bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone H3E50K remodels chromatin to confer oncogenic activity and support an EMT phenotype
Authors: Sad Kirti , Fawwal Dorelle V , Jones Celina Y , Hill Emily J , Skinner Katie T , Adams Miranda L , Lustenberger Severin , Lee Richard S , Lohano Sandhya V , Elayavalli Satvik R , Farhi Jonathan , Mehta Christina C , Lemon Laramie D , Fasken Milo B , Hong Andrew L , Sloan Steven A , Corbett Anita H , Spangle Jennifer M
Published: February 2025

Sequencing of human patient tumors has identified recurrent missense mutations in genes encoding core histones. We report that mutations that convert histone H3 amino acid 50 from a glutamate to a lysine (H3E50K) support an oncogenic phenotype. Expression of H3E50K is sufficient to transform human cells as evidenced by an increase in cell migration and invasion, and an increase in proliferation and clonogenicity. H3E50K also increases the invasive phenotype in the context of co-occurring BRAF mutations, which are present in patient tumors characterized by H3E50K. H3E50 lies on the globular domain surface in a region that contacts H4 within the nucleosome. We find that H3E50K selectively increases chromatin accessibility and perturbs proximal H3 post-translational modifications including H3K27me3; together these changes to chromatin dynamics dysregulate gene expression to support the epithelial-to-mesenchymal transition. Functional studies using Saccharomyces cerevisiae reveal that, while yeast cells that express H3E50K as the sole copy of histone H3 show sensitivity to cellular stressors, including caffeine, H3E50K cells display some genetic interactions that are distinct from the characterized H3K36M oncohistone yeast model. Taken together, these data suggest that additional H3 mutations have the potential to support oncogenic activity and function through distinct mechanisms that dysregulate gene expression.
In vivo selection of anti-glioblastoma DNA aptamers in an orthotopic patient-derived xenograft model
Authors: Doherty Caroline D , Wilbanks Brandon A , Jain Sonia , S Pearson Keenan , Bakken Katie K , Burgenske Danielle M , Lett Nay Won , Sarkaria Jann N , Maher Louis J
Published: February 2025

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor of adults. Current therapeutic options yield dismal prognoses that have remained essentially unchanged over nearly two decades. Diffuse growth patterns, high intratumoral heterogeneity, and variable blood–brain barrier integrity limit treatment efficacy, creating challenges that rational small molecule design has not overcome. Antibody–drug conjugates have shown some promise, leading us to hypothesize that smaller folded DNA aptamers, developed in vivo via principles of natural selection, might eventually have advantages for drug delivery. Here, we document the first in vivo DNA aptamer selection involving an orthotopic patient-derived xenograft GBM mouse model to identify tumor-homing DNA aptamers. We demonstrate the preferential accumulation of these aptamers in the tumor relative to other tissues 4 h after intraperitoneal injection. The aptamers can be detected by quantitative polymerase chain reaction, fluorescent tumor staining, and stain GBM tumor section from untreated mice and the GBM tumor cells in culture. Two of three candidates are selective for the target cell line in vitro and do not bind other human tumor cells. In vivo selection of tumor-specific DNA aptamers demonstrates a novel approach for diagnostics or toxin delivery that might allow for the development of individualized therapies.
Diminished Mycobacterium tuberculosis–specific T-cell Responses During Pregnancy in Women With HIV and Receiving Isoniazid Preventive Therapy
Authors: Saha Aparajita , Escudero Jaclyn N , Layouni Troy , Mecha Jerphason , Maleche-Obimbo Elizabeth , Matemo Daniel , Kinuthia John , John-Stewart Grace , Richardson Barbra A , LaCourse Sylvia M , Shah Javeed A
Published: February 2025

Background

Pregnancy increases Mycobacterium tuberculosis (Mtb) reactivation risk and alters immune responses. We assessed Mtb-specific CD4+ T-cell responses in pregnant women with HIV (WLHIV) and without, including those receiving isoniazid preventive therapy (IPT).

Methods

We measured adaptive immune responses from 33 participants (HIV+ 21, HIV− 12) with positive interferon-gamma release assay during pregnancy (20–34 weeks’ gestation), 6 weeks, and 12 months postpartum by intracellular cytokine staining. We measured overall responses using COMPASS and made comparisons by nonparametric analysis of variance.

Result

We observed diminished Mtb-specific CD4+ T-cell responses in WLHIV during pregnancy versus 12 months postpartum (COMPASS median functional score [FS] .009 vs 0.12, P = .03). WLHIV who received IPT (n = 8) during concurrent pregnancy had attenuated Mtb-specific CD4+ T-cell responses during pregnancy versus 12 months postpartum (median FS 8.3 × 10−7 vs 0.13, P = .02), but WLHIV who did not receive IPT during pregnancy had similar responses in pregnancy and postpartum. Mtb-specific CD8+ FS was increased postpartum in all groups. We found preexisting Mtb-specific CD4+ T-cell responses in participants who converted interferon-gamma release assay tests postpartum (n = 10).

Conclusions

Pregnant WLHIV, especially those on IPT, showed reduced Mtb-specific CD4+ T-cell responses. Understanding the impact of pregnancy on Mtb-specific T-cell responses may improve diagnostic approaches.
Immunogenicity and Safety of the Higher-Valent Pneumococcal Conjugate Vaccine vs the 13-Valent Pneumococcal Conjugate Vaccine in Older Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ngamprasertchai Thundon , Ruenroengbun Narisa , Kajeekul Rattagan
Published: February 2025

Background

The immunogenicity of the 15-valent pneumococcal conjugate vaccine (PCV15) and PCV20 in older adults was approved on the basis of comparative data with PCV13, although their relative immunogenicity and safety in this population remain undetermined. A systematic review and meta-analysis were conducted to provide insights, addressing the lack of large-scale efficacy studies.

Methods

This analysis included phase 2 and 3 randomized controlled trials evaluating the immunogenicity of a single dose of PCV15 or PCV20 in older adults by opsonophagocytic assay geometric mean titer (GMT) response at 1 month postvaccination as compared with PCV13.

Results

In total, 8 trials were eligible. PCV15 demonstrated superior immunogenicity vs PCV13 among older adults (GMT ratio, 1.11; 95% CI, 1.02–1.20). In immunogenicity vs PCV13, PCV20 demonstrated noninferiority, exceeding 0.5 at 1 month postvaccination (GMT ratio, 0.84; 95% CI, .81–.87). The incidence of local and systemic reactions was higher in the PCV15 group as compared with the PCV13 group, with risk ratios of 1.23 (95% CI, 1.14–1.32) and 1.15 (95% CI, 1.02–1.29), respectively. PCV20 is well tolerated and exhibits a comparable rate of local and systemic reactions to PCV13.

Conclusions

These findings support the immunogenicity and safety of PCV15 and PCV20 for pneumococcal vaccination in older adults. Given its superior immune response, PCV15 may address the gaps left by PCV13. Despite higher antibody levels, the clinical effectiveness of these vaccines remains uncertain. Ongoing surveillances are essential to evaluate the impact of both vaccines on remaining vaccine-type pneumococcal disease.
Comparing the influence of Atlantic Multidecadal Variability and spring soil moisture on European summer heat waves
Authors: Mascolo Valeria , Le Priol Clément , D’Andrea Fabio , Bouchet Freddy
Published: February 2025

In this work, we study and compare the influence of the Atlantic Multidecadal Variability (AMV) and spring soil moisture in Southern Europe on the duration and intensity of European summer heat waves. We study heat waves with return times of a few years and also propose a new methodological approach, return time maps, that allows us to study rare heat waves with return times of 10 or 50 years. We use the outputs from three climate models, namely IPSL-CM6A-LR, EC-Earth3, and CNRM-CM6-1, in which North Atlantic sea surface temperatures are restored towards the observed AMV anomalies. The three models give consistent results, with the exception of EC-Earth simulating a much greater influence of soil moisture. Our main conclusion is that spring soil moisture in Southern Europe is a slow driver of greater importance than the AMV for European summer heat waves, both in terms of the extension of the region of influence and in terms of amplitude. While the influence of the AMV concentrates over the very south of Europe, around the Mediterranean Basin, spring soil moisture influence extends over large parts of Europe. As might be expected, a positive AMV phase or low soil moisture generally induces hotter and longer heat waves. For more extreme events, the influences of the AMV and soil moisture increase, according to regional patterns that seem to be the same as for typical heat waves. However, confirming this statement would require datasets with more extreme events.
Origin and Evolution of the Holocene Magmatic System at Sakurajima Volcano, Japan
Authors: Kuritani Takeshi , Nakagawa Mitsuhiro , Matsumoto Akiko , Nishihara Ayumu
Published: February 2025

Sakurajima volcano has developed since 26 ka through post-caldera magmatic activity at the Aira caldera (formed at 30 ka) and is one of the most active volcanoes in Japan. In this study, new petrological and geochemical analyses were conducted on proximal volcanic products to understand the origin and evolution of the magmatic system during the Holocene. The volcanic products have andesitic and dacitic compositions (58–69 wt % SiO2), and relatively older products (9–1.6 ka) and younger products (<1.3 ka) are characterised by having lower and higher P2O5 contents, respectively (low- and high-P2O5 groups, respectively). The low-P2O5 group products had lower TiO2 and Y contents, higher 87Sr/86Sr, 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios, and lower 143Nd/144Nd ratios than the high-P2O5 group products. It is suggested that the low-P2O5 group magmas were produced by the partial melting of lower crustal materials, and the compositional variations primarily reflected the variation in the degree of melting, with some contribution from mixing with mafic magmas. In contrast, the high-P2O5 group magmas were produced by mixing mafic and felsic magmas in varying proportions. The mafic end-member magmas evolved from mantle-derived primitive magmas with some contribution from crustal assimilation. The felsic end-member magmas were produced by fractional crystallisation following the melting of lower crustal materials with higher melting degrees than those of the low-P2O5 group magmas. In summary, the geochemical evolution of Holocene magmatic activity at Sakurajima was essentially controlled by intermittent discharges of partial melts from the lower crustal source region with increasing melting degrees. The remnants of the voluminous Aira rhyolitic magmas from caldera-forming eruptions were not involved in the Holocene magmatic system. Lower crustal source materials that produced the Aira rhyolites were also not involved. The lower crustal melting region, which was the main source of Holocene magmatism at Sakurajima, may have already existed at ~100 ka, well before the caldera-forming eruption at 30 ka.
COP9 SIGNALOSOME SUBUNIT 5A facilitates POLYAMINE OXIDASE 5 degradation to regulate strawberry plant growth and fruit ripening
Authors: Huang Yun , Gao Jiahui , Ji Guiming , Li Wenjing , Wang Jiaxue , Wang Qinghua , Shen Yuanyue , Guo Jiaxuan , Gao Fan
Published: February 2025

Polyamines (PAs), such as putrescine, spermidine, and spermine, are essential for plant growth and development. However, the post-translational regulation of PA metabolism remains unknown. Here, we report the COP9 SIGNALOSOME SUBUNIT 5A (FvCSN5A) mediates the degradation of the POLYAMINE OXIDASE 5 (FvPAO5), which catalyzes the conversion of spermidine/spermine to produce H2O2 in strawberry (Fragaria vesca). FvCSN5A is localized in the cytoplasm and nucleus, is ubiquitously expressed in strawberry plants, and is rapidly induced during fruit ripening. FvCSN5A RNA interference (RNAi) transgenic strawberry lines exhibit pleiotropic effects on plant development, fertility, and fruit ripening due to altered PA and H2O2 homeostasis, similar to FvPAO5 transgenic overexpression lines. Moreover, FvCSN5A interacts with FvPAO5 in vitro and in vivo, and the ubiquitination and degradation of FvPAO5 are impaired in FvCSN5A RNAi lines. Additionally, FvCSN5A interacts with cullin 1 (FvCUL1), a core component of the E3 ubiquitin-protein ligase complex. Transient genetic analysis in cultivated strawberry (Fragaria × ananassa) fruits showed that inhibiting FaPAO5 expression could partially rescue the ripening phenotype of FaCSN5A RNAi fruits. Taken together, our results suggest that the CSN5A-CUL1-PAO5 signaling pathway responsible for PA and H2O2 homeostasis is crucial for strawberry vegetative and reproductive growth in particular fruit ripening. Our findings present a promising strategy for improving crop yield and quality.
The DNA methylation–demethylation balance prevents development of multiple megaspore mother cells in Arabidopsis
Authors: Jiang Ting , Li Lei , Hu Qianqian , Kuang Xianyu , Zhang Lei , Zeng Wenjie , Miki Daisuke , Zheng Binglian
Published: February 2025

Female gametophyte development initiates from the megaspore mother cell (MMC), and only 1 somatic cell develops into an MMC. Here, we report that the balance between DNA methylation and demethylation ensures the maintenance of a single MMC in Arabidopsis (Arabidopsis thaliana). Surprisingly, a decrease or an increase of all 3 DNA methylation types (mCG, mCHG, and mCHH) caused abnormal enlargement of MMC-like cells and re-balancing DNA methylation rescued the enlarged MMC-like cells in the mutants of regulators for DNA methylation and demethylation. Systematic quantification of DNA methylation at the single-cell level demonstrated that mCHH levels begin to decrease from the central precursor MMC, preceding expression of the MMC marker KNUCKLES(KNU). Disrupting the regulation of DNA methylation caused the mCHH levels to become similar in the MMC and its neighboring cells, and these neighbors usually developed into MMC-like cells. Levels of the de novo DNA methyltransferase DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) in the precursor MMC decreased before KNU expression, but the levels of the DNA glycosylase DEMETER decreased after KNU expression. Re-introduction of DRM2 or knockdown of DEMETER specifically in neighboring cells rescued the defects in drm1 drm2 double mutants. Collectively, our findings demonstrate that the balance of DNA methylation, rather than total methylation levels, facilitates maintenance of a single MMC.
The Power of the Pen: Do Poets, Fiction Literature, and Culture Affect the Politics of (Education) Policy-Making?
Authors: Garritzmann Julian L
Published: February 2025

Culture is neglected or downplayed in the political economy and public policy literature in general and the politics of education literature in particular. An important recent book by Cathie Jo Martin—Education for All? Literature, Culture, and Education Development in Britain and Denmark—sets out to change this by studying the role of fiction literature and fiction writers in education policy-making in Britain and Denmark from 1700 until today. Education for all? highlights that and how fiction and fiction writers have played an important role in the politics of education and offers both quantitative text-analysis evidence and historical case studies to demonstrate the power of the pen. This article discusses Martin's crucial contribution, aiming to help contribute to develop a systematic research agenda on the role of culture in the politics of (education) policy. Among other things, the review develops a new typology of different kinds of cultural influences and sets out several avenues for future research.
Benefits of movement-based Behaviors on improving erectile function in American men: a nationwide survey study
Authors: Chen Yiming , Zhuang Qianfeng , Xia Wei , Shao Naiyuan , Zhang Bo , Feng Xingliang
Published: February 2025

Background

Erectile dysfunction (ED) is a prevalent condition with significant psychological and physiological impacts. Recently, a new concept called movement-based behaviors (MBB) has been proposed, which includes four types of PA: vigorous PA (VPA), moderate-intensity PA (MPA), walking/cycling, and muscle-strengthening activities (MSA), and uses an MBB index (range 0–4) to estimate the combined effects of these activities on health outcomes.

Aim

This study aims to evaluate the relationship between different types of physical activities (PA) and ED using the MBB index in a nationally representative sample of U.S. men.

Methods

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2001-2004, including 3435 male participants. Multivariate logistic regressions were performed to explore the associations, supplemented with subgroup analysis and sensitivity analysis.

Outcomes

The assessment of PA in this study is based on four self-reported questions from the NHANES Mobile Examination Center interview, including VPA, MPA, walking/cycling, and MSA. The MBB index, ranging from 0 to 4, was used to assess combined PA types. ED was evaluated using a single-question self-assessment.

Results

Higher MBB index values were associated with lower ED risk. Participants with an MBB index of 2 had a significantly lower risk of ED in Model 3 (OR = 0.65, 95% CI: 0.43-0.97, P = 0.04). Those with an MBB index of 3 or 4 had the lowest risk of ED across all models, with OR_Model1 = 0.29 (95% CI: 0.21-0.40, P < 0.0001), OR_Model2 = 0.52 (95% CI: 0.37-0.73, P < 0.001), and OR_Model3 = 0.61 (95% CI: 0.41-0.90, P = 0.02). However, this relationship was not significant in subgroups with severe ED or comorbid conditions.

Clinical Implications

Our findings can provide clinicians with guidance to help patients personalize their selection of different exercise combinations.

Strengths and Limitations

We explored the impact of different exercise combinations on reducing ED risk and innovatively proposed the MBB index for a comprehensive assessment of exercise benefits, supported by a large sample size and multivariable adjustments. However, the limitations of cross-sectional design and recall bias cannot be overlooked.

Conclusion

The MBB index effectively demonstrates that combined PA can reduce ED risk, supporting tailored exercise recommendations for patients.
Exploring industry perspectives and preferences about calf handling and restraint methods used during spring processing of calves in western Canada
Authors: Arkangel Lindsey , Windeyer Claire , Goldhawk Christy , Adams Cindy , Pajor Ed
Published: February 2025

Calf processing events have important animal health, management, and sociocultural roles in the beef cattle industry. In western Canada, the three most commonly used methods for spring processing are roping and wrestling (RW), roping and Nord fork (NF), and tilt table (TT). The objective of this study was to understand the preferences and perceptions of handling event participants about calf handling and restraint methods commonly used during western Canadian beef calf processing events during the spring season. Data were collected using a mixed-methods online questionnaire. Quantitative analysis was used to describe the study participants and determine preference rankings. Qualitative, thematic analysis was used to explore participants’ perceptions about the common handling and restraint methods and to identify values within and across participants. The majority of participants were farm hands or staff members (92.8%), followed by owners (4.9%), family members (1.4%), friends (0.5%), and others (0.4%). The most preferred method to use was RW, and TT was the least preferred (χ2 = 3239.1, df = 6, p < 0.001). Participants shared values regarding calf safety and stress, processing efficiency, convenience, human safety, and labour intensity when explaining their preference to use calf handling and restraint methods for spring processing. Responses highlighted the need for understanding and skill in low stress handling and processing tasks in order for any of the methods to be effective. These values identify aspects to address when developing best practice recommendations for calf handling and restraint. Furthermore, focusing communication through the lens of these shared values will likely positively engage participants in extension efforts and community discussions.
Bacteriophage therapy in women with chronic recurrent cystitis caused by multidrug-resistant bacteria: A prospective, observational, comparative study
Authors: Krakhotkin Denis , Iglovikov Nikolai , Blecher Gideon , Chernylovskyi Vladimir , Greco Francesco , Gayvoronskaya Svetlana A. , El Meliegy Amr
Published: February 2025

Objectives

The aim of this study was to evaluate the effects of the combination of bacteriophage therapy with antibiotics and bacteriophage treatment alone on relieving clinical symptoms of chronic recurrent cystitis caused by multidrug-resistant bacteria.

Materials and methods

This clinical trial compared the treatment methods of 217 female patients with chronic recurrent cystitis caused by multidrug-resistant bacteria, who were investigated from June 2020 to May 2023. Patients were allocated into 4 groups: group I: received bacteriophage (Sextaphage) therapy alone; group II: received a combination of bacteriophages (Sextaphage) and furazidin; group III: received a combination of bacteriophage (Sextaphage) and furazidin with cefixime; and group IV: received furazidin and cefixime (without bacteriophage). The primary outcome included changes in the acute cystitis symptom scale and the pain visual analog scale, which were completed on days 7 and 14 following treatment. Secondary outcome measures included bladder diary records of urinary symptoms, median voided volumes, level of bacteriuria, and degree of leukocyturia.

Results

Initially, 217 female patients were presented during baseline visits. Those who did not meet the criteria inclusions were excluded, and 178 female patients were included in the final analysis. Statistically significant improvements from baseline in acute cystitis symptom scale scores for differential, typical symptoms, and quality of life domains were observed after 14 days of treatment in groups II, III, and IV. The pain level measured on the 14th day with the visual analog scale significantly decreased in groups II, III, and IV compared with group I. The patients of group I had a reduction of mean level bacteriuria of Escherichia coli from 106 to 102 CFU/mL at 14 days of therapy. Significant improvement of voided volume from baseline was observed in groups II, III, and IV. Episodes of urinary frequency, both daytime and night-time, reduced significantly from baseline in all 4 groups only at 14 days of treatment.

Conclusions

Bacteriophage cocktail alone or with antibiotics may improve clinical symptoms in women with chronic recurrent cystitis caused by multidrug-resistant bacterial pathogens. In addition to improving clinical symptoms, the therapy with a phage cocktail may restore antibiotic sensitivity and increase the efficacy of antimicrobial agents.
Who is living near different types of US Superfund sites: A latent class analysis considering site contaminant profiles
Authors: Trottier Brittany A. , Olshan Andrew , Edwards Jessie K. , Engel Lawrence S. , Nichols Hazel B. , White Alexandra J.
Published: February 2025

Background:

Millions of people in the United States live near Superfund sites and may be exposed to hazardous chemicals from those sites. However, there is limited research on chemicals present at sites and the demographics of nearby communities. We aimed to identify subgroups of Superfund sites with similar contaminant profiles and evaluate whether sociodemographic characteristics vary by type of site.

Methods:

We used US Environmental Protection Agency Superfund data to identify sites active in the year 2000. Census tract centroids located within 3 miles of every Superfund site were identified and a weighted average of census tract-level sociodemographics using the 2000 US Census was calculated. Superfund sites with similar contaminant profiles were identified using latent class analysis. We compared the median sociodemographic characteristics, overall and by contaminant latent class, with those of the overall 2000 US Census.

Results:

We identified seven latent classes based on 12 contaminant categories from 1332 Superfund sites active in 2000. Overall, there were few differences in sociodemographics observed by the presence of any Superfund site compared with the overall US Census. After stratifying by contaminant profile, we observed evidence of disparities for two classes of sites, defined by (1) high diversity of chemical exposure and lumber industry and (2) batteries and metals, which were more likely to have higher hazard scores and to be near communities with higher proportions of non-White individuals, lower socioeconomic status, and higher social vulnerability.

Conclusion:

Disadvantaged communities, with higher social vulnerability, were more likely to be near certain Superfund sites with higher hazard scores.
Burnout in modern-day health care: Where are we, and how can we markedly reduce it? A meta-narrative review from the EUREKA* project
Authors: Linzer Mark , O'Brien Emily C. , Sullivan Erin , Rathert Cheryl , Simmons Derick R. , Johnson Dawn H. , McKinney Warren T. , Mallick Sanjoyita , Porta Carolyn M. , Poplau Sara , Wambua Mike , Bosquet Alli , Farley Heather , Montori Victor M. , Goelz Elizabeth
Published: February 2025

Background

Burnout is disrupting the health care workforce, threatening the livelihoods of health care workers and the probability of safe and effective patient care.

Purposes

The aims of this study were to describe the evolution and gaps in burnout research and identify next steps to advance the field and reduce burnout.

Methodology/Approach

We formed a learning community of burnout scholars and Chief Wellness Officers, sought recent review articles for a meta-narrative synthesis of themes on health care worker burnout, and conducted focus groups with learning community members.

Results

In 1,425 systematic burnout studies found in a Medline database search of systematic reviews published since 2018, 68 were retained for analysis. Many focused on individual interventions (e.g., mindfulness), paying inconsistent attention to (a) what comprises burnout, (b) prevalence and contributors, (c) theories underlying it, (d) presence in marginalized populations, and (e) innovative research methods. There was consensus that burnout poses a global crisis, but there was no agreement on how to address it. Focus group participants noted that although burnout research is now “mainstream,” health systems commit insufficient resources to addressing it. They proposed that emphasizing organizational finances and patient safety may make burnout a priority for health systems.

Practice Implications

Despite burnout's progressing unabated, many organizations do not employ known burnout indicators (worker dissatisfaction or turnover) as wellness metrics. Research into organizational contributors to burnout, rigorous evaluation of interventions, and organizational adoption of research findings into systemic action are urgently needed. A well-supported international research agenda is required to quickly move the field ahead and reduce or ultimately eliminate burnout.
Nasopharyngeal Carriage and Antibiotic Resistance in Children With Sickle Cell Disease: The DREPANOBACT French Multicenter Prospective Study
Authors: Pham Luu-Ly , Varon Emmanuelle , Bonacorsi Stéphane , Boubaya Marouane , Benhaim Patricia , Amor-Chelihi Lahoueri , Houlier Marine , Koehl Bérengère , Missud Florence , Brousse Valentine , Gajdos Vincent , Bizot Etienne , Briand Coralie , Malka Alexandra , Odièvre Marie-Hélène , Romain Anne-Sophie , Hau Isabelle , Pondarré Corinne , See Hélène , Guitton Corinne , Zenkhri Férielle , Holvoet Laurent , Benkerrou Malika , Da Silveira Charlène , Belaid Nabil , Laurent Odile , Vassal Mélanie , Basmaci Romain , Aupiais Camille , Bloch-Queyrat Coralie , Lévy Corinne , Cohen Robert , Ouldali Naïm , De Pontual Loïc , Carbonnelle Etienne , Gaschignard Jean
Published: February 2025

Background:

Children with sickle cell disease (SCD) are susceptible to invasive bacterial infections, particularly those caused by Streptococcus pneumoniae. Data concerning nasopharyngeal carriage remain scarce in this population at high risk of resistant bacteria owing to antibiotic pressure and frequent hospitalizations.

Methods:

We conducted this prospective trial, DREPANOBACT, in 7 French hospitals to assess the nasopharyngeal carriage rate for S. pneumoniae among children with SCD aged 6 months–15 years between September 2022 and April 2024. The secondary aim was to determine the serotype distribution and proportion of penicillin nonsusceptible S. pneumoniae isolates and the carriage and antibiotic resistance rates for Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae.

Results:

In total, 300 children were enrolled [median age, 8 years (interquartile range: 4–12 years)]. S. pneumoniae carriage accounted for 32 cases (11%), including 21 penicillin nonsusceptible S. pneumoniae strains (66%). The main serotypes were 23A (n = 4), 35B (n = 4), 11A (n = 3) and 15C (n = 3). Overall, 75% of the serotypes were non-13-valent pneumococcal conjugate vaccine (PCV) serotypes, with 19% and 53% covered by PCV20 and PCV21, respectively. The carriage rates for S. aureus, M. catarrhalis and H. influenzae were 31%, 17% and 11%, respectively. Methicillin resistance was observed in 5% of S. aureus strains. Age ≤5 years was significantly associated with S. pneumoniae, M. catarrhalis, and H. influenzae carriage, while age ≥11 years was associated with S. aureus carriage.

Conclusions:

Surveillance of nasopharyngeal carriage in children with SCD is warranted to monitor changes in predominant serotypes and resistance patterns.
A Checklist to Improve Acute Stroke Evaluation and Treatment in the Emergency Department
Authors: Elam Meagan , Moyal-Smith Rachel , Canfora Madison , Cohen Wendy , Eum Ki-Do , Fischer Christopher , Margo Judy , McCune Marie , Moin Omer , Selim Magdy , Wendell Linda , Kumar Sandeep
Published: February 2025

Narrow therapeutic time windows and delays in assessing acute ischemic stroke patients limit the access to and effectiveness of reperfusion therapies. A 2-year quality improvement project codesigned and tested a checklist for quicker evaluation of suspected stroke cases in 2 emergency departments (EDs). Utility, feasibility, and implementation barriers were assessed through semistructured interviews. The impact on stroke quality metrics was analyzed using bivariate and multivariate regression models with data from the American Heart Association’s Get With the Guidelines registry. Implementing the checklist was significantly associated with higher odds of receiving intravenous thrombolytics within 60 minutes of ED arrival (odds ratio: 6.4, 95% confidence interval: 1.1–68.7, P = 0.03). Users felt the checklist improved the standardization of stroke care and promoted teamwork, especially in a time of higher staff turnover. An ED-based stroke checklist resulted in timelier stroke care for acute ischemic stroke patients, meriting further testing in larger, more diverse settings.
Treatment of T-cell Leukemia/Lymphoma in Children and Young Adults With the Memorial Sloan Kettering Cancer Center New York IIB Protocol
Authors: Steinherz Peter G. , Mauguen Audrey , Suser Stephanie , Ramaswamy Kavitha , Kobos Rachel , Forlenza Christopher J. , Shukla Neerav , Trippett Tanya , Wolden Suzanne , Steinherz Laurel
Published: February 2025

We described the Memorial Sloan Kettering Cancer Center New York IIB (MSK-NYII) protocol pilot in 1993, for the treatment of acute lymphoblastic leukemia (ALL) in children at high risk of early relapse. We now report MSK-NYII for the treatment of T-ALL/T-lymphoma over a 15-year period. A review of all patient charts identified 63 treated from 1/1/2000-12/31/2015, with a median follow-up of 9.9 years. Further follow-ups were confounded by the COVID pandemic. Remissions (CR) were defined as <5% marrow blast count on Day 28 and resolution of extramedullary disease. Forty-four had T-ALL, and 19 had stage III/IV lymphoblastic lymphoma (T-LL). Median age at diagnosis was 13.6 years (range 0.4 to 23.7). At diagnosis central nervous system (CNS) leukemia was present in 7/63 patients (11%), cranial nerve palsy in 3 (5%), CNS2 [<5cells/µL cerebrospinal fluid with blasts seen on cytospin] in 11 (17%), testicular enlargement in 3 (5%), and mediastinal mass in 45 (71%). On Day 8, 37 T-ALL (86%) were rapid early responders with <25% marrow blasts. 54 patients had an examination, cerebrospinal fluid, and marrow evaluation on day 28. Remission was demonstrated in 53 (98%) after prior marrow and CNS disease. The 19 T-lymphoma patients had no evidence of disease on day 28. Four relapses in marrow were recorded during therapy. Second remissions were able to be achieved. One patient died without having relapsed and is counted as an event in the event-free survival (EFS) analysis. Four patients, including 3 after the second CR transplant, died during follow-up. One unusual case of T-ALL recurred as T-LL of the colon 5.5 years after diagnosis, 3.5 years after therapy discontinuation. Fifteen years after diagnosis 88% (95% CI=78%-98%) survived event-free, and 91% (95% CI=82%-100%) survived. Twenty-five patients received irradiation. Three had RT to the testes, 3 had cranial RT for cranial nerve palsies, and 19 had cranial radiation for either CNS leukemia, CNS2, or for initial white blood cell >100,000/ µL. The MSK-NYIIB protocol, with a 94% 5-year and 88% 15-year EFS, is an effective therapy for the treatment of T-ALL/lymphoma, with similar toxicity to other high-risk regimens.
The Diagnostic Yield of Panel Versus Exome Sequencing to Identify Hereditary Cancer Disorders in Pediatric Cancer
Authors: Lozinsky Shannon M. , Iezzi Carina A. , Gruber Dorota , Onel Kenan , Fein Levy Carolyn
Published: February 2025

This study aimed to assess whether targeted exome sequencing (TES) outperforms next- generation sequencing (NGS) panels in detecting clinically actionable cancer predisposition syndromes (CPS) in pediatric cancer patients. Patients with cancer underwent genetic counseling and NGS panel testing (27 or 64 genes). Simultaneously, a 616-gene targeted exome, including the NGS panel genes and 552 additional potential cancer-related genes, was conducted on the patients and their parents. Of 42 patients undergoing both tests, NGS panels identified an APC risk allele (RA) in a patient with ganglioglioma and a pathogenic RB1 variant in a patient with retinoblastoma. In addition to the variants found by NGS panels, TES detected a pathogenic MUTYH variant in a patient with acute lymphoblastic leukemia (ALL) and a likely pathogenic (LP) BLM variant in another patient with ALL. TES also revealed a variant in candidate CPS genes, MC1R (RA) and EXT2 (LP), in a patient with embryonal rhabdomyosarcoma and Ewing sarcoma, respectively. Despite identifying variants in candidate CPS genes (MC1R, EXT2) not included on common NGS panels and known CPS genes (MUTYH, BLM) absent from this study’s panels, the diagnostic yield of clinically actionable CPS variants did not substantially increase with TES compared with standard NGS panels in pediatric cancer patients. In conclusion, for most cases, panel testing remains appropriate for CPS diagnosis in pediatric cancer within typical clinical settings.
Parents' Experiences of Palliative Care Decision Making for Children With Terminal Cancer
Authors: Liang Lichan , Ye Hongyu , Liu Weifei , Yi Fangling , Jiang Rong , Hu Yanqun , Shi Lei
Published: February 2025

The objective of this study was to describe the experiences and perceptions of parents making palliative care decisions for children with end-stage malignancies. This qualitative study was conducted with 13 parents from 9 families of children with end-stage malignant tumors. Data were analyzed using thematic content analysis. Three interrelated themes were identified: (1) parental knowledge of the child's condition influences palliative care decision making, (2) the establishment of a mutually trusting relationship between parents and health care professionals is key to implementing palliative care decision making, and (3) the influence of family background and traditional culture on parental palliative care decision making. This study adds to the evidence related to parents' experiences of end-of-life care decision making and provides findings of international significance, particularly concerning the place of care and the introduction of end-of-life care discussions. Parents' expert knowledge of their child's condition is important and should be recognized. End-of-life care decision making is a complex and delicate process; each family's information needs and preferences are individualized and need to be understood by the professionals involved in care.
The Lupus Foundation of America Rapid Evaluation of Activity in Lupus Patient-Reported Outcome Predicts Health-Related Quality of Life, Fatigue, and Work Productivity Impairment: Data From the Almenara Lupus Cohort
Authors: Ugarte-Gil Manuel F. , Gamboa-Cárdenas Rocío V. , Pimentel-Quiroz Victor R. , Reátegui-Sokolova Cristina , Elera-Fitzcarrald Claudia , García-Hirsh Samira , Pastor-Asurza César , Rodriguez-Bellido Zoila , Perich-Campos Risto , Alarcón Graciela S
Published: February 2025

Objective

The study aims to evaluate the impact of patient-reported disease activity in other patient-reported outcomes (PROs) in systemic lupus erythematosus (SLE) patients.

Methods

SLE patients from the Almenara Lupus Cohort were included, and visits were performed every 6 months. Disease activity was assessed with the Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) PRO, health-related quality of life (HRQoL) with the LupusQoL, fatigue with the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), and work productivity impairment with the work productivity and activity impairment (WPAI). Generalized estimating equations were performed for each domain of the LupusQoL, the FACIT-F, and the WPAI. The LFA-REAL PRO measured at the previous visit; multivariable models were adjusted for possible confounders measured at the same visit as the LFA-REAL PRO. The Β (regression unstandardized coefficient) is reported per an increase of 10 units of the LFA-REAL PRO.

Results

A total of 316 patients and 1116 visits were included. Mean (SD) LFA-REAL PRO at baseline was 240.9 (182.1). LFA-REAL PRO predicted a worse HRQoL in all domains of the LupusQoL, the WPAI, and the FACIT-F, even after adjustment for confounders.

Conclusions

A higher patient-reported disease activity predicted a worse HRQoL and fatigue as well as a higher work productivity impairment in SLE patients. Patient-reported disease activity should be included in the evaluation of SLE patients on a regular basis as such provides the patients' own perception of their disease. This may have an impact on their adherence to treatment and may result in better outcomes.
Assessing the Relationship Between Mandibular Contouring and Iatrogenic Jowling in Facial Feminization Surgery
Authors: Flores-Pérez Paula , Rancu Albert , Allam Omar , Vassallo Melanie , Shen Yizhuo , Kauke-Navarro Martin , Parikh Neil , Alperovich Michael
Published: February 2025

Lower-third facial feminization procedures have been associated with the development of postoperative jowling, yet quantitative evaluations of this outcome remain limited. This study evaluated the relationship between patient risk factors and bony volume reduction with postoperative jowling. Chin and gonial angle bony measurements were obtained from preoperative and postoperative computed tomography imaging, whereas changes in jowling were assessed using a validated photonumeric jowling scale on preoperative and postoperative patient images. Associations between skeletal changes, demographic variables, and soft tissue outcomes were statistically analyzed. The study included 35 patients with a mean age of 36 ± 12 years. The average time between surgery and postoperative photographs was 10.0 ± 7.5 months. Gonial angle volume decreased by 9.48% (P < 0.001), whereas chin volume decreased by 3.06% (P = 0.051). Average jowling grade increased significantly from 2.3 to 2.6 postoperatively (P = 0.03), with higher age correlating to a greater increase in jowling (r = 0.35, P = 0.037). Postoperatively, only body mass index was significantly correlated with absolute jowling score (r = 0.51, P = 0.0018). However, no significant associations were found between changes in bony measurements and changes in jowling scores. These findings underscore the importance of further investigating the interplay between patient risk factors and bony and soft tissue changes in facial feminization surgery. Future studies will focus on expanded cohorts and more sensitive assessment tools to better define risk factors and optimize surgical strategies for minimizing jowling.
American Association for the Surgery of Trauma pancreatic organ injury scale: 2024 revision
Authors: Notrica David M. , Tominaga Gail T. , Gross Joel A. , Southard Richard N. , McOmber Mark E. , Crandall Marie , Kozar Rosemary , Kaups Krista L. , Schuster Kevin M. , Ball Chad G.
Published: February 2025

BACKGROUND

The American Association for the Surgery of Trauma Organ Injury Scale (OIS) Committee published the original pancreatic OIS in 1990 with the authors acknowledging at the time that the classification would need to undergo “continued refinement as clinical experience dictates.” The current OIS overemphasizes injury location over ductal integrity; modifications are needed to improve concordance between OIS, therapy, and outcomes and promote accuracy in quality assessment and research.

METHODS

A subcommittee of the American Association for the Surgery of Trauma and invited experts in radiology and interventional gastroenterology were chosen. Contemporary literature was reviewed, and a standardized iterative and collegial process was used to arrive at consensus.

RESULTS

The pancreatic OIS is anatomically based on operative, radiographic, or pathologic findings. Major changes to the grading system include moving lacerations of the pancreatic head without ductal injury from Grade IV to Grade II. Injuries to the duct in the neck, body, or tail remain Grade III but are further subclassified to distinguish between deep parenchymal injuries without ductal interrogation, partial ductal injuries, and complete ductal transection. Grade IV injuries follow the same nomenclature but for injuries to the right of the portal vein or superior mesenteric vein. Grade V injuries are destructive injuries of the pancreatic head with nonviable parenchyma. These injuries are further subgraded based on ductal injuries.

CONCLUSION

The pancreatic OIS schema is revised based on contemporary experience informed by the current understanding of outcomes and treatment, including operative management and outcomes. Increasing grades now more closely reflect increasing severity.
Indoor air quality at a French university:a participatory CO2 measurement campaign highlights the wide gap between reality and the law
Authors: Cinquin Philippe
Published: February 2025

Poor indoor air quality has been demonstrated to increase the risk of transmitting infectious agents and to expose individuals to the phenomenon of sick building syndrome. In light of these findings, most countries have established specific guidelines regarding indoor air quality in university rooms. In France, for instance, the maximum permissible concentration of carbon dioxide (CO2) in university rooms without mechanical ventilation is set at 1,300 parts per million (ppm), and the minimum volume per occupant is 15 m3. For rooms with mechanical ventilation, the minimum clean air flow rate is 25 m3/h/occupant.

The primary objective of this study was to design and demonstrate the feasibility of a simple, cost-effective method for comparing the reality of indoor air quality in all university rooms with legal requirements. The secondary objectives of the present study were to demonstrate the efficacy of the proposed method in identifying and reporting problematic situations, and in issuing practical recommendations.

Mobile CO2sensors (Aranet4) were provided to volunteer lecturers to measure the CO2concentration during and after classes. The number of occupants and the condition of openings were also recorded. These data were supplemented by measurements from 117 fixed Carbon Nexelec sensors. The data were then fitted to a model, which enabled the characterization of air quality and the estimation of the gauge reduction required to comply with the law.

None of the 14 rooms without mechanical ventilation complied with the legal minimum of 15 m3/occupant. 75% of the third quartiles of CO2concentrations during classes exceeded 2692 ppm. In rooms with mechanical ventilation, median clean air flow was 15 m3/h/occupant at 100% occupancy (9 m3/h/occupant for the first quartile). In 32 out of 41 rooms with mechanical ventilation (78%), the clean air flow was estimated to be below the legal minimum of 25 m3/h/occupant at 100% occupancy. Concentrations in excess of 5,000 ppm were observed in 23 of the 101 rooms equipped with fixed sensors.

The proposed method has demonstrated its feasibility in real-life conditions. For the purpose of evaluating the air quality of all rooms affiliated with universities, it is recommended that this method be used in a systematic manner. The findings of this study indicate that a significant proportion of the examined rooms may not be in accordance with the relevant legislation, thereby jeopardizing the health of the occupants. In order to comply with the law, the method proposed here to estimate gauge reduction should be applied.