bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance against aminoglycoside antibiotics via drug or target modification enables community-wide antiphage defense
Authors: Kever Larissa , Zhang Qian , Hardy Aël , Westhoff Philipp , Yu Yi , Frunzke Julia
Published: August 2024

The ongoing arms race between bacteria and phages has forced bacteria to evolve a sophisticated set of antiphage defense mechanisms that constitute the bacterial immune system. In our previous study, we highlighted the antiphage properties of aminoglycoside antibiotics, which are naturally secreted by Streptomyces. Successful inhibition of phage infection was achieved by addition of pure compounds and supernatants from a natural producer strain emphasizing the potential for community-wide antiphage defense. However, given the dual functionality of these compounds, neighboring bacterial cells require resistance to the antibacterial activity of aminoglycosides to benefit from the protection they confer against phages. In this study, we tested a variety of different aminoglycoside resistance mechanisms acting via drug or target (16S rRNA) modification and demonstrated that they do not interfere with the antiphage properties of the molecules. Furthermore, we confirmed the antiphage impact of aminoglycosides in a community context by coculturing phage-susceptible, apramycin-resistant Streptomyces venezuelae with the apramycin-producing strain Streptoalloteichus tenebrarius. Given the prevalence of aminoglycoside resistance among natural bacterial isolates, this study highlights the ecological relevance of chemical defense via aminoglycosides at the community level.
Automated cell lineage reconstruction using label-free 4D microscopy
Authors: Waliman Matthew , Johnson Ryan L , Natesan Gunalan , Peinado Neil A , Tan Shiqin , Santella Anthony , Hong Ray L , Shah Pavak K
Published: August 2024

Patterns of lineal descent play a critical role in the development of metazoan embryos. In eutelic organisms that generate a fixed number of somatic cells, invariance in the topology of their cell lineage provides a powerful opportunity to interrogate developmental events with empirical repeatability across individuals. Studies of embryonic development using the nematode Caenorhabditis elegans have been drivers of discovery. These studies have depended heavily on high-throughput lineage tracing enabled by 4D fluorescence microscopy and robust computer vision pipelines. For a range of applications, computer-aided yet manual lineage tracing using 4D label-free microscopy remains an essential tool. Deep learning approaches to cell detection and tracking in fluorescence microscopy have advanced significantly in recent years, yet solutions for automating cell detection and tracking in 3D label-free imaging of dense tissues and embryos remain inaccessible. Here, we describe embGAN, a deep learning pipeline that addresses the challenge of automated cell detection and tracking in label-free 3D time-lapse imaging. embGAN requires no manual data annotation for training, learns robust detections that exhibits a high degree of scale invariance, and generalizes well to images acquired in multiple labs on multiple instruments. We characterize embGAN's performance using lineage tracing in the C. elegans embryo as a benchmark. embGAN achieves near–state-of-the-art performance in cell detection and tracking, enabling high-throughput studies of cell lineage without the need for fluorescent reporters or transgenics.
Cancer Stemness Online: A Resource for Investigating Cancer Stemness and Associations with Immune Response
Authors: Zhou Weiwei , Su Minghai , Jiang Tiantongfei , Xie Yunjin , Shi Jingyi , Ma Yingying , Xu Kang , Xu Gang , Li Yongsheng , Xu Juan
Published: August 2024

Cancer progression involves the gradual loss of a differentiated phenotype and the acquisition of progenitor and stem cell-like features, which are potential culprits of immunotherapy resistance. Although the state-of-the-art predictive computational methods have facilitated the prediction of cancer stemness, there remains a lack of efficient resources to accommodate various usage requirements. Here, we present the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at both bulk and single-cell levels. This resource integrates eight robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting stemness scores. Downstream analyses were performed from five distinct aspects: identifying the signature genes of cancer stemness; exploring the associations with cancer hallmarks and cellular states; exploring the associations with immune response and the communications with immune cells; investigating the contributions to patient survival; and performing a robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualizations of the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and expanding downstream functional interpretation, including immune response and cancer hallmarks. Cancer Stemness Online is freely accessible at http://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.
Histone deacetylase SlHDA7 impacts fruit ripening and shelf life in tomato
Authors: Zhou Yijie , Li Zhiwei , Su Xinguo , Hou Huiyu , Jiang Yueming , Duan Xuewu , Qu Hongxia , Jiang Guoxiang
Published: August 2024

Fruit ripening depends on the accurate control of ripening-related genes expression, with histone deacetylases (HDACs) playing crucial roles in transcriptional regulation. However, the functions of HDACs in fruit maturation remain largely unexplored. Here, we show that SlHDA7 acts as a suppressor of fruit ripening and functions as an H4ac HDAC in tomato. Deletion of SlHDA7 accelerated fruit ripening, while overexpression of SlHDA7 delayed the maturation process. Additionally, ethylene production and carotenoid biosynthesis significantly increased in slhda7 mutant fruits but decreased in SlHDA7-overexpressing fruits. Furthermore, SlHDA7 repress the expression of ethylene production and signaling, carotenoid metabolism, cell wall modification, and transcriptional regulation-related genes. RT-qPCR and ChIP-qPCR analyses indicated that SlHDA7 may deacetylate H4ac, leading to reduced transcript levels of ACO1, GGPPS2, Z-ISO, EXP1, and XYL1 mRNA, consequently suppressing fruit ripening. Moreover, SlHDA7 suppresses fruit ripening by targeting specific ripening-associated transcription factors (TFs) like RIN, FUL1, and ERF.E1, ultimately leading to delayed ripening and prolonged fruit shelf life. In summary, our findings indicate that SlHDA7 negatively modulates tomato fruit maturation by adjusting H4ac levels of these ripening-associated genes and key TFs.
Computational and Physical Modeling to Understand Form–Function Relationships
Authors: Schwaner M Janneke , Hsieh S Tonia
Published: August 2024

Synopsis

The morphology-performance-fitness paradigm has long been a guiding principle inspiring a great deal of laboratory and field studies fundamental to understanding functional-morphology relationships across the tree of life. Despite the power of experimental approaches, they also come with inherent limitations associated with equipment and animal costs, as well as ethical considerations for the types of manipulations that can be implemented. Modeling can provide an opportunity to surmount some of these challenges by offering greater flexibility in manipulating variables and exploring a wider parameter space than is tractable during animal experimentation. However, effective implementation of these tools requires careful consideration of the limitations and benefits they convey, requiring both greater interdisciplinary training from early stages of educational development and increased collaboration and synergies among scientists from traditionally separate disciplines. With institutions increasingly recognizing the need for and investing in providing universal access to computational and rapid prototyping resources, we believe that it is an opportune moment to prioritize greater synergy to accelerate discovery and innovation across fields.
Lyme Arthritis: A 50-Year Journey
Authors: Steere Allen C
Published: August 2024

Lyme arthritis (LA) was recognized as a separate entity in 1975 because of geographic clustering of children often diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut. After identification of erythema migrans as a common early feature of the illness, a prospective study of such patients implicated Ixodes scapularis ticks in disease transmission. In 1982, the causative agent, now called Borrelia burgdorferi, was cultured from these ticks and from Lyme disease patients. Subsequently, it was shown that LA could usually be treated successfully with oral antibiotics but sometimes required intravenous antibiotics. Yet, a small percentage of patients developed a dysregulated, proinflammatory immune response leading to persistent postinfectious synovitis with vascular damage, cytotoxic and autoimmune responses, and fibroblast proliferation, a lesion similar to that of rheumatoid arthritis. The message from postinfectious LA for other autoimmune arthritides is that a complex immune response with autoimmune features can begin with a microbial infection.
Male–female spatio-temporal differences of age-related bone changes show faster bone deterioration in older women at femoral regions associated with incident hip fracture
Authors: Carballido-Gamio Julio , Marques Elisa A , Sigurdsson Sigurdur , Siggeirsdottir Kristin , Jensen Alexandria , Sigurdsson Gunnar , Aspelund Thor , Gudnason Vilmundur , Lang Thomas F , Harris Tamara B
Published: August 2024

A better understanding of how age-related bone loss affects the fracture-prone regions of the proximal femur could lead to more informed fracture-prevention strategies. Therefore, the aim of this work was to assess the spatio-temporal distribution of bone deterioration in older men and women with aging. A subset of 305 men (74.87 ± 4.76 years; mean ± SD) and 371 age-matched women (74.84 ± 4.71 years) with no history of fracture was randomly selected from the Age, Gene/Environment Susceptibility-Reykjavik study. Quantitative computed tomography (QCT) scans of the left proximal femur obtained at baseline and at 5.2 ± 0.4 years follow-up were processed to assess local changes in volumetric bone mineral density (vBMD), cortical bone thickness (Ct.Th), and internal bone structure using voxel-based morphometry (VBM), surface-based statistical parametric mapping (surf-SPM), and tensor-based morphometry (TBM). Local parametric changes within each sex and sex differences in these changes were statistically assessed using linear mixed effects models allowing for baseline and time-varying covariates, yielding Student’s t-test and p-value statistical maps of the proximal femur. The statistical maps indicated regions with significant parametric changes in each sex and with significant different parametric changes between older men and older women with aging. Older women manifested significantly larger losses in vBMD, (Ct.Th), and structure than older men, and they did so in regions where deficiency in these parameters has been associated with incident hip fracture. Using longitudinal QCT scans of the proximal femur and Computational Anatomy, we provided new insights into the higher fracture rates of the proximal femur in older women compared with men of similar age providing new information on the pathophysiology of osteoporosis.
Cognitive function in long-term testicular cancer survivors: impact of modifiable factors
Authors: Dinh Paul C , Monahan Patrick O , Fung Chunkit , Sesso Howard D , Feldman Darren R , Vaughn David J , Hamilton Robert J , Huddart Robert , Martin Neil E , Kollmannsberger Christian , Althouse Sandra , Einhorn Lawrence H , Frisina Robert , Root James C , Ahles Tim A , Travis Lois B
Published: August 2024

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) affecting cognitive function in long-term testicular cancer survivors (TC survivors). TC survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those that assessed cognition. Medical record abstraction provided cancer and treatment history. Multivariable logistic regression examined relationships between potential associated factors and cognitive impairment. Among 678 TC survivors (median age = 46; interquartile range [IQR] = 38-54); median time since chemotherapy = 10.9 years, IQR = 7.9-15.9), 13.7% reported cognitive dysfunction. Hearing loss (odds ratio [OR] = 2.02; P = .040), neuropathic pain (OR = 2.06; P = .028), fatigue (OR = 6.11; P < .001), and anxiety/depression (OR = 1.96; P = .029) were associated with cognitive impairment in multivariable analyses. Being on disability (OR = 9.57; P = .002) or retired (OR = 3.64; P = .029) were also associated with cognitive decline. Factors associated with impaired cognition identify TC survivors requiring closer monitoring, counseling, and focused interventions. Hearing loss, neuropathic pain, fatigue, and anxiety/depression constitute potential targets for prevention or reduction of cognitive impairment in long-term TC survivors.
Homer’s The Odyssey: education as Phaeacian (hospitable) or as Laestrygonian (hostile)
Authors: Guilherme Alexandre , Cardozo Artur Magoga
Published: August 2024

The issue of hospitality in education has become prominent in the philosophy of education, with various articles and books being published recently. This is so for a number of reasons, such as the necessity to harbour and include immigrants and refugees in our schools and education systems, the rising levels of violence being experienced by individuals in school communities, and the importance of establishing dialogical relations between teacher and students and between students. In this article, we discuss the concept of hospitality by turning to Homer (eighth Century Bce) and his classic work, The Odyssey (Ὀδ”σσεια), connecting it to the issue of hospitality in education. The article is divided into two sections. In the first, we refer to two passages in Homer’s The Odyssey that are very pertinent to the issue of the issue at hand; the Phaeacian passage, which stands for a prime example of hospitality, and the Laestrygonian case, a seminal example of non-hospitality, of hostility. In the second, we conduct a philosophical inquiry into hospitality and education.
Ruptured large hepatic cyst with elevated serum and ascites CA19-9 level
Authors: Mizukami Ryosuke , Nakazawa Akiko , Einama Takahiro , Kariya Risa , Ohara Mayuko , Ichio Koki , Konno Fukumi , Kobayashi Kazuki , Yonamine Naoto , Fujinuma Ibuki , Tsunenari Takazumi , Takihata Yasuhiro , Takao Mikiya , Shinto Eiji , Ueno Hideki , Kishi Yoji
Published: August 2024

Tumor markers such as carbohydrate antigen 19-9 (CA19-9) are generally useful in ruling out malignancy of hepatic cysts. The patient was a 72-year-old man who had a ruptured liver cyst in the right liver, which had been noted since he was 67 years old at another hospital. The initial laboratory tests demonstrated elevated CA19-9 (193 784.3 U/mL). We made the diagnosis with a simple ruptured liver cyst from magnetic resonance imaging and cytological examination of ascites, and laparoscopic fenestration with drainage of the abdominal fluid was performed. Pathological diagnosis of the resected wall cyst was non-parasitic simple hepatic cyst with acute inflammation and hemorrhage. The patient’s serum levels of CA19-9 were 164.0 U/mL on postoperative day 23. The follow-up abdominal computed tomography scan performed 2 months later did not any finding of tumor.
CNGC15 and DMI1 ion channel gating in nuclear calcium signaling: opening new questions and closing controversies
Authors: Jacott Catherine N , del Cerro Pablo
Published: August 2024

Nuclear calcium (Ca2+) signaling is crucial for symbiotic interactions between legumes and beneficial microbes, such as rhizobia and arbuscular mycorrhizal fungi. The ion channels DMI1 and CNGC15 are key to generating repetitive nuclear Ca2+ oscillations. Despite more than 20 years of research on symbiotic nuclear Ca2+ spiking, important questions remain, including the exact function of the DMI1 channel. This review highlights recent developments that have filled knowledge gaps regarding the regulation of CNGC15 and its interplay with DMI1. We also explore new insights into the evolutionary conservation of DMI1-induced symbiotic nuclear Ca2+ oscillations and the roles of CNGC15 and DMI1 beyond symbiosis, such as in nitrate signaling, and discuss new questions this raises. As we delve deeper into the regulatory mechanisms and evolutionary history of these ion channels, we move closer to fully understanding the roles of nuclear Ca2+ signaling in plant life.
A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole
Authors: Thompson George R , Chen Sharon C-A , Alfouzan Wadha Ahmed , Izumikawa Koichi , Colombo Arnaldo L , Maertens Johan
Published: August 2024

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.
Late-end reionization with aton-he: towards constraints from Ly α emitters observed with JWST
Authors: Asthana Shikhar , Haehnelt Martin G , Kulkarni Girish , Aubert Dominique , Bolton James S , Keating Laura C
Published: August 2024

We present a new suite of late-end reionization simulations performed with aton-he, a revised version of the GPU-based radiative transfer code aton that includes helium. The simulations are able to reproduce the Ly $\alpha$ flux distribution of the E-XQR-30 sample of QSO absorption spectra at $5 \lesssim z \lesssim 6.2$, and show that a large variety of reionization models are consistent with these data. We explore a range of variations in source models and in the early-stage evolution of reionization. Our fiducial reionization history has a mid-point of reionization at $z = 6.5$, but we also explore an ‘Early’ reionization history with a mid-point at $z = 7.5$ and an ‘Extremely Early’ reionization history with a mid-point at $z = 9.5$. Haloes massive enough to host observed Ly $\alpha$ emitters are highly biased. The fraction of such haloes embedded in ionized bubbles that are large enough to allow high Ly $\alpha$ transmission becomes close to unity much before the volume filling factor of ionized regions. For our fiducial reionization history this happens at $z = 8$, probably too late to be consistent with the detection by JWST of abundant Ly $\alpha$ emission out to $z = 11$. A reionization history in our ‘Early’ model or perhaps even our ‘Extremely Early’ model may be required, suggesting a Thomson scattering optical depth in tension with that reported by Planck, but consistent with recent suggestions of a significantly higher value.
Capture of field stars by dark substructures
Authors: Peñarrubia Jorge , Errani Raphaël , Walker Matthew G , Gieles Mark , Boekholt Tjarda C N
Published: August 2024

We use analytical and N-body methods to study the capture of field stars by gravitating substructures moving across a galactic environment. The majority of stars captured by a substructure move on temporarily bound orbits that are lost to galactic tides after a few orbital revolutions. In numerical experiments where a substructure model is immersed into a sea of field particles on a circular orbit, we find a population of particles that remain bound to the substructure potential for indefinitely long times. This population is absent from substructure models, initially placed outside the galaxy on an eccentric orbit. We show that gravitational capture is most efficient in dwarf spheroidal galaxies (dSphs) on account of their low velocity dispersions and high stellar phase-space densities. In these galaxies, ‘dark’ sub-subhaloes, which do not experience in situ star formation, may capture field stars and become visible as stellar overdensities with unusual properties: (i) they would have a large size for their luminosity, (ii) contain stellar populations indistinguishable from the host galaxy, and (iii) exhibit dark matter (DM)-dominated mass-to-light ratios. We discuss the nature of several ‘anomalous’ stellar systems reported as star clusters in the Fornax and Eridanus II dSphs that exhibit some of these characteristics. DM sub-subhaloes with a mass function ${\rm d}N/{\rm d}M_\bullet \sim M_\bullet ^{-\alpha }$ are expected to generate stellar systems with a luminosity function, ${\rm d}N/{\rm d}M_\star \sim M_\star ^{-\beta }$, where $\beta =(2\alpha +1)/3=1.6$ for $\alpha =1.9$. Detecting and characterizing these objects in dSphs would provide unprecedented constraints on the particle mass and cross-section of a large range of DM particle candidates.
Positive and unlabelled machine learning reveals new fast radio burst repeater candidates
Authors: Sharma Arjun , Rajpaul Vinesh Maguire
Published: August 2024

Fast radio bursts (FRBs) are astronomical radio transients of unknown origin. A minority of FRBs have been observed to originate from repeating sources, and it is unknown which apparent one-off bursts are hidden repeaters. Recent studies increasingly suggest that there are intrinsic physical differences between repeating and non-repeating FRBs. Previous research has used machine learning classification techniques to identify apparent non-repeaters with repeater characteristics, whose sky positions would be ideal targets for future observation campaigns. However, these methods have not sufficiently accounted for the positive and unlabelled (PU) nature of the data, wherein true labels are only available for repeaters. Modified techniques that do not inadvertently learn properties of hidden repeaters as characteristic of non-repeaters are likely to identify additional repeater candidates with greater accuracy. We present in this paper the first known attempt at applying PU-specific machine learning techniques to study FRBs. We train an ensemble of five PU-specific classifiers on the available data and use them to identify 66 repeater candidates in burst data from the CHIME/FRB collaboration, 18 of which were not identified with the use of machine learning classifiers in past research. Our results additionally support repeaters and non-repeaters having intrinsically different physical properties, particularly spectral index, frequency width, and burst width. This work additionally opens new possibilities to study repeating and non-repeating FRBs using the framework of PU learning.
Incidence Rate and Risk Factors for Developing Active Tuberculosis Among People Living With HIV in Georgia 2019–2020 Cohort
Authors: Buziashvili Mariana , Djibuti Mamuka , Tukvadze Nestani , DeHovitz Jack , Baliashvili Davit
Published: August 2024

Background

Tuberculosis (TB) is a leading cause of morbidity and mortality among people with HIV (PHIV) globally. Our study is the first to evaluate TB incidence and its risk factors among PHIV in the country of Georgia, where previously no data were available.

Methods

A retrospective cohort study was conducted among persons newly diagnosed with HIV in Georgia during 2019–2020. Active TB incidence was calculated within a minimum of 2-year follow-up period from HIV diagnosis. Cox proportional hazard model was used for evaluating risk factors for TB development.

Results

The median age in the final cohort of 1165 PHIV was 38 (interquartile range, 30–48) and 76.3% were male. Twenty-nine percent of patients had a CD4 cell count <200 at HIV diagnosis and 89.9% initiated antiretroviral therapy (ART). TB incidence rate was 10/1000 person-years (p-y; 95% confidence interval [CI], 9.6–10.4), with rates being higher within several subgroups, mainly: PHIV aged 40–49 years (17.5/1 000 p-y [95% CI, 16.8–18.2]); those not receiving ART (22/1000 p-y [95% CI, 20.9–23.1]); those with CD4 < 200 at baseline (28/1000 p-y [95% CI, 27.4–28.6]); and those who developed AIDS (29.1/1 000 p-y [95% CI, 28.6–29.6]). Age (aHR, 1.2; 95% CI, 1.03–1.39; P = .01) and AIDS diagnosis (aHR, 3.2; 95% CI, 3.06–27.9; P = .001) were associated with TB development, whereas high CD4 count was protective against TB (aHR, 0.18; 95% CI, .06–.61; P = .005).

Conclusions

Study results highlight an imperative role of CD4 cell count management and the need for early HIV diagnosis and timely initiation of ART to ensure an effective immune response against tuberculosis, stressing the need for further in-depth evaluation of the TB preventive treatment delivery system's efficiency and gaps.
Playing with labels: Identity terms as tools for building agency
Authors: Camp Elisabeth , Flores Carolina
Published: August 2024

Identity labels like “woman”, “Black,” “mother,” and “evangelical” are pervasive in both political and personal life, and in both formal and informal classification and communication. They are also widely thought to undermine agency by essentializing groups, flattening individual distinctiveness, and enforcing discrimination. While we take these worries to be well-founded, we argue that they result from a particular practice of using labels to rigidly label others. We identify an alternative practice of playful self-labelling, and argue that it can function as a tool for combating oppression by expressing and enhancing individual and collective agency.
Pulmonary delivery of cell membrane-derived nanovesicles carrying anti-miRNA155 oligonucleotides ameliorates LPS-induced acute lung injury
Authors: Zhuang Chuanyu , Kang Minji , Oh Jihun , Lee Minhyung
Published: August 2024

Acute lung injury (ALI) is a devastating inflammatory disease. MicroRNA155 (miR155) in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1 (SOCS1) in ALI. Anti-miR155 oligonucleotide (AMO155) have been suggested as a potential therapeutic reagent for ALI. However, a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy. In this study, cell membrane-derived nanovesicles (CMNVs) were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs. For preparation of CMNVs, cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion. Cholesterol-conjugated AMO155 (AMO155c) was loaded into CMNVs and extracellular vesicles (EVs) by sonication. The physical characterization indicated that CMNVs with AMO155c (AMO155c/CMNV) were membrane-structured vesicles with a size of ∼120 nm. The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine (25 kDa, PEI25k). The delivery efficiency of AMO155c by CMNVs was similar to that by EVs. As a result, the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV. AMO155c/CMNV were administered intratracheally into the ALI models. The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others, suggesting that miR155 effectively was inhibited by AMO155c/CMNV. In addition, the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k, reducing inflammation reactions. The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.
The implication of anti-Ro60 with or without anti-Ro52 antibody in patients with systemic lupus erythematosus
Authors: Liao Katie , Li Ning , Bonin Julie , Koelmeyer Rachel , Kent Joanna , Pellicano Rebecca , De Silva Thilinie , Yap Kristy , Golder Vera , Kitching A Richard , Morand Eric F , Hoi Alberta
Published: August 2024

Objectives

Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjögren’s disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterized.

Methods

Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity. Patient characteristics and disease outcomes, including High Disease Activity Status (HDAS) defined as an ever attainment of SLEDAI2K ≥10, adjusted mean SLEDAI (AMS), and time-adjusted mean clinical SLEDAI (excluding serologic activities) were compared using linear or logistic regressions. Furthermore, isolated or dual positivity of anti-Ro60 and anti-Ro52 were studied.

Results

Out of 409 patients, 47.2% were Ro+. Ro+ patients were predominantly Asian, had positive dsDNA and hypocomplementemia. They showed a higher likelihood of HDAS (OR 1.65, 95% CI 1.10–2.48, P = 0.015), AMS >4 (OR 1.84, 1.18–2.88, P = 0.007) and more frequent use of glucocorticoids (OR 1.87, 1.16–3.03, P = 0.011) and immunosuppressants (OR 2.0, 1.26–3.17, P = 0.003). Additionally, 24.4% of Ro+ patients experienced sicca symptoms, and hypergammaglobulinemia was significantly more common. Multivariate analysis confirmed that Asian ethnicity, severe flares, AMS, hypocomplementemia, rheumatoid factor, proteinuria, leucopenia and sicca symptoms were significantly linked to Ro positivity.

Conclusion

Anti-Ro positivity is associated with higher disease activity and increased treatment needs. Ro positivity correlates with laboratory abnormalities such as hypocomplementemia and leucopenia. These findings highlight the importance of anti-Ro60/Ro52 testing in the clinical evaluation of SLE.
Approaches in care for people with variations of sex characteristics—focus groups in the European context on the strengths and challenges of multidisciplinary teams
Authors: Gramc Martin
Published: August 2024

Background

New guidelines in the Consensus Statement on Management of Intersex Disorders by the Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group 2006 introduced multidisciplinary teams (MDTs) to provide care that involves collaboration between healthcare professionals, parents, and children with variations of sex characteristics (VSC).

Aim

The aim of this study was to examine a neglected but important field of collaboration among healthcare professionals and peer support groups who provide care for people with VSC.

Outcomes

The study outcome was the information obtained regarding the actual composition and collaboration of the multidisciplinary teams caring for children with VSC, including their collaboration with parents, peer support groups, and other care providers.

Methods

In this study we used an exploratory qualitative design based on mixed focus groups (in terms of professional background) and reflexive thematic analysis. Semi-structured focus group interview guides were used to obtain information about the participants’ viewpoints on the composition and challenges of, and collaboration between, peer support groups and members of multidisciplinary teams working to care for children with VSC and their parents. Seven focus groups were conducted with healthcare professionals and peer support groups in care teams in Central, Northern, and Western Europe. The data from the focus groups were examined using reflexive thematic analysis.

Results

The participants in the focus groups provided information regarding the use of multidisciplinary and interdisciplinary child- and family-oriented approaches and the strengths and challenges of collaboration and peer support groups. The results showed that the teams used a predominantly multidisciplinary approach and suffered from a lack of psychosocial providers, poor collaboration with peer support groups, and poor implementation of shared decision-making to address the clinical uncertainty of parents and people with VSC.

Clinical Implications

Clinicians should provide more psychosocial support and improve collaboration with peer support groups and nonmedical professionals.

Strengths and Limitations

This study is one of the first qualitative studies to provide information on the collaboration of multidisciplinary teams working to provide care for children with VSC and collaborate with their parents in the European context. However, due to language barriers, the dropout rate of participants, and the under-representation of peer support groups in the sample there was a lack of information on collaboration among healthcare professionals and peer support groups.

Conclusions

The collaboration between MDTs and parents does not involve adequate psychosocial and peer support or shared decision-making to address the uncertainty experienced by children and families when faced with information about variations of sex characteristics.
Ejaculatory-sparing transurethral prostatectomy: a meta-analysis of randomized controlled trials
Authors: Ramez Mohamed , Abolazm Ahmed E , El-Nahas Ahmed R
Published: August 2024

Introduction

Benign prostatic hyperplasia (BPH) is a prevalent urologic condition leading to lower urinary tract symptoms (LUTS). Transurethral prostatectomy has been a cornerstone for surgical management of LUTS due to BPH. A growing interest has recently emerged to develop a surgical approach that can decrease the effect on sexual and ejaculatory functions while maintaining its efficacy in treating LUTS.

Objective

The aim of this meta-analysis is to assess patient-reported outcomes of ejaculatory-sparing transurethral prostatectomy in management of BPH.

Methods

Cochrane Library, Scopus, PubMed, and Web of Science databases were searched systematically until July 6, 2024. Randomized controlled trials reporting data on ejaculatory-sparing techniques during transurethral prostatectomy were included. The Cochrane risk-of-bias tool for randomized trials was used for quality assessment. The meta-analysis was conducted with Review Manager software. Numerical data were analyzed by standardized mean difference (SMD), while the risk ratio was used for analysis of categorical data. Fixed or random effects models were used according to heterogeneity.

Results

Five randomized controlled trials were included with 274 patients. No statistically significant differences were found between groups for International Prostate Symptom Score (SMD, 0.07; 95% CI, –0.45 to 0.59; P = .79), Qmax (SMD, –0.53; 95% CI, –1.11 to 0.06; P = .08), and International Index of Erectile Function (SMD, 0.89; 95% CI, –0.07 to 1.84; P = .07). Ejaculation was better preserved in ejaculatory-sparing techniques (risk ratio, 0.19; 95% CI, 0.12-0.30; P < .00001).

Conclusions

Ejaculatory-sparing transurethral prostatectomy techniques are feasible to preserve ejaculation while improving outcomes without compromising functional voiding outcomes.
Emerging trends in pediatric candidemia: mapping the rise in Candida parapsilosis incidence and antifungal resistance in Turkey
Authors: Önal Pınar , Aygün Fatma Deniz , Sever Gözde Apaydın , Eren Beste Akdeniz , Kes Gülşen , Aygün Fatih , Zübarioğlu Tanyel , Beşer Ömer Faruk , Ocak Süheyla , Yazgan Zeynep , Zeybek Çiğdem Aktuglu , Aygün Gökhan , Camcıoğlu Yıldız , Çokuğraş Haluk
Published: August 2024

Candidemia is emerging as a significant concern in children, particularly among those with underlying conditions like malignancies or prematurity. The interpretation of epidemiological data on candidemias and their antifungal resistance plays a vital role in aiding diagnosis and guiding clinicians in treatment decisions. From 2014 to 2021, a retrospective analysis was conducted in İstanbul, Turkey; comparing Candida albicans and non-albicans (NAC) spp in both surviving and deceased groups. Furthermore, an examination of Candida parapsilosis and other species was performed, assessing various clinical and laboratory parameters. Among 93 patients, with a median age of 17 months, C. parapsilosis emerged as the predominant isolated species (44%), followed by C. albicans (34.4%). Resistance to fluconazole, voricanozole, and echinocandins, along with a history of broad-spectrum antibiotic use were found to be significantly higher in the non-albicans Candida group compared to C. albicans group. In the C. parapsilosis group, statistically lower age was identified in comparison to the other groups (P = .018). In addition, high fluconazole and voriconazole resistance was detected in Candida parapsilosis spp. Our study highlights a notable prevalence of C. parapsilosis, particularly in younger children, which is different from similar studies in childhood. This trend may be attributed to the common use of total parenteral nutrition and central venous catheter in gastrointestinal disorders and metabolic diseases. Furthermore, as anticipated, high azole resistance is noted in C. parapsilosis and other non-albicans Candida species. Interestingly, resistance to both amphotericin B and echinocandins within this group has been notably high. It is crucial to emphasize the considerable antifungal resistance seen in C. parapsilosis isolates.
Prevalence of overweight and obesity, dietary behaviors, and physical activities among sixth graders: a cross-sectional study in Ho Chi Minh City, Vietnam
Authors: Nguyen Ngoc-Trinh T , Nguyen Trang H H D , Pham Lan-Anh T , Dibley Michael J , Tang Hong K
Published: August 2024

The prevalence of overweight and obesity among adolescents has been increasing worldwide and is a significant public health challenge. Obesity is linked to several non-communicable diseases. This study aimed to determine the prevalence of overweight and obesity based on three growth references and described physical activities and dietary patterns among sixth graders in Ho Chi Minh City (HCMC). From 2018 to 2020, a cross-sectional study was conducted on 1375 students from 16 junior high schools in HCMC. We applied Probability Proportional to Size sampling to select schools. Anthropometric measurements, pubertal status assessment, and diet and physical activity data were collected through Food Frequency and Physical Activity Questionnaires. The study revealed a high prevalence of overweight and obesity among grade 6 students, with ∼45%–56% of students classified as overweight or obese using various growth references. Moreover, most students did not meet the World Health Organization’s physical activity and sedentary behavior recommendations. Most students spent <60 min/day on moderate to vigorous physical activity, and over 70% spent at least 120 min/day on sedentary activities during weekdays and weekends. The diet of the students was also imbalanced, with high intakes of protein, lipids, and carbohydrates and low consumption of fruits and vegetables. Nutritionists and policymakers should inform and encourage opportunities for healthier food and more daily activity for children, starting before the sixth-grade, so they can learn how to make healthier choices and change their behavior before they reach adolescence.
Medicaid Reimbursement for Common Orthopaedic Trauma Procedures Is 16.0% Less Compared With Medicare With Substantial Variability Between States
Authors: Moore Michael Lane , Henderson Adam , Haglin Jack M. , Brinkman Joseph C. , Van Schuyver Paul R. , Bingham Joshua S. , Miller Brian
Published: August 2024

OBJECTIVES:

This study seeks to evaluate the variability of Medicaid reimbursement and compare it with Medicare reimbursement using the 20 most commonly billed orthopaedic trauma Current Procedural Terminology (CPT) codes nationwide. The authors anticipate significant variability between states and hypothesize that Medicaid payment will be significantly less than Medicare payment.

METHODS:

The top 20 most common orthopaedic trauma surgery procedural codes were identified from a previous analysis performed by Haglin et al. The Centers for Medicare and Medicaid Services Physician Fee Schedule was used to determine reimbursement rates from Medicare, and state Medicaid fee schedules were used to determine reimbursement rates for Medicaid. State Medicaid rates were compared with their corresponding Medicare rates to determine a dollar difference. In addition, the dollar difference for each CPT code was divided by its respective physician relative value unit. This was used to acknowledge the possible variability in the complexity of orthopaedic procedures and the related physician effort. The Medicare Wage Index was used to adjust Medicaid rates based on the cost of living for the state as well. Coefficients of variation were calculated to represent overall variability in Medicaid and Medicare reimbursement rates.

RESULTS:

The mean reimbursement rates for Medicaid were lower for all 20 procedures compared with Medicare. On average, Medicaid reimbursed 16.0% less than Medicare and 29.6% less when adjusting for cost of living. MCD reimbursed at a higher rate than MCR for all procedures in only 9 states (Alaska, Arizona, Arkansas, Montana, Nebraska, New Jersey, New Mexico, North Dakota, and South Dakota) while 38 states reimbursed at a lower rate than MCR, on average. The coefficient of variation ranged from 0.24 to 0.34 for the Medicaid unadjusted group and from 0.35 to 0.46 for the Medicare Wage Index–adjusted group. By contrast, the Medicare group was consistent at 0.06 for all 20 procedures. The average dollar difference across the 20 CPT codes for Medicaid reimbursement compared with Medicare reimbursement ranged from −$76.89 to −$225.17, and the dollar difference per relative value unit ranged from −$5.96 to −$15.16.

CONCLUSIONS:

This study found a high amount of variation between state Medicaid reimbursement rates and average rates that were significantly lower than Medicare reimbursement rates for the top 20 most used orthopaedic trauma CPT codes as identified by Haglin et al. The discrepancy in reimbursement was increased when Medicaid rates were adjusted for state cost of living.

LEVEL OF EVIDENCE:

Prognostic, Level III. See Instructions for Authors for a complete description of levels of evidence.
Adding “Unlikely” as a Clinical Qualifier Is Unlikely to Be of Help: A Retrospective, Single-Center, Cross-Sectional Cohort Study
Authors: Hong Jinpyo , Shoemaker Joshua , Scott Jennifer , Helm Klaus
Published: August 2024

Clinical correlation is essential to accurate and efficient diagnosis and differential diagnosis in dermatopathology. Poor-quality clinical information can lead to failures and delays in patient care. Some clinicians use the term “unlikely” when submitting a specimen. How frequently the “unlikely” clinical diagnosis correlates with the final pathologic diagnosis is unknown. We studied 203 dermatopathology reports from December 8, 2020, to July 1, 2021, that included the qualifier “unlikely” on the requisition sheet. Samples were stratified into either an inflammatory or neoplastic cohort based on final histopathologic diagnosis, with the neoplastic cohort being further stratified into pigmented and nonpigmented cohorts. Statistical analyses were conducted. The “unlikely” diagnosis in the clinical differential diagnosis and the final histologic diagnosis were the same in 7.9% of the 203 samples studied. This occurred in 8.5% of the inflammatory cohort and 7.6% of the neoplastic cohort. We concluded that the use of the qualifier “unlikely” is not helpful. We acknowledge the limitations of our study because of a small sample.
Utility of PRAME Immunohistochemistry in the Detection of Subtle Melanoma Microsatellites
Authors: Daruish Maged , Karunaratne Sanwadana , Duffy-Gadd Paula , Hansford Samantha , Taibjee Saleem
Published: August 2024

Microsatellitosis is well established as a prognostic factor in malignant melanoma. Its identification leads to subsequent upstaging with implications for further management. We describe 6 cases in which immunohistochemical staining for PReferentially expressed Antigen in MElanoma facilitated detection of small foci of micrometastasis on scanning magnification, which may be potentially missed in routine sections.
Clinicopathologic Correlation and Routine Immunostains Help Distinguish Congenital Disseminated Pyogenic Granuloma From Other Cutaneous Disseminated Vascular Proliferations of Infancy: Case Report and Literature Review
Authors: Schiele Kristan , Voronina Veronica , Marka Arthur , Mann Julianne , LeBlanc Robert E.
Published: August 2024

The presence of multiple cutaneous vascular lesions in infancy can signal the possibility of visceral involvement. Dermatopathologists must appreciate how the differential diagnosis includes entities that have distinct therapeutic and prognostic implications. Fortunately, these rare entities can be distinguished histopathologically with the help of clinicopathologic correlation and immunohistochemistry. In this article, we discuss congenital disseminated pyogenic granuloma, multifocal infantile hemangioma, and multifocal lymphangioendotheliomatosis with thrombocytopenia. Subtle morphologic and immunophenotypic features permit their distinction, which in turn is important for identifying extracutaneous manifestations and effective treatments. We present a case of a 3-week-old infant with congenital disseminated pyogenic granuloma involving the skin and the liver whose lesions regressed without therapeutic intervention over 6 months of close follow-up. We review the literature on these rare, overlapping entities and present an approach to resolving the differential diagnosis.