bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of the BioFire® FilmArray® pneumonia panel in COVID-19 patients with ventilator-associated pneumonia
Authors: Cojuc-Konigsberg Gabriel , Moscona-Nissan Alberto , Guijosa Alberto , Mireles Dávalos Christian D. , Martínez María E. Jiménez , Mújica Sánchez Mario A. , Hernández Huizar Víctor F. , Durán Barrón Martha A. , Gómez Karen Villarreal , Andrade-Galindo Regina , Ordóñez-Oviedo Montserrat , Brito Grecia Deloya , Vargas Eduardo Becerril
Published: August 2023

Background

Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance.

Methods

We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared.

Results

We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%).

Conclusion

The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.
Risk factors associated with the prevalence of neck and shoulder pain among high school students: a cross-sectional survey in China
Authors: Wang Ruilong , Yin Yue , Zhang Haoliang , Pan Letian , Zhu Yuanting , Wang Mingxiu , Huang Ziyin , Wang Weiheng , Deng Guoying
Published: August 2023

Background

After the COVID-19 outbreak, many Chinese high school students have increased their dependence on electronic devices for studying and life, which may affect the incidence of neck and shoulder pain (NSP) in Chinese adolescents.

Methods

To evaluate the prevalence of NSP in high school students and its associated risk factors during COVID-19, a survey was conducted among 5,046 high school students in Shanghai, Qinghai, Henan and Macao during the second semester and summer vacation of the 2019–2020 academic year. The questionnaire included questions regarding demographic characteristics, the prevalence of NSP and lifestyle factors such as sedentary behavior, poor posture and electronic device usage. Univariable and multivariable logistic regression was used to analyze the possible influencing factors for neck and shoulder pain.

Results

A total of 4793 valid questionnaires (95.0%) were collected. The results indicated that the prevalence of NSP was 23.7% among high school students. Binary logistic regression analysis revealed that female gender (P < 0.05, OR = 1.82), grade (P < 0.05, range OR 1.40–1.51) and subject selection (P < 0.05, range OR 0.49–0.68) were risk factors for NSP in high school students. Sedentary behavior (P < 0.05, range OR 1.74–2.36), poor posture (P < 0.05, range OR 1.19–2.56), backpack weight (P < 0.05, range OR 1.17–1.88), exercise style and frequency (P < 0.05, range OR 1.18–1.31; P < 0.05, range OR 0.76–0.79, respectively), and the time spent using electronic devices (P < 0.05, range OR 1.23–1.38)had a significant correlation with NSP in high school students.

Conclusions

NSP is currently very common among high school students during the outbreak of COVID-19. Sedentary behavior, poor posture and other factors have a great impact on the occurrence of NSP in high school students. Education regarding healthy lifestyle choices should be advocated for to decrease NSP among high school students, such as more physical activity, changing poor postures and reducing the amount of time spent using electronic devices.
Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China
Authors: Wang Wenhui , Wang Tiejun , Liu Zi , He Jianli , Sun Xiaoge , Zhong Wei , Zhao Fengjv , Li Xiaomei , Li Sha , Zhu Hong , Ma Zhanshu , Hu Ke , Zhang Fuquan , Hou Xiaorong , Wei Lichun , Zou Lijuan
Published: August 2023

Background

This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers.

Methods

We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014).

Results

A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients.

There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy.

Conclusion

We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China.

Trial registration

The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).
Phytochemistry, antioxidant, anticancer, and acute toxicity of traditional medicinal food Biarum bovei (Kardeh)
Authors: Wahab Bassam Ali Abed , Alamri Zaenah Zuhair , Jabbar Ahmed A.j. , Ibrahim Ibrahim Abdel Aziz , Almaimani Riyad A. , Almasmoum Hussain A. , Ghaith Mazen M. , Farrash Wesam F. , Almutawif Yahya A. , Ageeli Khalid Aidarous , Alfaifi Soliman Mohammed , Alharthi Rahaf Frehan
Published: August 2023

Background

The Biarum species (Kardeh) has been consumed as a traditional functional food and medicine for decades. The current study investigates the phytochemistry, in-vitro and in-vivo bioactivities of methanol extracts of B. bovei.

Methods

The Gas-chromatography mass spectrophotometer (GS/GS-MS) was used to analyze the phytochemical profile of the methanol extracts of B. bovei leaves and corms. The B. bovei extracts (BBE) were also investigated for in-vitro antioxidant, anticancer, and in-vivo acute toxicity (2000 mg/kg) activities.

Results

The chemical profiling of BBE revealed mainly fatty acids, phytosterol, alcohols, and hydrocarbon compounds. Namely, Linoleic acid, eliadic acid, palmitic acid, 22,23-dihydro-stigmasterol, and campesterol. The antioxidant activity of BBE ranged between 0.24–3.85 μg TE/mL based on different assays. The extracts also exhibited significant anticancer activity against DU-145 (prostate cancer cells), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical cancer) cell lines with IC50 values ranging between 22.73–44.24 μg/mL. Rats fed on 2000 mg/kg dosage of BBE showed absence of any toxicological sign or serum biochemical changes.

Conclusion

The detected phytochemicals and bioactivities of BBE scientifically backup the folkloric usage as an important source of nutraceuticals and alternative medicine for oxidative stress-related diseases and carcinogenesis inhibition.
Online case-based learning in medical education: a scoping review
Authors: Donkin Rebecca , Yule Heather , Fyfe Trina
Published: August 2023

Background

Case-Based Learning (CBL) in medical education is a teaching approach that engages students as learners through active learning in small, collaborative groups to solve cases from clinical patients. Due to the challenges afforded by the COVID-19 pandemic, small group learning such as CBL, transitioned quickly to include technology-enhanced learning to enable distance delivery, with little information on how to apply pedagogical frameworks and use learning theories to design and deliver online content.

Methods

To extend understanding of online CBL a scoping review protocol following the PRISMA-ScR framework explored the literature that describes the use of online CBL application in medical education and the outcomes, perceptions, and learning theories. A literature search was conducted in January 2022 followed by a subsequent review in October 2022. After peer review using the PRESS guidelines, the CASP appraisal tool was used to assess the rigor of each study design.

Results

The scoping review identified literature published between 2010 and 2022 (n = 13 articles), on online CBL in the field of medical education with 11 observational studies describing student and facilitator perceptions and two randomized controlled studies. Positive perceptions of online learning included a flexible work-life balance, connection with learners, and improved accessibility. Negative experiences of online CBL included poor internet access, a distracting learning environment, and loss of communication. In the studies that collected student performance data, results showed equivalent or improved outcomes compared to the control. The CASP appraisal tool highlighted the deficiencies in most study designs, lack of framework or learning theory, and poor reproducibility of the methods to answer the research questions.

Conclusion

This scoping review identified literature to describe the academic outcomes, and student and facilitator perceptions of online CBL in medical education. However, the CASP tool uncovered deficiencies in study descriptions and design leading to poor quality evidence in this area. The authors provide recommendations for frameworks and learning theories for the future implementation of online CBL.
The accuracy of artificial intelligence in predicting COVID-19 patient mortality: a systematic review and meta-analysis
Authors: Xin Yu , Li Hongxu , Zhou Yuxin , Yang Qing , Mu Wenjing , Xiao Han , Zhuo Zipeng , Liu Hongyu , Wang Hongying , Qu Xutong , Wang Changsong , Liu Haitao , Yu Kaijiang
Published: August 2023

Background

The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients.

Methods

The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158).

Findings

Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05).

Interpretation

Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy.
Interest in using patient portals among adolescents in mental health care - a cross-sectional study
Authors: Nielsen Martine Stecher , Steinsbekk Aslak , Nøst Torunn Hatlen
Published: August 2023

Introduction

Adolescents in mental health care may benefit from using patient portals to access personalised information about their health and treatment. While no studies have considered the interest in using patient portals among adolescents in mental health care, factors such as patient activation, self-reported health, depressive symptoms, diagnosis, healthcare utilisation, and eHealth literacy have been found to be associated with interest in and use of patient portals in other patient groups. Therefore, the aim was to explore the associations between interest in using patient portals and patient activation, self-reported health, depressive symptoms, diagnosis, healthcare utilisation and eHealth literacy among adolescents in specialist mental health care.

Methods

A cross-sectional study among adolescents between 12 and 18 years of age receiving or having received treatment at four different specialist child and adolescent mental healthcare services across Norway. The adolescents´ answers to the questionnaire were linked to data on their healthcare utilisation and ICD-10 diagnoses from the Norwegian Patient Registry. The data were analysed using descriptive statistics and bivariate tests.

Results

The 53 adolescents who participated, had a mean age of 15 years and 68% of them identified as female. Two out of three (64%) were interested in using patient portals. Most of the factors were not associated with interest in using patient portals. However, adolescents with mental and behavioural disorders (F diagnoses, 75% interested) were more interested in using patient portals compared to those with symptoms and signs involving cognition, perception, emotional state, and behaviour (R diagnoses, 31% interested).

Conclusion

Except for mental health diagnosis, this study did not identify any specific factors likely to impact patient portal interest among adolescents in specialist mental health care.
Improvement and enhancement of oligosaccharide production from Lactobacillus acidophilus using statistical experimental designs and its inhibitory effect on colon cancer
Authors: Abo-Zaid Gaber A. , Kenawy Ahmed M. , El-Deeb Nehal M. , Al-Madboly Lamiaa A.
Published: August 2023

Colorectal cancer (CRC) is the third cause of death by cancers worldwide and is one of the most common cancer types reported in both Egypt and the United States. The use of probiotics as a dietary therapy is increasing either as a prevention or as a treatment for many diseases, particularly, in the case of CRC. The increasing acceptance of lactic acid bacterial (LAB) oligosaccharides as bioactive agents has led to an increase in the demand for the large-scale production of LAB-oligosaccharides using fermentation technology. Therefore, in the current study, we are using the Plackett- Burman design (PBD) approach, where sixteen experimental trials were applied to optimize the production of the target oligosaccharide LA-EPS-20079 from Lactobacillus acidophilus. Glucose, yeast extract and sodium acetate trihydrate were the top three significant variables influencing LA-EPS production. The maximum concentration of LA-EPS-20079 achieved by L. acidophilus was 526.79 μg/ml. Furthermore, Box–Behnken design (BBD) as response surface methodology (RSM) was used to complete the optimization procedure. The optimal levels of the chosen variables which were 30.0 g/l, glucose; 5 g/l, yeast extract and 10.0 g/l sodium acetate trihydrate with the predicted LA-EPS-20079 concentration of 794.82 μg/ml. Model validity reached 99.93% when the results were verified. Both optimized trials showed great cytotoxic effects against colon cancer line (CaCo-2) with inhibition percentages ranging from 64.6 to 81.9%. Moreover, downregulation in the expression level of BCL2 and Survivin genes was found with a fold change of 3.377 and 21.38, respectively. Finally, we concluded that the optimized LA-EPS-20079 has maintained its anticancer effect against the CaCo-2 cell line that was previously reported by our research group.
Apolipoprotein B is associated with CT-angiographic progression beyond low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in patients with coronary artery disease
Authors: Shui Xing , Wen Zheqi , Dong Ruimin , Chen Zefeng , Tang Leile , Tang Wenyu , Wu Zhen , Chen Lin
Published: August 2023

Background

Accumulating evidence indicated that apolipoprotein B (apoB) was the principal lipid determinant of coronary artery disease (CAD). Nevertheless, the connection between apoB and angiographic progression of CAD remained undetermined.

Methods

Five hundred and forty-four CAD patients with twice coronary computed tomography angiography experiences were enrolled. The Gensini scoring system was used to assess angiographic progression. Incident angiographic progression was defined as an annual change rate of the Gensini score of > 1 point. The predictive efficacy of baseline apoB levels for angiographic progression was assessed using a receiver operating characteristic (ROC) curve. For comparative purposes, patients were categorized into three groups according to their baseline apoB tertiles. Furthermore, discordance analyses defined by the median were performed to assess the superiority of apoB over lipoprotein cholesterol in predicting angiographic progression of CAD.

Results

Angiographic progression was observed in 184 patients (33.8%) during a follow-up period of 2.2-year. The area under the ROC curve was 0.565 (0.522–0.607, P = 0.013). The incidence of angiographic progression was elevated with increasing apoB tertile after adjusting for confounding factors [odds ratio (OR) for the medium apoB tertile: 1.92, 95% confidence interval (CI): 1.15–3.19, P = 0.012; OR for the high apoB tertile: 2.05, 95%CI:1.17–3.60, P = 0.013]. Additionally, discordance analyses showed that the higher apoB group had a significantly higher risk of CAD progression in the fully adjusted model (all P < 0.05).

Conclusions

ApoB could be used as an accurate and comprehensive indicator of angiographic progression in patients with CAD.
Substance use, harm reduction attitudes and behaviors among attendees of nature rave parties in Israel
Authors: Bonny-Noach Hagit , Shapira Barak , Baumol Pinchas , Tadmor Nir , Rosca Paola , Shoshan Stacy , Harel-Fisch Yossi , Caduri Ariel
Published: August 2023

Background

Few studies have analyzed harm reduction behaviors and attitudes among rave party attendees. Since the late 1980s, there has been a large Israeli rave scene, also known as 'Nature Parties'. However, only a few studies have been conducted among nature party attendees and almost all of them are from a qualitative perspective. This study's aim was to fill the gap and conduct quantitative research to investigate the patterns of substance use, harm reduction attitudes and behaviors among Israeli nature rave party attendees.

Methods

A cross-sectional online survey recruited 1,206 people who reported having attended nature rave parties. All of the participants were aged 18–60 years (M = 29.9; SD = 7.4), and 770 (64%) were male.

Results

The most common illicit substances used at Israeli nature rave parties in the past year were cannabis (62.2%), followed by LSD (41.4%), MDMA (31.7%), mushrooms/psilocybin (23.9%), ketamine (19.6%) and cocaine (17.2%). A significant but weak association was found between harm reduction behaviors and attitudes toward harm reduction interventions (r = .26, p < .001) and attitudes toward drug testing kits (r = .33, p < .001). It seems that although we found higher positive harm reduction attitudes, it is harder to implement harm reduction behaviors. Logistic regressions demonstrated stronger associations with high harm reduction behaviors and higher levels of positive attitudes toward drug testing kits (OR = 4.53; CI 2.97–6.90; p < .001), higher levels of positive attitudes toward harm reduction interventions (OR = 4.06; CI 2.62–6.29; p < .001), marital status of widower/divorced (OR = 2.22; CI 1.49–3.32; p < .001), using MDMA (OR = 1.63; CI 1.19–2.23; p <  = .01) and using LSD (OR = 1.41; CI 1.03–1.94; p <  = .05).

Conclusions

Formal harm reduction policies and interventions are needed for Israeli nature rave parties in addition to prevention and information programs, which are also very rare. Future studies should examine the subjects of harm reduction attitudes and behaviors among the public, policy makers and professionals.
Anti-inflammatory and antioxidant efficacy of lavender oil in experimentally induced thrombosis
Authors: But Valeriu Mihai , Bulboacă Adriana Elena , Rus Vasile , Ilyés Tamás , Gherman Mădălina Luciana , Bolboacă Sorana D.
Published: August 2023

Background

Lavender oil (LO) possesses anti-inflammatory, antioxidant, antifungal, antibacterial, sedative, cardio-protective, and antinociceptive properties. Thrombosis and inflammation are interplayed processes that interact and influence one another. Our research compared three routes of administration to assess the efficacy of pretreatment with LO on carrageenan-induced thrombosis in rat tail.

Materials and methods

Wistar-Bratislava white rats were randomly divided into five groups of ten rats each and pretreated 3 consecutive days prior the inducement of thrombosis to with one dose of LO (150 mg/kg body weight (b.w.)): per os by gavage (TLOPO group), intraperitoneal (TIPLO group) and subcutaneous (TSCLO group). We also have a control (C, received saline solution 0.9% and DMSO (vehicle) 1 ml intraperitoneal (i.p.)) group and a group with thrombosis (T group, received saline solution 0.9% plus vehicle 1 ml i.p.). Histopathological examinations were conducted together with measurements of the circulating levels of three oxidative stress markers, antioxidant effect (TAC and THIOL), and three proinflammatory cytokines (TNF- α, RANTES, and MCP-1).

Results

When administered intraperitoneally, lavender oil has the best efficacy on circulating levels of oxidative stress parameters (MDA, NOx, TOS), one oxidative stress marker (THIOL), and all studied proinflammatory cytokines (p-values < 0.02). Moreover, TIPLO displayed the closest values for bleeding and clotting time to the C group, as well as the lowest length of the thrombus than the T, TPOLO, and TSCLO groups (p-values < 0.001). The TIPLO group has histological appearance comparable to the C group, with the exception of the presence of oedema.

Conclusions

Lavender oil pretreatment with intraperitoneal administration as three days, one-dose per day, showed anti-inflammatory and antioxidant efficacy in experimentally induced thrombosis.
Cost-effectiveness of 20-valent pneumococcal conjugate vaccine compared with 23-valent pneumococcal polysaccharide vaccine among adults in a Norwegian setting
Authors: Malene B Mikkelsen , Oyvind Husby , Tor Molden , David N Mwaura , Jens Olsen , Nanna V Kristensen , Jeffrey Vietri
Published: August 2023

Background

The morbidity and mortality of adult diseases caused by S. pneumoniae increase with age and presence of underlying chronic diseases. Currently, two vaccine technologies against S. pneumoniae are used: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccines, one of which is the 20-valent pneumococcal conjugate vaccine (PCV20) that has recently been approved for adults.

Objective

This study was conducted to investigate the cost-effectiveness of implementing PCV20 in a reimbursement scheme for Norwegian adults aged 18–99 years at risk of pneumococcal diseases and those aged 65 years and older at low risk compared to PPV23.

Methods

An established Markov model was adapted to a Norwegian setting to estimate the economic and clinical consequences of vaccinating the Norwegian population in specific age and risk groups against pneumococcal diseases. Inputs for the model were found in Norwegian or Danish real-world evidence or retrieved from available studies. The costs and clinical outcomes were assessed using a health sector perspective and a lifetime time horizon.

Results

The results showed that PCV20 was associated with better health outcomes including fewer disease cases, fewer disease-attributable fatalities, a higher gain of life years and quality-adjusted life years compared to PPV23. In addition, PCV20 had a lower total cost compared to PPV23. Therefore, PCV20 was the dominant vaccination strategy. The base case result was investigated in multiple sensitivity analyses, which showed that the results were robust to changes in input parameters and methodological assumptions, as PCV20 remained the dominant vaccination strategy in almost all scenarios.

Conclusion

Results showed that vaccinating the Norwegian adults with PCV20 was cost-effective compared to PPV23. Changes in the hospital cost of pneumonia, the price of PCV 20, the effectiveness of PCV20 against pneumonia, and the pneumonia disease incidence had the highest impact on the ICER, i.e., were the main drivers of the results.
The indirect impact of COVID‐19 pandemic on limb preservation care– a retrospective analysis of trends in lower limb revascularisation
Authors: Anthony Lakmali , Gillies Madeline , Tran Morica , Goh David
Published: August 2023

Background

Disruptions caused by COVID‐19 pandemic have profoundly influenced the management of many conditions, especially vascular pathologies including limb preservation care. The aim of this study is to evaluate the impact of the pandemic on patients with peripheral arterial disease (PAD) focusing on lower limb revascularisation procedure volume, their indication and urgency of surgery.

Methods

The Australian Vascular Audit (AVA) was used to capture data on revascularisation procedures before and after the onset of the pandemic in Victoria, Australia. Information on patient demographics, procedures performed, their indication and urgency of surgery were collected.

Results

There was a significant 22.7% increase in revascularisations for PAD during the COVID‐19 pandemic, driven solely by a 31.9% increase in endovascular revascularisation procedures. Revascularisation procedures for all indications of PAD, namely claudication, rest pain and tissue loss, increased by 14.8%, 39.2% and 27.4% respectively, during the pandemic compared to pre‐pandemic times. Open procedures declined by 10.2% during the pandemic. There were significant 13.9% and 62.2% increases in elective and semi‐urgent revascularisations respectively during the pandemic while emergency revascularisations for PAD fell by 4.2%. There were no significant increases in toe, forefoot or below knee amputations during the pandemic compared to pre‐pandemic times.

Conclusions

This study found that the volume of revascularisation for PAD increased significantly during the pandemic indicating that patients with PAD had significant deterioration of their condition during the pandemic. This is likely multifactorial; due to disruptions to standard provision of podiatry, vascular surgery and endocrinology services to these patients, a decline in overall health and changes in health‐related behaviours due to restrictions and infection control methods imposed during the pandemic. The number of elective and semi‐urgent procedures also increased during the pandemic which reflects the significant deterioration of PAD patients during the pandemic. This study highlights a concerning trend of worsening PAD when routine care of these patients is disrupted. Such data should be instrumental in contingency planning and resource allocation for managing the ongoing pandemic.
SMAD2 inhibits pyroptosis of fibroblast-like synoviocytes and secretion of inflammatory factors via the TGF-β pathway in rheumatoid arthritis
Authors: Mao Xingxing , Wu Weijie , Nan Yunyi , Sun Weiwei , Wang Youhua
Published: August 2023

Objective

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease. Over-activation of fibroblast-like synoviocytes is responsible for the hyperplasia of synovium and destruction of cartilage and bone and pyroptosis of FLS plays a key role in those pathological processes during RA. This study investigated the detailed mechanisms that SMAD2 regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis.

Methods

We collected synovial tissues of RA patients and FLS-RA and cultured FLS for detection of expression of SMAD2. ASC, NLRP3, cleaved-caspase-1, and GSDMD-N were detected by Western blot after overexpression of SMAD2. Besides, flow cytometry, electron microscope, ELISA, HE staining, and Safranin O staining were performed to further demonstrate that SMAD2 can affect the pyroptosis of FLS-RA.

Results

The expression of SMAD2 was down-regulated in synovial tissues of RA patients and FLS-RA. Overexpression of SMAD2 can inhibit the expression of ASC, NLRP3, cleaved-caspase-1, and GSDMD-N. Flow cytometry and electron microscope further demonstrated that SMAD2 attenuated pyroptosis of FLS-RA. In addition, overexpression of SMAD2 also inhibited inflammatory factors such as IL-1β, IL-18, IL-6, and IL-8 secretion and release of LDH. Besides, overexpression of SMAD2 can reverse the decrease of p-SMAD2 and TGF-TGF-β induced by nigericin. In vivo experiments on CIA rats further demonstrated that overexpression of SMAD2 by local intra-articular injection of LV-SMAD2 can effectively alleviate joint redness, swelling, and destruction of cartilage and bones.

Conclusion

SMAD2 inhibited FLS-RA pyroptosis by down-regulating of NLRP3 inflammasomes (NLRP3, ASC, and caspase-1 complex) and eased the secretion of inflammatory factors via the TGF-β signaling pathway, thereby improving the symptom of RA. We hope that this study may provide a new research idea for RA and a potential target for the treatment of RA.
Nocardia brain abscess in a patient with diabetes: a case report
Authors: Boctor Noelle , Aronowitz Paul
Published: August 2023

Background

Nocardia are aerobic Gram-positive bacilli that can invade multiple organ systems, including the brain and lungs. It is most frequently found in patients who are immunocompromised. Invasive nocardial disease is a potentially life-threatening infection that can pose a diagnostic challenge.

Case presentation

Our case details a 76-year-old Indian woman with poorly-controlled diabetes mellitus admitted for confusion and falls. Imaging revealed intracranial abscesses and necrotic masses in the mediastinum and lungs. The suspected diagnosis was tuberculosis; however, she underwent extensive workup without a final diagnosis. Ultimately, a craniotomy with partial brain abscess resection was performed. Dura matter samples revealed Nocardia farcinica.

Conclusions

This case illustrates the importance of considering Nocardia in patients with brain abscesses, particularly in those with immunocompromised states and demonstrates the diagnostic challenges that may arise in definitively making this diagnosis. Invasive procedures may be needed for diagnostic confirmation.
Xeno-free generation of human induced pluripotent stem cells from donor-matched fibroblasts isolated from dermal and oral tissues
Authors: Ali Hassan R. W. , Suliman Salwa , Osman Tarig Al-Hadi , Carrasco Manuel , Bruland Ove , Costea Daniela-Elena , Ræder Helge , Mustafa Kamal
Published: August 2023

Background

Induced pluripotent stem cells (iPS) can be generated from various somatic cells and can subsequently be differentiated to multiple cell types of the body. This makes them highly promising for cellular therapy in regenerative medicine. However, to facilitate their clinical use and to ensure safety, iPS culturing protocols must be compliant with good manufacturing practice guidelines and devoid of xenogenic products. Therefore, we aimed to compare the efficiency of using humanized culture conditions, specifically human platelet lysate to fetal bovine serum, for iPS generation from different sources, and to evaluate their stemness.

Methods

iPS were generated via a platelet lysate or fetal bovine serum-based culturing protocol from matched dermal, buccal and gingival human fibroblasts, isolated from healthy donors (n = 2) after informed consent, via episomal plasmid transfection. Pluripotency, genotype and phenotype of iPS, generated by both protocols, were then assessed by various methods.

Results

More attempts were generally required to successfully reprogram xeno-free fibroblasts to iPS, as compared to xenogenic cultured fibroblasts. Furthermore, oral fibroblasts generally required more attempts for successful iPS generation as opposed to dermal fibroblasts. Morphologically, all iPS generated from fibroblasts formed tight colonies surrounded by a reflective “whitish” outer rim, typical for iPS. They also expressed pluripotency markers at both gene (SOX2, OCT4, NANOG) and protein level (SOX2, OCT4). Upon stimulation, all iPS showed ability to differentiate into the three primary germ layers via expression of lineage-specific markers for mesoderm (MESP1, OSR1, HOPX), endoderm (GATA4) and ectoderm (PAX6, RAX). Genome analysis revealed several amplifications and deletions within the chromosomes of each iPS type.

Conclusions

The xeno-free protocol had a lower reprogramming efficiency compared to the standard xenogenic protocol. The oral fibroblasts generally proved to be more difficult to reprogram than dermal fibroblasts. Xeno-free dermal, buccal and gingival fibroblasts can successfully generate iPS with a comparable genotype/phenotype to their xenogenic counterparts.
Biocontrol of Lysobacter enzymogenes CQ18 against the tobacco powdery mildew fugus, Erysiphe cichoracearum
Authors: Yang Hongjun , Peng Liyuan , Li Zhimo , Huang Chunyang , Huang Jianguo
Published: August 2023

Background

Powdery mildew is a common leaf disease of crops worldwide. A large quantity of chemical fungicides is used to control this disease in horticulture and agriculture, producing serious safety and environmental problems. To suppress this disease in safe and environment-friendly ways, the biocontrol of a self-isolated new strain ofLysobacter enzymogenes(CQ18) was studied against flue-cured tobacco powdery mildews.

Results

L. enzymogenesCQ18 produced chitinase, protease, β-1,3-glucanase, phosphatase, and siderophore, which may enable this biocontrol bacterium to degrade pathogen cell membranes and walls and deprive pathogens of iron. HPLC/MS analysis identified 14 antifungal metabolites present inL. enzymogenesCQ18 fermentation liquid (LEFL), which were grouped into organic acids, azoles, and pyrimidines. The variable targets in or on pathogen cells and combinative effects of these multiple metabolites may potently suppress the powdery mildew and be less likely to makeErysiphe cichoracearumdevelop resistance. LEFL was rich in L-pyroglutamate. Both LEFL and L-pyroglutamate inhibited the germination ofE. cichoracearumconidia in vitro and reduced the powdery mildew index in the greenhouse and field. L-Pyroglutamate at a concentration of 0.50% achieved the same control efficacy as the chemical fungicide triadimefon (91–94%).

Conclusions

L. enzymogenesCQ18 and the metabolite L-pyroglutamate effectively controlled flue-cured tobacco powdery mildew.L. enzymogenesCQ18 grows rapidly and is resilient to adversity. L-Pyroglutamate has no toxicity to humans and is easy to synthesize at a low cost. Both show potential use in controlling plant powdery mildews.

Graphical Abstract
Identification and analysis of key hypoxia- and immune-related genes in hypertrophic cardiomyopathy
Authors: Yu Haozhen , Gu Lanxin , Du Linfang , Dong Zhao , Li Zhuang , Yu Mujun , Yin Yue , Wang Yishi , Yu Lu , Ma Heng
Published: August 2023

Background

Hypertrophic cardiomyopathy (HCM), an autosomal dominant genetic disease, is the main cause of sudden death in adolescents and athletes globally. Hypoxia and immune factors have been revealed to be related to the pathology of HCM. There is growing evidence of a role for hypoxia and inflammation as triggers and enhancers in the pathology in HCM. However, the role of hypoxia- and immune-related genes in HCM have not been reported.

Methods

Firstly, we obtained four HCM-related datasets from the Gene Expression Omnibus (GEO) database for differential expression analysis. Immune cells significantly expressed in normal samples and HCM were then screened by a microenvironmental cell population counter (MCP-counter) algorithm. Next, hypoxia- and immune-related genes were screened by the LASSO + support vector machine recursive feature elimination (SVM-RFE) and weighted gene co-expression network analysis (WGCNA). Single-gene enrichment analysis and expression validation of key genes were then performed. Finally, we constructed a competing endogenous RNA (ceRNA) network of key genes.

Results

In this study, 35 differentially expressed hypoxia genes were found. By using LASSO + SVM-RFE analysis, 10 more targets with differentially expressed hypoxia genes were identified. The MCP-count algorithm yielded five differentially expressed immune cells, and after assessing them for WGCNA characteristics, 612 immune genes were discovered. When hypoxia and immune genes were combined for cross-tabulation analysis, three hypoxia- and immune-related genes (ATP2A2, DDAH1, and OMA1) were identified.

Conclusion

Based on hypoxia characteristic genes, three key genes were identified. These were also significantly related to immune activation, which proves a theoretical basis and reference value for studying the relationship between HCM and hypoxia and immunity.

Graphical Abstract
Skeletal structure of asymmetric mandibular prognathism and retrognathism
Authors: Xi Tong , Vinayahalingam Shankeeth , Bergé Stefaan , Maal Thomas , Kwon Tae-Geon
Published: August 2023

Background

This study aimed to compare the skeletal structures between mandibular prognathism and retrognathism among patients with facial asymmetry.

Results

Patients who had mandibular asymmetry with retrognathism (Group A) in The Netherlands were compared with those with deviated mandibular prognathism (Group B) in Korea. All the data were obtained from 3D-reformatted cone-beam computed tomography images from each institute. The right and left condylar heads were located more posteriorly, inferiorly, and medially in Group B than in Group A. The deviated side of Group A and the contralateral side of Group B showed similar condylar width and height, ramus-proper height, and ramus height. Interestingly, there were no inter-group differences in the ramus-proper heights. Asymmetric mandibular body length was the most significantly correlated with chin asymmetry in retrognathic asymmetry patients whereas asymmetric elongation of condylar process was the most important factor for chin asymmetry in deviated mandibular prognathism.

Conclusion

Considering the 3D positional difference of gonion and large individual variations of frontal ramal inclination, significant structural deformation in deviated mandibular prognathism need to be considered in asymmetric prognathism patients. Therefore, Individually planned surgical procedures that also correct the malpositioning of the mandibular ramus are recommended especially in patients with asymmetric prognathism.
Circularity-based decision-making framework for the integrated conservation of built heritage: the case of the Medina of Tunis
Authors: Tira Yasmine , Türkoğlu Handan
Published: August 2023

Several factors overlap in making urban heritage conservation vulnerable in terms of long-term sustainability. The purpose of this study is to offer insights into the dynamic role that heritage governance plays in the current sustainability debate. This purpose is achieved by investigating the shift from a ‘governing for culture’ approach to a ‘governing through culture’ approach in heritage conservation. Subsequently, a case is built for a circularity-based conservation strategy applicable to the governance of historic cities. Different indicators of the circular governance approach are considered, and useful data are collected in comparative form. The cross-matching relationship between the factors is then evaluated by employing the analytic hierarchy process (AHP) on the collected data. As a test case, the conservation strategy of the Medina of Tunis is presented. For a more general conservation model, case-specific data are acquired. Finally, the same framework is applied to compare the case-dependent and case-independent data to define an integrated conservation framework. The obtained results show that the knowledge and data exchange factor, carries the highest significance. This result translates into heritage-led urban regeneration through knowledge sharing and the effective redistribution of cultural activities in historic city centres.
Postoperative constrictive pericarditis caused rupture of lymphatic collaterals: a rare etiology of chylothorax
Authors: Nakamura Yasuhito , Doi Kiyoshi , Fujii Ryo , Ogura Hiroki , Umeda Etsuji , Kato Takayoshi , Sakai Osamu , Shimabukuro Katsuya
Published: August 2023

Background

Chylothorax after cardiovascular surgery is primarily caused by direct injury to the thoracic duct or its branches, and occurs in early postoperative period. In the present case, we describe a rare case of chylothorax manifesting three months after surgery secondary to constrictive pericarditis.

Case presentation

A 71-year-old man underwent mitral valve replacement, tricuspid valve annuloplasty, and the maze procedure. He developed acute perioperative myocardial infarction on postoperative day one due to plaque rupture in the left anterior descending artery and underwent percutaneous coronary intervention. Although the patient was discharged on postoperative day 36, he required readmission on postoperative day 83 because of right side chylothorax associated with constrictive pericarditis. Lymphangiography revealed thoracic duct interruption and development of lymphatic collateral vessels via the right hilum. Single-photon emission computed tomography revealed abnormal tracer accumulation in the right hilum, suggesting a lymphatic leakage site. A catheter study indicated biventricular dip and plateau patterns with a reduced cardiac index (1.6 L/min/m2) and elevated central venous pressure (18 mmHg). Conservative treatment for chylothorax, including a low-fat diet and continuous drainage with chest tube, was unsuccessful. Drainage of chyle at approximately 500 mL/day continued. On hospitalization day 50, complete pericardiectomy via median sternotomy was performed because the patient’s cardiac function deteriorated. The central venous pressure dramatically decreased, and the chylothorax gradually subsided. There was no recurrence of symptoms 1 year postoperatively.

Conclusions

Chylothorax associated with constrictive pericarditis subsequent to cardiac surgery is extremely rare. Although conservative management failed, the present case was successfully treated via pericardiectomy alone and did not require any additional precedures, such as thoracic duct ligation via a right thoracotomy.
Political trust in the handling of the COVID-19 pandemic: a survey in Denmark and Sweden
Authors: Kallemose Thomas , Kirk Jeanette Wassar , Karlsson Elin , Seing Ida , Stefánsdóttir Nina Thórný , Vrangbæk Karsten , Andersen Ove , Nilsen Per
Published: August 2023

Background

The initial responses to the COVID-19 pandemic in Denmark and Sweden differed markedly. Balancing disparate concerns was crucial to generate trust in the COVID-19 restrictions. The aim was to investigate the extent to which there was trust in the handling of the pandemic by the Danish and Swedish governments and public health authorities in each country. A further aim was also to investigate the characteristics of those in Denmark and Sweden who expressed the lowest degree of trust.

Methods

Cross-sectional surveys were conducted in 2021, using web panels that are nationally representative of the socio-demographic characteristics. The population consisted of 2619 individuals from Denmark and 2633 from Sweden, representative of the age, sex and region of residence of the populations aged ≥ 18 years. Trust in government and health authorities was captured in two separate trust questions on a 5-point Likert scale and dichotomized into low trusters and non-low trusters for analysis.

Results

Approximately, 61% of the Danish respondents expressed moderately large or very large trust in the government’s handling of the pandemic. The corresponding proportion for Sweden was 42%. The proportion of low trusters was 11% in Denmark and 34% in Sweden (p < 0.001). Moderately large or very large trust in the public health authority’s handling was expressed by 83% of the Danish respondents and 74% of the Swedish respondents. The proportion of low trusters was 5% in Denmark and 17% in Sweden (p < 0.001). In both countries, trust was lower among men than among women. Age and education were associated with trust but differed between countries (p <  = 0.011).

Conclusions

In this study, differences in trust between Denmark and Sweden and both overall and within socio-demographic factors were observed. However, given the limitations and bias in the study, it is difficult to determine the cause and true size of these differences. With that in mind, we still believe specific populations and subgroups within those populations have the potential to affect trust in handling of the COVID-19 pandemic, and that these should be kept in mind when developing and communicating responses to pandemics.
Viewpoint: Assessing the value of mental health treatments in Europe
Authors: Simon Judit , Boyer Patrice , Caldas-de-Almeida Jose M. , Knapp Martin , McCrone Paul , Gorwood Philip , Oertel Wolfgang , Arango Celso , Treasure Janet , Young Allan H. , Destrebecq Frederic , Quoidbach Vinciane
Published: August 2023

One in eight individuals worldwide lives with a mental health disorder. For many European countries, the prevalence is even higher, with one in four people reporting mental health problems [1]. Three-quarters of all mental health disorders develop before age 25, with many presenting initially in undiagnosed forms already in the mid-teens and eventually manifesting as severe disorders and lasting into old age [2]. There is also growing evidence that mental health disorder symptoms cross diagnoses and people frequently have more than one mental health disorder [3].