bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological characteristics of manganese transporter MntP in
Klebsiella pneumoniae
Authors: Peng Wei , Xu Yafei , Yin Yilin , Xie Jichen , Ma Renhui , Song Guoyuan , Zhang Zhiqiang , Quan Qiuhang , Jiang Qinggen , Li Moran , Li Bei
Published: June 2024

Klebsiella pneumoniae
is an important opportunistic pathogen that causes a variety of infections. It is critical for bacteria to maintain metal homeostasis during infection. By using an isogenic
mntP
deletion mutant of
K. pneumoniae
strain NTUH-K2044, we found that MntP was a manganese efflux pump. Manganese increased the tolerance to oxidative stress, and oxidative stress could increase the intracellular manganese concentration. In oxidative stress, the
mntP
deletion mutant exhibited significantly higher sensitivity to manganese. Furthermore, iron could increase the tolerance of the
mntP
deletion mutant to manganese. Inductively coupled plasma mass spectrometry analysis revealed that the
mntP
deletion mutant had higher intracellular manganese and iron concentrations than wild-type and complementary strains. These findings suggested that iron could increase manganese tolerance in
K. pneumoniae
. This work elucidated the role of MntP in manganese detoxification and Mn/Fe homeostasis in
K. pneumoniae
.

IMPORTANCE

Metal homeostasis plays an important role during the process of bacterial infection. Herein, we revealed that MntP was involved in intracellular manganese homeostasis. Manganese promoted resistance to oxidative stress in
Klebsiella pneumoniae
. Furthermore, we demonstrated that the
mntP
deletion mutant exhibited significantly lower survival under manganese and H
2
O
2
conditions. Oxidative stress increased the intracellular manganese content of the
mntP
deletion mutant. MntP played a critical role in maintaining intracellular manganese and iron concentrations. MntP contributed to manganese detoxification and Mn/Fe homeostasis in
K. pneumoniae
.
Integrative RNA-seq and ChIP-seq analysis unveils metabolic regulation as a conserved antiviral mechanism of chicken p53
Authors: Cui Lu , Li Xuefeng , Chen Zhijie , Liu Zheyi , Zhang Yu , Han Zongxi , Liu Shengwang , Li Hai
Published: June 2024

The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53’s antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53’s genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.

IMPORTANCE

The current study conducted a comprehensive analysis, comparing molecular networks underlying chp53’s antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.
Recognition of Neogene tin mineralization in the Southeast Asian tin belt
Authors: Huang Wen-Qing , Pan Jun-Yi , Ni Pei , Zhou Jun-Gui , Shui Ting , Chen Hui , Fan Ming-Sen , Cui Jian-Ming
Published: June 2024

The Southeast (SE) Asian tin belt is a major tin producer globally, with a prolonged mineralization history from the Permian to Paleogene (ca. 285–45 Ma). Tin deposits in this region are typically associated with tectonic settings that involve subduction and collision of the Paleo-, Meso-, and Neo-Tethys slabs. Ca. 40 Ma, a notable transition occurred in the tectonic regime of SE Tibet, with the Neo-Tethys subduction giving way to lateral extrusion of the Indochina block along major strike-slip faults. Previously, it was believed that this shift had brought tin mineralization to a halt. In this study, we present in situ laser ablation–inductively coupled plasma–mass spectrometry U-Pb cassiterite ages of 21–19 Ma from the Yunling tin deposit located in western Yunnan, China.

Yunling produces gem-quality cassiterite that is transparent but contains low U contents, which renders usual U-Pb dating techniques unusable. To address this, a customized dating protocol involving cathodoluminescence (CL) imaging and testing of U distribution on crystallographically well-defined cassiterite crystals was applied. The study revealed two types of primary microstructures in cassiterite: volumetrically dominant concentric oscillatory growth zones and subordinate CL-dark sector zones. The U content shows a preferential enrichment in the CL-dark sector zones, typically tens of parts per million (ppm), which is two orders of magnitude greater than the U content in the concentric zone. This is significant, as the dating results (21–19 Ma) obtained through the targeted selection of CL-dark sector zones represent the youngest tin mineralization event in the SE Asian tin belt. Additionally, these results challenge the established belief that the ore-hosting Indosinian granite, dated to ca. 215 Ma, was related to Sn mineralization in the Yunling area. We suggest that emplacement of the early Neogene Sn mineralization at Yunling may be genetically connected to extensive delamination of the lithosphere in southeastern Tibet. The lithospheric delamination led to the upwelling and decompression partial melting of the asthenosphere, which provides a plausible explanation for the high temperature required for the release of Sn from biotite-dehydration melting of sedimentary protolith. The study also highlights the potential of Oligocene–Miocene-aged granites situated in the Sanjiang Tethys and adjacent areas of western Yunnan as prospective exploration targets for tin mineralization.
Exudative pleural effusion during sunitinib treatment
Authors: Gupta Deepansh , Sivaramakrishnan Prakash , Layek Avishek , Mishra Mayank
Published: June 2024

Drug-induced pleural effusion is one of the rare causes of exudative pleural effusion and a high index of suspicion is necessary to lead to early diagnosis. We hereby present the case of a young male in his late 30s, known case of metastatic gastrointestinal stromal tumour on sunitinib therapy, who presented with right-sided mild pleural effusion. Diagnostic thoracentesis showed the effusion to be a monomorphic exudate with low adenosine deaminase, which was negative for malignant cells on cytopathology. A contrast-enhanced CT chest revealed an enlarged lymph node (LN) at the 4R station, cytological analysis of which was suggestive of reactive lymphoid hyperplasia. Infective workup of the LN aspirate and bronchoalveolar lavage taken from the right middle lobe was negative. After systematically excluding the usual causes of exudative pleural effusion, sunitinib was considered to be a possible cause and was, therefore, withheld. A repeat chest X-ray after 3 weeks of stopping the drug showed resolution of the pleural effusion.
Severe psychiatric disorders are associated with increased risk of dementia
Authors: Stevenson-Hoare Joshua , Legge Sophie E , Simmonds Emily , Han Jun , Owen Michael J , O’Donovan Michael , Kirov George , Escott-Price Valentina
Published: June 2024

Background

Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited evidence from longitudinal studies on the role of anxiety, bipolar and psychotic disorders. Electronic health records (EHRs) permit large cohorts to be followed across the lifespan and include a wide range of diagnostic information.

Objective

To assess the association between four groups of psychiatric disorders (schizophrenia, bipolar disorder/mania, depression and anxiety) with dementia in two large population-based samples with EHR.

Methods

Using EHR on nearly 1 million adult individuals in Wales, and from 228 937 UK Biobank participants, we studied the relationships between schizophrenia, mania/bipolar disorder, depression, anxiety and subsequent risk of dementia.

Findings

In Secure Anonymised Information Linkage, there was a steep increase in the incidence of a first diagnosis of psychiatric disorder in the years prior to the diagnosis of dementia, reaching a peak in the year prior to dementia diagnosis for all psychiatric diagnoses. Psychiatric disorders, except anxiety, were highly significantly associated with a subsequent diagnosis of dementia: HRs=2.87, 2.80, 1.63 for schizophrenia, mania/bipolar disorder and depression, respectively. A similar pattern was found in the UK Biobank (HRs=4.46, 3.65, 2.39, respectively) and anxiety was also associated with dementia (HR=1.34). Increased risk of dementia was observed for all ages at onset of psychiatric diagnoses when these were divided into 10-year bins.

Conclusions

Psychiatric disorders are associated with an increased risk of subsequent dementia, with a greater risk of more severe disorders.

Clinical implications

A late onset of psychiatric disorders should alert clinicians of possible incipient dementia.
Nutritional interventions and related efforts addressing undernutrition during rehabilitation after acquired brain injury: a scoping review protocol
Authors: Aadal Lena , Holst Mette , Poulsen Ingrid , Siig Margrethe , Odgaard Lene
Published: June 2024

Introduction

Patients with an acquired brain injury (ABI) are at an increased risk of undernutrition due to the disease-related inflammation and other numerous symptoms that impact their nutrition. Unfortunately, recommendations related to nutritional interventions and related efforts vary. The objective of this scoping review is to map the body of literature on nutritional interventions and related efforts provided by health professionals, such as screening or assessments, addressing undernutrition in adults with a moderate to severe ABI during the subacute rehabilitation pathway.

Methods and analysis

The review follows the Joanna Briggs Institute methodology for scoping reviews. The librarian-assisted search strategy will be conducted in the bibliographical databases: MEDLINE (PubMed), Embase, CINAHL, Web of Science and OpenGrey. Indexed and grey literature in English, German or Scandinavian languages from January 2010 will be considered for inclusion. Two independent reviewers will conduct the iterative process of screening the identified literature, paper selection and data extraction. Disagreements will be resolved by discussion until a consensus is reached. A template will be used to guide the data extraction. This scoping review will include research articles, methodological papers and clinical guidelines reporting on nutritional interventions or related efforts to prevent or address undernutrition in adult patients (≥18 years) with moderate to severe ABI within the first year after admission to rehabilitation hospital. We will map all kinds of nutritional efforts provided by professionals in different settings within high-income countries, including interventions targeting relatives.

Ethics and dissemination

This review will involve the collection and analysis of secondary sources that have been published and/or are publicly available. Therefore, ethics approval is not required. The results will be published in an international peer-reviewed journal, presented at scientific conferences and disseminated through digital science communication platforms.

Study registration

Open Science Framework:https://doi.org/10.17605/OSF.IO/H5GJX.
Real-world clinical validation of the Qatar pre-diabetes risk score: a cross-sectional study
Authors: Sallahi Narjiss , Zainel Abduljaleel Abdullatif , Bensmail Halima None , Syed Mohamed Ahmed , Arredouani Abdelilah
Published: June 2024

Introduction

Pre-diabetes stands as a prominent, independent risk factor for the onset of type 2 diabetes (T2D), with 5%–10% of individuals with pre-diabetes progressing to T2D annually. The effectiveness of rigorous lifestyle interventions in averting the transition from pre-diabetes to T2D has been substantiated across multiple investigations and populations. Consequently, the clinical imperative of early pre-diabetes detection becomes unequivocal. This study assessed the validity of the recently developed pre-diabetes risk score in Qatar (PRISQ) in a real-world clinical setting.

Research design and methods

We recruited 1021 walk-in participants from 3 different health centres of Qatar’s Primary Health Care Corporation. Only adult people without known pre-diabetes or diabetes were included in the study. Along with blood collected for the haemoglobin A1c (HbA1c) test to confirm pre-diabetes, we recorded the age, gender, weight, waist circumference, systolic and diastolic blood pressure, nationality, smoking state and family history of diabetes. Negative predictive value, positive predictive value, sensitivity and specificity of PRISQ were computed.

Results

Of the 1021 participants, 797 agreed to provide blood. HbA1ctest revealed that 21.9% of the 797 subjects had pre-diabetes (HbA1cbetween 5.7% and 6.5%) while 3.3% had undiagnosed diabetes (HbA1c≥ 6.5%). Using a PRISQ cut-off of 16, PRISQ sensitivity exceeded 90% in all subgroups of individuals aged 40 years and above, regardless of ethnicity. We did not see any significant improvement in PRISQ sensitivity when we considered the family history of diabetes.

Conclusions

We confirmed a good PRISQ diagnostic rate for pre-diabetes from a representative sample of the Qatar population recruited in a real-world clinical setting. PRISQ can potentially play a significant role in curbing the T2D epidemic sweeping Qatar and beyond.
Hypothesis: AdAPT-001 and pseudoprogression – when seeing is not necessarily believing
Authors: Conley Anthony , Larson Christopher , Oronsky Bryan , Stirn Meaghan , Caroen Scott , Reid Tony R
Published: June 2024

The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.
Deep learning-based classification of erosion, synovitis and osteitis in hand MRI of patients with inflammatory arthritis
Authors: Schlereth Maja , Mutlu Melek Yalcin , Utz Jonas , Bayat Sara , Heimann Tobias , Qiu Jingna , Ehring Chris , Liu Chang , Uder Michael , Kleyer Arnd , Simon David , Roemer Frank , Schett Georg , Breininger Katharina , Fagni Filippo
Published: June 2024

Objectives

To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis.

Methods

Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort.

Results

In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset.

Conclusions

We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.
Rheumatoid arthritis and changes on spirometry by smoking status in two prospective longitudinal cohorts
Authors: Hayashi Keigo , McDermott Gregory C , Juge Pierre-Antoine , Moll Matthew , Cho Michael H , Wang Xiaosong , Paudel Misti L , Doyle Tracy J , Kinney Gregory L , Sansone-Poe Danielle , Young Kendra , Dellaripa Paul F , Wallace Zachary S , Regan Elizabeth A , Hunninghake Gary M , Silverman Edwin K , Ash Samuel Y , San Jose Estepar Raul , Washko George R , Sparks Jeffrey A
Published: June 2024

Objective

To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.

Methods

We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5–7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV
1
%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV
1
/FVC <0.7).

Results

Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV
1
% decline (β=−0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV
1
% decline than non-RA comparators (β=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (β=1.12, p=0.01). Results were similar for FEV
1
/FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA.

Conclusions

Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV
1
% and FEV
1
/FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV
1
% decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA.
Impact of premorbid hypertension and renin-angiotensin-aldosterone system inhibitors on the severity of aneurysmal subarachnoid haemorrhage: a multicentre study
Authors: Zhong Ping , Lu Zhiwen , Li Zhangyu , Li Tianxiao , Lan Qing , Liu Jianmin , Chen Sifang , Wang Zhanxiang , Huang Qinghai
Published: June 2024

Background

Hypertension is widely acknowledged as a significant contributory factor to the heightened risk of intracranial aneurysm rupture. Nevertheless, the impact of hypertension management on the outcomes subsequent to aneurysmal subarachnoid haemorrhage (aSAH), particularly concerning the severity of aSAH, remains an underexplored area.

Methods

We conducted a retrospective analysis using data from a prospectively multicentre cohort of 4545 patients with aSAH in China. Premorbid hypertension status and the utilisation of antihypertensive medications prior to admission were set as key exposure factors. The primary outcomes encompassed unfavourable clinical grading scales observed on admission. Employing multivariable logistic regression, we explored the association between premorbid hypertension status, preadmission use of renin-angiotensin-aldosterone system (RAAS) inhibitors and unfavourable clinical grading scales.

Results

In comparison to patients with normal blood pressure, only uncontrolled hypertension demonstrated a significant and independent association with an elevated risk of poor outcomes on the Hunt-Hess scale (OR=1.799, 95% CI 1.413 to 2.291, p<0.001) and the World Federation of Neurological Surgeons (WFNS) scale (OR=1.721, 95% CI 1.425 to 2.079, p<0.001). Furthermore, the antecedent use of RAAS inhibitors before admission was markedly and independently linked to a diminished risk of adverse outcomes on the Hunt-Hess scale (OR=0.653, 95% CI 0.430 to 0.992, p=0.046) and the WFNS scale (OR=0.656, 95% CI 0.469 to 0.918, p=0.014).

Conclusions

Uncontrolled hypertension markedly elevates the risk of adverse clinical outcomes following an aSAH. Conversely, the preadmission utilisation of RAAS inhibitors demonstrates a noteworthy association with a favourable clinical outcome after aSAH.
In Silico Human Mobility Data Science: Leveraging Massive Simulated Mobility Data (Vision Paper)
Authors: Züfle Andreas , Pfoser Dieter , Wenk Carola , Crooks Andrew , Kavak Hamdi , Anderson Taylor , Kim Joon-Seok , Holt Nathan , Diantonio Andrew
Published: June 2024

Human mobility data science using trajectories or check-ins of individuals has many applications. Recently, we have seen a plethora of research efforts that tackle these applications. However, research progress in this field is limited by a lack of large and representative datasets. The largest and most commonly used dataset of individual human trajectories captures fewer than 200 individuals, while datasets of individual human check-ins capture fewer than 100 check-ins per city per day. Thus, it is not clear if findings from the human mobility data science community would generalize to large populations. Since obtaining massive, representative, and individual-level human mobility data is hard to come by due to privacy considerations, the vision of this work is to embrace the use of data generated by large-scale socially realistic microsimulations. Informed by both real data and leveraging social and behavioral theories, massive spatially explicit microsimulations may allow us to simulate entire megacities at the person level. The simulated worlds, which do not capture any identifiable personal information, allow us to perform “in silico” experiments using the simulated world as a sandbox in which we have perfect information and perfect control without jeopardizing the privacy of any actual individual. In silico experiments have become commonplace in other scientific domains such as chemistry and biology, permitting experiments that foster the understanding of concepts without any harm to individuals. This work describes challenges and opportunities for leveraging massive and realistic simulated alternate worlds for in silico human mobility data science.
Research on Differences in Knowledge Demand of Sustainability Learning of Teams in Mega Engineering Construction Project in China
Authors: Zhang Jinfan , Chen Yun , Zhu Wenxi , Cai Jianrong
Published: June 2024

Knowledge plays a vital role in achieving sustainable development goals (SDGs) in construction industry. According to the view of organization learning, heterogeneous teams have heterogeneous core knowledge. The main aim of this study is to explore the differences in demand for sustainability learning knowledge (SLK) among the mega engineering construction project (MECP) teams, which has important implications for improving the performance of team learning and achieving SDGs in MECPs. This study followed a research design that included identifying SLK and the stakeholder teams that needed SLK and investigating the respondents’ perception of the level of demands for SLK through semistructured interviews and survey questionnaires executed in China. The statistical test results indicated that there were some significant differences in demands for some SLK among the MECP teams and MECPs. All types of MECP teams had a common high demand for SLK on environment, safety, and health in China. This study contributes to research on sustainable construction in MECPs in two main ways: (1) it reveals novel insights related to the integration of SL into the MECPs sustainable construction practices for developing countries and (2) it offers the possibility for practitioners to identify the most crucial knowledge and focus their efforts and resources efficiently.
CFD Modeling for Estimating Consequences of Liquid Hydrogen Release Transported by Road Tankers through Tunnels
Authors: Caliendo Ciro , Genovese Gianluca , Markert Frank , Russo Paola
Published: June 2024

Among the new energy carriers targeted at mitigating greenhouse gas emissions, the use of hydrogen is likely to experience substantial growth in the future. In this context, the transport of liquid hydrogen by means of road tankers might represent the most cost‐effective option for delivery over long distances in the short‐term perspective. Liquid hydrogen, however, entails non‐negligible risks, especially in confined spaces like road tunnels. An accidental release might form a flammable hydrogen cloud that might deflagrate or even detonate. Nevertheless, the consequences on users in the event of accidental leakage of liquid hydrogen from road tankers have not yet been sufficiently investigated. Therefore, this paper regards specific 3D computational fluid dynamics models to quantify the effects due to both liquid hydrogen release and potential deflagration and/or detonation within road tunnels. The proposed models were calibrated and subsequently validated with the findings of certain literature studies. Since the effects on tunnel users might be influenced, apart from tunnel geometry, by the type of ventilation and traffic flow, tunnel environmental conditions involving natural or mechanical ventilation, as well as off or peak traffic hours (i.e., night or day traffic) were more especially investigated. The results of simulations, in terms of overpressures generated from a potential hydrogen explosion, showed benefits due to mechanical ventilation and/or under lower traffic flows. By providing additional knowledge to the field of hydrogen safety, this study might help tunnel management agencies to make improved management and/or traffic control strategies (e.g., decisions on whether or not mechanical ventilation should be installed also in tunnels less than 1,000 m long and/or allowing the transit of road tankers transporting liquid hydrogen only at night rather than day).
Long‐Term Quality of Life in Patients with Intracanalicular Vestibular Schwannomas after Gamma Knife Surgery Treatment: A Follow‐Up Study
Authors: Ząbek Mirosław , Turek Grzegorz , Bieńkowska Katarzyna , Kokoszka Andrzej , Dzierzęcki Sebastian , Kostecka Barbara
Published: June 2024

Introduction. Our previous research showed that the gamma knife surgery (GKS) is a highly effective treatment for intracanalicular vestibular schwannomas (IVS). In the current study, we aimed to evaluate long‐term quality of life (QoL) as a follow‐up to the assessment of baseline clinical and demographic parameters in the original study. Moreover, QoL outcomes were compared with norms for the general population and for patients who underwent different ear, nose, and throat (ENT) procedures. Materials and Methods. The follow‐up study included 92 patients (59 women and 33 men; mean age, 61.71 ± 12.55 years; range: 32‐85 years) with unilateral IVS who underwent GKS. Patients completed the Assessment of Quality of Life, Penn Acoustic Neuroma Quality‐of‐Life, Glasgow Benefit Inventory, and WHO‐5 Well‐being Index questionnaires as well as a demographic survey. Neurosurgical parameters were assessed using the Koos and House‐Brackmann scales and the results of audiological examinations. Results and Conclusions. QoL scores were within or above the norm in 38% of patients. There were significant differences in terms of comorbidities and emotional well‐being between patients with QoL scores within or above the norm and patients with QoL scores below the norm. Comorbidities were more common in patients with QoL scores below the norm, and they influenced reported QoL (p = 0.009). Patients with QoL scores within or above the norm reported better emotional well‐being than those with QoL scores below the norm. Long‐term QoL outcomes were satisfactory, consistent with the results of the original study. Although GKS is a complex procedure, patients reported higher QoL than those using hearing aids and the same QoL as those after ENT surgery or reassurance. However, they reported a slightly lower QoL than patients taking ENT medications. GKS appears to be a promising treatment option for patients with IVS.
A Qualitative Evaluation of the Warm Banks Scheme as a Response to the Cost‐of‐Living Crisis in North East England
Authors: Teodorowski Piotr , Trevor Miranda
Published: June 2024

Fuel poverty was a significant problem during the cost‐of‐living crisis that started in 2021 as energy prices increased. Local authorities launched warm bank schemes around the United Kingdom to address this problem by providing warm spaces for residents to visit who could not heat their homes. This paper reports on an evaluation of the warm bank scheme launched by South Tyneside Council in winter 2022, locally known as Welcoming Places. Over 70 locations were opened around the borough. The evaluation consisted of two stages. In stage 1, we conducted semistructured interviews (n = 16) with residents who attended Welcoming Places and two focus groups with people running them (n = 9). In stage 2, we discussed the initial findings from stage 1 in a focus group with residents (n = 8). Three major themes are presented: “help and support with the cost‐of‐living crisis,” “it’s worth its weight in gold,” and “capability and strength of Welcoming Places.” This is one of the first evaluations of a warm bank scheme in England. We illustrate how the Welcoming Places in South Tyneside were used and experienced by residents. The scheme was valued by residents, provided significant support during the cost‐of‐living crisis, and had a positive impact on self‐reported mental health among participants. Warm bank schemes offer a practical, rapid public health response to the cost‐of‐living crisis for local authorities as well as improving residents’ mental health and well‐being; however, holistic approaches must be taken to address the underlying causes of fuel poverty.
Impact of Artificial Aging on the Physical and Mechanical Characteristics of Denture Base Materials Fabricated via 3D Printing
Authors: Altarazi Ahmed , Haider Julfikar , Alhotan Abdulaziz , Silikas Nick , Devlin Hugh
Published: June 2024

Three‐dimensional (3D) printing is becoming more prevalent in the dental sector due to its potential to save time for dental practitioners, streamline fabrication processes, enhance precision and consistency in fabricating prosthetic models, and offer cost‐effective solutions. However, the effect of aging in artificial saliva of this type of material has not been explored. To assess the physical and mechanical properties of the two types of 3D‐printed materials before and after being subjected to artificial saliva, a total of 219 acrylic resin specimens were produced. These specimens were made with two types of 3D‐printed materials, namely, NextDent (ND) and Formlabs (FLs), and a Schottlander heat‐cured (HC) resin material that was used as a control. Water sorption and solubility specimens (n = 5) were tested after three months of storage in artificial saliva. Moreover, the Vickers hardness, Martens hardness, flexural strength/modulus, and impact strength were evaluated both under dry conditions and after three months of storage in artificial saliva. The degree of conversion (DC), elemental analysis, and filler content were also investigated. The ANOVA showed that 3D‐printed resins had significantly greater sorption than the control group (p < 0.05). However, the flexural strength values of the 3D‐printed materials were significantly greater (p < 0.05) than those of the heat‐cured material. The DC of the 3D‐printed resins was lower than that of the control group, but the difference was not significant (p > 0.05). The 3D‐printed materials contained significantly more filler than the control (p < 0.05). Moreover, the artificial saliva had a significant effect on the Vickers hardness for all tested groups and on the Martens hardness for the control group only (p < 0.05). Compared with conventional heat‐cured materials, 3D‐printed denture base materials demonstrated relatively poorer performance in terms of sorption, solubility, and DC but exhibited either comparable or superior mechanical properties. The aging process also influenced the Vickers and Martens’ hardness. The strength of the 3D‐printed materials was in compliance with ISO recommendations, and the materials could be used alongside conventional heat‐cured materials.
Table S3 from HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Kim Byung-Gyu , Malek Ehsan , Federov Yuriy , Adams Drew , Chan Timothy , Driscoll James J.
Published: June 2024

Table S3. Target specificity of HDA6 inhibitors. Compounds were tested in 10-dose IC50 mode, in triplicate, with 3-fold serial dilution starting at 1 uM. The HDAC reference compound Trichostatin A (TSA) was tested in a 10-dose IC50 with 3-fold serial dilution starting at 10 uM. HDAC6 reference compound TMP269 was tested in a 10-dose IC50 with 3-fold serial dilution starting at 10 uM. HDAC10 reference compound Quinostat was tested in a 10-dose IC50 with 3-fold serial dilution starting at 10 uM. SIRT reference compound Nicotinamide was tested in a 10-dose IC50 with 3-fold serial dilution starting at 10 uM. SIRT reference compound Suramin was tested in a 10-dose IC50 with 3-fold serial dilution starting at 100 uM. Substrates used for HDAC 1, 2, 3, and 6 were fluorogenic peptide p53 (residues 379-382) RHKK(Ac)-AMC; HDAC 4, 5, 7, 9, 11 were fluorogenic HDAC classic 2a substrate trifluoroacetyl lysine; HDAC8 was fluorogenic peptide p53 residues 379-382 and NAD; HDAC10 was Ac- spermidine-AMC; SIRTs 1, 2, and 3- fluorogenic peptide p53 residues 379-382 and NAD; SIRT5- fluorogenic peptide Ac-Lys-succ and NAD. Curve fits were performed where enzyme activities at the highest compound concentration were <65%. No inhibition indicates that compound activity was negligible and could not be fit to an IC50 curve. IC50 value higher than 1.00E-06 M was estimated based on the best curve fitting available. Assays were determined in collaboration with Reaction Biology (Malvern, PA).
Figure S9 from HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Kim Byung-Gyu , Malek Ehsan , Federov Yuriy , Adams Drew , Chan Timothy , Driscoll James J.
Published: June 2024

Fig. S9. Effect of the top pharmacologics that increased proteasome ChT-like activity on presentation of the SIINFEKL-MHC class I molecule complex. E.G7-Ova cells were treated with pharmacologics at 3 uM for 72 h. Cells were then stained with a monoclonal antibody to Ova 257-264 (SIINFEKL) peptide bound to H2Kb and quantitated using a BD-LSRII sorter interfaced with FlowJo software.
Navigating Challenges in a Case of Unusual Hepatic and Pulmonar Sarcoidosis: A Comprehensive Clinical Journey
Authors: Gonçalves André , Simas Diogo , Gomes Plácido , Leal Carina , Atalaia-Martins Catarina , Vasconcelos Helena
Published: June 2024

Introduction: Sarcoidosis, a systemic granulomatous disorder with uncertain etiology, commonly involves the lungs and, to a lesser extent, the liver. Case Presentation: A previously healthy 35-year-old Congolese female was admitted with a 7-month history of jaundice, itching, and weight loss. Despite markedly mixed hepatitis of a cholestatic pattern of liver injury, liver function tests remained normal in admission laboratory work. Enlarged ethiological study was negative for infections, autoimmunity, heavy metal poisoning, and metabolic diseases. Imaging aligned with compatible biopsy histology led to the diagnosis of hepatic and pulmonary sarcoidosis with vanishing bile duct syndrome. Despite initial treatment with ursodeoxycholic acid and corticosteroid therapy, the patient exhibited an unexpected exacerbation of liver enzymes, prompting a careful consideration of second-line interventions. Following discussion with a tertiary center and a comprehensive review of the literature, it was determined not to intensify therapy due to an inadequate response. Recognizing the persistent challenge of managing advanced cases and the potential progressive course of the disease, the patient was referred to a tertiary transplant center. Currently, she is under outpatient follow-up, clinical and analytically stable with no targeted therapy. Conclusion: This case report details a rare presentation of hepatic sarcoidosis with an unusual laboratory pattern, emphasizing diagnostic and management challenges in recognizing atypical presentations of hepatic sarcoidosis. The complexity of managing advanced cases warrants a multidisciplinary approach and the limited literature on this subject emphasizes the urgency for a more comprehensive understanding of sarcoidosis to improve diagnostic accuracy and refine therapeutic approaches.
Altered Cerebrospinal Fluid Neurofilament Light Chain but Not Neurogranin Levels Are Associated with Response to Ocrelizumab Treatment in Relapsing-Remitting Multiple Sclerosis: A Preliminary Study
Authors: Kızılay Tuğçe , Akbayir Ece , Erol Ruziye , Demir Ayça Simay , Özkan Yaşargün Duygu , Yilmaz Vuslat , Tuzun Erdem , Turkoglu Recai
Published: June 2024

Introduction: Ocrelizumab is a CD20-targeting monoclonal antibody used for treatment of multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) neurofilament light (NFL) chain levels are reduced in MS patients under ocrelizumab treatment indicating a preventive action against neuro-axonal degeneration. Our aim, in this preliminary study, was to explore the impact of ocrelizumab treatment on synaptic integrity through assessment of neurogranin levels. Methods: Thirteen relapsing-remitting multiple sclerosis (RRMS) patients resistant to first-line immunomodulating agents were enrolled and followed up for 24 months under ocrelizumab treatment. Disease activity was monitored by periodic EDSS, MSSS, and cranial-spinal MRI assessments. No evidence of disease activity (NEDA)-3 was determined, and CSF levels of NFL (marker of neuro-axonal integrity) and neurogranin (marker of synaptic integrity) were measured by ELISA at baseline and 12-month ocrelizumab treatment. Results: Seven RRMS patients, who preserved NEDA-3 status during 24-month follow-up, showed ≥30% NFL level decrease, whereas 6 patients with stable/increased NFL levels displayed relapse, MRI lesion, or disability progression. Although most RRMS patients exhibited increased CSF levels of neurogranin under ocrelizumab treatment, patients with and without neurogranin level increase did not differ in terms of clinical features and NEDA-3 status. Baseline neurogranin levels negatively correlated with baseline EDSS scores. Conclusion: Our results confirm that NFL effectively monitors treatment response of RRMS patients under ocrelizumab treatment. Neurogranin does not appear to exhibit a similar benefit in screening of RRMS disease activity. Nevertheless, lower neurogranin levels are associated with increased disability in RRMS indicating a potential disease activity biomarker function.
Cost-Effectiveness of a Biomarker-Based Screening Strategy for Hepatocellular Carcinoma in Patients with Cirrhosis
Authors: Singal Amit G. , Chhatwal Jagpreet , Parikh Neehar , Tapper Elliot
Published: June 2024

Introduction: Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis. Methods: We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis. Model inputs for adherence, benefits, and harms of each strategy were based on literature review, and costs were derived from the Medicare fee schedule. Primary outcomes were quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) of the surveillance strategies, with cost-effectiveness assessed at a threshold of USD 150,000 per QALY. We performed sensitivity analyses for HCC incidence, test performance characteristics, surveillance adherence, and biomarker costs. Results: In the base case, both ultrasound/AFP and biomarker-based surveillance were cost-effective versus no surveillance, with ICERs of USD 105,620, and USD 101,295, per QALY, respectively. Biomarker-based surveillance was also cost-effective versus ultrasound/AFP, with an ICER of USD 14,800 per QALY. Biomarker sensitivity exceeding 80%, cost below USD 210, or adherence exceeding 58% were necessary for biomarker-based screening to be cost-effective versus ultrasound/AFP. In two-way sensitivity analyses, biomarker costs were directly related with test sensitivity and adherence, whereas sensitivity and adherence were inversely related. In a probabilistic sensitivity analysis, biomarker-based screening was the most cost-effective strategy in most (65%) simulations. Conclusion: Biomarker-based screening appears cost-effective for HCC screening, but results are sensitive to test sensitivity, adherence, and costs.
Perfect Match: Radiomics and Artificial Intelligence in Cardiac Imaging
Authors: Baeßler Bettina , Engelhardt Sandy , Hekalo Amar , Hennemuth Anja , Hüllebrand Markus , Laube Ann , Scherer Clemens , Tölle Malte , Wech Tobias
Published: June 2024

Cardiovascular diseases remain a significant health burden, with imaging modalities like echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging playing a crucial role in diagnosis and prognosis. However, the inherent heterogeneity of these diseases poses challenges, necessitating advanced analytical methods like radiomics and artificial intelligence. Radiomics extracts quantitative features from medical images, capturing intricate patterns and subtle variations that may elude visual inspection. Artificial intelligence techniques, including deep learning, can analyze these features to generate knowledge, define novel imaging biomarkers, and support diagnostic decision-making and outcome prediction. Radiomics and artificial intelligence thus hold promise for significantly enhancing diagnostic and prognostic capabilities in cardiac imaging, paving the way for more personalized and effective patient care. This review explores the synergies between radiomics and artificial intelligence in cardiac imaging, following the radiomics workflow and introducing concepts from both domains. Potential clinical applications, challenges, and limitations are discussed, along with solutions to overcome them.
American Heart Association Cardiogenic Shock Registry: Design and Implementation
Authors: Morrow David A. , Jessup Mariell , Abraham William T. , Acker Michael , Aringo Angeline , Batchelor Wayne , Chikwe Joanna , Costello Shaina , Drakos Stavros G. , Farmer Steven , Gelijns Annetine , Gillette Nicole , Hochman Judith S. , Isler Maria , Kapur Navin K. , Kilic Arman , Kormos Robert , Lewis Eldrin F. , Lindenfeld JoAnn , Lombardi Pierluca , Mancini Donna , Rao Sunil V. , Rutan Christine , Samsky Marc , Krucoff Mitchell W.
Published: June 2024

BACKGROUND:

Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States.

METHODS:

Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association’s Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating.

CONCLUSIONS:

The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.