bluuebunny/crossref_metadata_2025 huggingface dataset:
Photothermally responsive graphene hybrid dry powders for diabetic wound healing
Authors: Chen Mei , Wang Fengyuan , Yan Qiao , Da Meihong , Wang Fei
Published: May 2024

The treatment of diabetic wounds remains a significant challenge in the medical field. In this study, we present a novel approach using photothermally responsive graphene hybrid dry powders for the treatment of diabetic wounds. These powders, derived from polyacrylic acid (PAA) and polyethyleneimine (PEI), exhibit rapid water absorption at the interface, leading to the in situ formation of physically crosslinked hydrogels due to interactions between polymers. Furthermore, by incorporating graphene into the PAA/PEI powder mixture, we establish a multifunctional platform with capabilities such as photothermal antibacterial effects and drug release. Given the outstanding performance of this hybrid material, we demonstrate its potential in wound healing by incorporating the tumor necrosis factor-alpha (TNF-α) inhibitor Etanercept into the PAA/PEI powder. This intervention resulted in a significant improvement in the wound healing process in diabetic rats, as evidenced by the downregulation of inflammatory factors, promotion of collagen deposition, and enhanced vascularization. These remarkable attributes underscore the enormous potential value of the presented hydrogel patches in the field of biomedicine.
Spin resonance spectroscopy with an electron microscope
Authors: Haslinger Philipp , Nimmrichter Stefan , Rätzel Dennis
Published: May 2024

Coherent spin resonance methods, such as nuclear magnetic resonance and electron spin resonance spectroscopy, have led to spectrally highly sensitive, non-invasive quantum imaging techniques. Here, we propose a pump-probe spin resonance spectroscopy approach, designed for electron microscopy, based on microwave pump fields and electron probes. We investigate how quantum spin systems couple to electron matter waves through their magnetic moments and how the resulting phase shifts can be utilized to gain information about the states and dynamics of these systems. Notably, state-of-the-art transmission electron microscopy provides the means to detect phase shifts almost as small as that due to a single electron spin. This could enable state-selective observation of spin dynamics on the nanoscale and indirect measurement of the environment of the examined spin systems, providing information, for example, on the atomic structure, local chemical composition and neighboring spins.
Design of herringbone grooved thrust bearing for locomotive turbocharger rotor
Authors: Mishra Hara Prakash , Behera Suraj Kumar
Published: May 2024

The herringbone texture exhibited excellent tribological performance to minimize friction and wear. However, the application of this texture in the development of grooved thrust bearings is limited. Therefore, in this study, an attempt was made to design an oil-lubricated herringbone grooved thrust bearing for high-speed locomotive turbochargers. The designed bearing accommodates the axial load generated due to the pressure difference between the turbine and compressor wheel. The bearing design starts with applying Newton’s second law to predict the thrust load acting on the locomotive turbocharger rotor. The thrust load is calculated analytically and is found to be 4.54 kN for a design rotor speed of 1,00,000 rpm. Further, the herringbone grooved thrust bearing has been modeled numerically using non-linear Reynolds equation. The modified Reynolds equation is discretized using the finite volume method (FVM) and solved by successive over-relaxation (SOR) methodology to determine the static characteristics over the bearing surface. The developed HGTB is found to have a suitable load-carrying capacity of 4.6 kN, frictional torque of 0.25 N.m, and power loss of 2.98 kW. Further, a parametric analysis has been carried out to study the influence of design parameters such as the number of grooves, helix angle, angular groove width, groove depth, and speed on load-carrying capacity, frictional torque, and power loss.
Synergistic effect of niobium carbide and titanium nanoparticles on the mechanical and microstructural properties of Al-Zn-Mg-Cu alloy hybrid composites
Authors: Vijaya D Joslin , Robinson Smart D S , K Leo Dev Wins , Dhas D S Ebenezer Jacob
Published: May 2024

In this study, an Al-Zn-Mg-Cu alloy matrix serves as the matrix material, with Niobium Carbide (NbC) and Titanium (Ti) nanoparticles acting as reinforcements to enhance composite strength. Incorporating nano-structured reinforcements significantly enhance both strength and toughness, surpassing micro-sized counterparts. To prevent nanoparticle agglomeration during manufacturing, we employ vigorous stirring via the stir casting technique to ensure uniform dispersion within the composite matrix. SEM analysis confirms uniform dispersion of NbC and Ti nanoparticles within the matrix. Experimentally, the composite exhibits exceptional tensile strength, with sample B achieving the highest load of 5500 N, correlated with an optimal NbC percentage of 5 wt% and Ti percentage of 2 wt%. However, increasing NbC percentage from 5 wt% to 10 wt% results in decreased ductility and tensile strength for composite C. Similar trends are observed in bending strength, with composite B exhibiting the highest load at 9023.8 N, surpassing samples C and D. Microhardness results demonstrate an increase with NbC content, peaking at 230 HV, but declining to 185 HV with reduced NbC and Ti concentrations. Charpy impact tests reveal a consistent rise in impact energy from samples B to D, attributed to the escalating proportion of NbC relative to Ti. Overall, meticulous material selection and processing optimization are essential for developing high-performance metal matrix composites with enhanced mechanical properties.
An investigation of machinability in micro-EDM drilling of ZrB2/Fly ash/AA7075 hybrid aluminium metal matrix composite
Authors: Kumar Prakash , Pratap Suresh , Kumar Binay , Datta Somak
Published: May 2024

This work investigates the importance of micro-drilling in Hybrid aluminum metal matrix composites (HAMMCs), particularly for the aerospace and automotive industries. The HAMMCs (AA7075/5% ZrB2/2% fly) ash was fabricated using the ultrasonic assisted stir casting method. Taguchi’s design of experiments is employed to optimize the material removal rate (MRR) and tool wear rate (TWR). Analysis of variance (ANOVA) is then used to determine the significance of the model. The study also utilizes a hybrid artificial neural network-genetic algorithm (ANN-GA) approach to optimize both MRR and TWR. By optimizing machining processes for HAMMCs, manufacturers can achieve high-precision micro holes. The optimal input parameters were found to be a feed rate of 10 μm sec−1, a capacitance of 1 nF, and a voltage of 85 V, achieving the minimum TWR and maximum MRR.
Design and simulation of a novel reactor for the H2 storage mechanism in methylcyclohexane
Authors: Akram Muhammad S , Usman Muhammad R
Published: May 2024

The present study addresses the modeling and simulation of an intensified dehydrogenation reactor-heat exchanger system designed for a H2-based 2.0 MW mobile power plant. The reactor consisted of a multiple triple-tube system where the catalyst was packed in the middle tube while hot exhaust gases passed through the innermost and outermost tubes. A basecase design was defined and the reactor was simulated using the rigorous kinetics developed elsewhere for the MCH dehydrogenation. The parabolic differential equations of mass and heat energy were solved and the axial and radial conversion and temperature profiles were computed. Moreover, the effects of the number of longitudinal fins on the reactor tubes as well as the flow direction were also studied. With 12 number of fins on the reactor tube, the MCH conversion increased from 70.8% to 81.8%, with a corresponding increase in the average bed temperature from 569.3 K to 577.6 K and hydrogen yield from 37.05 kmol h−1 to 42.79 kmol h−1.
TomOpt: differential optimisation for task- and constraint-aware design of particle detectors in the context of muon tomography
Authors: Strong Giles C , Lagrange Maxime , Orio Aitor , Bordignon Anna , Bury Florian , Dorigo Tommaso , Giammanco Andrea , Heikal Mariam , Kieseler Jan , Lamparth Max , Martínez Ruíz del Árbol Pablo , Nardi Federico , Vischia Pietro , Zaraket Haitham
Published: May 2024

We describe a software package, TomOpt, developed to optimise the geometrical layout and specifications of detectors designed for tomography by scattering of cosmic-ray muons. The software exploits differentiable programming for the modeling of muon interactions with detectors and scanned volumes, the inference of volume properties, and the optimisation cycle performing the loss minimisation. In doing so, we provide the first demonstration of end-to-end-differentiable and inference-aware optimisation of particle physics instruments. We study the performance of the software on a relevant benchmark scenario and discuss its potential applications. Our code is available on Github (Strong et al 2024 available at: https://github.com/GilesStrong/tomopt).
Deep artificial neural network-powered phase field model for predicting damage characteristic in brittle composite under varying configurations
Authors: Nguyen Hoang-Quan , Le Ba-Anh , Tran Bao-Viet , Vu Thai-Son , Bui Thi-Loan
Published: May 2024

This work introduces a novel artificial neural network (ANN)-powered phase field model, offering rapid and precise predictions of fracture propagation in brittle materials. To improve the capabilities of the ANN model, we incorporate a loop of conditions into its core to regulate the absolute percentage error for each observation point, that filters and consistently selects the most accurate outcome. This algorithm enables our model to better adapt to the highly sensitive validation data arising from varying configurations. The effectiveness of the approach is illustrated through three examples involving changes in the microgeometry and material properties of steel fiber-reinforced high-strength concrete structures. Indeed, the predicted outcomes from the improved ANN phase field model in terms of stress–strain relationship, and crack propagation path demonstrates an outperformance compared with that based on the extreme gradient boosting method, a leading regression machine learning technique for tabular data. Additionally, the introduced model exhibits a remarkable speed advantage, being 180 times faster than traditional phase field simulations, and provides results at nearly any fiber location, demonstrating superiority over the phase field model. This study marks a significant advancement in the application of artificial intelligence for accurately predicting crack propagation paths in composite materials, particularly in cases involving the relative positioning of the fiber and initial crack location.
Development of an aptasensor to target metallo-β-lactamase through Förster resonance energy transfer
Authors: Ayed Zeineb , Davis Nathaniel , Goreham Renee V
Published: May 2024

The escalating issue of antibiotic resistance in bacteria necessitates innovative detection methods to identify resistance mechanisms promptly. In this study, we present a novel approach for detecting resistance in Pseudomonas aeruginosa, a bacterium known for its metallo-β-lactamase production during the development of antibiotic resistance. We have designed an aptasensor employing Förster resonance energy transfer utilising two distinct methodologies. Initially, indium phosphide quantum dots with a zinc sulphide shell, and gold nanoparticles were utilised as the Förster resonance energy transfer donor-acceptor pair. Although this system demonstrated a response, the efficiency was low. Subsequently, optimisation involved relocating the donor and acceptor in close proximity and incorporating two quantum dots with varying emission wavelengths as the acceptor and donor. This optimisation significantly enhanced the Förster resonance efficiency, resulting in a novel method for detecting metallo-β-lactamase. Förster resonance energy transfer efficiency was increased from 31% to 63% by optimising the distance and donor using a quantum dot-quantum dot pair. Our findings showcase a cheap, rapid and versatile aptasensor with potential applications beyond antibiotic resistance, highlighting its adaptability for diverse scenarios.
Influence of different annealing ambient on terbium oxide passivation layers sputtered using the RF sputtering on silicon substrate
Authors: Sifawa Abubakar A , Mohammad Sabah M , Muhammad A , Abed Shireen Mohammed , Lim Way Foong
Published: May 2024

This study investigates the influence of different annealing ambient on terbium oxide (Tb4O7) passivation layers sputtered using radio frequency (RF) sputtering on silicon (Si) substrates. The passivation layers were subjected to annealing in various ambient, including oxygen (O2), nitrogen (N2), argon (Ar), and nitrogen-oxygen-nitrogen (NON). The structural, morphological, compositional, topological, and optical properties of the passivation layers were characterized using various techniques. The obtained results indicate that the annealing ambient has a significant impact on the properties of Tb4O7 passivation layers. Annealing in Ar ambient leads to the formation of Tb4O7 with improved crystallinity close to 49.75 nm and higher surface roughness at (2.32 nm). In contrast, annealing in the O2 ambient results in broad GIXRD peaks with the lowest surface roughness around (1.34 nm). Notably, annealing in N2 ambient exhibits an intermediate behavior, with partial crystallized size values (31.80 nm) compared to the Tb4O7 passivation layer annealed in Ar ambient and moderate surface roughness. The optical bandgap (Eg) was estimated by applying the Kubelka–Munk (KM) approach and the obtained values were 3.28, 3.17, 2.37, and 2.27 eV for annealed in O2, N2, Ar, and NON ambients, respectively. The investigation of Tb4O7 as a passivation material expands the range of materials available for semiconductor device fabrication, offering potential advancements in optoelectronics applications. Therefore, the significance of this study lies in its contribution to the optimization of Tb4O7 passivation layers in the field of semiconductor device technology. Hence, the sample annealed in an Ar ambient demonstrated the best results in terms of structural, morphological, compositional, topological, and optical properties of Tb4O7 passivation layers as compared to other samples.
Design of GaAs microcavity on SiN waveguide for efficient single-photon generation by resonant excitation
Authors: Pholsen Natthajuks , Ota Yasutomo , Iwamoto Satoshi
Published: May 2024

Silicon nitride (SiN) photonic circuits are attracting significant interest as a platform for photonic quantum information processing. Integration of deterministic single photon sources (SPSs) is required for large-scale single-photon-based quantum applications. InAs/GaAs quantum dots (QDs) have been demonstrated to be state-of-the-art deterministic SPSs under resonant excitation. However, InAs/GaAs QD SPSs integrated on chip often suffer from unwanted crosstalk from scattering of resonant excitation laser. Moreover, the mismatch in refractive indices of SiN and GaAs impedes efficient coupling of single photons into the photonic circuit. In this work, we design a GaAs photonic crystal (PhC) nanobeam cavity with an embedded QD on top of a SiN waveguide in SiO2 that can suppress crosstalk from resonant excitation and realize high coupling efficiency at the same time. The crosstalk is reduced by employing a carefully designed nanobeam cavity that removes complex structures around the excitation spot. The high coupling efficiency is achieved with a weak hybridized mirror formed by proximity of GaAs PhC nanobeam and SiN waveguide that makes the cavity and helps transferring photons into the waveguide. This enables more than 90% coupling efficiency. The designed device is expected to be a bright source of indistinguishable photons.
Milton and the Performing Arts
Authors: Campbell Gordon
Published: May 2024

Milton’s engagement with the performing arts was centred on three of those arts: drama, music, and the performance of literature. As a young man he was interested in theatre, both in London’s playhouses and in private venues. He had a lifelong passion for music, both as performer and listener. The most notable instances of his enthusiasm for the performance of literature are his youthful prolusions and his recitations in the Italian academies to which he was admitted. This chapter will trace the contours of Milton’s evolving tastes in these three areas, and their refractions in his poetry and prose.
‘There you shall enjoy your friends again’
Authors: Owens W R
Published: May 2024

In the second part of The Pilgrim’s Progress (1684), Bunyan includes a conversation between Great-heart and Mr Valiant-for-Truth about whether pilgrims would meet their friends in heaven. It is not the first time that Bunyan describes heaven as a place of social interaction as well as of eternal worship of God. This chapter argues that Bunyan’s concept of heaven is very much in line with earlier Puritan discussions of the nature of heaven, which had come to stress that we would recognize and be reunited with friends and family members there. One of the most influential Puritan treatments was Richard Baxter’s The Saints Everlasting Rest, in which Baxter writes with emotion of his expectation that he will meet earthly friends again in heaven. The endings of both parts of The Pilgrim’s Progress present an equally stirring depiction of heaven as a place of human fellowship, where pilgrims ‘will enjoy their friends again’.
Richard Baxter and International Protestantism
Authors: Smith Nigel
Published: May 2024

Richard Baxter and his writings are usually considered in an insular context, limited very much to England, especially by scholarship in the English-speaking world. Baxter encouraged this view by stating his incompetence in European vernaculars, especially French, and his disapproval of several kinds of continental thought, especially the radical reformers, aspects of Grotian theology and Cartesian and Spinozian rationalism and materialism. However, this essay shows that Baxter was greatly admired in many parts of Protestant Europe and that several of his writings were widely available in editions, principally in German and Dutch translations, with consequences for the nature of continental prose writing. He was popular with some early Pietists, and his writings were regarded as highly effective means of arousing and sustaining faith, even when some disagreed with his soteriology.
Outrage and Empathy
Authors: Finkel Stuart
Published: May 2024

This chapter marks the emergence from the mid-1870s of significant informal political prisoner aid groupings in St. Petersburg and elsewhere, which mirrored the flourishing and then repression of revolutionary populism. It highlights how the humanitarianist “Red Cross fervor” during the Balkan and Russo-Turkish conflicts was provocatively appropriated by radical women organizing to help arrested comrades. As arrests of young populists crescendoed in the late 1870s, the educated public expressed increasing sympathy. Liberal newspapers used the short-lived glasnost’ of Count Loris-Melikov’s “Dictatorship of the Heart” in 1880–81 to expose and criticize conditions of political exile in the European north and Siberia, sometimes printing extended correspondence from exiles in various locations. For a time in late 1880 to early 1881, the prominent daily Golos (The Voice) even accepted donations on behalf of recently released exiles still under police surveillance. All of this, however, came to an immediate halt with the assassination of Tsar Alexander II in March 1881, forcing assistance to political exiles and prisoners and even expressions of concern for them to go back underground.
Political Philanthropy Goes Abroad
Authors: Finkel Stuart
Published: May 2024

Part III of the book looks at the development of aid organization abroad over the same period. Chapter 5 begins by examining the ways in which both established émigrés like Pëtr Lavrov and recently arrived revolutionary “celebrities” in the late 1870s were able to draw Western attention to the Russian radical movement and to the desperate fate of their arrested comrades. In 1880 detailed blueprints for an “Amelioration Committee” for prisoners and exiles were developed by Vera Zasulich and Lev Gartman, whose fantastically ambitious plans for a British-funded émigré press organ along with this Committee went unrealized. The following year, however, when Zasulich and Lavrov were approached by the Moscow-based “Red Cross of the People’s Will” (KKNV) to coordinate a “foreign branch,” they were ready to do so, even though neither was a member of People’s Will itself. The chapter then documents how, with the help of other prominent émigrés, they quickly drafted a charter, donation forms, and an appeal, which appeared in French, German, Italian, and English-language newspapers. The effort attracted significant initial attention, with Zasulich leading efforts in Switzerland, Lavrov in France, Pëtr Kropotkin and Nikolai Chaikovskii in Britain, and Anna Kuliscioff in Italy; this attention in turn drew the ire of Russian diplomats, who succeeded in pressuring the French authorities into temporarily expelling Lavrov from the country in February 1882. Although this briefly reinvigorated interest in the cause, his absence, together with the arrest of the Moscow KKNV leadership, soon cast doubt on its sustainability.
Using network pharmacology to discover potential drugs for hypertrophic scars
Authors: Zhang Yi , Li Xiu , Yu Qian , Lv Xiaoyan , Li Chen , Wang Lianzhao , Liu Yue , Wang Qian , Yang Zhigang , Fu Xin , Xiao Ran
Published: May 2024

Background

Hypertrophic scarring is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation. Existing drugs have not achieved satisfactory therapeutic effects.

Objectives

To explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for their treatment.

Methods

Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model.

Results

WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, the transforming growth factor (TGF)-β signalling pathway and other biologic pathways. Integrin β1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and profibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA can also inhibit mouse scar hyperplasia.

Conclusions

ITGB1 and TGF-β signalling pathways are important for hypertrophic scar formation. Crizotinib could be a potential treatment drug for hypertrophic scars.
Lymphatic spread patterns in young versus elderly patients with stage III colon cancer
Authors: Song Jihyung , Kataoka Kozo , Inoue Manabu , Yamada Takeshi , Shiozawa Manabu , Beppu Naohito , Kuriyama Sho , Suto Takeshi , Matsuhashi Nobuhisa , Sakura Yusuke , Kanazawa Akiyoshi , Kagawa Hiroyasu , Kanemitsu Yukihide , Ceelen Wim , Ikeda Masataka
Published: May 2024

Background

The anatomical pattern of lymph nodes spread differs between young (aged 45 years or younger) and elderly (aged 80 years or older) patients with stage III colon cancer and is poorly investigated.

Methods

Two groups of patients (young and elderly) with stage III colon cancer who underwent upfront extensive (D3) lymphadenectomy at eight Japanese centres between 1998 and 2018 were retrospectively analysed. The primary endpoint was the proportion of positive central lymph nodes. The lymph nodes spreading pattern and its prognostic impact on recurrence-free survival and overall survival in the two groups were also compared.

Results

Two hundred and ten young patients and 348 elderly patients were identified and compared. The total number of lymph nodes harvested and the total number of invaded lymph nodes were significantly higher in younger patients compared with elderly patients (median of 31.5 (3–151) versus 21 (3–116), P < 0.001 and median of 3 (1–21) versus 2 (1–25), P < 0.001 respectively). The proportion of positive central lymph nodes were higher in younger patients than in elderly patients (9.52% (95% c.i. 6.24 to 14.2%) versus 4.59% (95% c.i. 2.84 to 7.31%), P = 0.012). In multivariate models for recurrence-free survival, central lymph nodes invasion were identified as a poor prognostic factor in younger patients (HR 5.21 (95% c.i. 1.76 to 15.39)) but not in elderly patients (HR 1.73 (95% c.i. 0.80 to 3.76)).

Conclusion

Young patients with stage III colon cancer have a higher risk of central lymph nodes invasion, suggesting a more aggressive disease biology. The presence of central lymph nodes invasion are associated with a worse outcome in young patients.
Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study
Authors: de la Motte Louise , Nordenvall Caroline , Martling Anna , Buchli Christian
Published: May 2024

Background

Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics.

Method

This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I–III in Sweden in 2007–2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure.

Results

In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity.

Conclusion

Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.
The PREVENT dementia programme: baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia
Authors: Ritchie Craig W , Bridgeman Katie , Gregory Sarah , O’Brien John T , Danso Samuel O , Dounavi Maria-Eleni , Carriere Isabelle , Driscoll David , Hillary Robert , Koychev Ivan , Lawlor Brian , Naci Lorina , Su Li , Low Audrey , Mak Elijah , Malhotra Paresh , Manson Jean , Marioni Riccardo , Murphy Lee , Ntailianis Georgios , Stewart William , Muniz-Terrera Graciela , Ritchie Karen
Published: May 2024

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery and are imaged using multi-modal 3-T MRI scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies that supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data include 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40–59, SD ± 5.47), with the majority female (n = 433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% versus 48.6%) and a relatively high prevalence of APOEɛ4 carriers (n = 264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n = 672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (total score 95.6 ± 4.06). Mean white matter hyperintensity volume at recruitment was 2.26 ± 2.77 ml (median = 1.39 ml), with hippocampal volume being 8.15 ± 0.79 ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel data set to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer’s Disease Data Initiative platform and Dementia Platforms UK platform pending approval of the data access request from the PREVENT steering group committee.
Paediatrics and genetics
Authors: Bali Radhika , Simpson Jacqueline K , Hussain Khawar
Published: May 2024

We describe an 8-month-old girl who presented with irritability and recurrent perioral crusted plaques that were poorly responsive to topical steroid therapy. The clinical presentation, investigation, treatment and prognosis are illustrated along with the most important initial investigation.
Comprehensive Quality Evaluation of Danggui–Jianzhong Decoction by Fingerprint Analysis, Multi-Component Quantitation and UPLC-Q-TOF-MS
Authors: Huang Lanyi , Liu Qing , Zhang Wenfang , Lin Bishan , Gao Yongjian , Deng Hong , Zhang Shu
Published: May 2024

Danggui–Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.
Using vitality indicators to predict survival of aquatic animals released from fisheries
Authors: Lennox R J , Donaldson M R , Raby G D , Cook K V , LaRochelle L , Madden J C , Cooke S J , Patterson D A , Hinch S G
Published: May 2024

Estimating the survival probability of animals released from fisheries can improve the overall understanding of animal biology with implications for fisheries management, conservation and animal welfare. Vitality indicators are simple visual measures of animal condition that change in response to stressors (like fisheries capture) and can be assessed to predict post-release survival. These indicators typically include immediate reflex responses which are typically combined into a score. Vitality indicators are straight-forward and non-invasive metrics that allow users to quantify how close (or far) an animal is from a normal, ‘healthy’ or baseline state, which in turn can be correlated with outcomes such as survival probability, given appropriate calibration. The literature on using vitality indicators to predict post-release survival of animals has grown rapidly over the past decade. We identified 136 papers that used vitality indicators in a fisheries context. These studies were primarily focused on marine and freshwater fishes, with a few examples using herptiles and crustaceans. The types of vitality indicators are diverse and sometimes taxa-specific (e.g. pinching leg of turtles, spraying water at nictitating membrane of sharks) with the most commonly used indicators being those that assess escape response or righting response given the vulnerability of animals when those reflexes are impaired. By presenting Pacific salmon fisheries as a case study, we propose a framework for using vitality indicators to predict survival across taxa and fisheries.
The minimal important difference in orthodontic treatment duration: a survey across adult patients
Authors: Mheissen Samer , Koletsi Despina , Joria Aya Bassam , Khan Haris , Alharbi Fahad , Koretsi Vasiliki , Awaisi Zubair Hassan , Qamar Rehan , Saeed Hassan , Alrefaiy Yaser Ali , Eliades Theodore , Guyatt Gordon
Published: May 2024

Background

The minimal important difference (MID) is defined as the smallest difference that the patient perceives as important. Furthermore, the smallest worthwhile effect (SWE) is the important change measured with the benefit-harm trade-off method. The aim of this study was to evaluate the MID in orthodontic treatment duration to inform the decision regarding seeking procedures to accelerate orthodontic tooth movement and reduce treatment duration.

Methods

We constructed a survey eliciting views of the MID from adult participants from four countries undergoing orthodontic treatment. Ten questions addressed reduction in the treatment duration for both durations 12 and 24 months, and four questions were related to the reduction in treatment duration that the patients would require to undergo surgical or non-surgical adjunctive procedures. We applied a univariable random effects logistic regression model to examine the association between the participants’ characteristics and the MID. Then, we fitted a multivariable logistic random effects regression including significant predictors.

Results

Four hundred and fifty adults, with a median age of 21 (interquartile range: 19–24), undergoing orthodontic treatment participated in the survey. Of the respondents, 60% considered 15 days as a trivial reduction from 12 months duration of therapy and 70% considered 15 days a trivial reduction from 24 months. Of the respondents, 48% considered the period of 2 months a moderate reduction from 12 months, and 60% considered 2 months a moderate reduction from 24 months. From these results, we inferred that patients considered reductions of approximately 1 month as the MID in the treatment duration for both 12 and 24 months. However, SWE was considerably more than the MID for most of the participants to decide undergoing surgical adjunctive procedures to reduce the time of therapy. The participants required smaller SWE to undergo non-surgical procedures compared to surgical procedures.

Conclusion

The MID in the treatment duration is one month for both treatment durations 12 and 24 months. Patients require a greater SWE than the MID to undergo adjunctive procedures to shorten the duration, particularly for surgical procedures.
Chlamydia trachomatis upregulates lncRNA CYTOR to mediate autophagy through miR-206/MAPK1 axis
Authors: Cheng Shan , Liu Yi , He Bei , Zhang Jinrong , Yang Yewei , Wang Xinglv , Li Zhongyu
Published: May 2024

Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.
‘Ein Strudel der Selbstauflösung’: The Contested Role of Form in Poetry from the Concentration Camps
Authors: Robinson-Self Elizabeth
Published: May 2024

German-language concentration camp poetry has been frequently criticized for its formal failings, particularly its lack of innovation and overreliance on traditional forms. In this article, I undertake close readings of three formally conventional texts: Alfred Kittner’s ‘Molotschna’ (composed in Obodowka, a Transnistrian extermination camp, in 1943), Fritz Löhner-Beda’s ‘Sonett auf das Revier im KZ-Buchenwald’ (composed in Buchenwald in 1940) and Heinrich Steinitz’s ‘Wo bist Du, Gott?’ (composed in Buchenwald between 1938 and 1942). I will demonstrate how traditional forms provided stability in the midst of extremity through their regularity, structure and link to a more stable past and identity. Moreover, I will propose that they were not simply readily available containers for the poet’s suffering, but also enabled the poet to shape their individual depiction of the camps and therefore provide as valid an insight as those works which respond to extremity with fragmentation and innovation.
Tumor regression pattern may impact the prognosis of rectal cancer patients with tumor regression grade 1 after neoadjuvant chemoradiotherapy
Authors: Tang Yuan-Ling , Zhou Ji-Tao , Gu Xia-Fei , Yang Li-Juan , Li Dan-Dan , Duan Jia-Yu , Jiang Dan , Wang Xin
Published: May 2024

Background

Tumor regression grade (TRG) is evaluated by calculating the proportion of residual tumor to stromal fibrosis, which can reflect the tumor response to neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). Overall, patients with TRG1 show good sensitivity to NCRT but the long-term survival for these patients remains different. This study aimed to assess the prognostic factors in patients with TRG1.

Methods

LARC patients who underwent NCRT and radical surgery were included. TRG was evaluated according to the National Comprehensive Cancer Network guidelines. The association between clinicopathological factors and survival outcomes was assessed in patients with TRG1. Overall survival (OS) and disease-free survival (DFS) were evaluated using both Kaplan–Meier analyses and Cox proportional hazards models.

Results

Of the 393 LARC patients, 104 (26.5%) were diagnosed with TRG1. The 5-year OS rates and 5-year DFS rates of patients with TRG1 were 90.9% and 72.2%, respectively. In patients with TRG1, the tumor regression pattern (P = 0.001), pathologic tumor node metastasis (TNM) stage (P = 0.002), neoadjuvant rectal score (P = 0.024), T downstaging (P = 0.022), and baseline carcinoembryonic antigen level (P = 0.038) were associated with DFS in univariate analysis. Only the tumor regression pattern showed prognostic significance for DFS in multivariate analysis (P = 0.003). The group with tumor shrinkage had a higher OS rate than the tumor fragmentation group but the difference in the OS rates between the two groups was not significant (P = 0.196).

Conclusions

TRG could be a prognostic variable for LARC patients receiving NCRT. In patients with TRG1, the tumor regression pattern may represent another useful prognostic factor to better individualize the prognosis.
Quantifying public and private investment in European biopharmaceutical research and development
Authors: Fowler Annabelle , Grieve Kathleen , Maos Andreas , Wilsdon Tim
Published: May 2024

Robust biopharmaceutical research and development (R&D) ecosystems require investment from both the public and private sectors. In Europe, there is an interest in growing biopharmaceutical R&D given its contribution to public health and the economy, which requires an understanding of current public and private investment. In addition, recent European draft legislation has focused on the public sector's contributions to biopharmaceutical R&D to inform pharmaceutical prices. However, there is little empirical evidence on the specifics of public and private funding for medicine R&D in Europe. This paper performs aggregative data collection to quantify 2019 investment in biopharmaceutical R&D by the public and private sectors in 6 countries: Belgium, France, Germany, Norway, Poland, and the United Kingdom. We find that, across these countries, the private sector accounts for just under two-thirds of investment. We contrast results to those obtained using high-level R&D indicators from the Organization for Economic Co-operation and Development (OECD) and contextualize differences. We then provide 2013–2019 estimates for Belgium, France, Germany, and the United Kingdom (countries with data to support such analysis), and show that total spending grew over those years, although proportions attributable to each sector remained stable. These findings should provide further evidence for debates on policies to effectively grow the biopharmaceutical R&D sector.
Measuring productivity dispersion: a parametric approach using the Lévy alpha-stable distribution
Authors: Yang Jangho , Heinrich Torsten , Winkler Julian , Lafond François , Koutroumpis Pantelis , Farmer J. Doyne
Published: May 2024

It is well known that value added (VA) per worker is extremely heterogeneous among firms, but relatively little has been done to characterize this heterogeneity more precisely. Here, we show that the distribution of VA per worker exhibits heavy tails, a very large support, and consistently features a proportion of negative values, which prevents log transformation. We propose to model the distribution of VA per worker using the four-parameter Lévy stable distribution, a natural candidate deriving from the generalized central limit theorem, and we show that it is a better fit than key alternatives. Fitting a distribution allows us to capture dispersion through the tail exponent and scale parameters separately. We show that these parametric measures of dispersion can be useful to characterize the evolution of dispersion in recent years.
Undergraduate pharmacy students’ perceptions and experiences of a student-led clinic providing preventative services
Authors: Abdul-Salam Prince , Richardson Charlotte , Nazar Hamde
Published: May 2024

Objectives

Authentic work-based learning is crucial to facilitate the development and preparedness for training healthcare professionals. Such experiences are challenging to design and secure within the clinical environment. One School of Pharmacy established a student-led clinic to provide undergraduate pharmacy students the opportunity to practise physical assessment and communication skills with members of the public. The aim of this study was to explore students’ thoughts and perspectives on this experience.

Methods

Undergraduate students were invited to participate in a semi-structured interview after their clinic experience. Transcriptions of the interviews were analysed by reflexive thematic analysis.

Results

Twelve students agreed to an interview that took place between October and December 2022. Three themes were identified from the qualitative data which related to external factors that influenced student experience of the clinic, for example, organizational issues and impact of the physical environment; interactions within the clinic environment; and internalized learning for example, professional growth and development, and the appreciating the learning opportunity.

Conclusions

In the current climate, where securing valuable work-based learning opportunity is challenging, student-led clinics offer an environment that is well-received by students and appears to facilitate student professional development. Student clinics are receiving more attention and investment across undergraduate healthcare programmes around the world given advantages such as these. However, they need to be well integrated and structured into the existing training and education and students need appropriate induction to prepare them for the experience and manage expectations.
Effect of Smoking on Longitudinal Interferon γ Release Assay Results Among Close Contacts of People with Pulmonary Tuberculosis
Authors: Arriaga María B , Amorim Gustavo , Figueiredo Marina C , Staats Cody , Kritski Afrânio L , Cordeiro-Santos Marcelo , Rolla Valeria C , Andrade Bruno B , Sterling Timothy R ,   for the RePORT-Brazil consortium, Andrade Alice M S , Rocha Michael S , Nascimento Vanessa , Cubillos-Angulo Juan M , Rebouças-Silva Jéssica , Viana Sayonara M , Brito Pedro , Santos Saulo R N , Ramos André , Costa Alysson G , Silva Jaquelane , de Oliveira Jamile G , Benjamin Aline , Gomes-Silva Adriano , Sant'Anna Flavia M , Ignácio Francine P , Lourenço Maria Cristina , Silva Elisangela C , Moreira Adriana S R , Mello Mayla , Turner Megan
Published: May 2024

Diagnosis of Mycobacterium tuberculosis infection in close contacts is critical for tuberculosis control. Smoking is a risk factor for M. tuberculosis infection and tuberculosis disease but its effect on longitudinal interferon γ release assay (IGRA) results remains unknown. We conducted a multisite prospective study in Brazil between 2015 and 2019, among close contacts of adults with culture-confirmed pulmonary tuberculosis. IGRA was performed at baseline, at month 6 if results were negative at baseline, and at months 24–30 after enrollment. IGRA results were categorized as IGRA positive (maintained from baseline to the last visit), IGRA conversion (from negative to positive at any time), IGRA reversion (from positive to negative at any time), and IGRA negative (maintained from baseline to the last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA positive, IGRA conversion, IGRA reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA reversion (adjusted odds ratio, 0.16 [95% confidence interval, .03–.70]). We did not detect associations between smoking and IGRA positive or IGRA conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.