bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α‐Chiral Primary Amines
Authors: Zhang Mangang , Li Hui , Wu Keqin , Rong Nianxin , Lin Shaoquan , Yang Hua , Yin Qin
Published: May 2024

Comprehensive Summary

Although it offers a direct route to access synthetically valuable α‐chiral primary amines, asymmetric transfer hydrogenation of NH imines has been rarely studied, due in large part to the inaccessibility and instability of NH imines. Herein, we report a Rh‐catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2’‐aminoacetophenones with NH3 in methanol. With this method, enantioenriched chiral 2‐(1‐aminoalkyl)anilines, which are privileged pharmacore groups, have been synthesized with good functional group compatibility, and with up to 99% ee. A gram‐scale reaction using 0.2 mol% of catalyst has been successfully performed to highlight the practicality. Furthermore, the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis.
Complications of transcatheter paravalvular leak device closure of mitral valve: An updated review of the literature and a rare case presentation
Authors: Jenab Yaser , Nourian Saeed , Hosseini Mohammadi Negin Sadat , Mohseni‐Badalabadi Reza , Hosseini Kaveh , Zakavi Sarina , Ates Ismail
Published: May 2024

Paravalvular leak (PVL) is an uncommon complication of prosthetic valve implantation, which can lead to infective endocarditis, heart failure, and hemolytic anemia. Surgical reintervention of PVLs is associated with high mortality rates. Transcatheter PVL closure (TPVLc) has emerged as an alternative to surgical reoperation. This method provides a high success rate with a low rate of complications. This article reviews the pathogenesis, clinical manifestation, diagnosis, and management of PVL and complications following TPVLc. Besides, we presented a case of a patient with severe PVL following mitral valve replacement, who experienced complete heart block (CHB) during TPVLc. The first TPVLc procedure failed in our patient due to possible AV‐node insult during catheterization. After 1 week of persistent CHB, a permanent pacemaker was implanted. The defect was successfully passed using the previous attempt. Considering the advantages of TPVLc, procedure failure should be regarded as a concern. TPVLc should be performed by experienced medical teams in carefully selected patients.
Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study
Authors: Guo De‐Zhen , Huang Ao , Wang Ying‐Chao , Zhou Shuang , Wang Hui , Xing Xiang‐Lei , Zhang Shi‐Yu , Cheng Jian‐Wen , Xie Ke‐Hui , Yang Qi‐Chang , Ma Cheng‐Cheng , Li Qing , Chen Yan , Su Zhi‐Xi , Fan Jia , Liu Rui , Liu Xiao‐Long , Zhou Jian , Yang Xin‐Rong
Published: May 2024

Background

Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood‐based assay to aid in the diagnosis, detection and prognostic evaluation of HCC.

Methods

A three‐phase multicentre study was conducted to screen, optimise and validate HCC‐specific differentially methylated regions (DMRs) using next‐generation sequencing and quantitative methylation‐specific PCR (qMSP).

Results

Genome‐wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre‐ and postoperative plasma samples from 103 HCC patients and correlated with 2‐year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001).

Conclusions

HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC‐specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at‐risk populations.
Histologic, metabolomic, and transcriptomic differences in fir trees from a peri‐urban forest under chronic ozone exposure
Authors: Reyes‐Galindo Verónica , Jaramillo‐Correa Juan P. , Shishkova Svetlana , Sandoval‐Zapotitla Estela , Flores‐Ortiz César Mateo , Piñero Daniel , Spurgin Lewis G. , Martin Claudia A. , Torres‐Jardón Ricardo , Zamora‐Callejas Claudio , Mastretta‐Yanes Alicia
Published: May 2024

Urbanization modifies ecosystem conditions and evolutionary processes. This includes air pollution, mostly as tropospheric ozone (O3), which contributes to the decline of urban and peri‐urban forests. A notable case are fir (Abies religiosa) forests in the peripheral mountains southwest of Mexico City, which have been severely affected by O3 pollution since the 1970s. Interestingly, some young individuals exhibiting minimal O3—related damage have been observed within a zone of significant O3 exposure. Using this setting as a natural experiment, we compared asymptomatic and symptomatic individuals of similar age (≤15 years old; n = 10) using histologic, metabolomic, and transcriptomic approaches. Plants were sampled during days of high (170 ppb) and moderate (87 ppb) O3 concentration. Given that there have been reforestation efforts in the region, with plants from different source populations, we first confirmed that all analyzed individuals clustered within the local genetic group when compared to a species‐wide panel (Admixture analysis with ~1.5K SNPs). We observed thicker epidermis and more collapsed cells in the palisade parenchyma of needles from symptomatic individuals than from their asymptomatic counterparts, with differences increasing with needle age. Furthermore, symptomatic individuals exhibited lower concentrations of various terpenes (ß‐pinene, ß‐caryophylene oxide, α‐caryophylene, and ß‐α‐cubebene) than asymptomatic trees, as evidenced through GC–MS. Finally, transcriptomic analyses revealed differential expression for 13 genes related to carbohydrate metabolism, plant defense, and gene regulation. Our results indicate a rapid and contrasting phenotypic response among trees, likely influenced by standing genetic variation and/or plastic mechanisms. They open the door to future evolutionary studies for understanding how O3 tolerance develops in urban environments, and how this knowledge could contribute to forest restoration.
May brood desertion be ruled by partner parenting capability in a polygamous songbird? An experimental study
Authors: Zheng Jia , Wang Hui , Jiang Jiayao , Versteegh Maaike A. , Zhou Zhuoya , Zhang Zhengwang , Chen De , Komdeur Jan
Published: May 2024

Parents confront multiple aspects of offspring demands and need to coordinate different parental care tasks. Biparental care is considered to evolve under circumstances where one parent is not competent for all tasks and cannot efficiently raise offspring. However, this hypothesis is difficult to test, as uniparental and biparental care rarely coexist. Chinese penduline tits (Remiz consobrinus) provide such a system where both parental care types occur. Here, we experimentally investigated whether parents in biparental nests are less capable of caring than parents in uniparental nests. We monitored parenting efforts at (1) naturally uniparental and biparental nests and (2) biparental nests before and during the temporary removal of a parent. Given the relatively small sample sizes, we have employed various statistical analyses confirming the robustness of our results. We found that total feeding frequency and brooding duration were similar for natural uniparental and biparental nests. Feeding frequency, but not brooding duration, contributed significantly to nestling mass. In line with this, a temporary parental removal revealed that the remaining parents at biparental nests fully compensated for the partner's feeding absence but not for brooding duration. This reflects that the manipulated parents are confronted with a trade‐off between feeding and brooding and were selected to invest in the more influential one. However, such a trade‐off may not occur in parents of natural uniparental care nests. The different capabilities of a parent independently coordinating feeding and brooding tasks suggest that parents from biparental and uniparental nests were exposed to different resource conditions, thereby foraging efficiency may differ between care types.
Determinants of taxonomic, functional, and phylogenetic beta diversity in breeding birds within urban remnant woodlots: Implications for conservation
Authors: Liu Yu , Zhu Yun , Wu Su , Wang Yan , Xie Jie , Zhang Kai , Xu Yu
Published: May 2024

Examining beta diversity of animal assemblages in fragmented habitats, which measures variation in species composition among different fragments, is important for understanding the impact of habitat fragmentation on biodiversity. However, relying solely on taxonomic composition may not provide a comprehensive understanding. Incorporating measures of functional and phylogenetic diversities is essential for elucidating the ecological mechanisms underlying changes in community composition. In addition, prevailing studies often prioritize the evaluation of landscape characteristics within fragments as determinants of beta diversity, neglecting differences in habitat type and plant community composition. In this study, we surveyed birds in 26 remnant woodlot patches (ranging from 0.3 to 290.4 ha) in an urban landscape, southwest China, during the breeding season from 2017 to 2022. We recorded 70 bird species (excluding those recorded only once and high‐flying birds, including raptors, swallows, and swifts), with the number of species per patch varying from 14 to 56. The overall bird taxonomic and phylogenetic beta diversities were primarily contributed by the turnover component, while functional beta diversity was dominated by the nestedness‐resultant component. Patch area and perimeter area ratio significantly influenced the taxonomic, functional, and phylogenetic beta diversities, primarily mediated through the nestedness‐resultant component, while inter‐patch distance had a significant effect via the turnover component. In addition, there was a considerable correlation of bird taxonomic, functional, and phylogenetic beta diversities with habitat type and woody plant beta diversities, including their respective partitioned turnover and nestedness‐resultant components. Our results suggest that bird assemblages in these patches may be regulated by selective extinction, interspecific competition, and environmental filtering. The findings have significant implications for sustainable landscape planning and habitat restoration. Conserving habitat patches of different sizes and maintaining or enhancing habitat heterogeneity between patches can facilitate the persistence of metacommunities.
404‐error “Disease not found”: Unleashing the translational potential of ‐omics approaches beyond traditional disease classification in heart failure research
Authors: Esquivel Gaytan Antonio , Bomer Nils , Grote Beverborg Niels , van der Meer Peter
Published: May 2024

The emergence of personalized medicine, facilitated by the progress in ‐omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of ‐omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi‐omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of ‘one size fits all’. Our review examines how omics can enhance understanding of heart failure's molecular foundations and contribute to a more comprehensive disease classification. We draw attention to the current state of medical practice that only relies on clinical evidence and a number of standard laboratory tests. At the same time, we propose a shift towards a universal approach that uses quantitative data from multi‐omics to unravel complex molecular interactions. The discussion centres around the potential of the transition as a means to enhance individual risk assessment and emphasizes management within clinical settings. While the use of omics in cardiovascular research is not recent, many past studies have focused only on a single omics approach. In order to achieve a better understanding of disease mechanisms, we explore more holistic approaches using genomics, transcriptomics, epigenomics, and proteomics. This review concludes with a call to action to adopt multi‐omics in clinical trials and practice to pave the way for more personalized disease management and more effective heart failure interventions.
Measuring congestion with a non‐invasive monitoring device in heart failure and haemodialysis: CONGEST‐HF
Authors: Curtain James P. , Talebi Atefeh , McIntosh Alasdair , McConnachie Alex , O'Donnell Joanne , Welsh Paul , Osmanska Joanna , Lee Matthew M.Y. , Sonecki Piotr , Akl Tony , Seo Joohyun , Gopinathan Venugopal , Hurwitz Jed , Thiagarajan Srikanth , Pettit Stephen , Kalra Paul R. , Patel Rajan K. , Mark Patrick B. , Lang Ninian N. , McMurray John J.V. , Petrie Mark C. , Gardner Roy S. , Jhund Pardeep S.
Published: May 2024

Aims

We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion.

Methods and results

We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B‐lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub‐acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [rsp] = −0.64, p = 0.002) and change in device S3 (rsp = −0.53, p = 0.014). In the haemodialysis cohort (n = 21), B‐lines and TI were strongly correlated before (rsp = −0.71, p < 0.001) and after (rsp = −0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (rsp = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (rsp = 0.230, p = 0.204). There were no device‐related adverse events.

Conclusions

A non‐invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations.
High‐yield upcycling of feather wastes into solid‐state ultra‐long phosphorescence carbon dots for advanced anticounterfeiting and information encryption
Authors: Chen Dongzhi , Guo Xin , Sun Xuening , Feng Xiang , Chen Kailong , Zhang Jinfeng , Zhu Zece , Zhang Xiaofang , Liu Xin , Liu Min , Li Li , Xu Weilin
Published: May 2024

Recently, biomass‐derived carbon dots (CDs) have attracted considerable attention in high‐technology fields due to their prominent merits, including brilliant luminescence, superior biocompatibility, and low toxicity. However, most of the biomass‐derived CDs only show bright fluorescence in diluted solution because of aggregation‐induced quenching effect, hence cannot exhibit solid‐state long‐lived room‐temperature phosphorescence (RTP) in ambient conditions. Herein, matrix‐free solid‐state RTP with an average lifetime of 0.50 s is realized in the CDs synthesized by one‐pot hydrothermal treatment of duck feather waste powder. To further enhance RTP lifetime, hydrogen bonding is introduced by employing polyols like polyvinyl alcohol (PVA) and phytic acid (PA), and a bimodal luminescent CDs/PVA/PA ink is exploited by mixing the CDs and polyols. Astonishingly, the CDs/PVA/PA ink screen‐printed onto cellulosic substrates exhibits unprecedented green RTP with average lifetime of up to 1.97 s, and the afterglow lasts for more than 14 s after removing UV lamp. Such improvement on RTP is proposed to the populated excited triplet excitons stabilized by rigid chains. Furthermore, the CDs/PVA/PA ink demonstrates excellent potential in anticounterfeiting and information encryption. To the best of the authors' knowledge, this work is the first successful attempt to fabricate matrix‐free ultra‐long RTP CDs by reclamation of the feather wastes for environmental sustainability.
Forecasting stock returns with industry volatility concentration
Authors: Zhang Yaojie , He Mengxi , Zhang Zhikai
Published: May 2024

In this paper, we show that industry volatility concentration is a strong predictor for aggregate stock market returns. Our monthly industry volatility concentration (IVC) index displays significant predictive ability, with in‐sample and out‐of‐sample R2 statistics of 0.686% and 0.712%, respectively, which outperforms a host of prevailing return predictors. Moreover, the IVC index can generate high utility gains of 143.8 basis points above the historical average benchmark for mean–variance investors. We find that the IVC index is countercyclical. Furthermore, the predictive source of the IVC index not only stems from the cash flow and discount rate channels but is also explained by the channels of investor attention and sentiment. The predictive ability of our IVC index also remains significant under a broad range of robustness tests.
Metabolomic insights into Monascus‐fermented rice products: Implications for monacolin K content and nutritional optimization
Authors: Zhao Yongxia , Luo Mingxia , Jiang Qin , Ma Yuhan , Liu Xiaoqi , Bai Xue , Zhou Lihong , Xie Jian
Published: May 2024

This study aims to elucidate the detailed metabolic implications of varying monacolin K levels and sterilization methods on Monascus‐fermented rice products (MFRPs), acclaimed for their health benefits and monacolin K content. Advanced metabolite profiling of various MFRP variants was conducted using ultrahigh‐performance liquid chromatography coupled with tandem time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF MS). Statistical analysis encompassed t‐tests, ANOVA, and multivariate techniques including PCA, PLS‐DA, and OPLS‐DA. Notable variations in metabolites were observed across MFRPs with differing monacolin K levels, particularly in variants such as MR1‐S, MR1.5‐S, MR2‐S, and MR3‐S. Among the 524 identified metabolites, significant shifts were noted in organic acids, derivatives, lipids, nucleosides, and organic oxygen compounds. The study also uncovered distinct metabolic changes resulting from different sterilization methods and the use of highland barley as a fermentation substitute for rice. Pathway analysis shed light on affected metabolic pathways, including those involved in longevity regulation, cGMP‐PKG signaling, and the biosynthesis of unsaturated fatty acids. The research provides critical insights into the complex metabolic networks of MFRPs, underscoring the impact of fermentation substrates and conditions on monacolin K levels and their health implications. This study not only guides the nutritional optimization of MFRPs but also emphasizes the strategic importance of substrate choice and sterilization techniques in enhancing the nutritional and medicinal value of these functional foods.
Restriction on molecular fluxionality by substitution: A case study for the 1,10‐dicyanobullvalene
Authors: Pei Bin‐Bin , Yang Hongjuan , Gao Cai‐Yue , Man Yuan , Yang Yonggang , Li Si‐Dian
Published: May 2024

We show herein that 1,10‐dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10‐dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born‐Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long‐time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the “14 Cs → C7v” thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un‐explored properties e.g. for the equilibration dynamics of C10H10.
t2gd orbital ordering patterns in KBF3 (B = Sc, Ti, Fe, Co) perovskites
Authors: Pascale Fabien , D'Arco Philippe , Mustapha Sami , Dovesi Roberto
Published: May 2024

The orbital ordering (OO) resulting from the partial occupancy of the subshell of the transition metals in KBF (B = Sc, Ti, Ffe, Co) perovskites, and the many possible patterns arising from the coupling between the B sites, have been investigated at the quantum mechanical level ( Gaussian type basis set, B3LYP hybrid functional) in a 40 atoms supercell. The numerous patterns are distributed into 162 classes of equivalent configurations. For each fluoroperovskite, one representative per class has been calculated. The four compounds behave similarly: an identical dependence of the energy and volume (or cell parameters) on the OO pattern; the spanned energy interval is small (1 to 2 mE per formula unit), suggesting that most of the configurations are occupied at room and even at low temperature. A linear model, taking into account the relative orbital order in contiguous sites, reproduces the energy order in the full set for each compound, suggesting that it could be used for studying OO in larger supercells.
How people react to suicidal ideation: The effect of suicide literacy, suicide stigma, and expressive suppression
Authors: An Soontae , Lee Hannah , Lee Jiyoon
Published: May 2024

Introduction

The purpose of this study is to understand the role of suicide literacy and suicide stigma in laypeople's intention to recommend professional help in Korea. Additionally, the study focuses on the role of expressive suppression as a sociocultural factor.

Methods

Participants read vignettes depicting either subclinical distress or suicidal ideation and answered questions measuring suicide literacy, stigma, and expressive suppression. Mediated moderation analyses were used to examine the interactions between these factors.

Results

The result found the significant effect of expressive suppression. The mediating effect of suicide stigma on the relationship between suicide literacy and recommendation of professional help was significant for those who do not suppress their emotions. This result indicates that when individuals were not hesitant to express negative emotions, high suicide literacy lowered suicide stigma and led to more willingness to recommend professional help.

Conclusions

The results showed that expressive suppression acts as a barrier deterring Koreans from professional help for their mental health. The findings underscore the importance of sociocultural factors such as expressive suppression in developing suicide prevention strategies.
FTO blocks RNA translational activity via the loss of N6‐methyladenosine methylation at 5′ UTR regulated by RBM5 in cisplatin‐resistant NSCLC
Authors: Li Liantao , Qu Debao , Wang Bo , Yuan Shiwang , Zhao Yang , Liu Nianli , Huo Fuchun , Zhang Dan , Zhang Longzhen
Published: May 2024

N6‐methyladenosine (m6A) methylation has been widely regarded in numerous biological functions including CR. Nonetheless, the molecular process of m6A methylation behind CR in non‐small cell lung cancer (NSCLC) has no apparent significance. We identified in this study that the expression of FTO alpha‐ketoglutarate dependent dioxygenase (FTO) was downregulated in CR NSCLC tissues and cells in vivo and in vitro. Additionally, RIP‐seq indicated that loss of FTO contributed to the elevated m6A methylation at 5′‐untranslated region of RNAs which were closely connected with tumor resistance and malignancy, and FTO exerted to exclude the recruitment of eIF3A to these target genes in CR NSCLC. Moreover, FTO‐enriched transcripts displayed a reduced translational capability in CR NSCLC compared to the regular NSCLC cells. Finally, we also identified RNA binding motif protein 5 (RBM5) that could specially interact with FTO in regular NSCLC compared to CR NSCLC. Deficiency of RBM5 resulted in the abnormal recognition of transcripts by FTO, and led to the translation silencing of genes associated with CR such as ATP7A, ERCC1, CD99, CDKN3, XRCC5, and NOL3. Taken together, our data characterized FTO as a novel translation regulator and revealed the molecular mechanism on gene translation through the synergistic effects with RBM5 and m6A methylation in CR NSCLC cells.
Exploring the role of digital tools in rare disease management: An interview‐based study
Authors: Chang Andrea , Huang Sarah D. , Benjamin Daniel J. , Schmidt Johanna L. , Palmer Christina G. S. , Garrison Nanibaa’ A.
Published: May 2024

While digital tools, such as the Internet, smartphones, and social media, are an important part of modern society, little is known about the specific role they play in the healthcare management of individuals and caregivers affected by rare disease. Collectively, rare diseases directly affect up to 10% of the global population, suggesting that a significant number of individuals might benefit from the use of digital tools. The purpose of this qualitative interview‐based study was to explore: (a) the ways in which digital tools help the rare disease community; (b) the healthcare gaps not addressed by current digital tools; and (c) recommended digital tool features. Individuals and caregivers affected by rare disease who were comfortable using a smartphone and at least 18 years old were eligible to participate. We recruited from rare disease organizations using purposive sampling in order to achieve a diverse and information rich sample. Interviews took place over Zoom and reflexive thematic analysis was utilized to conceptualize themes. Eight semistructured interviews took place with four individuals and four caregivers. Three themes were conceptualized which elucidated key aspects of how digital tools were utilized in disease management: (1) digital tools should lessen the burden of managing a rare disease condition; (2) digital tools should foster community building and promote trust; and (3) digital tools should provide trusted and personalized information to understand the condition and what the future may hold. These results suggest that digital tools play a central role in the lives of individuals with rare disease and their caregivers. Digital tools that centralize trustworthy information, and that bring the relevant community together to interact and promote trust are needed. Genetic counselors can consider these ideal attributes of digital tools when providing resources to individuals and caretakers of rare disease.
What do patients and families observe about pediatric safety?: A thematic analysis of real‐time narratives
Authors: Studenmund Christine , Lyndon Audrey , Stotts James R. , Peralta‐Neel Caroline , Sharma Anjana E. , Bardach Naomi S.
Published: May 2024

Objectives

Data on inpatient safety are documented by hospital staff through incident reporting (IR) systems. Safety observations from families or patients are rarely captured. The Family Input for Quality and Safety (FIQS) study created a mobile health tool for pediatric patients and their families to anonymously report safety observations in real time during hospitalization. The study objectives were to describe these observations and identify domains salient to safety.

Methods

In this observational study, we analyzed pediatric patient safety reports from June 2017 to April 2018. Participants were: English‐speaking family members and hospitalized patients ≥13 years old. The analysis had two stages: (1) assessment of whether narratives met established safety event criteria and whether there were companion IRs; (2) thematic analysis to identify domains.

Results

Of 248 enrolled participants, 58 submitted 120 narrative reports. Of the narratives, 68 (57%) met safety event criteria, while only 1 (0.8%) corresponded to a staff‐reported IR. Twenty‐five percent of narratives shared positive feedback about patient safety efforts; 75% shared constructive feedback. We identified domains particularly salient to safety: (1) patients and families as safety actors; (2) emotional safety; (3) system‐centered care; and (4) shared safety domains, including medication, communication, and environment of care. Some domains capture data that is otherwise difficult to obtain (#1–3), while others fit within standard healthcare safety domains (#4).

Conclusions

Patients and families observe and report salient safety events that can fill gaps in IR data. Healthcare leaders should consider incorporating patient and family observations—collected with an option for anonymity and eliciting both positive and constructive comments.
Revitalizing brain perfusion: Unveiling advancements through rhythm control strategies in atrial fibrillation—A systematic review
Authors: Rasti Shinta Dewi , Sugiarto Adra Achirultan Ramainaldo , Nuryandi Audia Putri Amalia , Arvianti Militanisa Zamzara , Yomara Romadhana Trisnha , Nagasastra Jeffri , Julario Rerdin , Fagi Rosi Amrilla , Windrati Diah Mustika Hesti
Published: May 2024

Background

Recent evidence suggests an elevated risk of cognitive impairment and dementia in individuals with atrial fibrillation (AF), irrespective of stroke occurrence. AF, known to reduce brain perfusion, particularly through silent cerebral ischemia, underscores the intricate relationship between cardiac and cerebral health. The heart plays a crucial role in supporting normal brain function, and rhythm control, a standard AF treatment, has demonstrated enhancements in brain perfusion. This systematic review aimed to examine published data concerning the influence of rhythm control on brain perfusion in patients with atrial fibrillation.

Methods

A systematic search for relevant studies was carried out in Scopus, PubMed, Cochrane Reviews, ProQuest, and EBSCOhost, spanning from their inception until April 30, 2023. Studies that specifically examined brain perfusion following any form of rhythm control in atrial fibrillation were included in the review.

Results

The review encompassed 10 studies involving 436 participants. Among these, six utilized electrical cardioversion for rhythm control. The majority (8 out of 10) demonstrated that restoring sinus rhythm markedly enhances brain perfusion. In one of the two remaining studies, notable improvement was observed specifically in a region closely linked to cognition. Additionally, both studies reporting data on the Mini‐Mental State Examination (MMSE) showed a consistent and significant increase in scores following rhythm control.

Conclusion

Successful rhythm control in AF emerges as a significant contributor to enhanced brain perfusion, suggesting a potential therapeutic avenue for reducing cognitive impairment incidence. However, further validation through larger prospective studies and randomized trials is warranted.
Prospective Outcomes of Microlaryngoscopy Versus Office Laser Photoangiolysis for Vocal Fold Polyps
Authors: Chadwick Keith A. , Andreadis Katerina , Sulica Lucian
Published: May 2024

Objective(s)

The objective of this study is to compare treatment outcomes for vocal fold polyps (VFPs) between operating room microlaryngoscopy and office‐based photoangiolysis with the potassium titanyl phosphate (KTP) laser.

Methods

Prospective nonrandomized cohort study of patients with VFPs undergoing microlaryngoscopy (“OR group”) or KTP laser photoangiolysis (“KTP group”). Voice outcomes (patient‐reported outcome measures [Voice Handicap Index‐10 (VHI‐10) and Singing VHI‐10 (SVHI‐10)], auditory‐perceptual measures [Consensus Auditory‐Perceptual Evaluation of Voice (CAPE‐V)], videostroboscopic characteristics [Voice‐Vibratory Assessment of Laryngeal Imaging (VALI)], and acoustic and aerodynamic measures) were performed at baseline and regular intervals after intervention.

Results

Forty‐four subjects (17 OR group, 27 KTP group) with VFPs were enrolled. Mean VHI‐10 significantly improved from baseline to each follow‐up interval in both groups, except for the 1–2‐week interval in the OR group. Mean SVHI‐10 improved for both groups at some intervals. Growth curve models and time‐to‐event analyses for patient‐reported outcomes did not differ between groups. There were significant improvements in all categories of auditory‐perceptual voice quality and some categories of videostroboscopic characteristics in both groups. No significant trends were identified in acoustic and aerodynamic measures. Improvements in most outcomes did not significantly differ between groups or based on polyp size. There were no major complications.

Conclusions

Significant improvements in patient‐reported voice outcomes measures, auditory‐perceptual voice evaluation, and videostroboscopic characteristics occur following surgical treatment of vocal fold polyps with either microlaryngoscopy or office‐based KTP laser. Long‐term voice outcomes do not significantly differ between treatment modalities.

Level of Evidence

3 Laryngoscope, 134:S1–S20, 2024
Immune Checkpoint Inhibitor Induced Supraglottitis: A Case Series
Authors: Gascon Laurence , Benyo Sarah , Nelson Rebecca C.
Published: May 2024

Objective

To report a series of two cases of unusual airway complications with immunotherapy.

Method

Case series and review of literature.

Results

We report two cases of significant supraglottitis in patients treated with immunotherapy. The first patient is a 62‐year‐old male receiving treatment for a stage 4 melanoma with Nivolumab and Relatlimab. He presented in Otolaryngology clinic for subacute dysphonia and dysphagia. Flexible laryngoscopy showed significant airway edema, mucopurulent secretions, and inflammation. He was admitted inpatient and treated with high dose systemic steroids and intravenous antibiotics. Daily airway examination with flexible laryngoscopy showed improvement with this medical management. The patient was discharged with antibiotics and a steroid taper. Treatment with immunotherapy was held due to this severe and potentially life‐threatening complication. The second patient is a 76‐year‐old male with bladder cancer treated with Pembrolizumab. Four months after beginning treatment, he experienced hoarseness and throat discomfort. His laryngoscopic examination showed diffuse supraglottic swelling. He was treated inpatient with high dose systemic steroids, intravenous antibiotics, and antifungals, which resulted in improvement of supraglottic swelling. He remained on his immunotherapy treatment. Repeat examination demonstrated persistent supraglottic swelling without airway obstruction. Regarding airway‐related complications with immunotherapy, the literature reports three other cases of tracheitis related to immune checkpoint inhibitors.

Conclusion

This is the first case series of supraglottitis in patients treated with immune checkpoint inhibitors. This adds to the emerging literature of the potential respiratory implications of these medications. Laryngoscope, 134:4304–4306, 2024
High rates of erosion on a wave‐exposed fringing coral reef
Authors: Thomson Damian P. , Dee Shannon , Doropoulos Christopher , Orr Melanie , Wilson Shaun K. , Hoey Andrew S.
Published: May 2024

Erosion is a key process in shaping the physical structure of coral reefs, yet due to erosion being semi‐cryptic and difficult to quantify, information remains limited. Here, we investigate erosional processes along Ningaloo Reef, an extensive fringing coral reef in Western Australia. We employed both direct and indirect methods to measure erosion in wave‐exposed reef slopes and protected lagoonal habitats. Direct measurements of erosion on coral blocks were among the highest found globally, with total erosion of 3.07 kg m−2 yr−1 (4% from micro, 0.6% from macro, and 94% from external), whilst indirect rates were estimated at 2.4 ± 0.20 kg m−2 yr−1 (78% from parrotfish, 22% from urchins). Indirect erosion rates were influenced by the species and size of parrotfish, with Chlorurus microrhinos removing 0.44 ± 0.19 kg m−2 yr−1 (22% of parrotfish erosion). Scanning electron microscopy and computed tomography show that micro and macroborer erosion contributions to direct erosion were low, most likely due to heavy grazing by parrotfish and the short deployment period of experimental substrates. A substantial portion of external erosion on blocks (0.53 ± 0.23 kg m−2 yr−1) could not be attributed to bioeroders and was poorly correlated with wave exposure, suggesting processes not quantified contribute to this unaccounted aspect of erosion. Our results confirm that bioerosion by parrotfish is especially significant at Ningaloo Reef, and large‐bodied individuals of C. microrhinos are key in conserving this key ecological process.
The effect of green influencer message characteristics: Framing, construal, and timing
Authors: König Sarah , Maier Erik
Published: May 2024

This research explores the characteristics of green influencer messages on follower engagement by examining the interplay between message framing (gain vs. loss), construal level (high vs. low), and post timing (weekdays vs. weekends). Green influencers (also: greenfluencers or sustainable influencers) are considered a key agent for a change to more sustainable consumption. A pilot field study of 1000 green influencers, however, indicates that the current communication practices of green influencers (which strongly focus on gain frames, low construal, and posts during the week) are not ideal for maximizing engagement and sustainable behavioral intentions. Two experiments replicate this finding and establish the process through which green influencer posts affect engagement: gain frames increase fluency, which increases engagement; low construal levels decrease psychological distance, which increases engagement. Timing moderates these processes in that weekend posts increase the engagement with gain frames and week posts increase the engagement with low‐construal frames. These findings highlight that there is no silver bullet in green influencer messages, but that green influencers need to adapt the framing and construal of their messages to the posts' timing to increase their contribution to more sustainable lifestyles and the greater good.
Welfare effects of variable and fixed cost subsidies in profit, non‐profit and mixed markets
Authors: Jegers Marc , Buts Caroline , Van Puyvelde Stijn
Published: May 2024

Whereas various support mechanisms are in place to correct market failures, knowledge on their welfare effects is still incomplete. This paper, applying a Bertrand approach, studies and compares the effects of variable and fixed cost subsidies on consumer surplus, producer surplus, total surplus and total surplus net of distorting tax effects (‘overall surplus’) in three different market settings: a for‐profit duopoly, a duopoly with two non‐profit organisations and a mixed duopoly, the duopolists in each case supplying mutually exclusive goods or services. In a for‐profit duopoly, more variable cost subsidies lead to an increase of both consumer and producer surpluses, where the latter is impacted most. The higher the level of demand interaction between the two products, the higher the welfare impact. In the non‐profit setting, we establish that the effects of changing fixed cost subsidies on the fiscal cost are more substantial than in the for‐profit duopoly. Subsidies in mixed competition also generate an impact on both producer and consumer surpluses. The effects on overall surplus are shown to depend in complex ways on the level of demand interaction between the products, the shadow cost of taxation and the firms' cost levels.
Generalizations of Riemann–Liouville fractional integrals and applications
Authors: Lan Kunquan
Published: May 2024

The notion of a generalized Riemann–Liouville fractional integral is introduced, and its domain, range, and properties are studied. The new notion and properties provide new insight and understanding into the classical Riemann–Liouville fractional integral and its properties. Based on the generalized Riemann–Liouville fractional integral, equivalences between linear first ‐order fractional differential equations (FDEs) and integral equations are established. These equivalence results are applied to obtain solutions of Abel type integral equations and to study the existence and uniqueness of generalized normal solutions of initial value problems for nonlinear first‐order FDEs.
Efficient proton arc optimization and delivery through energy layer pre‐selection and post‐filtering
Authors: Wuyckens Sophie , Wase Viktor , Marthin Otte , Sundström Johan , Janssens Guillaume , Borderias‐Villarroel Elena , Souris Kevin , Sterpin Edmond , Engwall Erik , Lee John A.
Published: May 2024

Background

Proton arc therapy (PAT) has emerged as a promising approach for improving dose distribution, but also enabling simpler and faster treatment delivery in comparison to conventional proton treatments. However, the delivery speed achievable in proton arc relies on dedicated algorithms, which currently do not generate plans with a clear speed‐up and sometimes even result in increased delivery time.

Purpose

This study aims to address the challenge of minimizing delivery time through a hybrid method combining a fast geometry‐based energy layer (EL) pre‐selection with a dose‐based EL filtering, and comparing its performance to a baseline approach without filtering.

Methods

Three methods of EL filtering were developed: unrestricted, switch‐up (SU), and switch‐up gap (SU gap) filtering. The unrestricted method filters the lowest weighted EL while the SU gap filtering removes the EL around a new SU to minimize the gantry rotation braking. The SU filtering removes the lowest weighted group of EL that includes a SU. These filters were combined with the RayStation dynamic proton arc optimization framework energy layer selection and spot assignment (ELSA). Four bilateral oropharyngeal and four lung cancer patients' data were used for evaluation. Objective function values, target coverage robustness, organ‐at‐risk doses and normal tissue complication probability evaluations, as well as comparisons to intensity‐modulated proton therapy (IMPT) plans, were used to assess plan quality.

Results

The SU gap filtering algorithm performed best in five out of the eight cases, maintaining plan quality within tolerance while reducing beam delivery time, in particular for the oropharyngeal cohort. It achieved up to approximately 22% and 15% reduction in delivery time for oropharyngeal and lung treatment sites, respectively. The unrestricted filtering algorithm followed closely. In contrast, the SU filtering showed limited improvement, suppressing one or two SU without substantial delivery time shortening. Robust target coverage was kept within 1% of variation compared to the PAT baseline plan while organs‐at‐risk doses slightly decreased or kept about the same for all patients.

Conclusions

This study provides insights to accelerate PAT delivery without compromising plan quality. These advancements could enhance treatment efficiency and patient throughput.
Ultrahigh field diffusion magnetic resonance imaging uncovers intriguing microstructural changes in the adult zebrafish brain caused by Toll‐like receptor 2 genomic deletion
Authors: Singer Rico , Oganezova Ina , Hu Wanbin , Liu Li , Ding Yi , de Groot Huub J. M. , Spaink Herman P. , Alia A.
Published: May 2024

Toll‐like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2‐deficient (tlr2−/−) zebrafish using state‐of‐the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2−/− zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain‐wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2−/− zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2−/− compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases.