bluuebunny/crossref_metadata_2025 huggingface dataset:
Two rare flavonoid glycosides from Litsea glutinosa (Lour.) C. B. Rob.: experimental and computational approaches endorse antidiabetic potentiality
Authors: Bulbul Israt Jahan , Hossain Md. Jamal , Haque Mohammad Rashedul , Al-Mansur Muhammad Abdullah , Hasan Choudhury M. , Al Hasan Abdullah , Rashid Mohammad A.
Published: February 2024

Background

Litsea glutinosa(Lour.) C. B. Rob. belongs to theLitseagenus and is categorized under the family ofLauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques.

Methods

Extensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from theL. glutinosaplant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques.

Results

In the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by1H and13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract ofL. glutinosaat doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption.

Conclusion

According to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.
Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats
Authors: Kawara Ragaa SM , Moawed Fatma SM , Elsenosi Yakout , Elmaksoud Hussein Abd , Ahmed Esraa S. A. , Abo-Zaid Omayma AR
Published: February 2024

Background

Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation.

Methods

Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined.

Results

MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes’ activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway.

Conclusion

Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.
The effectiveness of a virtual reality teaching module on advance care planning and advance decision for medical professionals
Authors: Chang You-Kang , Wu Yao-Kuang , Liu Tzu-Hung
Published: February 2024

Background

The concepts of advance care planning (ACP) and advance decisions/directives (ADs) are widely recognized around the world. The Patient Right to Autonomy Act in Taiwan, the first of its kind in Asia, went into effect in 2019. However, a lack of knowledge and confidence regarding ACP and ADs is a barrier for medical professionals in discussing ACP and ADs with their patients. In addition, in Asian countries, physicians tend to make family-centered decisions, which influence how they can implement ADs.

Methods

Virtual reality (VR) is known for its immersive and interactive simulation experience and can upgrade medical education. We developed a VR teaching module to help medical professionals better understand ACP and ADs, with assessment tools integrated into the module. The participants were asked to answer seven knowledge items embedded in the module and fill out the surveys regarding attitudes toward ACP and ADs and confidence in implementing ADs before and after the module. They also reported behaviors related to ADs before and three months after the VR experience.

Results

From July 2020 to June 2022, 30 physicians and 59 nurses joined the study, and 78.7% of them had no prior experience in hospice care. After learning from the VR module, all 89 participants were able to answer all seven items correctly. The results showed a slightly more positive attitude toward ACP and ADs (scores: 32.29 ± 3.80 versus 33.06 ± 3.96, p < .05) and more confidence in implementing ADs (scores: 13.96 ± 2.68 versus 16.24 ± 2.67, p < .001) after the VR module. Changes in AD-related behaviors (scores: 11.23 ± 4.01 versus 13.87 ± 4.11, p < .001) were also noted three months after the VR experience.

Conclusions

This study found that medical professionals may have better knowledge of ACP and ADs, slightly improved attitudes toward ACP and ADs, and greater confidence in implementing ADs after experiencing the VR module. Most importantly, the findings suggested that using a VR format may help motivate medical professionals to perform essential behaviors related to ADs, including introducing ADs to their patients and discussing ADs with their own family.
Low prevalence of mcr-1 in Escherichia coli from food-producing animals and food products in China
Authors: Mei Cai-Yue , Jiang Yue , Ma Qin-Chun , Lu Meng-Jun , Wu Han , Wang Zhen-Yu , Jiao Xinan , Wang Jing
Published: February 2024

Background

mcr-1-positive Escherichia coli has emerged as a significant threat to human health, veterinary health, and food safety in recent years. After the prohibition of colistin as a feed additive in animal husbandry in China, a noticeable reduction in both colistin resistance and the prevalence of mcr-1 was observed in E. coli from animals and humans.

Objectives

To assess the prevalence of the colistin resistance gene mcr-1 and characterize its genetic context in E. coli strains derived from fecal and meat samples from food-producing animals in China.

Methods

A total of 1,353 fecal samples and 836 food samples were collected between 2019 and 2020 in China. E. coli isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and their susceptibility to colistin were determined using the broth microdilution method. The colistin-resistant E. coli isolates were screened for the presence of mcr by PCR analysis and sequencing. The minimal inhibitory concentrations (MICs) of 15 antimicrobial agents against the mcr-1-positive strains were further tested using the agar dilution method, conjugation assays were performed, and whole genome sequencing was performed using Illumina HiSeq.

Results

In total, 1,403 E. coli strains were isolated. Thirteen isolates from chicken meat (n = 7), chickens (n = 3), and pigs (n = 3) were resistant to colistin with MIC values of 4 to 16 mg/L, and carried mcr-1. All mcr-1-positive strains, except for isolate AH20PE105, contained multiple resistance genes and exhibited multidrug-resistant phenotypes. They belonged to 10 sequence types (STs), including a novel ST (ST14521). mcr-1 was located on IncI2 (n = 9), IncX4 (n = 2), and IncHI2 (n = 2) plasmids, which were highly similar to other mcr-1-carrying plasmids sharing the same incompatibility type. Seven mcr-1-carrying plasmids could be successfully conjugally transferred to E. coli C600.

Conclusions

While the low prevalence of mcr-1 (0.93%) identified in this study may not immediately seem alarming, the very emergence of this gene merits attention given its implications for colistin resistance and public health. Hence, ongoing surveillance of mcr-1 in E. coli remains crucial.
Single-cell analysis reveals alterations in cellular composition and cell-cell communication associated with airway inflammation and remodeling in asthma
Authors: Yu Xiu , Li Lifei , Cai Bicheng , Zhang Wei , Liu Quan , Li Nan , Shi Xing , Yu Li , Chen Rongchang , Qiu Chen
Published: February 2024

Background

Asthma is a heterogeneous disease characterized by airway inflammation and remodeling, whose pathogenetic complexity was associated with abnormal responses of various cell types in the lung. The specific interactions between immune and stromal cells, crucial for asthma pathogenesis, remain unclear. This study aims to determine the key cell types and their pathological mechanisms in asthma through single-cell RNA sequencing (scRNA-seq).

Methods

A 16-week mouse model of house dust mite (HDM) induced asthma (n = 3) and controls (n = 3) were profiled with scRNA-seq. The cellular composition and gene expression profiles were assessed by bioinformatic analyses, including cell enrichment analysis, trajectory analysis, and Gene Set Enrichment Analysis. Cell-cell communication analysis was employed to investigate the ligand-receptor interactions.

Results

The asthma model results in airway inflammation coupled with airway remodeling and hyperresponsiveness. Single-cell analysis revealed notable changes in cell compositions and heterogeneities associated with airway inflammation and remodeling. GdT17 cells were identified to be a primary cellular source of IL-17, related to inflammatory exacerbation, while a subpopulation of alveolar macrophages exhibited numerous significantly up-regulated genes involved in multiple pathways related to neutrophil activities in asthma. A distinct fibroblast subpopulation, marked by elevated expression levels of numerous contractile genes and their regulators, was observed in increased airway smooth muscle layer by immunofluorescence analysis. Asthmatic stromal-immune cell communication significantly strengthened, particularly involving GdT17 cells, and macrophages interacting with fibroblasts. CXCL12/CXCR4 signaling was remarkedly up-regulated in asthma, predominantly bridging the interaction between fibroblasts and immune cell populations. Fibroblasts and macrophages could jointly interact with various immune cell subpopulations via the CCL8/CCR2 signaling. In particular, fibroblast-macrophage cell circuits played a crucial role in the development of airway inflammation and remodeling through IL1B paracrine signaling.

Conclusions

Our study established a mouse model of asthma that recapitulated key pathological features of asthma. ScRNA-seq analysis revealed the cellular landscape, highlighting key pathological cell populations associated with asthma pathogenesis. Cell-cell communication analysis identified the crucial ligand-receptor interactions contributing to airway inflammation and remodeling. Our findings emphasized the significance of cell-cell communication in bridging the possible causality between airway inflammation and remodeling, providing valuable hints for therapeutic strategies for asthma.
Low-frequency ultrasound for pulmonary hypertension therapy
Authors: Ostasevicius Vytautas , Jurenas Vytautas , Venslauskas Mantas , Kizauskiene Laura , Zigmantaite Vilma , Stankevicius Edgaras , Bubulis Algimantas , Vezys Joris , Mikuckyte Sandra
Published: February 2024

Background

Currently, there are no reliable clinical tools that allow non-invasive therapeutic support for patients with pulmonary arterial hypertension. This study aims to propose a low-frequency ultrasound device for pulmonary hypertension therapy and to demonstrate its potential.

Methods

A novel low-frequency ultrasound transducer has been developed. Due to its structural properties, it is excited by higher vibrational modes, which generate a signal capable of deeply penetrating biological tissues. A methodology for the artificial induction of pulmonary hypertension in sheep and for the assessment of lung physiological parameters such as blood oxygen concentration, pulse rate, and pulmonary blood pressure has been proposed.

Results

The results showed that exposure of the lungs to low-frequency ultrasound changed physiological parameters such as blood oxygen concentration, pulse rate and blood pressure. These parameters are most closely related to indicators of pulmonary hypertension (PH). The ultrasound exposure increased blood oxygen concentration over a 7-min period, while pulse rate and pulmonary blood pressure decreased over the same period. In anaesthetised sheep exposed to low-frequency ultrasound, a 10% increase in SpO2, a 10% decrease in pulse rate and an approximate 13% decrease in blood pressure were observed within 7 min.

Conclusions

The research findings demonstrate the therapeutic efficiency of low-frequency ultrasound on hypertensive lungs, while also revealing insights into the physiological aspects of gas exchange within the pulmonary system.
Integrated approach for detection of SARS-CoV-2 and its variant by utilizing LAMP and ARMS-PCR
Authors: Nawab Maryam , Riaz Syeda Kiran , Ismail Eiman , Ahamed Alfar , Tariq Aaysha , Malik Muhammad Faraz Arshad , Qusty Naeem F. , Bantun Farkad , Slama Petr , Umair Massab , Haque Shafiul , Bonilla-Aldana D. Katterine , Rodriguez-Morales Alfonso J.
Published: February 2024

Global impact of COVID-19 pandemic has heightened the urgency for efficient virus detection and identification of variants such as the Q57H mutation. Early and efficient detection of SARS-CoV-2 among densely populated developing countries is paramount objective. Although RT-PCR assays offer accuracy, however, dependence on expansive kits and availability of allied health resources pose an immense challenge for developing countries. In the current study, RT-LAMP based detection of SARS-Cov-2 with subsequent confirmation of Q57H variant through ARMS-PCR was performed. Among the 212 collected samples, 134 yielded positive results, while 78 tested negative using RT-LAMP. Oropharyngeal swabs of suspected individuals were collected and processed for viral RNA isolation. Isolated viral RNA was processed further by using either commercially available WarmStart Master Mix or our in house developed LAMP master mix separately. Subsequently, the end results of each specimen were evaluated by colorimetry. For LAMP assays, primers targeting three genes (ORF1ab, N and S) were designed using PrimerExplorer software. Interestingly, pooling of these three genes in single reaction tube increased sensitivity (95.5%) and specificity (93.5%) of LAMP assay. SARS-CoV-2 positive specimens were screened further for Q57H mutation using ARMS-PCR. Based on amplicon size variation, later confirmed by sequencing, our data showed 18.5% samples positive for Q57H mutation. Hence, these findings strongly advocate use of RT-LAMP-based assay for SARS-CoV-2 screening within suspected general population. Furthermore, ARMS-PCR also provides an efficient mean to detect prevalent mutations against SARS-Cov-2.
Preference for hotline versus mobile application/countdown-based mobile overdose response services: a qualitative study
Authors: Rioux William , Teare Adrian , Rider Nathan , Jones Stephanie , Ghosh S. Monty
Published: February 2024

Background

In response to the exacerbated rates of morbidity and mortality associated with the overlapping overdose and COVID-19 epidemics, novel strategies have been developed, implemented, operationalized and scaled to reduce the harms resulting from this crisis. Since the emergence of mobile overdose response services (MORS), two strategies have aimed to help reduce the mortality associated with acute overdose including staffed hotline-based services and unstaffed timer-based services. In this article, we aim to gather the perspectives of various key interest groups on these technologies to determine which might best support service users.

Methods

Forty-seven participants from various interested groups including people who use substances who have and have not used MORS, healthcare workers, family members, harm reduction employees and MORS operators participated in semi-structured interviews. Transcripts were coded and analyzed using a thematic analysis approach.

Results

Four major themes emerged regarding participant perspectives on the differences between services, namely differences in connection, perceived safety, privacy and accessibility, alongside features that are recommended for MORS in the future.

Conclusions

Overall, participants noted that individuals who use substances vary in their desire for connection during a substance use session offered by hotline and timer-based service modalities. Participants perceived hotline-based approaches to be more reliable and thus potentially safer than their timer-based counterparts but noted that access to technology is a limitation of both approaches.
The siRNA-mediated knockdown of AP-1 restores the function of the pulmonary artery and the right ventricle by reducing perivascular and interstitial fibrosis and key molecular players in cardiopulmonary disease
Authors: Comarița Ioana Karla , Tanko Gabriela , Anghelache Iliuță Laurențiu , Georgescu Adriana
Published: February 2024

Background

Pulmonary hypertension (PH) is a complex multifactorial vascular pathology characterized by an increased pulmonary arterial pressure, vasoconstriction, remodelling of the pulmonary vasculature, thrombosis in situ and inflammation associated with right-side heart failure. Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial hypertension (PAH), right ventricular dysfunction along with perivascular and interstitial fibrosis in pulmonary artery-PA, right ventricle-RV and lung in an experimental animal model of monocrotaline (MCT)-induced PAH.

Methods

Golden Syrian hamsters were divided into: (1) C group-healthy animals taken as control; (2) MCT group obtained by a single subcutaneous injection of 60 mg/kg MCT at the beginning of the experiment; (3) MCT-siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100 nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 12 weeks.

Results

In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects on investigated tissues contributing to: (1) a reduction in TGF-β1/ET-1/IL-1β/TNF-α plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung and notable improvements regarding the ultrastructure of these tissues; a decrease of inflammatory and fibrotic marker expressions in PA (COL1A/Fibronectin/Vimentin/α-SMA/CTGF/Calponin/MMP-9), RV and lung (COL1A/CTGF/Fibronectin/α-SMA/F-actin/OB-cadherin) and an increase of endothelial marker expressions (CD31/VE-cadherin) in PA; (4) structural and functional recoveries of the PA [reduced Vel, restored vascular reactivity (NA contraction, ACh relaxation)] and RV (enlarged internal cavity diameter in diastole, increased TAPSE and PRVOFs) associated with a decrease in systolic and diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3/ pFAK/FAK/pERK/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204.

Conclusions

The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.
SeptoSympto: a precise image analysis of Septoria tritici blotch disease symptoms using deep learning methods on scanned images
Authors: Mathieu Laura , Reder Maxime , Siah Ali , Ducasse Aurélie , Langlands-Perry Camilla , Marcel Thierry C. , Morel Jean-Benoît , Saintenac Cyrille , Ballini Elsa
Published: February 2024

Background

Investigations on plant-pathogen interactions require quantitative, accurate, and rapid phenotyping of crop diseases. However, visual assessment of disease symptoms is preferred over available numerical tools due to transferability challenges. These assessments are laborious, time-consuming, require expertise, and are rater dependent. More recently, deep learning has produced interesting results for evaluating plant diseases. Nevertheless, it has yet to be used to quantify the severity of Septoria tritici blotch (STB) caused by Zymoseptoria tritici—a frequently occurring and damaging disease on wheat crops.

Results

We developed an image analysis script in Python, called SeptoSympto. This script uses deep learning models based on the U-Net and YOLO architectures to quantify necrosis and pycnidia on detached, flattened and scanned leaves of wheat seedlings. Datasets of different sizes (containing 50, 100, 200, and 300 leaves) were annotated to train Convolutional Neural Networks models. Five different datasets were tested to develop a robust tool for the accurate analysis of STB symptoms and facilitate its transferability. The results show that (i) the amount of annotated data does not influence the performances of models, (ii) the outputs of SeptoSympto are highly correlated with those of the experts, with a similar magnitude to the correlations between experts, and (iii) the accuracy of SeptoSympto allows precise and rapid quantification of necrosis and pycnidia on both durum and bread wheat leaves inoculated with different strains of the pathogen, scanned with different scanners and grown under different conditions.

Conclusions

SeptoSympto takes the same amount of time as a visual assessment to evaluate STB symptoms. However, unlike visual assessments, it allows for data to be stored and evaluated by experts and non-experts in a more accurate and unbiased manner. The methods used in SeptoSympto make it a transferable, highly accurate, computationally inexpensive, easy-to-use, and adaptable tool. This study demonstrates the potential of using deep learning to assess complex plant disease symptoms such as STB.
Young children’s development after forced displacement: a systematic review
Authors: Bernhardt Katharina , Le Beherec Saskia , Uppendahl Jana R. , Fleischmann Melia , Klosinski Matthias , Rivera Luisa M. , Samaras Georgia , Kenney Martha , Müller Ruth , Nehring Ina , Mall Volker , Hahnefeld Andrea
Published: February 2024

Objectives

To examine the impact of displacement experiences on 0- to 6-year-old children’s social-emotional and cognitive development, as well as influencing factors on reported outcomes.

Study design

We systematically searched MEDline, Psyndex, Cochrane Library, Web of Science, Elsevier, TandF, Oxford Journal of Refugee Studies, Journal of Immigrant & Refugee Studies, and Canada’s Journal on Refugees for existing literature regarding social-emotional and cognitive outcomes in children directly exposed to forced displacement due to political violence. Results were synthesized in the discussion and displayed using harvest plots.

Results

Our search generated 9,791 articles of which 32 were selected for review and evaluation according to NICE criteria. Included studies provided results for 6,878 forcibly displaced children. Measured outcomes were diverse and included areas such as peer relations, prosocial behavior, family functioning, play, intelligence, learning performance, and language development. Repeated exposure to adverse experiences, separation from parents, parental distress, as well as duration and quality of resettlement in the host country were reported as influencing factors in the reviewed studies.

Conclusion

As protective factors like secure and stable living conditions help to promote children’s development, we call for policies that enhance participation in the welcoming society for refugee families. Early integration with low-threshold access to health and educational facilities can help to mitigate the wide-ranging negative consequences of forced displacement on young children’s development.
Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study
Authors: Petit Matthieu , Bidar Frank , Fosse Quentin , Lefevre Lucie , Paul Marine , Urbina Tomas , Masi Paul , Bavozet Florent , Lemarié Jérémie , de Montmollin Etienne , Andriamifidy-Berti Chloé , Dessajan Julien , Zuber Benjamin , Zafrani Lara , Peju Edwige , Meng Paris , Charrier Liliane , Le Guennec Loic , Simon Marie , Luyt Charles-Edouard , Haudebourg Luc , Geri Guillaume
Published: February 2024

Background

Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged.

Methods

Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death.

Results

From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21–42), 40% (95% CI 26–55) and 21% (95% CI 15–28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92–61.91)].

Conclusion

Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.
Simple but powerful interactive data analysis in R with R/LinkedCharts
Authors: Ovchinnikova Svetlana , Anders Simon
Published: February 2024

In research involving data-rich assays, exploratory data analysis is a crucial step. Typically, this involves jumping back and forth between visualizations that provide overview of the whole data and others that dive into details. For example, it might be helpful to have one chart showing a summary statistic for all samples, while a second chart provides details for points selected in the first chart. We present R/LinkedCharts, a framework that renders this task radically simple, requiring very few lines of code to obtain complex and general visualization, which later can be polished to provide interactive data access of publication quality.
The ROCK trial—a multidisciplinary Rehabilitation intervention for sudden Out-of-hospital Cardiac arrest survivors focusing on return-to-worK: a pragmatic randomized controlled trial protocol
Authors: Christensen Jan , Winkel Bo Gregers , Kirkeskov Lilli , Folke Fredrik , Winther-Jensen Matilde , Eckhardt-Bentsen Christine , Kjærgaard Jesper , Hassager Christian , Wagner Mette Kirstine
Published: February 2024

Introduction

Most cardiac arrest survivors are classified with mild to moderate cognitive impairment; roughly, 50% experience long-term neurocognitive impairment. Postarrest challenges complicate participation in society and are associated with social issues such as failure to resume social activities and impaired return to work. The effectiveness of rehabilitation interventions for out-of-hospital cardiac arrest survivors are sparsely described, but the body of evidence describes high probabilities of survivors not returning to work, returning to jobs with modified job descriptions, returning to part-time employment, and often in combination with extensive unmet rehabilitation needs. Hence, there is a need to develop and test a pragmatic individual targeted intervention to facilitate return to work (RTW) in survivors of OHCA. The overall aim of the ROCK trial is to evaluate the effectiveness of a comprehensive individually tailored multidisciplinary rehabilitation intervention for survivors of OHCA on RTW compared to usual care.

Methods and analysis

The ROCK trial is a two-arm parallel group multicentre investigator-initiated pragmatic randomized controlled superiority trial with primary endpoint measured 12 months after the cardiac arrest. Adult survivors who were part of the labour force prior to the OCHA and had at least 2 years until they are qualified to receive retirement state pensions are eligible for inclusion. Survivors will be randomized 1:1 to usual care group or usual care plus a comprehensive tailored rehabilitation intervention focusing on supporting RTW. After comprehensive assessment of individual rehabilitation needs, the intervention is ongoingly coordinated within a multidisciplinary rehabilitation team, and the intervention can be delivered for up until 12 months. Data for the primary outcome will be obtained from the national register on social transfer payments. The primary outcome will be analysed using logistic regression assessing RTW status at 12 months adjusting for the intervention and age at OHCA, sex, marital status, and occupation prior to OHCA.

Discussion

The ROCK trial is the first RCT to investigate the effectiveness of a rehabilitation intervention focusing on return to work after cardiac arrest.

Trial registration

ClinicalTrials.gov NCT05173740. Registered on May 2018
Effect of emerging digital technologies and methodologies combined with incentives on HbA1c in patients with type 2 diabetes mellitus: study protocol for a parallel, open randomized controlled trial
Authors: Zhong Shao , Jiang Jingyi , Liu Hongying , Pan Ying
Published: February 2024

Background

Type 2 diabetes mellitus (T2DM) is a common metabolic disease that requires long-term management and treatment. Digital intervention, as an emerging medical model, has been widely used in the treatment of T2DM patients. Behavioral economics theory provides a favorable perspective for studying the effect of digital intervention because it can reveal the decision-making mechanisms behind human behavior and provide more effective interventions for digital intervention. The purpose of this trial is to evaluate the impact of behaviorally based digital intervention on T2DM patients’ HbA1c, self-monitoring of blood glucose (SMBG) testing rate, diabetes self-efficacy, and other indicators compared to conventional treatment.

Methods

This trial is a prospective randomized controlled trial conducted at the First People’s Hospital of Kunshan City from April 1, 2023, to December 31, 2024, with a follow-up period of 3 months. The specific randomization method was established and implemented through the EDC clinical trial center’s randomization system. We will measure and collect baseline data from three groups, including Group A: digital intervention + virtual incentives + conventional treatment, Group B: digital intervention + physical incentives + conventional treatment, and Group C: conventional treatment. HbA1c, weight, SMBG testing rate, diabetes self-efficacy, and diabetes-related medical expenses will be recorded at baseline, 1 month, 2 months, and 3 months for all three groups. The Shapiro-Wilk test will be used to test for normality, and Pearson correlation analysis will be used for correlation analysis. Dropouts will be analyzed separately. Analysis of variance or exact probability calculation will be used to compare demographic data and other baseline indicators.

Discussion

This study is a novel clinical trial that integrates multiple disciplines (economics and medicine) and uses digital technology to deliver the intervention. Most published studies were offline interventions based on behavioral economics theory, but very few were on online interventions for T2DM patients. This study has both novelty and social value.

Trial registration

Chinese Clinical Trial Registry ChiCTR2300070753. Registered on 2023/04/22.
First report on the molecular phylogenetics and population genetics of Aedes aegypti in Iran
Authors: Paksa Azim , Azizi Kourosh , Yousefi Saideh , Dabaghmanesh Sorna , Shahabi Saeed , Sanei-Dehkordi Alireza
Published: February 2024

Background

Aedes aegypti, the primary vector of various human arboviral diseases, is a significant public health threat. Aedes aegypti was detected in Iran in 2018, in Hormozgan province, but comprehensive information regarding its genetic diversity and origin within the country remains scarce. This study aimed to determine the origin and genetic diversity of Ae. aegypti in southern Iran.

Methods

Aedes aegypti mosquitoes were collected from Bandar Abbas City, Hormozgan Province, southern Iran, between May and July 2022. Specimens were morphologically identified. Origin and assess genetic diversity were assessed based on the mitochondrial DNA-encoded cytochrome c oxidase subunit I (mtDNA-COI) gene.

Results

BLAST (basic local alignment search tool) analysis confirmed the accuracy of the morphological identification of all specimens as Ae. aegypti, with 100% similarity to GenBank sequences. Calculated variance and haplotype diversity were 0.502 and 0.00157, respectively. Among the 604 examined nucleotide sequences, only a single site was non-synonymous. Total nucleotide diversity and average pairwise nucleotides were determined as 0.00083 and 0.502, respectively. Fu and Li's D test values were not statistically significant. Strobeck’s S statistic value was 0.487, and Tajima’s D value was 1.53395; both were not statistically significant (P > 0.10).

Conclusions

Phylogenetic analysis revealed two distinct clades with minimal nucleotide differences and low haplotype diversity, suggesting the recent establishment of Ae. Aegypti in the southern region of Iran. The phylogenetic analysis also indicated an association between Ae. aegypti populations and mosquitoes from Saudi Arabia and Pakistan.

Graphical Abstract
Historic methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection
Authors: Benvenga Vanni , Cuénod Aline , Purushothaman Srinithi , Dasen Gottfried , Weisser Maja , Bassetti Stefano , Roloff Tim , Siegemund Martin , Heininger Ulrich , Bielicki Julia , Wehrli Marianne , Friderich Paul , Frei Reno , Widmer Andreas , Herzog Kathrin , Fankhauser Hans , Nolte Oliver , Bodmer Thomas , Risch Martin , Dubuis Olivier , Pranghofer Sigrid , Calligaris-Maibach Romana , Graf Susanne , Perreten Vincent , Seth-Smith Helena M. B , Egli Adrian
Published: February 2024

Background

Few methicillin-resistantStaphylococcus aureus(MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes.

Methods

We accessed 451 historic (1965–1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmeccassette types, AMR, and virulence genes.

Results

Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally.

Conclusions

The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time.
Post-treatment surveillance imaging in head and neck cancer: a systematic review
Authors: Van Hoe Stefaan , Hermans Robert
Published: February 2024

Background

In patients treated for head and neck cancer, imaging studies are usually obtained within 3–6 months after treatment for assessment of treatment response. After 6 months, most guidelines advocate clinical follow-up, with imaging reserved for patients with clinically suspect or equivocal findings. However, some guidelines do recommend systematic imaging surveillance, and many clinicians tend to include some type of imaging in their follow-up schemes.

Objectives

This systematic review focuses on the usefulness of routine (systematic) post-treatment imaging surveillance of head and neck cancer beyond the first 3–6-month baseline imaging study.

Methods

A systematic literature search was conducted using PubMed and Google Scholar. Additional studies were identified by reviewing reference lists. Only original studies and review papers were considered. Results obtained with systematic post-treatment surveillance imaging were compared to symptom-directed imaging and/or clinical finding-directed imaging.

Results

Five hundred twenty-one records were identified through the database search, and 44 additional records were identified through other sources. Forty-eight articles were selected for the final review.

Analysis of these records showed that almost half of cases of locoregional recurrences and/or metastases were only detected by imaging (40.9%), and the mean time of detection of recurrent or metastatic disease (11.5 months) was well beyond the period of the first post-treatment scan. Most authors reported superior results with PET-CT when compared to other imaging techniques.

Conclusion

Strong arguments were found in favor of systematic imaging surveillance in locoregional advanced head and neck cancer during at least one and preferably 2 years after treatment.

Critical relevance statement

Analysis of the selected records showed that almost half of cases of locoregional recurrences and/or metastases were only detected by imaging. This systematic review suggests that imaging may currently be underused in the post-treatment surveillance of patients with head and neck cancer.

Key points

• This systematic review focuses on the usefulness of long-term systematic imaging surveillance in patients treated for head and neck cancer.

• Analysis of 521 articles revealed that systematic imaging allowed the initial detection of locoregional recurrences and/or metastases in more than 40% of patients.

• Imaging may currently be underused in the post-treatment surveillance of patients with advanced head and neck cancer.

Graphical Abstract
Mesenchymal stem cell-derived exosomes: a promising alternative in the therapy of preeclampsia
Authors: Shi Haoran , Yang Zejun , Cui Jianjian , Tao Hui , Ma Ruilin , Zhao Yin
Published: February 2024

Preeclampsia (PE) is a common morbid complication during pregnancy, affecting 2%-8% of pregnancies globally and posing serous risks to the health of both mother and fetus. Currently, the only effective treatment for PE is timely termination of pregnancy, which comes with increased perinatal risks. However, there is no effective way to delay pathological progress and improve maternal and fetal outcomes. In light of this, it is of great significance to seek effective therapeutic strategies for PE. Exosomes which are nanoparticles carrying bioactive substances such as proteins, lipids, and nucleic acids, have emerged as a novel vehicle for intercellular communication. Mesenchymal stem cell-derived exosomes (MSC-Exos) participate in various important physiological processes, including immune regulation, cell proliferation and migration, and angiogenesis, and have shown promising potential in tissue repair and disease treatment. Recently, MSC-Exos therapy has gained popularity in the treatment of ischaemic diseases, immune dysfunction, inflammatory diseases, and other fields due to their minimal immunogenicity, characteristics similar to donor cells, ease of storage, and low risk of tumor formation. This review elaborates on the potential therapeutic mechanism of MSC-Exos in treating preeclampsia, considering the main pathogenic factors of the condition, including placental vascular dysplasia, immunological disorders, and oxidative stress, based on the biological function of MSC-Exos. Additionally, we discuss in depth the advantages and challenges of MSC-Exos as a novel acellular therapeutic agent in preeclampsia treatment.
Complex dental wear analysis reveals dietary shift in Triassic placodonts (Sauropsida, Sauropterygia)
Authors: Gere Kinga , Nagy András Lajos , Scheyer Torsten M. , Werneburg Ingmar , Ősi Attila
Published: February 2024

Placodonts were durophagous reptiles of the Triassic seas with robust skulls, jaws, and enlarged, flat, pebble-like teeth. During their evolution, they underwent gradual craniodental changes from the Early Anisian to the Rhaetian, such as a reduction in the number of teeth, an increase in the size of the posterior palatal teeth, an elongation of the premaxilla/rostrum, and a widening of the temporal region. These changes are presumably related to changes in dietary habits, which, we hypothesise, are due to changes in the type and quality of food they consumed. In the present study, the dental wear pattern of a total of nine European Middle to Late Triassic placodont species were investigated using 2D and 3D microwear analyses to demonstrate whether there could have been a dietary shift or grouping among the different species and, whether the possible changes could be correlated with environmental changes affecting their habitats. The 3D analysis shows overlap between species with high variance between values and there is no distinct separation. The 2D analysis has distinguished two main groups. The first is characterised by low number of wear features and high percentage of large pits. The other group have a high feature number, but low percentage of small pits. The 2D analysis showed a correlation between the wear data and the size of the enlarged posterior crushing teeth. Teeth with larger sizes showed less wear feature (with higher pit ratio) but larger individual features. In contrast, the dental wear facet of smaller crushing teeth shows more but smaller wear features (with higher scratch number). This observation may be related to the size of the food consumed, i.e., the wider the crown, the larger food it could crush, producing larger features. Comparison with marine mammals suggests that the dietary preference of Placochelys, Psephoderma and Paraplacodus was not exclusively hard, thick-shelled food. They may have had a more mixed diet, similar to that of modern sea otters. The diet of Henodus may have included plant food, similar to the modern herbivore marine mammals and lizards.
DenMerD: a feature enhanced approach to radar beam blockage correction with edge-cloud computing
Authors: Liu Qi , Sun Jiawei , Zhang Yonghong , Liu Xiaodong
Published: February 2024

In the field of meteorology, the global radar network is indispensable for detecting weather phenomena and offering early warning services. Nevertheless, radar data frequently exhibit anomalies, including gaps and clutter, arising from atmospheric refraction, equipment malfunctions, and other factors, resulting in diminished data quality. Traditional radar blockage correction methods, such as employing approximate radial information interpolation and supplementing missing data, often fail to effectively exploit potential patterns in massive radar data, for the large volume of data precludes a thorough analysis and understanding of the inherent complex patterns and dependencies through simple interpolation or supplementation techniques. Fortunately, edge computing possesses certain data processing capabilities and cloud center boasts substantial computational power, which together can collaboratively offer timely computation and storage for the correction of radar beam blockage. To this end, an edge-cloud collaborative driven deep learning model named DenMerD is proposed in this paper, which includes dense connection module and merge distribution (MD) unit. Compared to existing models such as RC-FCN, DenseNet, and VGG, this model greatly improves key performance metrics, with 30.7$$\%$$
%
improvement in Critical Success Index (CSI), 30.1$$\%$$
%
improvement in Probability of Detection (POD), and 3.1$$\%$$
%
improvement in False Alarm Rate (FAR). It also performs well in the Structure Similarity Index Measure (SSIM) metrics compared to its counterparts. These findings underscore the efficacy of the design in improving feature propagation and beam blockage accuracy, and also highlights the potential and value of mobile edge computing in processing large-scale meteorological data.