bluuebunny/crossref_metadata_2025 huggingface dataset:
SPOT-RASTR—A cryo-EM specimen preparation technique that overcomes problems with preferred orientation and the air/water interface
Authors: Esfahani Behrouz G , Randolph Peter S , Peng Ruizhi , Grant Timothy , Stroupe M Elizabeth , Stagg Scott M
Published: August 2024

In cryogenic electron microscopy (cryo-EM), specimen preparation remains a bottleneck despite recent advancements. Classical plunge freezing methods often result in issues like aggregation and preferred orientations at the air/water interface. Many alternative methods have been proposed, but there remains a lack a universal solution, and multiple techniques are often required for challenging samples. Here, we demonstrate the use of lipid nanotubes with nickel NTA headgroups as a platform for cryo-EM sample preparation. His-tagged specimens of interest are added to the tubules, and they can be frozen by conventional plunge freezing. We show that the nanotubes protect samples from the air/water interface and promote a wider range of orientations. The reconstruction of average subtracted tubular regions (RASTR) method allows for the removal of the nanotubule signal from the cryo-EM images resulting in isolated images of specimens of interest. Testing with β-galactosidase validates the method's ability to capture particles at lower concentrations, overcome preferred orientations, and achieve near-atomic resolution reconstructions. Since the nanotubules can be identified and targeted automatically at low magnification, the method enables fully automated data collection. Furthermore, the particles on the tubes can be automatically identified and centered using 2D classification enabling particle picking without requiring prior information. Altogether, our approach that we call specimen preparation on a tube RASTR holds promise for overcoming air–water interface and preferred orientation challenges and offers the potential for fully automated cryo-EM data collection and structure determination.
Clustering of negative topological charges precedes plastic failure in 3D glasses
Authors: Bera Arabinda , Baggioli Matteo , Petersen Timothy C , Sirk Timothy W , Liu Amelia C Y , Zaccone Alessio
Published: August 2024

The deformation mechanism in amorphous solids subjected to external shear remains poorly understood because of the absence of well-defined topological defects mediating the plastic deformation. The notion of soft spots has emerged as a useful tool to characterize the onset of irreversible rearrangements and plastic flow, but these entities are not clearly defined in terms of geometry and topology. In this study, we unveil the phenomenology of recently discovered, precisely defined topological defects governing the microscopic mechanical and yielding behavior of a model 3D glass under shear deformation. We identify the existence of vortex-like and antivortex-like topological defects within the 3D nonaffine displacement field. The number density of these defects exhibits a significant anticorrelation with the plastic events, with defect proliferation–annihilation cycles matching the alternation of elastic-like segments and catastrophic plastic drops, respectively. Furthermore, we observe collective annihilation of these point-like defects via plastic events, with large local topological charge fluctuations in the vicinity of regions that feature strong nonaffine displacements. We reveal that plastic yielding is driven by several large sized clusters of net negative topological charge, the massive annihilation of which triggers the onset of plastic flow. These findings suggest a geometric and topological characterization of soft spots and pave the way for the mechanistic understanding of topological defects as mediators of plastic deformation in glassy materials.
Deep learning-based amyloid PET harmonization to predict cognitive decline in non-demented elderly
Authors: Choi Yoon Seong , Ngam Pei Ing , Lee Jeong Ryong , Hwang Dosik , Tan Eng-King ,   for the Harvard Aging Brain Study,   for the Australian Imaging Biomarkers and Lifestyle Study of Aging,   for the Japanese Alzheimer’s Disease Neuroimaging Initiative,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2024

Background

The robustness of conventional amyloid PET harmonization across tracers has been questioned.

Purpose

To evaluate deep learning-based harmonization of amyloid PET in predicting conversion from cognitively unimpaired (CU) to mild cognitive impairment (MCI) and MCI to Alzheimer’s disease (AD).

Materials and Methods

We developed an amyloid PET-based deep-learning model to classify participants with a clinical diagnosis of AD-dementia vs CU across different tracers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Japanese ADNI, and Australian Imaging, Biomarker, and Lifestyle cohorts (n = 1050). The model output [deep learning-based probability of Alzheimer’s disease-dementia (DL-ADprob)], with other prognostic factors, was evaluated for predicting cognitive decline in ADNI-MCI (n = 451) and Harvard Aging Brain Study (HABS)-CU (n = 271) participants using Cox regression and area under time-dependent receiver operating characteristics curve (tdAUC) at 4-year follow-up. Subgroup analyses were performed in the ADNI-MCI group for conversion from amyloid-positive to AD and from amyloid negative to positive. Intraclass correlation coefficient (ICC) of DL-ADprob between tracers was calculated in the Global Alzheimer’s Association Interactive Network dataset (n = 155).

Results

DL-ADprob was independently prognostic in both ADNI-MCI (P < .001) and HABS-CU (P = .048) sets. Adding DL-ADprob to other factors increased prognostic performances in both ADNI-MCI (tdAUC 0.758 [0.721-0.792] vs 0.782 [0.742-0.818], tdAUC difference 0.023 [0.007-0.038]) and HABS-CU (tdAUC 0.846 [0.755-0.925] vs 0.870 [0.773-0.943], tdAUC difference 0.022 [−0.004 to 0.053]). DL-ADprob was independently prognostic in amyloid-positive (P < .001) and amyloid-negative subgroups (P = .007). DL-ADprob showed incremental prognostic value in amyloid-positive (tdAUC 0.666 [0.623-0.713] vs 0.706 [0.657-0.755], tdAUC difference 0.039 [0.016-0.064]), but not in amyloid-negative (tdAUC 0.818 [0.757-0.882] vs 0.816 [0.751-0.880], tdAUC difference −0.002 [−0.031 to 0.029]) subgroup. The pairwise ICCs of DL-ADprob between Pittsburgh compound B and florbetapir, florbetaben, and flutemetamol, respectively, ranged from 0.913 to 0.935.

Conclusion

Deep learning-based harmonization of amyloid PET improves cognitive decline prediction in non-demented elderly, suggesting it could complement conventional amyloid PET measures.
CorrSim: a multiwavelength timing observation simulator
Authors: Paice J A , Misra R , Gandhi P
Published: August 2024

Studying the rapid variability of many astronomical objects is key to understanding the underlying processes at play. However, obtaining data well-suited to this task can be tricky, especially for simultaneous multiwavelength observations. Parameters often have to be fine-tuned while ‘on-site,’ or observations may only be found to not achieve their goals later. Here, we present CorrSim; a program tailored to X-ray Binary analysis, and expandable to many kinds of multiwavelength coordinated observations. CorrSim takes power spectra, coherence, and lags, and returns a simulated multiwavelength observation. The goals of this are: (i) To simulate a potential observation; (ii) To investigate how different Fourier models affect a system’s variability, including data products like cross-correlation functions); and (iii) To simulate existing data and investigate its trustworthiness. We outline CorrSim’s methodology, show how a variety of parameters (e.g. noise sources, observation length, telescope choice) can affect data, and present examples of the software in action. Through CorrSim, we also detail the effects of the length of the data train on Fourier and correlation function uncertainties. We also highlight previous CorrSim modelling, noting that the ‘pre-cognition dip’ seen in X-ray binaries can be constructed by periodic processes, and discuss this result in the wider context.
Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study
Authors: Gialouri Chrysoula G , Chalkia Aglaia , Koutsianas Christos , Chavatza Katerina , Argyriou Evangelia , Panagiotopoulos Alexandros , Karamanakos Anastasios , Dimouli Aikaterini , Tsalapaki Christina , Thomas Konstantinos , Orfanos Philippos , Lagiou Pagona , Katsikas George , Boki Kyriaki , Boumpas Dimitrios , Petras Dimitrios , Vassilopoulos Dimitrios
Published: August 2024

Objectives

There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission maintenance agent in microscopic polyangiitis (MPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well for serious adverse events (SAEs) in MPA/GPA patients during RTX maintenance.

Methods

A retrospective cohort of newly diagnosed/relapsing GPA/MPA patients who received RTX maintenance (≥1 RTX cycle, ≥6 months follow-up) following complete remission (BVAS version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious infections, COronaVIrus-Disease 2019 (COVID-19)–associated hospitalizations, deaths, cardiovascular events, malignancies and hypogammaglobulinemia. The incidence rates (IRs) and relapse-free survival were estimated through Kaplan–Meier plots. Cox regression was conducted to investigate factors associated with the time-to-relapse.

Results

A total of 101 patients were included: 48% females, 69% GPA, 53% newly diagnosed, median age 63 years. During follow-up (294.5 patient-years, median: 3 RTX cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted hazard ratio/aHR: 0.20; 95% CI: 0.06–0.74, P = 0.016), prior induction with RTX plus CYC (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001–0.43, P = 0.012) and shorter time interval until complete remission (aHR = 1.07; 95% CI: 1.01–1.14, P = 0.023) were associated with decreased relapse risk. We recorded 17 serious infections (IR 5.8/100 patient-years), 11 COVID-19–associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years).

Conclusion

In this real-world study, relapses during RTX maintenance occurred in approximately 1 out of 4 patients. Kidney involvement, induction with RTX plus CYC, and earlier achievement of complete remission were associated with lower relapse risk. The serious infections rate was consistent with previous reports, whereas an increased rate of COVID-19–associated hospitalizations was observed.
CT-based comprehensive scoring system for assessing hip arthropathy in ankylosing spondylitis: feasibility study with clinical correlation
Authors: Duarte Silva Flavio , Ormond Filho Alipio G , de Oliveira Thauana L , Andrew Dhilip , Chhabra Avneesh , Pinheiro Marcelo M , Xi Yin , Fernandes Artur da Rocha Correa , Nico Marcelo A C , Aihara Andre Y
Published: August 2024

Objective

To develop a CT-based scoring system for assessment of hip arthropathy in AS.

Methods

All AS patients were prospectively recruited, consented and underwent whole-body stereoradiographs and pelvis CT, which were assessed by two independent radiologists. Stereoradiographs were assessed according to Kellgreen-Lawrence and BASRI-h. For the Hip arthropathy CT score in AS (HACTSAS), joints were divided into 7 segments and scored for joint space, osteophytes, subchondral cysts/erosions. Patients were clinically assessed for range of motion (ROM), pain and clinical scores (BASMI, BASFI, ASQol, BASDAI and ASDAS). Radiological scores correlations with clinical parameters were compared. ROM sensitivity and specificity for hip arthropathy (BASRI-h ≥ 2) were calculated.

Results

Sample included 112 patients, with 36/112 females and 76/112 males. Average age was 51.0 ± 11.2 years and mean duration of AS was 20.9 ± 9.6 years. Intraclass correlation coefficients (ICC) for HACTSAS, Kellgreen-Lawrence and BASRI-h were 0.89, 0.89 and 0.82, respectively. HACTSAS showed moderate absolute correlation with ROM (ρ = −0.41) and BASMI (ρ = 0.45), and weak with pain (ρ = 0.18) and BASFI (ρ = 0.25). BASRI-h and Kellgreen-Lawrence exhibited moderate correlation with ROM (ρ = −0.44 and ρ = −0.40, respectively), weak with pain (ρ = −0.27and ρ = −0.23, respectively) and BASFI (ρ = −0.16 and ρ = −0.18, respectively), but only weak with BASMI (ρ = −0.34 and ρ = −0.36, respectively). Internal rotation <15°, abduction <31° and intermalleolar distance <75cm were, respectively, 73%, 70% and 73% sensitivity and 81%, 65% and 68% specific for hip arthropathy.

Conclusion

HACTSAS exhibited higher correlation with BASMI and BASFI when compared with BASRI-h, but less correlation with pain and ROM. Internal rotation was the best clinical discriminator for hip arthropathy.
Circulating cell-free DNA promotes inflammation in dermatomyositis patients with anti-NXP2 antibodies via the cGAS/STING pathway
Authors: Wang Yikang , Zhao Yawen , Gang Qiang , Hao Hongjun , Gao Feng , Deng Jianwen , Wang Zhaoxia , Zhang Wei , Yuan Yun , Zheng Yiming
Published: August 2024

Objectives

DM is a rare type I IFN (IFN-I)-driven autoimmune disease, and anti-nuclear matrix protein 2 (NXP2) antibody is related to severe muscle disease and poor prognosis. Circulating cell-free DNA (ccf-DNA), including ccf-mitochondrial DNA and ccf-nuclear DNA, activates the cGAS/STING pathway to induce IFN-I production in autoimmune diseases. We investigated whether serum-derived ccf-DNA had a pathogenic effect on skeletal muscle in anti-NXP2 antibody–positive DM.

Methods

Serum ccf-DNA levels were measured, and correlations between ccf-DNA and clinicopathological indicators were performed. RNA sequencing, immunofluorescence, western blotting and reverse transcriptase quantitative polymerase chain reaction were performed on skeletal muscle samples. The serum-induced expression of p-STING in C2C12 cells was assessed in vitro.

Results

We found that increased ccf-DNA levels were positively correlated with MYOACT scores in anti-NXP2 antibody-positive DM. RNA sequencing and immunofluorescence results revealed that the cytosolic DNA-sensing pathway was upregulated and that increased cytosolic dsDNA was colocalized with cGAS in skeletal muscle in anti-NXP2 antibody-positive DM. Western blot analysis revealed activation of the cGAS/STING pathway in patients with perifascicular atrophy (PFA) but not in patients without PFA. Reverse transcriptase quantitative polymerase chain reaction showed increased IFN-I scores in both patients with PFA and patients without PFA. Sera from patients with PFA increased p-STING expression in C2C12 cells, and DNase I treatment and STING inhibitor efficiently inhibited p-STING expression, respectively.

Conclusion

Increased ccf-DNA levels may be potential biomarkers for monitoring disease activity in anti-NXP2 antibody–positive DM. Activation of the cGAS/STING pathway is associated with PFA. Our findings identified a pathogenic effect of ccf-DNA on skeletal muscle via the cGAS/STING pathway.
Microbial antibiotic resistance genes across an anthropogenic gradient in a Canadian High Arctic watershed
Authors: Provencher Juliette , George Paul B L , Thaler Mary , Vincent Warwick F , Duchaine Caroline , Culley Alexander I , Girard Catherine
Published: August 2024

Antibiotic resistance is one of the biggest challenges to public health. While the discovery of antibiotics has decreased pathogen-caused mortality, the overuse of these drugs has resulted in the increased transfer and evolution of antibiotic resistance genes (ARGs) in bacteria. ARGs naturally occur in wild bacterial communities, but are also found in increased concentrations in environments contaminated by wastewater effluent. Although such ARGs are relatively well described in temperate environments, little is known about the distribution and dissemination of these genes in the Arctic. We characterized the ARGs in microbial communities from aerosols, lakes and microbial mats around a remote Arctic hamlet using metagenomic approaches. Specific objectives were to (i) compare ARGs across habitats, (ii) to characterize ARG populations along a continuum of anthropogenically influenced environments, and (iii) to identify ARGs of viral origin. We identified ARGs in all habitats throughout the watershed, and found that microbial mats in the most impacted area had the highest diversity of ARGs relative to uncontaminated sites, which may be a remnant signal of wastewater effluent inputs in the area during the 20th century. Although we identified ARGs predominantly in bacterial genomes, our data suggests that mimiviruses may also harbor ARGs.
Full-Length ITS Amplicon Sequencing Resolves Phytophthora Species in Surface Waters Used for Orchard Irrigation in California’s San Joaquin Valley
Authors: Ott Natalia J. , Nouri Mohamed T. , Browne Greg T.
Published: August 2024

Diverse Phytophthora species, including many important plant pathogens, have been widely detected among surface water irrigation sources. In the past decade, metabarcoding has been used to characterize waterborne Phytophthora populations. Metabarcoding typically involves amplification of portions of the nuclear ribosomal internal transcribed spacers (ITSs) ITS1 or ITS2 from Phytophthora species, followed by indexed high-throughput sequencing. However, full-length sequences of the entire ITS region are required for resolution of many Phytophthora species. We used metabarcoding with Pacific Biosciences (PacBio) sequencing of full-length ITS amplicons to analyze populations of Phytophthora in waterways of the Stockton East Water District (SEWD) in the northern San Joaquin Valley of California. This approach yielded species-level resolution of many members of the Phytophthora community. Results were compared with those obtained by using ITS1 or ITS2 regions alone and were found to provide superior species resolution for P. pini, P. capsici, and P. gregata. Samples were collected throughout the 2021 irrigation season from five waterways across the SEWD. Thirty-eight Phytophthora species were detected in the waterways, including tree-crop pathogens P. acerina, P. cactorum, P. pini, P. × cambivora, P. niederhauserii, P. mediterranea, and P. taxon walnut. These pathogenic species were detected throughout the SEWD during most of the irrigation season. The results demonstrated the usefulness of full-length ITS amplicon sequencing for identifying Phytophthora species in environmental samples and suggested that some disease risk may be incurred by orchardists irrigating with SEWD water. Additional epidemiological studies will be required to critically evaluate this risk.
Epigenetic mechanisms differentially regulate blood pressure and renal dysfunction in male and female Npr1 haplotype mice
Authors: Kumar Prerna , Neelamegam Kandasamy , Ramasamy Chandramohan , Samivel Ramachandran , Xia Huijing , Kapusta Daniel R. , Pandey Kailash N.
Published: August 2024

We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor‐A (GC‐A/NPRA) gene‐targeted mice. The Npr1 (encoding NPRA) gene‐targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex‐specific manner. Adult male and female Npr1 haplotype (1‐copy; Npr1+/−), wild‐type (2‐copy; Npr1+/+), and gene‐duplicated heterozygous (3‐copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One‐copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2‐copy and 3‐copy mice. Furthermore, HDAC1/2, collagen1alpha‐2 (Col1α‐2), and alpha smooth muscle actin (α‐SMA) were significantly increased in 1‐copy mice compared with 2‐copy controls. The expression of antifibrotic microRNA‐133a was attenuated in 1‐copy mice but to a greater extent in males than females. NF‐κB was localized at significantly lower levels in cytoplasm than in the nucleus with stronger DNA binding activity in 1‐copy mice. MGCD significantly lowered BP, improved creatinine clearance, and repaired renal histopathology. The inhibition of class I HDACs led to a sex‐dependent distinctive stimulation of acetylated positive histone marks and inhibition of methylated repressive histone marks in Npr1 1‐copy mice; however, it epigenetically lowered MAP, repaired renal fibrosis, and proteinuria and suppressed NF‐kB differentially in males versus females. Our results suggest a role for epigenetic targets affecting hypertension and renal dysfunction in a sex‐specific manner.
Low bone turnover is associated with advanced glycation end‐products, oxidative stress, and inflammation induced by type 2 diabetes mellitus
Authors: Shi Peipei , Gong He , Lyu Linwei , Liu Shuyu , Jia Shaowei , Li Chenchen , Wu Xiaodan , Li Xitong
Published: August 2024

Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM‐related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high‐fat diet combined with a single streptozotocin injection in 7‐week‐old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end‐products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE‐RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.
“I Think Many of Them Want to Appear to Have a Growth Mindset”: Exploring Supervisors’ Perceptions of Feedback-Seeking Behavior
Authors: Ginsburg Shiphra , Lingard Lorelei , Sugumar Vijithan , Watling Christopher J.
Published: August 2024

Purpose

Feedback seeking is an expected learner competency. Motivations to seek feedback are well explored, but we know little about how supervisors perceive such requests for feedback. These perceptions matter because how supervisors judge requests can affect the feedback they give. This study explores how supervisors perceive and attribute motivations behind feedback requests to better understand the benefits and hazards of feedback seeking.

Method

Constructivist grounded theory was used to interview supervisors at the Temerty Faculty of Medicine, University of Toronto, from February 2020 to September 2022. Supervisors were asked to describe instances when they perceived feedback requests as being sincere or insincere, what led to their opinions, and how they responded. Transcripts were analyzed and coded in parallel with data collection; data analysis was guided by constant comparison.

Results

Seventeen faculty were interviewed. Participants perceived 4 motivations when learners sought feedback: affirmation or praise; a desire to improve; an administrative requirement, such as getting forms filled out; and hidden purposes, such as making a good impression. These perceptions were based on assumptions regarding the framing of the initial request; timing; preexisting relationship with the learner; learner characteristics, such as insecurity; and learner reactions to feedback, particularly defensiveness. Although being asked for feedback was generally well received, some participants reported irritation at requests that were repetitive, were poorly timed, or did not appear sincere.

Conclusions

Feedback seeking may prompt supervisors to consider learners’ motivations, potentially resulting in a set of entangled attributions, assumptions, and reactions that shape the feedback conversation in invisible and potentially problematic ways. Learners should consider these implications as they frame their feedback requests and be explicit about what they want and why they want it. Supervisors should monitor their responses, ask questions to clarify requests, and err on the side of assuming feedback-seeking requests are sincere.
Treatment of Syndesmotic Instability: The Importance of Malleolar Fixation
Authors: Kim Jaeyoung , Ellis Scott
Published: August 2024

A significant proportion of syndesmotic injuries often occur simultaneously with malleolar fractures. The existing literature emphasizes that even slight misalignments in the malleolar structures can lead to altered talar motion, ultimately resulting in post-traumatic ankle arthritis. Rotational ankle fractures with syndesmotic injury can manifest with isolated or a combination of lateral, medial, and/or posterior malleolar fractures, and an accurate anatomic restoration of malleolar fractures has been emphasized. One such reason for anatomic reduction is that the fracture fragment may have an important attachment site for ligaments that contributes to the stability of the ankle and syndesmotic joints. While the biomechanical impact of malreduction of the lateral and medial malleolus osteoligamentous complex has been well documented and understood, controversy persists regarding the optimal surgical treatment of posterior malleolar fractures in the context of syndesmosis instability. Advanced imaging and biomechanical studies have shed new light on the role of the posterior malleolus in syndesmosis stability, suggesting that anatomic reduction of the posterior malleolar fragment could decrease the necessity of transfixation of the syndesmosis, lowering the risk of malreduction. As a result, there is growing advocacy for anatomically reducing and fixing the posterior malleolus in ankle fractures with syndesmotic injuries. This review focuses on the critical role of malleolar fixation in the management of syndesmotic injuries.

Level of Evidence
: Diagnostic Level V—expert opinion. See Instructions for Authors for a complete description of levels of evidence.
Targeting MCM2 activates cancer-associated fibroblasts-like phenotype and affects chemo-resistance of liposarcoma cells against doxorubicin
Authors: Bai Chujie , Li Shu , Tan Zhichao , Fan Zhengfu
Published: August 2024

Liposarcoma is one of the most common soft tissue malignancies. We previously discovered upregulation of minichromosome maintenance 2 (MCM2) expression in liposarcoma tissues. Hereon, we attempt to clarify the biological influence and mechanisms of MCM2 in liposarcoma. The mRNA level of MCM2 expression was detected through the use of quantitative real-time PCR. Immunohistochemistry staining and western blot were employed to detect protein expression of MCM2. The protein expression of fibroblast-activation protein and α-smooth muscle actin was examined by immunofluorescence. Protein concentrations of interleukin (IL)-6, transforming growth factor β, and IL-8 were measured via ELISA. Furthermore, liposarcoma cell viability was assessed through cell counting kit-8 assay, and liposarcoma cell invasiveness and migration were evaluated through transwell assay. For assessing proliferation and apoptosis of liposarcoma cells, colony formation assay and flow cytometry were used. For constructing a mouse tumor model, SW872 cells were introduced into mouse flank via subcutaneous injection. MCM2 expression was boosted in liposarcoma tissues and cells when compared with the controls. MCM2-activated cancer-associated fibroblasts (CAFs)-like phenotype, presenting as increased fibroblast-activation protein expression, α-smooth muscle actin expression, cell migration, IL-6 concentration, IL-8 concentration, and transforming growth factor β concentration. Functional experiments indicated that MCM2-activated-CAFs facilitated proliferation, migration, and invasion of liposarcoma cells. Additionally, 1 μM doxorubicin treatment could not affect proliferation and apoptosis of liposarcoma cells, whereas combined use of MCM2 knockdown and 1 μM doxorubicin evidently repressed cell proliferation and promoted apoptosis. In vivo, silencing of MCM2 impaired tumor growth in mice. MCM2 overexpression promoted CAFs formation and tumor progression, showing potential value in treatment of liposarcoma.
Association Between Korean Adults' Electronic Health Literacy and Active Participation in Health Decision-Making
Authors: Lee Seonah
Published: August 2024

This study aimed to investigate the association between Korean adults' electronic health literacy and active participation in health decision-making while communicating with healthcare providers. A total of 421 adults 18 years and older were recruited from a survey panel developed by a survey company and completed an online survey asking about individual characteristics and electronic health literacy. Data were analyzed using descriptive statistics, independent-samples t tests, analysis of variance, and binomial logistic regression analysis. In results, for every one-unit increase in electronic health literacy, the rate of active participation in health decision-making was likely to increase by 3.62 times compared with the rate of passive participation in health decision-making. It was also likely to increase in those with a college degree or higher, those who used both Web sites and YouTube, those who perceived online health information to be useful, those who actively participated as a patient, and those with a desire to actively participate as a patient. To encourage active participation in health-related situations or decision-making processes, educational programs or interventions to improve individuals' electronic health literacy are needed. Healthcare providers must ensure that individuals feel comfortable expressing their preferences, needs, and values.
Pediatric perspective: the microbiome in vertical HIV-infection: unravelling gaps, challenges, and therapeutic potential
Authors: Sainz Talía , Aldrovandi Grace
Published: August 2024

Purpose of review

The intricate interplay between HIV and the host microbiota has emerged as a significant area of investigation with therapeutic potential. Despite numerous studies on this complex interaction in adults, vertically acquired infections, which have distinct immunological and virological characteristics, remain relatively understudied.

Recent findings

Disturbances, including prolonged exposure to HIV and antiretroviral therapy, significantly impact the gut microbiome, though isolating these effects from other influencing factors is challenging. Children and adolescents living with HIV exhibit reduced microbiome diversity and potential imbalances between beneficial and pathogenic taxa. However, most available data focus on microbiome composition rather than function. The observed variations in specific microbial phyla are intriguing, but their health effects are unknown. Although modulating the microbiota may be theoretically easier during childhood, few interventional trials have included children.

Therapeutic interventions aimed at modulating the gut microbiome in children with HIV have shown limited impact, and their ability to induce long-term microbiome changes remains uncertain. A more functional, longitudinal approach, along with an ecological perspective, is needed to understand the complex interplay between the microbiome and the host. This will help clarify the relevance of microbiota alterations and their potential implications for clinical outcomes, such as inflammation and immune reconstitution in pediatric HIV.
New management approaches for female sexual dysfunction
Authors: Brotto Lori A. , Altas Melanie
Published: August 2024

Purpose of review

The goal of this paper is to review the most recent studies evaluating treatments for female sexual dysfunction (FSD), including distressing symptoms of desire, arousal, and orgasm disorder. We divide the sections into psychological and pharmacological.

Recent findings

There is excellent evidence in favour of mindfulness, cognitive behavioural therapy, and psychoeducation for improving low sexual desire in women, and less evidence in support of these approaches to address other sexual dysfunctions in women. There are two US Food and Drug Administration (FDA) approved pharmacological treatments for low desire in premenopausal women that have modest benefits above placebo, and a significant proportion of users will experience side effects. Evidence also supports the use of transdermal testosterone for low desire in postmenopausal women.

Sexual dysfunction in women is common and distressing, and there are a variety of psychological and pharmacological treatments. More research is needed to better understand the predictors of a positive treatment response in order to deliver more personalized care.
REVIVED BCIS-2: update and key learnings
Authors: Betemariam Tesfamariam Aklilu , Morgan Holly , Perera Divaka
Published: August 2024

Purpose of review

This review summarises the shifting paradigms in the treatment of ischemic left ventricular dysfunction, spotlighting the revascularization for ischemic ventricular dysfunction-British cardiovascular intervention society-2 (REVIVED-BCIS2) trial results and its impact on key therapeutic goals: survival, left ventricular function, arrhythmia prevention, quality of life and viability testing.

Recent findings

The REVIVED-BCIS2 trial, and its subsequent sub studies highlighted that (PCI) does not provide additional benefits to optimal medical therapy in terms of improving survival, left ventricular (LV) function, arrhythmic risk or quality of life. Additionally, viability testing did not differentiate patients who could benefit from PCI, although scar burden was found to be a significant predictor of outcome in these patients.

The outcomes of REVIVED have challenged multiple existing beliefs in the field of ischaemic left ventricular dysfunction management, emphasising the importance of investigating evidence free areas in our practice. Future work, including the STICH3 international consortium of trials, aims to answer some of the remaining unanswered questions.
Device therapy for heart failure management
Authors: Chouairi Fouad , Levin Allison , Fudim Marat
Published: August 2024

Purpose of review

Given the prevalence of heart failure (HF) and the interdisciplinary nature of device therapy, it is paramount that cardiologists not only understand the current landscape of goal-directed medical therapy, but also the ongoing efforts in device development. Thus, we aim to provide a practical overview of the broad approaches being utilized in the burgeoning field of device-based therapies for heart failure.

Recent Findings

Currently, a diverse array of devices for HF treatment is being developed and tested, each targeting distinct aspects of HF pathophysiology. These innovative solutions encompass a wide spectrum, ranging from devices enabling remote monitoring of HF associated physiological parameters, to those focused on creating interatrial shunts and effecting structural modifications of the left ventricle, as well as to those designed to modulate the autonomic nervous system and diaphragm. Notably, a subset of these emerging devices is directed towards treating patients with heart failure with preserved ejection fraction, a population that has traditionally not been served by device-based therapies.

In recent decades, there has been a remarkable surge in the development and utilization of device-based treatments for managing HF. It is important for physicians to be familiar with these devices, their mechanisms of action, and their applications.
Biliary atresia with rare associations: a case report and literature review
Authors: Zaben Basel A. , Abualrub Ahmad M. , Malhes Waleed M. , Barabrah Anas M. , Tuqan Anas R. , Tahhan Ibrahem A. , Amro Wael
Published: August 2024

Introduction and importance:

Biliary atresia is a rare, progressive cholangiopathy that affects newborns, causing jaundice and other manifestations of hyperbilirubinemia. The incidence is higher in Asia than in Europe. The only available treatment is a surgical operation called Kasai portoenterostomy. In this case, the authors highlighted rare congenital anomalies that came with biliary atresia.

Case presentation:

A 10-day-old male infant was admitted to the hospital due to recurrent vomiting, yellowish skin, and scleral icterus. Laboratory investigations revealed elevated total serum and direct bilirubin levels. An atrophic gallbladder was observed on ultrasound. Intrahepatic cholangiography confirmed the diagnosis of biliary atresia, leading to the performance of a Kasai procedure. Additionally, the patient had intestinal malrotation and volvulus, which were managed with a Ladd’s procedure. Following surgery, there was notable improvement in liver enzymes and bilirubin levels, and the patient was discharged after 7 days. The infant has been initiated on oral vitamins, ursodeoxycholic acid, and antibiotics.

Clinical discussion:

Biliary atresia is a challenging condition characterized by progressive narrowing and fibrosis of the biliary tree. It is rarely associated with rare congenital anomalies like situs inversus totalis, intestinal malrotation, and volvulus. Diagnosis involves abdominal ultrasound and MRCG. The biliary atresia was managed by the Kasai procedure and the intestinal malrotation, and volvulus were managed by Ladd’s procedure.

Conclusion:

This case report highlights the importance of considering rare associations such as situs inversus, intestinal malrotation and volvulus in the diagnosis of biliary atresia in newborn. Early diagnosis and prompt intervention are crucial for optimal outcomes.
The Relationship of a Predictable Ability Measurement Examination and NCLEX-RN Disposition
Authors: Chery Sheila , Larson Erica , Madden Sara , Moran Vicki , Israel Heidi
Published: August 2024

Background:

End-of-program examinations have been used to determine nursing students’ readiness for the National Licensure Examination for Registered Nurses (NCLEX-RN). The Clinical Judgment Registered Nurse Readiness Examinations (CJE-RN REs) have been adopted by nursing schools for the last 5 years.

Purpose:

The purpose of this study was to validate the use of the CJE-RN REs by examining the relationship with first-time pass rates among nursing students.

Method:

Over 1000 students who took the CJE-RN REs and Next Generation NCLEX-RN from February 1 through August 31, 2023, participated in the study.

Results:

Students who achieved 70% or higher on the CJE-RN REs had a 99% chance of passing the NCLEX-RN on the first attempt.

Conclusion:

The findings of the study support the use of a valid and reliable measurement examination for nursing schools to assist students in preparing for the NCLEX-RN.
Current Status of Magnetic Resonance Imaging Use in Bladder Cancer
Authors: Ahn Hyungwoo
Published: August 2024

Bladder cancer (BC) is a significant global health concern, with over 500,000 new cases and 200,000 deaths annually, emphasizing the need for accurate staging and effective management. Traditional diagnostic techniques, such as cystoscopy and transurethral resection, are fundamental but have limitations in accurately assessing the depth of invasion. These limitations include the possibility of understaging and procedural variability, which can significantly impact treatment decisions. This review focuses on the role of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis and staging of BC, particularly emphasizing the Vesical Imaging-Reporting and Data System (VI-RADS) framework. By enhancing interpretive consistency and diagnostic accuracy, mpMRI and VI-RADS offer detailed visualization of tumor characteristics and depth of invasion, while reducing the need for more invasive traditional methods. These advancements not only improve staging accuracy but also enhance treatment planning, underscoring the importance of advanced imaging in evolving BC management and positively influencing patient outcomes.
A Comparative Assessment of Outcomes Following Mandibular Distraction Osteogenesis and Tongue-Lip Adhesion in Pierre Robin Sequence
Authors: Ai Jeffrey B. , McQueen Ryan G. , McCarty Riley M. , Sharda Mukul , Zagloul Maie , Shakir Sameer , Yi Cleo , Klement Kristen , Lin Kant Y.
Published: August 2024

The purpose of this study was to assess long-term outcomes of tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) to resolve upper airway obstruction in patients with Robin sequence (RS). A retrospective cohort study was performed of subjects presenting to a tertiary care pediatric center who underwent either primary MDO or TLA for the treatment of RS between 2004 and 2020. N=59 subjects met inclusion criteria (n=34 MDO, n=25 TLA), and there were no significant differences in preoperative patient characteristics other than age at surgery (MDO 31 d vs. TLA 17 d, P=0.049). Preoperative apnea-hypopnea index (AHI) was similar between cohorts (33.9 and 46.7, P=0.38). Subjects who underwent MDO demonstrated improved AHI on initial postoperative polysomnogram performed at 2 weeks (3.4 vs. 11.6, P=0.014), however AHI at the second postoperative timepoint (270 vs. 142 d, P=0.007) was no different between cohorts (2.8 vs. 2.6, P=0.89). No subject in either group required enteral nutrition or supplemental oxygen at last follow-up. In subjects undergoing MDO, 14.7% demonstrated temporary asymmetric marginal mandibular nerve dysfunction. Forty-seven percent of MDO patients had injury to first primary molars. MDO and TLA both ultimately achieved similar long-term resolution of upper airway obstruction and associated feeding difficulties in patients with Robin sequence. MDO offered a more immediate airway improvement, but the procedure carried a potential risk of neurosensory and dental injury when compared with TLA.
Introduction to the Contemporary Assessment and Recommendations to Enhance Surgical Education and Training
Authors: Ellison Edwin Christopher , Stain Steven C. , Lillemoe Keith D.
Published: August 2024

Objective:

Provide reports of the Blue Ribbon II Subcommittees.

Background:

The Blue Ribbon Committee II (BRC II) was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training.

Methods:

It was organized into subcommittees, each of which was asked to prepare a manuscript on their findings and recommendations. The BRC II Subcommittees were: Blue Ribbon Committee 1 Review and Assessment, Surgical Workforce, Medical Student Education, Work Life Integration, Resident Education, Goals, Structure and Financing of Training, Education Support and Faculty Development, Research Training, and Educational Technology and Assessment. BRC II used the Delphi approach with consensus defined as equal to or greater than 80% and identified and recommended 31 priorities for surgical education in 2024.

Results:

The initial findings were presented to a general surgery and related specialty resident and fellow focus group for comments and written feedback, and they were asked to prepare a manuscript as well.

Conclusions:

The reports of the Subcommittees of the BRC II provide an assessment and key recommendations concerning surgical education and training in 2024.
Mitochondrial Function After Normothermic Regional Perfusion or Direct Procurement Followed by Hypothermic Oxygenated Machine Perfusion in Heart Transplantation After Circulatory Death
Authors: Berg Katrine , Ertugrul Imran , Seefeldt Jacob M. , Jespersen Nichlas R. , Dalsgaard Frederik F. , Ryhammer Pia K. , Pedersen Michael , Ilkjaer Lars Bo , Hu Michiel , Erasmus Michiel E. , Nielsen Bent R. R. , Bøtker Hans Erik , Moeslund Niels , Westenbrink Daan , Eiskjær Hans
Published: August 2024

Background.

Strategies to minimize ischemic damage during heart transplantation (HTX) by donation after circulatory death (DCD) are warranted because the inevitable ischemic injury linked to DCD HTX deteriorates mitochondrial respiratory capacity and ultimately graft quality. This study aimed to examine the myocardial mitochondrial function during DCD HTX with hypothermic oxygenated machine perfusion (HOPE) and compare the effect of normothermic regional perfusion (NRP) with that of direct procurement and perfusion (DPP).

Methods.

A porcine DCD HTX model was used with hearts subjected to either DPP (n = 6) or NRP (n = 7) followed by HOPE and orthotopic HTX. Mitochondrial respiratory function was analyzed by high-resolution respirometry in left ventricle biopsies at baseline, after 180 min of HOPE, and after 60 min of reperfusion post-HTX.

Results.

Mitochondrial oxidative phosphorylation (P = 0.0008), respiratory control ratio (P = 0.04), and coupling efficiency (P = 0.04) declined during DCD HTX. Fatty acid oxidation was preserved after 3 h of HOPE with a modest, statistically nonsignificant decline after reperfusion (P = 0.2). Oxidative phosphorylation was inversely correlated with troponin-T levels (r = –0.70, P = 0.0004). No statistically significant difference in mitochondrial respiratory capacity was observed between participants exposed to NRP and DPP.

Conclusions.

Mitochondrial respiratory capacity declined gradually throughout the course of DCD HTX and correlated with the degree of myocardial damage. Following HOPE, the extent of mitochondrial deterioration was comparable between NRP and DPP.
Epidemiological inference at the threshold of data availability: an influenza A(H1N2)v spillover event in the United Kingdom
Authors: Fozard John A. , Thomson Emma C. , Illingworth Christopher J. R.
Published: August 2024

Viruses that infect animals regularly spill over into the human population, but individual events may lead to anything from a single case to a novel pandemic. Rapidly gaining an understanding of a spillover event is critical to calibrating a public health response. We here propose a novel method, using likelihood-free rejection sampling, to evaluate the properties of an outbreak of swine-origin influenza A(H1N2)v in the United Kingdom, detected in November 2023. From the limited data available, we generate historical estimates of the probability that the outbreak had died out in the days following the detection of the first case. Our method suggests that the outbreak could have been said to be over with 95% certainty between 19 and 29 days after the first case was detected, depending upon the probability of a case being detected. We further estimate the number of undetected cases conditional upon the outbreak still being live, the epidemiological parameter
R
0
, and the date on which the spillover event itself occurred. Our method requires minimal data to be effective. While our calculations were performed after the event, the real-time application of our method has potential value for public health responses to cases of emerging viral infection.