bluuebunny/crossref_metadata_2025 huggingface dataset:
Low expression of miR-182 caused by DNA hypermethylation accelerates acute lymphocyte leukemia development by targeting PBX3 and BCL2: miR-182 promoter methylation is a predictive marker for hypomethylation agents + BCL2 inhibitor venetoclax
Authors: Li Danyang , Yuan Yigang , Meng Chen , Lin Zihan , Zhao Min , Shi Liuzhi , Li Min , Ye Daijiao , Cai Yue , He Xiaofei , Ye Haige , Zhou Shujuan , Zhou Haixia , Gao Shenmeng
Published: March 2024

Background

miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined.

Methods

To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro.

Results

miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation.

Conclusions

Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.
Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma
Authors: Casale Thomas B , Corbridge Thomas , Germain Guillaume , Laliberté François , MacKnight Sean D , Boudreau Julien , Duh Mei S , Deb Arijita
Published: March 2024

Background

Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications.

Objective

Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma.

Methods

This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models.

Results

SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort.

Conclusion

SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.
Menarche, pubertal timing and the brain: female-specific patterns of brain maturation beyond age-related development
Authors: Gottschewsky Nina , Kraft Dominik , Kaufmann Tobias
Published: March 2024

Background

Puberty depicts a period of profound and multifactorial changes ranging from social to biological factors. While brain development in youths has been studied mostly from an age perspective, recent evidence suggests that pubertal measures may be more sensitive to study adolescent neurodevelopment, however, studies on pubertal timing in relation to brain development are still scarce.

Methods

We investigated if pre- vs. post-menarche status can be classified using machine learning on cortical and subcortical structural magnetic resonance imaging (MRI) data from strictly age-matched adolescent females from the Adolescent Brain Cognitive Development (ABCD) cohort. For comparison of the identified menarche-related patterns to age-related patterns of neurodevelopment, we trained a brain age prediction model on data from the Philadelphia Neurodevelopmental Cohort and applied it to the same ABCD data, yielding differences between predicted and chronological age referred to as brain age gaps. We tested the sensitivity of both these frameworks to measures of pubertal maturation, specifically age at menarche and puberty status.

Results

The machine learning model achieved moderate but statistically significant accuracy in the menarche classification task, yielding for each subject a class probability ranging from 0 (pre-) to 1 (post- menarche). Comparison to brain age predictions revealed shared and distinct patterns of neurodevelopment captured by both approaches. Continuous menarche class probabilities were positively associated with brain age gaps, but only the menarche class probabilities—not the brain age gaps—were associated with age at menarche.

Conclusions

This study demonstrates the use of a machine learning model to classify menarche status from structural MRI data while accounting for age-related neurodevelopment. Given its sensitivity towards measures of puberty timing, our work suggests that menarche class probabilities may be developed toward an objective brain-based marker of pubertal development.
Non-specific effects of inactivated Mycobacterium bovis oral and parenteral treatment in a rabbit scabies model
Authors: Casais Rosa , Iglesias Natalia , Sevilla Iker A. , Garrido Joseba M. , Balseiro Ana , Dominguez Mercedes , Juste Ramon A.
Published: March 2024

Tuberculosis BCG vaccination induced non-specific protective effects in humans led to postulate the concept of trained immunity (TRAIM) as an innate type of immune mechanism that triggered by a pathogen, protects against others. Killed vaccines have been considered not to be effective. However, field efficacy of a commercial vaccine against paratuberculosis, as well as of a recently developed M. bovis heat-inactivated vaccine (HIMB) prompted to test whether it could also induce TRAIM. To this, we used a sarcoptic mange rabbit model. Twenty-four weaned rabbits were treated orally or subcutaneously with a suspension of either HIMB (107 UFC) or placebo. Eighty-four days later the animals were challenged with approximately 5000 S. scabiei mites on the left hind limb. Skin lesion extension was measured every 2 weeks until 92 days post-infection (dpi). Two animals were killed at 77 dpi because of extensive skin damage. The rest were euthanized and necropsied and the lesion area and the mite burden per squared cm were estimated. Specific humoral immune responses to S. scabiei and to M. bovis were investigated with the corresponding specific ELISA tests. Subcutaneously and orally HIMB vaccinated animals compared with placebo showed reduced lesion scores (up to 74% and 62%, respectively) and mite counts (−170% and 39%, respectively). This, together with a significant positive correlation (r = 0.6276, p = 0.0031) between tuberculosis-specific antibodies and mite count at 92 dpi supported the hypothesis of non-specific effects of killed mycobacterial vaccination. Further research is needed to better understand this mechanism to maximize cross protection.
Unveiling the functional heterogeneity of cytokine-primed human umbilical cord mesenchymal stem cells through single-cell RNA sequencing
Authors: Hu Zhiwei , Li Duanduan , Wu Shiduo , Pei Ke , Fu Zeqin , Yang Yulin , Huang Yinfu , Yang Jian , Liu Chuntao , Hu Junyuan , Cai Cheguo , Liao Yan
Published: March 2024

Background

Mesenchymal stem cells (MSCs) hold immense promise for use in immunomodulation and regenerative medicine. However, their inherent heterogeneity makes it difficult to achieve optimal therapeutic outcomes for a specific clinical disease. Primed MSCs containing a certain cytokine can enhance their particular functions, thereby increasing their therapeutic potential for related diseases. Therefore, understanding the characteristic changes and underlying mechanisms of MSCs primed by various cytokines is highly important.

Results

In this study, we aimed to reveal the cellular heterogeneity, functional subpopulations, and molecular mechanisms of MSCs primed with IFN-γ, TNF-α, IL-4, IL-6, IL-15, and IL-17 using single-cell RNA sequencing (scRNA-seq). Our results demonstrated that cytokine priming minimized the heterogeneity of the MSC transcriptome, while the expression of MSC surface markers exhibited only slight changes. Notably, compared to IL-6, IL-15, and IL-17; IFN-γ, TNF-α, and IL-4 priming, which stimulated a significantly greater number of differentially expressed genes (DEGs). Functional analysis, which included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, indicated that IFN-γ, TNF-α, and IL-4-primed hUC-MSCs are involved in interferon-mediated immune-related processes, leukocyte migration, chemotaxis potential, and extracellular matrix and cell adhesion, respectively. Moreover, an investigation of various biological function scores demonstrated that IFN-γ-primed hUC-MSCs exhibit strong immunomodulatory ability, TNF-α-primed hUC-MSCs exhibit high chemotaxis potential, and IL-4-primed hUC-MSCs express elevated amounts of collagen. Finally, we observed that cytokine priming alters the distribution of functional subpopulations of MSCs, and these subpopulations exhibit various potential biological functions. Taken together, our study revealed the distinct regulatory effects of cytokine priming on MSC heterogeneity, biological function, and functional subpopulations at the single-cell level.

Conclusions

These findings contribute to a comprehensive understanding of the inflammatory priming of MSCs, paving the way for their precise treatment in clinical applications.
The ENJOY Seniors Exercise Park IMP-ACT project: IMProving older people’s health through physical ACTivity: a hybrid II implementation design study protocol
Authors: Levinger Pazit , Fearn Marcia , Dreher Bronwyn , Bauman Adrian , Brusco Natasha K. , Gilbert Andrew , Soh Sze-Ee , Burton Elissa , James Lisa , Hill Keith D.
Published: March 2024

Introduction

The health benefits of physical activity are well established; however, most older people are not sufficiently physically active. Despite the availability of various physical activity interventions and programs, implementation of effective prevention strategies to reduce older people’s physical inactivity are lacking. The ENJOY IMP-ACT project is an implementation research project, based on a previous evidence-based physical and social activity program utilising specialised outdoor exercise equipment (the Seniors Exercise Park) for older people. The ENJOY IMP-ACT aims to increase participation in physical activity to improve health outcomes for older people in Victoria, Australia.

Method

The ENJOY IMP-ACT is a hybrid II implementation-effectiveness pre-post mixed method study design. Five local governments (6 public sites/parks) will undergo a 3-month control period followed by 9-months implementation intervention (TERM framework intervention: Training, Engagement, Resources development, Marketing and promotion), and a maintenance phase (3 months). Various methodologies will be employed throughout the project at each site and will include direct observations of park users, intercept surveys with park users, online access monitor platform (using an online app), interviews with stakeholders and exercise program leaders, a process evaluation of physical activity programs, a social return-on-investment analysis, and other related activities.

Discussion

Through the implementation framework design, the ENJOY IMP-ACT is uniquely placed to translate an evidenced-based physical and social activity program into real world settings and increase physical activity among older people. If successful, this program will inform scale up across Australia with the goal of improving the health and wellbeing of older people.

Trial registration

This registration trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial number ACTRN12622001256763. Date registered 20/09/2022.
Sex-dependent resilience to extreme drought events: implications for climate change adaptation of a South American endangered tree species
Authors: Piraino Sergio , Hadad Martín Ariel , Ribas‑Fernández Yanina Antonia , Roig Fidel Alejandro
Published: March 2024

Background

Recent changes in climatic trends are resulting in an increased frequency and intensity of extreme events, with unknown effect on ecosystem dynamics in the near future. Extreme drought episodes are recognized as disturbance factors capable of modifying forest dynamics and tree growth. Within this context, dioecious tree species may be impacted by climatic extremes, affecting male/female proportions and, consequently, reproductive processes and species persistence. Therefore, there is an urgent need for species-specific assessments of growth tolerance to extreme dry spells in dioecious tree species, to establish effective conservation strategies for these particular natural resources. Araucaria araucana (araucaria), an endangered dioecious Patagonian tree species, has recently undergone decay and mortality episodes in response to increasing dry climatic conditions. While sex-dependent tolerance to extreme drought episodes has been assessed in the species’ humid distribution range, there is still a lack of information on the gender-based resilience of trees growing in the drier environments of the species’ distribution.

Methods

We reconstructed, through dendrochronological methods, the sex-dependent response of 105 araucaria individuals (55 female and 50 male trees) to five regional extreme dry spells employing a set of different indices. Resistance, recovery period, and average growth reduction of standardized tree-ring growth were examined, analysing the effect of biotic (sex, pre-drought stem tree growth) and abiotic (local climatic conditions before, during, and after extreme climatic episodes) factors on tree resilience.

Results

Sex influences only the species resistance to climatic disturbance, with male individuals showing lower tolerance to extreme drought events. Pre-drought radial growth rates and local meteorological conditions preceding, during, and following extreme dry spells strongly modulated araucaria radial growth resilience regardless of tree sex, influencing the species resistance, recovery period, and average growth reduction.

Conclusions

We provide novel and crucial information for the species conservation and management in the current climate change scenario, and contribute to the debate regarding the role of tree sex as a factor influencing woody species growth under particularly adverse climatic conditions. In the face of climate change, an increase in extreme drought events is expected in the easternmost araucaria xeric end distribution area, which will likely decrease the species resilience.
Regional climate models and bias correction methods for rainfall-runoff modeling in Katar watershed, Ethiopia
Authors: Yersaw Babur Tesfaye , Chane Mulusew Bezabih
Published: March 2024

Systematic errors in regional climate models (RCMs) hinder their implementation and lead to uncertainties in regional hydrological climate change studies. As a result, checking the accuracy of climate model simulations and applying bias correction are preliminary methods for achieving consistent findings. Therefore, identifying suitable RCM models for bias correction is important for providing reliable inputs for evaluating climate change impacts. The impacts of bias correction methods on streamflow were assessed on the Katar catchment within the Lake Ziway subbasin using coordinated regional climate downscaling experiments with a spatial resolution of 50 km (CORDEX-44) RCMs through the Integrated Hydrological Modelling System (IHMS) version 6.3. This study evaluated fourteen RCM models under five precipitation and three temperature bias correction methods for the Katar catchment. Statistical approaches, such as bias (PBIAS), the root mean square error (RMSE), the mean absolute error (MAE), the coefficient of variation (CV), the coefficient of determination (R2), and the relative volume error (RVE), are used for performance analysis. GERICS-MPI, RAC4-NOAA-2G, and CCLM4-NCCR-AFR-22 have better performances for both rainfall and temprature. The empirical cumulative distribution function (ECDF) method performed best in removing bias from the frequency-based statistics of rainfall and streamflow, followed by the power transformation (PT), distribution mapping (DM), local intensity scaling (LOCI), and linear scaling (LS) methods. Specifically, for temperature, the VARI and DM methods perform better in frequency-based statistics than the LS method. The performance of hydrological modeling is strongly affected by the selection of rainfall bias correction methods. In addition, the effect of the temperature bias correction method was not significant. The adequacy of the BCM depends on the RCM models and regional context. Therefore, the BCM implementation procedure can be adapted from region to region. This study revealed that the performance of the RCM models differed and that the errors in the RCM model outputs were reduced by the use of bias correction methods.
Profile and burden of the family caregiver: the caring experience in multiple sclerosis. An observational study
Authors: Ponzio Michela , Tacchino Andrea , Verri Anna , Battaglia Mario Alberto , Brichetto Giampaolo , Podda Jessica
Published: March 2024

Background

The broad implications of caring for a family member with a chronic medical condition, such as MS, can lead caregivers to experience a high burden of care. The aim of the study was to describe profile of MS caregivers and their burden and to explore potential factors influencing this burden.

Methods

200 family caregivers of a person with MS completed survey questionnaires across a cross-sectional study. Many information were collected: caregiver socio-demographic and health-related data, caregiving activities, knowledge of MS, coping strategies, mood, social support received and care recipient information. Caregiving burden was measured by the ZBI (Zarit Burden Interview). The extent to which the variables explained caregiver burden was analyzed using a hierarchical approach.

Results

68% of the caregivers reported a perceived burden of care (ZBI score > 20). Our results show that physical and mental related-health variables are important predictive factors of the care burden, explaining much of the observed variance (40.9%).

Conclusion

Family caregivers in MS continue to make up the shortfall produce by national health and welfare systems. We highlighted the importance of good physical and mental health in decreasing perceived burden. Working to alleviate psychological distress through mechanisms focus on reducing worries and perceived burden may be a valid approach.
Impact of permafrost degradation on the extreme increase of dissolved iron concentration in the Amur river during 1995–1997
Authors: Tashiro Yuto , Hiyama Tetsuya , Kanamori Hironari , Kondo Masayuki
Published: March 2024

Primary production in the Sea of Okhotsk is largely supported by dissolved iron (dFe) transported by the Amur river, indicating the importance of dFe discharge from terrestrial environments. However, little is known about the mechanisms of dFe discharge into the Amur river, especially in terms of long-term change in dFe concentration. In the Amur river, extreme increase in dFe concentration was observed between 1995 and 1997, the cause of which remains unclear. As a cause of this iron anomaly, we considered the impact of permafrost degradation. To link the permafrost degradation to long-term variation in dFe concentration, we examined the changes in annual air temperature (Ta), accumulated temperature (AT), and net precipitation for three regions (northeast, south, and northwest) of the basin between 1960 and 2006. Ta and AT were relatively high in one out of every few years, and were especially high during 1988–1990 continuously. Net precipitation in late summer (July to September) has increased since 1977 and has stayed positive until 2006 throughout the basin. Most importantly, we found significant correlations between Ta and late summer dFe concentration with a 7-year lag (r = 0.54–0.69, p < 0.01), which indicate a close relationship between high Ta in year Y and increased late summer dFe concentration in year Y + 7. This correlation was the strongest in northeastern Amur basin where permafrost coverage is the highest. Similar 7-year lag correlation was also found between AT in the northeastern basin and late summer dFe concentration (r = 0.51, p < 0.01). Based on our findings, we propose the following hypothesis as a cause of iron anomaly. (1) Increased net precipitation since 1977 has increased soil moisture, which created suitable conditions for microbial dFe generation; (2) permafrost degradation during the warm years of 1988–1990 promoted iron bioavailability and led to the intensive dFe generation in the deeper part of the active layer; and (3) dFe took approximately 7 years to reach the rivers and extremely increased dFe concentration during 1995–1997. This is the first study to suggest the time-lagged impact of permafrost degradation on iron biogeochemistry in the Amur river basin.
A ball-jointed tendon-driven continuum robot with multi-directional operability for grasping objects
Authors: Onose Ryo , Sawada Hideyuki
Published: March 2024

A continuum robot, inspired by biological features, flexibly bends its body and conforms to various shapes. The high compliance and low stiffness, however, causes low rigidity and ambiguity in control when it is applied to grasping and manipulating an object. In this study, we develop a ball-jointed tendon-driven continuum robot that can bend to arbitrary directions for manipulating and grasping an object. Discs are connected by ball joints, together with coil springs coupled with tendon threads, and form a backbone of the robotic body. The continuum robot is operated to bend to an arbitrary direction by pulling the tendons using three servomotors, and returns to the original straight shape by releasing the pulling force of the contracted coil springs. The robot is constructed by using 3D-printed parts. In the experiment, the ability of the multi-directional operation was tested by bending the continuum body to specific directions, and then performing arc-following motion. Furthermore, the manipulator's grasping performance was demonstrated by preparing five objects that have various shapes, sizes, and softness. The robot successfully grasped all the objects by wrapping around them and adapting its shape to the object's shapes. The experiments verified the satisfactory operability of the continuum robot.
Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial
Authors: Kazawa Masahiro , Kabata Daijiro , Yoshida Hisako , Minami Kimito , Maeda Takuma , Yoshitani Kenji , Matsuda Hitoshi , Shintani Ayumi
Published: March 2024

Background

This study aimed to examine the preventive effect of amino acids on postoperative acute kidney injury (AKI).

Methods

This was single-center, patient- and assessor-blinded, randomized controlled trial. Patients who underwent aortic surgery with cardiopulmonary bypass were included. The intervention group received 60 g/day of amino acids for up to 3 days. The control group received standard care. The primary outcome was the incidence of AKI. We assessed the effect of amino acids on AKI using a Cox proportional hazards regression model.

Results

Sixty-six patients were randomly assigned to the control or intervention group. One patient in the control group withdrew consent after randomization. The incidence of AKI was 10 patients (30.3%) in the intervention group versus 18 patients (56.2%) in the control group (adjusted hazard ratio, 0.44; 95% confidence interval, 0.20–0.95; P = 0.04).

Conclusions

This trial demonstrated a significant reduction in AKI incidence with amino acid supplementation.

Trial registration

jRCT, jRCTs051210154. Registered 31 December 2021, https://jrct.niph.go.jp/re/reports/detail/69916
Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections
Authors: Bhatt Mitra Jyotsna , Chatterjee Saurav , Kumar Anuj , Khatoon Elina , Chandak Ashok , Rakshit Sutapa , Bandyopadhyay Anupam , Mukherjee Archana
Published: March 2024

Background

The urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting focal infections has yielded promising results. Augmenting the sensitivity of current PET and SPECT tracers could enable effective imaging of pathogenic bacteria, including drug-resistant strains.UBI (29–41), an antimicrobial peptide (AMP) fragment recognizes the S. aureus membrane through electrostatic binding. Radiolabeled UBI (29–41) is a promising SPECT and PET-based tracer for detecting focal infections. 2-APBA (2-acetyl-phenyl-boronic acid), a non-natural amino acid, specifically targets lysyl-phosphatidyl-glycerol (lysyl-PG) on the S. aureus membranes, particularly in AMP-resistant strains. We propose that combining UBI with 2-APBA could enhance the diagnostic potential of radiolabeled UBI.

Results

Present work aimed to compare the diagnostic potential of two radiolabeled peptides, namely UBI (29–41) and 2-APBA modified UBI (29–41), referred to as UBI and UBI-APBA. APBA modification imparted antibacterial activity to the initially non-bactericidal UBI against S. aureus by inducing a loss of membrane potential. The antibacterial activity demonstrated by UBI-APBA can be ascribed to the synergistic interaction of both UBI and UBI-APBA on the bacterial membrane. To enable PET imaging, we attached the chelator 1,4,7-triazacyclononane 1-glutaric acid 4,7-acetic acid (NODAGA) to the peptides for complexation with the positron emitter Gallium-68 (68Ga). Both NODAGA conjugates were radiolabeled with 68Ga with high radiochemical purity. The resultant 68Ga complexes were stable in phosphate-buffered saline and human serum. Uptake of these complexes was observed in S. aureus but not in mice splenocytes, indicating the selective nature of their interaction. Additionally, the APBA conjugate exhibited superior uptake in S. aureus while preserving the selectivity of the parent peptide. Furthermore, [68Ga]Ga-UBI-APBA demonstrated accumulation at the site of infection in rats, with an improved target-to-non-target ratio, as evidenced by ex-vivo biodistribution and PET imaging.

Conclusions

Our findings suggest that linking UBI, as well as AMPs in general, with APBA shows promise as a strategy to augment the theranostic potential of these molecules.
An unknown wide persistent ductus arteriosus debuting with atrial fibrillation in older adult: a case report
Authors: Pierro Antonio , Totaro Antonio , Colavita Angela Rita , Apollonio Biagio Francesco Pio , Florio Severino , Petrucci Pasquale , Cilla Savino
Published: March 2024

Background

The persistently patent ductus arteriosus represents a well-known common congenital heart defect; it is uncommon in adult patients, and in any case, it debuts with atrial fibrillation.

Case presentation

A 75-year-old woman suffering from persistent ductus arteriosus (PDA) was admitted to the cardiology department because of atrial fibrillation, dyspnea and exercise intolerance. A PDA was detected on echocardiography and globally assessed through ECG-gated CT angiography.

Conclusions

Patent ductus arteriosus is an uncommon clinical finding in adulthood, and atrial fibrillation, as a consequence of chronic, progressive left atrial enlargement, may be the initial symptom. We describe the ECG-gated CT angiography imaging features of unknown patent ductus arteriosus in an elderly patient who debuted with atrial fibrillation.
Evaluation of knowledge of healthcare professionals regarding tracheostomy care: a cross-sectional study at a tertiary care hospital in Pakistan
Authors: Saleem Alisha , Khan Ashar Masood , Dhanani Rahim , Wasif Muhammad , Ikram Mubasher , Shabbir Ruby
Published: March 2024

Background

Tracheostomy is considered the oldest and the most effective operative procedure for patients admitted to intensive care units and in emergencies. The study’s objective was to evaluate healthcare providers’ knowledge regarding tracheostomy care.

Results

All healthcare professionals directly involved in the provision of care to patients with tracheostomy were included and asked to fill out the questionnaire. The response rate was 87.63%. Out of 50, the mean comfort score was 37.69. 70.6% of participants reported having a comfort score equal to or more than 70%. Out of 10, the mean score was 5.29. Only 20.9% of participants were able to score equal to or more than 70%. The results demonstrate that healthcare professionals’ knowledge of tracheostomy care was below par. Only those who were experienced in this field were able to score above average.

Conclusion

The assessment of knowledge in tracheostomy care highlights the significance of ongoing education and training in the healthcare field. As medical practices evolve, it is imperative for healthcare providers to stay updated with the latest guidelines and techniques to provide the highest standard of care.
Blood eosinophil variability in patients presenting with acute exacerbations of COPD within the past year and its correlation with treatment plan
Authors: Fahyim Samir Mohamed Mahmoud , AbdelHalim Hesham Atef , Hassan El Shaimaa Sabry Mohammed
Published: March 2024

Background

Chronic obstructive pulmonary disease (COPD) is an acknowledged contributor to universal fatality and morbidity. Using biomarkers to pinpoint its phenotypes is crucial, enabling individualized treatment and enhancing prognosis.

Objective

Studying the steadiness of blood eosinophi1s in cases who experienced repeated hospital admissions for acute worsening of COPD during a year and its correlation to the treatment plan.

Methods

A retrospective cohort study includes 270 COPD male patients with acute exacerbations. The patients were divided into three groups: fluctuating (ranges between ≥ 150 cells/ul and < 150 cells/ul), non-EOS (< 150 cells/ul), and Eosinophil (EOS) (≥ 150 cells/ul).

Results

Most patients were in the fluctuating blood EOS group (53.3%). The median length of hospital stay was longer in the fluctuating group (5 days). There was a significant positive correlation between the number of exacerbations and both EOS count and EOS/WBCs. A higher eosinophilic count was associated with an increased risk of eosinophilic exacerbations. Most patients used steroids (higher in the EOS group, 61.6%).

Conclusion

Blood eosinophilic count is promising for investigating acute COPD exacerbations. Peripheral blood eosinophilia is a relevant biomarker for directing the management of COPD exacerbations, including steroids.
The validity of the selection methods for recruitment to UK core psychiatry training: cohort study
Authors: Tiffin Paul A. , Morley Emma , Paton Lewis W. , Chakraborty Nandini , Patterson Fiona
Published: March 2024

Aims and method

Selection into core psychiatry training in the UK uses a computer-delivered Multi-Specialty Recruitment Assessment (MSRA; a situational judgement and clinical problem-solving test) and, previously, a face-to-face Selection Centre. The Selection Centre assessments were suspended during the COVID-19 pandemic. We aimed to evaluate the validity of this selection process using data on 3510 psychiatry applicants. We modelled the ability of the selection scores to predict subsequent performance in the Clinical Assessment of Skills and Competencies (CASC). Sensitivity to demographic characteristics was also estimated.

Results

All selection assessment scores demonstrated positive, statistically significant, independent relationships with CASC performance and were sensitive to demographic factors.

Implications

All selection components showed independent predictive validity. Re-instituting the Selection Centre assessments could be considered, although the costs, potential advantages and disadvantages should be weighed carefully.
Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?
Authors: Hamed Amr A. , Muhammed Amr , Abdelbary Ebtsam A.M. , Elsharkawy Ramy M. , Ali Moustafa A.
Published: March 2024

PURPOSE

The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response.

PATIENTS AND METHODS

A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled.

RESULTS

One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set.

CONCLUSION

Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.
The Student Labor Camp Movement, Postcolonial Development, and the Shaping of Citizens-to-Be in Independent India, 1954–65
Authors: Wilkinson Tom
Published: March 2024

The Government of India organized over ten thousand student labor camps for the purposes of village development between 1954 and 1965. This camp movement functions as a key to the novel idealizations of youth in the postcolonial world and the shifting development agendas of independent India. The image of the toiling and vigorous camper committed to serving the newly created nation-state came to be constructed as India's model citizen-to-be, and this figure embodies the emergent forms of postcolonial nationalist politics and ideologies of the 1950s and 1960s. This youthful labor force was depicted in the developmentalist imagination of India as literally building and metaphorically embodying the nation-state and its ideologies of physical fitness, secularism, anti-casteism, and national discipline. This article will argue that camp life negotiated a hierarchy of citizens that made the educated youth the agent of development and the villager the object of development. The running of these camps by volunteer movements such as the National Cadet Corps, the Bharat Scouts and Guides, and the Bharat Sevak Samaj brings to light how the developmental apparatus in India worked or did not work in practice for the students and the poorer classes.
Disputes over Burial Mountains
Authors: Lim Sungyun
Published: March 2024

This article examines legal decisions in lineage property disputes from the Korean Empire period (1897–1910) to the first two decades of the Japanese colonial rule to trace the effect of Japanese efforts to implement property rights reforms in colonial Korea. Lineage properties were heavily concentrated in the mountains in the form of communal burial sites; thus, to ease acceptance of colonial rule, such Japanese objectives as forest cultivation needed to accommodate long-established Korean practices of mountain burial. In addition, Japanese perceptions of Koreans as primitively collective in their property relations led to initial suppression of the rights of heirs over lineage property. The colonial court's subsequent gradual and uneven invocation of the principle of exclusive individual property rights became a source of both legal and physical conflicts. The case of how lineage property rights were reorganized in colonial Korea shows the compromised nature of the colonial property regime as it sought to balance traditional claims and modern concepts of property ownership, with long-term consequences for property rights in Korea.
Diffusion, Polyphony, and Diversity
Authors: Guo Ting
Published: March 2024

This forum explicates Hong Kong's complex religious and ritual landscape and the ways in which it influences social movements and identity making, in response to large forces of religion and protest around the world today, including in Ukraine and places in Asia such as Iran and Myanmar. Scholars have noted how various forms of Christianity, Buddhism, Islam, and popular Chinese religions have been diffused into the secular spaces of Hong Kong's governing state structures, formal and informal economies, and ad hoc protest organizations in civil society. Recent work has also emphasized the ways that race, ethnicity, and gender have been shaped not only by institutions with religious ties but also by theological and cosmological narratives that circulate through the public sphere. Religiosity in the Hong Kong protests might also be conceived as polyphonic, layering over familial practices with structures that have colonial baggage and postcolonial aspirations. Religion, in such senses, tends to be unbound by secular attempts to fence it into private spheres; it might be seen as forging a new civil society and civil identity through recent protests and shaping new theoretical frameworks.
“The Catholic Church Has a Big Structure”
Authors: Herasym Halyna , Tse Justin
Published: March 2024

The general body of literature on the theology of liberation tends to focus either on ecclesiastical debate, theological intricacies, or discussion within the church. Not much attention is paid to the empirical investigation of how civil society members might be influencing the rhetoric of the local church. This article takes a different approach and explores how liberation movements in Ukraine and Hong Kong inform and inspire elements of the theology of social justice within local Catholic communities through bringing to life their social dreams and engaging the churches in action. Looking at how churches and activists interact in the aftermath of the Euromaidan and the Umbrella Movement, we explore how grassroots activists approach religious hierarchies and how, in these circumstances, the clergy of the churches might be pressured into maneuvering between the social dreams of civil society and the Vatican.
Posterior Transdural Approach for Thoracic Corpectomies in the Setting of Complex Spine Deformity Reconstruction
Authors: Brehm Samuel , Ruiz-Cardozo Miguel A. , Cadieux Magalie , Barot Karma , Joseph Karan , Bui Tim , Kann Michael Ryan , Lopez-Alviar Sofia , Trevino Gabriel , Yahanda Alexander T. , LeRoy Taryn E. , Jauregui Julio J. , Pallotta Nicholas A. , Molina Camilo A.
Published: March 2024

BACKGROUND AND OBJECTIVE:

There are many surgical approaches for execution of a thoracic corpectomy. In cases of challenging deformity, traditional posterior approaches might not be sufficient to complete the resection of the vertebral body. In this technical note, we describe indications and technique for a transdural multilevel high thoracic corpectomy.

METHODS:

A 25-year-old man with a history of neurofibromatosis type 1 presented with instrumentation failure after a previous T1–T12 posterior spinal fusion, extensive laminectomy, and tumor resection. The patient presented with progressive back pain, had broad dural ectasia, and a progressive kyphotic rotational and anteriorly translated spinal deformity. To resect the medial-most aspect of the vertebral body, a bilateral extracavitary approach was attempted, but was found insufficient. A transdural approach was subsequently performed. A left paramedian durotomy was made, followed by generous arachnoid dissection, bilateral dentate ligament division, and T4 rootlet sacrifice to mobilize the spinal cord. A ventral durotomy was then made and the ventral dura was reflected over the spinal cord to protect it while drilling. The corpectomy was then completed. The ventral and dorsal durotomies were closed primarily and reinforced with fibrin glue and fibrin sealant patch. The corpectomy defect was filled with nonstructural autograft.

RESULTS:

The focal kyphosis was corrected with a combination of rod contouring, compression, and in situ bending. During the surgery, the patient had stable neuromonitoring data, and postoperatively had no neurological deficits. On follow-up until 1 year, the patient presented with no signs of cerebrospinal spinal leaks, no motor or sensory deficits, minimal incisional pain, and significantly improved posture.

CONCLUSION:

Complex high thoracic (T3–5) ventral pathology inaccessible via a bilateral extracavitary approach may be accessed via a transdural approach as opposed to an anterior/lateral transthoracic approach that requires mobilization of cardiovascular structures or scapula.
Hard Candy Production and Quality Parameters: A review
Authors: Ozel Baris , Kuzu Sena , Marangoz Mehmet Ali , Dogdu Sarper , Morris Robert H. , Oztop Mecit H.
Published: March 2024

Hard candies are sugar confections comprising mainly water and sucrose. Corn syrup, colorants and flavors are also usually added to hard candy formulations. The production of hard candy requires heating of the ingredients to very high temperatures to reduce moisture content and subsequent cooling to obtain a solid matrix. Cooling of the mixtures achieves the final, well known glassy state of the products. In this glassy state, the system is kinetically stable and molecular mobility is restricted, providing longer shelf life to hard candies. There are, however, several factors affecting the final quality and consumer acceptance of hard candies. Production methods and parameters, initial formulations as well as storage conditions all play a crucial role in the physicochemical, textural and sensory properties of hard candies. Addition of colorants and flavors also plays a vital role in the final quality. Although hard candy production is a simple process with few production stages, even small changes in the method of production and process parameters may induce substantial changes in the final product characteristics. Additionally, storage conditions such as temperature and humidity can change the product properties leading to graining and stickiness which are the two major problems for hard candies during storage. Both production and storage conditions should therefore be carefully chosen and controlled for desirable hard candy properties. This review addresses the general production methods and considers process parameters and quality parameters of hard candy products. Moreover, a comprehensive review of the related hard candy literature is also presented. The majority of hard candy reviews focus on specific methods and processes, but this review will present a more general frame on the subject.
Lyophilized fecal microbiome transfer for primary Clostridioides difficile infection: a multicenter randomized controlled trial (DONATE Study)
Authors: Pitashny Milena , Kao Dina , Ianiro Gianluca , Mullish Benjamin , Nagy Gergely , Urbonas Tadas , Kesten Inbar , Stabholz Yoav , Kupcinskas Juozas , Franz Rose , Rondinella Debora , Tamburini Sabrina , Tudlik Zsuzsa , Masucci Luca , Quaranta Gianluca , Fusco William , Cammarota Giovanni , Skieceviciene Jurgita , Wong Karen , Segata Nicola , Paul Mical , Bar-Yoseph Haggai
Published: March 2024

Background Primary Clostridioides difficile infection (pCDI) carries high recurrence and mortality rates and is globally spread. pCDI is often a consequence of exposure to antibiotics, disrupting the healthy intestinal microbiota composition. Not surprisingly, in this antibiotic-associated infection, failure of the standard antibiotic treatment is high. Frozen fecal microbiota transplantation (FMT), the introduction of the microbial community from a healthy donor, has been shown to be safe and highly effective in cases of recurrent CDI, reaching >90% cumulative success rate. Importantly, FMT has shown potential for intestinal decolonization of multidrug-resistant organisms (MDRO), and/or mitigation of their ability to cause invasive infection. The use of FMT for pCDI, has been tested in small studies, showing promising results. The use of frozen FMT graft is often administered via colonoscopy or enteral (naso-jejunal) tubes, which are invasive procedures, placing significant burden on these often frail patients and the institutions providing the services. Moreover, frozen FMT is hampered by storage needs which limit accessibility and spread. Methods We have developed a lyophilized FMT product (Lyo-FMT - a dry compound that does not need freezing) that retains viability, prolongs the shelf time of the product and improves patient acceptance. In a randomized controlled multicenter trial, we aim to assess the efficacy of Lyo-FMT for pCDI in comparison to standard antibiotic therapy. Expected results This easy-to-administer product will restore the microbial community, fight the infective agent and reduce the overall antibiotic-resistant gene burden. This, in turn, will lower the recurrence rate and decrease carriage of other MDRO, coupled with a reduction in antibiotic use. Data on microbial shifts during treatment will shed light on our understanding of the pathophysiology of the disease. Clinicaltrials.gov registration NCT05709184, 2023-02-24