bluuebunny/crossref_metadata_2025 huggingface dataset:
ProInfer: inference of binary protocol keywords based on probabilistic statistics
Authors: Guo Maohua , Zhu Yuefei , Fei Jinlong
Published: September 2024

Protocol reverse engineering is crucial in normative verification, and malware behavior analysis and vulnerability discovery. However, uncovering the structural features of binary protocols concealed within dense data representations remains a significant challenge. Accurately identifying keyword segments associated with message types is a prerequisite for meaningful semantic analysis and protocol state machine reduction. In this work, we introduce a novel approach for inferring keywords from binary protocols based on probabilistic statistics. Our method in terms of Byte employs heuristic rules to filter offset positions that are clearly unrelated to message types. We further filter candidate Byte-offsets utilizing constraint relations and provide the probabilistic ranking of each offset as the keyword segment. To enhance the reliability of keyword segment inference, we utilize the Monte Carlo algorithm to assess the difference between message clustering with candidate Byte-offset and random message clustering, and reorder candidate offsets according to the results. Then we can observe optimal values from both orderings and present the ultimate inference results. Experimental results demonstrate that our method excels in the accuracy of keyword segments identification compared with previous techniques.
In vitro early proximal caries detection using trilateral short-wave infrared reflection at 1050 and 1550 nm
Authors: Heck Katrin , Werner Nils , Hoffmann Lea , Schwendicke Falk , Litzenburger Friederike
Published: September 2024

Objectives

This in vitro study evaluated the diagnostic potential of short-wave infrared reflection (SWIRR) at 1050 and 1550 nm for proximal caries detection from the occlusal, buccal, and lingual surfaces of posterior teeth under clinically relevant conditions. Bitewing radiography (BWR) was the alternative index test and micro-computed tomography (μCT) was the reference standard.

Methods

Two hundred and fifty proximal surfaces of extracted human teeth were examined using SWIRR at 1050 and 1550 nm and BWR. SWIRR, BWR, and μCT findings were evaluated twice by 2 trained examiners. SWIRR images were evaluated from occlusal and trilateral (occlusal, buccal, and lingual combined) views. Sensitivity, specificity, and area under the curves were calculated. Reliability assessment was performed using κ statistics.

Results

Short-wave infrared reflection (1050 nm) showed sensitivity of 0.44 for occlusal and 0.55 for trilateral assessment, paired with specificity of 0.96 and 0.90, whereas SWIRR (1550 nm) showed sensitivity of 0.73 and 0.85 paired with specificity of 0.76 and 0.59. Compared to occlusal view, trilateral SWIRR view revealed ≈10% higher sensitivity and lower specificity. BWR revealed lowest sensitivity (0.30) and highest specificity (0.99). Over- and underestimation of caries demonstrated opposite trends: from 1050 to 1550 nm, overestimation of trilateral SWIRR increased (0.08-0.29), while underestimation decreased (0.15-0.06).

Conclusion

Trilateral SWIRR has higher sensitivity and lower specificity for proximal caries, than occlusal SWIRR. For trilateral SWIRR, wavelengths around 1050 nm are more suitable, while 1550 nm is better for occlusal examinations. A combination of SWIRR at 1050 and 1550 nm may exhibit a balanced sensitivity and specificity for proximal caries.
NT-proBNP levels in patients with primary hyperaldosteronism and autonomous cortisol cosecretion
Authors: Hirsch Anna , Adolf Christian , Stüfchen Isabel , Beuschlein Felix , Brüdgam Denise , Bidlingmaier Martin , Reincke Martin , Quinkler Marcus
Published: September 2024

Context

Patients with primary aldosteronism (PA) have higher cardiac comorbidities including more pronounced left ventricular hypertrophy than patients with essential hypertension.

Objective

Autonomous cortisol cosecretion (ACS) is a common subtype in PA associated with a worse metabolic profile.

Hypothesis

Autonomous cortisol cosecretion may affect myocardial parameters and result in a worse cardiac outcome compared to patients with PA and without ACS.

Methods

Three hundred and sixty-seven patients with PA undergoing 1 mg dexamethasone suppression test (DST) and echocardiography at baseline from 2 centers of the German Conn’s Registry were included. Follow-up for up to 3.8 years was available in 192 patients.

Results

Patients with PA and ACS had higher NT-proBNP levels at baseline compared to patients with PA without ACS (114 vs 75.6 pg/mL, P = .02), but showed no difference in echocardiography values. NT-proBNP levels showed a significant positive correlation (r = 0.141, P = .011) with cortisol levels after DST at baseline. In response to therapy of PA, NT-proBNP levels decreased, but remained significantly higher in patients with ACS compared to patients without ACS. At follow-up, left ventricle end-diastolic dimension (LVEDD) decreased significantly only in patients without ACS. Left atrial diameter (LAD) decreased significantly in patients without ACS and in female patients with ACS but not in male patients. Left ventricular mass index (LVMI) significantly improved in female patients without ACS but remained unchanged in female patients with ACS as well as in male patients at follow-up.

Conclusions

In patients with PA, concomitant ACS is associated with a worse cardiac profile and only partial recovery even years after initiation of targeted PA therapy.
Clinical Characteristics and Management of Patients with Heart Failure in Egypt: Real-world Insights from iCaReMe Global Registry
Authors: Zarif Bassem , Elgendy Khaled , Louis Osama , Enen Mohamed , Aboutaleb Ahmed , Samy Eman , Hassanein Abdelrahman
Published: September 2024

Background

There is a paucity of data regarding the clinical characteristics, management practices and burden of disease in patients (pts) with HF, assessment of which may help in understanding the treatment gaps and facilitating the best possible HF care.

Aim and objectives

The HF cohort of iCaReMe (NCT03549754) aims to describe the clinical profile, treatment patterns, and comorbidities in pts with HF.

Methods

This prospective, investigator-led, multinational, cloud-based, observational registry enrolled eligible adults with HF, T2D, HTN and/or CKD during their routine clinical care from Feb 2018 to Dec 2022.

A descriptive analysis of baseline clinical characteristics and treatment patterns of the Egypt-HF cohort is presented.

1400 patients were enrolled in the Egyptian cohort of this study from mainly from the National Heart Institute.

Results

This cohort enrolled 1111 pts with HF (mean±SD age 56.8±11.8 years); 60.9% were males. Overall, 66.6% (740) pts had HFrEF (≤40%), 14.8% (164) had HFmrEF (41%-49%), and 18.6% (207) had HFpEF (≥50%). The majority (68.0%) had NYHA class II HF. Only 1 pt had a BNP report (150 pg/mL) and 18 pts had proBNP levels (mean±SD, 354.4±189.6 pg/mL). Almost half pts reported a history of coronary artery disease (48.9%) and T2D (48.0%). About 20.2% pts reported a history of hospitalization.

Conclusion

The Egyptian cohort of iCaReMe registry results emphasize a high HF burden in Egypt with more than two-thirds having a reduced EF, about half of them had associated comorbidities and the number 1 co-morbidity in overall HF and HFrEF is CAD, while in HFmrEF it is HTN and in HFpEF it is T2D while the mean EF in HFpEF is 60.3%, the mean NT-Pro BNP in HF is 395.5 ng/L.
Unveiling the Genome-Wide Consequences of Range Expansion and Mating System Transitions in Primula vulgaris
Authors: Mora-Carrera Emiliano , Stubbs Rebecca L , Potente Giacomo , Yousefi Narjes , Aeschbacher Simon , Keller Barbara , Choudhury Rimjhim Roy , Celep Ferhat , Kochjarová Judita , de Vos Jurriaan M , Szövényi Peter , Conti Elena
Published: September 2024

Genetic diversity is heterogeneously distributed among populations of the same species, due to the joint effects of multiple demographic processes, including range contractions and expansions, and mating systems shifts. Here, we ask how both processes shape genomic diversity in space and time in the classical Primula vulgaris model. This perennial herb originated in the Caucasus region and was hypothesized to have expanded westward following glacial retreat in the Quaternary. Moreover, this species is a long-standing model for mating system transitions, exemplified by shifts from heterostyly to homostyly. Leveraging a high-quality reference genome of the closely related Primula veris and whole-genome resequencing data from both heterostylous and homostylous individuals from populations encompassing a wide distribution of P. vulgaris, we reconstructed the demographic history of P. vulgaris. Results are compatible with the previously proposed hypothesis of range expansion from the Caucasus region approximately 79,000 years ago and suggest later shifts to homostyly following rather than preceding postglacial colonization of England. Furthermore, in accordance with population genetic theoretical predictions, both processes are associated with reduced genetic diversity, increased linkage disequilibrium, and reduced efficacy of purifying selection. A novel result concerns the contrasting effects of range expansion versus shift to homostyly on transposable elements, for the former, process is associated with changes in transposable element genomic content, while the latter is not. Jointly, our results elucidate how the interactions among range expansion, transitions to selfing, and Quaternary climatic oscillations shape plant evolution.
Interpersonal, Community, and Societal Stressors Mediate Black–White Memory Disparities
Authors: Morris Emily P , Palms Jordan D , Scambray Kiana , Lee Ji Hyun , Sol Ketlyne , Jones Lenette M , Smith Jacqui , Kobayashi Lindsay C , Zahodne Laura B
Published: September 2024

Objectives

Structural racism creates contextual stressors that disproportionately affect Black, relative to White, older adults in the United States and may contribute to worse cognitive health. We examined the extent to which interpersonal, community, and societal stressors uniquely explain Black–White disparities in initial memory and memory change.

Methods

The sample included 14,199 non-Latino Black and White older adults (Mage = 68.32, 19.8% Black) from the U.S. Health and Retirement Study who completed psychosocial questionnaires at baseline and a word list memory task every 2 years over an 8-year period. Interpersonal, community, and societal stressors were operationalized as self-reported everyday discrimination, neighborhood physical disorder, and subjective societal status, respectively. Latent growth curves modeled longitudinal memory performance. Stressors were modeled simultaneously and allowed to correlate. Covariates included age, sex, education, wealth, parental education, and Southern residence.

Results

Compared to White participants, Black participants experienced more discrimination (β = −0.004, standard error [SE] = 0.001, p < .001), more neighborhood physical disorder (β = −0.009, SE = 0.002, p < .001), and lower perceived societal status (β = −0.002, SE = 0.001, p = .001), each of which uniquely mediated the racial disparity in initial memory. Sensitivity analyses utilizing proxy-imputed memory scores revealed an additional racial disparity in memory change, wherein Black participants evidenced a faster decline than White participants. This disparity in memory change was only uniquely mediated by more everyday discrimination among Black participants.

Discussion

Elements of structural racism may contribute to cognitive disparities via disproportionate stress experiences at multiple contextual levels among Black older adults. Future research should consider multilevel protective factors that buffer against negative impacts of racism on health.
Cross-fade sampling: extremely efficient Bayesian inversion for a variety of geophysical problems
Authors: Minson Sarah E
Published: September 2024

This paper introduces cross-fade sampling, a computationally efficient Markov Chain Monte Carlo simulation method that uses a semi-analytical approach to quickly solve Bayesian inverse problems that do not themselves have an analytical solution. Cross-fading is efficient in two ways. First, it requires fewer samples to obtain the same quality simulation of the target probability density function (PDF). Secondly, it is much faster to evaluate the posterior probability of each sample than conventional sampling methods for simulating Bayesian posterior PDFs. Conventional methods require evaluating the prior probability (which describes your a priori constraints) and data likelihood (which describes the fit between the observations and the predictions of the model) for each sample model. However, cross-fading does not require evaluating the data likelihood, meaning that ‘big data’ can be fit with zero additional computational cost. Further, the cross-fading approach can be used to calculate the marginal likelihood associated with a model design, facilitating model comparison and Bayesian model averaging. Topics covered in this paper include derivation of the cross-fade approach and how it can be used to simulate Bayesian posterior PDFs and compute the marginal likelihood, discussion of the class of problems to which cross-fading can be applied (with examples from earthquake statistics, earthquake ground motion modelling, volcanic eruption forecasting, and finite fault slip modelling), demonstration of efficiency relative to existing sampling methods and discussion of how cross-fading can be used to account for prediction errors (i.e. epistemic errors) as part of the geophysical inverse problem.
The molecular pathways leading to GABA and lactic acid accumulation in florets of organic broccoli rabe (Brassica rapa subsp. sylvestris) stored as fresh or as minimally processed product
Authors: Testone Giulio , Sobolev Anatoly Petrovich , Lambreva Maya Dimova , Aturki Zeineb , Mele Giovanni , Lamprillo Michele , Magnanimi Francesco , Serino Giovanna , Arnesi Giuseppe , Giannino Donato
Published: September 2024

In the context of organic farming, the introduction of a local product to wider markets and an evaluation of storage effects, metabolic and transcriptomic variations in two broccoli rabe genotypes from production cycles of two different years were studied by comparing florets of stored fresh (SF) and packaged (P) for 4 days with those harvested fresh from the field (H). Twenty-five hydrosoluble compounds, including amino acids, carbohydrates, and organic acids, were quantified by untargeted nuclear magnetic resonance (NMR). Principal component analysis produced a neat separation among the three commodity statuses with P being the most divergent and SF closer to H. In the packaged florets, carbohydrate levels dropped significantly (over −52%), while the levels of amino acids and organic acids varied. There was an increase in stress-responsive phenylalanine and valine (over 30%) and succinic and α-ketoglutaric acids (over 75%). Compound correlation analyses indicated a carbohydrate sink towards γ-aminobutyric acid (GABA) and lactic acid (LA) metabolism under hypoxic conditions in packaged florets. RNA-seq analysis revealed that over 4000 genes were differentially expressed in SF vs H and 8000 in P vs H. Several CAR and AA pathways were significantly enriched in S and even more significantly in P, when compared to H. A map of gene expression (175 genes) and metabolite contents (14 compounds) was constructed to elucidate the gene routes that lead to accumulation of GABA and LA, known for healthy properties, in P. WGCNA and promoter binding site analyses enabled the identification of transcription factors (bZIP, WRKY, ERF types), interactions, and targeted genes encoding key enzymes in GABA and LA accumulation.
BcWRKY25-BcWRKY33A-BcLRP1/BcCOW1 module promotes root development for improved salt tolerance in Bok choy
Authors: Wang Huiyu , Zheng Yushan , Wang Meiyun , Liu Wusheng , Li Ying , Xiao Dong , Liu Tongkun , Hou Xilin
Published: September 2024

Root development is a complex process involving phytohormones and transcription factors. Our previous research has demonstrated that BcWRKY33A is significantly expressed in Bok choy roots under salt stress, and heterologous expression of BcWRKY33A increases salt tolerance and promotes root development in transgenic Arabidopsis. However, the precise molecular mechanisms by which BcWRKY33A governs root development remain elusive. Here, we investigated the role of BcWRKY33A in both root elongation and root hair formation in transgenic Bok choy roots. Our data indicated that overexpression of BcWRKY33A stimulated root growth and stabilized root hair morphology, while silencing BcWRKY33A prevented primary root elongation and resulted in abnormal root hairs morphology. Meanwhile, our research uncovered that BcWRKY33A directly binds to the promoters of BcLRP1 and BcCOW1, leading to an upregulation of their expression. In transgenic Bok choy roots, increased BcLRP1 and BcCOW1 transcript levels improved primary root elongation and root hair formation, respectively. Additionally, we pinpointed BcWRKY25 as a NaCl-responsive gene that directly stimulates the expression of BcWRKY33A in response to salt stress. All results shed light on the regulatory mechanisms governing root development by BcWRKY25-BcWRKY33A-BcLRP1/BcCOW1 module and propose potential strategies for improving salt tolerance in Bok choy.
A Review of Cutaneous Extraintestinal Manifestations of Inflammatory Bowel Disease in Skin of Color
Authors: Odufalu Florence-Damilola , Gonzalez Sarah , Hurtado Arielle Carolina Mora , Hsiao Jennifer , Xu Mimi , Elbuluk Nada
Published: September 2024

The incidence of inflammatory bowel disease (IBD) is increasing in racial and ethnic minority groups. Cutaneous extraintestinal manifestations (EIMs) of IBD are well-known comorbid conditions that can occur in both active and quiescent IBD. Historically, cutaneous EIMs of IBD are described in White skin with a lack of literature describing these conditions in darker skin tones. This potentially creates a knowledge gap and awareness among providers in recognizing these conditions and offering therapy in a timely manner to non-White patients. This review aims to describe the cutaneous manifestations of IBD in a wide range of skin tones with several examples to improve awareness. With further awareness, this review will enable to provide equitable care to IBD patients with cutaneous EIMs.
Why States Arm and Why, Sometimes, They Do So Together
Authors: Anicetti Jonata , Krotz Ulrich
Published: September 2024

Why do states arm? And why do they, sometimes, do so together with other states? International relations and security studies scholars have long explored the causes that propel states to arm. However, the extant literature has yet to provide a coherent theoretical framework to explain arms production and collaboration. Drawing from work in eclectic theorizing, this article contributes a systematizing, integrative perspective. States arm, and sometimes arm together with other states, for a variety of reasons, often with very diverse theoretical roots and origins; frequently, causes mix, mingle, and intertwine. Two case studies serve as building blocks for our eclectic theory, illustrating and buttressing our framework. A study of Brazil’s KC-390 military transport aircraft demonstrates the value of eclectic theorizing in explaining arms production. European (fragmented) collaboration to develop a sixth-generation fighter aircraft documents the benefits of applying an eclectic theory of arms collaboration augmented with a “domain of application” approach. That is, explanations rooted in particular theoretical traditions apply and play out strengths in specific domains, and may thus complement one another to generate comprehensive explanations. Among numerous other promising domain differentiations, we distinguish here between “high-end” and “low-end” arming. Our findings have important policy implications. If states’ arming, alone or with others, is multicausal, then no single policy alone will suffice to channel, control, limit, or reduce the proliferation of weapons.
A bee’s-eye view of landscape change: differences in diet of 2 Andrena species (Hymenoptera: Andrenidae) between 1943 and 2021
Authors: Boyes Clare , Rowntree Jennifer K , Coulthard Emma
Published: September 2024

Declines in pollinating insects have been linked to changes in land cover, affecting the availability of nesting sites and floral resources. Our study is the first analysis of changes in pollen load composition of 2 mining bees, Andrena barbilabris (Kirby) and Andrena flavipes (Panzer) (Hymenoptera: Andrenidae), at the same sites in central England, over 75 years. This provides a unique opportunity to remove spatial variation and review temporal changes in pollen diet within the context of landscape change. We analyzed modern-day pollen load composition for these species and compared it with historical data from the same sites. We then examined potential links between land-use change and the bees’ diets. Both bees showed dietary flexibility and lower diet breadth for A. barbilabris, and the bees’ foraging strategies appear to have changed. Andrena flavipes collected more pollen taxa in a single load, while A. barbilabris appeared to source pollen from greater distances. Landscape changes at the studied sites have affected the nutritional environment for these bees. Our findings are supported by an existing assessment of floral resources, which found floral diversity has decreased overall in both the habitats used by these bees. However, more research is needed on the nutritional content of pollens used by these bees, both now and historically, to estimate how pollen diversity has changed. The bee’s-eye view underlines the importance of understanding how species respond to local changes so that effective conservation strategies can be developed.
Amorphous 1-propanol in interstellar ices – crystallization revisited
Authors: Hudson Reggie L
Published: September 2024

A recent publication described laboratory measurements of infrared spectra of solid 1-propanol, a likely interstellar ice component. The authors concluded that amorphous 1-propanol does not produce crystalline 1-propanol on warming and that 1-propanol remains as a solid far above its melting point. New laboratory results presented here show that both conclusions are false. A spectrum of crystalline 1-propanol is presented along with the first band strengths for two infrared features in both the amorphous and crystalline forms of the compound. Extensions and astrochemical applications are described.
Biomineralization and biomechanical trade-offs under heterogeneous environments in the eastern oyster Crassostrea virginica
Authors: Telesca Luca , Linsley Braddock K , Witek Lukasz , Hönisch Bärbel
Published: September 2024

Accurate biological models are critical to reliably predict vulnerability of marine organisms and ecosystems to rapid environmental changes. Current predictions on the biological impacts of climate change and human-caused disturbances primarily stem from controlled experiments but lack assessments of the mechanisms underlying biotic variations in natural systems, especially for habitat-forming, climate-sensitive species with key ecological roles. This study aimed to characterize and quantify spatial patterns of shell biomineralization and biomechanical properties in a key reef-building oyster, Crassostrea virginica, collected from restored reefs along natural estuarine gradients in the Hudson River Estuary (NY, USA). We characterized patterns of oyster shell deposition, structure, composition and mechanical performance at the macro- and microscale. Eastern oysters show a strong capacity for adjustments in shell biomineralization and biomechanics to maintain shell production and protective functions. We reveal salinity as a key predictor of oyster shell structure, mechanical integrity and resistance to dissolution, and describe the functional role of chalky calcite in shaping shell mechanical performance. Changes in shell production along salinity gradients indicate formation of shells with (1) high mechanical resistance but increased vulnerability to dissolution under marine conditions and (2) lower structural integrity but higher protection from dissolution under brackish conditions. Our work illustrates that biomineralization and biomechanical trade-offs may act as mechanisms in eastern oysters to maintain overall performance under heterogeneous estuarine environments and could represent a cornerstone for calcifying organisms to acclimate and maintain their ecological functions in a rapidly changing climate.
Development observed in the field of the Antarctic bivalve mollusc Aequiyoldia eightsii at Signy Island, South Orkney Islands
Authors: Peck Lloyd S , Colman Jeremy G , Clarke Andrew
Published: September 2024

The embryonic development of marine ectotherms has been shown to be strongly temperature dependent across the world's oceans. However, at the coldest sites, in the polar regions, development is even slower than would be predicted on the basis of the temperature dependence of development in warmer waters, and this is thought to be a consequence of changes in physical characteristics of cytoplasm near 0 °C—such as viscosity and osmolyte packing that slow protein folding and increase the likelihood of interference by charged particles, and their effect on protein synthesis. The overwhelming majority of studies of rates of embryonic development have been laboratory-based, with animals either collected directly from the sea and spawned in the laboratory or held first in the laboratory and preconditioned to set environments before spawning. Few studies have assessed development from regularly collected samples and assessed field development, especially from polar latitudes. Here we present data for the Antarctic bivalve mollusc Aequiyoldia eightsii, tracking its development from spawning on 25/26 May to hatching of pelagic veligers on 12 June and the disappearance of pediveliger larvae from the water column at the end of September or early October, 108–114 days later. Larval dry mass was constant at 16.7 µg (SE = 0.19) across the pelagic phase, except for the initial few days after hatching when it was 9.55 µg (SE = 0.60). The difference was likely the calcification of the larval shell. The development time to trochophore was 189 h, and this was in line with previous studies showing larval development at temperatures around 0 °C is around 4–22 times slower than would be predicted from the general effect of temperature on development rates.
The interplay between peptides and RNA is critical for protoribosome compartmentalization and stability
Authors: Codispoti Simone , Yamaguchi Tomoko , Makarov Mikhail , Giacobelli Valerio G , Mašek Martin , Kolář Michal H , Sanchez Rocha Alma Carolina , Fujishima Kosuke , Zanchetta Giuliano , Hlouchová Klára
Published: September 2024

The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core. This research highlights the significance of rPeptides in stability and coacervation of two distinct protoribosomal evolutionary stages. The 617nt ‘big’ protoribosome model, which associates with rPeptides specifically, exhibits a structurally defined and rigid nature, further stabilized by the peptides. In contrast, the 136nt ‘small’ model, previously linked to peptidyltransferase activity, displays greater structural flexibility. While this construct interacts with rPeptides with lower specificity, they induce coacervation of the ‘small’ protoribosome across a wide concentration range, which is concomitantly dependent on the RNA sequence and structure. Moreover, these conditions protect RNA from degradation. This phenomenon suggests a significant evolutionary advantage in the RNA–protein interaction at the early stages of ribosome evolution. The distinct properties of the two protoribosomal stages suggest that rPeptides initially provided compartmentalization and prevented RNA degradation, preceding the emergence of specific RNA–protein interactions crucial for the ribosomal structural integrity.
Stereotactic radiosurgery for 1–10 brain metastases to avoid whole-brain radiotherapy: Results of the CYBER-SPACE randomized phase 2 trial
Authors: El Shafie Rami A , Bernhardt Denise , Welzel Thomas , Schiele Annabella , Schmitt Daniela , Thalmann Paul , Erdem Sinem , Paul Angela , Höne Simon , Lang Kristin , König Laila , Weykamp Fabian , Adeberg Sebastian , Lentz-Hommertgen Adriane , Jäkel Cornelia , Bozorgmehr Farastuk , Nestle Ursula , Thomas Michael , Sander Anja , Kieser Meinhard , Debus Jürgen , Rieken Stefan
Published: September 2024

Background

Stereotactic radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity, and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1–10 BM.

Methods

Patients with 1–10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of >10 new BM, leptomeningeal disease, or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life.

Results

A total of 202 patients were randomized; SPACE n = 99, MPRAGE n = 103. Twelve-month WBRTi-free survival was 77.1% (95% CI: 69.5%–83.1%) overall, 78.5% (95% CI: 66.7%–86.5%) for SPACE, and 76.0% (95% CI: 65.2%–83.9%) for MPRAGE (hazard ratio [HR] = 0.84, 95% CI: 0.43–1.63, P = .590). Patients with 5–10 BM had shorter WBRTi-free survival (HR = 3.13, 95% CI: 1.53–6.40, P = .002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR = 1.10, 95% CI: 0.78–1.56, P = .585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status >80% (HR = 0.51, 95% CI: 0.33–0.77, P = .002) and concurrent immunotherapy (HR = 0.34, 95% CI: 0.23–0.52, P < .001).

Conclusions

The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1–10 BM.
Development of an intraventricular adeno-associated virus-based labeling strategy for glioblastoma cells nested in the subventricular zone
Authors: Lombard Arnaud , Isci Damla , Reuter Gilles , Di Valentin Emmanuel , Hego Alexandre , Martin Didier , Rogister Bernard , Neirinckx Virginie
Published: September 2024

Background

Glioblastoma (GBM) is a dreadful brain tumor, with a particular relationship to the adult subventricular zone (SVZ) that has been described as relevant to disease initiation, progression, and recurrence.

Methods

We propose a novel strategy for the detection and tracking of xenografted GBM cells that are located in the SVZ, based on an intracerebroventricular (icv) recombinant adeno-associated virus (AAV)-mediated color conversion method. We used different patient-derived GBM stem-like cells (GSCs), which we transduced first with a retroviral vector (LRLG) that included a lox-dsRed-STOP-lox cassette, upstream of the eGFP gene, then with rAAVs expressing the Cre-recombinase. Red and green fluorescence is analyzed in vitro and in vivo using flow cytometry and fluorescence microscopy.

Results

After comparing the efficiency of diverse rAAV serotypes, we confirmed that the in vitro transduction of GSC-LRLG with rAAV-Cre induced a switch from red to green fluorescence. In parallel, we verified that rAAV transduction was confined to the walls of the lateral ventricles. We, therefore, applied this conversion approach in 2 patient-derived orthotopic GSC xenograft models and showed that the icv injection of an rAAV-DJ-Cre after GSC-LRLG tumor implantation triggered the conversion of red GSCs to green, in the periventricular region. Green GSCs were also found at distant places, including the migratory tract and the tumor core.

Conclusions

This study not only sheds light on the putative outcome of SVZ-nested GBM cells but also shows that icv injection of rAAV vectors allows to transduce and potentially modulate gene expression in hard-to-reach GBM cells of the periventricular area.
Pretreatment Computed Tomography–Defined Sarcopenia, Treatment-Associated Muscle Loss, and Survival in Patients With Cervical Cancer: A Systematic Review and Meta-Analysis
Authors: Tian Mengxing , Xu Huiting , Wang Hongbin , Wang Huifen , Dai Zhu , Ding Chenchen , Guo Huan , Jin Xin
Published: September 2024

Context

Sarcopenia has been identified as a potential predictor of poor prognosis in various types of cancer. However, the impact of pretreatment sarcopenia and the reduction of skeletal muscle mass during treatment on survival outcomes of patients with cervical cancer is still not well understood.

Objective

This meta-analysis was conducted to investigate the impact of pretreatment sarcopenia and treatment-associated muscle loss on survival outcomes in patients with cervical cancer.

Data Sources

The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies exploring the relationship between muscle loss and the prognosis of cervical cancer until January 1, 2023.

Data Extraction

The hazard ratios (HRs) and 95% CIs for overall survival (OS) and progression-free survival (PFS) were extracted.

Data Analysis

The data were analyzed using R software. The studies’ quality was assessed using the Quality in Prognostic Studies tool. Twelve observational studies involving 1498 patients with cervical cancer were included in the analysis, with a prevalence of sarcopenia ranging from 24.8% to 57.5%. Sarcopenia was an independent predictor of poor OS (HR, 1.68; 95% CI, 1.28–2.21; P < .01) and PFS (HR, 1.53; 95% CI, 1.19–1.98; P < .01) in patients with cervical cancer. Additionally, the decrease in skeletal muscle during treatment was also significantly related to the OS (HR, 4.46; 95% CI, 2.87–6.94; P < .01) and PFS (HR, 2.89; 95% CI. 1.83–4.55; P < .01).

Conclusions

The prevalence of pretreatment sarcopenia was high among patients with cervical cancer. Pretreatment sarcopenia and skeletal muscle loss during treatment both negatively affected prognosis in cervical cancer.
Ailing Empires: The Morphine Issue in Sino-foreign Relations at the Dawn of the Twentieth Century
Authors: Huang Yun
Published: September 2024

This article explores morphine as an issue in the foreign relations between China and several colonial powers, notably Britain and the USA in the 1900s. The drug diplomacy on morphine in Sino-foreign relations during this period is mainly reflected in three events: the revisions of relevant commercial treaties in 1902–4, the negotiations about morphine import control in 1906–8, and related discussions at the Shanghai Opium Commission of 1909. A mixture of cooperation and competition marked the positions of the participating empires on morphine. The serpentine process of drug diplomacy on the morphine issue in the 1900s indicates the struggle of the Chinese authorities to assert themselves under the hegemony of the colonial powers. It also reflected the changing power balance and the ailing features of the empires at the dawn of the twentieth century.
Holistic Review in Applicant Selection: A Scoping Review
Authors: Gottlieb Michael , Davenport Dayle , Landry Adaira , Bailey Jacob , Westrick Jennifer , Daniel Michelle
Published: September 2024

Purpose

To avoid overreliance on metrics and better identify candidates who add value to the learning environment, some medical schools and residency programs have begun using holistic review for screening and selection, but limited data support or refute this use. This scoping review examines holistic review definitions and practice in medical education, summarizes research findings, and identifies gaps for future research.

Method

The authors searched 7 databases using a comprehensive search strategy including the keywords holistic, attributes, mission-based, mission-centric, and socially accountable for articles on holistic review within undergraduate medical education (UME) and graduate medical education (GME) published from database inception through July 5, 2024. Author pairs independently screened articles for inclusion and extracted data. Discrepancies were resolved via discussion. Quantitative and qualitative synthesis was performed.

Results

6,511 articles were identified, with 33 included in this review. Twenty-five studies (76%) focused exclusively on GME, with only a few assessing holistic review in UME. Holistic review was implemented at 3 main stages: screening, interviewing, and ranking. Common rationales included service patterns, patient-physician identity concordance, enhancing patient trust, professional advocacy, and educational benefits. Holistic review elements varied, with most falling within the Association of American Medical Colleges experiences, attributes, and metrics framework. Nearly all studies reported an increase in the percentage of underrepresented in medicine trainees interviewed or selected. Several studies also demonstrated increases in other groups (e.g., women, lower socioeconomic status). Many studies included additional interventions to promote diversity, limiting the ability to assess holistic review in isolation.

Conclusions

This scoping review summarizes the literature on the rationale, development and implementation process, structure and components, outcomes assessed, barriers, and strategies for success for holistic review. This work can inform institutions and departments seeking to develop or refine their own holistic review systems and serve as a nidus for future research.
Current Science and Practice of Surgical and Nonsurgical Opportunities for Ovarian Cancer Prevention
Authors: MacArthur Emily , Stone Rebecca
Published: September 2024

Due to improved understanding of ovarian cancer pathogenesis, we have an unprecedented chance to decrease the burden of disease by maximizing opportunities for prevention. Innovations in surgical options for prevention stem from the discovery that many cases directly or indirectly arise from the fallopian tube. Surgical prevention with salpingectomy alone decreases risk by ≥50%. Effective hormonal and nonhormonal chemopreventive agents are also available. Risk stratification is key to ensuring that options for prevention are appropriately matched to individual risk profile. This evidence-based review provides a critical appraisal of the translational health research endeavors supporting ovarian cancer prevention in clinical practice.
Early Bone Ischemia in Pediatric Acute Hematogenous Osteomyelitis and its Association With Progression to Chronic Osteomyelitis: New Insights From Gadolinium-enhanced Subtraction MRI
Authors: Al-Alawi Ahmed , Raniga Sameer , Michelow Ian C. , Al-Yazidi Laila , Alhinai Zaid
Published: September 2024

Background:

Acute hematogenous osteomyelitis (AHO), the most common osteoarticular infection in children, carries a significant risk for chronic complications. Predicting chronic complications early in the course of disease is challenging. The underlying pathogenesis of complications is not fully understood.

Methods:

Children who presented to Sultan Qaboos University Hospital, Muscat, Oman between January 2015 and April 2022 for AHO were identified by a search of magnetic resonance imaging (MRI) records. Children between 1 month and 18 years of age who did not meet exclusion criteria, and whose MRI also included gadolinium-enhanced subtraction (GES) sequences were included in the analysis. Outcomes were compared between patients who showed early evidence of bone ischemia and those who did not.

Results:

The analysis included 11 children who had GES MRI sequences from among 18 AHO cases in total. Median age was 5 years (IQR, 4–9), and 82% were males. Median duration of symptoms at presentation was 5 days (IQR, 3–7). GES sequences showed early bone ischemia in 6 of 11 (55%) patients. Patients with early bone ischemia were treated with significantly longer durations of IV antibiotics (median 23 vs. 10 days, P = 0.017) and oral antibiotics (median 134 vs. 29 days, P = 0.004), and required more surgical debridements (median 3 vs. 0 debridements, P = 0.017). Chronic osteomyelitis only developed among patients with early bone ischemia (5/6 vs. 0/5, P = 0.015).

Conclusions:

In pediatric AHO, GES MRI sequences revealed early bone ischemia in a significant proportion of patients. Early bone ischemia was strongly associated with progression to chronic osteomyelitis.
Genomically-supported Redefinition of an Outbreak in a Pediatric Unit Caused by bla VIM-harboring Klebsiella michiganensis
Authors: López-Camacho Elena , Aguilera-Alonso David , Buenestado-Serrano Sergio , Marín Mercedes , Molero-Salinas Andrea , López Fresneña Nieves , Cercenado Emilia , Vicente Teresa , Herrera Laura , Slocker-Barrio María , Muñoz Patricia , Saavedra Lozano Jesús , Navarro Gómez María Luisa , García de Viedma Darío , Pérez-Lago Laura
Published: September 2024

Background:

Klebsiella michiganensis, a member of the Klebsiella oxytoca complex, is an emerging nosocomial pathogen known to frequently carry plasmids with antibiotic-resistance genes, including carbapenemases. Using genomics, this study redefined an outbreak alert of K. michiganensis carrying a blaVIM carbapenemase in a pediatric ward in a Spanish hospital.

Methods:

A total of 31 isolates of Verona integron-encoded metallo-β-lactamase (VIM)-carbapenemase K. oxytoca from suspected outbreak cases and unrelated controls from 2015 to 2022 were analyzed. Whole-genome sequencing (both short and long reads) was applied to determine phylogenetic relationships based on single-nucleotide polymorphisms (SNPs) and identify plasmids and antimicrobial resistance genes.

Results:

The sequences from 12 isolates identified in 2021 showed pairwise SNP distances ranging from 0 to 16 SNPs, confirming the outbreak. Examination of isolates before and after the study period revealed 7 additional cases, 2 in 2020 and 5 in 2022. The outbreak comprised 18 isolates from 17 patients in 3 different pediatric wards, together with 1 environmental sample. In all outbreak isolates, the bla

VIM-1
gene was located within a gene cassette carried by a class 1 integron on an IncFIB(pQil) plasmid. A genomic network based on SNPs revealed 5 unsampled intermediate nodes, suggesting additional subclones that may have involved healthcare staff, patient relatives or environmental reservoirs. Blood and rectal isolates obtained from the same patient were positioned on separate branches of the network, making a direct evolutionary pathway between them unlikely.

Conclusions:

Our study redefined the full extent of this K. michiganensis-VIM outbreak and highlights the critical importance of genomic analysis in accurately understanding outbreaks in healthcare settings.
Racial and Ethnic Disparities in Neonatal Sepsis
Authors: Nandakumar Vanishree , Hazzaa Shady , Saker Firas , Aly Hany , Mohamed Mohamed A.
Published: September 2024

Background:

Sepsis is a significant health burden in the neonatal population. Although disparities in neonatal care have been reported, there are no data on racial/ethnic disparities in the context of sepsis. Therefore, we aimed to assess racial/ethnic disparities in the prevalence and outcomes of neonatal sepsis.

Methods:

The national inpatient Kids’ Inpatient Database produced by the Healthcare Cost and Utilization Project was used for the year 2019. The International Classification of Diseases, 10th revision codes were used to identify the primary outcome of the neonates diagnosed with sepsis. The χ2 and Fisher tests were used to calculate odds ratios for categorical variables, and logistic regression was performed to calculate adjusted odds ratio (aOR) to account for confounders in neonatal sepsis.

Results:

Of the total 3,512,817 patients, 202,103 patients with neonatal sepsis were identified across all racial and ethnic groups. Overall prevalence was statistically significant in Black [aOR, 1.13 (95% confidence interval [CI], 1.10–1.17)], Hispanic [aOR, 1.19 (95% CI, 1.15–1.22)], Asian/Pacific Islander [aOR, 1.10 (95% CI, 1.05–1.16)] and Native Americans [aOR, 1.17 (95% CI, 1.04–1.31)] compared with Whites. In Black infants, the OR for the overall mortality was 1.35 (95% CI, 1.28–1.42), and sepsis-related mortality was 1.20 (95% CI, 1.06–1.35) compared to Whites.

Conclusions:

Although the prevalence of sepsis is marginally higher in Hispanic infants compared with Whites, the overall and sepsis-related mortalities are the highest in Black infants compared with all races and ethnic groups.
Improving the evaluation of novice advanced practice nurse transition
Authors: Wyly Donna R.
Published: September 2024

Background:

Novice advanced practice registered nurses (RNs) experience decreased self-confidence, anxiety, and identity confusion in their first year of practice, which leads to poor job satisfaction and turnover. Advanced practice RN fellowship programs, developed to bridge the gap from the RN to the advanced practice role, lack standardized measures for program evaluation.

Local Problem:

A large Midwestern pediatric hospital's advanced practice nurse fellowship program lacks a structured program evaluation.

Methods:

A quasi-experimental evidence-based improvement project was implemented to evaluate fellowship program outcomes for novice nurse practitioner transition and retention.

Interventions:

All novice advanced practice RNs (APRNs) were enrolled in the site's 12-month APRN fellowship program. The transition experiences of enrollees who completed the fellowship program were assessed using the novice nurse practitioner role transition scale. In addition, role transition scores were compared for two subgroups: fellows in acute care and fellows in primary care roles. Fellowship participant retention 1 year after hire was measured.

Results:

Postintervention data showed that most fellowship graduates had a positive transition experience as evidenced by at least a 4.33/6.0 mean total novice nurse practitioner role transition score. There was not a statistically significant difference between the transition scores of the acute care fellows and primary care fellows.

Conclusions:

The APRN fellowship program was effective in promoting a successful role transition from RN to novice APRN. Similar APRN fellowship programs may benefit from using this tool for program evaluation.
Hair Today, OR Tomorrow
Authors: Shah Rahul D. , Grither Allie , Cohen Stephanie G. , Morales-Perez Liliana , Rabiner Joni , Riera Antonio
Published: September 2024

Point-of-care ultrasound (POCUS) can expedite the diagnosis of pediatric abdominal pathologies including appendicitis and intussusception. In this patient series, we present cases from multiple pediatric emergency departments that demonstrate the use of POCUS in the diagnosis of trichobezoars in children. POCUS findings include the presence of an intragastric hyperechoic mass or a hyperechoic arch and associated posterior acoustic shadowing. These findings in the appropriate clinical context should prompt further diagnostic imaging and/or surgical consultation for removal.