bluuebunny/crossref_metadata_2025 huggingface dataset:
Obese adolescents have higher risk for severe lower extremity fractures after falling
Authors: Gonzalez Nicolas , Nahmias Jeffry , Schubl Sebastian , Swentek Lourdes , Smith Brian R. , Nguyen Ninh T. , Grigorian Areg
Published: July 2023

Introduction

Reports vary on the impact of obesity on the incidence of lower extremity fractures after a fall. We hypothesized that obese adolescents (OA) presenting after a fall have a higher risk of any and severe lower extremity fractures compared to non-OAs.

Methods

A national database was queried for adolescents (12–17 years old) after a fall. Primary outcome included lower extremity fracture. Adolescents with a body mass index (BMI) ≥ 30 (OA) were compared to adolescents with a BMI < 30 (non-OA).

Results

From 20,264 falls, 2523 (12.5%) included OAs. Compared to non-OAs, the rate of any lower extremity fracture was higher for OAs (51.5% vs. 30.7%, p < 0.001). This remained true for lower extremity fractures at all locations (all p < 0.05). After adjusting for sex and age, associated risk for any lower extremity fracture (OR 2.41, CI 2.22–2.63, p < 0.001) and severe lower extremity fracture (OR 1.31, CI 1.15–1.49, p < 0.001) was higher for OAs. This remained true in subset analyses of ground level falls (GLF) and falls from height (FFH) (all p < 0.05).

Conclusions

Obesity significantly impacts adolescents’ risk of all types of lower extremity fractures after FFH or GLF. Hence, providers should have heightened awareness for possible lower extremity fractures in OAs.

Level of evidence

IV.
The role of family history of preterm delivery in the individual risk of spontaneous preterm delivery: a case–control study
Authors: Huri Mor , Strambi Noemi , Finazzi Marta , Manciucca Giulia , Catalano Giovanna , Seravalli Viola , Di Tommaso Mariarosaria
Published: July 2023

Purpose

To investigate the role of family history of preterm delivery (PTD) in the individual risk of spontaneous preterm delivery.

Methods

A retrospective case–control study was conducted on 354 patients who delivered between 2018 and 2020. 177 women who delivered preterm were matched with 177 controls who had full-term delivery. A questionnaire was administered to investigate the family history of PTD of both the patient and her partner. Cases and controls were matched for the anamnestic risk factors for PTD.

Results

Seventeen of 173 women (9.8%) in the PTD group reported being born preterm, compared to five of 169 women (2.9%) in the control group (p = 0.01), with an odds ratio (OR) of 3.57 (95% confidence interval, CI 1.29–9.92). Women who delivered preterm also reported more frequently having a sibling who was born preterm (12.4% vs. 4.2%, p = 0.01), with an OR of 3.18 (95% CI 1.31–7.7). No association was found between the partner’s family history of premature delivery and the patient’s risk of preterm delivery in the present pregnancy.

Conclusions

Pregnant patients who were born prematurely or who have siblings born preterm have an increased risk of preterm delivery in their own pregnancies. Assessment of female personal and family history of PTD should be used to identify women at risk of having a PTD in the present pregnancy.
Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial
Authors: van der Wielen Nicole , Daams Freek , Rosati Riccardo , Parise Paolo , Weitz Jürgen , Reissfelder Christoph , del Val Ismael Diez , Loureiro Carlos , Parada-González Purificación , Pintos-Martínez Elena , Vallejo Francisco Mateo , Achirica Carlos Medina , Sánchez-Pernaute Andrés , Campos Adriana Ruano , Bonavina Luigi , Asti Emanuele L. G. , Poza Alfredo Alonso , Gilsanz Carlos , Nilsson Magnus , Lindblad Mats , Gisbertz Suzanne S. , van Berge Henegouwen Mark I. , Romario Uberto Fumagalli , De Pascale Stefano , Akhtar Khurshid , Cuesta Miguel A. , van der Peet Donald L. , Straatman Jennifer
Published: July 2023

Background

Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy.

Methods

This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined.

Results

A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7–12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024).

Conclusion

No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.
Atlasblockade und Lig.-alare-Läsion – unterschätzt oder übertrieben?
Authors: Wölfle-Roos J.
Published: July 2023

Hintergrund

Störungen der Kopfgelenke – allen voran die Läsion der Ligg. alaria sowie die Blockierung des Atlas – werden insbesondere in der Laienpresse mit zahlreichen Symptomen assoziiert. Dementsprechend häufig werden Ärzte mit Patienten konfrontiert, die darin eine monokausale Ursache komplexer Beschwerden sehen und auf eine schnelle Lösung hoffen.

Fragestellung

Diese Übersicht stellt die aktuell verfügbare evidenzbasierte Literatur zu Atlasblockade und Lig.-alare-Läsion dar, um ihre Bedeutung differenziert einschätzen zu können.

Material und Methoden

Zusammenfassung und kritische Bewertung einer umfangreichen Literaturrecherche zu Diagnostik, Symptomatik und Therapie der Atlasblockade und Lig.-alare-Läsion.

Ergebnisse

Die Studienlage zeigt, dass Lig.-alare-Läsionen nur durch extreme Hochrasanztraumata entstehen und im MRT nur mit mäßiger Reliabilität nachgewiesen werden können. Da zudem in mehreren Studien kein Zusammenhang zwischen Symptomen und Auffälligkeiten im MRT gezeigt werden konnte, ist eine operative Stabilisierung der Kopfgelenke nicht indiziert. Die Vielzahl der Symptome bei Atlasblockade kann durch Konvergenz der Afferenzen C1–C3 auf verschiedene Hirnnervenkerne in neuroanatomischen Untersuchungen erklärt werden, der Zusammenhang ist jedoch bisher nicht bewiesen. Erste Studien zeigen eine hochsignifikante Besserung von zervikalen Schmerzen und Bewegungsumfang durch manualtherapeutische Lösung der Blockierung auch 6 Monate nach Behandlung.

Schlussfolgerung

Die Bedeutung der Lig.-alare-Läsion wurde in der Vergangenheit häufig überschätzt, diesbezüglich sollte dem Patienten ein differenziertes, multifaktorielles Krankheitsbild vermittelt werden. Die Atlasblockade ist in erster Linie als mögliche Ursache von Schmerzen und Bewegungseinschränkungen der Halswirbelsäule zu sehen, in diesem Kontext ist manuelle Therapie eine wirksame Option.
Paediatric spine injuries in the thoracic and lumbar spine—results of the German multicentre CHILDSPINE study
Authors: Herren Christian , Jarvers Jan-Sven , Jung Matthias K. , Blume Christian , Meinig Holger , Ruf Michael , Weiß Thomas , Rüther Hauke , Welk Thomas , Badke Andreas , Gonschorek Oliver , Heyde Christoph E. , Kandziora Frank , Knop Christian , Kobbe Philipp , Scholz Matti , Siekmann Holger , Spiegl Ulrich , Strohm Peter , Strüwind Christoph , Matschke Stefan , Disch Alexander C. , Kreinest Michael ,   Pediatric Spinal Trauma Working Group, Spine Section of the German Society for Orthopaedics, Trauma (DGOU)
Published: July 2023

Background

Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking.

Objectives

The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients.

Materials and Methods

A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0–6 years), age group II (7–9 years) and age group III (10–16 years).

Results

A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%).

Conclusions

The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed.
The economics of art history
Authors: Etro Federico G. , Galenson David W.
Published: July 2023

The study of art history has been traditionally focused on the description of artistic innovations, the role of the artists and the meaning of the artworks. It has often neglected the broader reasons why certain innovations took place in certain places, in specific times and in particular ways. We believe that the impact of institutional and economic factors has been critical in shaping the evolution of art history, and quantitative methods can be useful to improve our understanding of the history of figurative arts and the relationship between market structure and creativity.
Mild pyrolysis of cotton coated with graphene-like materials as a method to produce superhydrophobic and highly absorptive oil sorbents
Authors: Łukawski Damian , Widelicka Małgorzata , Martin Anna , Lisiecki Filip , Dudkowiak Alina
Published: July 2023

In recent years, hydrophobized cellulose-based materials have been proposed as oil spill sorbents. We investigate the possibility of using cheap, industrialgrade, graphene-like materials (GM), such as graphite flakes (GrF), exfoliated graphene nanoplatelets (xGNP) and microwave-plasma turbostratic graphene nanoplatelets (mGNP) as hydrophobic agents for naturally hydrophilic cotton. From among investigated GM, mGNP showed the highest ability to form superhydrophobic coating due to small flake size and small amount of impurities. Furthermore, we showed that mild pyrolysis not only makes cotton more hydrophobic, but also increases its sorption capacity towards organic solvents and oils. Pyrolyzed and coated with mGNP and xGNP cotton showed exceptional superhydrophobic properties and water contact angle equal 148° and 142°, respectively, besides the sorption capacity towards motor oil of 46 g/g and 51 g/g, respectively. What is more important, the price of graphene oxide used in previous research is still very high (approx. 100 $/g), while the price of xGNP and mGNP is 0.45 $/g, 7.3 $/g, respectively. This difference may be crucial for the implementation of graphene-based sorbents in the remediation of massive oil spill remediation.
Comparative Study of Using Displacement Influence Lines and Their Derivatives for Structural Damage Identification
Authors: Nady Hazem O. , Abdo Mohamed A.-B. , Kaiser Fayez
Published: July 2023

Structural damage identification has recently become one of the most important topics for engineering structures due to its benefits in enhancing safety, reducing life-cycle cost, and providing guidance for system construction and maintenance. This research studies the accuracy of using displacement influence lines (DIL) and their derivatives (first and second derivative) for detecting structural damage characteristics (location and severity). The study includes analytical and numerical studies to investigate the sensitivity of displacement influence lines and their derivatives (first and second derivative) as a main parameter for damage identification. The results illustrate that the method can locate and quantify damage in both simply supported and continuous beams without the need for an optimization algorithm. Although, for simply supported beam, the optimal location of the displacement measurement point is at the middle of span. While, for continuous beam, one displacement sensor at the middle of each span enables locating the damages reliably. The advantages and disadvantages of using this index are also discussed.
Higher-order error estimates for physics-informed neural networks approximating the primitive equations
Authors: Hu Ruimeng , Lin Quyuan , Raydan Alan , Tang Sui
Published: July 2023

Large-scale dynamics of the oceans and the atmosphere are governed by primitive equations (PEs). Due to the nonlinearity and nonlocality, the numerical study of the PEs is generally challenging. Neural networks have been shown to be a promising machine learning tool to tackle this challenge. In this work, we employ physics-informed neural networks (PINNs) to approximate the solutions to the PEs and study the error estimates. We first establish the higher-order regularity for the global solutions to the PEs with either full viscosity and diffusivity, or with only the horizontal ones. Such a result for the case with only the horizontal ones is new and required in the analysis under the PINNs framework. Then we prove the existence of two-layer tanh PINNs of which the corresponding training error can be arbitrarily small by taking the width of PINNs to be sufficiently wide, and the error between the true solution and its approximation can be arbitrarily small provided that the training error is small enough and the sample set is large enough. In particular, all the estimates are a priori, and our analysis includes higher-order (in spatial Sobolev norm) error estimates. Numerical results on prototype systems are presented to further illustrate the advantage of using the $$H^s$$

H
s

norm during the training.
Evaluating Inventory Management Policies of Platelets at Regional-Block Blood Centers in Japan
Authors: Ito Mari , Takashima Ryuta
Published: July 2023

With the decreasing proportion of blood donors to patients undergoing transfusion in Japan, optimal blood-product management is becoming increasingly important. Accordingly, we evaluate blood-product inventory management by means of mathematical optimization techniques. Using numerical analyses, we determine the effect of differences in the priority of collections on the units of discarded platelets, and demonstrate the impact of safety-stock levels upon these units. Our results suggest that policymakers should implement the following measures to minimize their disposal rates. Regional-block blood centers with significant fluctuations in demand must generate schedules that minimize both the units of platelets collected, and those interchanged to the maximal extent. Conversely, centers with smaller fluctuations in demand must generate schedules wherein a constant number of platelets is collected every day. Safety-stock levels should be revised in accordance with demands. Furthermore, our policy proposals should be able to mitigate social damage to the blood-supply chain over the course of the COVID-19 pandemic.
DNA methylation in the genesis, progress and prognosis of head and neck cancer
Authors: Guo Zijian , Liu Wenwen , Yang Yuhan , Zhang Shunhao , Li Chunjie , Yang Wenbin
Published: July 2023

Epigenetic alteration studies in cancer research have been progressing rapidly in recent years. DNA methylation, including DNA hypermethylation and DNA hypomethylation, is one of the main epigenetic alterations in head and neck cancer development. Here, we review recent advances in DNA methylation and factors affecting DNA methylation, including DNA methylation enzymes, HPV status and smoking and drinking habits, in the field of head and neck cancer occurrence, progression, metastasis, and prognosis, hoping to shed light on how DNA methylation interacts with head and neck cancer and lay a foundation for future prognosis prediction and therapy.
Sliding, vibrating and swinging droplets on an oscillating fibre
Authors: Poulain Stéphane , Carlson Andreas
Published: July 2023

We study experimentally the dynamics of a water droplet on a tilted and vertically oscillating rigid fibre. As we vary the frequency and amplitude of the oscillations the droplet transitions between different modes: harmonic pumping, subharmonic pumping, a combination of rocking and pumping modes, and a combination of pumping and swinging modes. We characterize these responses and report how they affect the sliding speed of the droplet along the fibre. The swinging mode is explained by a minimal model making an analogy between the droplet and a forced elastic pendulum.
Coupling the interactive effects of solar radiation, temperature and nitrogen on performance of transplanted rice
Authors: Garima  , Sandhu S. S. , Bons M. S. , Kaur Amarjeet , Prabhjyot-Kaur  , Kaur Simerjeet , Gill K. K. , Walia S. S.
Published: July 2023

Field experiment to assess the impact of radiation, temperature and foliar N application on rice was conducted. The treatments comprised of four sunlight levels, [control, 50% intensity during start to maximum tillering (R15–45), maximum tillering to booting (R46–75) and panicle emergence to maturity (R76–105) corresponding to 15–45, 46–75 and 76–105 days after transplanting] and 5 levels of foliar nitrogen [control, spray of 3% urea solution in water before (NB), midway (NM), afterwards (NA) and midway + afterwards (NMA) reduction in sunlight]. Results showed that leaf chlorophyll had an inverse relationship with radiation intensity. The R46–75 significantly reduced effective tillers (13.1–16.4%), R46–75 and R76–105 reduced grains/panicle (7.15–12.5%) as compared to control. NB produced significantly higher effective tillers (21.9–24.7%) and grains/panicle (12.2–12.9%) as compared to control. The reduction in sunlight and application of foliar nitrogen increased the minimum cooking time and decreased elongation ratio. Averaged over locations, R15–45, R46–75 and R76–105 decreased the yield significantly as compared to control by 9.29–11.3, 14.4–16.3 and 8.17–10.6%, respectively. The NB significantly increased grain yield as compared to control by 10.3% (Ludhiana) and 9.45% (Hoshiarpur). A decrease in maximum temperature (Tmax) by 2.85–5.70% (1–2°C) of 35.1°C, at 1416 μmol/m2/s of photosynthetically active radiation (PAR) increased rice productivity by 10.6–21.0%, while a similar decrease in PAR by 2.85–5.70% at a Tmax of 35.1°C, decreased the productivity by 2.05–4.10%. So, decrease in Tmax due to cloudy weather might have a positive influence while negative impact of deficit radiation may be mitigated by foliar application of 3% urea prior to/during the cloudy weather.
Investigation of the presence of atopy in children visiting the paediatric cardiology department due to chest pain
Authors: Duksal Fatma , Doğan Melih Timuçin
Published: July 2023

Background:

The cases of chest pain in children are usually not of cardiac origin.

Objectives:

To investigate asthma and other atopic diseases in children with chest pain not of cardiac origin.

Patients and Methods:

Children aged 6–18 years who were seen for chest pain were included in the study. Haematologic parameters, pulmonary function tests, and skin prick tests were performed. Atopic diseases and environmental factors were investigated.

Results:

The non-cardiac chest pain group (Group 1) included 88 children (female: 53.4%) with a mean age of 11.9 ± 3.4 years; the control group (Group 2) included 29 children (female: 53.8%) with a mean age of 11.4±2 years (p > 0.05). A family history of atopy (22.7%) and skin prick test positivity (28.4%) was more common in Group 1 than Group 2 (p = 0.006 and p = 0.017, respectively). The rate of presence of all environmental factors except stove use and mould was significantly higher in Group 1 (54.5%) than Group 2 (3.4%) (p < 0.001). Asthma was diagnosed in 44.3% and allergic rhinitis in 9.1% of patients in Group 1. Idiopathic chest pain, musculoskeletal system disorders, gastroesophageal reflux, and pneumonia were identified in 23.9%, 11.4%, 8%, and 3.4% of patients in Group 1, respectively.

Conclusions:

In this study, the most common cause of non-cardiac chest pain was asthma. The local prevalence of asthma is higher than normal, and this may have affected the results of this study. A detailed history and physical examination will accurately establish the cause of chest pain in most children.
Reversible complete atrioventricular block in a neonate with maternal anti-Sjögren’s syndrome-associated antibody: atypical phenotype of autoimmune congenital heart block
Authors: Saiki Hirofumi , Saito Kanchi , Sato Akira
Published: July 2023

The fetus of anti-Sjögren’s syndrome-associated antibody-positive mother developed complete atrioventricular block at 39 weeks of gestation and required urgent ventricular pacing after birth. Unexpectedly, the patient recovered from the atrioventricular block within a few days. Fraction analysis of maternal anti-Sjögren’s syndrome-associated antibody revealed positivity for isolated anti-Ro/SSA 60 kDa antibody, which is abnormal as most patients with complete atrioventricular block present with anti-Ro/SSA 52 kDa positivity, which may indicate a potentially atypical late and reversible manifestation of an autoimmune congenital atrioventricular block in this patient.
Combination of Vegetation Indices and SIF Can Better Track Phenological Metrics and Gross Primary Production
Authors: Zheng Chen , Wang Shaoqiang , Chen Jing M. , Chen Jinghua , Chen Bin , He Xinlei , Li Hui , Sun Leigang
Published: July 2023

Accurate phenological extraction is important for estimating carbon uptake in terrestrial ecosystems under climate change. The emergence of remotely sensed vegetation indices (VIs) and solar‐induced chlorophyll fluorescence (SIF) provides multiple approaches for extracting land surface phenology. However, there is lacking studies to track phenological metrics via multiple VIs and SIF. Therefore, the advantage of combining VIs and SIF to estimate more accurate phenology requires exploration. In this study, we combined the advantages of the normalized difference, enhanced, green‐red, near‐infrared reflectance vegetation indices from MCD43A4 data set, and SIF from CSIF data set to estimate hybrid phenology at 20 eddy flux sites in North America. Results showed that the hybrid phenology derived from the best‐performing start (SOS) and end (EOS) of the growing season among multiple VIs and SIF for each plant functional type and site were both more consistent with those derived from gross primary production (GPP). Specifically, the R2 of hybrid phenology increased by 0.11–0.4 (0.04–0.4) for SOS, 0.01–0.24 (0.09–0.22) for EOS, 0.01–0.7 (0.05–0.34) for the length of the growing season (LOS) based on Gaussian (logistic) method. Moreover, hybrid phenology can improve the explanation of the seasonal and annual variations in GPP. The explanatory power of hybrid phenology for GPP variations increased by 0.05–0.15 (0.02–0.23) for SOS, 0–0.36 (0.11–0.27) for EOS, 0.01–0.51 (0.03–0.4) for LOS, 0.04–0.18 (0.04–0.16) for LOS  seasonal GPP maximum based on Gaussian (logistic) method. These findings highlight the potential of combining high‐spatiotemporal structural and coarse‐spatiotemporal physiological vegetation indicators in tracking phenology and GPP.
Marine Dimethyl Sulfide Fluxes in the Yellow and East China Seas: Scenario Variation During the 1980s–2090s and Its Drivers
Authors: Shen Jia‐Wei , Zhao Liang , Wei Hao
Published: July 2023

Shedding light on the response of oceanic dimethyl sulfide flux (FDMS) on the sea shelf to multi‐pressures (intensified terrigenous nutrient inputs and climate change) is of great importance for regional aerosol budget. Here, we designed 4‐group experiments in scenario (the 1980s, 2010s, 2050s, and 2090s) for the Yellow and East China seas (YECS) based on climate change signals gained from CMIP6 and a 3‐dimension biophysical and geochemical model. Results show that the climatological annual mean of YECS's FDMS will rise from ∼6 μmol m−2 day−1 in the 1980s to >9 μmol m−2 day−1 in the 2090s under Shared Socioeconomic Pathway (SSP) 2−4.5/5−8.5 scenario, and with multi‐pressures, the FDMS peak in the 2050s is one season earlier when compared to that in the 1980s. The elevated terrigenous inputs affect the phytoplankton biomass and/or community on the inner shelf, leading to the rise and phenology change in the YECS's FDMS between the1980s and 2010s, while climate change has little impact. The influence of climate change on the FDMS is projected to increase in the 2050s; climate change will change seasonal pattern of the FDMS on the central part (middle and outer shelves) of East China Sea (CECS) under every SSP scenario. Thereinto, wind change exerts a crucial role, it will enhance summertime offshore transport and, accordingly, stimulate phytoplankton growth in summer changing the phenology of FDMS on the CECS.
SPRR1A is a key downstream effector of MiR-150 during both maladaptive cardiac remodeling in mice and human cardiac fibroblast activation
Authors: Kawaguchi Satoshi , Moukette Bruno , Sepúlveda Marisa N. , Hayasaka Taiki , Aonuma Tatsuya , Haskell Angela K. , Mah Jessica , Liangpunsakul Suthat , Tang Yaoliang , Conway Simon J. , Kim Il-man
Published: July 2023

MicroRNA-150 (miR-150) is conserved between rodents and humans, is significantly downregulated during heart failure (HF), and correlates with patient outcomes. We previously reported that miR-150 is protective during myocardial infarction (MI) in part by decreasing cardiomyocyte (CM) apoptosis and that proapoptotic small proline-rich protein 1a (Sprr1a) is a direct CM target of miR-150. We also showed that Sprr1a knockdown in mice improves cardiac dysfunction and fibrosis post-MI and that Sprr1a is upregulated in pathological mouse cardiac fibroblasts (CFs) from ischemic myocardium. However, the direct functional relationship between miR-150 and SPRR1A during both post-MI remodeling in mice and human CF (HCF) activation was not established. Here, using a novel miR-150 knockout;Sprr1a-hypomorphic (Sprr1ahypo/hypo) mouse model, we demonstrate that Sprr1a knockdown blunts adverse post-MI effects caused by miR-150 loss. Moreover, HCF studies reveal that SPRR1A is upregulated in hypoxia/reoxygenation-treated HCFs and is downregulated in HCFs exposed to the cardioprotective β-blocker carvedilol, which is inversely associated with miR-150 expression. Significantly, we show that the protective roles of miR-150 in HCFs are directly mediated by functional repression of profibrotic SPRR1A. These findings delineate a pivotal functional interaction between miR-150 and SPRR1A as a novel regulatory mechanism pertinent to CF activation and ischemic HF.
Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin
Authors: Erazo-Oliveras Alfredo , Muñoz-Vega Mónica , Mlih Mohamed , Thiriveedi Venkataramana , Salinas Michael L. , Rivera-Rodríguez Jaileen M. , Kim Eunjoo , Wright Rachel C. , Wang Xiaoli , Landrock Kerstin K. , Goldsby Jennifer S. , Mullens Destiny A. , Roper Jatin , Karpac Jason , Chapkin Robert S.
Published: July 2023

Although the role of the Wnt pathway in colon carcinogenesis has been described previously, it has been recently demonstrated that Wnt signaling originates from highly dynamic nano-assemblies at the plasma membrane. However, little is known regarding the role of oncogenic APC in reshaping Wnt nanodomains. This is noteworthy, because oncogenic APC does not act autonomously and requires activation of Wnt effectors upstream of APC to drive aberrant Wnt signaling. Here, we demonstrate the role of oncogenic APC in increasing plasma membrane free cholesterol and rigidity, thereby modulating Wnt signaling hubs. This results in an overactivation of Wnt signaling in the colon. Finally, using theDrosophilasterol auxotroph model, we demonstrate the unique ability of exogenous free cholesterol to disrupt plasma membrane homeostasis and drive Wnt signaling in a wildtype APC background. Collectively, these findings provide a link between oncogenic APC, loss of plasma membrane homeostasis and CRC development.
Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach
Authors: Hogan Alexandra B. , Doohan Patrick , Wu Sean L. , Mesa Daniela Olivera , Toor Jaspreet , Watson Oliver J. , Winskill Peter , Charles Giovanni , Barnsley Gregory , Riley Eleanor M. , Khoury David S. , Ferguson Neil M. , Ghani Azra C.
Published: July 2023

With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the ancestral vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.
Water nanolayer facilitated solitary-wave-like blisters in MoS2 thin films
Authors: Wang Enze , Xiong Zixin , Chen Zekun , Xin Zeqin , Ma Huachun , Ren Hongtao , Wang Bolun , Guo Jing , Sun Yufei , Wang Xuewen , Li Chenyu , Li Xiaoyan , Liu Kai
Published: July 2023

Solitary waves are unique in nonlinear systems, but their formation and propagation in the nonlinear fluid-structure interactions have yet to be further explored. As a typical nonlinear system, the buckling of solid thin films is fundamentally related to the film-substrate interface that is further vulnerable to environments, especially when fluids exist. In this work, we report an anomalous, solitary-wave-like blister (SWLB) mode of MoS2 thin films in a humid environment. Unlike the most common telephone-cord and web buckling deformation, the SWLB propagates forward like solitary waves that usually appear in fluids and exhibits three-dimensional expansions of the profiles during propagation. In situ mechanical, optical, and topology measurements verify the existence of an interfacial water nanolayer, which facilitates a delamination of films at the front side of the SWLB and a readhesion at the tail side owing to the water nanolayer-induced fluid-structure interaction. Furthermore, the expansion morphologies and process of the SWLB are predicted by our theoretical model based on the energy change of buckle propagation. Our work not only demonstrates the emerging SWLB mode in a solid material but also sheds light on the significance of interfacial water nanolayers to structural deformation and functional applications of thin films.
GPCRome-wide analysis of G-protein-coupling diversity using a computational biology approach
Authors: Matic Marin , Miglionico Pasquale , Tatsumi Manae , Inoue Asuka , Raimondi Francesco
Published: July 2023

GPCRs are master regulators of cell signaling by transducing extracellular stimuli into the cell via selective coupling to intracellular G-proteins. Here we present a computational analysis of the structural determinants of G-protein-coupling repertoire of experimental and predicted 3D GPCR-G-protein complexes. Interface contact analysis recapitulates structural hallmarks associated with G-protein-coupling specificity, including TM5, TM6 and ICLs. We employ interface contacts as fingerprints to cluster Gs vs Gi complexes in an unsupervised fashion, suggesting that interface residues contribute to selective coupling. We experimentally confirm on a promiscuous receptor (CCKAR) that mutations of some of these specificity-determining positions bias the coupling selectivity. Interestingly, Gs-GPCR complexes have more conserved interfaces, while Gi/o proteins adopt a wider number of alternative docking poses, as assessed via structural alignments of representative 3D complexes. Binding energy calculations demonstrate that distinct structural properties of the complexes are associated to higher stability of Gs than Gi/o complexes. AlphaFold2 predictions of experimental binary complexes confirm several of these structural features and allow us to augment the structural coverage of poorly characterized complexes such as G12/13.
A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs
Authors: Sutherland Jeffrey J. , Yonchev Dimitar , Fekete Alexander , Urban Laszlo
Published: July 2023

In vitro secondary pharmacology assays are an important tool for predicting clinical adverse drug reactions (ADRs) of investigational drugs. We created the Secondary Pharmacology Database (SPD) by testing 1958 drugs using 200 assays to validate target-ADR associations. Compared to public and subscription resources, 95% of all and 36% of active (AC50 < 1 µM) results are unique to SPD, with bias towards higher activity in public resources. Annotating drugs with free maximal plasma concentrations, we find 684 physiologically relevant unpublished off-target activities. Furthermore, 64% of putative ADRs linked to target activity in key literature reviews are not statistically significant in SPD. Systematic analysis of all target-ADR pairs identifies several putative associations supported by publications. Finally, candidate mechanisms for known ADRs are proposed based on SPD off-target activities. Here we present a freely-available resource for benchmarking ADR predictions, explaining phenotypic activity and investigating clinical properties of marketed drugs.
Crystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity
Authors: Liu Bin , Wang Weiwu , Qiu Jiguo , Huang Xing , Qiu Shenshen , Bao Yixuan , Xu Siqiong , Ruan Luyao , Ran Tingting , He Jian
Published: July 2023

SulE, an esterase, which detoxifies a variety of sulfonylurea herbicides through de-esterification, provides an attractive approach to remove environmental sulfonylurea herbicides and develop herbicide-tolerant crops. Here, we determined the crystal structures of SulE and an activity improved mutant P44R. Structural analysis revealed that SulE is a dimer with spacious binding pocket accommodating the large sulfonylureas substrate. Particularly, SulE contains a protruding β hairpin with a lid loop covering the active site of the other subunit of the dimer. The lid loop participates in substrate recognition and binding. P44R mutation altered the lid loop flexibility, resulting in the sulfonylurea heterocyclic ring repositioning to a relative stable conformation thus leading to dramatically increased activity. Our work provides important insights into the molecular mechanism of SulE, and establish a solid foundation for further improving the enzyme activity to various sulfonylurea herbicides through rational design.
IKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection
Authors: Pritzl Curtis J. , Luera Dezzarae , Knudson Karin M. , Quaney Michael J. , Calcutt Michael J. , Daniels Mark A. , Teixeiro Emma
Published: July 2023

CD8+ T cell tissue resident memory (TRM) cells are especially suited to control pathogen spread at mucosal sites. However, their maintenance in lung is short-lived. TCR-dependent NFkB signaling is crucial for T cell memory but how and when NFkB signaling modulates tissue resident and circulating T cell memory during the immune response is unknown. Here, we find that enhancing NFkB signaling in T cells once memory to influenza is established, increases pro-survival Bcl-2 and CD122 levels thus boosting lung CD8+ TRM maintenance. By contrast, enhancing NFkB signals during the contraction phase of the response leads to a defect in CD8+ TRM differentiation without impairing recirculating memory subsets. Specifically, inducible activation of NFkB via constitutive active IKK2 or TNF interferes with TGFβ signaling, resulting in defects of lung CD8+ TRM imprinting molecules CD69, CD103, Runx3 and Eomes. Conversely, inhibiting NFkB signals not only recovers but improves the transcriptional signature and generation of lung CD8+ TRM. Thus, NFkB signaling is a critical regulator of tissue resident memory, whose levels can be tuned at specific times during infection to boost lung CD8+ TRM.
Cultural differences in joint attention and engagement in mutual gaze with a robot face
Authors: Marchesi Serena , Abubshait Abdulaziz , Kompatsiari Kyveli , Wu Yan , Wykowska Agnieszka
Published: July 2023

Joint attention is a pivotal mechanism underlying human ability to interact with one another. The fundamental nature of joint attention in the context of social cognition has led researchers to develop tasks that address this mechanism and operationalize it in a laboratory setting, in the form of a gaze cueing paradigm. In the present study, we addressed the question of whether engaging in joint attention with a robot face is culture-specific. We adapted a classical gaze-cueing paradigm such that a robot avatar cued participants’ gaze subsequent to either engaging participants in eye contact or not. Our critical question of interest was whether the gaze cueing effect (GCE) is stable across different cultures, especially if cognitive resources to exert top-down control are reduced. To achieve the latter, we introduced a mathematical stress task orthogonally to the gaze cueing protocol. Results showed larger GCE in the Singapore sample, relative to the Italian sample, independent of gaze type (eye contact vs. no eye contact) or amount of experienced stress, which translates to available cognitive resources. Moreover, since after each block, participants rated how engaged they felt with the robot avatar during the task, we observed that Italian participants rated as more engaging the avatar during the eye contact blocks, relative to no eye contact while Singaporean participants did not show any difference in engagement relative to the gaze. We discuss the results in terms of cultural differences in robot-induced joint attention, and engagement in eye contact, as well as the dissociation between implicit and explicit measures related to processing of gaze.
von Willebrand factor-binding protein (vWbp)-activated factor XIII and transglutaminase 2 (TG2) promote cross-linking between FnBPA from Staphylococcus aureus and fibrinogen
Authors: Motta Chiara , Pellegrini Angelica , Camaione Stefano , Geoghegan Joan , Speziale Pietro , Barbieri Giulia , Pietrocola Giampiero
Published: July 2023

The secreted von Willebrand factor-binding protein (vWbp) from Staphylococcus aureus interacts with the coagulation factors prothrombin and fibrinogen (Fbg), leading to the non-proteolytic transglutaminase activation of Factor XIII (FXIII). In this study we found that vWbp-activated FXIII catalyses the incorporation of amino-donor dansylcadaverine into region A of fibronectin-binding protein A (FnBPA). Incubation of Fbg with recombinant region A of S. aureus Fbg-binding proteins FnBPA, FnBPB, ClfA or ClfB in presence of vWbp-activated FXIII resulted in the formation of high molecular heteropolymers with FnBPA only, suggesting a specificity of the cross-linking reaction between fibrin(ogen) and the staphylococcal surface. As previously observed, cross-linking sites were mapped to the α-chain and the N1 subdomain of fibrin(ogen) and region A of FnBPA, respectively. Comparable results were obtained when tissue tranglutaminase-2 (TG2) was tested for cross-linking of FnBPA and Fbg. Of note, FnBPA-mediated covalent cross-linking promoted by vWbp-activated FXIII was also observed when bacteria were allowed to attach to fibrin(ogen). Together these findings suggest a novel pathogenetic mechanism by which the transglutaminase action of FXIII and/or TG2 contributes to entrapment and persistence of S. aureus in blood and host tissues.
FASDetect as a machine learning-based screening app for FASD in youth with ADHD
Authors: Ehrig Lukas , Wagner Ann-Christin , Wolter Heike , Correll Christoph U. , Geisel Olga , Konigorski Stefan
Published: July 2023

Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0–19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0–19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables – body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance – yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect – a user-friendly, clinically scalable FASD risk calculator that is freely available athttps://fasdetect.dhc-lab.hpi.de.
Identifying dysregulated immune cell subsets following volumetric muscle loss with pseudo-time trajectories
Authors: Hymel Lauren A. , Anderson Shannon E. , Turner Thomas C. , York William Y. , Zhang Hongmanlin , Liversage Adrian R. , Lim Hong Seo , Qiu Peng , Mortensen Luke J. , Jang Young C. , Willett Nick J. , Botchwey Edward A.
Published: July 2023

Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis techniques to elucidate the cellular players underlying a functional or pathological outcome as a result of subcritical injury or critical VML in the murine quadriceps, respectively. We found that critical VML resulted in a sustained presence of M2-like and CD206hiLy6Chi ‘hybrid’ macrophages whereas subcritical defects resolved these populations. Notably, the retained M2-like macrophages from critical VML injuries presented with aberrant cytokine production which may contribute to fibrogenesis, as indicated by their co-localization with fibroadipogenic progenitors (FAPs) in areas of collagen deposition within the defect. Furthermore, several T cell subpopulations were significantly elevated in critical VML compared to subcritical injuries. These results demonstrate a dysregulated immune response in critical VML that is unable to fully resolve the chronic inflammatory state and transition to a pro-regenerative microenvironment within the first week after injury. These data provide important insights into potential therapeutic strategies which could reduce the immune cell burden and pro-fibrotic signaling characteristic of VML.
3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging
Authors: Ghose Soumya , Ju Yingnan , McDonough Elizabeth , Ho Jonhan , Karunamurthy Arivarasan , Chadwick Chrystal , Cho Sanghee , Rose Rachel , Corwin Alex , Surrette Christine , Martinez Jessica , Williams Eric , Sood Anup , Al-Kofahi Yousef , Falo Louis D. , Börner Katy , Ginty Fiona
Published: July 2023

Mapping the human body at single cell resolution in three dimensions (3D) is important for understanding cellular interactions in context of tissue and organ organization. 2D spatial cell analysis in a single tissue section may be limited by cell numbers and histology. Here we show a workflow for 3D reconstruction of multiplexed sequential tissue sections: MATRICS-A (Multiplexed ImageThree-DReconstruction andIntegratedCellSpatial -Analysis). We demonstrate MATRICS-A in 26 serial sections of fixed skin (stained with 18 biomarkers) from 12 donors aged between 32–72 years. Comparing the 3D reconstructed cellular data with the 2D data, we show significantly shorter distances between immune cells and vascular endothelial cells (56 µm in 3Dvs108 µm in 2D). We also show 10–70% more T cells (total) within 30 µm of a neighboring T helper cell in 3Dvs2D. Distances of p53, DDB2 and Ki67 positive cells to the skin surface were consistent across all ages/sun exposure and largely localized to the lower stratum basale layer of the epidermis. MATRICS-A provides a framework for analysis of 3D spatial cell relationships in healthy and aging organs and could be further extended to diseased organs.
Energetic Materials Based on Nanoporous Carbon
Authors: Van Riet R. , Lefebvre M. H.
Published: July 2023

This work explores a new family of energetic materials produced by filling the porosity of a nanoporous carbon acting as a reducing agent with a solid oxidizing agent. A new pore filling process was developed to efficiently fill the porosity of nanoporous carbons with solid oxidizing agents, allowing selective filling of pores of widths less than 4 nm to be achieved, thus ensuring a homogeneous mixing of the oxidizing and reducing agent at the nanometer scale. The concept is then demonstrated experimentally by proving the ability of nanoporous carbons filled with an oxidizing agent to sustain a detonation and by assessing their fundamental properties as energetic materials. It is demonstrated that a selected material is capable of detonating when initiated by a standard detonator, with measured detonation velocities ranging from 3000 to 4200 m/s for different charge densities and diameters. These properties are impressive for a composite energetic material with a very high fraction of solid decomposition products, indicating very fast dynamic decomposition kinetics favored by the nanometer scale. The concept of a new family of energetic materials based on nanoporous carbons filled with an oxidizing agent is demonstrated in this work, opening new horizons in the path towards efficient, safe and non-toxic energetic nanomaterials with a wide spectrum of applications. The unique properties and versatility of nanoporous carbons, combined with the large number of degrees of freedom of the pore filling process developed in this work, further offer promising perspectives in this field.