bluuebunny/crossref_metadata_2025 huggingface dataset:
Days Alive and Out of Hospital as an Outcome Measure in Patients Receiving Hyperacute Stroke Intervention
Authors: Donnelly Joseph , Hong Jae Beom , Boyle Luke , Yong Vivien TY , Diprose William K. , Meyer Juliette , Campbell Douglas , Barber P. Alan
Published: July 2024

Background

Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH‐90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy.

Methods and Results

Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH‐90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS‐90) was assessed with in‐person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59–79], median National Institutes of Health Stroke Scale score 14 [9–20]). Median DAOH‐90 was 71 [29–84] and median mRS‐90 score was 3 [2–5]. DAOH‐90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho −0.44,
P
<0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24,
P
<0.001). There was a strong association between mRS‐90 and DAOH‐90 (Spearman rho correlation −0.79,
P
<0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84–0.88), mRS score >1 was 0.88 (95% CI, 0.86–0.90) and mRS score >2 was 0.90 (95% CI, 0.89–0.92).

Conclusions

In patients with stroke treated with reperfusion therapies, DAOH‐90 shows reasonable comparability to the more established outcome measure of mRS‐90. DAOH‐90 can be readily obtained from administrative databases and therefore has the potential to be used in large‐scale clinical trials and comparative effectiveness studies.
Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability Via Changes in Protein Expression During Inflammation
Authors: Sherratt Samuel C. R. , Libby Peter , Dawoud Hazem , Bhatt Deepak L. , Mason R. Preston
Published: July 2024

Background

Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE‐IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) in relation to on‐treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium.

Methods and Results

In this study, human ECs were treated with EPA and challenged with the cytokine IL‐6 (interleukin‐6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM‐1 (soluble intercellular adhesion molecule‐1) and TNF‐α (tumor necrosis factor‐α). Global protein expression was determined using liquid chromatography–mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL‐6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM‐1 and TNF‐α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1‐fold (
P
<0.05), compared with IL‐6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase‐1 and dimethylarginine dimethylaminohydrolase‐1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL‐6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (
P
<0.05).

Conclusions

These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.
An anesthetic protocol for preserving functional network structure in the marmoset monkey brain
Authors: Ortiz-Rios Michael , Sirmpilatze Nikoloz , König Jessica , Boreitus Susann
Published: July 2024

Initiatives towards acquiring large-scale neuroimaging data in non-human primates promise improving translational neuroscience and cross-species comparisons. Crucial among these efforts is the need to expand sample sizes while reducing the impact of anesthesia on the functional properties of brain networks. Yet, the effects of anesthesia on non-human primate brain networks remain unclear. Here, we demonstrate using functional magnetic resonance imaging (fMRI) at 9.4 tesla that isoflurane anesthesia induces a variety of brain states in the marmoset brain with dramatically altered functional connectivity profiles. As an alternative, we recommend using a continuous infusion of the sedative medetomidine, supplemented with a low concentration of isoflurane. Using this protocol in eight marmosets, we observed robust visual activation during flickering light stimulation and identified resting-state networks similar to the awake state. In contrast, isoflurane alone led to a suppressed visual activation and the absence of awake-like network patterns. Comparing states using a graph-theoretical approach, we confirmed that the structure of functional networks is preserved under our proposed anesthesia protocol but is lost using isoflurane alone at concentration levels greater than 1%. We believe that the widespread adoption of this protocol will be a step towards advancing translational neuroscience initiatives in non-human primate neuroimaging. To promote the collaborative use of neuroimaging resources, we openly share our datasets (https://zenodo.org/records/11118775).
Descriptions of new and rare crabs associated with coral rubble and sponges from Kanyakumari, southeastern Arabian Sea, southern India (Decapoda: Brachyura: Epialtidae and Pilumnidae)
Authors: NG PETER K. L. , PREMA MANI , RAVICHANDRAN SAMUTHIRAPANDIAN
Published: July 2024

Three new brachyuran crab species are described from coral rubble and sponges collected in the southern Indian state of Tamil Nadu. The epialtid, Acanthophrys keeae n. sp., was obtained from coral rubble and is the first species from the genus reported from the Indian Ocean. It is most similar to A. costatus Griffin & Tranter 1986, from eastern Australia, but can be distinguished by the proportionately longer postorbital spine, more strongly granulated gastric region, relatively less inflated and narrower branchial region, sinuous outer margin of the basal antennal article which has the median part concave, almost smooth merus of the cheliped, more elongate male anterior thoracic sternum, more triangular male pleon, and the distal two-thirds of the male first gonopod being almost straight. The pilumnid, Latopilumnus ajmali n. sp., was found in the sponge, Callyspongia (Cladochalina) diffusa (Ridley, 1884), and is characterised by its carapace and pereiopods being covered by a relatively dense coat of short setae with only scattered simple long setae, and the dorsal carapace surface being almost smooth with the regions poorly demarcated. Vellumnus intonsus n. sp. (Pilumnidae) was present in coral rubble, is morphologically most similar to V. penicillatus (Gordon, 1930) (Hong Kong) and V. pygmaeus Takeda, 1977 (Japan) but can be separated by the lateral lobule of the front being separated from the frontal lobes by a deep cleft, the more prominently convex supraorbital margin, triangular external orbital tooth, presence of larger granules on the cheliped carpus and chela, and the distal part of the male first gonopod is proportionately stouter and distinctly hooked.
Actumnus ngankeeae sp. nov. and Pilumnus swajayai Ng & Rahayu, 2021, pilumnid crabs from Japan (Crustacea: Decapoda: Brachyura)
Authors: TAKEDA MASATSUNE , KOMATSU HIRONORI
Published: July 2024

New and rare crab species of the family Pilumnidae, Actumnus ngankeeae sp. nov. and Pilumnus swajayai Ng & Rahayu, 2021, are reported from Japan. Actumnus ngankeeae from the Ogasawara (Bonin) Islands is characterized by the following features: the carapace is transversely ovate and strongly convex longitudinally and transversely; the dorsal surface is uniformly covered with small granules and sparse short setae, with the regions defined by narrow furrows; the anterolateral margin is narrowly crested along its whole length and separated into four convex lobes by three V-shaped notches. Both chelipeds are stout, with short, strongly curved fingers. Its specific affinity to A. obesus Dana, 1852, is briefly discussed. Pilumnus swajayai from the Ryukyu Islands is wholly covered with tomentum; the carapace anterolateral margin is armed with three sharp teeth directed obliquely forwards, the second of which is the largest; the subhepatic tooth is distinct, but smaller than the carapace anterolateral teeth; the hepatic region is armed with a dentiform lobe; both chelipeds are armed with scattered conical granules on the carpi and palms; and the ambulatory legs are armed with some spinules on the dorsal margins of the carpi and propodi. The generic affiliation to Pilumnus is acceded to the original description after discussion on the related genera. The present record of P. swajayai from the Ryukyu Islands is the second since the original description from Indonesian waters.
Two new freshwater crab species from the Eastern Arc Mountains, Tanzania, East Africa (Brachyura: Potamoidea: Potamonautidae)
Authors: CUMBERLIDGE NEIL , JONAS GABRIELLE I.
Published: July 2024

This work focuses on two new freshwater crab species from Tanzania, East Africa: Arcopotamonautes parekeeae n. sp. and A. ngae n. sp. The new species are described based on newly identified museum material. Diagnoses, illustrations, and distribution maps are provided for these species, and their conservation status is discussed.
Effect of dynamic exclusion and the use of FAIMS, DIA and MALDI-mass spectrometry imaging with ion mobility on amyloid protein identification
Authors: Aguilan Jennifer T. , Lim Jihyeon , Racine-Brzostek Sabrina , Fischer Joshua , Silvescu Cristina , Cornett Shannon , Nieves Edward , Mendu Damodara Rao , Aliste Carlos-Madrid , Semple Stacia , Angeletti Ruth , Weiss Louis M. , Cole Adam , Prystowsky Michael , Pullman James , Sidoli Simone
Published: July 2024

Amyloidosis is a disease characterized by local and systemic extracellular deposition of amyloid protein fibrils where its excessive accumulation in tissues and resistance to degradation can lead to organ failure. Diagnosis is challenging because of approximately 36 different amyloid protein subtypes. Imaging methods like immunohistochemistry and the use of Congo red staining of amyloid proteins for laser capture microdissection combined with liquid chromatography tandem mass spectrometry (LMD/LC–MS/MS) are two diagnostic methods currently used depending on the expertise of the pathology laboratory. Here, we demonstrate a streamlined in situ amyloid peptide spatial mapping by Matrix Assisted Laser Desorption Ionization–Mass Spectrometry Imaging (MALDI-MSI) combined with Trapped Ion Mobility Spectrometry for potential transthyretin (ATTR) amyloidosis subtyping. While we utilized the standard LMD/LC–MS/MS workflow for amyloid subtyping of 31 specimens from different organs, we also evaluated the potential introduction in the MS workflow variations in data acquisition parameters like dynamic exclusion, or testing Data Dependent Acquisition combined with High-Field Asymmetric Waveform Ion Mobility Spectrometry (DDA FAIMS) versus Data Independent Acquisition (DIA) for enhanced amyloid protein identification at shorter acquisition times. We also demonstrate the use of Mascot’s Error Tolerant Search and PEAKS de novo sequencing for the sequence variant analysis of amyloidosis specimens.
Comparative Field Evaluation and Transcriptome Analysis Reveals that Chromosome Doubling Enhances Sheath Blight Resistance in Rice
Authors: Liu Sanglin , Liu Jiahao , Wang Wei , Yan Yugang , Wang Tianya , Wu Jinwen , Liu Xiangdong , Wu Jian , Zeng Yuxiang
Published: July 2024

Rice sheath blight, caused by Rhizoctonia solani Kihn (R. solani), poses a significant threat to rice production and quality. Autotetraploid rice, developed through chromosome doubling of diploid rice, holds great potential for enhancing biological and yield traits. However, its resistance to sheath blight in the field has remained unclear. In this study, the field resistance of 35 autotetraploid genotypes and corresponding diploids was evaluated across three environments from 2020 to 2021. The booting stage was optimal for inoculating period based on the inoculation and analysis of R. solani at five rice growth stages. We found autotetraploids generally exhibited lower disease scores than diploids, indicating enhanced resistance after chromosome doubling. Among the 35 genotypes, 16 (45.71%) displayed increased resistance, 2 (5.71%) showed decreased resistance, and 17 (48.57%) displayed unstable resistance in different sowing dates. All combinations of the genotype, environment and ploidy, including the genotype-environment-ploidy interaction, contributed significantly to field resistance. Chromosome doubling increased sheath blight resistance in most genotypes, but was also dependent on the genotype-environment interaction. To elucidate the enhanced resistance mechanism, RNA-seq revealed autotetraploid recruited more down-regulated differentially expressed genes (DEGs), additionally, more resistance-related DEGs, were down-regulated at 24 h post inoculation in autotetraploid versus diploid. The ubiquinone/terpenoid quinone and diterpenoid biosynthesis pathways may play key roles in ploidy-specific resistance mechanisms. In summary, our findings shed light on the understanding of sheath blight resistance mechanisms in autotetraploid rice.
Key gene modules and hub genes associated with pyrethroid and organophosphate resistance in Anopheles mosquitoes: a systems biology approach
Authors: Odhiambo Cynthia Awuor , Derilus Dieunel , Impoinvil Lucy Mackenzie , Omoke Diana , Saizonou Helga , Okeyo Stephen , Dada Nsa , Mulder Nicola , Nyamai Dorothy , Nyanjom Steven , Lenhart Audrey , Djogbénou Luc S. , Ochomo Eric
Published: July 2024

Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.
Genetic factors explaining anthocyanin pigmentation differences
Authors: Marin-Recinos Maria F. , Pucker Boas
Published: July 2024

Background

Anthocyanins are important contributors to coloration across a wide phylogenetic range of plants. Biological functions of anthocyanins span from reproduction to protection against biotic and abiotic stressors. Owing to a clearly visible phenotype of mutants, the anthocyanin biosynthesis and its sophisticated regulation have been studied in numerous plant species. Genes encoding the anthocyanin biosynthesis enzymes are regulated by a transcription factor complex comprising MYB, bHLH and WD40 proteins.

Results

A systematic comparison of anthocyanin-pigmented vs. non-pigmented varieties was performed within numerous plant species covering the taxonomic diversity of flowering plants. The literature was screened for cases in which genetic factors causing anthocyanin loss were reported. Additionally, transcriptomic data sets from four previous studies were reanalyzed to determine the genes possibly responsible for color variation based on their expression pattern. The contribution of different structural and regulatory genes to the intraspecific pigmentation differences was quantified. Differences concerning transcription factors are by far the most frequent explanation for pigmentation differences observed between two varieties of the same species. Among the transcription factors in the analyzed cases, MYB genes are significantly more prone to account for pigmentation differences compared to bHLH or WD40 genes. Among the structural genes, DFR genes are most often associated with anthocyanin loss.

Conclusions

These findings support previous assumptions about the susceptibility of transcriptional regulation to evolutionary changes and its importance for the evolution of novel coloration phenotypes. Our findings underline the particular significance of MYBs and their apparent prevalent role in the specificity of the MBW complex.
Assembly and comparative analysis of the complete mitochondrial and chloroplast genome of Cyperus stoloniferus (Cyperaceae), a coastal plant possessing saline-alkali tolerance
Authors: Miao Xiaorong , Yang Wenwen , Li Donghai , Wang Aiqin , Li Juanyun , Deng Xu , He Longfei , Niu Junqi
Published: July 2024

Background

Cyperus stoloniferus is an important species in coastal ecosystems and possesses economic and ecological value. To elucidate the structural characteristics, variation, and evolution of the organelle genome of C. stoloniferus, we sequenced, assembled, and compared its mitochondrial and chloroplast genomes.

Results

We assembled the mitochondrial and chloroplast genomes of C. stoloniferus. The total length of the mitochondrial genome (mtDNA) was 927,413 bp, with a GC content of 40.59%. It consists of two circular DNAs, including 37 protein-coding genes (PCGs), 22 tRNAs, and five rRNAs. The length of the chloroplast genome (cpDNA) was 186,204 bp, containing 93 PCGs, 40 tRNAs, and 8 rRNAs. The mtDNA and cpDNA contained 81 and 129 tandem repeats, respectively, and 346 and 1,170 dispersed repeats, respectively, both of which have 270 simple sequence repeats. The third high-frequency codon (RSCU > 1) in the organellar genome tended to end at A or U, whereas the low-frequency codon (RSCU < 1) tended to end at G or C. The RNA editing sites of the PCGs were relatively few, with only 9 and 23 sites in the mtDNA and cpDNA, respectively. A total of 28 mitochondrial plastid DNAs (MTPTs) in the mtDNA were derived from cpDNA, including three complete trnT-GGU, trnH-GUG, and trnS-GCU. Phylogeny and collinearity indicated that the relationship between C. stoloniferus and C. rotundus are closest. The mitochondrial rns gene exhibited the greatest nucleotide variability, whereas the chloroplast gene with the greatest nucleotide variability was infA. Most PCGs in the organellar genome are negatively selected and highly evolutionarily conserved. Only six mitochondrial genes and two chloroplast genes exhibited Ka/Ks > 1; in particular, atp9, atp6, and rps7 may have undergone potential positive selection.

Conclusion

We assembled and validated the mtDNA of C. stoloniferus, which contains a 15,034 bp reverse complementary sequence. The organelle genome sequence of C. stoloniferus provides valuable genomic resources for species identification, evolution, and comparative genomic research in Cyperaceae.
Physical enhancement of older adults using hyperbaric oxygen: a randomized controlled trial
Authors: Hadanny Amir , Sasson Efrat , Copel Laurian , Daniel-Kotovsky Malka , Yaakobi Eldad , Lang Erez , Fishlev Gregory , Polak Nir , Friedman Mony , Doenyas Keren , Finci Shachar , Zemel Yonatan , Bechor Yair , Efrati Shai
Published: July 2024

Introduction

Aging is associated with a progressive decline in the capacity for physical activity. The objective of the current study was to evaluate the effect of an intermittent hyperbaric oxygen therapy (HBOT) protocol on maximal physical performance and cardiac perfusion in sedentary older adults.

Methods

A randomized controlled clinical trial randomized 63 adults (> 64yrs) either to HBOT (n = 30) or control arms (n = 33) for three months. Primary endpoint included the maximal oxygen consumption (VO2Max) and VO2Max/Kg, on an E100 cycle ergometer. Secondary endpoints included cardiac perfusion, evaluated by magnetic resonance imaging and pulmonary function. The HBOT protocol comprised of 60 sessions administered on a daily basis, for 12 consecutive weeks, breathing 100% oxygen at 2 absolute atmospheres (ATA) for 90 min with 5-minute air breaks every 20 min.

Results

Following HBOT, improvements were observed in VO2Max/kg, with a significant increase of 1.91 ± 3.29 ml/kg/min indicated by a net effect size of 0.455 (p = 0.0034). Additionally, oxygen consumption measured at the first ventilatory threshold (VO2VT1) showed a significant increase by 160.03 ± 155.35 ml/min (p < 0.001) with a net effect size of 0.617. Furthermore, both cardiac blood flow (MBF) and cardiac blood volume (MBV) exhibited significant increases when compared to the control group. The net effect size for MBF was large at 0.797 (p = 0.008), while the net effect size for MBV was even larger at 0.896 (p = 0.009).

Conclusion

The findings of the study indicate that HBOT has the potential to improve physical performance in aging adults. The enhancements observed encompass improvements in key factors including VO2Max, and VO2VT1. An important mechanism contributing to these improvements is the heightened cardiac perfusion induced by HBOT.

Trial registration

ClinicalTrials.gov Identifier NCT02790541 (registration date 06/06/2016).
Mammary fat globules as a source of mRNA to model alterations in the expression of some milk component genes during lactation in bovines
Authors: Shaban Samar M. , Hassan Rania A. , Hassanin Abeer A. I. , Fathy Ahmed , El Nabtiti Adel A. S.
Published: July 2024

Background

The milk's nutritional value is determined by its constituents, including fat, protein, carbohydrates, and minerals. The mammary gland's ability to produce milk is controlled by a complex network of genes.

Thereby, the fat, protein, and lactose synthesis must be boost in milk to increase milk production efficiency. This can be accomplished by fusing genetic advancements with proper management practices. Therefore, this study aimed to investigate the association between the Lipoprotein lipase (LPL), kappa casein CSN3, and Glucose transporter 1 (GLUT1) genes expression levels and such milk components as fat, protein, and lactose in different dairy breeds during different stages of lactation.

Methods

To achieve such a purpose, 94 milk samples were collected (72 samples from 36 multiparous black-white and red-white Holstein–Friesian (HF) cows and 22 milk samples from 11 Egyptian buffaloes) during the early and peak lactation stages. The milk samples were utilized for milk analysis and genes expressions analyses using non- invasive approach in obtaining milk fat globules (MFGs) as a source of Ribonucleic acid (RNA).

Results

LPL and CSN3 genes expressions levels were found to be significantly higher in Egyptian buffalo than Holstein–Friesian (HF) cows as well as fat and protein percentages. On the other hand, GLUT1 gene expression level was shown to be significantly higher during peak lactation than early lactation. Moreover, lactose % showed a significant difference in peak lactation phase compared to early lactation phase. Also, fat and protein percentages were significantly higher in early lactation period than peak lactation period but lactose% showed the opposite pattern of Egyptian buffalo.

Conclusion

Total RNA can be successfully obtained from MFGs. The results suggest that these genes play a role in glucose absorption and lactose synthesis in bovine mammary epithelial cells during lactation. Also, these results provide light on the differential expression of these genes among distinct Holstein–Friesian cow breeds and Egyptian buffalo subspecies throughout various lactation phases.
More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers
Authors: Chen Yuxin , Deng Kaiyi , Hughes Ian M. , Smith Claire E. , Meng Hongdao , Le Minh Quan , Sun Min , Zhang Xianyan , Liu Danping
Published: July 2024

Background

The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking).

Methods

A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants.

Results

After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking.

Conclusions

Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers’ QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.
Is the burden of metastatic lymph node stations a prognostic factor in patients with resected lung cancer?
Authors: Çitak Necati , Erdogu Volkan , Aksoy Yunus , Ciftci Ayşegül , Yildiz Nisa , İsgörücü Özgür , Ozdemir Servet , Kose Selçuk , Ceylan Kenan Can , Metin Muzaffer
Published: July 2024

Objectives

The burden of metastatic lymph node (LN) stations might reflect a distinct N subcategory with a more aggressive biology and behaviour than the traditional N classification.

Methods

Between 2008 and 2018, we analyzed 1236 patients with pN1/2 lung cancer. Survival was analyzed based on LN station metastasis, determining the optimal threshold for the number of metastatic LN stations that provided additional prognostic information. N prognostic subgrouping was performed using thresholds for the number of metastatic LN stations with the maximum chi-square log-rank value, and validated at each pT-stage.

Results

Survival showed stepwise statistical deterioration with an increase in the number of metastatic LN stations., Threshold values for the number of metastatic LN stations were determined and N prognostic subgroupswas created as sN-alpha; one LN station metastases (n = 632), sN-beta; two-three LN stations metastases (n = 505), and sN-gamma; ≥4 LN stations metastasis (n = 99). The 5-year survival rate was 57.7% for sN-alpha, 39.2% for sN-beta, and 12.7% for sN-gamma (chi-square log rank = 97.906, p < 0.001). A clear tendency of survival deterioration was observed from sN-alpha to sN-gamma in the same pT stage, except for pT4 stage. Multivariate analysis showed that age (p < 0.001), sex (p = 0.002), tumour histology (p < 0.001), IASLC-proposed N subclassification (p < 0.001), and sN prognostic subgroups (p < 0.001) were independent risk factors for survival.

Conclusion

The burden of metastatic LN stations is an independent prognostic factor for survival in patients with lung cancer. It could provide additional prognostic information to the N classification.
A critically prolonged avalanche burial with recorded cardiac electrical activity and complete recovery - a case report
Authors: Bracco C. , Strapazzon G. , Sciolla A. , Dupuis A. , Lauria G. , Fenoglio L.
Published: July 2024

The probability of survival in avalanche accidents is time-dependent. Critically buried victims who undergo a long burial duration (over 60 min) face a possible mortality rate of over 80%. Understanding the physiological response during critical avalanche burial is crucial for improving rescue strategies and outcomes. We present the case of a 55-year-old male skier buried under an avalanche for 4 h and 51 min in the Italian Alps. Continuous heart rate monitoring revealed distinct phases of cardiac activity during burial. Despite severe hypothermia, the victim survived without extracorporeal rewarming. This case highlights the importance of continuous monitoring and appropriate on-site management in avalanche accidents. Factors such as the presence of an air pocket may positively influence survival. This case underscores the importance of comprehensive resuscitative measures and guidelines for managing avalanche victims with prolonged burial durations.
Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis
Authors: Heuts Samuel , Ubben Johannes F. H. , Kawczynski Michal J. , Gabrio Andrea , Suverein Martje M. , Delnoij Thijs S. R. , Kavalkova Petra , Rob Daniel , Komárek Arnošt , van der Horst Iwan C. C. , Maessen Jos G. , Yannopoulos Demetris , Bělohlávek Jan , Lorusso Roberto , van de Poll Marcel C. G.
Published: July 2024

Background

The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence.

Methods

A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated.

Results

Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73–3.32) with a mean absolute risk difference of 8.7% (− 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79–3.71) with a mean absolute risk difference of 10.8% (95%CrI − 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively.

Conclusion

The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials.

Registration

INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060).
A hybrid digital parenting programme to prevent abuse of adolescents in Tanzania: statistical analysis plan for a pragmatic cluster randomised controlled trial
Authors: Klapwijk Jonathan , Melendez-Torres G. J. , Ornellas Abigail , Wambura Mwita , Chetty Angelique N. , Baerecke Lauren , Wamoyi Joyce , Cluver Lucie D.
Published: July 2024

Background

Globally, violence against children poses substantial health and economic challenges, with estimated costs nearing USD 7 trillion. This prompts the urgent call for effective evidence-based interventions in preventing and mitigating violence against children. ParentApp is a mobile, open-source application designed to offer a remote version of the Parenting for Lifelong Health (PLH) programme. ParentApp is the first digital parenting intervention for caregivers of adolescents aged 10–17 years to be tested in low- and middle-income settings.

Methods

This study is a pragmatic, two-arm, cluster-randomised trial in Mwanza, Tanzania’s urban and peri-urban areas. Assessments are set for baseline, 1 month post-intervention, and 12 months post-intervention. We randomised 80 clusters, each with about 30 caregiver-adolescent dyads, with a 1:1 ratio stratified by urban or peri-urban location. Both arms receive an entry-level smartphone preloaded with Kiswahili apps—ParentApp for intervention and WashApp control.

The primary method of analysis will be generalised linear mixed-effects models with adjustment for person-level characteristics and multiple imputation. In three-level models, measurement waves are nested within a person, nested within a sub-ward. Regressions will constrain groups to be equal at baseline and include covariates for stratification, percentage of male caregivers, and individual-level characteristics.

Discussions

Preparations for the trial began in December 2022, including community mobilisation and sensitisation. Rolling recruitment, baseline data collection, and implementation onboarding took place between April and September 2023. One-month post-test data collection began in August 2023 and thus far achieved 97% and 94% retention rates for caregivers and adolescents respectively. Final post-test data collection will begin in September 2024, anticipated to run until April 2025. This SAP was submitted to the journal before the interim analysis to preserve scientific integrity under a superiority hypothesis testing framework.

Trial registration

The trial was registered on the Open Science Framework on 14 March 2023: https://doi.org/10.17605/OSF.IO/T9FXZ.

The trial protocol was published in Trials 25, 119 (2024): Baerecke, L., Ornellas, A., Wamoyi, J. et al. A hybrid digital parenting programme to prevent abuse of adolescents in Tanzania: study protocol for a pragmatic cluster-randomised controlled trial. Trials 25, 119 (2024). https://doi.org/10.1186/s13063-023-07893-x.
Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning
Authors: Zhang Li , Yan Qing , Lin Miao , He Juanjuan , Tian Jie , Chen Zhihan , Hong Fuyuan
Published: July 2024

Background

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients.

Methods

Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls.

Results

A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN.

Conclusion

The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.
Significance of physical factors on activities of daily living in patients with tetraplegia after spinal cord injury: a retrospective study
Authors: Yun Kimin , Lim Jin-cheol , Kim Onyoo
Published: July 2024

Background

Tetraplegia is a debilitating sequela of spinal cord injury (SCI). However, comprehensive approaches for determining the influence of various factors on activities of daily living (ADL) in patients with tetraplegia are limited. Therefore, this study aimed to determine the influence of physical factors on ADL in patients with tetraplegia after adjusting for demographic, SCI-related, and cognitive factors.

Methods

This retrospective cross-sectional study enrolled 201 patients with tetraplegia who underwent inpatient rehabilitation at the National Rehabilitation Center in South Korea between 2019 and 2021. Patients’ mean age was 50.5 years (standard deviation, 16.3), and 170 (84.6%) were men. The Korean Spinal Cord Independence Measure III (K-SCIM III) was used as the main outcome measure to assess patients’ ADL ability. Hierarchical multiple regression modeling was conducted with K-SCIM as the dependent variable to examine the level of functioning and relative influencing factors.

Results

Upper-extremity motor score (UEMS), upper-extremity spasticity and sitting balance scores were significant predictors of self-care; lower-extremity motor score (LEMS), musculoskeletal pain of shoulder, and sitting balance were significant predictors of respiratory and sphincter management; UEMS, LEMS, and sitting balance score were significant predictors of mobility; and UEMS, LEMS, musculoskeletal pain of shoulder, and sitting balance scores were significant predictors of the K-SCIM III total score after adjustment for demographic, SCI-related, and cognitive factors.

Conclusions

Physical factors had the greatest impact on all subscores and the K-SCIM III total score. Upper- and lower-extremity muscle strength and sitting balance significantly affected functional ability across all subscores.
Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways
Authors: Martino David , Schultz Nikki , Kaur Ravinder , van Haren Simon D. , Kresoje Nina , Hoch Annmarie , Diray-Arce Joann , Su Jessica Lasky , Levy Ofer , Pichichero Michael ,   in association with the IDEAL Consortium
Published: July 2024

Background

Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).

Results

An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.

Conclusions

This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.
Heat-related illness and dementia: a study integrating epidemiological and experimental evidence
Authors: Kuo Wan-Yin , Huang Chien-Cheng , Chen Chi-An , Ho Chung-Han , Tang Ling‑Yu , Lin Hung-Jung , Su Shih-Bin , Wang Jhi-Joung , Hsu Chien-Chin , Chang Ching-Ping , Guo How-Ran
Published: July 2024

Background

Heat-related illness (HRI) is commonly considered an acute condition, and its potential long-term consequences are not well understood. We conducted a population-based cohort study and an animal experiment to evaluate whether HRI is associated with dementia later in life.

Methods

The Taiwan National Health Insurance Research Database was used in the epidemiological study. We identified newly diagnosed HRI patients between 2001 and 2015, but excluded those with any pre-existing dementia, as the study cohort. Through matching by age, sex, and the index date with the study cohort, we selected individuals without HRI and without any pre-existing dementia as a comparison cohort at a 1:4 ratio. We followed each cohort member until the end of 2018 and compared the risk between the two cohorts using Cox proportional hazards regression models. In the animal experiment, we used a rat model to assess cognitive functions and the histopathological changes in the hippocampus after a heat stroke event.

Results

In the epidemiological study, the study cohort consisted of 70,721 HRI patients and the comparison cohort consisted of 282,884 individuals without HRI. After adjusting for potential confounders, the HRI patients had a higher risk of dementia (adjusted hazard ratio [AHR] = 1.24; 95% confidence interval [CI]: 1.19–1.29). Patients with heat stroke had a higher risk of dementia compared with individuals without HRI (AHR = 1.26; 95% CI: 1.18–1.34). In the animal experiment, we found cognitive dysfunction evidenced by animal behavioral tests and observed remarkable neuronal damage, degeneration, apoptosis, and amyloid plaque deposition in the hippocampus after a heat stroke event.

Conclusions

Our epidemiological study indicated that HRI elevated the risk of dementia. This finding was substantiated by the histopathological features observed in the hippocampus, along with the cognitive impairments detected, in the experimental heat stroke rat model.
Prevalence, trends, and specialized palliative care utilization in Taiwanese children and young adults with life-limiting conditions between 2008 and 2017: a nationwide population-based study
Authors: Lin Shih-Chun , Huang Mei-Chih
Published: July 2024

Background

Previous studies have shown a growing need for pediatric palliative care, but there is a lack of knowledge in many countries concerning prevalence of service use among children and young adults with life-limiting conditions. This study aimed to estimate (1) the annual prevalence of children and young adults with a life-limiting condition, and (2) their specialized palliative care and other healthcare utilization.

Methods

Data from the Health and Welfare Data Science Center in Taiwan were used. All children and young adults aged 0–25 years recorded in inpatient or outpatient data, and infants aged < 1 year in death data with a life-limiting condition diagnostic code from 2008 to 2017 were recruited. Poisson regression was used to estimate the crude and adjusted relative risk of prevalence of life-limiting conditions with 95% confidence intervals, adjusted for age and sex, and to evaluate the trend in prevalence of each life-limiting diagnostic groups, in specialized palliative care and other service use.

Results

Data contained 236,250 individuals with a life-limiting condition, of which oncological and congenital abnormalities were the most common. There was an annualized increase over 10 years in the prevalence of life-limiting conditions of 36.4%, from 45,311 cases (59.4 per 10,000 population) to 52,226 cases (81.0 per 10,000 population), with the highest prevalence in individuals aged 21–25 years. All diagnostic groups showed significant increases in prevalence (p < .001) with the exception of oncology, circulatory, and “other” group. Specialized palliative care services, including family consultation, shared care, home visits have increased in use over time (p < .001), while inpatient hospice has slightly decreased. The highest prevalence of healthcare use was for traditional Chinese medicine (237.1 per 1,000 population in 2017), but this decreased over time (p < .001).

Conclusions

Due to a growing trend towards multidisciplinary care, healthcare professionals and policymakers must engage and take action to expand specialized palliative care and integrate delivery of other healthcare services. Traditional Chinese medicine having a decreasing slope, yet still the highest prevalence of use, needs further attention.