bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry
Authors: Crotti Lia , Spazzolini Carla , Nyegaard Mette , Overgaard Michael T , Kotta Maria-Christina , Dagradi Federica , Sala Luca , Aiba Takeshi , Ayers Mark D , Baban Anwar , Barc Julien , Beach Cheyenne M , Behr Elijah R , Bos J Martijn , Cerrone Marina , Covi Peter , Cuneo Bettina , Denjoy Isabelle , Donner Birgit , Elbert Adrienne , Eliasson Håkan , Etheridge Susan P , Fukuyama Megumi , Girolami Francesca , Hamilton Robert , Horie Minoru , Iascone Maria , Jaimez Juan Jiménez , Jensen Henrik Kjærulf , Kannankeril Prince J , Kaski Juan P , Makita Naomasa , Muñoz-Esparza Carmen , Odland Hans H , Ohno Seiko , Papagiannis John , Porretta Alessandra Pia , Prandstetter Christopher , Probst Vincent , Robyns Tomas , Rosenthal Eric , Rosés-Noguer Ferran , Sekarski Nicole , Singh Anoop , Spentzou Georgia , Stute Fridrike , Tfelt-Hansen Jacob , Till Jan , Tobert Kathryn E , Vinocur Jeffrey M , Webster Gregory , Wilde Arthur A M , Wolf Cordula M , Ackerman Michael J , Schwartz Peter J
Published: August 2023

Aims

Calmodulinopathy due to mutations in any of the three CALM genes (CALM1–3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms.

Methods and results

The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5–19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing.

Conclusion

Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter–defibrillator.
Dietary fruits and vegetables and risk of cardiovascular diseases in elderly Chinese
Authors: Wang Kang , Chen Zhangling , Shen Maoqi , Chen Pengfei , Xiao Yichao , Fang Zhenfei , Hu Xinqun , Tang Jianjun , Liu Qiming , Zhou Shenghua
Published: August 2023

Background

Evidence regarding the potential effect of fruit and vegetable consumption on cardiovascular diseases (CVD) was limited and inconsistent among Asian people.

Methods

We prospectively examined associations of fruit and vegetable consumption with the risk of CVD among 9740 participants aged 65 years and older (mean baseline age: 88 years) in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (2008–2018). Dietary data were collected using a validated food frequency questionnaire.

Results

During 37 366 person-years of follow-up, a total of 3738 CVD cases were recorded. After adjusting for demographics, dietary, lifestyle and economical social factors, higher intakes of total fruits and vegetables were associated with lower risk of CVD [comparing with extreme quintiles, hazard ratio and 95% confidence interval: 0.84 (0.74, 0.95)]. The inverse association was mainly driven by vegetable consumption [0.86 (0.77, 0.95)]. Furthermore, the inverse association was stronger for the risk of hypertension [0.84 (0.72, 0.98)]. These associations were consistent across age, sex, body mass index, residence, exercise status, smoking, drinking, meat intake, modified hPDI and health status.

Conclusions

This study suggests higher intakes of total fruits and vegetables are associated with a lower risk of CVD among elderly Chinese people, supporting the current recommendations of increasing fruit and vegetable consumption as part of a healthy diet for the prevention of CVD.
Effectiveness of primary care interventions in conjointly treating comorbid chronic pain and depression: a systematic review and meta-analysis
Authors: Patel Krishna H , Chrisinger Benjamin
Published: August 2023

Background

Chronic pain and depression are highly comorbid, but the lack of consensus on the best treatment strategies puts patients at high risk of suboptimal care-coordination as well as health and social complications. Therefore, this study aims to quantitatively assesses how effective different primary care interventions have been in treating the comorbid state of chronic pain and depression. In particular, this study evaluates both short-term outcomes—based specifically on measures of chronic pain and depression during an intervention itself—and long-term outcomes or measures of pain and depression in the months after conclusion of the formal study intervention.

Methods

This study is a systematic review and meta-analysis of randomised-controlled trials (RCTs) enrolling patients with concurrent chronic pain and depression. Intensity and severity of pain and depression symptoms were the primary outcomes. The main inclusion criteria were RCTs that: (i) enrolled patients diagnosed with depression and chronic pain, (ii) occurred in primary care settings, (iii) reported baseline and post-intervention outcomes for chronic pain and depression, (iv) lasted at least 8 weeks, and (v) used clinically validated outcome measures. Risk of bias was appraised with the Risk of Bias 2 tool, and GRADE guidelines were used to evaluate the quality of evidence.

Results

Of 692 screened citations, 7 multicomponent primary care interventions tested across 891 patients were included. Meta-analyses revealed significant improvements in depression at post-intervention (SMD = 0.44, 95% CI [0.17, 0.71], P = 0.0014) and follow-up (SMD = 0.41, 95% CI [0.01, 0.81], P = 0.0448). Non-significant effects were observed for chronic pain at post-intervention (SMD = 0.27, 95% CI [−0.08, 0.61], P = 0.1287) and follow-up (SMD = 0.13, 95% CI [−0.3, 0.56], P = 0.5432).

Conclusions

Based on the results of the meta-analysis, primary care interventions largely yielded small to moderate positive effects for depressive symptoms and no significant effects on pain. In one study, stepped-care to be more effective in treatment of comorbid chronic pain and depression than other interventions both during the intervention and upon post-intervention follow-up. As such, depression appears more amenable to treatment than pain, but the number of published RCTs assessing both conditions is limited. More research is needed to further develop optimal treatment strategies.
Histology, physiology, and transcriptomic and metabolomic profiling reveal the developmental dynamics of annual shoots in tree peonies (Paeonia suffruticosa Andr.)
Authors: Tong Ningning , Shu Qingyan , Wang Baichen , Peng Liping , Liu Zheng'an
Published: August 2023

The development of tree peony annual shoots is characterized by “withering”, which is related to whether there are bud points in the leaf axillaries of annual shoots. However, the mechanism of “withering” in tree peony is still unclear. In this study, Paeonia ostii ‘Fengdan’ and P. suffruticosa ‘Luoyanghong’ were used to investigate dynamic changes of annual shoots through anatomy, physiology, transcriptome, and metabolome. The results demonstrated that the developmental dynamics of annual shoots of the two cultivars were comparable. The withering degree of P. suffruticosa ‘Luoyanghong’ was higher than that of P. ostii ‘Fengdan’, and their upper internodes of annual flowering shoots had a lower degree of lignin deposition, cellulose, C/N ratio, showing no obvious sclerenchyma, than the bottom ones and the whole internodes of vegetative shoot, which resulted in the “withering” of upper internodes. A total of 36 phytohormone metabolites were detected, of which 33 and 31 were detected in P. ostii ‘Fengdan’ and P. suffruticosa ‘Luoyanghong’, respectively. In addition, 302 and 240 differentially expressed genes related to lignin biosynthesis, carbon and nitrogen metabolism, plant hormone signal transduction, and zeatin biosynthesis were screened from the two cultivars. Furtherly, 36 structural genes and 40 transcription factors associated with the development of annual shoots were highly co-expressed, and eight hub genes involved in this developmental process were identified. Consequently, this study explained the developmental dynamic on the varied annual shoots through multi-omics, providing a theoretical foundation for germplasm innovation and the mechanized harvesting of tree peony annual shoots.
Motivational Interviewing and Chronic Care Management Using the Transtheoretical Model of Change
Authors: Wood Angela R , Ross Levi , Wood Ralph J
Published: August 2023

The number of Americans living with chronic health conditions has steadily increased. Chronic diseases are the leading causes of death and disability in the United States and cost the healthcare system an estimated $4.1 trillion dollars a year. The role of social workers in assisting patients in the management of their chronic diseases is vital. The behavioral health changes often required of chronic care management (CCM) patients require support and intervention by professionals to help the patient improve self-management of their chronic health conditions. Motivational interviewing (MI) is an evidence-based practice that helps people change by paying attention to the language patients use as they discuss their change goals and behaviors. Applying the principles and strategies of MI within the stages of change model (transtheoretical model of change) can help social workers better understand and assist patients receiving CCM. This article outlines specific strategies the social worker can use to address motivation at different stages of change.
Genomics of Marine Larval Evolution and Development
Authors: Zakas Christina , Martín-Durán José M
Published: August 2023

Synopsis

Functional and ecological genomics in emerging marine models is shaping our views on new and fundamental biological questions. Representing a wealth of morphological, behavioral, and developmental adaptations, marine organisms are a key group for studying ancestral and shared body plan patterns, as well as some of the most intriguing novelties in animals. Here, we outline key questions, resources, and approaches to advance our understanding of marine larva biology and evolution that were covered in the recent symposium “Genomics of marine larval evolution and development.” Over 2 days, researchers from multiple continents, career stages, and research interests, covering a range of taxonomic diversity, contributed to three emerging topics: (1) Understanding the genetic basis of larval morphology and behaviors; (2) Finding the genomic basis for body plan development and novel morphologies; and (3) Constructing genomic tools in development for comparative insights. In this short piece, we highlight some of the most relevant findings on how different developmental modes and larval forms evolve.
Innovation on technological “islands”: domain contrast, boundary spanning, knowledge depth and breadth
Authors: Ubisch Sverre , Wang Pengfei
Published: August 2023

Prior literature has long examined innovation as a recombination process within or across the boundaries of technological domains. However, limited attention is paid to boundaries per se. Building upon recent development of categorical contrast, this study distinguishes domains with crisp boundaries from those with fuzzy boundaries and examines their effects on innovation outputs. Analyzing a large sample of US patents, we find that spanning crisp boundaries is more likely to generate impactful inventions but at the same time leads to significantly higher recombinant uncertainty. We continue to explore what types of inventors are better able to span such types of domain boundaries. Focusing specifically on the role of inventors’ knowledge expertise, we find that while both knowledge depth and breadth enhance the impact of technologies that span crisp boundaries, knowledge breadth is also found to escalate the associated uncertainty. Our emphasis on the contrast of technological domains contributes to the literature on recombinative innovation and boundary spanning.
Risk of Subsequent Respiratory Virus Detection After Primary Virus Detection in a Community Household Study—King County, Washington, 2019–2021
Authors: Heimonen Jessica , Chow Eric J , Wang Yongzhe , Hughes James P , Rogers Julia , Emanuels Anne , O’Hanlon Jessica , Han Peter D , Wolf Caitlin R , Logue Jennifer K , Ogokeh Constance E , Rolfes Melissa A , Uyeki Timothy M , Starita Lea , Englund Janet A , Chu Helen Y
Published: August 2023

Background

The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described.

Methods

From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection.

Results

Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03–2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant.

Conclusions

Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.
P25 Healthcare associated candiduria in ICU patients: experience from a surveillance network in India, 2017–22
Authors: Vedachalam Srividya K , Thakur Arpan Kumar , Parveen Rasna , Puraswani Mamta , Srivastav Sharad , Ningombam Aparna , Walia Kamini , Siromany Valan A , VanderEnde Daniel , Malpiedi Paul A , Vasquez Amber M , Mathur Purva ,   Indian Healthcare Associated Infection Surveillance Network Collaborators
Published: August 2023

Background

Urinary tract infections (UTI) are common healthcare associated infections (HAI) in low-and-middle-income countries including India, with limited information on Candida UTI. An ICU-based HAI surveillance network of tertiary care hospitals across India, coordinated by the All-India Institute of Medical Sciences, New Delhi and the Indian Council of Medical Research, modified the US CDC’s National Healthcare Safety Network (NHSN) case definitions to record UTI. Unlike NHSN, India surveillance includes fungal pathogens, such as Candida spp., as eligible pathogens causing HAI-UTI. We describe the epidemiology, microbiology and antimicrobial resistance (AMR) profile of candiduria cases reported to this network to address the knowledge gap on Candida UTI in India.

Methods

Patients with at least one UTI symptom and a positive urine culture with Candida sp. who had spent at least 2 calendar days in a participating ICU were included as candiduria events. All candiduria events reported by participating sites from 1 November 2017 to 31 May 2022 were extracted from overall UTI reported for all pathogens. The distribution of events by age, gender, ICU type, urinary catheterization, pathogen and drug resistance profile were performed. UTI rate and device utilization ratio (DUR) were calculated. Network sites performed antifungal susceptibility testing (AST) on Candida isolates using MIC-based method as per CLSI guidelines.

Results

Data was reported by 131 ICUs in 39 hospitals. Overall network UTI events including all pathogens were 3600; UTI rates were 2.6 (adult ICUs) and 1.3 (paediatric ICUs); DUR was 0.8 (adult ICUs) and 0.4 (paediatric ICUs). There were 1111 candiduria events, 95% were classified as catheter-associated UTI (CAUTI), and the median age of patients was 65 years (IQR 32–74 years) and 58% were male. Among 739 Candida isolates speciated, Candida tropicalis (37%), Candida albicans (36%), Candida glabrata (6%) and Candida auris (6%) were the top four species isolated. Among 220 C. tropicalis isolates tested with AST, 6.9% were fluconazole resistant and 2% of 140 were caspofungin resistant; 7% of 177 C. albicans isolates were fluconazole resistant and 6.5% of 92 isolates were caspofungin resistant; and 48% of 28 C. glabrata isolates were fluconazole resistant and 44% of 18 isolates were caspofungin resistant.

Conclusions

Candiduria events reported from ICUs to the HAI surveillance network-India are common and the majority are classified as CAUTI. Most of the species isolated are susceptible to fluconazole and caspofungin. Additional work is needed to understand the clinical significance of candiduria events reported to the network.
Two complementary AI approaches for predicting UMLS semantic group assignment: heuristic reasoning and deep learning
Authors: Mao Yuqing , Miller Randolph A , Bodenreider Olivier , Nguyen Vinh , Fung Kin Wah
Published: August 2023

Objective

Use heuristic, deep learning (DL), and hybrid AI methods to predict semantic group (SG) assignments for new UMLS Metathesaurus atoms, with target accuracy ≥95%.

Materials and Methods

We used train-test datasets from successive 2020AA–2022AB UMLS Metathesaurus releases. Our heuristic “waterfall” approach employed a sequence of 7 different SG prediction methods. Atoms not qualifying for a method were passed on to the next method. The DL approach generated BioWordVec and SapBERT embeddings for atom names, BioWordVec embeddings for source vocabulary names, and BioWordVec embeddings for atom names of the second-to-top nodes of an atom’s source hierarchy. We fed a concatenation of the 4 embeddings into a fully connected multilayer neural network with an output layer of 15 nodes (one for each SG). For both approaches, we developed methods to estimate the probability that their predicted SG for an atom would be correct. Based on these estimations, we developed 2 hybrid SG prediction methods combining the strengths of heuristic and DL methods.

Results

The heuristic waterfall approach accurately predicted 94.3% of SGs for 1 563 692 new unseen atoms. The DL accuracy on the same dataset was also 94.3%. The hybrid approaches achieved an average accuracy of 96.5%.

Conclusion

Our study demonstrated that AI methods can predict SG assignments for new UMLS atoms with sufficient accuracy to be potentially useful as an intermediate step in the time-consuming task of assigning new atoms to UMLS concepts. We showed that for SG prediction, combining heuristic methods and DL methods can produce better results than either alone.
Northeast Regional Center for Excellence in Vector-Borne Diseases’ Master of Science training program: a curriculum to support future capacity in public health entomology
Authors: Harrington Laura C , Mader Emily M
Published: August 2023

A major lack of expertise in vector biology, surveillance, and control for public health professionals has been acknowledged over the past several decades, especially in light of the introduction of West Nile and Zika viruses to the United States. To address this growing need, the Northeast Regional Center for Excellence in Vector-Borne Diseases (NEVBD) designed a unique educational program to cross-train students in the fundamentals of vector biology and public health. Here, we summarize the formation, evaluation, and outcomes of NEVBD’s Master of Science in Entomology: Vector-Borne Disease Biology program and provide details on core competencies to enable adoption and adaptation of the program to other institutions and contexts. A discussion of major barriers to filling the nation’s need for public health personnel with medical entomology training, such as financial barriers and recruitment of underrepresented students, is presented. We conclude with considerations for administering these training programs.
Racial and ethnic and socioeconomic disparities in childhood cancer incidence trends in the United States, 2000-2019
Authors: Monterroso Pablo S , Li Zhaoheng , Domingues Allison M , Sample Jeannette M , Marcotte Erin L
Published: August 2023

Background

Population-based surveillance of pediatric cancer incidence trends is critical to determine high-risk populations, drive hypothesis generation, and uncover etiologic heterogeneity. We provide a comprehensive update to the current understanding of pediatric cancer incidence trends by sex, race and ethnicity, and socioeconomic status (SES).

Methods

The Surveillance, Epidemiology, and End Results 22 data (2000-2019) was used to summarize age-adjusted incidence rates for children and adolescents aged 0-19 years at diagnosis. The annual percentage change (APC) and 95% confidence interval (CI) were estimated to evaluate incidence trends by sex, race and ethnicity, and SES overall and for cancer subtypes. Tests of statistical significance were 2-sided.

Results

Substantial variation was observed overall and for several histologic types in race and ethnicity– and SES–specific rates. Overall, we observed a statistically significant increase in incidence rates (APC = 0.8%, 95% CI = 0.6% to 1.1%). All race and ethnic groups saw an increase in incidence rates, with the largest occurring among non-Hispanic American Indian and Alaska Native children and adolescents (APC = 1.7%, 95% CI = 0.5% to 2.8%) and the smallest increase occurring among non-Hispanic White children and adolescents (APC = 0.7%, 95% CI = 0.5% to 1.0%). The lowest SES quintiles saw statistically significant increasing trends, while the highest quintile remained relatively stable (quintile 1 [Q1] APC = 1.6%, 95% CI = 0.6% to 2.6%; quintile 5 [Q5] APC = 0.3%, 95% CI = –0.1% to 0.7%).

Conclusions

Childhood cancer incidence is increasing overall and among every race and ethnic group. Variation by race and ethnicity and SES may enable hypothesis generation on drivers of disparities observed.
Wasserstein barycenter for link prediction in temporal networks
Authors: Spelta Alessandro , Pecora Nicolò
Published: August 2023

We propose a flexible link forecast methodology for weighted temporal networks. Our probabilistic model estimates the evolving link dynamics among a set of nodes through Wasserstein barycentric coordinates arising within the optimal transport theory. Optimal transport theory is employed to interpolate among network evolution sequences and to compute the probability distribution of forthcoming links. Besides generating point link forecasts for weighted networks, the methodology provides the probability that a link attains weights in a certain interval, namely a quantile of the weights distribution. We test our approach to forecast the link dynamics of the worldwide Foreign Direct Investments network and of the World Trade Network, comparing the performance of the proposed methodology against several alternative models. The performance is evaluated by applying non-parametric diagnostics derived from binary classifications and error measures for regression models. We find that the optimal transport framework outperforms all the competing models when considering quantile forecast. On the other hand, for point forecast, our methodology produces accurate results that are comparable with the best performing alternative model. Results also highlight the role played by model constraints in the determination of future links emphasising that weights are better predicted when accounting for geographical rather than economic distance.
Spectropolarimetric study of 4U 1630−47 in steep power-law state with IXPE and NICER
Authors: Rawat Divya , Garg Akash , Méndez Mariano
Published: August 2023

We probe the spectropolarimetric properties of the black hole binary source 4U 1630−47 in the steep power-law state. We detect a significant polarization fraction of ∼7 per cent at a polarization angle of ∼21°. The 2–12 keV NICER spectrum can be fitted with a combination of a thermal and a Comptonization component, the latter characterized by a spectral index, Γ ∼ 2.1, along with a reflection feature at ∼7.0 keV. In the 2–8 keV band, the degree of polarization of 4U 1630−47 in the steep power-law state is 4.4σ different from the value previously measured in the high-soft state. In the steep power-law state, the polarization fraction increases as a function of energy but exhibits an overall drop in each energy band compared to that of the high-soft state. We propose that the decrease in the polarization fraction in the steep power-law state could be attributed to the presence of a corona. The observed polarization properties in both states can be explained by the self-irradiation of the disc around a Kerr black hole, likely influenced by the frame dragging effect.
Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells
Authors: Zanin Irene , Ruggiero Emanuela , Nicoletto Giulia , Lago Sara , Maurizio Ilaria , Gallina Irene , Richter Sara N
Published: August 2023

i-Motifs (iMs) are four-stranded DNA structures that form at cytosine (C)-rich sequences in acidic conditions in vitro. Their formation in cells is still under debate. We performed CUT&Tag sequencing using the anti-iM antibody iMab and showed that iMs form within the human genome in live cells. We mapped iMs in two human cell lines and recovered C-rich sequences that were confirmed to fold into iMs in vitro. We found that iMs in cells are mainly present at actively transcribing gene promoters, in open chromatin regions, they overlap with R-loops, and their abundance and distribution are specific to each cell type. iMs with both long and short C-tracts were recovered, further extending the relevance of iMs. By simultaneously mapping G-quadruplexes (G4s), which form at guanine-rich regions, and comparing the results with iMs, we proved that the two structures can form in independent regions; however, when both iMs and G4s are present in the same genomic tract, their formation is enhanced. iMs and G4s were mainly found at genes with low and high transcription rates, respectively. Our findings support the in vivo formation of iM structures and provide new insights into their interplay with G4s as new regulatory elements in the human genome.
Isocitrate dehydrogenase wt and IDHmut adult-type diffuse gliomas display distinct alterations in ribosome biogenesis and 2’O-methylation of ribosomal RNA
Authors: Paraqindes Hermes , Mourksi Nour-El-Houda , Ballesta Samantha , Hedjam Jordan , Bourdelais Fleur , Fenouil Tanguy , Picart Thiébaud , Catez Frédéric , Combe Théo , Ferrari Anthony , Kielbassa Janice , Thomas Emilie , Tonon Laurie , Viari Alain , Attignon Valéry , Carrere Marjorie , Perrossier Jessie , Giraud Stéphane , Vanbelle Christophe , Gabut Mathieu , Bergeron Danny , Scott Michelle S , Castro Vega Luis , Magne Nathalie , Huillard Emmanuelle , Sanson Marc , Meyronet David , Diaz Jean-Jacques , Ducray François , Marcel Virginie , Durand Sébastien
Published: August 2023

Background

High-grade adult-type diffuse gliomas (HGGs) constitute a heterogeneous group of aggressive tumors that are mostly incurable. Recent advances highlighting the contribution of ribosomes to cancer development have offered new clinical perspectives. Here, we uncovered that isocitrate dehydrogenase (IDH)wt and IDHmut HGGs display distinct alterations of ribosome biology, in terms of rRNA epitranscriptomics and ribosome biogenesis, which could constitute novel hallmarks that can be exploited for the management of these pathologies.

Methods

We analyzed (1) the ribosomal RNA 2’O-ribose methylation (rRNA 2’Ome) using RiboMethSeq and in-house developed bioinformatics tools (https://github.com/RibosomeCRCL/ribomethseq-nfandrRMSAnalyzer) on 3 independent cohorts compiling 71 HGGs (IDHwt n = 30, IDHmut n = 41) and 9 non-neoplastic samples, (2) the expression of ribosome biogenesis factors using medium throughput RT-qPCR as a readout of ribosome biogenesis, and (3) the sensitivity of 5 HGG cell lines to RNA Pol I inhibitors (CX5461, BMH-21).

Results

Unsupervised analysis demonstrated that HGGs could be distinguished based on their rRNA 2’Ome epitranscriptomic profile, with IDHwt glioblastomas displaying the most significant alterations of rRNA 2’Ome at specific sites. In contrast, IDHmut HGGs are largely characterized by an overexpression of ribosome biogenesis factors compared to non-neoplastic tissues or IDHwt glioblastomas. Finally, IDHmut HGG-derived spheroids display higher cytotoxicity to CX5461 than IDHwt glioblastoma, while all HGG spheroids display a similar cytotoxicity to BMH-21.

Conclusions

In HGGs, IDH mutational status is associated with specific alterations of the ribosome biology and with distinct sensitivities to RNA Pol I inhibitors.
Long-term outcomes with reduced-dose whole-brain radiotherapy and a stereotactic radiosurgery boost for primary central nervous system lymphoma
Authors: Foreman Bronwen E , Mullikin Trey C , Floyd Scott R , Kelsey Chris R , Patel Mallika P , Peters Katherine B , Kirkpatrick John P , Reitman Zachary J , Vaios Eugene J
Published: August 2023

Background

Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized that reduced dose-WBRT (rd-WBRT) followed by a stereotactic radiosurgery (SRS) boost could provide durable disease control without significant adverse effects.

Methods

We retrospectively reviewed PCNSL patients treated with rd-WBRT plus an SRS boost at Duke University between 2008 and 2021. Progression-free survival and overall survival (OS) were estimated using competing risk and Kaplan–Meier methods.

Results

We identified 23 patients with pathologically confirmed PCNSL. Median age at diagnosis was 69 years (Q1Q3: 52–74) and median Karnofsky Performance Scale (KPS) was 80 (Q1Q3: 70–80). Median follow-up was 21 months. Median doses for rd-WBRT and SRS were 23.4 Gy (Q1Q3: 23.4–23.4) and 12 Gy (Q1Q3: 12–12.5), respectively. The cumulative incidence of intracranial progression at 2 years was 23% (95% CI: 8–42). Six patients (26%) developed distant radiographic progression while 2 patients (9%) developed both distant and local progression. Ten patients (44%) were alive without progression at last follow-up. By Kaplan–Meier estimate, the 2-year OS was 69% (95% CI: 46–84). There were no reported grade 3 + radiation-induced toxicities.

Conclusions

The combination of rd-WBRT with an SRS boost appears well-tolerated with durable intracranial control. This approach may represent a treatment option for select patients, such as those with progressive or refractory disease. Further prospective studies are needed to validate these findings and determine whether this approach could be incorporated into consolidation strategies.
The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration
Authors: Cooper Skylar Y , Olszewski Nathan A , Tetteh-Quarshie Samuel , Hill Sean P , Ghodsi Saaman , González-Castro Astrid , Willis Clay V , Henderson Brandon J
Published: August 2023

Introduction

A wide variety of nicotine concentrations and formulations are available to users of electronic nicotine delivery systems (ENDS). This is increasingly true when considering the many flavors available with ENDS products. To date, there have been few preclinical investigations into the impact of nicotine doses, with and without flavors, on vaping-related behaviors. This present study evaluated how nicotine concentrations relevant to tank-based and pod-based ENDS, with and without flavors, impact reinforcement-related behavior in a mouse model.

Aims and Methods

Adult male and female C57/BL6J mice were used in vapor-inhalation self-administration assays. Mice were assigned e-liquids containing 6 mg/mL or 60 mg/mL nicotine. Additional mice were assigned these nicotine doses with green apple or menthol flavorants. Mice were trained on fixed-ratio 1 for 10, 2-hour sessions, then five sessions at FR3, three progressive ratio sessions, and two FR3 sessions.

Results

We observed male mice exhibited higher reinforcement-related behavior to menthol-flavored 6 mg/mL nicotine when compared to female mice. Males were only observed to have a menthol-induced enhancement of self-administration at 6 mg/mL nicotine and not 60 mg/mL nicotine. However, female mice exhibited significant menthol-induced increases in reinforcement-related behaviors with 60 mg/mL nicotine.

Conclusions

These data provide evidence that males and females exhibit different dose sensitivities to nicotine. These sex-dependent differences in nicotine sensitivity also indicate that flavor-induced enhancement in nicotine intake is dependent on the different doses for each sex.

Implications

There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our current study may support prior investigations that suggest flavors enhance the palatability of nicotine-containing products. However, this current study provides evidence that males and females exhibit different sensitivities to nicotine.
Potential Implications for Tobacco Industry Transformation of the Acquisition of Swedish Match by Philip Morris International
Authors: Levy David T , Warner Kenneth E , Liber Alex C , Travis Nargiz , Sweanor David T , Meza Rafael , Cummings K Michael
Published: August 2023

Philip Morris International’s recent purchase of Swedish Match may prove to be a vital tobacco industry development. We focus on PMIs potential progress in moving from primarily selling cigarettes toward primarily selling noncombustible nicotine delivery products (NCNDPs). We also consider the potential contribution of the acquisition to industry transformation whereby other cigarette firms may potentially move toward primarily selling NCNDPs. We examine the potential impact on noncombustible nicotine delivery product use, including nicotine pouches (a major Swedish Match product), e-cigarettes, heated tobacco products, and, most importantly, on sales of the industry’s staple, combustible cigarettes. We focus on the United States as a special case, where PMI is limited from entering the cigarette market.

Implications: Philip Morris International’s purchase of Swedish Match and policies regarding nicotine pouches (NPs) have been overlooked in the tobacco control literature. The acquisition indicates the importance of the NP market to the largest nonstate-owned tobacco company. The acquisition has the potential through pricing and marketing tactics to either encourage or discourage the use of NPs, e-cigarettes, heated tobacco products, and most importantly cigarettes. Due to its inability to sell cigarettes in the United States, PMI will have incentives to use its alternative nicotine delivery products, including its newly acquired NPs, to reduce the sale of cigarettes by other companies. However, the potential effects in other countries, where PMI does sell cigarettes, are less clear. Monitoring and analyzing tobacco company acquisitions is essential to studying future transitions in using different kinds of tobacco products, especially from cigarettes to lower-risk alternative nicotine delivery products.
The effects of time-restricted eating and Ramadan fasting on gut microbiota composition: a systematic review of human and animal studies
Authors: Pieczyńska-Zając Joanna Maria , Malinowska Anna , Łagowska Karolina , Leciejewska Natalia , Bajerska Joanna
Published: August 2023

Context

It is well known that the microbiome undergoes cyclical diurnal rhythms. It has thus been hypothesized that meal timing may affect gut microbial composition, function, and host health.

Objective

This review aims to examine the effects of time-restricted eating (TRE) and Ramadan fasting (RF) on the composition of the gut microbiota in animal and human studies. The associations between composition of microbiota and host metabolic parameters are also examined.

Data Sources

A search was performed on the PubMed, Cochrane, Scopus, and Web of Science databases up to December 31, 2022. The search strategy was performed using the Medical Subject Heading (MeSH) terms “intermittent fasting” and “gastrointestinal microbiome” and the key words “Ramadan fasting” and “microbes.”

Data Extraction

Seven human studies (4 TRE and 3 RF) and 9 animal studies (7 TRE, 2 RF-like) were retrieved.

Data Analysis

TRE and RF in human studies lead to an increase in gut microbial community alpha-diversity. In animal studies (both TRE and RF-like), fasting is not associated with improved alpha-diversity, but enhancement of microbial fluctuation is observed, compared with high-fat diet ad libitum groups. Within Firmicutes and Bacteroidetes phyla, no specific direction of changes resulting from fasting are observed in both animals and human. After TRE or RF, a greater abundance of the Faecalibacterium genus is observed in human studies; changes in Lactobacillus abundance are found in animal studies; and increases in Akkermansia are seen both in humans and in animals fed a feed-pellet diet. Only 2 human studies show a beneficial correlation between microbiota changes and host metabolic (HDL cholesterol) or anthropometric parameters (body mass index).

Conclusions

These findings support the importance of both regimens in improving the gut microbiota composition. However, based on results of animal studies, it can be suggested that diet remains the essential factor in forming the microbiota’s environment.

Systematic Review Registration

PROSPERO registration no. CRD42021278918.
Introduction to the special issue on ‘new directions in understanding philanthropic activities’
Authors: Adena Maja , Drouvelis Michalis , Huck Steffen
Published: August 2023

The papers in this Special Issue contribute to a rich literature on the economics of charitable giving. They address several novel questions covering a wide range of open issues in the philanthropic realm. For example, many of our papers study what works and what does not work for a charitable organization to boost giving money or time. Other papers examine fundraising mechanisms and possible underlying motives shaping donors’ giving behaviour. Our papers combine multiple methodologies, such as theory, observational data as well as laboratory and field experiments, to address these issues. Taken together, our Special Issue offers novel insights and approaches in the field of charitable giving that will be of interest to academics and policymakers alike.
Rapid Recycling of Subducted Sediments in the Subcontinental Lithospheric Mantle
Authors: Wang Jian , Wang Qiang , Ma Lin , Hu Wan-Long , Wang Jun , Belousova Elena , Tang Gong-Jian
Published: August 2023

Subduction recycling of sediments plays a key role in the geochemical evolution of Earth. The presence of recycled terrigenous sediments in upwelling plumes has been cited to explain the EM2 signature in ocean island volcanics, characterized by particularly high 87Sr/86Sr (>0.706). However, the origin of such isotopic anomalies in continental regions and the role of subducted sediments in the subcontinental lithospheric mantle (SCLM) remain unclear. The Himalaya–Tibet orogen is one of the world’s best places for deciphering continental subduction and the fate of subducted crustal materials in the mantle. Here we present a systematic study of the geochronology, mineral chemistry (especially clinopyroxene), whole-rock chemistry and Sr–Nd–Pb–Hf–O isotopic compositions of Cenozoic potassic–ultrapotassic lavas from the western Kunlun area of northwestern Tibet. New secondary ion mass spectrometry (SIMS) zircon U–Pb dating, coupled with published age results, constrain the timing of volcanism from ~8.3 Ma to the present. These lavas show geochemical characteristics that closely resemble the EM2 mantle end-member represented by the Samoan hotspot. Both whole rocks and individual magmatic clinopyroxenes display arc-like trace-element patterns and remarkably enriched Sr–Nd–Pb–Hf isotope compositions (87Sr/86Sr ≥ 0.7080; εNd ≤ −4.8; 206Pb/204Pb ≥ 18.704; εHf ≤ −2.6). Together with high zircon δ18O values (6.3–10.4‰), the data point to a mantle source enriched by recycled sedimentary materials. Geochemical modeling and geophysical evidence further indicate that the sediments were directly derived from the subducted Indian continental lithosphere during India–Eurasia collision. Partial melting models assuming a hybridized mantle source that contains ~5% Indian continental crust suggest that the primary melts of the potassic–ultrapotassic lavas could be formed by melting of a phlogopite-bearing garnet lherzolite at low melting degrees (1–5%). The magma geochemistry is consistent with the model of mélange melting, implying that the subducted sediments may detach from the downgoing Indian slab and rise up diapirically into the overlying mantle lithosphere. Unlike traditional models of subducted sediments entering the deep mantle, the western Kunlun EM2-like lavas reveal that subducted sediments can be rapidly recycled into the SCLM during continental subduction (probably <50 Myr). We suggest that the SCLM could be an important reservoir for subducted sediments. The findings are important to our understanding of mantle circulation rates and chemical heterogeneities.
Model-free optimization of power/efficiency tradeoffs in quantum thermal machines using reinforcement learning
Authors: Erdman Paolo A , Noé Frank
Published: August 2023

A quantum thermal machine is an open quantum system that enables the conversion between heat and work at the micro or nano-scale. Optimally controlling such out-of-equilibrium systems is a crucial yet challenging task with applications to quantum technologies and devices. We introduce a general model-free framework based on reinforcement learning to identify out-of-equilibrium thermodynamic cycles that are Pareto optimal tradeoffs between power and efficiency for quantum heat engines and refrigerators. The method does not require any knowledge of the quantum thermal machine, nor of the system model, nor of the quantum state. Instead, it only observes the heat fluxes, so it is both applicable to simulations and experimental devices. We test our method on a model of an experimentally realistic refrigerator based on a superconducting qubit, and on a heat engine based on a quantum harmonic oscillator. In both cases, we identify the Pareto-front representing optimal power-efficiency tradeoffs, and the corresponding cycles. Such solutions outperform previous proposals made in the literature, such as optimized Otto cycles, reducing quantum friction.
The longitudinal role of family conflict and neural reward sensitivity in youth’s internalizing symptoms
Authors: Yang Beiming , Anderson Zachary , Zhou Zexi , Liu Sihong , Haase Claudia M , Qu Yang
Published: August 2023

Adolescence is often associated with an increase in psychopathology. Although previous studies have examined how family environments and neural reward sensitivity separately play a role in youth’s emotional development, it remains unknown how they interact with each other in predicting youth’s internalizing symptoms. Therefore, the current research took a biopsychosocial approach to examine this question using two-wave longitudinal data of 9353 preadolescents (mean age = 9.93 years at T1; 51% boys) from the Adolescent Brain Cognitive Development study. Using mixed-effects models, results showed that higher family conflict predicted youth’s increased internalizing symptoms 1 year later, whereas greater ventral striatum (VS) activity during reward receipt predicted reduced internalizing symptoms over time. Importantly, there was an interaction effect between family conflict and VS activity. For youth who showed greater VS activation during reward receipt, high family conflict was more likely to predict increased internalizing symptoms. In contrast, youth with low VS activation during reward receipt showed high levels of internalizing symptoms regardless of family conflict. The findings suggest that youth’s neural reward sensitivity is a marker of susceptibility to adverse family environments and highlight the importance of cultivating supportive family environments where youth experience less general conflict within the family.
Application of Hydrothermal Time Models to Predict Sclerotial Germination of Athelia rolfsii
Authors: Sanjel Santosh , Guerra Victor , Seepaul Ramdeo , Mackowiak Cheryl , Punja Zamir K. , Dufault Nicholas , Tillman Barry , Bradford Kent J. , Small Ian M.
Published: August 2023

Athelia rolfsii, causal agent of “southern blight” disease, is a soilborne fungal pathogen with a wide host range of more than 500 species. This study's objectives were to (i) quantify the effects of two environmental factors, temperature and soil moisture, on germination of A. rolfsii inoculum (sclerotia), which is a critical event for the onset of disease epidemics and (ii) predict the timing of sclerotial germination by applying population-based threshold-type hydrothermal time (HTT) models. We conducted in vitro germination experiments with three isolates of A. rolfsii isolated from peanuts, which were tested at five temperatures ( T), ranging from 17 to 40°C, four matric potentials (Ψ m) between −0.12 and −1.57 MPa, and two soil types (fine sand and loamy fine sand), using a factorial design. When Ψ m was maintained between −0.12 and −0.53 MPa, T from 22 to 34°C was found to be conducive to sclerotial germination (>50%). The HTT models were fitted for a range of T (22 to 34°C) and Ψ m (−0.12 to −1.57 MPa) that accounted for 84% or more of variation in the timing of sclerotial germination. The estimated base T ranged between 0 and 4.5°C and the estimated base Ψ m between −2.96 and −1.52 MPa. The results suggest that the HTT modeling approach is a suitable means of predicting the timing of A. rolfsii sclerotial germination. This HTT methodology can potentially be tested to fine-tune fungicide application timing and in-season A. rolfsii management strategies.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .