bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients
Authors: Ricklefs Franz L , Wollmann Kathrin , Salviano-Silva Amanda , Drexler Richard , Maire Cecile L , Kaul Michael G , Reimer Rudolph , Schüller Ulrich , Heinemann Sarina , Kolbe Katharina , Mummert Tobias , Glatzel Markus , Peine Sven , Gempt Jens , Westphal Manfred , Dührsen Lasse , Lamszus Katrin 
Published: April 2024

Abstract

Background
Extracellular vesicles (EVs) obtained by noninvasive liquid biopsy from patient blood can serve as biomarkers. Here, we investigated the potential of circulating plasma EVs to serve as an indicator in the diagnosis, prognosis, and treatment response of glioblastoma patients.

Methods
Plasma samples were collected from glioblastoma patients at multiple timepoints before and after surgery. EV concentrations were measured by nanoparticle tracking analysis and imaging flow cytometry. Tumor burden and edema were quantified by 3D reconstruction. EVs and tumors were further monitored in glioma-bearing mice.

Results
Glioblastoma patients displayed a 5.5-fold increase in circulating EVs compared to healthy donors (P &lt; .0001). Patients with higher EV levels had significantly shorter overall survival and progression-free survival than patients with lower levels, and the plasma EV concentration was an independent prognostic parameter for overall survival. EV levels correlated with the extent of peritumoral fluid-attenuated inversion recovery hyperintensity but not with the size of the contrast-enhancing tumor, and similar findings were obtained in mice. Postoperatively, EV concentrations decreased rapidly back to normal levels, and the magnitude of the decline was associated with the extent of tumor resection. EV levels remained low during stable disease, but increased again upon tumor recurrence. In some patients, EV resurgence preceded the magnetic resonance imaging detectability of tumor relapse.

Conclusions
Our findings suggest that leakiness of the blood-brain barrier may primarily be responsible for the high circulating EV concentrations in glioblastoma patients. Elevated EVs reflect tumor presence, and their quantification may thus be valuable in assessing disease activity.
Preoperative growth dynamics of untreated glioblastoma: Description of an exponential growth type, correlating factors, and association with postoperative survival
Authors: Feucht Daniel , Haas Patrick , Skardelly Marco , Behling Felix , Rieger David , Bombach Paula , Paulsen Frank , Hoffmann Elgin , Hauser Till-Karsten , Bender Benjamin , Renovanz Mirjam , Niyazi Maximilian , Tabatabai Ghazaleh , Tatagiba Marcos , Roder Constantin 
Published: April 2024

Abstract

Background
Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival.

Methods
We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable.

Results
Out of 749 patients screened, 13 had ≥3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = −0.59, P &lt; .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection.

Conclusions
Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.
Effects of group size on movement patterns and clustering dynamics in rats
Authors: Monfils Marie-H , Pasala Michael , Malone Cassidy , Agee Laura , Roquet Rheall , Cormack Lawrence 
Published: April 2024

Abstract
Environment is a determining factor that can facilitate or hinder social interactions. A precursor to meaningfully engaging with conspecifics is being exposed to opportunistic encounters with others. Increasing the number of individuals in a given space (thus increasing density) would, statistically speaking, increase the likelihood of accidental encounters. This might have consequences on the formation of social networks—an idea that has not reliably been explored. If true, we would expect that increasing density would lead to an increase in the number and the duration of ‘clusters’ of animals. Here, we examined whether varying the number of rats in an open field environment differentially affected their movement dynamics or their propensity to aggregate into clusters and, if so, whether such effects are dependent solely on statistical factors due to increases in density, the potential for actively-sought social interactions, or both. We found that the number of rats in an environment impacts ambulation speed, distance traveled, cluster formation and approaches, and that number and duration of clusters are highly dependent on the propensity for the rats to engage in social interactions.
A secreted bacterial protein protects bacteria from cationic antimicrobial peptides by entrapment in phase-separated droplets
Authors: Ostan Nicholas K H , Cole Gregory B , Wang Flora Zhiqi , Reichheld Sean E , Moore Gaelen , Pan Chuxi , Yu Ronghua , Lai Christine Chieh-Lin , Sharpe Simon , Lee Hyun O , Schryvers Anthony B , Moraes Trevor F 
Published: April 2024

Abstract
Mammalian hosts combat bacterial infections through the production of defensive cationic antimicrobial peptides (CAPs). These immune factors are capable of directly killing bacterial invaders; however, many pathogens have evolved resistance evasion mechanisms such as cell surface modification, CAP sequestration, degradation, or efflux. We have discovered that several pathogenic and commensal proteobacteria, including the urgent human threat Neisseria gonorrhoeae, secrete a protein (lactoferrin-binding protein B, LbpB) that contains a low-complexity anionic domain capable of inhibiting the antimicrobial activity of host CAPs. This study focuses on a cattle pathogen, Moraxella bovis, that expresses the largest anionic domain of the LbpB homologs. We used an exhaustive biophysical approach employing circular dichroism, biolayer interferometry, cross-linking mass spectrometry, microscopy, size-exclusion chromatography with multi-angle light scattering coupled to small-angle X-ray scattering (SEC–MALS-SAXS), and NMR to understand the mechanisms of LbpB-mediated protection against CAPs. We found that the anionic domain of this LbpB displays an α-helical secondary structure but lacks a rigid tertiary fold. The addition of antimicrobial peptides derived from lactoferrin (i.e. lactoferricin) to the anionic domain of LbpB or full-length LbpB results in the formation of phase-separated droplets of LbpB together with the antimicrobial peptides. The droplets displayed a low rate of diffusion, suggesting that CAPs become trapped inside and are no longer able to kill bacteria. Our data suggest that pathogens, like M. bovis, leverage anionic intrinsically disordered domains for the broad recognition and neutralization of antimicrobials via the formation of biomolecular condensates.
HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir
Authors: Kazaoka Akira , Fujimori Sota , Yamada Yushiro , Shirayanagi Tomohiro , Gao Yuying , Kuwahara Saki , Sakamoto Naoki , Susukida Takeshi , Aoki Shigeki , Ito Kousei 
Published: April 2024

Abstract
Specific human leukocyte antigen (HLA) polymorphisms combined with certain drug administration strongly correlate with skin eruption. Abacavir hypersensitivity (AHS), which is strongly associated with HLA-B*57:01, is one of the most representative examples. Conventionally, HLA transmits immunological signals via interactions with T cell receptors on the cell surface. This study focused on HLA-mediated intracellular reactions in keratinocytes that might determine the onset of skin immunotoxicity by drug treatments. Abacavir exposure resulted in keratinocytes expressing HLA-B*57:01 exhibiting endoplasmic reticulum (ER) stress responses, such as immediate calcium release into the cytosol and enhanced HSP70 expression. In contrast, keratinocytes expressing HLA-B*57:03 (closely related to HLA-B*57:01) did not show these changes. This indicated that HLA-B*57:01 has a specific intracellular response to abacavir in keratinocytes in the absence of lymphocytes. Furthermore, abacavir exposure in HLA-B*57:01-expressing keratinocytes elevated the expression of cytokines/chemokines such as interferon-γ, interleukin-1β, and CCL27, and induced T lymphoblast migration. These effects were suppressed by ER stress relief using 4-phenylbutyrate (4-PB). HLA-B*57:01-transgenic mice also exhibited ER stress in epidermal areas following abacavir administration, and abacavir-induced skin toxicity was attenuated by the administration of 4-PB. Moreover, abacavir bound to HLA-B*57:01 within cells and its exposure led to HLA-B*57:01 protein aggregation and interaction with molecular chaperones in the ER of keratinocytes. Our results underscore the importance of HLA-mediated intracellular stress responses in understanding the onset of HLA-B*57:01-mediated AHS. We provide the possibility that the intracellular behavior of HLA is crucial for determining the onset of drug eruptions.
Efficacy of Rehabilitative Techniques on Pain Relief in Patients With Vulvodynia: A Systematic Review and Meta-Analysis
Authors: Calafiore Dario , Marotta Nicola , Curci Claudio , Agostini Francesco , De Socio Rita Ilaria , Inzitari Maria Teresa , Ferraro Francesco , Bernetti Andrea , Ammendolia Antonio , de Sire Alessandro 
Published: April 2024

Abstract

Objective
Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia.

Methods
On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale.

Results
Meta-analysis showed that all these rehabilitative approaches had an overall effect size of −1.43 (95% CI = −2.69 to −0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = −2.36; 95% CI = −3.83 to −0.89) and extracorporeal shockwave therapy (effect size = −2.94; 95% CI = −4.31 to −1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies.

Conclusion
Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future.

Impact
This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia.
The Heterogeneous Effects of Government Spending: It’s All About Taxes
Authors: Ferriere Axelle , Navarro Gaston 
Published: April 2024

Abstract
Historically, large changes in U.S. government spending induced fiscal efforts that were not all alike, with some using more progressive taxes than others. We develop a heterogeneous-agent New Keynesian model to analyse how the distribution of taxes across households shapes spending multipliers. The model yields empirically realistic distributions in marginal propensities to consume and labour elasticities, which result in lower responsiveness to tax changes for higher-income earners. In turn, multipliers are larger when spending is financed with higher tax progressivity—that is, when the tax burden falls more heavily on higher-income earners. This result is historically material. We estimate that, on average, tax rates increased more for top-income than for bottom-income earners after a spending shock. Thus, the typical U.S. spending shock was financed with higher tax progressivity. We further exploit the historical variation in the financing of spending to estimate progressivity-dependent multipliers, which we find consistent with the model.
Nutrition knowledge, attitudes, and perceptions of Greek menopausal women
Authors: Papadima Evgenia-Ioanna , Vassilakou Tonia , Grigoriadis Themos , Boutsiadis Anastasios , Ivanidou Sofia , Kalampalikis Andreas , Michala Lina 
Published: April 2024

Abstract

Objective
Nutritional guidelines for postmenopausal women differ. This study aimed to assess postmenopausal women's knowledge, beliefs, and practices regarding nutrition during menopause and their dietary habits.

Methods
This cross-sectional study was conducted in a menopause clinic, and data from 105 women were analyzed. A nutrition knowledge, attitudes, and perceptions (KAP) questionnaire was designed, structured, and piloted before implementation, based on the Hellenic dietary guidelines. International Physical Activity Questionnaire—Greek version, MedDietScore, and Menopause-specific Quality of Life questionnaires were administered.

Results
The mean ± SD age of the women was 56.9 ± 4.6 years. The mean ± SD KAP score was 12.2 ± 3.5. Those who lived in rural areas had lower KAP scores than those who lived in urban areas (P = 0.004). Of all the women, 74.5% knew the Mediterranean diet pyramid, whereas 9.8% knew the Hellenic dietary guidelines. Women who had read the guidelines showed better knowledge of Mediterranean diet food groups (Pearson, 0.309; P = 0.039). Knowledge of dairy services was correlated with consumption of dairy products (P = 0.002). Furthermore, 76.4% were willing to participate in nutrition education programs. The International Physical Activity Questionnaire score was positively correlated with years of smoking (P = 0.002). Physical activity correlated with adherence to the Mediterranean diet (P = 0.044).

Conclusions
The majority of postmenopausal Greek women in this study were unaware of the Hellenic dietary guidelines. In general, women's knowledge of nutrition during menopause was moderate. Greek postmenopausal women are willing to participate in nutrition education programs, which should raise awareness of healthy lifestyles through nutrition, exercise, and smoking cessation.
Emerging Clinical Features of Acute Mastoiditis in Israel: A Registry Based Cohort
Authors: Samuel Orit , Saliba Walid , Stein Nili , Shiner Yotam , Cohen-Kerem Raanan 
Published: April 2024

Background and Objectives:
Acute mastoiditis (AM) is a severe infection in the young population, with possible life-threatening complications. This study aimed to characterize AM presentation, symptoms and signs, complications, and management, over a period of 10 years.

Methods:
This large-scale population-based cohort studied “Clalit Health Care” records, to include patients <18 years diagnosed with AM, hospitalized between the years 2008–2018. After validation, we investigated clinical symptoms and signs, pneumococcal vaccination status, complications, laboratory and microbiological parameters, imaging, antibiotic treatment and surgical interventions.

Results:
AM was diagnosed in 1189 patients, mean age of 2.71 years and 591 (49.71%) were female. Most presented with protrusion of pinna (83.1%), retro auricular redness (73.5%) and fever (71.8%). Patients <2 years of age had more symptoms (3.8 ± 1.4, opposed to 3.6 ± 1.5, P = 0.006) and showed higher white blood cell count and C-reactive protein values. Local and intracranial complications occurred in 233 (20.8%) and 75 (6.5%) patients, respectively. Complications were associated with increased white blood cell count and C-reactive protein and related to bacterial type, specifically Fusobacterium necrophorum (P < 0.0001), for which 50% had an intracranial complication. Between the years 2008–2018, Streptococcus pneumoniae-positive cultures decreased (30.9% to 10.3%, P > 0.0001) as opposed to group-A Streptococcus (10.9% to 30.9%, P = 0.002).

Conclusions:
This study shows a difference in AM appearance in the <2 years population and the association between white blood cell count, C-reactive protein and microbiology results with the occurrence of a complication. This may play a role in the management process, such as imaging and intervention needs. Although performed during the pneumococcal vaccine era, the disease microbiology was shown to change significantly throughout the study.
Is beauty worth the risk? Self-confidence is the key motivating factor driving tanning bed use among undergraduate students at South Dakota universities
Authors: Newton Jazmin , Ochoa Lauren , Reinschmidt Aly , Vassar John , Wellman Allen , Vargas Minga , Kenyon DenYelle , Frohm Marcus 
Published: April 2024

Background:
Exposure to ultraviolet radiation is a leading risk factor for developing all types of skin cancer. In the United States, an estimated 7.8 million young adults engage in indoor tanning.

Objective:
Here, it is hypothesized that certain populations of students at undergraduate universities, namely sorority members, have a greater frequency of tanning bed usage than other groups of students and that regardless of sorority status, the most important motivating factor will be the intent to enhance one’s appearance.

Methods:
Undergraduate students at 2 state-funded universities were recruited for participation in this institutional review board-exempt survey via distribution to e-mail addresses and social media accounts affiliated with student organizations/clubs.

Results:
Among all respondents, the most common motivating factors for tanning bed use were the perception of improved self-appearance and boosted self-confidence. Female sorority members were more likely to use tanning beds and also more likely to report being motivated by enhanced appearance and self-confidence, than their female counterparts who were not sorority members.

Limitations:
The sample size (n = 321) and population of this study allows data to only be generalizable to surrounding states with similar demographics. The findings of this study are subject to recall bias as the data is self-reported.

Conclusion:
Tanning bed use remains a popular practice among young people. Understanding motivations for tanning bed use among populations at increased risk of partaking in this behavior allows for educating these groups on the risks associated with ultraviolet radiation exposure. It is crucial that providers continue to promote skin health and take steps to dissuade detrimental practices and possible habit-forming behaviors at the individual and state levels.
Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss
Authors: Harrison Megan S. , Driscoll Brittany G. , Farnsworth Jason , Hinton Ashley , Peppi Marcello , McLean Will , Parham Kourosh 
Published: April 2024

Hypothesis
Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss.

Background
Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model.

Methods
Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained.

Results
All three doses induced an N-glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs.

Conclusion
The ~134-kDa prestin burst induced after CDX administration is N-glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.
Thrombocytopenia and Adverse Bleeding Events in Neonatal Lumbar Punctures in the Emergency Department
Authors: Le Duyen My , Vezzetti Robert , Earp Ada , Jung Alexandra , Aufricht Graham 
Published: April 2024

Objective
Lumbar punctures are performed as part of a routine evaluation of neonates with fever in the emergency department. Current recommendations regarding performing a lumbar puncture in the presence of thrombocytopenia exist for children with leukemia and other cancers; however, there are no such recommendations for the general neonatal population. This study assesses the frequency of thrombocytopenia and adverse bleeding events in neonates who undergo a lumbar puncture to determine whether a complete blood count, and specifically the platelet count, should be reviewed before performing the lumbar puncture.

Methods
This is a retrospective chart review of neonates 30 days or younger presenting to a single freestanding pediatric emergency department who received a lumbar puncture over the course of 11 years. The complete blood count was reviewed for thrombocytopenia, determined to be platelet count of less than 150,000/μL. The chart was reviewed for any documented adverse bleeding events associated with the lumbar puncture.

Results
A total population of 2145 was studied with 56 patients determined to be thrombocytopenic. Seven total bleeding events were identified: 1 in the thrombocytopenic group and 6 in the nonthrombocytopenic group. All bleeding events were deemed to be clinically significant, either resulting in prolonged hospital stay or required further workup and medical intervention. The percentage of clinically adverse bleeding events that were related to the lumbar puncture was 0 (0.0%; 95% confidence interval, 0.0%–6.4%) and 2 (0.1%; 95% confidence interval, 0.0%–0.3%) (P = 1.0) in the thrombocytopenic and nonthrombocytopenic groups, respectively.

Conclusions
Our results demonstrated a very low risk of bleeding events associated with lumbar punctures in neonates, with no increased risk in the thrombocytopenic group. As such, we conclude that waiting for the results of a complete blood count before performing the lumbar puncture in neonates without a known bleeding disorder is unnecessary.