bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermophysical properties of H2O and D2O ice Ih with contributions from proton disorder, quenching, relaxation, and extended defects: A model case for solids with quenching and relaxation
Authors: Holzapfel W. B. , Klotz S.
Published: April 2024

Application of the coherent thermodynamic model [W. Holzapfel and S. Klotz, J. Chem. Phys. 155, 024506 (2021)] for H2O ice Ih to the more detailed data for D2O ice Ih provides better insight into the contributions from quenched proton disorder and offers a new basis for understanding the apparent differences between the data for thermal expansion measured with neutron diffraction on polycrystalline samples [A. Fortes, Acta Crystallogr., Sect. B: Struct. Sci., Cryst. Eng. Mater. 74, 196 (2018) and A. Fortes, Phys. Chem. Chem. Phys 21, 8264 (2019)] and macroscopic dilatation measurements on single crystals [D. Buckingham et al., Phys. Rev. Lett. 121, 185505 (2018)]. The comparison points to contributions from defects effecting the two techniques in different ways. The uncertainties in thermodynamic data due to the contributions from proton disorder and additional defects are compared with the “reference data” [R. Feistel and W. Wagner, J. Phys. Chem. Ref. Data 35, 1021 (2006)] for H2O ice Ih.
Understanding the role of the fructose-1,6-bisphosphatase gene for enhancing the photosynthetic rate in Arabidopsis thaliana
Authors: Gulzar Fatima , Ahmad Raza , Kwan Suk-Yoon , Khan Zulqurnain , Alharbi Sulaiman Ali , Shah Mohmmad Maroof , Rehman Shoaib ur , Siddique Maria , Ansari Mohammad Javed , Shahzadi Irum , Saddique Muhammad Abu Bakar , Ishaq Muhmmad Zahid , Waheed Ummara
Published: April 2024

Transgenic Arabidopsis thaliana (ecotype Columbia) was successfully transformed with the gene fructose-1,6-bisphosphatase (FBPase) and named as AtFBPase plants. Transgenic plants exhibited stable transformation, integration and significantly higher expressions for the transformed gene. Morphological evaluation of transgenic plants showed increased plant height (35 cm), number of leaves (25), chlorophyll contents (28%), water use efficiency (increased from 1.5 to 2.6 μmol CO2 μmol−1 H2O) and stomatal conductance (20%), which all resulted in an enhanced photosynthetic rate (2.7 μmol m−2 s−1) compared to wild type plants. This study suggests the vital role of FBPase gene in the modification of regulatory pathways to enhance the photosynthetic rate, which can also be utilised for economic crops in future.
The Myc-associated zinc finger protein epigenetically controls expression of interferon-γ-stimulated genes by recruiting STAT1 to chromatin
Authors: Xiao Tiaojiang , Li Xin , Felsenfeld Gary
Published: April 2024

The MYC-Associated Zinc Finger Protein (MAZ) plays important roles in chromatin organization and gene transcription regulation. Dysregulated expression of MAZ causes diseases, such as glioblastoma, breast cancer, prostate cancer, and liposarcoma. Previously, it has been reported that MAZ controls the proinflammatory response in colitis and colon cancer via STAT3 signaling, suggesting that MAZ is involved in regulating immunity-related pathways. However, the molecular mechanism underlying this regulation remains elusive. Here, we investigate the regulatory effect of MAZ on interferon-gamma (IFN-γ)-stimulated genes via STAT1, a protein that plays an essential role in immune responses to viral, fungal, and mycobacterial pathogens. We demonstrate that about 80% of occupied STAT1-binding sites colocalize with occupied MAZ-binding sites in HAP1/K562 cells after IFN
-
γ stimulation. MAZ depletion significantly reduces STAT1 binding in the genome. By analyzing genome-wide gene expression profiles in the RNA-Seq data, we show that MAZ depletion significantly suppresses a subset of the immune response genes, which include the IFN-stimulated genes IRF8 and Absent in Melanoma 2. Furthermore, we find that MAZ controls expression of the immunity-related genes by changing the epigenetic landscape in chromatin. Our study reveals an important role for MAZ in regulating immune-related gene expression.
Dual function of LapB (YciM) in regulating
Escherichia coli
lipopolysaccharide synthesis
Authors: Shu Sheng , Tsutsui Yuko , Nathawat Rajkanwar , Mi Wei
Published: April 2024

Levels of lipopolysaccharide (LPS), an essential glycolipid on the surface of most gram-negative bacteria, are tightly controlled—making LPS synthesis a promising target for developing new antibiotics.
Escherichia coli
adaptor protein LapB (YciM) plays an important role in regulating LPS synthesis by promoting degradation of LpxC, a deacetylase that catalyzes the first committed step in LPS synthesis. Under conditions where LPS is abundant, LapB recruits LpxC to the AAA+ protease FtsH for degradation. LapB achieves this by simultaneously interacting with FtsH through its transmembrane helix and LpxC through its cytoplasmic domain. Here, we describe a cryo-EM structure of the complex formed between LpxC and the cytoplasmic domain of LapB (LapB
cyto
). The structure reveals how LapB exploits both its tetratricopeptide repeat (TPR) motifs and rubredoxin domain to interact with LpxC. Through both in vitro and in vivo analysis, we show that mutations at the LapB
cyto
/LpxC interface prevent LpxC degradation. Unexpectedly, binding to LapB
cyto
also inhibits the enzymatic activity of LpxC through allosteric effects reminiscent of LpxC activation by MurA in
Pseudomonas aeruginosa.
Our findings argue that LapB regulates LPS synthesis in two steps: In the first step, LapB inhibits the activity of LpxC, and in the second step, it commits LpxC to degradation by FtsH.
Óláfr pái Hǫskuldsson’s landing in Ireland (Laxdæla saga) in light of the Irish law
of the shore
Authors: Sayers William
Published: April 2024

This article compares the commercial knowledge of a Norwegian skipper in the Icelandic Laxdæla
saga with the medieval Irish law of the shore, now accessible in recently edited Irish legal tracts. His knowledge of
Ireland is matched by the ship’s master, Óláfr paí Hǫskuldsson, son of an enslaved mother but grandson of an
Irish king. The essay reviews the possibility of cultural transfers from the medieval Norse-Celtic world of Ireland and the
Scottish Isles to settlement-era Iceland in the spheres of story-telling, law, and governance.
Addenda zum Etymologischen Wörterbuch der friesischen Adjektiva, Teil III
Authors: Faltings Volkert F.
Published: April 2024

When the Etymologisches Wörterbuch der friesischen Adjektiva appeared in 2010, the author was well aware that with the complexity of the Frisian linguistic situation and its often unpublished handwritten sources, he would have missed one or two interesting adjectives. Thirteen additional Frisian adjectives have meanwhile been found in other until now less regarded lexicographic material: germ. *auþa‑ ‘easy’, *ferhwta‑ ‘endowed with a good spirit’, *gillja‑ ‘gaping, protruding’, *hlaupja‑ ‘unpicking, riving’, *krupila‑ ‘crippled’, *lega‑ ‘lying’, *lunka‑ ‘smirched, blotted’, *mūka‑ ‘mellow’, *slunka‑ ‘of reduced quality’, *stamara‑ ‘stammering’, *stamma‑ ‘talking inhibited’, *straka‑ ‘streched’, *sturra‑ ‘stiff, standing off rigidly’. These adjectives will be subjected to an etymological investigation below. This article is the third supplement with such analyses.
A numerical investigation of a well-known nonlinear Newell-Whitehead-Segel equation using the rank polynomial of the star graph
Authors: Kumbinarasaiah S , Nirmala A N
Published: April 2024

Mathematical models of pattern formation are indispensable tools in various fields, from developmental biology to ecology, providing insights into complex phenomena and contributing to our understanding of the natural world. These patterns have been extensively studied using reaction-diffusion and NewellWhiteheadSegel models. This article intended to find an approximate numerical solution to the NewellWhiteheadSegel equation. The appearance of stripe patterns in two-dimensional systems is explained in nonlinear systems using the NewellWhiteheadSegel equation. Based on the function basis of rank polynomials of star graphs and the well-posed operational matrices, the rank polynomial collocation method is constructed. The alleged rank polynomial collocation method created a system of nonlinear algebraic equations from the nonlinear NewellWhiteheadSegel equation. The nonlinear NewellWhiteheadSegel equation solution is approximated by solving the resulting system via Newton’s Raphson method. Numerical instances are provided to illustrate the validity and effectiveness of the technique. Verification of accuracy is accomplished by calculating error norms. The obtained numerical results show a reasonable degree of consistency with the findings reported in the current literature. The scheme’s primary benefit is the algorithm’s ease of implementation.
Theoretical predicted Janus SrAlGaTe4: effects of strain and electric field and its topological properties
Authors: Gao Xiaojing , Niu Xiaobin , Wang Jianwei
Published: April 2024

The asymmetric Janus SrAlGaTe4, constructed from its parent SrGa2Te4 monolayer, was predicted theoretically by first principle calculations. Its stability was confirmed by phonon structure without imaginary frequency and ab initio molecular dynamics (AIMD) simulations. The Janus structure reduces the symmetry of SrGa2Te4 monolayer, which causes the absence of topological states in free-standing Janus SrAlGaTe4. To explore the possible electronic and topological properties, the effects of strain and external electric field, working as effective modulation methods for the electronic properties, were investigated. The SrAlGaTe4 monolayer undergoes a direct-to-indirect bandgap transition when the in-plane biaxial compressive strain is −8%. When the tensile strain is 9% or the electric field is 0.5 V Å−1, the Janus SrAlGaTe4 monolayer exhibits topological insulator (TI) characters, which was confirmed by the evolution of the Wannier charge centers (WCC). And the critical values for the topological transition are 2% for the biaxial tensile strain, and 0.2 V/Å for the applied electric field. The asymmetric Janus structure induces a Rashba spin splitting not only in the valence band but also in the conduction band near the Fermi level when the spin–orbit coupling (SOC) is present. Our findings offer theoretical insights into the exotic physical properties of SrAlGaTe4 and also provide guides to new spintronic device designs.
Analyzing magnetic dipole impact in fluid flow with endothermic/exothermic reactions: neural network simulation
Authors: R S Varun Kumar , K Chandan , Sharma Naman , K Karthik , R Naveen Kumar , Punith Gowda R J , Muhammad Taseer , Singh Gill Harjot
Published: April 2024

The consequence of exothermic/endothermic chemical reactions and Arrhenius activation on the heat and mass transport of the liquid flow past a cylinder in the incidence of a magnetic dipole is considered in the current investigation. Magnetic dipoles are used in medical applications such as magnotherapy and spectroscopy, to produce static magnetic fields. Scientists and engineers can improve the effectiveness of chemical reactions or heat transfer operations by analyzing the impact of reactions on flow and building systems with optimized flows. The modelled equations are converted into non-dimensional ordinary differential equations (ODEs) by using similarity variables. The resultant equations are solved by employing the physics-informed neural network (PINN) technique. Additionally, the comparison of PINN with the numerical method Runge–Kutta Fehlberg’s fourth-fifth order (RKF-45) is studied. The effects of different parameters on the temperature, concentration, and velocity profiles for endothermic/exothermic instances are shown graphically. The thermal, velocity, and concentration profiles get stronger as the curvature parameter values increase for both endothermic and exothermic cases. The influence of activation energy parameters, chemical reaction parameters, and endothermic/exothermic reaction parameters on the thermal and concentration is also depicted.
Anharmonic effects on the squeezing of axion perturbations
Authors: Danieli Valentina , Kobayashi Takeshi , Bartolo Nicola , Matarrese Sabino , Viel Matteo
Published: April 2024

It is assumed in standard cosmology that the Universe underwent a period of inflation in its earliest phase, providing the seeds for structure formation through vacuum fluctuations of the inflaton scalar field. These fluctuations get stretched by the quasi-exponential expansion of the Universe and become squeezed.
The aim of this paper is to deepen the understanding of the squeezing process, considering the effect of self-interactions.
Axion-like particles can provide a useful setup to study this effect.
Specifically we focus on the consequences that a non-trivial evolution of the background axion field has on the squeezing of the perturbations.
We follow the evolution of the axion's fluctuation modes from the horizon exit during inflation to the radiation-dominated epoch.
We compute Bogoliubov coefficients and squeezing parameters, which are linked to the axion particle number and isocurvature perturbation. We find that the quantum mechanical particle production and the squeezing of the perturbations are enhanced, if one accounts for anharmonic effects, i.e., the effect of higher order terms in the potential. This effect becomes particularly strong towards the hilltop of the potential.
Biogas Production in a Variety of Sawdust and Cow Dung Mixtures Using the Intermittent Mixing Method
Authors: Mochtar A A , Jalaluddin  , Mangkau A , Sakka A , Aqsa I , Khoir M
Published: April 2024

Cow dung is livestock waste that is very useful for renewable energy sources. The acceleration of the gas rate in cow dung biogas fermentation can be accelerated by the addition of secondary material, sawdust is one of the organic materials that can accelerate the rate of gas production in the formation of cow dung biogas. This study used a mixture composition: (B1) 675 g cow dung and 0 g sawdust, (B2) 472.5 g cow dung and 202.5 sawdust, (B3) 450 g cow dung and 225 g sawdust, and (B4) 427.5 g cow dung and 247.5 g of sawdust by fermentation for 20 days. In the research process, measurements of pH at the beginning and at the end of the study, gas pressure, gas volume, biodigester temperature, production rate, methane gas content, and flame test were carried out. In this study, the pH values ranged from 7-7.5 and the biodigester temperature was 27.5-31°C. The results of this study indicate that an organic mixture with a mixture of sawdust can accelerate production faster than without organic sawdust. Optimal results are found in the variation of the organic mixture of sawdust with a mixture of 450 g cow dung and 250 g sawdust having the highest production rate of 281.72 ml/day.
Experimental Study of the Influence of Flap Angle Configuration on the Drag Coefficient of Airfoil Model of Homebuilt Aircraft
Authors: Salam N , Tarakka R , Kasim L , Wahab M A
Published: April 2024

Homebuilt aircraft are experimental aircraft, of which at least 51% of the aircraft parts are self-supporting and not factory-made. The purpose of this study was to describe the characteristics of the flap angle configuration of a homebuilt aircraft airfoil and determine the drag coefficient (CD) of the airfoil on the flap angle configuration. This research method uses an experimental approach, which is carried out in a wind tunnel at the Fluid Mechanics Laboratory, Faculty of Engineering, Hasanuddin University Gowa. The homebuilt aircraft wing model uses the NACA 23012 airfoil model, by treating the main airfoil flap angle configuration (Fu) with the same control airfoil or aileron (Fk) flap angle at 5 (five) levels of flap angle variations, namely -150, 00, 150, 300, and 450. Furthermore, each configuration of the airfoil flap is flowed with air at the same speed of 22 m/s or at Reynolds number Re = 270,886 at 6 (six) levels of angle of attack (α), namely at angles of -150, -100, 00, 50, 100 and 150. The results of this study indicate that the maximum value of CD always occurs at 150 and angle Fk = 450 for all variations of the Fu angle. The maximum value of CD = 2.8656 occurs at the same angle Fu and angle Fk, namely at angles of 450 and α = 150, while the minimum value of CD = 0.3144 occurs at the same angle Fu and Fk, namely at angles 00 and α = -100.
Investigation of surface roughness and tool wear in milling of AISI 4340 steel
Authors: Aminy A Y , Arsyad H , Fahri  , Hayat A
Published: April 2024

Investigation of surface roughness and tool wear in milling of AISI 4340 steel has been conducted with a 4-flutes endmill. The relationships between cutting force, surface roughness and cutting parameter were investigated To determine the tool life of the tool. It is required to research the wear of the tool and the roughness of the machining results on the material tested. In this research, the test material used is AISI 4340 steel with a cooling method in the cutting process. The cutting model is slot mill cutting. To determine the wear of the cutting, a variation of the cutting thickness was performed where the selected cutting thickness was 0.5mm, 1mm, and 1.75mm. The tests that have been done are surface roughness testing, tool wear, and tool photos after cutting. The result obtained from the study is the highest level of roughness on the material cutting poses with a cutting thickness of 1.75 mm. In addition, the most optimal wear results on cutting with a cutting depth of 1 mm.
Development of Amplitude Measurement System for Ultrasonic Vibration Assisted Micro Forming
Authors: Kiswanto G , Dwiyati S T , Adityawarman R A , Mendrofa E J P , Tjong H T , Abdurrohman W Z
Published: April 2024

Microforming is a process that involves forming a material through plastic deformation at a micro level. However, this method encounters an issue at the micro-scale known as the size effect. There are several new approaches to overcome these difficulties, one of which is using Ultrasonic Vibration Assisted (UVA) micro forming. UVA micro forming is a forming method by applying high-frequency vibrations to the workpiece to reduce forming forces, increase smooth zone, reduce surface roughness, and increase accuracy. A bolted Langevin transducer is needed to produce vibration, which converts electrical signals into acoustic signals in the ultrasonic frequency range. Therefore, the vibration characteristics must be considered in detail to find the best parameters in the micro forming process. This study aims to develop an amplitude measurement system for UVA micro forming. Several things that need to be considered in designing a measurement system are pre-stress characteristics, resonant frequency of the machine, and the amplitude of the vibration generated by the system. Firstly, a pre-stress test was carried out by tightening the pre-stress bolt slowly until the resonant frequency did not change. Then, the resonant frequency is measured using signal generator, oscilloscope, transducer, and resistor to determine the system’s resonant frequency. Finally, the vibration amplitude is measured by observing the displacement at the end of the punch using a digimatic indicator. The result shows that the resonance frequency that produces longitudinal vibration for UVA micro forming system is 28,720 Hz, with a pre-stress of 30 MPa with torque of 14.36 Nm, and total displacement on the normal axis is 9 μm.
Topological and geometric analysis of cell states in single-cell transcriptomic data
Authors: Huynh Tram , Cang Zixuan
Published: April 2024

Single-cell RNA sequencing (scRNA-seq) enables dissecting cellular heterogeneity in tissues, resulting in numerous biological discoveries. Various computational methods have been devised to delineate cell types by clustering scRNA-seq data, where clusters are often annotated using prior knowledge of marker genes. In addition to identifying pure cell types, several methods have been developed to identify cells undergoing state transitions, which often rely on prior clustering results. The present computational approaches predominantly investigate the local and first-order structures of scRNA-seq data using graph representations, while scRNA-seq data frequently display complex high-dimensional structures. Here, we introduce scGeom, a tool that exploits the multiscale and multidimensional structures in scRNA-seq data by analyzing the geometry and topology through curvature and persistent homology of both cell and gene networks. We demonstrate the utility of these structural features to reflect biological properties and functions in several applications, where we show that curvatures and topological signatures of cell and gene networks can help indicate transition cells and the differentiation potential of cells. We also illustrate that structural characteristics can improve the classification of cell types.
The city nature challenge: A global citizen science phenomenon contributing to biodiversity knowledge and informing local government practices
Authors: Palma Estibaliz , Mata Luis , Cohen Kylie , Evans Doug , Gandy Bernard , Gaskell Nadine , Hatchman Hiliary , Mezzetti Anna , Neumann Deborah , O'Keefe Jessica , Shaw Amy , Wells Millie , Williams Laurence , Hahs Amy K
Published: April 2024

The bioblitz phenomenon has recently branched into cities, presenting exciting opportunities for local governments to channel participants’ efforts toward local issues. The City Nature Challenge (CNC) is one such initiative that has been quickly taken up by hundreds of municipalities worldwide. Despite high levels of participation, we still lack a framework for evaluating how the CNC contributes to local biodiversity knowledge and to inform local government practices. In the present article, we develop such a tool and present a case study that illustrates its applicability. We demonstrate that the collected records contributed to a better understanding of contemporary, local biodiversity patterns and provide a more realistic representation of understudied groups such as insects and fungi. Importantly, we show that the CNC presented local governments with a cost-effective tool to make informed, evidence-based management and policy decisions, improve education and engagement programs, foster cross-council collaborations, and support a stronger sense of environmental stewardship within the local community.
Insulin resistance impairs biologic agent response in moderate-to-severe plaque psoriasis: insights from a prospective cohort study in China
Authors: Huang Dawei , Zhong Xiaoyuan , Jiang Yuxiong , Kong Luyang , Ma Rui , Lu Jiajing , Li Ying , Shi Yuling
Published: April 2024

Background

Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis.

Objective

To investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis.

Methods

This project was based on a prospective cohort study design. Data were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using triglyceride glucose–body mass index (TyG-BMI). Psoriasis severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results.

Results

A total of 290 patients were included in the analysis. Based on median TyG-BMI, the patients were divided into two groups: high and low IR. The high IR group exhibited a higher prevalence of diabetes, a higher BMI, and higher fasting blood glucose and triglyceride levels than the low IR group. Further analysis of treatment efficacy revealed that patients in the high IR group had lower PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and PGA 0/1 (‘clear’ or ‘almost clear’) response rates after 12 weeks of treatment. In the low IR group, 81.9% of patients achieved PASI 75, 58.3% achieved PASI 90 and 75.7% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the high IR group compared with the low IR group. The reduced PGA 0/1 response rate was more significant in the high IR group, indicated by lower odd ratios. Subsequent subgroup and sensitivity analyses produced consistent results.

Conclusion

IR is associated with lower effectiveness of biologics in patients with psoriasis.
Filling the prescription gap: the value of community support in psoriasis management
Authors: Leeolou Melissa C , Sarin Kavita Y , Fiorentino David F
Published: April 2024

This perspectives article is co-authored with Melissa Leeolou, patient advocate, whose personal experiences with severe psoriasis have provided invaluable insights into the emotional and social dimensions of living with this condition. We offer a unique perspective on dermatological care by highlighting the importance of community support networks and hope to contribute to a more holistic understanding of patient needs.
Isthmin-1 alleviates cardiac ischaemia/reperfusion injury through cGMP-PKG signalling pathway
Authors: Hu Min , Zhang Xin , Hu Can , Ma Zhen-Guo , Wang Sha-Sha , Teng Teng , Zeng Xiao-Feng , Tang Qi-Zhu
Published: April 2024

Aims

Ischaemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization; however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches.

Methods and results

Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodelling and dysfunction. Mechanistically, ISM1 targeted αvβ5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients.

Conclusion

ISM1 can protect against cardiac I/R injury through cGMP-PKG signalling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.
The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling
Authors: He Zongsheng , IJpma Arne S , Vreeken Dianne , Heijsman Daphne , Rosier Karen , Verhagen Hence J M , de Bruin Jorg L , Brüggenwirth Hennie T , Roos-Hesselink Jolien W , Bekkers Jos A , Huylebroeck Danny F E , van Beusekom Heleen M M , Creemers John W M , Majoor-Krakauer Danielle
Published: April 2024

Aims

Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signalling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation.

Methods and results

Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection. FURIN maturation and activity of these variants were decreased in vitro. Patient-derived fibroblasts showed decreased pro-TGF-β processing, phosphorylation of downstream effector SMAD2 and kinases ERK1/2, and steady-state mRNA levels of the TGF-β-responsive ACTA2 gene. In aortic tissue, collagen and fibrillin fibres were affected. One variant (R745Q), observed in 10 unrelated cases, affected TGF-β signalling variably, indicating effect modification by individual genetic backgrounds.

Conclusion

FURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-β signalling, depending on individual genetic backgrounds.
Patient-specific ascending aortic intervention criteria
Authors: Kalogerakos Paris D , Zafar Mohammad A , Li Yupeng , Ellauzi Hesham , Mukherjee Sandip K , Ziganshin Bulat A , Rizzo John A , Elefteriades John A
Published: April 2024

OBJECTIVES

Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area and aneurysm location (root versus ascending).

METHODS

Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analysed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age and body surface area, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with ‘hinge points’ of steep risk, constructed separately for the aortic root and mid-ascending aorta.

RESULTS

A total of 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root and z = 5 for the mid-ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75-year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented, which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size.

CONCLUSIONS

This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient.
Yeast sexes: mating types do not determine the sexes in Metschnikowia species
Authors: Lachance Marc-André , Burke Christopher , Nygard Karen , Courchesne Marc , Timoshenko Alexander V
Published: April 2024

Although filamentous Ascomycetes may produce structures that are interpreted as male and female gametangia, ascomycetous yeasts are generally not considered to possess male and female sexes. In haplontic yeasts of the genus Metschnikowia, the sexual cycle begins with the fusion of two morphologically identical cells of complementary mating types. Soon after conjugation, a protuberance emerges from one of the conjugants, eventually maturing into an ascus. The originating cell can be regarded as an ascus mother cell, hence as female. We tested the hypothesis that the sexes, female or male, are determined by the mating types. There were good reasons to hypothesize further that mating type α cells are male. In a conceptually simple experiment, we observed the early stages of the mating reaction of mating types differentially labeled with fluorescent concanavalin A conjugates. Three large-spored Metschnikowia species, M. amazonensis, M. continentalis, and M. matae, were examined. In all three, the sexes were found to be independent of mating type, cautioning that the two terms should not be used interchangeably.
Evolutionary graph theory beyond single mutation dynamics: on how network-structured populations cross fitness landscapes
Authors: Kuo Yang Ping , Carja Oana
Published: April 2024

Spatially resolved datasets are revolutionizing knowledge in molecular biology, yet are under-utilized for questions in evolutionary biology. To gain insight from these large-scale datasets of spatial organization, we need mathematical representations and modeling techniques that can both capture their complexity, but also allow for mathematical tractability. Evolutionary graph theory utilizes the mathematical representation of networks as a proxy for heterogeneous population structure and has started to reshape our understanding of how spatial structure can direct evolutionary dynamics. However, previous results are derived for the case of a single new mutation appearing in the population and the role of network structure in shaping fitness landscape crossing is still poorly understood. Here we study how network-structured populations cross fitness landscapes and show that even a simple extension to a two-mutational landscape can exhibit complex evolutionary dynamics that cannot be predicted using previous single-mutation results. We show how our results can be intuitively understood through the lens of how the two main evolutionary properties of a network, the amplification and acceleration factors, change the expected fate of the intermediate mutant in the population and further discuss how to link these models to spatially resolved datasets of cellular organization.
Silyl enol ethers and related silyl ethers
Authors: Thomas Susan E.
Published: April 2024

This chapter focuses on related silyl ethers and silyl enol ethers. It defines silyl enol ethers as stable molecules which may be isolated, purified, and characterized using standard organic procedures. The chapter contends that they are sources of regiochemically-pure enolate ions and their equivalents, and as such, they play an important role in modern synthetic organic chemistry. The chapter then moves to explicate the formation of silyl enol ethers. It illustrates the deprotonation of an unsymmetrically substituted ketone such as 2-methylcyclohexanone, then explores the process of conjugate additions/silylation and hydrosilylation. The chapter discusses the reactions of silyl enol ethers, then elaborates on the silyl ketene acetals which are derived from ester enolates and are closely related to silyl enol ethers.
A Positive Right to Rehabilitation? An Examination of the ‘Principle of Rehabilitation’ in the Caselaw of the European Court of Human Rights
Authors: Lawrence Rebecca
Published: April 2024

This article analyses the development and the role of the ‘principle of rehabilitation’ in the European Court of Human Rights’ caselaw on prisoner rights. It will be demonstrated that, outside of the context of whole-life sentences, the impact of the principle on the Court’s reasoning process has been relatively limited, despite increasing reference by the Court to the growing importance of the principle. Further, that the Court allowing the pursuit of rehabilitation to be used as justification for interferences with other Convention rights within its caselaw undermines the link made by the Court between rehabilitation and human dignity. Finally, it is argued that a conception of rehabilitation that is underpinned by human dignity requires recognition of a positive duty on states to provide access to appropriate rehabilitative treatment for all prisoners.
The impact and user experience of a student-led clinic providing preventative services
Authors: Chin Sophie , Richardson Charlotte Lucy , Gardner Adam , Nazar Hamde
Published: April 2024

Objectives

Preventative services are required to address the risk factors for chronic conditions such as cardiovascular disease. The National Health Service Health Checks in England were introduced to provide such services. One School of Pharmacy established a student-led clinic to provide this service to the local community. The clinic was provided by undergraduate pharmacy students and delivered free of charge within a central city locality. The aim was to explore the impact of the clinic on user thoughts and motivations around healthy living and investigate user experience.

Methods

A sequential explanatory mixed methods approach was used consisting of a survey that measured users’ thoughts about their health and well-being and experience of the clinic. Qualitative interviews explored the user experience and barriers and facilitators to making healthier lifestyle choices.

Results

One hundred and fifty-four members of the public accessed the clinic over the evaluative period. Ninety-six (60%) completed the pre–post survey and 12 participated in follow-up interviews. Users reported statistically significant improvements in how informed, competent and motivated they felt towards making healthier lifestyle choices after the clinic consultation. Interview findings highlighted the positive user experience, reported appreciation for clinic accessibility, availability of healthy lifestyle education, and a desire for more preventative services being as readily available.

Conclusions

The student-led clinic has demonstrated positive impacts on user experience, knowledge, competence, and motivation to make healthier lifestyle choices. The clinic provides proof-of-concept for pharmacy students to deliver preventative community services that aim to improve population health at a time when primary care is experiencing unprecedented challenges.
UNIFIL’s “Blue Line” Demarcation: Spatial Ordering, Political Subjectivity, and Settler Colonialism in South Lebanese Borderlands
Authors: Kassem Susann
Published: April 2024

This article offers an ethnographic account of ongoing border conflicts in south Lebanon between members of the United Nations Interim Force in Lebanon (UNIFIL) and residents in a south Lebanese border village. It emphasizes the specific experiences of this border population with foreign intervention and land expropriations. It places UNIFIL’s current intervention in a long history of Western imperialism in the region. It underlines how UNIFIL weakens the Lebanese state by taking over the sovereign functions a state typically performs. It examines current border contestations in a context of Israeli settler colonialism and its long-term role in shaping the livelihoods in south Lebanese border villages. It argues for the importance of understanding border conflicts and the work of international interventions in their specific local and historical contexts.
39 Deep Learning and Mechanical Ventilation Period Based Inhalational Injury Score
Authors: Pang Alan , Li Yifan , Chong Jowoon
Published: April 2024

Introduction

Smoke inhalation is a serious complication associated with burn injuries. It notably increases mortality rates and prolongs hospital stays due to the thermal, chemical, and metabolic injuries inflicted on the airways by smoke. The current mainstream grading system, the Abbreviated Injury Score (AIS), a macroscopic evaluation of a microscopic disease process, has shown inconsistencies in accurately diagnosing and grading inhalation injury severity, largely due to its subjective nature. Our study aims to bridge these gaps by utilizing deep learning and artificial intelligence, proposing a novel method utilizing a Convolutional Neural Network (CNN) for more objective grading. Given the difficulty in collecting bronchoscopy images, we employed Contrastive Unpaired Translation (CUT) for data augmentation and conducted statistical analysis on lab work to pinpoint features impacting inhalation injury severity.

Methods

We categorize the inhalation injuries into 6 degrees based on ventilator days: 1) under 24 hours as degree 1, 2) 1-2 days as degree 2, 3) 3-7 days as degree 3, 4) 8-14 days as degree 4, 5) 15-30 days as degree 5, and 6) after 30 days as degree 6. To augment the dataset volume, graphic transformations, and Contrastive Unpaired Translation (CUT) were utilized. The augmented dataset was then evaluated using GoogLeNet, and a Random Forest algorithm was implemented to assess feature importance meticulously.

Results

Graphic transformations increased the image dataset from 153 to 1377 images, while Contrastive Unpaired Translation (CUT) further doubled the dataset to 2754 images. For evaluation, 30% of the original images were designated as the testing set and subjected to classification analysis via GoogLeNet. The enhancements through transformations and CUT propelled the classification accuracy from 36% (on original images) to a significant 91%. Statistical analysis highlighted that Total Body Surface Area (TBSA), Initial PH, Initial PaCO2, Pressors, Carboxyhemoglobin Level, and Resuscitation Fluid Amount Needed during the first 24 hours are pivotal determinants in assessing the severity of inhalation injuries.

Conclusions

This study underscores the potential of leveraging advanced computational techniques to ameliorate the accuracy of inhalation injury grading in burn victims. Through graphic transformations and Contrastive Unpaired Translation (CUT), a significant augmentation in the image dataset was achieved, facilitating a more robust analysis. The proposed methodology not only elevates the precision in grading inhalation injuries but also initiates a path towards more objective evaluations in clinical settings, thus aiding in better-informed medical interventions for burn victims.

Applicability of Research to Practice

If we can develop an objective measurement of inhalational injury with prognostic ability, then we can develop novel therapeutics and objectively measure their efficacy in treatment.
55 Assessing Pediatric Burn Wound Infection Using a Point-of-Care Autofluorescence Imaging Device
Authors: Turner Evan , Zuccaro Jennifer , Chakera Hawwa , Kelly Charis , Fish Joel
Published: April 2024

Introduction

Wound infection is the most common complication among pediatric burn patients and when not treated promptly, delayed healing, failure of skin grafts, or death can result. Standard burn wound assessment includes inspection for visual signs and symptoms of infection and microbial sampling. To aid in the assessment of burn wound infection, a point-of-care autofluorescence imaging device was introduced at the study institution in 2020. This imaging device uses violet light to illuminate the wound bed causing clinically relevant quantities of bacteria to fluoresce in real-time. The objectives of this study were to evaluate the role of the autofluorescence imaging device in the management of pediatric burn wounds and determine if the imaging findings corresponded to visual signs and symptoms of infection and/or microbial sampling.

Methods

A retrospective review of patients aged 0-18 years who had their burn wounds assessed with the autofluorescence imaging device between 2020-11-01 and 2023-06-08 was conducted. All imaged wounds were inspected for visual signs and symptoms of infection and had swabs collected for the purpose of microbial sampling. Sensitivity and specificity analyses were carried out on a subset of wounds that were imaged after initial wound cleaning was performed.

Results

Data were extracted from the medical records of 178 eligible burn patients with 218 wounds imaged. The mean age of patients was 3.2 years (SD 3.7), and most burns were partial thickness (78%) and due to scalds (81%). Fluorescence was detected by imaging in 16% of wounds, while 11% of wounds had visual signs and symptoms of infection and 16% had positive wound swab findings. Autofluorescence imaging corresponded with visual signs and symptoms of infection in 81% of wounds and microbial findings in 82% of wounds. Sixty-three patients with 77 wounds were included in sensitivity and specificity analyses. Relative to visual signs and symptoms of infection alone, combining autofluorescence imaging with visual signs and symptoms of infection resulted in a 39% increase in sensitivity and 19% decrease in specificity.

Conclusions

Autofluorescence imaging correlates well with visual signs and symptoms of infection and microbial sampling in pediatric burn wounds and complements inspection for visual signs and symptoms of infection by improving detection.

Applicability of Research to Practice

Incorporation of this autofluorescence imaging device in standard burn wound assessments can augment identification of wound infections, which can enhance diagnostic confidence at the point-of-care and ultimately improve wound healing outcomes.
59 Prevalence, Risk Factors, and Outcomes Associated with Food Insecurity in a Burn Clinic
Authors: Ross Erin E , Fobar Megan C , Gomez Laura Herrera , Gillenwater Justin , Yenikomshian Haig A
Published: April 2024

Introduction

Adequate nutrition in burn care is paramount to wound healing. As a result, food insecurity may pose a significant risk to burn patients. Due to increased caloric need, burn patients may be at increased risk for food insecurity. Here, we assess food insecurity prevalence, risk factors, and possible associated complications of wound healing.

Methods

Adult patients at a outpatient burn clinic answered the US Department of Agriculture Household Food Security Survey Module and questions about employment status and supplemental food resource use. Clinical data was abstracted from the medical record. Wound complication was defined as graft loss requiring regrafting or wound infection. Bivariate analysis by food security level was conducted by Chi-square, Fisher’s Exact test, or Mann-Whitney test. Association of age, race/ethnicity, total body surface area burned (TBSA), surgery count, hand or face burn, and unemployment to food insecurity were assessed by logistic regression, with significant predictors included in a multiple logistic regression model.

Results

104 patients completed surveys, with 44.3% of patients experiencing food insecurity in the past 12 months. Only 48.9% of food insecure patients were using any supplemental resources for food access. Among 88 patients with complete healing data, wound complications in food secure and insecure patients were 21.3% and 38.7% respectively, (p= .57, power = 43%). Of the 22 patients with wound complications, 45% had diabetes (p=.022, Chi-square). In our final regression model, food insecurity was associated with TBSA (p=.045) and unemployment (p =.0075).

Conclusions

Many patients are experiencing food insecurity during a time of increased metabolic need, and resources for food access are underutilized. Further research is needed to determine if food insecurity is associated with increased wound healing complications.

Applicability of Research to Practice

Screening for food insecurity should be a routine component of outpatient burn care, and processes to connect patients to benefits for which they may be eligible are also needed.