bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Mental Health Symptoms, Nicotine Product Use, and their Association Over Time Among Adolescents in Canada, England, and the US: Findings from the ITC Adolescents Tobacco and Vaping Survey, 2020-2023
Authors: Hackworth Emily E , Vidaña-Pérez Desiree , O’Neal Riley , Kim Minji , Fillo Jennifer , Hammond David , Thrasher James F
Published: January 2025

Introduction

There is a well-established bi-directional relationship between cigarette smoking and internalizing mental health (IMH) symptoms (e.g., symptoms of depression, symptoms of anxiety). However, it is unclear whether IMH symptoms are associated with using different types or combinations of nicotine products (e.g., combustible, non-combustible, exclusive product use or multi-product use). The purpose of this study is to improve our understanding of the relationship between adolescent IMH symptoms and use of a wide variety of nicotine products by examining the association between IMH symptoms and current nicotine use from 2020-2023.

Methods

Data come from the 2020-2023 waves of the International Tobacco Control (ITC) Adolescents Tobacco and Vaping Survey, an online repeat cross-sectional survey of adolescents aged 16-19 in Canada, England, and the US (n=80,427). Current nicotine use was examined in four categories: 1) no use, 2) exclusive non-combustible product use, 3) exclusive combustible product use, and 4) use of both product types. Respondents reported current symptoms of depression or anxiety, and we generated a dichotomous IMH symptoms variable (yes vs. no). We examined the association between IMH symptoms and current nicotine use using multinomial logistic regression models that adjusted for covariates.

Results

IMH symptoms were most strongly associated with use of both product types (adjusted relative risk ratio [ARRR]: 1.91, 95% confidence interval [CI] 1.80-2.03), followed by exclusive non-combustible use (ARRR: 1.70, 95% CI=1.61-1.80), and then exclusive combustible use (ARRR: 1.29, 95% CI=1.21-1.37).

Conclusions

Adolescents with IMH symptoms are more likely to use nicotine products in general than adolescents without IMH symptoms. Specifically, non-combustible product use may have a particularly strong relationship with poor mental health among adolescents. Longitudinal research is needed to better understand directionality.

Implications

This study provides an up-to-date understanding of how mental health and nicotine use are related among adolescents, particularly during the COVID-19 pandemic and its aftermath. Results indicate that youth mental health may be related to nicotine use, particularly non-combustible use, which is largely driven by e-cigarette use. Efforts to reduce youth e-cigarette use may consider emphasizing its relationship with mental health. Efforts to promote e-cigarette use as a less harmful alternative to cigarette smoking should be aware of the association between vaping and youth mental health.
Strong inorganic acid mists and respiratory tract cancers: a meta-analysis
Authors: Seyyedsalehi M S , Di Lorenzo A , Vimercati L , Boffetta P
Published: January 2025

Background

Exposure to strong inorganic acid mists (SIAMs) in the workplace has been linked to respiratory tract cancers.

Aims

We conducted a meta-analysis of cohort and case–control studies examining the association between occupational SIAMs and respiratory tract cancers other than laryngeal cancer, which is already established.

Methods

Studies mentioned in the 1992 IARC Monograph on carcinogenicity of SIAMs were combined with later studies identified from a systematic search of Scopus, PubMed and Embase. Forest plots of relative risks (RR) and odds ratios were constructed for the 34 identified studies. A random-effects model was used to address heterogeneity.

Results

An association between the roles associated with occupational SIAMs exposure and risk of lung (RR = 1.17; 95% confidence interval [CI] = 1.05–1.32), and nasal cancers (RR = 3.30, 95% CI = 1.16–9.41) was found. The risk of oral and pharyngeal cancer was also associated with SIAMs exposure-related roles (RR = 1.59, 95% CI = 0.98–2.57). Results did not differ by study design, gender or outcome for all three cancers. A positive association for lung cancer was found with chemical (RR = 1.25, 95% CI = 1.13–1.38), and metal and steel industries (RR = 1.19, 95% CI = 1.04–1.37), as well as for oral and pharyngeal cancer with chemical industry (RR = 1.72, 95% CI = 1.57–1.89). We checked publication bias for lung (p = 0.35), oral and pharyngeal (p = 0.02) and nasal cancer (p = 0.40).

Conclusions

Our study showed an association between occupational SIAM exposure and risk of lung, nasal, and possibly oral and pharyngeal cancers. However, weaknesses in the recording of confounding and exposure data in the currently available literature were found.
North Pole holiday elves: occupational health and the workshop
Authors: Persaud E
Published: January 2025

This paper reviewed physical hazards, chemical exposures, musculoskeletal disorders and occupational stress relevant to North Pole holiday elves in the workshop. The Clauses provide a workshop designed to eliminate or reduce health and safety hazards and promote well-being. This strong employer and employee relationship was strengthened by a union endorsement.
Breakthrough Invasive Mold Infections in Hematologic Cases: Relevance of the Host's Factors
Authors: Rodríguez-Goncer Isabel , Boán Jorge , Carrero-Arribas Riansares , Sanchez-Pina José María , Lizasoaín Manuel , Fernández-Ruiz Mario , San-Juan Rafael , López-Medrano Francisco , Pérez-Ayala Ana , Caro-Teller José Manuel , Martínez-López Joaquín , Aguado José María , Calbacho María
Published: January 2025

Background

Breakthrough invasive mold infections (bIMIs) are life-threatening complications in hematologic cases. Most previous studies in this field covered the whole spectrum of fungal pathogens, including yeasts, and antifungal agents.

Methods

We conducted a retrospective study including all hematologic cases of patients diagnosed with a bIMI while receiving a mold-active antifungal agent at our center between January 2017 and June 2022.

Results

Overall 37 patients were diagnosed with bIMI: 6 (16.2%) proven, 18 (48.6%) probable, and 13 (35.1%) possible. The highest incidence rate was found for micafungin (1.31 bIMI episodes per 1000 treatment-days), although with no significant differences across antifungal agents. Most patients (90.9%) for whom therapeutic drug monitoring was performed exhibited adequate through levels. Ten (27.0%) patients had undergone allogeneic hematopoietic stem cell transplantation. Aspergillus species was the most common pathogen in cases with microbiological identification. Regarding risk factors, 67.6% had severe neutropenia at diagnosis and 40.5% had received high-intensity chemotherapy. Rates of clinical response and attributable mortality by day +30 were 64.9% and 23.3%, respectively. Poorer performance status, higher Charlson Comorbidity index, older age, and higher C-reactive protein by day +7 were associated with 30-day attributable mortality.

Conclusions

Aspergillus was the predominant pathogen in our cohort of bIMIs, with a significant proportion of episodes occurring despite adequate triazole levels. Thirty-day attributable mortality was lower than previously reported. Poorer performance status, higher comorbidity burden, and older age had a relevant role in the outcome of bIMI.
Real-world Rollout of Injectable Antiretrovirals for HIV Prevention and Treatment: Correlates of Early Adoption
Authors: Koshy Liza , Payne Erika , Barakat Lydia , Hao Ritche , Sureshanand Soundhari , Cedillo Ornelas Andrea , Dewan Andrew , Meyer Jaimie P
Published: January 2025

Background

Data are limited on implementation of long-acting injectable (LAI) HIV treatment (ART) and preexposure prophylaxis (PrEP). We characterized “early adopters” of LAI ART and PrEP in terms of social determinants of health using a health equity lens.

Methods

Our retrospective cohort included patients prescribed ART or PrEP through a large urban health system (January 2021–September 2023) in the Northeastern United States. We used electronic health record data for PrEP and ART to examine group differences between those on LAI or oral medications using analysis of variance, chi-square tests, or Fisher exact tests. Bivariate logistic regression modeled associations between LAI ART or LAI PrEP and social determinants of health.

Results

In the PrEP group, 238 patients were prescribed LAI (n = 63) or oral (n = 193) PrEP. Most PrEP patients were men (80.7%), non-Hispanic (79.5%), and White (60.7%) and had public insurance (83.1%). Compared with patients on oral PrEP, those on LAI less often experienced food insecurity, financial strain, depression, anxiety, or substance use disorders. In bivariate models, LAI PrEP inversely correlated with female sex, current smoking, depression, anxiety, and substance use disorders. In the treatment group, 1194 patients were prescribed LAI (n = 76) or oral (n = 1118) ART, with a median age of 57.0 years; 63.6% were from minoritized groups. Only age was significantly associated with LAI ART (odds ratio, 0.97; 95% CI, 0.961–0.993; P = .005).

Conclusions

In this large retrospective cohort of patients on LAI PrEP and ART, patients receiving LAI less often experienced social barriers to accessing care. Public health interventions are needed to overcome health inequities tied to access of LAI ART for HIV prevention and treatment.
Contribution of nebulized budesonide before bronchoscopy, a prospective clinical study
Authors: Zhang Guoxin , Yu Hu , Zhang Li , Zhao Xiaoyun
Published: January 2025

Purpose

This study evaluated the efficacy of adding budesonide to nebulized lidocaine in patients undergoing flexible bronchoscopy (FB) under topical anaesthesia.

Study design

Patients aged ≥18 years, scheduled for FB under topical anaesthesia were randomized into two groups: the combination group received a pre-treatment of 2 ml 1 mg budesonide with 5 ml 2% lidocaine, whilst the lidocaine group received 5 ml 2% lidocaine with 2 ml saline solution, both administered via nebulization. Blood pressure (BP), heart rate, and percutaneous oxygen saturation were recorded before, during, and 10 min after FB. The Visual Analogue Scale (VAS) and Wong-Baker FACES Pain Rating Scale (FPS-R) were used to evaluate cough severity, discomfort, willingness to accept reoperation, and the operator’s satisfaction with patient cooperation. In addition, the duration of the procedure, total lidocaine dosage instilled through the bronchoscope during the procedure, and types of procedures performed were documented.

Results

Compared to the lidocaine group, the combination group showed lower maximum systolic and diastolic BP, higher minimum percutaneous oxygen saturation, and lower cough and discomfort severity scores. Operator’s satisfaction, as measured via the VAS or FPS-R, was greater in the combination group, which also exhibited shorter procedure times and required lower lidocaine dosages. There were no significant differences between the groups in terms of willingness to accept reoperation or types of procedures performed.

Conclusions

In patients undergoing FB with topical anaesthesia, pre-treatment with a combination of nebulized lidocaine and budesonide is more effective than nebulized lidocaine alone.

Key message What is already known on this topic?  Flexible bronchoscopy (FB) with topical anaesthesia remains a common practice in many settings, although it can cause significant discomfort for patients. What this study adds?  Pre-treatment with a combination of nebulized budesonide and lidocaine was more effective and safer than nebulized lidocaine alone for improving patient tolerance during FB. How this study might affect research, practice, or policy?  In settings where conscious sedation is not feasible, the combined nebulization of lidocaine and budesonide may offer an optimized approach for FB, enhancing patient comfort and procedural efficiency.
Prediction of scleroderma renal crisis in patients of SSc: insight from the CRDC cohort study
Authors: Huang Haochen , Xu Shihan , Li Hongbin , Duan Xinwang , Hui Min , Zhou Jiaxin , Zhang Ling-ling , Li Mengtao , Zeng Xiaofeng , Xu Dong
Published: January 2025

Objective

Early personalized identification of SSc patients at risk of scleroderma renal crisis (SRC) can help provide better treatment and improve outcomes. This study aimed to create and validate a new multi-predictor Nomogram to predict SRC risk and compare it to an existing model.

Methods

A retrospective multicentre observational study was conducted using clinical data from SSc patients with SRC registered in the Chinese Rheumatism Data Center (CRDC) database. Each SSc patient with SRC was matched with four SSc patients without SRC, registered consecutively afterward, as controls. Differences between the two groups were analysed using Student’s t-test, Mann–Whitney U test, χ2 test, or Fisher’s exact test. Key risk factors were identified using univariate and multivariate logistic regression, as well as LASSO regression. The Nomogram’s performance was assessed with receiver operating characteristic curves, calibration plots, decision curve analysis (DCA), and bootstrap resampling for internal and external validation. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare models.

Results

The Nomogram incorporated predictive factors such as myocardial involvement, SSc subtype, anaemia, platelet count, and disease duration. The area under the ROC curve showed strong discrimination in both the training and validation datasets. Calibration curves and the Hosmer–Lemeshow test indicated good agreement between predicted and actual outcomes. DCA demonstrated greater clinical net benefit. The NRI and IDI results showed significant improvement over the previous model.

Conclusion

A Nomogram with improved predictive performance compared with the previous one was developed in a larger sample size in China.
Polysomnographic endotypes of successful multilevel upper airway surgery for obstructive sleep apnea
Authors: Wang Xiaoting , Zhang Jingyu , Zou Jianyin , Zhou Tianjiao , Zhou Enhui , Shen Li , Yang Siyu , Huang Weijun , Zhu Huaming , Guan Jian , Yi Hongliang , Yin Shankai
Published: January 2025

Study Objectives

Multilevel upper airway surgery is effective for some patients with obstructive sleep apnea (OSA), but predicting the response to surgery remains a challenge. The underlying endotypes of OSA include upper airway collapsibility, muscle compensation, loop gain, and the arousal threshold. This study aimed to explore the effect of surgery on polysomnography (PSG)-derived OSA endotypes and establish a surgical response prediction model.

Methods

Our study included 54 Chinese patients with OSA who underwent multilevel upper airway surgery. Participants underwent PSG before and after surgery with a median follow-up time of 6.5 months. Using AHIBaseline/AHIpost-surgery ≥ 2 and AHIpost-surgery < 10 events/h as criteria, participants were classified as surgery responders and non-responders. The surgical success rate was 26%. These endotypic traits were derived from a standard PSG data by validated methods.

Results

The surgery altered both anatomical and non-anatomical endotypic traits, including increased Vpassive (baseline vs post-surgery: 51.5 [18.7–84.2] vs 86.8 [67.4–93.7] %Veupnea, p < .001), decreased loop gain (baseline vs post-surgery: 0.7 [0.7–0.8] vs 0.6 [0.5–0.6]; p < .001), and a higher arousal threshold (baseline vs post-surgery: 202.9 [183.7–222.0] vs 160.7 [143.9–177.4] %Veupnea; p < .001). However, it did not significantly affect muscle compensation. Fully adjusted logistic regression analyses indicated that a favorable response to surgery was independently associated with a lower LG (OR [CI 95%], 0.1 [0.0–0.5], p = .032). In patients with improved muscle compensation or a more collapsible airway (lower Vpassive), a lower loop gain was more strongly indicative of success. However, when muscle compensation was lower or collapsibility was less severe (higher Vpassive), a lower loop gain was less predictive of success.

Conclusions

This study demonstrated that multilevel upper airway surgery altered both anatomical and non-anatomical endotypes in Chinese patients with OSA. An endotype based regression model may meaningfully predict surgical success.
Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary and neurocognitive complications in elderly patients: study protocol for an observative cohort study
Authors: Abramova Dayana , Haase Paula Marie , Just Anne-Marie , Frank Sandra , Saller Thomas
Published: January 2025

Background

Postoperative delirium is considered a serious complication in elderly patients. Elderly patients often suffer from several concomitant diseases. The reduced physical condition can increase the risk of cardiac, pulmonary and neurocognitive complications during and after surgery. SARS-CoV-2 infection primarily affects the respiratory tract but can also damage other organ systems such as the heart and brain. Given the wide range of pulmonary, cardiac and neurocognitive complications caused by SARS-CoV-2, these risks must be given special consideration during planned surgical procedures. Both surgical procedures and anesthesia are risk factors for postoperative complications in themselves. The specific impact of prior SARS-CoV-2 infection on perioperative complications in elderly patients has not been sufficiently researched. The aim of this study is to understand how a previous SARS-CoV-2 infection influences the occurrence of perioperative complications.

Methods

In this case-control study, the data of patients over 60 years of age undergoing elective surgery are analyzed. Subjects are divided into two groups based on their SARS-CoV-2 infection status: those with a documented previous infection and those without. Confirmation of infection will be based on written evidence and anamnestic information. The primary endpoint of the examination is the occurrence of delirium within the first five postoperative days. In addition, further cardiac, pulmonary and neurocognitive complications are recorded in the perioperative period.

The occurrence of postoperative delirium is recorded during the daily ward round in the first five days after the operation. The 3DCAM test and the 4AT are used for this purpose. In addition, the CAM-ICU will be used in the intensive care unit. The recruitment will include 266 patients. Statistical analyses will be performed to determine the correlation between a previous SARS-CoV-2 infection and the observed clinical outcomes.

Discussion

The results of this study will provide new insights into the impact of prior SARS-CoV-2 infection on perioperative complications in elderly patients undergoing elective surgery.

Trial registration:

Deutsches Register Klinischer Studien DRKS00034861
In vivoMorphological Dynamics of Single Laser-Axotomized Corneal Nerve Fibers in Sarm1-Null Adult Mice
Authors: Íñigo-Portugués Almudena , Aleixandre-Carrera Fernando , Sala Salvador , Borrás Fernando , Gomez-Sanchez Jose A. , Arthur-Farraj Peter , Carmen Acosta M. , Belmonte Carlos , Gallar Juana , Meseguer Víctor
Published: January 2025

Axonal regeneration represents a pivotal aspect of the adult peripheral nervous system (PNS). When an injury occurs, peripheral axons are able to regenerate and reestablish connections with their original targets. Although several precision techniques for severing axons in various non-mammalian model organisms have allowed to study the dynamics of regeneration after injury, similar axonal injury models have yet to be fully developed in mammals. In this study, we introduced a novel experimental method for laser-induced axotomy of single corneal sensory subbasal nerve fibers. This method enables thein vivomonitoring and quantification of axonal degeneration and regeneration morphological dynamics in adult mice. Results revealed that the degeneration of the distal stump of the subbasal fiber was delayed in mice lacking the protein SARM1, which promotes degenerative process after injury. Meanwhile, the proximal stump maintained the regenerative dynamics of the subbasal fiber, but regeneration of its nerve terminals was impaired. The present study introduces a valuable model for thein vivostudy of the morphological plasticity dynamics of peripheral axons after injury in genetically tractable adult mammals.
VeCell: A Fiji Plugin to unveil differences in spatio-temporal dynamics of macroglial cell development and proximity to blood vessels
Authors: Guille Naomie , Monnet Héloïse , Hourcade Tristan , Mailly Philippe , Cohen-Salmon Martine , Boulay Anne-Cécile
Published: January 2025

Cortical development results from the proliferation, differentiation, migration and maturation of many cell types. While neuronal development has been extensively studied, the mechanisms regulating the development and maturation of macroglial cells (oligodendrocytes and astrocytes) are still largely to be determined. Here we present VeCell, a Fiji plugin designed to analyse the development of macroglial cells. Using immunolabeling for two transcription factors, Sox9 (specific to macroglial progenitors and astrocytes) and Sox10 (specific to oligodendrocyte lineage), we determined their density, distribution within and across cortical layers and distance to the blood vessels from postnatal day (P) 5 and P60 in the somatosensory cortex. We found that Sox9+ cells are evenly distributed in the cortex with regular intercellular distances and comparable densities between the upper and lower parts of the cortex. In contrast, Sox10+ cells are predominantly concentrated in the lower cortical layers, and exhibited a more random distribution with variable distances between cells. Finally, while confirming the increased density and branching of the vascular network after P5, we also showed that macroglial cells are closer to blood vessels from P15 onward. In summary,VeCellprovides a valuable tool for analyzing the development and spatial organization of macroglial cells. Our findings in the cortex reveal distinct patterns of distribution and proximity to the vasculature for macroglial cells during postnatal development. These insights contribute to a deeper understanding of glial maturation and highlight the dynamic interplay between macroglial cells and the vascular network, offering new avenues for future research into brain development and function.
Technical and biological sources of noise confound multiplexed enhancer AAV screening
Authors: Hunker Avery C. , Mich John K. , Taskin Naz , Torkelson Amy , Pham Trangthanh , Bertagnolli Darren , Chakka Anish Bhaswanth , Chakrabarty Rushil , Donadio Nicholas P. , Ferrer Rebecca , Gasperini Molly , Goldy Jeff , Guzman Junitta B. , Jin Kelly , Khem Shannon , Kutsal Rana , Lalanne Jean-Benoît , Martinez Refugio A. , Newman Dakota , Pena Nick , Shapovalova Nadiya V. , Weed Natalie , Zhou Thomas , Yao Shenqin , Shendure Jay , Smith Kimberly A. , Lein Ed S. , Tasic Bosiljka , Levi Boaz P. , Ting Jonathan T.
Published: January 2025

Cis-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patternsin vivo, a process that currently requires gold-standard one-by-one testing. Here we present a barcoded multiplex strategy for screening enhancer AAVs at cell type resolution using single cell RNA sequencing and taxonomy mapping. We executed a proof-of-concept study using a small pool of validated enhancer AAVs expressing in a variety of neuronal and non-neuronal cell types across the mouse brain. Unexpectedly, we encountered substantial technical and biological noise including chimeric packaging products, necessitating development of novel techniques to accurately deconvolve enhancer expression patterns. These results underscore the need for improved methods to mitigate noise and highlight the complexity of enhancer AAV biologyin vivo.
A compound heterozygosity of two haplotypes in the TTN gene contributes to risk for Cleft Lip and Palate in a recessive manner
Authors: Singh Ved Prakash , Singh Subodh Kumar , Ali Akhtar
Published: January 2025

Cleft lip and palate (CLP) are complex congenital anomalies with multifactorial etiology and significant genetic heterogeneity. This study aimed to elucidate the genetic basis of nonsyndromic CLP in an Indian family, wherein phenotypically normal parents had three affected offspring, including monozygotic twins, all presenting with bilateral complete CLP. Whole exome sequencing (WES) identified a compound heterozygous haplotype in theTTNgene shared by all affected siblings. The paternal haplotype comprised variants c.96140C>T (p.Thr32047Met), c.77412C>G (p.Phe25804Leu), c.2605A>T (p.Thr869Ser), and c.18663A>C (p.Glu6221Asp), while the maternal haplotype included variants c.107779G>A (p.Glu35927Lys), c.103147G>C (p.Glu34383Gln), c.63907G>A (p.Val21303Met), and c.26863A>G (p.Ile8955Val). In silico analyses predicted these variants to have deleterious effects on protein structure and function, consistent with a recessive mode of inheritance. AlthoughTTNis primarily known for its role in muscle structure and function, emerging evidence implicates its involvement in craniofacial development. This study expands the phenotypic spectrum ofTTN-associated disorders and suggests a novel role forTTNin nonsyndromic CLP. These findings underscore the importance of comprehensive genomic analyses in unraveling the molecular mechanisms underlying complex congenital anomalies.
Urban crops demonstrate comparable potential for organic carbon storage as natural ecosystems
Authors: Jiménez-Prieto Beatriz , García-Palacios Pablo , Lorenzo Carmen , Aguilar-Santana Elena , Algora Camelia , Armas Cristina , Bastida Felipe , Calvo Leonor , Casado Coy Nuria , Campos-Castro Axel , Centenaro Giada , Chamizo Sonia , Costa Joana , Martín-Bravo Santiago , Delgado-Baquerizo Manuel , Dashevskaya Svetlana , Carmona-Yáñez María Dolores , Durán Humia Jorge , Fernández-Alonso Maria José , Figueira Daniela , Garcia Eva , Alday Josu G. , de la Riva Enrique G. , Ladrón de Guevara Mónica , López-Velasco Ana , Lucas-Borja Manuel Esteban , Prieto Aguilar Ivan , Pérez-López Jesús , Plaza-Alvárez Pedro Antonio , Rodríguez Pereiras Alexandra , Sanz-Lazaro Carlos , Soliveres Santiago , Terrones Alejandro , Torres Aurora , Leo María
Published: January 2025

Urban greenspaces, encompassing parks, golf courses, roundabouts, and urban crops, have potential to offset urban carbon footprints by storing soil organic carbon (SOC). This study analyzed particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) stocks in topsoil across 27 Iberian cities, comparing urban greenspaces with natural ecosystems under varying climatic and edaphic conditions. Results revealed that urban greenspaces store comparable SOC stocks to natural ecosystems, with MAOC stocks being more dominant and stable across land-use types. POC stocks showed variability, particularly lower in roundabouts and parks compared to natural ecosystems, but remained similar in golf courses and urban crops. SOC fractions correlated inversely with mean annual temperature (MAT), emphasizing the need for cooling strategies in urban areas to preserve stable carbon pools. While MAOC exhibited saturation at higher SOC levels, POC showed a linear increase. This study highlights the importance of tailored management practices to enhance carbon storage in urban soils for climate change mitigation.
Remodeling of nucleosome by a DNA translocating bacterial restriction-modification enzyme
Authors: Sharma Sujata S. Gaiwala , Chand Mahesh Kumar , Ahmed Ishtiyaq , Haque Nibrasul , Saikrishnan Kayarat
Published: January 2025

A eukaryotic cell has specialized ATP-dependent chromatin remodelers, such as SWI/SNF, to unfurl DNA from nucleosome for functional processing. The ATPase that powers the movement of the chromatin remodeler on the DNA (translocation) is evolutionarily related to those powering the translocation of the functionally distinct bacterial restriction-modification (RM) enzymes. The collision of a SWI/SNF chromatin remodeler and a nucleosome, results in sliding/ejection of the constituent histone octamer, while two converging ATP-dependent RM enzymes catalyze DNA cleavage. Here, we investigate if an ATP-dependent Type ISP RM enzyme, an active and directional translocase, can remodel nucleosomes. Our results reveal that in presence of ATP, a Type ISP RM enzyme can displace the octamers from not just mononucleosomes but also two tandem nucleosomes. However, a Type III RM enzyme, which employs a homologous ATPase as a switch to facilitate bidirectional 1D diffusion along the DNA, fails to remodel the nucleosome. This implies that an actively translocating Type ISP RM enzyme generates sufficient force for chromatin remodeling, and may serve as artificial sequence-specific chromatin remodelers.
Stimulus-driven cerebrospinal fluid dynamics is impaired in glaucoma patients
Authors: Bang Ji Won , Parra Carlos , Yu Kevin , Lee Hyun Seo , Wollstein Gadi , Schuman Joel S. , Chan Kevin C.
Published: January 2025

Cerebrospinal fluid (CSF) dynamics, driven by sensory stimulation-induced neuronal activity, is crucial for maintaining homeostasis and clearing metabolic waste. However, it remains unclear whether such CSF flow is impaired in age-related neurodegenerative diseases of the visual system. This study addresses this gap by examining CSF flow during visual stimulation in glaucoma patients and healthy older adults using functional magnetic resonance imaging. The findings reveal that in glaucoma, CSF inflow becomes decoupled from visually evoked blood-oxygenation-level-dependent (BOLD) response. Furthermore, stimulus-locked CSF patterns, characterized by decreases following stimulus onset and increases after offset, diminish as glaucoma severity worsens. Mediation analysis suggests that this flattened CSF pattern is driven by a flatter BOLD slope, resulting in a shallower CSF trough and a reduced rebound. These findings unveil a novel pathophysiological mechanism underlying disrupted stimulation-driven CSF dynamics in glaucoma and highlight potentialin vivobiomarkers for monitoring CSF in the glaucomatous brain.
Large language models outperform traditional structured data-based approaches in identifying immunosuppressed patients
Authors: Guggilla Vijeeth , Kang Mengjia , Bak Melissa J , Tran Steven D , Pawlowski Anna , Nannapaneni Prasanth , Rasmussen Luke V , Schneider Daniel , Donnelly Helen , Agrawal Ankit , Liebovitz David , Misharin Alexander V , Budinger GR Scott , Wunderink Richard G , Walunas Theresa L , Gao Catherine A ,   The NU SCRIPT Study Investigators
Published: January 2025

Identifying immunosuppressed patients using structured data can be challenging. Large language models effectively extract structured concepts from unstructured clinical text. Here we show that GPT-4o outperforms traditional approaches in identifying immunosuppressive conditions and medication use by processing hospital admission notes. We also demonstrate the extensibility of our approach in an external dataset. Cost-effective models like GPT-4o mini and Llama 3.1 also perform well, but not as well as GPT-4o.
Pay-it-forward strategy reduced HPV vaccine delay and increased uptake among catch-up age girls: A randomized clinical trial
Authors: Li Jing , Li Yifan , Qi Chuanyu , He Yu , Lu Haidong , Xie Yewei , Ong Jason J. , Lu Yajiao , Yang Ying , Yang Fan , Du Heng , Gong Wenfeng , Zou Fei , Larson Heidi J. , Jit Mark , Lin Leesa , Smith Jennifer S. , Geng Elvin H. , Xu Dong , Tang Weiming , Tang Shenglan , Tucker Joseph D. , Wu Dan
Published: January 2025

Background

Catch-up HPV vaccination is challenging in many low and middle-income countries (LMICs). Pay-it-forward offers an individual a subsidized vaccine, then an opportunity to donate to help others access vaccinations. Our randomized control trial assessed the effectiveness of pay-it-forward in improving HPV vaccination among girls aged 15-18 years in China.

Methods and findings

Eligible participants were randomly assigned to either the pay-it-forward arm or standard-of-care arm (self-paid vaccination). The primary outcome was the first-dose HPV vaccination rate, verified against clinical records. Among 321 participants enrolled, most caregivers were female (80.1%). In the pay-it-forward arm, 55 of 161 (34.2%) girls received the HPV vaccine, compared with 28 of 160 (17.5%) girls in the standard-of-care arm (adjusted proportion difference = 17.9%, 95% CI: 8.7, 27.0, P<0.001). Among 55 girls in the pay-it-forward arm who received the vaccination, 37 (67.3%) wrote a postcard message, and 39 (70.9%) of their caregivers donated to support future girls. The financial cost per person vaccinated was $294 in the standard-of-care arm and $230 in the pay-it-forward arm.

Conclusions

The pro-social pay-it-forward strategy was effective to increase catch-up HPV vaccination among teenage girls with comparable costs.

Trial Registration

ChiCTR2200055542
A novel inhibitor against the bromodomainPfBDP1 of the malaria pathogenPlasmodium falciparum
Authors: Amann Marius , Warstat Robin , Rechten Kay Kristin , Theuer Philip , Schustereder Magdalena , Clavey Sophie , Breit Bernhard , Einsle Oliver , Huegle Martin , Petter Michaela , Guenther Stefan
Published: January 2025

The rise of drug resistances in malaria necessitates the exploration of novel therapeutic strategies. Targeting epigenetic pathways could open new, promising treatment avenues. In this study, we focus onPfBDP1, an essential bromodomain protein inP. falciparum. Utilizing the pan-selective bromodomain inhibitor MPM6, we identified a potent initial hit and subsequently developed it into a nanomolar binder. Through a combination of virtual docking, isothermal titration calorimetry, and X-ray crystallography, we elucidated the molecular interactions of the new inhibitors withPfBD1. Our findings include the first cocrystallized structures ofPfBD1 andPvBD1 with these inhibitors, providing insights into their binding mechanisms. Further validation using conditional knockdown ofPfBDP1 inP. falciparumdemonstrated parasite sensitivity to the inhibitor, underscoring its potential as a targeted therapeutic approach against malaria.
Electro-composting: an emerging technology
Authors: Hozad Ahmad Shabir , Abendroth Christian
Published: January 2025

The present study focuses on electrical stimulation for composting. Using the PSALSAR method, a systematic review resulted in 24 relevant articles. For each system, the review describes key materials, composter design, operating conditions, temperature evolution, compost maturity, microbial community, and outcome. The examined studies fall into four main systems: electric field-assisted aerobic composting (EAAC), electrolytic oxygen aerobic composting (EOAC), microbial fuel cells (MFC), and thermoelectric generators (TEG). Apart from the main systems highlighted above, there is a rare case, which remains hardly studied. This includes bioelectrochemically assisted anaerobic composting (AnCBE, III). EAAC and EOAC systems biologically balance microbial activity and organic matter decomposition, whereas MFC and TEG systems have dual functioning due to energy generated alongside waste degradation. These innovative systems significantly improve composting efficiency by speeding up organic matter breakdown, increasing oxygen supply, and facilitating energy recovery. Together, they overcome the drawbacks of conventional composting systems and promote more environmentally friendly waste management solutions.

Research Highlights

The four most frequently investigated electro-composting systems are EAAC, EOAC, MFC, and TEG.

MFCs make it easier to turn organic waste into electricity, which makes decomposition more environmentally friendly.

Thermal energy generated during decomposition is utilized by TEGs to produce electricity.

The research on AnCBEis highly limited.
Optimizing SARS-CoV-2 RBD Boundaries for EnhancedE. coliExpression
Authors: Biswas Anamika , Sarkar Arighna , Raran-Kurussi Sreejith , Mandal Kalyaneswar
Published: January 2025

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a significant risk to global health, warranting the formulation of efficient preventive and therapeutic measures to tackle its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of coronaviruses plays a pivotal role in viral attachment and entry into host cells. The receptor-binding domain (RBD) of the SARS-CoV-2 S protein has demonstrated a robust binding affinity to ACE2 receptors in humans. Consequently, it has become a prime target for therapeutic interventions using antibodies, vaccines, or other designed inhibitors. This paper presents an optimized RBD sequence that can be efficiently expressed inEscherichia coliand refolded to yield a functional protein. Using optimized refolding procedures, we obtained 10-12 mg of active protein from a one-liter LB culture. The biological activity of the refolded RBD was confirmed by monitoring its interaction with the designed LCB1 miniprotein ligand by surface plasmon resonance, wherein they exhibited significant affinity levels as reflected by their dissociation constants (KDs < 10 nM). The resulting RBD could be an ideal target for designing potent COVID-19 antivirals.
The quantitative spatiotemporal relationship of whole brain activity of human brains revealed by fMRI
Authors: Huang Jie
Published: January 2025

Human brain consists of many functional systems from the essential sensory, motor, attention and memory systems to higher order cognitive functions such as reasoning and language. Performing even a simple task may evoke multiple systems and cognitive functions, resulting in a whole brain activity across the entire brain. Despite the importance of studying task-evoked brain activated networks, investigating this whole brain activity may be crucial for understanding the neural bases of individual behavioral and clinical traits. BOLD-fMRI measures the four-dimensional (3 spatial and 1 temporal) neural activity across the entire brain at large-scale systems level. All local activities across the entire brain constitute the whole brain activity and each local activity is a part of that whole brain activity. Unlike a local activity that is characterized by its temporal neural activity, the whole brain activity is characterized by its spatial variation across the entire brain. We present a novel data-driven method to analyze the whole brain activity when performing tasks. The method enabled us to analyze the whole brain activity for each task trial and each individual subject with no requirement of a priori knowledge of task-evoked BOLD response. Our study revealed a quantitative spatiotemporal relationship of the whole brain activity with the local activities. The whole brain activity demonstrated a remarkable dynamic activity that varied from trial to trial when performing the same task repeatedly, showing the importance of analyzing the whole brain activity for investigating the neural bases of personal traits.
Thalamic involvement defines distinct slow-wave subtypes in NREM sleep
Authors: Bergamo Damiana , Handjaras Giacomo , Picchioni Dante , Ricciardi Emiliano , Özbay Pınar S. , de Zwart Jacco A. , Duyn Jeff H. , Bernardi Giulio , Betta Monica
Published: January 2025

Slow waves (0.5–4 Hz) are a key feature of non-rapid-eye-movement (NREM) sleep, traditionally believed to arise from neocortical circuits. However, growing evidence suggests that subcortical structures, particularly the thalamus, may play a crucial role in initiating and synchronizing slow waves. We tested the hypothesis that slow waves may arise from distinct cortico-cortical and thalamo-cortical mechanisms using simultaneous EEG-fMRI in healthy adults. Spatial mapping based on thalamic fMRI responses revealed two slow-wave associated clusters. Cluster-1 C1, characterized by an early thalamic fMRI-signal increase, corresponded to large, efficiently synchronized waves associated with sleep spindles and with markers of higher arousal and autonomic activation. Cluster-2 C2, marked by an initial negative fMRI response, corresponded to smaller slow waves potentially resulting from cortico-cortical synchronization. These waves tended to more often occur during low-fragility phases of NREM sleep. These findings highlight distinct slow-wave subtypes with different thalamic involvement and, potentially, synchronization mechanisms.
Isometric handgrip contraction increases tibialis anterior intrinsic motoneuron excitability in a dose-dependent manner
Authors: Ugliara L. , Orssatto L. B. R. , Vieira A. , Trajano G. S.
Published: January 2025

Persistent inward currents (PICs) contribution to motoneuron firing in the lower limb typically increase after a remote handgrip contraction, believed to result from diffuse increases of serotonergic input on the spinal cord. We investigated whether handgrip contraction intensity, duration, and/or impulse would affect tibialis anterior estimates of PICs. High-density electromyograms were recorded from the tibialis anterior of 21 participants (18-40 years) during 20% dorsiflexion before and after four handgrip conditions: i)80%15s, 80% of their maximal handgrip strength sustained for 15s; ii)40%15s, 40% sustained for 15s; iii)40%30s, 40% sustained for 30s; and iv)Control(no handgrip). PICs contribution to motoneuron firing was estimated with the delta frequency (ΔF) using the paired motor unit analysis. The ‘brace height’, normalised as a percentage of a right triangle (%rTri), was used to quantify the effects of PICs on the non-linearity of firing patterns, representing the neuromodulatory drive (regulation of neural activity via neurotransmitter actions) onto the motoneurons. ΔF increased by 0.30 peaks per second (pps; 95%CI 0.11–0.49,d=0.37) after40%30sand by 0.20 pps (0.04–0.36,d=0.24) after80%15sbut remained unchanged after40%15sandControl. Similarly, brace height increased by 2.39 %rTri (0.55–4.23,d=0.25) after40%30sand by 2.74 %rTri (1.14–4.34,d=0.28) after80%15s;remaining unchanged after40%15sandControl. The increase in PICs contribution to motoneuron firing induced by a remote handgrip contraction is impulse-dependent rather than intensity or duration. The parallel increases in ΔF and brace height suggest augmented neuromodulatory input onto the spinal cord.
The impact of EEG preprocessing parameters on ultra-low-power seizure detection
Authors: Reisinger Patrick , Larochelle Jonathan , Abkai Ciamak , Kalousios Sotirios , Zabler Nico , Dümpelmann Matthias , Schulze-Bonhage Andreas , Woias Peter , Comella Laura
Published: January 2025

Objective

Closed-loop neurostimulation is a promising treatment for drug-resistant focal epilepsy. A major challenge is fast and reliable seizure detection via electroencephalography (EEG). While many approaches have been published, they often lack statistical power and practical utility. The use of various EEG preprocessing parameters and performance metrics hampers comparability. Additionally, the critical issue of energy consumption for an application in medical devices is rarely considered. Addressing these points, we present a systematic analysis on the impact of EEG preprocessing parameters on seizure detection performance and energy consumption, using one to four EEG channels.

Methods

We analyzed in 145 focal epilepsy patients the impact of different sampling rates, window sizes, digital resolutions and number of EEG channels on seizure detection performance and energy consumption. Focusing on practice-relevant metrics, we evaluated seizure detection performance of a state-of-the-art convolutional neural network (CNN) via the Seizure Community Open-Source Research Evaluation (SzCORE) framework. Statistical relevance of parameter changes was assessed using linear mixed-effects models. Energy consumption was analyzed using an ultra-low-power microcontroller.

Results

Reducing the sampling rate from 256 to 64 Hz led to a decrease in sensitivity and false detections per hour (FD/h; allpvalues < .001). Longer window sizes reduced the number of FD/h and increased average detection delays between one second and all other sizes (allpvalues < .001). Lower digital resolutions decreased sensitivity between 16 and 8 bits (p< .001). Using only one EEG channel led to a decrease in sensitivity (p< .001) and FD/h (p= .008) compared to four channels. Energy consumption was especially decreased when reducing the sampling rate and number of EEG channels.

Significance

This study provides guidance on choosing EEG preprocessing parameters for innovative developments of closed-loop neurostimulation devices to further advance the treatment of drug-resistant focal epilepsy.

Key points

A major challenge in closed-loop neurostimulation is fast and reliable seizure detection, ideally with minimal energy consumption.

Many published seizure detection approaches are not ready for application and lack statistical power and comparability.

The impact of EEG preprocessing parameters was systematically evaluated in 145 focal epilepsy patients.

The chosen window size and number of channels had the strongest impact on seizure detection performance and energy consumption.

Our results offer guidance for EEG preprocessing choices to advance the treatment of drug-resistant focal epilepsy.
OpenEMMU: a versatile, open-source EdU multiplexing methodology for studying DNA replication and cell cycle dynamics
Authors: Contreras Osvaldo , Thekkedam Chris , Zaunders John , Aguirre-MacLennan Ismael , Murray Nicholas J. , Gonzalez-Cordero Anai , Harvey Richard P.
Published: January 2025

5-Ethynyl-2’-deoxyuridine (EdU) has transformed DNA replication and cell cycle analyses through fast and efficient click chemistry detection. However, commercial EdU kits are expensive, contain proprietary reagents, are suboptimal for antibody multiplexing, and are challenging to use with larger biological specimens, highlighting the need for innovation. Here, we report Open-source EdU Multiplexing Methodology for Understanding DNA replication dynamics (OpenEMMU), an optimized, affordable, and user-friendly click chemistry resource using off-the-shelf reagents. OpenEMMU improves the efficiency, brightness, and multiplexing capabilities of EdU thymidine analog staining with both non-conjugated and conjugated antibodies across various cell types. We validated its effectiveness for fluorescent imaging of nascent DNA in developing embryos and organs, including the embryonic heart and forelimbs, and in 3D hiPSC-derived cardiac organoids. OpenEMMU also enabled 3D imaging of DNA synthesis in zebrafish larvae at fine resolution. This opens new avenues for insights into organismal development and growth, cell proliferation, and DNA replication, with precision and flexibility that surpass traditional methods.

Teaser

An open-source and cost-effective resource for DNA replication profiling and cell cycle analysis using click chemistry.