bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyruvate kinase M2 sustains cardiac mitochondrial quality surveillance in septic cardiomyopathy by regulating prohibitin 2 abundance via S91 phosphorylation
Authors: Du Yingzhen , Li Jialei , Dai Zhe , Chen Yuxin , Zhao Yao , Liu Xiaoman , Xia Tian , Zhu Pingjun , Wang Yijin
Published: June 2024

The endogenous mitochondrial quality control (MQC) system serves to protect mitochondria against cellular stressors. Although mitochondrial dysfunction contributes to cardiac damage during many pathological conditions, the regulatory signals influencing MQC disruption during septic cardiomyopathy (SC) remain unclear. This study aimed to investigate the involvement of pyruvate kinase M2 (PKM2) and prohibitin 2 (PHB2) interaction followed by MQC impairment in the pathogenesis of SC. We utilized LPS-induced SC models in PKM2 transgenic (PKM2TG) mice, PHB2S91D-knockin mice, and PKM2-overexpressing HL-1 cardiomyocytes. After LPS-induced SC, cardiac PKM2 expression was significantly downregulated in wild-type mice, whereas PKM2 overexpression in vivo sustained heart function, suppressed myocardial inflammation, and attenuated cardiomyocyte death. PKM2 overexpression relieved sepsis-related mitochondrial damage via MQC normalization, evidenced by balanced mitochondrial fission/fusion, activated mitophagy, restored mitochondrial biogenesis, and inhibited mitochondrial unfolded protein response. Docking simulations, co-IP, and domain deletion mutant protein transfection experiments showed that PKM2 phosphorylates PHB2 at Ser91, preventing LPS-mediated PHB2 degradation. Additionally, the A domain of PKM2 and the PHB domain of PHB2 are required for PKM2-PHB2 binding and PHB2 phosphorylation. After LPS exposure, expression of a phosphorylation-defective PHB2S91A mutant negated the protective effects of PKM2 overexpression. Moreover, knockin mice expressing a phosphorylation-mimetic PHB2S91D mutant showed improved heart function, reduced inflammation, and preserved mitochondrial function following sepsis induction. Abundant PKM2 expression is a prerequisite to sustain PKM2-PHB2 interaction which is a key element for preservation of PHB2 phosphorylation and MQC, presenting novel interventive targets for the treatment of septic cardiomyopathy.
On the initial boundary values problem for a mixture of two Cosserat bodies with voids
Authors: Marin Marin , Öchsner Andreas , Vlase Sorin
Published: June 2024

In this study it is approached a linear model for the mixture of two Cosserat bodies having pores. It is formulated the mixed problem with initial and boundary data in this context. The main goal is to show that the coefficients that realize the coupling of the elastic effect with the one due to voids can vary, without the mixture being essentially affected. In a more precise formulation, this means that a small variation of the coefficients in the constitutive equations of the two continua causes only a small variation of the solutions of the corresponding mixed problems, that is, the continuous dependence of the solutions in relation to these coefficients is ensured. The considered mixture model is consistent because all estimates, specific to continuous dependence, are made based on rigorous mathematical relationships.
Is Europe prepared to live without emissions? A dynamic analysis of the energy transition in economic sectors
Authors: Lucindo Jesús , Feijóo Marisa , González-Álvarez María A.
Published: June 2024

Europe has experienced the adverse effects of climate change due to the human footprint on a scale never seen before. The region's future appears challenging as it persistently adheres to conventional practices. To address this, social movements in Europe must advocate for policymakers to earnestly undertake the widely advocated energy transition within the existing socioeconomic model. A crucial aspect for governments is to comprehend the status along the trajectory of this transition. In this study, we investigate the intricate relationship between emissions, economy, and energy spanning the years 1990 to 2019 across 32 European countries. Our analysis differentiates among major polluting sectors, utilizing a dynamic model that accounts for potential structural breaks. Our findings confirm the presence of ruptures in the stability of the parameters, revealing three distinct periods marked by historical shocks. While the majority of European countries exhibit a decoupling between emissions and economic growth, a contrasting trend is observed between emissions and energy consumption. Notably, the energy supply and residential sectors emerge as the most problematic due to their high carbon intensity. However, the decoupling process remains distant in terms of energy, underscoring the imperative shift toward renewable energy sources over conventional fossil-based fuels. This study emphasizes the urgency of adopting sustainable practices to mitigate climate change and encourages a revaluation of current energy paradigms.
Structural characterization of the extracellular stalk material of the diatom Didymosphenia geminata
Authors: Dütsch Lara , Brendler Erica , Zuber Jan , Viehweger Christine , Ehrlich Hermann , Jesionowski Teofil , Vogt Carla
Published: June 2024

The study represents new bioanalytical characterization of mainly organic components of the poorly investigated extracellular polymeric substances (EPS) of the enigmatic diatom Didymosphenia geminata, an invasive, worldwide expanding species endangering diverse ecosystems. This microalga attaches its siliceous cells to rocky substrates using fibrous stalks, which are made of an EPS-based matrix stabilized by crystalline calcite. The EPS were analyzed using selected methods, including microscopic, spectroscopic, and spectrometric techniques. We identified diverse types of biomolecules. The presence of lipids, condensed aromatics, and heteroaromatic compounds in the EPS has been confirmed using high-resolution mass spectrometry (HR-MS). Additionally, both sulfur-containing functionalities and carboxylic acids were determined too using infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. For the first time, lignin compounds have been detected as one of the components of the EPS of the D. geminata diatom, using HR-MS and fluorescence microscopy (FM) in combination with specific staining techniques. By increasing the understanding of the chemistry and structural features of the stalks, we aim to develop potential applications and methods for removing these stalks from affected regions in the future, or, alternatively, to use them as a large-scale source of sustainable biocomposite material.

Graphical abstract
Two Weeks of Continuous Opioid Treatment in an Adenine-Induced Mouse Model of Chronic Kidney Disease Exacerbates the Bone Inflammatory State and Increases Osteoclasts
Authors: Metzger Corinne E. , Grecco Gregory G. , Tak Landon Y. , Atwood Brady K. , Allen Matthew R.
Published: June 2024

Patients with chronic kidney disease (CKD) report high pain levels, but reduced renal clearance eliminates many analgesic options; therefore, 30–50% of CKD patients have chronic opioid prescriptions. Opioid use in CKD is associated with higher fracture rates. Opioids may directly alter bone turnover directly through effects on bone cells and indirectly via increasing inflammation. We hypothesized that continuous opioid exposure would exacerbate the high bone turnover state of CKD and be associated with elevated measures of inflammation. Male C57Bl/6J mice after 8 weeks of adenine-induced CKD (AD) and non-AD controls (CON) had 14-day osmotic pumps (0.25-µL/hr release) containing either saline or 50-mg/mL oxycodone (OXY) surgically implanted in the subscapular region. After 2 weeks, all AD mice had elevated blood urea nitrogen, parathyroid hormone, and serum markers of bone turnover compared to controls with no effect of OXY. Immunohistochemical staining of the distal femur showed increased numbers of osteocytes positive for the mu opioid and for toll-like receptor 4 (TLR4) due to OXY. Osteocyte protein expression of tumor necrosis factor-α (TNF-α) and RANKL were higher due to both AD and OXY so that AD + OXY mice had the highest values. Trabecular osteoclast-covered surfaces were also significantly higher due to both AD and OXY, resulting in AD + OXY mice having 4.5-fold higher osteoclast-covered surfaces than untreated CON. These data demonstrate that opioids are associated with a pro-inflammatory state in osteocytes which increases the pro-resorptive state of CKD.
Hybrid Chin Advancement: Combining Fat and Sliced Cartilage Grafts for Chin Augmentation During Rhinoplasty
Authors: Selamioğlu Engin , Küçüker İsmail
Published: June 2024

Background

Facial balance significantly impacts aesthetics, particularly in the middle and lower thirds. Patients with chin retrusion often benefit from sagittal plane chin advancement in rhinoplasty, enhancing surgical outcomes and satisfaction.

Objectives

This article presents a method for analyzing chin deformities and discusses a hybrid treatment approach to harmonize facial features, complementing rhinoplasty.

Methods

The chin positions of patients treated by the senior author were assessed. A retrospective analysis included 49 patients with chin retrusion of 2.5–6 mm. Among them, 22 patients initially offered chin implants declined, leading to planned chin augmentation. Fat grafting was exclusively performed for 20 patients lacking sufficient cartilage. The "Hybrid Chin Advancement" technique involved supporting tissues beneath muscles with nasal septum cartilage and fat injections and tissues above muscles with fat injection alone.

Results

Pre- and postoperative Legan angle measurements and chin advancements were compared across three groups. While preoperative Legan angles were statistically similar, postoperative Legan angles and advancement changes were significantly higher in the implant group (p < 0.0001). Comparing hybrid chin advancement and fat grafting groups, postoperative Legan angles and advancement changes were significantly higher in the hybrid chin group (p < 0.0001).

Conclusions

Fat grafting suffices for mild advancements (~ 2 mm), while the hybrid chin method is effective for moderate advancements (~ 4 mm). For advancements exceeding 6 mm, implants or osseous genioplasty are optimal. Our study’s hybrid approach offers an easy, safe, and reliable method for achieving facial harmony in the lower two-thirds without compromising patient expectations.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Efficacy and safety of fostamatinib in refractory immune thrombocytopenia: a meta-analysis from randomized controlled trials
Authors: Tungjitviboonkun Songphol , Bumrungratanayos Naharuthai , Jitwimungsanon Jedsadakorn , Kheamakulvanich Thanat , Siramongkholkarn Smuch
Published: June 2024

Background

Immune thrombocytopenia (ITP) is an immune-mediated disease that results in low platelet counts. Despite appropriate treatment, many patients continue to experience refractory disease. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, has emerged as a promising option for refractory ITP.

Objective

This meta-analysis aims to evaluate the efficacy and safety of fostamatinib compared to conventional therapy in adults aged ≥ 18 years with refractory ITP.

Materials and methods

Literature search was conducted in PubMed, Scopus, Embase, and clinicaltrials.gov databases from inception to March 31, 2024. Randomized controlled trials (RCTs) assessing the safety and efficacy of fostamatinib in adults with refractory ITP were included. Data extraction, risk of bias assessment, and statistical analysis were performed following PRISMA guideline.

Results

A total of 495 articles were screened, with three RCTs meeting the inclusion criteria. Fostamatinib therapy demonstrated superior efficacy in achieving stable platelet response by week 24 (ORR 0.80; 95%CI 0.72–0.88), platelet count ≥ 50,000/µL at weeks 12 (ORR 0.80; 95%CI 0.72–0.90) and week 24 (ORR 0.82; 95%CI 0.72–0.90). Additionally, fostamatinib improves platelet counts in subjects with a baseline count of < 15,000/µL. The Number Needed to Treat (NNT) was calculated as 10. Adverse effects include diarrhea (RR 2.32; 95%CI 1.11–4.84), hypertension (RR 2.33; 95%CI 1.00-5.43), and abnormal liver function tests (RR 4.18; 95% CI 1.00-17.48). Interestingly, the occurrences of nausea (RR 1.77; 95% CI 0.33–9.67) and rash (RR 2.28; 95% CI 0.50-10.29) did not achieve statistical significance.

Conclusion

This meta-analysis provides robust evidence supporting the efficacy of fostamatinib in improving platelet counts and achieving therapeutic goals in adults with refractory ITP. However, fostamatinib’s safety profile warrants consideration due to higher rates of diarrhea, hypertension, and abnormal liver function tests.
Dorsal wrist ganglion: clinical and imaging correlation in symptomatic population based on high-field MRI
Authors: Ferreira Branco David , Botti Paul , Bouvet Cindy , Abs Bilal , Buzzi Marcello , Beaulieu Jean Yves , Poletti Pierre-Alexandre , Bouredoucen Hicham , Boudabbous Sana
Published: June 2024

Objectives

To determine prevalence in the symptomatic population of dorsal mucoid cysts centered on dorsal capsuloscapholunate septum (DCSS) using high-field magnetic resonance imaging (MRI) for anatomoclinical and epidemiological correlations.

Materials and methods

This single-center retrospective study analyzed all 3-Tesla MRIs consecutively performed for painful wrists in 295 patients. Two blinded readers performed measurements. The protocol included T1 spin echo and 3D proton density sequences with fat saturation. Inter-observer reliability was assessed using kappa and intra-class correlation coefficients for cyst detection and volumetry, respectively. Disagreements concerning cyst detection were resolved by a consensus reading. Cyst size, relationship to extrinsic and scapholunate ligaments (SL), continuity of SL, minimum distance to the posterior interosseous nerve (PIN), cyst communication with joint, and anatomical classifications of cysts were analyzed. Correlation tests were performed to assess associations.

Results

Two-hundred ninety-five patients (mean age 39.6 +/− 15.6 (standard deviation), 161 males) were evaluated for detection of dorsal wrist cysts identified in 150/295. In this subgroup, the mean age was 38.7 years (15–75), the sex ratio of 0.6 (59% women), and the median volume cyst of 8.7 mm3 (0.52–2555). Cyst detection, volume, and major axis measurements showed very high agreement between observers, respectively, 0.89, 0.96, and 0.91. 42 patients had dorsal SL pain. A weak negative correlation was found between distance to PIN and dorsal SL pain (r = −0.2415; p < 0.05) and a weak positive correlation between Guérini’s classification and dorsal SL pain (r = 0.2466; p < 0.05).

Conclusion

High-field MRI is the modality of choice for the detection, anatomical, and volumetric assessment of dorsal cysts. Preoperative assessment will be aided by the proposed revised anatomical classification.

Clinical relevance statement

High-field MRI is the modality of choice for the anatomical study of dorsal ganglion cysts. It allows the radiologist to accurately describe the anatomical relationships, size, and visibility of the pedicle, essential information for the surgeon’s preoperative assessment.

Key Points

Dorsal mucoid wrist ganglion is a condition for which prevalence remains to be determined.

High-field MRI is a reproducible imaging modality for the detection and assessment of dorsal wrist cysts.

High-field MRI has a key role in the preoperative management of dorsal mucoid cysts.
Sulphate reduction and carbonate precipitation in a high-energy algal rim framework
Authors: Leplastrier Aero , Rintoul Max , Opdyke Bradley , Nand Vikashni , Branson Oscar , Eggins Stephen M. , Ellwood Michael J.
Published: June 2024

Algal ridges are protective features for coral reefs that form through the accretion and encrustation of reef rubble and debris by crustose coralline algae (CCA) and processes of diagenetic cementation. Carbonate precipitation and dissolution dynamics on and within algal ridge frameworks are poorly understood. We studied the surface and subsurface geochemistry of the algal ridge framework at One Tree Island, Australia. Measurable quantities of hydrogen sulphide were detected in most porewater samples collected from bores, indicating a largely anoxic ridge framework. Total alkalinity (TA) and pH measurements indicate that the precipitation of carbonate minerals within the interior of the ridge framework occurs under largely anoxic conditions and is likely to be driven by TA changes associated with sulphate-reducing bacteria. Modelling of porewater hydrogen sulphide concentrations in combination with TA and dissolved inorganic carbon (DIC) indicates anoxic respiration processes produce alkalinity within the algal ridge framework. However, significantly more TA is removed via the precipitation of mineral carbonate, resulting in porewater TA concentrations falling below the open seawater values. The precipitation of mineral carbonate also lowers interstitial water pH, such that pH changes are not solely from organic carbon diagenesis. The simultaneous precipitation and dissolution of carbonate minerals within the algal ridge framework are key to forming and cementing algal ridges, which are important physical protective features for coral reefs.
Vertebrate centromere architecture: from chromatin threads to functional structures
Authors: Andrade Ruiz Lorena , Kops Geert J. P. L. , Sacristan Carlos
Published: June 2024

Centromeres are chromatin structures specialized in sister chromatid cohesion, kinetochore assembly, and microtubule attachment during chromosome segregation. The regional centromere of vertebrates consists of long regions of highly repetitive sequences occupied by the Histone H3 variant CENP-A, and which are flanked by pericentromeres. The three-dimensional organization of centromeric chromatin is paramount for its functionality and its ability to withstand spindle forces. Alongside CENP-A, key contributors to the folding of this structure include components of the Constitutive Centromere-Associated Network (CCAN), the protein CENP-B, and condensin and cohesin complexes. Despite its importance, the intricate architecture of the regional centromere of vertebrates remains largely unknown. Recent advancements in long-read sequencing, super-resolution and cryo-electron microscopy, and chromosome conformation capture techniques have significantly improved our understanding of this structure at various levels, from the linear arrangement of centromeric sequences and their epigenetic landscape to their higher-order compaction. In this review, we discuss the latest insights on centromere organization and place them in the context of recent findings describing a bipartite higher-order organization of the centromere.
Dentition patterns and molecular diversity of Mastophorus muris (Gmelin, 1790) (Nematoda: Spiruroidea) support a host-associated subdivision
Authors: Jost Jenny , Hirzmann Jörg , Ďureje Ľudovít , Maaz Denny , Martin Peer , Stach Thomas , Heitlinger Emanuel , Jarquín-Díaz Víctor Hugo
Published: June 2024

Mastophorus muris (Gmelin, 1790) is a globally distributed parasitic nematode of broad range mammals. The taxonomy within the genus Mastophorus and the cryptic diversity among the genus are controversial among taxonomists. This study provides a detailed morphological description of M. muris from Mus musculus combined with a molecular phylogenetic approach. Moreover, descriptions and molecular data of M. muris from non-Mus rodents and wildcats complement our findings and together provide new insights into their taxonomy. The analysis of M. muris was based on light microscopy and scanning electron microscopy. The morphological description focused on the dentition pattern of the two trilobed pseudolabia. Additionally, we described the position of the vulva, arrangement of caudal pairs of papillae, spicules and measured specimens from both sexes and the eggs. For the molecular phylogenetic approach, we amplified the small subunit ribosomal RNA gene and the internal transcribed spacer, and the cytochrome c oxidase subunit 1. Mastophorus morphotypes based on dentition patterns and phylogenetic clustering indicate a subdivision of the genus in agreement with their host. We recognize two groups without a change to formal taxonomy: One group including those specimens infecting Mus musculus, and the second group including organisms infecting non-Mus rodents. Our genetic and morphological data shed light into the cryptic diversity within the genus Mastopohorus. We identified two host-associated groups of M. muris. The described morphotypes and genotypes of M. muris allow a consistent distinction between host-associated parasites.
Morbidity and mortality following hiatal hernia repair in geriatric patients: a multicenter research network study
Authors: Kumar Sunjay S. , Rama Martina , Koeneman Scott , Tannouri Sami , Tatarian Talar , Palazzo Francesco
Published: June 2024

Background

Hiatal hernia is a common surgical pathology. Such hernias can be found incidentally and patients may opt for an initial nonoperative approach though many will pursue surgery after symptom progression. Data on the effects of age on the outcomes of hiatal hernia repair may help inform this decision-making process.

Methods

The TriNetX database was queried for all adult patients undergoing hiatal hernia repair from 2000 to 2023. Patients were divided into elective and emergent cohorts on the basis of diagnosis codes indicating obstruction or gangrene. Patients aged 80–89 were compared against those aged 65–79 in unadjusted analysis. Logistic regression models controlling for additional health history covariates were created to calculate odds ratios for primary outcomes.

Results

There were 2310 octogenarians and 15,295 seniors who underwent elective hiatal hernia repair, and 406 octogenarians and 1462 seniors who underwent emergent repair during the study period. The vast majority of patients in both groups underwent minimally invasive operations. In the elective cohort, octogenarians had higher rates of mortality, malnutrition, sepsis, respiratory failure, pneumonia, DVT, blood transfusion, and discharge to nursing facility. In the emergent cohort, octogenarians had higher rates of mortality, malnutrition, sepsis, and respiratory failure. The odds ratios for mortality in the elective and emergent cohorts were 3.9 (95% CI 3.1–5.0) and 3.5 (95% CI 2.1–5.6), respectively.

Conclusion

Octogenarians are at a meaningfully increased risk for mortality and morbidity after both elective and emergent hiatal hernia repair compared to senior-aged patients. Greater consideration should be given to surgical repair prior to the 8th decade of life.
2D Representations of 3D Point Clouds Via the Stereographic Projection with Encryption Applications
Authors: Annaby M. H. , Mahmoud M. E. , Abdusalam H. A. , Ayad H. A. , Rushdi M. A.
Published: June 2024

Using the topological equivalence between the Riemann sphere$$\mathbb {S}$$Sand the extended complex plane$$\overline{\mathbb {C}} = \mathbb {C} \cup \{\infty \}$$C¯=C∪{∞}, where$$\mathbb {C}$$Cis the field of complex numbers, we establish 2D-bijective representations of 3D point clouds. Points of 3D point clouds are mapped into the Riemann sphere$$\mathbb {S}$$S, and a stereographic projection is implemented to map the points into the complex plane$$\mathbb {C}$$C. The way the 3D objects are mapped into$$\mathbb {S}$$Smay be varied for various applications. To prove the accuracy and efficiency of the proposed 2D representation of 3D objects, we apply this correspondence to 3D point cloud encryption. We utilize chaotic permutations, chaotic circuits, and Latin cubes in addition to the stereographic projection representation to construct our scheme. The permutation steps using chaotic maps and Latin cubes are carried out on the object data points in both$$\mathbb {S}$$Sand$$\overline{\mathbb {C}}$$C¯, while the chaotic circuits are applied to 2D projections of the 3D objects. To the best of our knowledge, no earlier work employed stereographic projections for 3D object encryption. Experimental simulations of this method show high encryption strength and strong confusion and diffusion properties based on quantitative and statistical measures.
Comparative study on muscle function in two different streptozotocin-induced diabetic models
Authors: Aisyah Rahmawati , Kamesawa Mion , Horii Mayu , Watanabe Daiki , Yoshida Yuki , Miyata Kenshu , Kumrungsee Thanutchaporn , Wada Masanobu , Yanaka Noriyuki
Published: June 2024

Aims

Streptozotocin (STZ) is widely used to study diabetic complications. Owing to the nonspecific cytotoxicity of high-dose STZ, alternative models using moderate-dose or a combination of low-dose STZ and a high-fat diet have been established. This study aimed to investigate the effects of these models on muscle function.

Methods

The muscle function of two STZ models using moderate-dose STZ (100 mg/kg, twice) and a combination of low-dose STZ and high-fat diet (50 mg/kg for 5 consecutive days + 45% high-fat diet) were examined using in vivo electrical stimulation. Biochemical and gene expression analysis were conducted on the skeletal muscles of the models immediately after the stimulation.

Results

The contractile force did not differ significantly between the models compared to respective controls. However, the moderate-dose STZ model showed more severe fatigue and blunted exercise-induced glycogen degradation possibly thorough a downregulation of oxidative phosphorylation- and vasculature development-related genes expression.

Conclusions

Moderate-dose STZ model is suitable for fatigability assessment in diabetes and careful understanding on the molecular signatures of each model is necessary to guide the selection of suitable models to study diabetic myopathy.
Climate change impact on barrier island freshwater lenses and their transition zones: a multi-parameter study
Authors: Thissen Lena , Greskowiak Janek , Gaslikova Lidia , Massmann Gudrun
Published: June 2024

Freshwater lenses and their freshwater–saltwater transition zones are affected by climate change. Both sea-level rise and groundwater recharge influence freshwater volume and transition zone thickness. This study used a semi-generic approach to investigate climate change effects on freshwater lenses: a hypothetical island cross-section was combined with real-world boundary conditions. Sea-level projections including tides and storm surges, annual mean sea-level rise data, and monthly recharge projections of several climate models of the German barrier island Norderney in the North Sea were used to evaluate changes in freshwater lens and transition zone size between 1971–2000 and 2071–2100. Firstly, impacts of sea-level and recharge boundary conditions were investigated on islands of different widths. Secondly, a multi-parameter study was conducted focussing on variations of several relevant hydrogeological parameters. Results showed that it is very likely but not certain that freshwater lens volume and depth will decrease and transition zone thickness increase as a consequence of climate change. Model predictions revealed a strong dependency on the employed climate models and to a lesser extent on the hydrogeological parameters, at least for the parameter ranges used in this study. Of all hydrogeological parameters tested, the largest effects were caused by the hydraulic conductivity and its anisotropy. Furthermore, the study showed that boundary conditions have larger impacts on smaller islands. These results illustrate the importance of using projections from climate models in a sufficiently high resolution. Furthermore, their uncertainties and changes in variability of boundary conditions should be considered in studies about climate change impacts on freshwater lenses.
Self-swabbing versus assisted swabbing for viral detection by qRT-PCR: the experience from SARS-CoV-2 based on a meta-analysis of six prospectively designed evaluations conducted in a UK setting
Authors: Fowler Tom , Chapman David , Futschik Matthias E. , Tunkel Sarah A. , Blandford Edward , Turek Elena , Kolade Olumide , da Cunha Sergio Souza , Dodgson Andrew , Klapper Paul , Sudhanva Malur , Davies Lindsey , Hill Sue , Hopkins Susan , Peto Tim
Published: June 2024

Purpose

In April 2020, the UK Government implemented NHS Test and Trace to provide SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (qRT-PCR) testing for the public, with nose-and-throat swabbing for samples performed by trained staff. Self-swabbing (SS) would allow rapid scale-up of testing capacity and access. Six studies were undertaken to determine whether SS was as effective for detecting SARS-CoV-2 as swabbing performed by trained staff.

Methods

Six prospective studies were conducted between April–October 2020, using six swab/media combinations. Differences between assisted swabbing (AS) and SS were evaluated for concordance, positivity, sensitivity, cycle threshold (Ct) values and void rates. Statistical analysis was performed using 95% confidence intervals (CIs), paired t-tests and model-based methods.

Results

Overall, 3,253 individuals were recruited (median age 37 years, 49% female), with 2,933 having valid paired qRT-PCR results. Pooled concordance rate was 98% (95% CI: 96%, 99%). Positivity rate differences for SS (8.1%) and AS (8.4%) and differences in pooled sensitivities between SS (86%; 95% CI: 78%, 92%) and AS (91%; 95% CI: 78%, 96%) were nonsignificant. Both types of swabbing led to pooled void rates below 2% and strongly correlated Ct values. Age, sex and previous swabbing experience did not have a significant impact on concordance or sensitivity.

Conclusion

The UK adopted a policy to promote self-testing for SARS-CoV-2 based on data demonstrating equivalence of SS versus AS. Positive outcomes with SS are likely generalisable to testing for other respiratory pathogens, and we consider self-sampling and self-testing essential for future pandemic preparedness.
Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for new-onset gastric cancer and gastric diseases in patients with type 2 diabetes mellitus: a population-based cohort study
Authors: Chou Oscar Hou In , Chauhan Vinod Kumar , Chung Cheuk To Skylar , Lu Lei , Lee Teddy Tai Loy , Ng Zita Man Wai , Wang Karin Kai Wing , Lee Sharen , Liu Haipeng , Pang Ronald Ting Kai , Kaewdech Apichat , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong
Published: June 2024

Objective

To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a).

Design

This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting.

Results

A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23–0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03–1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19–0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use.

Conclusions

The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use.

Graphical abstract
Appropriate definition of non-metastatic castration-resistant prostate cancer (nmCRPC) and optimal timing of androgen receptor signaling inhibitor (ARSI)
Authors: Matsumoto Kazuhiro , Kosaka Takeo , Takeda Toshikazu , Fukumoto Keishiro , Yasumizu Yota , Tanaka Nobuyuki , Morita Shinya , Mizuno Ryuichi , Asanuma Hiroshi , Oya Mototsugu
Published: June 2024

Background

Defined by rising PSA levels under androgen deprivation therapy (ADT) despite no visible metastases on conventional imaging, non-metastatic castration-resistant prostate cancer (nmCRPC) represents a complex clinical challenge. A significant subset of these patients rapidly develops metastatic disease, negatively impacting survival. We examined the difference in prognosis of nmCRPC patients according to the timing of therapeutic interventions with androgen receptor signaling inhibitor (ARSI).

Methods

We examined 102 nmCRPC patients treated with ARSI. We divided patients according to their PSA levels when ARSI was administered: Cohort A (PSA 0.5–2.0 ng/mL), Cohort B (PSA 2.0–4.0 ng/mL), and Cohort C (PSA > 4.0 ng/mL). Utilizing the Kaplan–Meier method for survival analysis, our analytical starting point was the moment when PSA levels exceeded 0.5 ng/mL post-ADT nadir, ensuring a fair comparison and minimizing lead-time bias.

Results

After excluding 5 patients whose PSA nadir after ADT > 0.5 ng/mL, patient distribution across Cohort A, Cohort B, and Cohort C was 32, 24, and 41 patients, respectively. Kaplan–Meier survival analysis highlighted a 2-year metastasis-free survival rate of 97% for Cohort A, 87% for Cohort B, and 73% for Cohort C. A marked statistical difference emerged when comparing Cohort A with Cohorts B and C, with a p-value of 0.043.

Conclusion

The timely initiation of ARSI is paramount in nmCRPC management. Our findings strongly advocate for consideration of ARSI administration in nmCRPC patients before their PSA levels exceed 2.0 ng/mL. Our results indicated a PSA threshold of 1.0 ng/mL for nmCRPC definition which is more reasonable to administer ARSI without delay.
MBFair: a model-based verification methodology for detecting violations of individual fairness
Authors: Ramadan Qusai , Konersmann Marco , Ahmadian Amir Shayan , Jürjens Jan , Staab Steffen
Published: June 2024

Decision-making systems are prone to discrimination against individuals with regard to protected characteristics such as gender and ethnicity. Detecting and explaining the discriminatory behavior of implemented software is difficult. To avoid the possibility of discrimination from the onset of software development, we propose a model-based methodology called MBFair that allows for verifying UML-based software designs with regard to individual fairness. The verification in MBFair is performed by generating temporal logic clauses, whose verification results enable reporting on the individual fairness of the targeted software. We study the applicability of MBFair using three case studies in real-world settings including a bank services system, a delivery system, and a loan system. We empirically evaluate the necessity of MBFair in a user study and compare it against a baseline scenario in which no modeling and tool support is offered. Our empirical evaluation indicates that analyzing the UML models manually produces unreliable results with a high chance of 46% that analysts overlook true-positive discrimination. We conclude that analysts require support for fairness-related analysis, such as our MBFair methodology.
Celebrating 10 Years of the HIMSS-SIIM Enterprise Imaging Community and Enterprise Imaging Informatics
Authors: Roth Christopher J. , Petersilge Cheryl A. , Cram Dawn , Garriott Kim , Lannum Lou , Carey Cheryl K. , Medina Nikki , Kwiatkoski Tammy , Whitfill James T. , Towbin Alexander J.
Published: June 2024

In response to the growing recognition of enterprise imaging as a critical component of healthcare’s digital transformation, in 2014, the Healthcare Information and Management Systems Society (HIMSS) and the Society for Imaging Informatics in Medicine (SIIM) signed a Memorandum of Understanding to form the HIMSS-SIIM Enterprise Imaging Community (HSEIC). At the time of the agreement, the two organizations decided to collaborate to lead enterprise imaging development, advancement, and adoption. This paper celebrates the past 10 years of the HSEIC’s thought leadership, industry partnerships, and impact while also looking ahead to identify enterprise imaging challenges to solve in the next decade.
Tight contact structures on some families of small Seifert fiber spaces
Authors: Wan S.
Published: June 2024

Suppose K is a knot in a 3-manifold Y, and that Y admits a pair of distinct contact structures. Assume that K has Legendrian representatives in each of these contact structures, such that the corresponding Thurston-Bennequin framings are equivalent. This paper provides a method to prove that the contact structures resulting from Legendrian surgery along these two representatives remain distinct. Applying this method to the situation where the starting manifold is $$-\Sigma(2,3,6m+1)$$

-
Σ
(
2
,
3
,
6
m
+
1
)

and the knot is a singular fiber, together with convex surface theory we can classify the tight contact structures on certain families of Seifert fiber spaces.
The climate niche of Homo Sapiens
Authors: Tol Richard S. J.
Published: June 2024

The increasing atmospheric concentrations of greenhouse gases will place humans in climates that are unprecedented in the evolution of the species. I use the ecological definition of the human niche in climate space, and combine this with a new constellation of methods from extreme value statistics to study human occupation near the boundaries of that niche. I find that the temperature distribution has a thin tail whereas the tail of precipitation is thick. This thick tail reflects that humans are used to a wide range of rainfall regimes, so future precipitation changes, although leading to unprecedented rainfall, are less likely to pose a major challenge. An increase in temperature, on the other hand, will put hundreds of millions of people in heat that is not just unprecedented and but also hard to imagine from extrapolating current temperatures. These findings are qualitatively similar but an order of magnitude smaller than previous studies.
Risk-Aware Framework Development for Disruption Prediction: Alcator C-Mod and DIII-D Survival Analysis
Authors: Keith Zander , Nagpal Chirag , Rea Cristina , Tinguely R. Alex
Published: June 2024

Survival regression models can achieve longer warning times at similar receiver operating characteristic performance than previously investigated models. Survival regression models are also shown to predict the time until a disruption will occur with lower error than other predictors. Time-to-event predictions from time-series data can be obtained with a survival analysis statistical framework, and there have been many tools developed for this task which we aim to apply to disruption prediction. Using the open-source Auton-Survival package we have implemented disruption predictors with the survival regression models Cox Proportional Hazards, Deep Cox Proportional Hazards, and Deep Survival Machines. To compare with previous work, we also include predictors using a Random Forest binary classifier, and a conditional Kaplan-Meier formalism. We benchmarked the performance of these five predictors using experimental data from the Alcator C-Mod and DIII-D tokamaks by simulating alarms on each individual shot. We find that developing machine-relevant metrics to evaluate models is an important area for future work. While this study finds cases where disruptive conditions are not predicted, there are instances where the desired outcome is produced. Giving the plasma control system the expected time-to-disruption will allow it to determine the optimal actuator response in real time to minimize risk of damage to the device.
The IFMIF-DONES Diagnostics and Control Systems: Current Design Status, Integration Issues and Future Perspectives Embedding Artificial Intelligence Tools
Authors: Cappelli M. , Torregrosa-Martin C. , Diaz J. , Ibarra A.
Published: June 2024

As an integral part of the European strategy for advancing fusion-generated electricity, IFMIF-DONES represents a high-intensity neutron irradiation plant with the main purpose of assessing the suitability of materials for fusion reactor applications. Its primary mission is to examine how materials respond to irradiation within a neutron flux that mimics the conditions expected in the first wall of the proposed DEMO reactor, which is intended to succeed ITER. Consequently, IFMIF-DONES, whose construction is slated to commence shortly, plays a pivotal role in aiding the development, approval, and safe operation of DEMO, as well as future fusion power plants. This paper provides a quick overview of the current development of the IFMIF-DONES neutron source with a particular snapshot of the present engineering design status for what concerns the instrumentation and control systems together with its complex diagnostics, that guarantees the safe monitoring, supervision and regulation of all operations. The current status of design, after the completion of the preliminary design phase is presented, as well as the existing and future plans for their integration also using some of the new capabilities offered by Artificial Intelligence tools.
Reflexives and politeness: possessive pronouns in Russian imperative sentences
Authors: Perevozchikova Tatiana
Published: June 2024

In Russian, a specialized reflexive possessive pronoun must be used to indicate coreference between the possessor and the subject. However, it has been observed that in the first and second person plural, the reflexivization rule is often violated, and a non-reflexive possessive is used for subject coreference. Existing studies do not distinguish between singular formal and plural informal readings in the second person, assuming no difference between the two contexts. Furthermore, there is limited knowledge regarding the use of possessives in imperative contexts, as previous research has primarily focused on indicatives.

This article aims to investigate the use of possessive pronouns in both formal and informal imperative contexts by addressing two questions. First, how often is a non-reflexive possessive used to indicate coreference with the subject in Russian imperative sentences? Second, what combination of semantic and pragmatic factors allows its use? Apart from the semantic factors that are well documented in the existing literature (referentiality, animacy and alienability of the possessum), we will consider three pragmatic dimensions of politeness that have not been considered so far: form or address (informal $ty$
t
y
/ formal $Vy$
V
y
), type of imperative (speaker- / hearer-oriented) and verbal aspect (perfective / imperfective).

The study analyzed the use of possessive pronouns in imperatives in the spoken subcorpus of the Russian National Corpus using generalized linear mixed models and random forests. The findings suggest that the choice of possessive is strongly influenced by the form of address ($ty$
t
y
/ $Vy$
V
y
). When addressing the listener with the informal $ty$
t
y
, a reflexive possessive is almost exclusively used. When addressing the listener with the formal $Vy$
V
y
, both possessives are used equally often. The choice between them depends on several factors, including the referentiality and alienability of the possessum, the type of imperative, and the verbal aspect. The non-reflexive form is preferred when the possessum is referential, the imperative is speaker-oriented, and, to a lesser extent, when the possessum is alienable and the verb is in the perfective aspect. Additionally, some verbs such as ‘give’ and ‘show’ strongly prefer a non-reflexive possessive.

The results suggest that a reflexive possessive has become the default for subject coreference in Russian second person singular informal contexts. In formal contexts, however, the change is still ongoing, and a non-reflexive possessive is used to express the referential uniqueness of the possessum and to convey negative politeness towards the addressee.
Association between triglyceride-glucose index and chronic kidney disease: results from NHANES 1999–2020
Authors: Li Xiaowan , Wang Lanyu , Zhou Hongyi , Xu Hongyang
Published: June 2024

Aims

Examining the connection between the triglyceride-glucose (TyG) index and chronic kidney disease (CKD) was the aim of this investigation.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999–2020 were analyzed in this study. The TyG index was calculated as Ln (triglycerides (mg/dl) * fasting glucose (mg/dl)/2). The two criteria used to diagnose CKD were low estimated glomerular filtration rate (eGFR) (eGFR < 60 mL/min/1.73m2) or albuminuria (urine albumin-to-creatinine ratio (ACR) ≥ 30 mg/g). To look into the independent associations between TyG index levels with CKD, albuminuria, and low-eGFR, weighted multivariable logistic regression and generalized additive models were employed. To assess and contrast the diagnostic ability, receiver operating characteristic (ROC) curves were employed.

Results

Out of 18,078 total participants recruited, 48.54% were male. 8.48 + 0.68 was the mean value of the TyG index. CKD, albuminuria, and low-eGFR were common, with respective prevalences of 17.06%, 11.26%, and 8.03%, respectively. The TyG index and CKD were observed to positively correlate (OR = 4.03; 95% CI 1.81, 8.96). In US adults between the ages of 41 and 60, a J-shaped connection was found between the two. Furthermore, a higher TyG index is associated with a higher prevalence of albuminuria (OR = 6.11; 95% CI 2.64, 14.14). Subgroup analyses and interaction tests revealed that different stratifications did not significantly affect the relationship between TyG index and CKD, albuminuria, and low-eGFR. Comparing the TyG index to other indicators [lipid accumulation product (LAP), Visceral adiposity index (VAI), and the triglyceride glucose–body mass index (TyG-BMI)], it may be more accurate and discriminative in predicting CKD and albuminuria.

Conclusion

When predicting CKD and albuminuria, the TyG index may be a more useful marker when compared to other markers (LAP, VAI, and TyG-BMI index). In addition, in American adults aged 41–60, the TyG index shows a J-shaped relationship with CKD. As a result, when assessing the kidney health of US adults, we must pay close attention to the significance of the TyG index.