bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of supplemental oxygen in reducing the need for laser or intravitreal bevacizumab in preterm infants with stage 2 retinopathy of prematurity
Authors: Minturn Robert , Hartigan Kelly , Vegunta Sravanthi , Boente Charline , Golzarri-Arroyo Lilian , Hynes Elizabeth , Laughlin Elleen , Haider Kathryn , Kua Kok Lim
Published: May 2024

Background

Retinopathy of prematurity (ROP) is a disease that affects preterm infants born younger than 30 weeks of gestation. The pathophysiology of ROP involves an initial vaso-obliterative phase followed by vaso-proliferative phase that leads to disease progression. The use of supplemental oxygen during the vaso-proliferative phase of ROP has been associated with reduced disease progression, but how this impacts the need for ROP treatment is unclear. The goal of this study was to compare the rate of laser or intravitreal bevacizumab after implementation of a new supplemental oxygen therapy protocol in preterm infants with stage 2 ROP.

Methods

This is a retrospective chart review of preterm infants diagnosed with stage 2 ROP at Riley Hospital for Children between 1/2017 and 12/2022. Patients diagnosed between 1/2017 and 6/2020 were classified as Cohort A, preprotocol implementation. Patients diagnosed from 8/2020 to 12/2022 were classified as Cohort B, postprotocol implementation. In Cohort A, oxygen saturation was kept at 91-95% through the entire hospitalization. In Cohort B, oxygen saturation was increased to 97–99% as soon as Stage 2 ROP was diagnosed. Statistical analyses were performed using chi-square and Student’s T test, followed by multivariate analyses to determine the impact of the oxygen protocol on the need for ROP treatment.

Results

A total of 211 patients were diagnosed with stage 2 ROP between 1/2017 and 12/2022. Of those patients, 122 were before protocol implementation therapy (Cohort A), and 89 were after implementation of supplemental oxygen protocol (Cohort B). Gestational age was slightly higher in Cohort B (Cohort A 25.3 ± 1.9, Cohort B 25.8 ± 1.84, p = 0.04). There was no difference in birth weight, NEC, BPD, or survival. Cohort B had lesser need for invasive mechanical ventilation and higher days on CPAP during hospitalization. Notably, Cohort A had 67 (55%) patients treated with laser photocoagulation or intravitreal bevacizumab versus 20 (22%) patients in Cohort B (OR 0.19, 0.08–0.40).

Conclusion

The need for laser photocoagulation or intravitreal bevacizumab was significantly decreased in high-risk patients treated with the supplemental oxygen protocol. This result supports the idea that targeted supplemental oxygen therapy to keep saturations between 97 and 99% can reduce disease progression in infants with stage 2 ROP and potentially decrease the burden of additional procedures.
I rely on a little help from my friends: the effect of interpersonal and intrapersonal emotion regulation on the relationship between FOMO and problematic internet use
Authors: Flack Mal , Burton William H , Caudwell Kim M
Published: May 2024

Background

This study investigated the role of emotion regulation in relation to the links between fear of missing out (i.e., FOMO) and two components of problematic internet use: problematic social media use and doomscrolling.

Methods

Participants (N = 603, Mage = 30.41, SDage = 7.64; 49.1% male-identifying) completed measures of fear of missing out, intrapersonal and interpersonal emotion regulation, and problematic social media use, and doomscrolling. A parallel mediation model was tested to examine the nature of the associations between fear of missing out, intrapersonal, and interpersonal emotion regulation, in accounting for variance in the outcome measures.

Results

Analyses revealed that the effect of fear of missing out on problematic social media use was fully mediated by both intrapersonal and interpersonal emotion regulation. In contrast, the effect on doomscrolling was fully mediated by intrapersonal emotion regulation only.

Conclusions

Findings clarify the role of emotion regulation in explaining the relationship between fear of missing out and two types of problematic internet use, indicating a need to consider individual differences in emotion regulation in an evolving social media landscape.
Co-overexpression of chitinase and β-1,3-glucanase significantly enhanced the resistance of Iranian wheat cultivars to Fusarium
Authors: Mohammadizadeh-Heydari Negin , Tohidfar Masoud , Maleki Zanjani Bahram , Mohsenpour Motahhareh , Ghanbari Moheb Seraj Rahele , Esmaeilzadeh-Salestani Keyvan
Published: May 2024

Fusarium head blight (FHB) is a devastating fungal disease affecting different cereals, particularly wheat, and poses a serious threat to global wheat production. Chitinases and β-glucanases are two important proteins involved in lysing fungal cell walls by targeting essential macromolecular components, including chitin and β-glucan micro fibrils. In our experiment, a transgenic wheat (Triticum aestivum) was generated by introducing chitinase and glucanase genes using Biolistic technique and Recombinant pBI121 plasmid (pBI-ChiGlu (-)). This plasmid contained chitinase and glucanase genes as well as nptII gene as a selectable marker. The expression of chitinase and glucanase was individually controlled by CaMV35S promoter and Nos terminator. Immature embryo explants from five Iranian cultivars (Arta, Moghan, Sisun, Gascogen and A-Line) were excised from seeds and cultured on callus induction medium to generate embryonic calluses. Embryogenic calluses with light cream color and brittle texture were selected and bombarded using gold nanoparticles coated with the recombinant pBI-ChiGlu plasmid. Bombarded calluses initially were transferred to selective callus induction medium, and later, they were transfferd to selective regeneration medium. The selective agent was kanamycin at a concentration of 25 mg/l in both media. Among five studied cultivars, A-Line showed the highest transformation percentage (4.8%), followed by the Sisun, Gascogen and Arta in descending order. PCR and Southern blot analysis confirmed the integration of genes into the genome of wheat cultivars. Furthermore, in an in-vitro assay, the growth of Fusarium graminearum was significantly inhibited by using 200 μg of leaf protein extract from transgenic plants. According to our results, the transgenic plants (T1) showed the resistance against Fusarium when were compared to the non-transgenic plants. All transgenic plants showed normal fertility and no abnormal response was observed in their growth and development.
Early diagnosis of melanoma: a randomized trial assessing the impact of the transmission of photographs taken with a smartphone from the general practitioner to the dermatologist on the time to dermatological consultation
Authors: Bouton Céline , Schmeltz Héloïse , Lévèque Charlotte , Gaultier Aurélie , Quereux Gaëlle , Dreno Brigitte , Nguyen JM , Rat Cédric
Published: May 2024

Background

Difficulty obtaining a dermatological consultation is an obstacle to the early diagnosis of melanoma. On the one hand, patients survival depends on the lesion thickness at the time of diagnosis. On the other hand, dermatologists treat many patients with benign lesions. Optimizing patient care pathways is a major concern. The aim of the present study was to assess whether the e-mail transmission of photographs of suspected melanoma lesions between general practitioners (GPs) and dermatologists reduces the time to dermatological consultation for patients whose suspicious skin lesions ultimately require resection.

Methods

We conducted a cluster-randomized controlled study in primary care involving 51 French GPs between April 2017 and August 2019. A total of 250 patients referred to a dermatologist for a suspected melanoma lesion were included GPs were randomized to either the smartphone arm or the usual care arm. In the smartphone arm, the GPs referred patients to the dermatologist by sending 2 photographs of the suspicious lesion using their smartphone. The dermatologist then had to set up an appointment at an appropriate time. In the usual care arm, GPs referred patients to a dermatologist according to their usual practice. The primary outcome was the time to dermatological consultation for patients whose lesion ultimately required resection.

Results

57 GPs volunteered were randomized (27 to the smartphone arm, and 30 to the usual care arm). A total of 125 patients were included in each arm (mean age: 49.8 years; 53% women) and followed 8 months. Twenty-three dermatologists participated in the study. The time to dermatological consultation for patients whose suspicious skin lesion required resection was 56.5 days in the smartphone arm and 63.7 days in the usual care arm (mean adjusted time reduction: -18.5 days, 95% CI [-74.1;23.5], p = .53).

Conclusions

The e-mail transmission of photographs from GPs to dermatologists did not improve the dermatological management of patients whose suspicious skin lesions ultimately required resection. Further research is needed to validate quality criteria that might be useful for tele-expertise in dermatology.

Trial Registration

Registered on ClinicalTrials.gov under reference number NCT03137511 (May 2, 2017).
Repurposing harmaline as a novel approach to reverse tmexCD1-toprJ1-mediated tigecycline resistance against klebsiella pneumoniae infections
Authors: Yang# Jindian , Xu# Lei , Zhou Yonglin , Cui Minhe , Liu Dejun , Wang Jianfeng , Wang Yang , Deng Xuming
Published: May 2024

Background

A novel plasmid-mediated resistance–nodulation–division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the “last-resort” antibiotic tigecycline.

Results

In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance.

Conclusion

These results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections.
Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better
Authors: Lee Ching-Chi , Chen Po-Lin , Ho Ching-Yu , Hong Ming-Yuan , Hung Yuan-Pin , Ko Wen-Chien
Published: May 2024

Background

Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia.

Methods

The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model.

Results

Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness.

Conclusions

Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.
Deep learning of mammogram images to reduce unnecessary breast biopsies: a preliminary study
Authors: Liu Chang , Sun Min , Arefan Dooman , Zuley Margarita , Sumkin Jules , Wu Shandong
Published: May 2024

Background

Patients with a Breast Imaging Reporting and Data System (BI-RADS) 4 mammogram are currently recommended for biopsy. However, 70–80% of the biopsies are negative/benign. In this study, we developed a deep learning classification algorithm on mammogram images to classify BI-RADS 4 suspicious lesions aiming to reduce unnecessary breast biopsies.

Materials and methods

This retrospective study included 847 patients with a BI-RADS 4 breast lesion that underwent biopsy at a single institution and included 200 invasive breast cancers, 200 ductal carcinoma in-situ (DCIS), 198 pure atypias, 194 benign, and 55 atypias upstaged to malignancy after excisional biopsy. We employed convolutional neural networks to perform 4 binary classification tasks: (I) benign vs. all atypia + invasive + DCIS, aiming to identify the benign cases for whom biopsy may be avoided; (II) benign + pure atypia vs. atypia-upstaged + invasive + DCIS, aiming to reduce excision of atypia that is not upgraded to cancer at surgery; (III) benign vs. each of the other 3 classes individually (atypia, DCIS, invasive), aiming for a precise diagnosis; and (IV) pure atypia vs. atypia-upstaged, aiming to reduce unnecessary excisional biopsies on atypia patients.

Results

A 95% sensitivity for the “higher stage disease” class was ensured for all tasks. The specificity value was 33% in Task I, and 25% in Task II, respectively. In Task III, the respective specificity value was 30% (vs. atypia), 30% (vs. DCIS), and 46% (vs. invasive tumor). In Task IV, the specificity was 35%. The AUC values for the 4 tasks were 0.72, 0.67, 0.70/0.73/0.72, and 0.67, respectively.

Conclusion

Deep learning of digital mammograms containing BI-RADS 4 findings can identify lesions that may not need breast biopsy, leading to potential reduction of unnecessary procedures and the attendant costs and stress.
Effect of genomic and cellular environments on gene expression noise
Authors: Hong Clarice K. Y. , Ramu Avinash , Zhao Siqi , Cohen Barak A.
Published: May 2024

Background

Individual cells from isogenic populations often display large cell-to-cell differences in gene expression. This “noise” in expression derives from several sources, including the genomic and cellular environment in which a gene resides. Large-scale maps of genomic environments have revealed the effects of epigenetic modifications and transcription factor occupancy on mean expression levels, but leveraging such maps to explain expression noise will require new methods to assay how expression noise changes at locations across the genome.

Results

To address this gap, we present Single-cell Analysis of Reporter Gene Expression Noise and Transcriptome (SARGENT), a method that simultaneously measures the noisiness of reporter genes integrated throughout the genome and the global mRNA profiles of individual reporter-gene-containing cells. Using SARGENT, we perform the first comprehensive genome-wide survey of how genomic locations impact gene expression noise. We find that the mean and noise of expression correlate with different histone modifications. We quantify the intrinsic and extrinsic components of reporter gene noise and, using the associated mRNA profiles, assign the extrinsic component to differences between the CD24+ “stem-like” substate and the more “differentiated” substate. SARGENT also reveals the effects of transgene integrations on endogenous gene expression, which will help guide the search for “safe-harbor” loci.

Conclusions

Taken together, we show that SARGENT is a powerful tool to measure both the mean and noise of gene expression at locations across the genome and that the data generatd by SARGENT reveals important insights into the regulation of gene expression noise genome-wide.
Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage
Authors: Rao Jingyou , Xin Ruiqi , Macdonald Christian , Howard Matthew K. , Estevam Gabriella O. , Yee Sook Wah , Wang Mingsen , Fraser James S. , Coyote-Maestas Willow , Pimentel Harold
Published: May 2024

Deep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when treating variants independently. We propose , a Bayesian framework for analyzing growth-based DMS data. leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. We also developed for simulating the distributional properties of DMS. We show that is robust to the violation of model assumptions and is more powerful than existing tools.
Development of orthogonal aminoacyl-tRNA synthetase mutant for incorporating a non-canonical amino acid
Authors: Lee Dongheon , Kim Ja Gyung , Kim Tae Wan , Choi Jong-il
Published: May 2024

Genetic code expansion involves introducing non-canonical amino acids (ncAAs) with unique functional groups into proteins to broaden their applications. Orthogonal aminoacyl tRNA synthetase (aaRS), essential for genetic code expansion, facilitates the charging of ncAAs to tRNA. In this study, we developed a new aaRS mutant from Methanosaeta concilii tyrosyl-tRNA synthetase (Mc TyrRS) to incorporate para-azido-l-phenylalanine (AzF). The development involved initial site-specific mutations in Mc TyrRS, followed by random mutagenesis. The new aaRS mutant with amber suppression was isolated through fluorescence-activated cell sorting. The M. concilii aaRS mutant structure was further analyzed to interpret the effect of mutations. This research provides a novel orthogonal aaRS evolution pipeline for highly efficient ncAA incorporation that will contribute to developing novel aaRS from various organisms.
Navigating the science policy interface: a co-created mind-map to support early career research contributions to policy-relevant evidence
Authors: Washbourne Carla-Leanne , Murali Ranjini , Saidi Nada , Peter Sophie , Pisa Paola Fontanella , Sarzynski Thuan , Ryu Hyeonju , Filyushkina Anna , Campagne Carole Sylvie , Kadykalo Andrew N. , Ávila-Flores Giovanni , Amiar Taha
Published: May 2024

The interface between science and policy is a complex space, in theory and practice, that sees the interaction of various actors and perspectives coming together to enable policy-relevant evidence to support decision-making. Early Career Researchers (ECRs) are increasingly interested in working at the science-policy interface to support evidence-informed policy, with the number of opportunities to do so increasing at national and international levels. However, there are still many challenges limiting ECRs participation, not least how such a complex space can be accessed and navigated. While recommendations for engaging at the science-policy interface already exist, a practical ‘map’ of the science-policy interface landscape which would allow for ECR participation in evidence co-production and synthesis in science-policy is missing. With the purpose of facilitating the engagement of ECRs producing biodiversity and ecosystem services policy-relevant evidence at the interface between science and policy, the authors have co-created a ‘mind-map’—a tool to review the landscape of and leverage access to the science-policy interface. This tool was developed through reviewing published literature, collating personal experiences of the ECR authors, and validating against wider peer perspectives in an ECR workshop during the 7th Plenary of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). This co-created tool sees ECR engagement in (co-)producing evidence at the science-policy interface as an interaction of three main factors: the environment of the ECR, which mediates their acts of engagement at the science-policy interface leading to outcomes that will ultimately have a reciprocal impact on the ECR’s environment.
Body composition and rupture risk of intracranial aneurysms
Authors: Løvik Katja , Laupsa-Borge Johnny , Logallo Nicola , Helland Christian A.
Published: May 2024

Background

Rupture of an intracranial aneurysm resulting in a subarachnoid hemorrhage (SAH) is a life-threatening situation. Obesity is an increasing health challenge associated with numerous comorbidities. However, recent studies have shown a surprising decreased risk of SAH with increasing body mass index (BMI). The aim was to explore associations between other anthropometric variables and the rupture risk of an intracranial aneurysm, which to our knowledge is lacking in present literature.

Methods

Using a bioelectrical impedance analysis device, we performed body composition analyses on 31 patients admitted with aneurysmal SAH (aSAH) and 28 patients with planned intervention on their unruptured aneurysm. We also collected information on comorbidities and relevant risk factors. Logistic regression was used to explore associations between anthropometric variables and patients with ruptured versus unruptured aneurysms.

Results

Unadjusted estimates showed a significant inverse relationship between body fat percent and aneurysmal rupture (OR [95% CI]: 0.92 [0.86, 0.97], P = 0.009), and between body fat mass and aneurysmal rupture (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.047). These risk relationships remained significant in age- and sex-adjusted analyses for body fat percent (OR [95% CI]: 0.93, [0.87, 0.97], P = 0.028), and body fat mass (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.041).

Conclusions

In recent studies showing a paradoxical relation between aSAH and obesity, BMI was the only parameter investigated. We further explored this “obesity paradox” and found lower body fat in aSAH patients compared to UIA. Future studies should investigate these relationships in larger samples.

Clinical Trial Registration NCT04613427, November 3, 2020, retrospectively registered
Disrupting Na+ ion homeostasis and Na+/K+ ATPase activity in breast cancer cells directly modulates glycolysis in vitro and in vivo
Authors: Michaels Aidan M. , Zoccarato Anna , Hoare Zoe , Firth George , Chung Yu Jin , Kuchel Philip W. , Shah Ajay M. , Shattock Michael J. , Southworth Richard , Eykyn Thomas R.
Published: May 2024

Background

Glycolytic flux is regulated by the energy demands of the cell. Upregulated glycolysis in cancer cells may therefore result from increased demand for adenosine triphosphate (ATP), however it is unknown what this extra ATP turnover is used for. We hypothesise that an important contribution to the increased glycolytic flux in cancer cells results from the ATP demand of Na+/K+-ATPase (NKA) due to altered sodium ion homeostasis in cancer cells.

Methods

Live whole-cell measurements of intracellular sodium [Na+]i were performed in three human breast cancer cells (MDA-MB-231, HCC1954, MCF-7), in murine breast cancer cells (4T1), and control human epithelial cells MCF-10A using triple quantum filtered 23Na nuclear magnetic resonance (NMR) spectroscopy. Glycolytic flux was measured by 2H NMR to monitor conversion of [6,6-2H2]d-glucose to [2H]-labelled l-lactate at baseline and in response to NKA inhibition with ouabain. Intracellular [Na+]i was titrated using isotonic buffers with varying [Na+] and [K+] and introducing an artificial Na+ plasma membrane leak using the ionophore gramicidin-A. Experiments were carried out in parallel with cell viability assays, 1H NMR metabolomics of intracellular and extracellular metabolites, extracellular flux analyses and in vivo measurements in a MDA-MB-231 human-xenograft mouse model using 2-deoxy-2-[18F]fluoroglucose (18F-FDG) positron emission tomography (PET).

Results

Intracellular [Na+]i was elevated in human and murine breast cancer cells compared to control MCF-10A cells. Acute inhibition of NKA by ouabain resulted in elevated [Na+]i and inhibition of glycolytic flux in all three human cancer cells which are ouabain sensitive, but not in the murine cells which are ouabain resistant. Permeabilization of cell membranes with gramicidin-A led to a titratable increase of [Na+]i in MDA-MB-231 and 4T1 cells and a Na+-dependent increase in glycolytic flux. This was attenuated with ouabain in the human cells but not in the murine cells. 18FDG PET imaging in an MDA-MB-231 human-xenograft mouse model recorded lower 18FDG tumour uptake when treated with ouabain while murine tissue uptake was unaffected.

Conclusions

Glycolytic flux correlates with Na+-driven NKA activity in breast cancer cells, providing evidence for the ‘centrality of the [Na+]i-NKA nexus’ in the mechanistic basis of the Warburg effect.
Aberrant myonuclear domains and impaired myofiber contractility despite marked hypertrophy in MYMK-related, Carey-Fineman-Ziter Syndrome
Authors: Dugdale Hannah F. , Levy Yotam , Jungbluth Heinz , Oldfors Anders , Ochala Julien
Published: May 2024

Carey Fineman Ziter Syndrome (CFZS) is a rare autosomal recessive disease caused by mutations in the MYMK locus which encodes the protein, myomaker. Myomaker is essential for fusion and concurrent myonuclei donation of muscle progenitors during growth and development. Strikingly, in humans, MYMK mutations appear to prompt myofiber hypertrophy but paradoxically, induce generalised muscle weakness. As the underlying cellular mechanisms remain unexplored, the present study aimed to gain insights by combining myofiber deep-phenotyping and proteomic profiling. Hence, we isolated individual muscle fibers from CFZS patients and performed mechanical, 3D morphological and proteomic analyses. Myofibers from CFZS patients were ~ 4x larger than controls and possessed ~ 2x more myonuclei than those from healthy subjects, leading to disproportionally larger myonuclear domain volumes. These greater myonuclear domain sizes were accompanied by smaller intrinsic cellular force generating-capacities in myofibers from CFZS patients than in control muscle cells. Our complementary proteomic analyses indicated remodelling in 233 proteins particularly those associated with cellular respiration. Overall, our findings suggest that myomaker is somewhat functional in CFZS patients, but the associated nuclear accretion may ultimately lead to non-functional hypertrophy and altered energy-related mechanisms in CFZS patients. All of these are likely contributors of the muscle weakness experienced by CFZS patients.
Emergence of two distinct phase transitions in monolayer CoSe2 on graphene
Authors: Rhee Tae Gyu , Lam Nguyen Huu , Kim Yeong Gwang , Gu Minseon , Hwang Jinwoong , Bostwick Aaron , Mo Sung-Kwan , Chun Seung-Hyun , Kim Jungdae , Chang Young Jun , Choi Byoung Ki
Published: May 2024

Dimensional modifications play a crucial role in various applications, especially in the context of device miniaturization, giving rise to novel quantum phenomena. The many-body dynamics induced by dimensional modifications, including electron-electron, electron-phonon, electron-magnon and electron-plasmon coupling, are known to significantly affect the atomic and electronic properties of the materials. By reducing the dimensionality of orthorhombic CoSe2 and forming heterostructure with bilayer graphene using molecular beam epitaxy, we unveil the emergence of two types of phase transitions through angle-resolved photoemission spectroscopy and scanning tunneling microscopy measurements. We disclose that the 2 × 1 superstructure is associated with charge density wave induced by Fermi surface nesting, characterized by a transition temperature of 340 K. Additionally, another phase transition at temperature of 160 K based on temperature dependent gap evolution are observed with renormalized electronic structure induced by electron-boson coupling. These discoveries of the electronic and atomic modifications, influenced by electron-electron and electron-boson interactions, underscore that many-body physics play significant roles in understanding low-dimensional properties of non-van der Waals Co-chalcogenides and related heterostructures.

Graphical Abstract
Bayesian earthquake forecasting approach based on the epidemic type aftershock sequence model
Authors: Petrillo Giuseppe , Zhuang Jiancang
Published: May 2024

The epidemic type aftershock sequence (ETAS) model is used as a baseline model both for earthquake clustering and earthquake prediction. In most forecast experiments, the ETAS parameters are estimated based on a short and local catalog, therefore the model parameter optimization carried out by means of a maximum likelihood estimation may be not as robust as expected. We use Bayesian forecast techniques to solve this problem, where non-informative flat prior distributions of the parameters is adopted to perform forecast experiments on 3 mainshocks occurred in Southern California. A Metropolis–Hastings algorithm is employed to sample the model parameters and earthquake events. We also show, through forecast experiments, how the Bayesian inference allows to obtain a probabilistic forecast, differently from one obtained via MLE.

Graphical Abstract
When you need them, they are not there: hedge capacities of cryptocurrencies disappear in downtrend markets
Authors: Bossman Ahmed , Gubareva Mariya , Agyei Samuel Kwaku , Vo Xuan Vinh
Published: May 2024

We provide empirical evidence supporting the economic reasoning behind the impossibility of diversification benefits and the hedge attributes of cryptocurrencies remaining in force during the downside trends observed in bearish financial markets. We employ a spillover connectedness model driven by time-varying parameter vector autoregressions on daily data covering January 2018 to November 2022 to analyze spillover transmissions between conventional and digital markets, focusing on the role of stablecoin issuances. We study the stock, bond, cryptocurrency, and stablecoin markets and find very high connectedness, which varies over time in response to up/down trends in financial markets. The results show that during financial turmoil, cryptocurrencies amplify downside risks rather than serve as diversifiers. In addition to risky assets from conventional financial markets, cryptocurrencies champion the transmission of spillovers to digital and conventional markets. In contrast, changes in stablecoin issuances produce few shocks because of their pegged prices, but they facilitate investors’ switch from volatile cryptos to more stable digital instruments; that is, we observe a phenomenon designated by us as the “flight-to-cryptosafety.” We draw insightful conclusions, provoking new thinking regarding portfolio hedge strategies that could potentially benefit investors when searching for less volatile investment performance.
A case of pediatric Perthes’ disease with unexplained hyperlactatemia at the time of initial surgery and anesthetic management with remimazolam for the subsequent surgery
Authors: Ishikawa Ko , Hiroki Tadanao , Ito Sachiko , Aso Chizu , Saito Shigeru
Published: May 2024

Background

The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam.

Case presentation.

An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred.

Conclusions

Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology.
A model for physical dislocation transmission through grain boundaries and its implementation in a discrete dislocation dynamics tool
Authors: Stricker M. , Weygand D.
Published: May 2024

The mechanical behavior of most metals in engineering applications is dominated by the grain size. Physics-based models of the interaction between dislocations and the grain boundary are important to correctly predict the plastic deformation behavior of polycrystalline materials. Dislocation-grain boundary interaction is complex and a challenge to model. We present a model for simulating the physical transmission of dislocations through grain boundaries within Discrete Dislocation Dynamics tools. The properties (glide plane, Burgers vector, initial length) of the transmitted dislocation are chosen based on geometric criteria as well as a maximization of the resolved shear stress of the transmitted dislocation. Additionally, stress and displacement transparency as well as the discontinuity are ensured via a grain boundary dislocation – a butterfly-like geometry in the general case – whose properties are selected to minimize the residual Burgers vector at the interface. This additional ‘grain boundary dislocation’ allows a direct comparison as well as a calibration of the model with experiments on the macroscale particularly for neighboring grains with a high dislocation density contrast. Two basic examples illustrate the model and an application to a 40-grain polycrystal demonstrates the scalability of the approach.
Estimating the expression levels of genes controlling biofilm formation and evaluating the effects of different conditions on biofilm formation and secreted aspartic proteinase activity in Candida albicans and Saccharomyces cerevisiae: a comparative study
Authors: Sobieh Shaimaa S. , Elshazly Rowida G. , Tawab Sahar A. , Zaki Sanaa S.
Published: May 2024

Background

Characterization of yeast virulence genes is an important tool for identifying the molecular pathways involved in switching yeast virulence. Biofilm formation (BF) and secreted aspartic proteinase (SAP) activity are essential virulence factors that contribute to yeast pathogenicity.

Results

Four Candida albicans and two Saccharomyces cerevisiae strains were tested for BF and SAP activity under optimum conditions, and the expression levels of several genes controlling BF were quantified under the optimal conditions. Biofilm formation was assessed by the microplate method at different pH values, incubation times and culture media. Similarly, SAP activity was assessed at different pH values and incubation periods. The expression levels of nine genes were determined via qRT-PCR technique. All tests were carried out in triplicate, and the values presented as the means ± standard deviations and were analysed with the SPSS programme. Only C. albicans (1), C. albicans (2) and S. cerevisiae 43 formed biofilms. The optimal BF was obtained after culture in sabouraud dextrose broth with 8% glucose at pH 7.5, 4 and 6, respectively, for 48h. Candida albicans biofilm production was more significant than that of S. cerevisiae 43. Moreover, the SAP activity was estimated under the optimum conditions. All yeasts showed optimal SAP activity at pH 4, but astonishingly the SAP activity of S. cerevisiae 44 was higher than that of C. albicans. The expression levels of EFG1 and ZAP1 (transcription factors); ALS3, HWP1and YWP1 (adhesion genes); SAP1 and SAP4 (aspartic proteinase) in C. albicans (1); and FLO11 (adhesion gene) and YPS3 (aspartic proteinase) in S. cerevisiae 43 were quantified during biofilm development at different time intervals. The expression levels of EFG1, ALS3, YWP1, SAP1, SAP4, FLO11 and YPS3 were upregulated at 8 h, while that of ZAP1 was upregulated at 48 h. Only HWP1 was downregulated.

Conclusions

The findings of the present study may provide information for overcoming yeast BF and pathogenicity by regulating specific genes at specific times. Additionally, this study revealed the virulence of the commensal S. cerevisiae, which may take the pathogenicity direction as C. albicans.
Response of semicircular canyons and movable cylindrical cavities to SH waves in anisotropic half-space geology
Authors: Guo Debao , Bian Jinlai , Song Yunqiu , Yang Yong , Yang Zailin
Published: May 2024

The development of tunnels or the laying of underground pipelines are essential engineering projects in modern society, and in canyon tunnels and underground pipeline projects, the surface motion and cavity edge motion have been topics of concern in ground vibration problems. We investigate the wave scattering problem in an elastic half-space anisotropic medium containing a semicircular canyon and a subsurface movable cylindrical cavity by using the wave function expansion method, the complex function method, and the mirror method. By deriving the governing equation and transforming it into the standard form of the Helmholtz equation satisfying the zero-stress boundary condition, we solve the corresponding displacement functions. Introducing a position correction coefficient, the scattered wavefield in a half-space anisotropic medium is constructed by the mirror method, which improves the problem of scattered wave source singularity in anisotropic half-space media. Then, combining the free boundary conditions with a Fourier series expansion method, we solve the unknown coefficients in the equations. The correctness of the method is verified by degenerating it to a classical analytic solution. Finally, using frequency- and time-domain analysis, we investigate the effects of the relevant parameters on the surface motion [Formula: see text], the dynamic stress concentration factor, and the displacement amplitude [Formula: see text]. The results indicate that rock anisotropy and the presence of semicircular canyons have a significant effect on the dynamic response of subsurface structures. This not only provides a theoretical basis for practical unlined tunnels or pipeline projects but also can provide a basis for seismic design of underground structures.
Moving Immunotherapy Into the Treatment of Resectable Non–Small Cell Lung Cancer
Authors: Chaft Jamie E. , Dziadziuszko Rafal , Haddock Lobo Goulart Bernardo
Published: May 2024

Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non–small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti–PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.
Simplified Risk Stratification Model for Patients With Waldenström Macroglobulinemia
Authors: Zanwar Saurabh , Le-Rademacher Jennifer , Durot Eric , D’Sa Shirley , Abeykoon Jithma P. , Mondello Patrizia , Kumar Shaji , Sarosiek Shayna , Paludo Jonas , Chhabra Saurabh , Cook Joselle M. , Parrondo Ricardo , Dispenzieri Angela , Gonsalves Wilson I. , Muchtar Eli , Ailawadhi Sikandar , Kyle Robert A. , Rajkumar S. Vincent , Delmer Alain , Fonseca Rafael , Gertz Morie A. , Treon Steven P. , Ansell Stephen M. , Castillo Jorge J. , Kapoor Prashant
Published: May 2024

PURPOSE

Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88 L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters.

PATIENTS AND METHODS

We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort.

RESULTS

In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively ( P < .0001).

CONCLUSION

Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.
Low Bone Mineral Density as a Predictor of Mortality and Infections in Stroke Patients: A Hospital-Based Study
Authors: Tsai Yu-Lin , Chuang Ya-Chi , Cheng Yuan-Yang , Deng Ya-Lian , Lin Shih-Yi , Hsu Chun-Sheng
Published: May 2024

Context

Low bone mineral density (BMD) has been linked to elevated risks of mortality and infections in the general population; however, its association with these outcomes in stroke patients remains unclear.

Objective

This study aims to investigate the correlation between low BMD and risks of mortality and infections among stroke patients in a Taiwanese cohort.

Methods

In this single-center retrospective cohort study, 905 stroke patients from a Taiwanese database (2000-2022) were analyzed. Patients were grouped based on BMD measurements of the femur and spine. The primary outcome was all-cause mortality, and secondary outcomes included urinary tract infection (UTI) and pneumonia. Accelerated failure time regression model analyses evaluated the association between BMD and these outcomes, while the Kaplan-Meier method and log-rank test assessed survival differences between groups.

Results

Among the participants (average age 76.1 years, 70.5% female), 33.82% had osteopenia and 55.25% had osteoporosis. Stroke patients with lower spine and right femur BMD had significantly reduced survival rates, especially when the BMD value fell below 0.842 g/cm2 (spine), and 0.624 g/cm2 (right femur), respectively. Regarding secondary outcomes, lower spine BMD was significantly associated with an increased risk of UTI.

Conclusion

Low BMD, particularly in the femur and spine, is a significant predictor of mortality and UTI in stroke patients. These findings highlight the importance of assessing and managing BMD in stroke patients to improve outcomes and reduce complications.
Mapping Thyroid Changes in Size and Position During Enlargement in Adult Mice With Hyperthyroidism
Authors: Li Zhongmin , Wenhart Clara , Reimann Andreas , Goebel Silvia , Cho Yi-Li , Muench Goetz
Published: May 2024

The thyroid in Graves’ disease undergoes a considerable divergence in size and position from the normal anatomy. However, knowledge of the pathological anatomy related to the change, which is required before planned surgical or local intervention, or diagnosis, is neglected. To investigate Graves’ disease, we established a model of mice that successfully mimicked all the signs presented in the clinic. Under a long-term immunization (35 weeks), the animals displayed large heterogeneity in thyroid size, such as the cases of natural occurrence. These thyroids in the model were sized into various phases and registered. A blend of the registered thyroids and the thyroid and tracheal cartilage landmarks led to the production of site-dependent incidence graphs of thyroid in the front view and on the section for each phase. The merger of the incidence graphs of all the phases resulted in thyroid phase-dependent topography. The depicted graphs illustrate the fine localization of the thyroid in various sizes and their dynamic changes during enlargement, which may facilitate currently used fine-needle aspiration biopsy and ultrasonography-guided biopsy techniques. Familiarity with this knowledge might avoid misclassifying an abnormality as normal, or vice versa, and be helpful for imaging diagnosis and local surgery therapy in Graves’ disease.
Anterior Cutaneous Nerve Entrapment Syndrome Caused by a Fixation Device: A Case Report
Authors: Miyamatsu Yayoi , Tanizaki Ryutaro , Ninomiya Takahito , Yoshida Kakunoshin
Published: May 2024

Anterior cutaneous nerve entrapment syndrome (ACNES) is characterized by abdominal wall neuralgia. We report an 85-year-old woman with ACNES caused by a fixation device during the bipolar hip arthroplasty. To prevent ACNES as a perioperative peripheral nerve injury, it is important to maintain patients in the appropriate position during the operation. A positive Carnett’s sign means the abdominal pain originates from the abdominal wall and is useful in diagnosing ACNES. Thus, physicians should examine Carnett’s sign to differentiate ACNES in patients with abdominal pain developing after an operation.