bluuebunny/crossref_metadata_2025 huggingface dataset:
Cements and concretes materials characterisation using machine‐learning‐based reconstruction and 3D quantitative mineralogy via X‐ray microscopy
Authors: Mitchell Ria L. , Holwell Andy , Torelli Giacomo , Provis John , Selvaranjan Kajanan , Geddes Dan , Yorkshire Antonia , Kearney Sarah
Published: March 2024

3D imaging via X‐ray microscopy (XRM), a form of tomography, is revolutionising materials characterisation. Nondestructive imaging to classify grains, particles, interfaces and pores at various scales is imperative for our understanding of the composition, structure, and failure of building materials. Various workflows now exist to maximise data collection and to push the boundaries of what has been achieved before, either from singular instruments, software or combinations through multimodal correlative microscopy. An evolving area on interest is the XRM data acquisition and data processing workflow; of particular importance is the improvement of the data acquisition process of samples that are challenging to image, usually because of their size, density (atomic number) and/or the resolution they need to be imaged at. Modern advances include deep/machine learning and AI resolutions for this problem, which address artefact detection during data reconstruction, provide advanced denoising, improved quantification of features, upscaling of data/images, and increased throughput, with the goal to enhance segmentation and visualisation during postprocessing leading to better characterisation of samples. Here, we apply three AI and machine‐learning‐based reconstruction approaches to cements and concretes to assist with image improvement, faster throughput of samples, upscaling of data, and quantitative phase identification in 3D. We show that by applying advanced machine learning reconstruction approaches, it is possible to (i) vastly improve the scan quality and increase throughput of ‘thick’ cores of cements/concretes through enhanced contrast and denoising using DeepRecon Pro, (ii) upscale data to larger fields of view using DeepScout and (iii) use quantitative automated mineralogy to spatially characterise and quantify the mineralogical/phase components in 3D using Mineralogic 3D. These approaches significantly improve the quality of collected XRM data, resolve features not previously accessible, and streamline scanning and reconstruction processes for greater throughput.
Testing pulmonary physiology in ventilated non‐human primates
Authors: Cervantes Orlando , Berg Melissa R. , Kapnadak Siddhartha G. , Miller Elizabeth , Fountain Connie , Curtis Britni , Thelen Sandi , Ruff Shannon , Huang Hazel , Altemeier William , Adams Waldorf Kristina M.
Published: March 2024

Background

Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow‐volume and pressure‐volume loops. Application of this protocol during mechanical ventilation in non‐human (NHP) models would represent a major advance in respiratory viral disease research.

Methods

We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation.

Results

The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%–81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2). There was also a 16%–45% decline in lung compliance.

Conclusion

We describe a new approach to performing pulmonary physiology testing protocol in non‐human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines.
Quality change in Bombay duck (Harpadon nehereus) surimi during frozen storage using different freezing methods
Authors: Yang Jing , Jiang Yuxin , Li Mingao , Deng Shanggui , Gao Yuanpei , Hu Yi
Published: March 2024

To inhibit the quality deterioration caused by the frozen storage of surimi products, this work investigated the effect of freezing methods, including raw‐freezing‐setting‐heating, raw‐setting‐freezing‐heating, and raw‐setting‐heating‐freezing, on quality changes in surimi gel. The moisture loss, physical–chemical properties, and protein structure conformation of surimi gel derived from Bombay duck (BD) were assessed following frozen storage periods of 20, 40, and 60 days. The findings suggest that the raw‐setting‐heating‐freezing method yielded optimal surimi gel properties with extended frozen storage time. Employing this approach led to a reduction in thawing loss, while cooking loss remained constant. After 60 days of frozen storage, the hardness exhibited an initial increase followed by a subsequent decrease, and water‐holding capacity increased to 68.2%. Notably, the impact on surimi gel during the late stage of frozen storage was more pronounced throughout the formation of ice crystals, resulting in decreased disulfide bond content. Scanning hematoxylin–eosin (HE) staining slices of samples following thawing and heating demonstrated that the raw‐setting‐heating‐freezing method could better resist the effect of ice crystals in frozen storage period on surimi tissue, while the gel on setting process could delay the erosion imposed on by ice crystals during frozen storage. This study provides a scientific foundation for the industrialization on frozen BD surimi products.
Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes
Authors: Chen Huey‐Ling , Lee Chien‐Nan , Chang Chin‐Hao , Lai Ming‐Wei , Tsai Ming‐Chieh , Mu Shu‐Chi , Liu Chun‐Jen , Shih Jin‐Chung , Wen Wan‐Hsin , Hu Rui‐Ting , Huang Chun‐Pin , Hu Kuang‐Chun , Chen Chie‐Pein , Lee Chyi‐Long , Chien Rong‐Nan , Chang Kai‐Chi , Hsu Hong‐Yuan , Lee Chien‐Chang , Ni Yen‐Hsuan , Chang Mei‐Hwei
Published: March 2024

Background

The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother‐to‐child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation.

Methods

The maternal and infant outcomes were compared in multi‐centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow‐ups. To explore the dynamic pre‐ and postpartum changes in ALT levels, we used a group‐based trajectory model for analysing data of 332 women from three prospective studies.

Results

After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg‐positive rates among 12‐month‐old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF‐treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%).

Conclusions

TAF effectively reduces mother‐to‐child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment.

Clinical trial number: NCT03695029 (ClinicalTrials.gov).
Liver transplantation and primary liver cancer in porphyria
Authors: Lissing Mattias , Wang Bruce , Wahlin Staffan
Published: March 2024

The porphyrias are a heterogeneous group of metabolic disorders that result from defects in heme synthesis. The metabolic defects are present in all cells, but symptoms are mainly cutaneous or related to neuropathy. The porphyrias are highly relevant to hepatologists since patients can present with symptoms and complications that require liver transplantation (LT), and some porphyrias are associated with a high risk for primary liver cancer (PLC). Among the cutaneous porphyrias, erythropoietic protoporphyria (EPP) can lead to cholestatic liver failure where LT cures the liver disease but not the porphyria. In acute porphyria (AP), neurotoxic porphyrin precursors are produced in the liver and LT is a curative treatment option in patients with recurrent severe neuropathic attacks. Patients with AP, mainly acute intermittent porphyria, have a significantly increased risk for PLC that warrants surveillance and adequate follow‐up of high‐risk groups. LT is well established in both EPP with liver failure and AP with recurrent attacks, but most transplant centres have little porphyria experience and cooperation between transplant hepatologists, and porphyria experts is important in the often‐difficult decisions on timing and management of comorbid conditions.
Radiopaque marker colonic transit study in the pediatric population BSPGHAN Motility Working Group consensus statement
Authors: Papadopoulos M. , Mutalib M. , Nikaki K. , Volonaki E. , Rybak A. , Thapar N. , Lindley K. , Borrelli O. , Das A. , Crespi D. , Cleeve S. , Athanasakos E.
Published: March 2024

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population.
Epidemiology of oral cancer in South and South‐East Asia: Incidence and mortality
Authors: Filho Adalberto M. , Warnakulasuriya Saman
Published: March 2024

Introduction

This study provides an epidemiological description of cancer in the lip, oral cavity, and oropharynx in the South and South‐East Asia region.

Methods

The number of new cases and deaths was extracted from the GLOBOCAN 2020 and the CI5 series. We present age‐standardized incidence and mortality rates per 100,000 inhabitants. To assess temporal trends, we estimated the annual percent change.

Results

The incidence rates (ASR) for lip and oral cavity cancer in South and South‐East Asia were highest in Taiwan (30.2), Sri Lanka (16.5), India (14.8), and Pakistan (13.2) among males. For oropharyngeal cancer, the highest rates were found in Taiwan (4.7), Bangladesh, Sri Lanka, and India (4.3, 2.9, and 2.6, respectively). Incidence rates were consistently higher in males compared to females. Overall, trends in lip and oral cavity cancer incidence were either stable or decreasing in most of the populations evaluated. In India, an increase in rates among males contrasted with a decline among females over the study period.

Conclusion

Incidence and mortality rates of oral cavity cancer in South and South‐East Asia are among the highest globally. Our results suggest an optimistic trend of reduction in oral cavity rates in the region, despite an increase in rates among Indian males.
Assessment of the effects of myopic and hyperopic anisometropia on choroidal vascular structure in children using SS‐OCTA
Authors: Cao Yiwen , Gu Xiaopeng , Zhang Yadi , Zhao Jingjing , Zhu Dehai
Published: March 2024

Objective

To compare large‐ and medium‐sized choroidal vascularity and the choriocapillaris (CC) flow area in children with different refractive errors using swept‐source optical coherence tomography angiography (SS‐OCTA).

Methods

Forty‐two anisometropic children were enrolled and divided into hyperopic anisometropia (HA) and myopic anisometropia (MA) groups. SS‐OCTA was performed to analyse choroidal vascularity. Mean choroidal thickness (CT), choroidal vascularity volume (CVV), choroidal vascularity index (CVI) and CC flow area were compared between the two eyes. The inter‐ocular differences between the two groups were also determined.

Results

Mean CT and CVV were highest in eyes with shorter axial lengths in both refractive groups, and the difference between the two eyes was positively correlated with the difference in axial length at the foveal region. Significant differences in the CVI in the MA group were only found in the parafoveal region. Inter‐ocular differences in the CC were significantly reduced in eyes with longer axial lengths in the foveal and parafoveal regions of the HA and MA groups, respectively. Comparing inter‐ocular differences, CC was significantly greater in the parafoveal region of the MA group than the HA group.

Conclusions

All layers of choroidal vasculature were thinner in eyes with longer axial lengths in all groups. The inter‐ocular CC difference was greater in the MA than in the HA group, with similar differences in axial length. This suggests that both medium‐to‐large choroidal vascular and choroidal capillaries may play a role in myopia development.
The experience of seeking and accessing help from mental health services among young people of Eastern European backgrounds: A qualitative interview study
Authors: Radez Jerica , Causier Chiara , Maughan Daniel , Waite Felicity , Johns Louise
Published: March 2024

Objectives

Most lifetime mental health problems (MHP) start before the age of 25. Yet young people—particularly those of minority backgrounds—often do not seek or access professional help. In the UK, young people of Eastern European (EE) backgrounds represent a large minority group; however, little is known about their experiences of MHP and help‐seeking. In this study, we aim to understand the help‐seeking process from the perspectives of EE young people.

Design

We used a qualitative study design with semi‐structured individual interviews. The results were analysed using reflexive thematic analysis.

Method

Twelve young people (18–25 years) of EE backgrounds, living in Oxfordshire, UK, took part. All participants had experienced a severe MHP and were identified in the community.

Results

EE young people's experiences of MHP and help‐seeking were driven by a sense of being caught between different cultures and simultaneously needing to navigate the potentially contrasting expectations of both cultures. This process was reinforced or tempered by the perceived continuing influence of young people's families, that is, families with more open views about MHP made it easier for young people to navigate through the process of help‐seeking. Young people's internalised cultural and familial beliefs about MHP affected their decision‐making when experiencing difficulties, their levels of trust in services, and perceived sense of resourcefulness and ability to cope.

Conclusions

Recognising and responding to the cultural tension that young people of EE backgrounds may experience can help us to develop more accessible and inclusive mental health services.
miR396b/GRF6 module contributes to salt tolerance in rice
Authors: Yuan Huanran , Cheng Mingxing , Wang Ruihua , Wang Zhikai , Fan Fengfeng , Wang Wei , Si Fengfeng , Gao Feng , Li Shaoqing
Published: March 2024

Salinity, as one of the most challenging environmental factors restraining crop growth and yield, poses a severe threat to global food security. To address the rising food demand, it is urgent to develop crop varieties with enhanced yield and greater salt tolerance by delving into genes associated with salt tolerance and high‐yield traits. MiR396b/GRF6 module has previously been demonstrated to increase rice yield by shaping the inflorescence architecture. In this study, we revealed that miR396b/GRF6 module can significantly improve salt tolerance of rice. In comparison with the wild type, the survival rate of MIM396 and OE‐GRF6 transgenic lines increased by 48.0% and 74.4%, respectively. Concurrent with the increased salt tolerance, the transgenic plants exhibited reduced H2O2 accumulation and elevated activities of ROS‐scavenging enzymes (CAT, SOD and POD). Furthermore, we identified ZNF9, a negative regulator of rice salt tolerance, as directly binding to the promoter of miR396b to modulate the expression of miR396b/GRF6. Combined transcriptome and ChIP‐seq analysis showed that MYB3R serves as the downstream target of miR396b/GRF6 in response to salt tolerance, and overexpression of MYB3R significantly enhanced salt tolerance. In conclusion, this study elucidated the potential mechanism underlying the response of the miR396b/GRF6 network to salt stress in rice. These findings offer a valuable genetic resource for the molecular breeding of high‐yield rice varieties endowed with stronger salt tolerance.
The Contemporary Presidency: Which presidents win more or less than expected in Congress? A Biden update
Authors: Bond Jon R.
Published: March 2024

This article updates estimates of which presidents won more or fewer votes than should be expected through President Biden's first two years in office. Multiple regression models estimating the effects of contextual variables (party, public approval, and party polarization plus interactions) establish a common baseline. Errors reveal which presidents won more or less than should be expected. Party polarization conditions relationships between party control and presidential success, but effects differ across chambers. As polarization increases in the House, majority presidents win more votes and minority presidents win fewer. The effects are less obvious in the Senate. Majority presidents win more than do minority presidents regardless of polarization. But polarization has led to a de facto 60‐vote Senate, as the minority party uses the supermajority required to invoke cloture to block confirmation of presidential appointments. Conclusions discuss limitations of roll‐call vote measures of presidential success.
Exploring mitochondrial metabolism of wild‐type and diabetic mice skin explants using the Seahorse technology
Authors: Dugrain Justine , Canaple Laurence , Picard Nicolas , Sigaudo‐Roussel Dominique , Bonod Christelle
Published: March 2024

Background

Skin wound healing is a complex mechanism which requires a lot of energy, mainly provided by mitochondrial respiration. However, little is known about the mitochondrial bioenergetics of mice skin. We sought to develop a microplate‐based assay to directly measure oxygen consumption in whole mice skin with the goal of identifying mitochondrial dysfunction in diabetic skin using an extracellular flux.

Materials and methods

Different parameters were optimized to efficiently measure the oxygen consumption rate (OCR). First, the most pertinent skin side of wild‐type mice was first determined. Then, concentrations of mitochondrial inhibitors were then optimized to get the best efficacy. Finally, punch sizes were modulated to get the best OCR profile.

Results

Dermis had the best metabolic activity side of the skin. Unlike the increased concentrations of carbonyl cyanide‐p‐trifluoromethoxyphenylhydrazone (FCCP) and rotenone/antimycin A, which showed no improvement of these drugs' effects, varying the skin punch size was successful. Finally, type II diabetic (T2D) skin produced less ATP through mitochondrial metabolism and had a greater non‐mitochondrial oxygen consumption than wild‐type or type I diabetic (T1D) skin.

Conclusion

Here we designed, for the first time, a reliable protocol to measure mitochondria function in whole mouse skin. Our optimized protocol was valuable in assessing alterations associated with diabetes and could be applied to future studies of pathological human skin metabolism.
“Churchill's Party”: A necessary experiment in personalization
Authors: Kowol Kit
Published: March 2024

Aim

This article aims to determine the extent of “personalization” and “de‐institutionalization” within the Conservative Party in Britain during the period 1940–1945 when the Party was under the leadership of Winston Churchill.

Materials and methods

The article examines the different dimensions of “personalization” and “de‐institutionalization” as defined by Harmel, Svåsand, and Mjelde in this special edition. To do so, it uses a variety of sources including: internal party records, memoirs and biographies, contemporaneous diaries, letters to party leaders, and survey research undertaken by the organization Mass Observation.

Results

The article identified that a limited degree of personalization took place during the period. This was largely in relation to the movement away from existing internal policy and procedures, especially those to do with electioneering. Evidence regarding other dimensions was mixed with a notable lack of change in the perceptions other parties and their leaders held about the Conservative Party.

Conclusion

The article suggests that the personalization that occurred within the Party was largely a product of necessity, notably the unpopularity of the Conservative “brand” during World War II, compared to Churchill's own personal popularity, as well as the disruptions caused by the war itself. The article argues that this was enabled, to an extent, by the already high degree of latitude that the Conservative Party afforded its leaders. At the same time, the article notes the way in which defeat at the 1945 general election led to the Conservative Party “snapping back” to its pre‐war highly institutionalized form. Both findings highlight the extent to which electoral calculations were central to the process of personalization and its subsequent reverse.
Thermal regulation of dormancy in Echinochloa crus‐galli (L.) P. Beauv. seeds: Development of a model to predict the temporal ‘window’ of emergence in the field
Authors: Malavert Cristian , Batlla Diego
Published: March 2024

Predicting weed emergence is of vital importance for weed management, since the seedling stage is the most effective plant stage for the application of control practices. In weeds species whose seeds present dormancy, as in Echinochloa crus‐galli, predicting emergence requires understanding how the environment regulates seed dormancy level. In the present work we studied the environmental regulation of dormancy in E. crus‐galli seeds. For this, E. crus‐galli seeds were stored under different conditions: (i) moist at 5, 10 and 15°C (stratification) and (ii) dry at 15 and 25°C (dry after‐ripening) for 80 days. During storage the seeds were tested for germination at regular intervals under a wide thermal range (10–30°C). The results showed that the changes in dormancy level were associated with a widening of the thermal range permissive for seed germination, which was mainly explained by a decrease in its lower limit temperature (Tl). This decrease in Tl was higher when the seeds were stratified at 10°C than at 5 and 15°C. Seeds exposed to dry after‐ripening showed an extremely low rate of dormancy release. Obtained results were used to establish functional relationships able to predict the temporal ‘window’ of field emergence of E. crus‐galli as a function of soil temperature.
Electrochemical Activity Measurements of UCl3 in Molten NaCl-MgCl2-UCl3
Authors: Yankey Jacob , Monreal Marisa , Jackson Matt , Simpson Michael
Published: March 2024

Open circuit potential (OCP) measurements were made to determine uranium chloride (UClx) species activity in NaCl–MgCl2, which is a candidate salt for use in a molten salt reactor fuel. The operating temperature ranged from 500 to 650 °C, and the measurement system used a U-Zr working electrode (WE) and Ag/AgCl reference electrode (RE). The activity was calculated to range from 2.52×10−6 to 2.99×10−8 (with uncertainties of ±1.0×10−7 and ±1.1×10−9, respectively), dependent upon the temperature and concentration of UCl3 (ranging from 0.25 to 11.55 wt.%). Fit of the OCP data to the Nernst equation resulted in values of 3.1 to 4.8 electrons transferred per U atom. This indicates the possibility for codeposition of Mg2+ and U3+ under certain conditions. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photo-electron spectroscopy analyses of cathodic deposits confirm the presence of metallic magnesium.
Effect of Gear Tooth Cracks on the Dynamic Characteristics of Gear Transmission System of High-Speed Train
Authors: Zhang Jian-Chao , Cai Li-Wei , Chen Zhan , Qi Xing-Ke
Published: March 2024

In order to study the dynamic characteristics of a high-speed train gear transmission system with cracks, time-varying meshing stiffness of gear teeth with different cracks was obtained using energy method. A torsional vibration model of the gear transmission system of a high-speed train was established. Based on the model, the ρ-value describing the change in stiffness was used to obtain the analytical solution of a system with crack faults. The influence of the degree of crack on the dynamic characteristics of a system under torque excitation of the driving end and load end was analyzed. In contrast with a normal gear system, a system containing a crack fault generated no harmonic response. Moreover, for a given set of working conditions, the degree of crack only affected the resonance amplitude and frequency of the system. These results form a robust guide for the detection of crack faults in the gear transmission system of a high-speed train.
Caffeine, but Not Creatine, Improves Anaerobic Power Without Altering Anaerobic Capacity in Healthy Men During a Wingate Anaerobic Test
Authors: Marinho Alisson Henrique , Silva-Cavalcante Marcos David , Cristina-Souza Gislaine , Sousa Filipe Antonio de Barros , Ataide-Silva Thays , Bertuzzi Romulo , de Araujo Gustavo Gomes , Lima-Silva Adriano Eduardo
Published: March 2024

There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p < .05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p = .01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p > .05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity.
Early Maladaptive Schemas, Cognitive Fusion, and Anabolic-Androgenic Steroid Use Attitudes: The Mediating Role of Muscle Dysmorphia in Iran
Authors: Ebrahimi Mehdi , Zamani Zahra , Bagheri Ebrahim
Published: March 2024

In recent decades, the interest in having an ideal body in men has caused a pathological tendency to be muscular, followed by a tendency to use anabolic-androgenic steroids (AASs). This study was designed to evaluate the mediating role of muscle dysmorphia in the relationship between early maladaptive schemas and body image-related cognitive fusion with the tendency to use AAS in male athletes. Out of the total number of men referring to fitness clubs in Isfahan, Iran, 474 men were evaluated using a multistage random cluster sampling method. The questionnaires used in this research included the Muscle Dysmorphic Disorder Inventory, Cognitive Fusion Questionnaire—Body Image, Young Schema Questionnaire—Short Form, and Prototype Willingness Model Questionnaire. The results demonstrated that the relationship of AAS use with body image-related cognitive fusion and the three maladaptive schemas with the mediation of muscle dysmorphia is significant. The present study provides significant implications in the discussion of prevention and treatment of AAS addiction.
Large-FOV 3D localization microscopy by spatially variant point spread function generation
Authors: Xiao Dafei , Kedem Orange Reut , Opatovski Nadav , Parizat Amit , Nehme Elias , Alalouf Onit , Shechtman Yoav
Published: March 2024

Accurate characterization of the microscopic point spread function (PSF) is crucial for achieving high-performance localization microscopy (LM). Traditionally, LM assumes a spatially invariant PSF to simplify the modeling of the imaging system. However, for large fields of view (FOV) imaging, it becomes important to account for the spatially variant nature of the PSF. Here, we propose an accurate and fast principal components analysis–based field-dependent 3D PSF generator (PPG3D) and localizer for LM. Through simulations and experimental three-dimensional (3D) single-molecule localization microscopy (SMLM), we demonstrate the effectiveness of PPG3D, enabling super-resolution imaging of mitochondria and microtubules with high fidelity over a large FOV. A comparison of PPG3D with a shift-variant PSF generator for 3D LM reveals a threefold improvement in accuracy. Moreover, PPG3D is approximately 100 times faster than existing PSF generators, when used in image plane–based interpolation mode. Given its user-friendliness, we believe that PPG3D holds great potential for widespread application in SMLM and other imaging modalities.
ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia
Authors: Behrens Kira , Brajanovski Natalie , Xu Zhen , Viney Elizabeth M. , DiRago Ladina , Hediyeh-Zadeh Soroor , Davis Melissa J. , Pearson Richard B. , Sanij Elaine , Alexander Warren S. , Ng Ashley P.
Published: March 2024

Philadelphia chromosome–positive B cell acute lymphoblastic leukemia (B-ALL), characterized by the
BCR::ABL1
fusion gene, remains a poor prognosis cancer needing new therapeutic approaches. Transcriptomic profiling identified up-regulation of oncogenic transcription factors ERG and c-MYC in
BCR::ABL1
B-ALL with ERG and c-MYC required for
BCR::ABL1
B-ALL in murine and human models. Profiling of ERG- and c-MYC–dependent gene expression and analysis of ChIP-seq data established ERG and c-MYC coordinate a regulatory network in
BCR::ABL1
B-ALL that controls expression of genes involved in several biological processes. Prominent was control of ribosome biogenesis, including expression of RNA polymerase I (POL I) subunits, the importance of which was validated by inhibition of
BCR::ABL1
cells by POL I inhibitors, including CX-5461, that prevents promoter recruitment and transcription initiation by POL I. Our results reveal an essential ERG- and c-MYC–dependent transcriptional network involved in regulation of metabolic and ribosome biogenesis pathways in
BCR::ABL1
B-ALL, from which previously unidentified vulnerabilities and therapeutic targets may emerge.
Engineered MgO nanoparticles for cartilage-bone synergistic therapy
Authors: Zheng Liming , Zhao Sheng , Li Yixuan , Xu Jiankun , Yan Wenjin , Guo Baosheng , Xu Jianbin , Jiang Lifeng , Zhang Yifeng , Wei Hui , Jiang Qing
Published: March 2024

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg
2+
on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-
co
-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration
Authors: Du Lin , Wu Jinfu , Han Yahui , Wu Chengtie
Published: March 2024

Limited motor activity due to the loss of natural structure impedes recovery in patients suffering from tendon-to-bone injury. Conventional biomaterials focus on strengthening the regenerative ability of tendons/bones to restore natural structure. However, owing to ignoring the immune environment and lack of multi-tissue regenerative function, satisfactory outcomes remain elusive. Here, combined manganese silicate (MS) nanoparticles with tendon/bone-related cells, the immunomodulatory multicellular scaffolds were fabricated for integrated regeneration of tendon-to-bone. Notably, by integrating biomimetic cellular distribution and MS nanoparticles, the multicellular scaffolds exhibited diverse bioactivities. Moreover, MS nanoparticles enhanced the specific differentiation of multicellular scaffolds via regulating macrophages, which was mainly attributed to the secretion of
PGE2
in macrophages induced by Mn ions. Furthermore, three animal results indicated that the scaffolds achieved immunomodulation, integrated regeneration, and function recovery at tendon-to-bone interfaces. Thus, the multicellular scaffolds based on inorganic biomaterials offer an innovative concept for immunomodulation and integrated regeneration of soft/hard tissue interfaces.
Bicontinuous vitrimer heterogels with wide-span switchable stiffness-gated iontronic coordination
Authors: Zhao Ziguang , Cao Ziquan , Wu Zhixin , Du Wenxin , Meng Xue , Chen Huawei , Wu Yuchen , Jiang Lei , Liu Mingjie
Published: March 2024

Currently, it remains challenging to balance intrinsic stiffness with programmability in most vitrimers. Simultaneously, coordinating materials with gel-like iontronic properties for intrinsic ion transmission while maintaining vitrimer programmable features remains underexplored. Here, we introduce a phase-engineering strategy to fabricate bicontinuous vitrimer heterogel (VHG) materials. Such VHGs exhibited high mechanical strength, with an elastic modulus of up to 116 MPa, a high strain performance exceeding 1000%, and a switchable stiffness ratio surpassing 5 × 10
3
. Moreover, highly programmable reprocessing and shape memory morphing were realized owing to the ion liquid–enhanced VHG network reconfiguration. Derived from the ion transmission pathway in the ILgel, which responded to the wide-span switchable mechanics, the VHG iontronics had a unique bidirectional stiffness-gated piezoresistivity, coordinating both positive and negative piezoresistive properties. Our findings indicate that the VHG system can act as a foundational material in various promising applications, including smart sensors, soft machines, and bioelectronics.
Suprachoroidal gene transfer with nonviral nanoparticles in large animal eyes
Authors: Shen Jikui , Lima e Silva Raquel , Zhang Mingliang , Luly Kathryn M. , Hackett Sean F. , Tzeng Stephany Y. , Lowmaster Shirley M. , Shannon Sydney R. , Wilson David R. , Green Jordan J. , Campochiaro Peter A.
Published: March 2024

Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human-sized minipig eye that suprachoroidal injection of 50 μl of NPs containing 19.2 μg of GFP expression plasmid caused GFP expression in photoreceptors and RPE throughout the entire eye with no toxicity. Two weeks after injection of 50, 100, or 200 μl, there was considerable within-eye and between-eye variability in expression that was reduced 3 months after injection of 200 μl and markedly reduced after three suprachoroidal injections at different locations around the eye. Reduction of bacterial
CpG
sequences in the expression plasmid resulted in a trend toward higher expression. These data indicate that nonviral suprachoroidal gene therapy with optimized polymer, expression plasmid, and injection approach has potential for treating photoreceptors throughout the entire retina of a human-sized eye.
Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment
Authors: Jogiraju Vamshi , Weber Elijah , Hindman Jason , West Steve , Ling John , Rhee Martin , Girish Sandhya , Palaparthy Ramesh , Singh Renu
Published: March 2024

Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child–Pugh–Turcotte (CPT) Class B: score 7–9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal (
n
= 10) or impaired (
n
= 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration–time curve from time 0 to infinity (AUC
inf
) and maximum concentration (C
max
)] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUC
inf
and C
max
were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe and well tolerated in both studies. These results support the use of approved lenacapavir dosing regimen in patients with mild (CPT Class A: score 5–6) or moderate hepatic impairment as well as in patients with mild (60 ≤ CLcr ≤ 89 mL/min), moderate (30 ≤ CLcr ≤ 59 mL/min), and severe renal impairment.
Exploring the prokaryote-eukaryote interplay in microbial mats from an Andean athalassohaline wetland
Authors: Cubillos Carolina F. , Aguilar Pablo , Moreira David , Bertolino Paola , Iniesto Miguel , Dorador Cristina , López-García Purificación
Published: March 2024

Microbial community assembly results from the interaction between biotic and abiotic factors. However, environmental selection is thought to predominantly shape communities in extreme ecosystems. Salar de Huasco, situated in the high-altitude Andean Altiplano, represents a poly-extreme ecosystem displaying spatial gradients of physicochemical conditions. To disentangle the influence of abiotic and biotic factors, we studied prokaryotic and eukaryotic communities from microbial mats and underlying sediments across contrasting areas of this athalassohaline ecosystem. The prokaryotic communities were primarily composed of bacteria, notably including a significant proportion of photosynthetic organisms like Cyanobacteria and anoxygenic photosynthetic members of Alpha- and Gammaproteobacteria and Chloroflexi. Additionally, Bacteroidetes, Verrucomicrobia, and Deltaproteobacteria were abundantly represented. Among eukaryotes, photosynthetic organisms (Ochrophyta and Archaeplastida) were predominant, alongside relatively abundant ciliates, cercozoans, and flagellated fungi. Salinity emerged as a key driver for the assembly of prokaryotic communities. Collectively, abiotic factors influenced both prokaryotic and eukaryotic communities, particularly those of algae. However, prokaryotic communities strongly correlated with photosynthetic eukaryotes, suggesting a pivotal role of biotic interactions in shaping these communities. Co-occurrence networks suggested potential interactions between different organisms, such as diatoms with specific photosynthetic and heterotrophic bacteria or with protist predators, indicating influences beyond environmental selection. While some associations may be explained by environmental preferences, the robust biotic correlations, alongside insights from other ecosystems and experimental studies, suggest that symbiotic and trophic interactions significantly shape microbial mat and sediment microbial communities in this athalassohaline ecosystem.

IMPORTANCE

How biotic and abiotic factors influence microbial community assembly is still poorly defined. Here, we explore their influence on prokaryotic and eukaryotic community assembly within microbial mats and sediments of an Andean high-altitude polyextreme wetland system. We show that, in addition to abiotic elements, mutual interactions exist between prokaryotic and eukaryotic communities. Notably, photosynthetic eukaryotes exhibit a strong correlation with prokaryotic communities, specifically diatoms with certain bacteria and other protists. Our findings underscore the significance of biotic interactions in community assembly and emphasize the necessity of considering the complete microbial community.
Improving medical record completeness at Wallaga University Referral Hospital: a multidimensional quality improvement project
Authors: Bayisa Gedefa , Gonfaa Lammii , Badasa Ketema , Dugasa Nemomsa , Abebe Mulugeta , Deressa Habtamu , Teshoma Regassa Misganu , Takele Amsalu , Tilahun Temesgen
Published: March 2024

Background

Appropriately documented medical records enhance coordination, patient outcomes and clinical research.

Objective

The aim of this project was to improve Wallaga University Referral Hospital’s (WURH) medical record completeness rate from 53% to 80% from 1 January 2023 to 31 August 2023.

Methods

A hospital-based interventional study was conducted at WURH. The Plan-Do-Study-Act cycle was used to test change ideas. A fishbone diagram and a driver diagram were used to identify root causes and address them. Key interventions consisted of supportive supervision, developing and distributing standardised formats, orientation for staff, establishing a chart audit team and assigning data owners.

Result

On the completion of the project, the overall implementation of inpatient medical record completeness increased from 53% to 82%. This improvement varies from department-to-department. It increased from 51% to 79%, 53% to 79%, 46% to 81% and 64% to 91% in the departments of internal medicine, paediatrics, obstetrics and gynaecology and surgery, respectively. The project brought improvements in the completeness of physician notes (84% to 100%), physician order sheet (54% to 84%), nursing care plan (26% to 69%), admission sheet (76% to 98%), discharge summary (94% to 98%), progress note (38% to 91%), medication administration (80% to 100%), appropriate attachment of documents (78% to 93%) and documentation of vital signs (50% to 100%).

Conclusion and recommendation

The rate of medical record completeness was significantly improved in the study area. This was achieved through the application of multidimensional change ideas related to health professionals, supplies, health management information systems and leadership. However, in some of the parameters, the national targets were not met. Therefore, we recommend providing regular technical updates, conducting frequent chart audits and providing supportive supervision for the enhancement of medical record completeness. It is also advisable for the hospital management to work on its sustainability.
Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases
Authors: Oltmanns Friederike , Vieira Antão Ana , Irrgang Pascal , Viherlehto Vera , Jörg Leticia , Schmidt Anna , Wagner Jannik T , Rückert Michael , Flohr Ann-Sophie , Geppert Carol Imanuel , Frey Benjamin , Bayer Wibke , Gravekamp Claudia , Tenbusch Matthias , Gaipl Udo , Lapuente Dennis
Published: March 2024

Background

Generally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome.

Methods

Here, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1β to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model.

Results

The mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice.

Conclusion

In summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments.
“QGP Signatures” revisited
Authors: Harris John W. , Müller Berndt
Published: March 2024

We revisit the graphic table of QCD signatures in our 1996 Annual Reviews article “The Search for the Quark–Gluon Plasma” and assess the progress that has been made since its publication towards providing quantitative evidence for the formation of a quark–gluon plasma in relativistic heavy-ion collisions and its characteristic properties.
NLO electroweak corrections to doubly-polarized $$W^+W^-$$ production at the LHC
Authors: Dao Thi Nhung , Le Duc Ninh
Published: March 2024

We present new results of next-to-leading order (NLO) electroweak corrections to doubly-polarized cross sections of $$W^+W^-$$

W
+

W
-

production at the LHC. The calculation is performed for the leptonic final state of $$e^{+}\mu _{e} \mu ^{-} {\bar{\nu }}_{\mu }$$

e
+

μ
e

μ
-

ν

¯

μ

using the double-pole approximation in the diboson center-of-mass frame. NLO QCD corrections and subleading contributions from the gg, $$b{\bar{b}}$$

b

b

¯

, $$\gamma \gamma $$

γ
γ

induced processes are taken into account in the numerical results. We found that NLO EW corrections are small for angular distributions but can reach tens of percent for transverse momentum distributions at high energies, e.g. reaching $$-40\%$$

-
40
%

at $$p_{T,e}\approx 300$$

p

T
,
e

≈
300

GeV. In these high $$p_T$$

p
T

regions, EW corrections are largest for the doubly-transverse mode.