influenced excellent services, which were considered to generate customer delight. Compared with customer satisfaction, customer delight was inferred to lead to higher customer loyalty. The results indicated that core services generated customer satisfaction, whereas enhancing services generated customer delight.

Practical implications

These findings provide important insights into the provision of services in rural tourism, which is becoming prevalent in society, and contribute to the diversification of agricultural management.

Originality/value

The originality of this study lies in the adoption of rural tourism to diversify farm management, revealing its structure as an experience that leads to customer delight through value co-creation. The author showed that customer experience as a form of value co-creation in rural tourism can lead to the creation of excellent services.
How promotion mix helps sustain brand sales during market transitions: insights from the pharmaceutical industry
Authors: Chaudhuri Malika , Hirunyawipada Tanawat , Pan Yue
Published: October 2024

Purpose

Pharmaceutical marketers use detailing, sampling and direct-to-consumer advertising (DTCA) to promote a branded prescription drug (brand drug) to health-care professionals and consumers. These promotion mix elements help raise brand awareness, increase prescription likelihood and guard a product market against competing brand drugs. However, the extent to which these elements remain effective when a brand drug goes off patent and its marketing exclusivity expires, allowing low-price generics to enter the market, remains unclear. This study aims to explore the effectiveness of promotion mix elements before and after the market entry of a generic drug.

Design/methodology/approach

The authors collected and analyzed a panel data set of 41 brand drugs from 7 therapeutic classes between 2007 and 2014 (3,201 observations) using the two-stage control function approach to address potential endogeneity.

Findings

The effectiveness of promotion mix elements changes significantly, but not in a universally uniform way, during a market transition. Detailing and DTCA are increasingly effective after a brand drug’s generics enter the market. In contrast, sampling is more effective before the market transition. The positive effects of sampling on brand sales are stronger when the price of a brand drug is higher than the average price of its competing brands. Sampling also helps amplify the positive influences of detailing and DTCA on brand sales.

Research limitations/implications

This study shows that pharmaceutical promotion is not equally effective in the brand drug market with/without generic competitors. Detailing and DTCA are increasingly effective when generic competition intensifies. In contrast, the distribution of free drug samples is less effective after more generic drugs enter the market.

Practical implications

Incumbent brands’ promotion expenditures often drop dramatically when the expiration of their patents is near, a practice that likely continues after generics enter the market. Taking into consideration these industry norms and their findings, the authors suggest that promotional decisions during a market transition should not overly focus on cutting promotional expenditures across the board. Since a firm’s promotional expenditure tends to be expensive, factoring in information on the effectiveness of each promotion mix element helps marketers make well-informed strategic decisions on resource allocation during the transition from a market without generics to a market with generics.

Originality/value

Previous studies do not explicitly account for structural changes in the brand drug market over time. However, the expiration of patent and marketing exclusivity marks a transitional period in which a brand drug eventually competes with its generic counterparts. Given the criticality of such structural change, the authors examine brand drugs’ promotion effectiveness in the presence of their generic counterparts.