bluuebunny/crossref_metadata_2025 huggingface dataset:
Satisfaction with clinical pathway implementation versus job performance of clinicians: empirical evidence on the mediating role of work engagement from public hospitals in Sichuan, China
Authors: Li Junlong , Ao Lu , Pan Jay
Published: March 2024

Background

The job performance of clinicians is a clear indicator of both hospital capacity and the level of hospital service. It plays a crucial role in maintaining the effectiveness and quality of medical care. Clinical pathways are a systematic method of quality improvement successfully recommended by broader healthcare systems. Since clinicians play a key role in implementing clinical pathways in public hospitals, this study aims to investigate the effect of the satisfaction of clinicians in public hospitals with clinical pathway implementation on their job performance.

Methods

A cross-sectional study design was used. Questionnaires were administered online. A total of 794 clinicians completed the questionnaires in seven tertiary public hospitals in Sichuan Province, China, of which 723 were valid for analysis. Questionnaires contained questions on social demographic characteristics, satisfaction with clinical pathway implementation, work engagement, and job performance. Structural Equation Model (SEM) was used to test the hypotheses.

Results

The satisfaction of clinicians in public hospitals with clinical pathway implementation was significantly positively correlated with work engagement (r = 0.570,P < 0.01) and job performance (r = 0.522,P < 0.01). A strong indirect effect of clinicians’ satisfaction with clinical pathway implementation on job performance mediated by work engagement was observed, and the value of this effect was 0.383 (boot 95%CI [0.323, 0.448]).

Conclusion

The satisfaction of clinicians in public hospitals with clinical pathway implementation not only directly influences their job performance, but also indirectly affects it through the mediating variable of work engagement. Therefore, managers of public hospitals need to pay close attention to clinicians’ evaluation and perception of the clinical pathway implementation. This entails taking adequate measures, such as providing strong organizational support and creating a favorable environment for the clinical pathway implementation. Additionally, focusing on teamwork to increase clinicians’ satisfaction can further enhance job performance. Furthermore, managers should give higher priority to increasing employees’ work engagement to improve clinicians’ job performance.
The rise of big data: deep sequencing-driven computational methods are transforming the landscape of synthetic antibody design
Authors: Gallo Eugenio
Published: March 2024

Synthetic antibodies (Abs) represent a category of artificial proteins capable of closely emulating the functions of natural Abs. Their in vitro production eliminates the need for an immunological response, streamlining the process of Ab discovery, engineering, and development. These artificially engineered Abs offer novel approaches to antigen recognition, paratope site manipulation, and biochemical/biophysical enhancements. As a result, synthetic Abs are fundamentally reshaping conventional methods of Ab production. This mirrors the revolution observed in molecular biology and genomics as a result of deep sequencing, which allows for the swift and cost-effective sequencing of DNA and RNA molecules at scale. Within this framework, deep sequencing has enabled the exploration of whole genomes and transcriptomes, including particular gene segments of interest. Notably, the fusion of synthetic Ab discovery with advanced deep sequencing technologies is redefining the current approaches to Ab design and development. Such combination offers opportunity to exhaustively explore Ab repertoires, fast-tracking the Ab discovery process, and enhancing synthetic Ab engineering. Moreover, advanced computational algorithms have the capacity to effectively mine big data, helping to identify Ab sequence patterns/features hidden within deep sequencing Ab datasets. In this context, these methods can be utilized to predict novel sequence features thereby enabling the successful generation of de novo Ab molecules. Hence, the merging of synthetic Ab design, deep sequencing technologies, and advanced computational models heralds a new chapter in Ab discovery, broadening our comprehension of immunology and streamlining the advancement of biological therapeutics.
Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial
Authors: Ojeda-Rodriguez Ana , Rangel-Zuñiga Oriol A. , Arenas-de Larriva Antonio P. , Gutierrez-Mariscal Francisco M. , Torres-Peña Jose D. , Romero-Cabrera Juan L. , Podadera-Herreros Alicia , García-Fernandez Helena , Porras-Pérez Esther , Luque Raul M. , Kales Stefanos N. , Perez-Martinez Pablo , Delgado-Lista Javier , Yubero-Serrano Elena M. , Lopez-Miranda Jose
Published: March 2024

Background

Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years.

Methods

The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements.

Findings

1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group.

Conclusion

Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease.

Trial Registration

Clinicaltrials.gov number NCT00924937.
Comparison of different trapping methods to collect malaria vectors indoors and outdoors in western Kenya
Authors: Kosgei Jackline , Gimnig John E. , Moshi Vincent , Omondi Seline , McDermott Daniel P. , Donnelly Martin J. , Ouma Collins , Abong’o Bernard , Ochomo Eric
Published: March 2024

Background

Vector surveillance is among the World Health Organization global vector control response (2017–2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors.

Methods

Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R.

Results

Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC.

Conclusions

Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results.
Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction
Authors: Bigger-Allen Alexander , Gheinani Ali Hashemi , Adam Rosalyn M.
Published: March 2024

Background

Injury to contractile organs such as the heart, vasculature, urinary bladder and gut can stimulate a pathological response that results in loss of normal contractility. PDGF and TGFβ are among the most well studied initiators of the injury response and have been shown to induce aberrant contraction in mechanically active cells of hollow organs including smooth muscle cells (SMC) and fibroblasts. However, the mechanisms driving contractile alterations downstream of PDGF and TGFβ in SMC and fibroblasts are incompletely understood, limiting therapeutic interventions.

Methods

To identify potential molecular targets, we have leveraged the analysis of publicly available data, comparing transcriptomic changes in mechanically active cells stimulated with PDGF and TGFβ. Additional Analysis of publicly available data sets were performed on SMC and fibroblasts treated in the presence or absence of the MYC inhibitor JQ1. Validation of in silico findings were performed with qPCR, immunoblots, and collagen gel contraction assays measure the effect of JQ1 on cytoskeleton associated genes, proteins and contractility in mechanically active cells. Likelihood ratio test and FDR adjustedp-values were used to determine significant differentially expressed genes. Student ttest were used to calculate statistical significance of qPCR and contractility analyses.

Results

Comparing PDGF and TGFβ stimulated SMC and fibroblasts identified a shared molecular profile regulated by MYC and members of the AP-1 transcription factor complex. Additional in silico analysis revealed a unique set of cytoskeleton-associated genes that were sensitive to MYC inhibition with JQ1. In vitro validation demonstrated JQ1 was also able to attenuate TGFβ and PDGF induced changes to the cytoskeleton and contraction of smooth muscle cells and fibroblasts in vitro.

Conclusions

These findings identify MYC as a key driver of aberrant cytoskeletal and contractile changes in fibroblasts and SMC, and suggest that JQ1 could be used to restore normal contractile function in hollow organs.
Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model
Authors: Hørsdal Oskar Kjærgaard , Moeslund Niels , Berg-Hansen Kristoffer , Nielsen Roni , Møller Niels , Eiskjær Hans , Wiggers Henrik , Gopalasingam Nigopan
Published: March 2024

Background

Lactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs.

Methods

In this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure–volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters.

Results

Lactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by  -1.0 mmHg/ml (95% CI  -2.0 to  -0.1) and systemic vascular resistance decreased by  -548 dynes/s/cm5 (95% CI  -261 to  -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed.

Conclusion

Lactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.

Graphical Abstract
Profiling of 1-aminocyclopropane-1-carboxylic acid and selected phytohormones in Arabidopsis using liquid chromatography-tandem mass spectrometry
Authors: Karady Michal , Hladík Pavel , Cermanová Kateřina , Jiroutová Petra , Antoniadi Ioanna , Casanova-Sáez Rubén , Ljung Karin , Novák Ondřej
Published: March 2024

Background

Gaseous phytohormone ethylene levels are directly influenced by the production of its immediate non-volatile precursor 1-aminocyclopropane-1-carboxylic acid (ACC). Owing to the strongly acidic character of the ACC molecule, its quantification has been difficult to perform. Here, we present a simple and straightforward validated method for accurate quantification of not only ACC levels, but also major members of other important phytohormonal classes – auxins, cytokinins, jasmonic acid, abscisic acid and salicylic acid from the same biological sample.

Results

The presented technique facilitates the analysis of 15 compounds by liquid chromatography coupled with tandem mass spectrometry. It was optimized and validated for 10 mg of fresh weight plant material. The extraction procedure is composed of a minimal amount of necessary steps. Accuracy and precision were the basis for evaluating the method, together with process efficiency, recovery and matrix effects as validation parameters. The examined compounds comprise important groups of phytohormones, their active forms and some of their metabolites, including six cytokinins, four auxins, two jasmonates, abscisic acid, salicylic acid and 1-aminocyclopropane-1-carboxylic acid. The resulting method was used to examine their contents in selected Arabidopsis thaliana mutant lines.

Conclusion

This profiling method enables a very straightforward approach for indirect ethylene study and explores how it interacts, based on content levels, with other phytohormonal groups in plants.
Characterizing reference genes for high-fidelity gene expression analysis under different abiotic stresses and elicitor treatments in fenugreek leaves
Authors: Ebrahimi Amin , Gharanjik Shahrokh , Azadvari Elham , Rashidi-Monfared Sajad
Published: March 2024

Background

Quantifying gene expression is a critical aspect of applied genomics research across all organisms, and real-time PCR has emerged as a powerful tool for this purpose. However, selecting appropriate internal control genes for data normalization presents specific challenges. This study aimed to identify suitable reference genes for gene expression analysis under various conditions, encompassing salinity, low and high-temperature stresses, and different elicitor treatments. These treatments included titanium dioxide, cold plasma, 24-epibrassinolide, and melatonin, resulting in a total of 13 unique treatments and 148 treatment combinations applied to fenugreek plants.

Results

As per the analysis performed with the BestKeeper tool, EEF-1α, and GAPDH were recognized as the most stable reference genes under the majority of conditions. Furthermore, the GeNorm and NormFinder tools identified β-tubulin and EEF-1α as the most stable reference genes. The findings of this research demonstrated that, although the stability of three reference genes expression was acceptable in almost all evaluated treatments, fluctuations in their expression were observed under the treatments of cold stress with TiO2 NPs application, cold plasma application with salinity stress, and cold plasma application with high-temperature stress compared to others. Simultaneously, the GeNorm analysis results demonstrated that in the mentioned treatments, relying on only one reference gene is inadequate. To corroborate the results, we examined the expression profile of the SSR gene, a pivotal gene in diosgenin biosynthesis, under all investigated treatments and treatment combinations. The outcomes suggested that employing stable reference genes yielded highly consistent results.

Conclusions

The varying expression patterns of the target genes emphasize the crucial need for precise optimization of experimental conditions and selecting stable reference genes to achieve accurate results in gene expression studies utilizing real-time PCR. These findings offer valuable insights into the selection of appropriate reference genes for gene expression analysis under diverse conditions using real-time PCR.
Association of systemic inflammatory markers with postoperative arrhythmias in esophageal cancer: a propensity score matching
Authors: Xiao Hongbi , lv Xiaoxia , Zhou Siding , Ren Qinglin , Zhang Ziang , Wang Xiaolin
Published: March 2024

Background

The severity and prognosis of an array of inflammatory diseases have been predicted using systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). The purpose of this study was to examine the association between systemic inflammatory markers and postoperative arrhythmias (PA) in esophageal cancer patients.

Methods

In the study, laboratory-related parameters were gathered and examined in 278 patients (non-PA = 221, PA = 57). Fit separate propensity score matching (PSM) within subgroup strata (surgery approaches); match within strata, and aggregate for main analysis. Finally, we established a 1:1(57:57) model. The ability of inflammatory makers on the first post-esophagectomy day to distinguish PA from postoperative non-arrhythmia (non-PA) by receiver operating characteristic (ROC) analysis.

Results

On the first post-esophagectomy day, there was a greater difference between PA and non-PA in terms of white blood cell (WBC) and neutrophil (NE), Neutrophil percentage (NE%), NLR, dNLR, LMR, and SII. After PSM, the following variables were substantially different between non-PA and PA: NE%, NLR, dNLR, and SII. It was found that WBC, NE, NE%, NLR, dNLR, LMR, and SII had the area under the curve (AUC) that was higher than 0.500 in ROC analysis, with NLR and SII having the highest AUC (AUC = 0.661). The indicators were subjected to binary logistic regression analysis, which increased the indicators' predictive ability (AUC = 0.707, sensitivity = 0.877).

Conclusion

On the first post-esophagectomy day, systemic inflammatory indicators were significantly correlated with both PA and non-PA, and high SII and NLR are reliable markers of PA.
The localization, origin, and impact of platelets in the tumor microenvironment are tumor type-dependent
Authors: Le Chapelain Ophélie , Jadoui Soumaya , Gros Angèle , Barbaria Samir , Benmeziane Keltouma , Ollivier Véronique , Dupont Sébastien , Solo Nomenjanahary Mialitiana , Mavouna Sabrina , Rogozarski Jasmina , Mawhin Marie-Anne , Caligiuri Giuseppina , Delbosc Sandrine , Porteu Françoise , Nieswandt Bernhard , Mangin Pierre H , Boulaftali Yacine , Ho-Tin-Noé Benoit
Published: March 2024

Background

How platelets interact with and influence the tumor microenvironment (TME) remains poorly characterized.

Methods

We compared the presence and participation of platelets in the TME of two tumors characterized by highly different TME, PyMT AT-3 mammary tumors and B16F1 melanoma.

Results

We show that whereas firmly adherent platelets continuously line tumor vessels of both AT-3 and B16F1 tumors, abundant extravascular stromal clusters of platelets from thrombopoietin-independent origin were present only in AT-3 mammary tumors. We further show that platelets influence the angiogenic and inflammatory profiles of AT-3 and B16F1 tumors, though with very different outcomes according to tumor type. Whereas thrombocytopenia increased bleeding in both tumor types, it further caused severe endothelial degeneration associated with massive vascular leakage, tumor swelling, and increased infiltration of cytotoxic cells, only in AT-3 tumors.

Conclusions

These results indicate that while platelets are integral components of solid tumors, their localization and origin in the TME, as well as their impact on its shaping, are tumor type-dependent.
Flexor Injury Rehabilitation Splint Trial (FIRST): protocol for a pragmatic randomised controlled trial comparing three splints for finger flexor tendon repairs
Authors: Bamford Emma , Berntsson Hannah , Beale Suzanne , Desoysa Lauren , Dias Joseph , Hamer-Kiwacz Sienna , Hind Daniel , Johnson Nick , Loban Amanda , Molloy Kaye , Morvan Emma , Rombach Ines , Selby Anna , Thokala Praveen , Turtle Chris , Walters Stephen , Drummond Avril
Published: March 2024

Background

Without surgical repair, flexor tendon injuries do not heal and patients’ ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap.

Methods

FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants’ preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness.

Discussion

FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes.

Trial registration

ISRCTN: 10236011
TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis
Authors: Wang Wenchao , Ma Zhenkai , Feng Xuemin , Ren Jiabin , Sun Shengyao , Shao Yuandong , Zhang Weimin , Yang Xiaoxia , Zhang Jiaming , Jing Xingzhi
Published: March 2024

Objective

Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms.

Methods

TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1β was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo.

Results

TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration.

Conclusion

Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.
Fulminant myocarditis during postoperative adjuvant chemotherapy for lung cancer with atezolizumab: a case report
Authors: Tokunaga Takuya , Aoki Masaya , Maruyama Koki , Nonaka Yuto , Kariatsumari Kota , Sakasegawa Koichi , Ueda Kazuhiro
Published: March 2024

Background

Postoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab.

Case presentation

The patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient’s shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient’s history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range.

Conclusion

Myocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.
O-GlcNAcylation: a pro-survival response to acute stress in the cardiovascular and central nervous systems
Authors: Xue Qiu , Ji Shengtao , Xu Hui , Yu Shu
Published: March 2024

O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.
Contigs directed gene annotation (ConDiGA) for accurate protein sequence database construction in metaproteomics
Authors: Wu Enhui , Mallawaarachchi Vijini , Zhao Jinzhi , Yang Yi , Liu Hebin , Wang Xiaoqing , Shen Chengpin , Lin Yu , Qiao Liang
Published: March 2024

Background

Microbiota are closely associated with human health and disease. Metaproteomics can provide a direct means to identify microbial proteins in microbiota for compositional and functional characterization. However, in-depth and accurate metaproteomics is still limited due to the extreme complexity and high diversity of microbiota samples. It is generally recommended to use metagenomic data from the same samples to construct the protein sequence database for metaproteomic data analysis. Although different metagenomics-based database construction strategies have been developed, an optimization of gene taxonomic annotation has not been reported, which, however, is extremely important for accurate metaproteomic analysis.

Results

Herein, we proposed an accurate taxonomic annotation pipeline for genes from metagenomic data, namely contigs directed gene annotation (ConDiGA), and used the method to build a protein sequence database for metaproteomic analysis. We compared our pipeline (ConDiGA or MD3) with two other popular annotation pipelines (MD1 and MD2). In MD1, genes were directly annotated against the whole bacterial genome database; in MD2, contigs were annotated against the whole bacterial genome database and the taxonomic information of contigs was assigned to the genes; in MD3, the most confident species from the contigs annotation results were taken as reference to annotate genes. Annotation tools, including BLAST, Kaiju, and Kraken2, were compared. Based on a synthetic microbial community of 12 species, it was found that Kaiju with the MD3 pipeline outperformed the others in the construction of protein sequence database from metagenomic data. Similar performance was also observed with a fecal sample, as well as in silico mixed datasets of the simulated microbial community and the fecal sample.

Conclusions

Overall, we developed an optimized pipeline for gene taxonomic annotation to construct protein sequence databases. Our study can tackle the current taxonomic annotation reliability problem in metagenomics-derived protein sequence database and can promote the in-depth metaproteomic analysis of microbiome. The unique metagenomic and metaproteomic datasets of the 12 bacterial species are publicly available as a standard benchmarking sample for evaluating various analysis pipelines. The code of ConDiGA is open access at GitHub for the analysis of microbiota samples.
Manipulating the physical distance between cells during soil colonization reveals the importance of biotic interactions in microbial community assembly
Authors: Romdhane Sana , Huet Sarah , Spor Aymé , Bru David , Breuil Marie-Christine , Philippot Laurent
Published: March 2024

Background

Microbial communities are of tremendous importance for ecosystem functioning and yet we know little about the ecological processes driving the assembly of these communities in the environment. Here, we used an unprecedented experimental approach based on the manipulation of physical distance between neighboring cells during soil colonization to determine the role of bacterial interactions in soil community assembly. We hypothesized that experimentally manipulating the physical distance between bacterial cells will modify the interaction strengths leading to differences in microbial community composition, with increasing distance between neighbors favoring poor competitors.

Results

We found significant differences in both bacterial community diversity, composition and co-occurrence networks after soil colonization that were related to physical distancing. We show that reducing distances between cells resulted in a loss of bacterial diversity, with at least 41% of the dominant OTUs being significantly affected by physical distancing. Our results suggest that physical distancing may differentially modulate competitiveness between neighboring species depending on the taxa present in the community. The mixing of communities that assembled at high and low cell densities did not reveal any “home field advantage” during coalescence. This confirms that the observed differences in competitiveness were due to biotic rather than abiotic filtering.

Conclusions

Our study demonstrates that the competitiveness of bacteria strongly depends on cell density and community membership, therefore highlighting the fundamental role of microbial interactions in the assembly of soil communities.
Errors in visual search: Are they stochastic or deterministic?
Authors: Li Aoqi , Hulleman Johan , Wolfe Jeremy M.
Published: March 2024

In any visual search task in the lab or in the world, observers will make errors. Those errors can be categorized as “deterministic”: If you miss this target in this display once, you will definitely miss it again. Alternatively, errors can be “stochastic”, occurring randomly with some probability from trial to trial. Researchers and practitioners have sought to reduce errors in visual search, but different types of errors might require different techniques for mitigation. To empirically categorize errors in a simple search task, our observers searched for the letter “T” among “L” distractors, with each display presented twice. When the letters were clearly visible (white letters on a gray background), the errors were almost completely stochastic (Exp 1). An error made on the first appearance of a display did not predict that an error would be made on the second appearance. When the visibility of the letters was manipulated (letters of different gray levels on a noisy background), the errors became a mix of stochastic and deterministic. Unsurprisingly, lower contrast targets produced more deterministic errors. (Exp 2). Using the stimuli of Exp 2, we tested whether errors could be reduced using cues that guided attention around the display but knew nothing about the content of that display (Exp3a, b). This had no effect, but cueing all item locations did succeed in reducing deterministic errors (Exp3c).
Development of the China’s list of ambulatory care sensitive conditions (ACSCs): a study protocol
Authors: Wang Jianjian , Xu Dong Roman , Zhang Yan , Fu Hongqiao , Wang Sijiu , Ju Ke , Chen Chu , Yang Lian , Jian Weiyan , Chen Lei , Liao Xiaoyang , Xiao Yue , Wu Ruixian , Jakovljevic Mihajlo , Chen Yaolong , Pan Jay
Published: March 2024

Background

The hospitalization rate of ambulatory care sensitive conditions (ACSCs) has been recognized as an essential indicator reflective of the overall performance of healthcare system. At present, ACSCs has been widely used in practice and research to evaluate health service quality and efficiency worldwide. The definition of ACSCs varies across countries due to different challenges posed on healthcare systems. However, China does not have its own list of ACSCs. The study aims to develop a list to meet health system monitoring, reporting and evaluation needs in China.

Methods

To develop the list, we will combine the best methodological evidence available with real-world evidence, adopt a systematic and rigorous process and absorb multidisciplinary expertise. Specific steps include: (1) establishment of working groups; (2) generations of the initial list (review of already published lists, semi-structured interviews, calculations of hospitalization rate); (3) optimization of the list (evidence evaluation, Delphi consensus survey); and (4) approval of a final version of China’s ACSCs list. Within each step of the process, we will calculate frequencies and proportions, use descriptive analysis to summarize and draw conclusions, discuss the results, draft a report, and refine the list.

Discussion

Once completed, China’s list of ACSCs can be used to comprehensively evaluate the current situation and performance of health services, identify flaws and deficiencies embedded in the healthcare system to provide evidence-based implications to inform decision-makings towards the optimization of China’s healthcare system. The experiences might be broadly applicable and serve the purpose of being a prime example for nations with similar conditions.
Accelerated IVIM-corrected DTI in acute hamstring injury: towards a clinically feasible acquisition time
Authors: Rauh Susanne S. , Suskens Jozef J. M. , Monte Jithsa R. , Smithuis Frank , Gurney-Champion Oliver J. , Tol Johannes L. , Maas Mario , Nederveen Aart J. , Strijkers Gustav J. , Hooijmans Melissa T.
Published: March 2024

Background

Intravoxel incoherent motion (IVIM)-corrected diffusion tensor imaging (DTI) potentially enhances return-to-play (RTP) prediction after hamstring injuries. However, the long scan times hamper clinical implementation. We assessed accelerated IVIM-corrected DTI approaches in acute hamstring injuries and explore the sensitivity of the perfusion fraction (f) to acute muscle damage.

Methods

Athletes with acute hamstring injury received DTI scans of both thighs < 7 days after injury and at RTP. For a subset, DTI scans were repeated with multiband (MB) acceleration. Data from standard and MB-accelerated scans were fitted with standard and accelerated IVIM-corrected DTI approach using high b-values only. Segmentations of the injury and contralateral healthy muscles were contoured. The fitting methods as well as the standard and MB-accelerated scan were compared using linear regression analysis. For sensitivity to injury, Δ(injured minus healthy) DTI parameters between the methods and the differences between injured and healthy muscles were compared (Wilcoxon signed-rank test).

Results

The baseline dataset consisted of 109 athletes (16 with MB acceleration); 64 of them received an RTP scan (8 with MB acceleration). Linear regression of the standard and high-b DTI fitting showed excellent agreement. With both fitting methods, standard and MB-accelerated scans were comparable. Δ(injured minus healthy) was similar between standard and accelerated methods. For all methods, all IVIM-DTI parameters except f were significantly different between injured and healthy muscles.

Conclusions

High-b DTI fitting with MB acceleration reduced the scan time from 11:08 to 3:40 min:s while maintaining sensitivity to hamstring injuries; f was not different between healthy and injured muscles.

Relevance statement

The accelerated IVIM-corrected DTI protocol, using fewer b-values and MB acceleration, reduced the scan time to under 4 min without affecting the sensitivity of the quantitative outcome parameters to hamstring injuries. This allows for routine clinical monitoring of hamstring injuries, which could directly benefit injury treatment and monitoring.

Key points

• Combining high-b DTI-fitting and multiband-acceleration dramatically reduced by two thirds the scan time.

• The accelerated IVIM-corrected DTI approaches maintained the sensitivity to hamstring injuries.

• The IVIM-derived perfusion fraction was not sensitive to hamstring injuries.

Graphical Abstract
Shorter ZK-SNARKs from square span programs over ideal lattices
Authors: Lin Xi , Cao Heyang , Liu Feng-Hao , Wang Zhedong , Wang Mingsheng
Published: March 2024

Zero-knowledge succinct non-interactive arguments of knowledge (zk-SNARKs) are cryptographic protocols that offer efficient and privacy-preserving means of verifying NP language relations and have drawn considerable attention for their appealing applications, e.g., verifiable computation and anonymous payment protocol. Compared with the pre-quantum case, the practicability of this primitive in the post-quantum setting is still unsatisfactory, especially for the space complexity. To tackle this issue, this work seeks to enhance the efficiency and compactness of lattice-based zk-SNARKs, including proof length and common reference string (CRS) length. In this paper, we develop the framework of square span program-based SNARKs and design new zk-SNARKs over cyclotomic rings. Compared with previous works, our construction is without parallel repetition and achieves shorter proof and CRS lengths than previous lattice-based zk-SNARK schemes. Particularly, the proof length of our scheme is around $$23.3\%$$

23.3
%

smaller than the recent shortest lattice-based zk-SNARKs by Ishai et al. (in: Proceedings of the 2021 ACM SIGSAC conference on computer and communications security, pp 212–234, 2021), and the CRS length is $$3.6\times$$

3.6
×

smaller. Our constructions follow the framework of Gennaro et al. (in: Proceedings of the 2018 ACM SIGSAC conference on computer and communications security, pp 556–573, 2018), and adapt it to the ring setting by slightly modifying the knowledge assumptions. We develop concretely small constructions by using module-switching and key-switching procedures in a novel way.
Embryo response to aneuploidy through self-correction mechanism: a literature review
Authors: Harzif Achmad Kemal , Andyra Azizah Fitriayu , Sayogo Atikah , Ummah Nafi’atul , Puspawardani Aisyah Retno , Nurbaeti Putri , Wiweko Budi
Published: March 2024

Background

Meiotic and mitotic errors often lead to aneuploidy and mosaicism. In this context, the self-correction mechanism enables the embryo to preferentially retain and preserve euploid cells through processes such as apoptosis, necrosis, or marginalization. This mechanism is thought to minimize the chance of genetic abnormalities during cell development.

Materials and methods

A literature search for articles written in English from January 2013 to October 2023 was conducted on PubMed, EBSCO, and Scopus, using the keywords “self-correction,” “self-repair,” “aneuploidy,” “mosaicism,” and “embryo.”

Results

A total of 308 articles were collected, out of which 5 retrospective and 1 prospective study were selected based on inclusion criteria.

Discussions

Investigations showed that embryos remove chromosomally abnormal cells, supporting the self-correction mechanism. aCGH has been used in 4 studies to demonstrate the presence of self-correction in mosaic embryos. Furthermore, a higher relative viability of polyploidies than complex aneuploidies was observed, suggesting early discrimination against complex aneuploidy, particularly those arising from mitotic origins. However, there are doubts about the reliability of preimplantation genetic testing for aneuploidy at the blastocyst stage, as it may lead to a high rate of false positives and the discarding of "good" embryos.

Conclusions

Studies showed a self-correction mechanism in human embryos through the ability to expel abnormal cells. Further investigation is needed to elucidate the underlying mechanisms and determine optimal strategies for preimplantation genetic testing to fully understand and optimize the use of self-correction mechanisms in embryo assessment and selection.
Randomized pilot trial of cell phone support to improve medication adherence among adolescents and young adults with chronic health conditions
Authors: Sayegh Caitlin S. , MacDonell Karen K. , Iverson Ellen , Beard Breaon , Chang Nancy , Vu My H. , Belzer Marvin
Published: March 2024

Introduction

Adolescents and young adults (AYA) living with chronic medical conditions often struggle to develop medication adherence skills. This pilot trial evaluated the impact of a mobile health coaching intervention, Cell Phone Support (CPS), on medication adherence.

Methods

Interventions in this randomized trial were CPS delivered by phone calls (CPS-C), CPS delivered by text messages (CPS-T), or automated text message reminders (ATR). Participants were AYA with different chronic medical conditions (i.e., sickle cell disease, solid organ transplant, type 2 diabetes), aged 15–20 years (N = 34). We examined the feasibility, acceptability, and preliminary efficacy of each intervention.

Results

We examined the feasibility, acceptability, and preliminary efficacy of both CPS interventions. CPS was feasible and acceptable. There was evidence that participants found CPS to be more useful than ATR. In this pilot trial, participants receiving CPS reported relatively stronger increases in adherence, compared to those assigned to ATR. CPS-C slightly outperformed CPS-T.

Conclusions

Providing coaching to AYA struggling with illness self-management via their cell phones may promote their acquisition of medication adherence skills. Although larger studies are needed to confirm the results of this pilot study, phone calls and text messages are both promising modalities for delivering human cell phone support.

Trial registration

This trial was registered prospectively at ClinicalTrials.gov (NCT04241627) on 1/27/2020.