bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of one-lung ventilation on the correlation between left and right cerebral saturation
Authors: Zhang Cai-Juan , Ma Jia-Hui , Jin Fan , Li Xiu-Hua , Jia Hui-Qun , Mu Dong-Liang
Published: February 2023

Background

To investigate if the correlation between left and right cerebral tissue oxygen saturation (SctO2) was affected by one-lung ventilation (OLV) in patients undergoing lung cancer surgery.

Methods

Patients who underwent surgery for lung cancer were enrolled. Left and right SctO2 were collected during anesthesia. The primary outcome was the correlation between left and right SctO2 at 30 min after OLV which was analysed by Pearson correlation and linear regression model. Secondary outcomes included the trend of left–right SctO2 change over the first 30 min after OLV, correlation of left–right SctO2 during OLV for each patient; maximal difference between left–right SctO2 and its relationship with postoperative delirium.

Results

Left–right SctO2 was moderately correlated at baseline (r = 0.690, P < 0.001) and poorly correlated at 30 min after OLV (r = 0.383, P < 0.001) in the Pearson correlation analysis. Linear regression analysis showed a poor correlation between left and right SctO2 at 30 min after OLV (r = 0.323, P < 0.001) after adjusting for confounders. The linear mixed model showed a change in left–right SctO2 over the first 30 min after OLV that was statistically significant (coefficient, -0.042; 95% CI, -0.070–-0.014; P = 0.004). For the left–right SctO2 correlation during OLV in each patient, 62.9% (78/124) patients showed a strong correlation, 19.4% (24/124) a medium correlation, and the rest a poor correlation. The maximal difference between the left and right SctO2 was 13.5 (9.0, 20.0). Multivariate analysis showed that it was not associated with delirium (odds ratio [OR], 1.023; 95% CI, 0.963–1.087; P = 0.463).

Conclusions

The correlation between left and right SctO2 was affected by one-lung ventilation in patients undergoing lung cancer surgery. This result indicates the requirement of bilateral SctO2 monitoring to reflect brain oxygenation.

Trial registration

This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017–1378) and was registered in the Chinese Clinical Trial Registry on 10/09/2017 (http://www.chictr.org.cn, ChiCTR-ROC-17012627).
Identification of key biomarkers and immune infiltration in the thoracic acute aortic dissection by bioinformatics analysis
Authors: Luo Jun , Shi Haoming , Ran Haoyu , Zhang Cheng , Wu Qingchen , Shao Yue
Published: February 2023

Background

Thoracic acute aortic dissection (TAAD), one of the most fatal cardiovascular diseases, leads to sudden death, however, its mechanism remains unclear.

Methods

Three Gene Expression Omnibus datasets were employed to detect differentially expressed genes (DEGs). A similar function and co-expression network was identified by weighted gene co-expression network analysis. The least absolute shrinkage and selection operator, random forest, and support vector machines-recursive feature elimination were utilized to filter diagnostic TAAD markers, and then screened markers were validated by quantitative real-time PCR and another independent dataset. CIBERSORT was deployed to analyze and evaluate immune cell infiltration in TAAD tissues.

Results

Twenty-five DEGs were identified and narrowed down to three after screening. Finally, two genes, SLC11A1 and FGL2, were verified by another dataset and qRT-PCR. Function analysis revealed that SLC11A1 and FGL2 play significant roles in immune-inflammatory responses.

Conclusion

SLC11A1 and FGL2 are differently expressed in aortic dissection and may be involved in immune-inflammatory responses.
Eradication therapy may decrease the risk of immune thrombocytopenia after Helicobacter pylori infection: a retrospective cohort study in Taiwan
Authors: Koseki Mitsuhiro , Sheu Ming‑Jen , Tsai Kang-Ting , Ho Chung-Han , Liu Hsiao-Hua , Lin Hung-Jung , Lin Chien-Liang , Huang Chien-Cheng
Published: February 2023

Background

Helicobacter pylori (HP) eradication therapy (HPE) is recommended for patients with unexplained immune thrombocytopenia (ITP); however, the role of HPE in preventing ITP in patients with HP infection remains unclear. Therefore, this study was designed to clarify it.

Methods

This study was conducted at a tertiary medical center and included all adult patients with HP infection between January 1, 2016 and December 31, 2018. We compared the risk of developing ITP between patients with and without HPE. All patients were followed up until December 31, 2020.

Results

After excluding patients with thrombocytopenia, 1995 adult patients with HP infection, including 1188 patients with HPE and 807 patients without HPE, were included in this study. The mean age of the patients with HPE was 57.9 years, whereas that of those without HPE was 61.6 years. The percentage of males was 56% in patients with HPE and 59% in those without HPE. Patients without HPE had a higher risk of ITP than those with HPE after adjusting for age, sex, the Charlson Comorbidity Index, and comorbidities [adjusted odds ratio (OR) 1.76; 95% confidence interval (CI) 1.16–2.68]. Stratified analyses showed that the higher risk was found only in males (adjusted OR: 1.70; 95% CI 1.03–2.80). In addition to HPE, male sex and anemia were independent predictors of ITP in patients with HP infection.

Conclusion

This study showed that adult patients with HP infection not receiving HPE had a higher risk of developing ITP. We suggest that HPE should be considered, particularly in males and those who have anemia, to prevent ITP.
Impact of the body mass index on the retention of the anorectal mucosa after double-stapled ileal pouch-anal anastomosis for ulcerative colitis
Authors: Kimura Hideaki , Toritani Kenichiro , Kunisaki Reiko , Tatsumi Kenji , Koganei Kazutaka , Sugita Akira , Endo Itaru
Published: February 2023

Background

Double-stapled ileal pouch-anal anastomosis (DS-IPAA) is easy to construct and has a good functional outcome in patients with ulcerative colitis (UC). However, retention of the anorectal mucosa may lead to a subsequent risk of inflammation and neoplasia. This study aimed to identify factors associated with the retention of a large amount of anorectal mucosa after DS-IPAA.

Methods

The medical records of 163 patients who had undergone one-stage total proctocolectomy and DS-IPAA for UC between 2007 and 2020 were retrospectively reviewed. The patients were divided into two groups according to the length of the retained mucosa. The high anastomosis group was defined as having a retained mucosal length of ≥ 30 mm in the anterior or posterior wall. Clinical factors were compared between the high and low anastomosis groups.

Results

The high anastomosis group showed a significantly higher body mass index (BMI) (high vs. low: 23.2 vs. 19.0), longer operation time (304 vs. 263) and greater blood loss (357 vs. 240). In the multivariate analysis, high BMI was the only factor significantly associated with high anastomosis (odds ratio 1.32). There was a positive correlation between BMI and the length of the retained mucosa.

Conclusions

In DS-IPAA, BMI showed the strongest association with the retention of a large amount of the anorectal mucosa. In high BMI patients, although the risk of inability of anastomosis is little than that of IPAA with mucosectomy, the possible retention of a large amount of mucosa should be considered.
New logarithm-based discrimination formula for differentiating thalassemia trait from iron deficiency anemia in pregnancy
Authors: Shuang Xiao , Zhenming Wang , Zhu Mei , Si Sun , Zuo Li
Published: February 2023

Background

Thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) in pregnant women. Accurate discrimination between TT and IDA is an important issue, and better methods are urgently needed. Although considerable RBC formulas and indices have been developed since 1973, distinguishing between IDA and TT is still a challenging problem due to the diversity of various anemic populations. To address this problem, we assessed the diagnostic function of 43 different differential formulas in patients with microcytic anemia by using accuracy measures and recommending a new log-based differential formula.

Methods

The data of 430 pregnant women (229 with TT and 201 with IDA) were enrolled, and 44 formula performances were evaluated with receiver operating characteristic (ROC) analysis.

Results

The newly introduced logarithm-based formula XS-1 performs better than the general discriminant index with sensitivity and specificity of 82.10 and 89.05, which are better than other formulas. In the pregnant population, the Shine and Lal and Roth..SVM. formulas have shown excellent performance, while other formulas showed poorer discriminative abilities in our study than in the original authors.

Conclusion

The logarithm-based formula XS-1 can be used to screen thalassemia and iron deficiency anemia during the first trimester. Considering the particularity of pregnancy, medical personnel in different regions should choose a screening formula similar to that of the local region and population when identifying thalassemia in pregnancy. Any formula should be independently verified locally before use. For the convenience of the health care team and experimental scientists, a web-based tool has been established at http://yyy.yiyiy.top/XS-1/ by which users can easily get their desired screening test result without going through the underlying mathematical and computational details.
Accurate diagnosis of isolated iliac vein thrombosis in third trimester pregnancy with clues on great saphenous vein reflux: a case report and review of literature
Authors: Wei Zhanghong , Li Jingzhi , Liang Lijun , Luo Hui
Published: February 2023

Background

Pregnancy is known to be a risk factor for venous thromboembolism (VTE). We report the case of a pregnant patient with difficult to diagnose iliac vein thrombosis, establishing a definite diagnosis by clues of great saphenous vein reflux.

Case presentation

A 37-year-old G1P0 woman at 35 weeks of assisted twin gestation presented with a complaint of persistent left lower limb edema and tenderness. A vascular ultrasound was used to examine the bilateral lower limb. Doppler of left lower extremity revealed continuous great saphenous vein reflux. Right saphenofemoral veins demonstrated venous stasis and no reflux. Unilateral continuous great saphenous vein reflux suggested left iliac veins obstruction or extrinsic compression. Anterograde venography showed a completely occlusive filling defect of the left external iliac vein, which is the definitive diagnosis of acute deep venous thrombosis. The patient underwent a cesarean delivery following inferior vena cava filter (IVCF) placement, and no signs of deep venous thrombosis (DVT) or pulmonary embolism (PE) were reported after delivery.

Conclusion

In pregnant women with suspected deep vein thrombosis, it is imperative to assess the presence of unilateral continuous great saphenous vein reflux.
Deep learning-based multifeature integration robustly predicts central lymph node metastasis in papillary thyroid cancer
Authors: Wang Zhongzhi , Qu Limeng , Chen Qitong , Zhou Yong , Duan Hongtao , Li Baifeng , Weng Yao , Su Juan , Yi Wenjun
Published: February 2023

Background

Few highly accurate tests can diagnose central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC). Genetic sequencing of tumor tissue has allowed the targeting of certain genetic variants for personalized cancer therapy development.

Methods

This study included 488 patients diagnosed with PTC by ultrasound-guided fine-needle aspiration biopsy, collected clinicopathological data, analyzed the correlation between CLNM and clinicopathological features using univariate analysis and binary logistic regression, and constructed prediction models.

Results

Binary logistic regression analysis showed that age, maximum diameter of thyroid nodules, capsular invasion, and BRAF V600E gene mutation were independent risk factors for CLNM, and statistically significant indicators were included to construct a nomogram prediction model, which had an area under the curve (AUC) of 0.778. A convolutional neural network (CNN) prediction model built with an artificial intelligence (AI) deep learning algorithm achieved AUCs of 0.89 in the training set and 0.78 in the test set, which indicated a high prediction efficacy for CLNM. In addition, the prediction models were validated in the subclinical metastasis and clinical metastasis groups with high sensitivity and specificity, suggesting the broad applicability of the models. Furthermore, CNN prediction models were constructed for patients with nodule diameters less than 1 cm. The AUCs in the training set and test set were 0.87 and 0.76, respectively, indicating high prediction efficacy.

Conclusions

The deep learning-based multifeature integration prediction model provides a reference for the clinical diagnosis and treatment of PTC.
Tenant perspectives on the implementation of the community homes for opportunity: a focused ethnographic study in Southwestern Ontario
Authors: Forchuk Cheryl , Gyamfi Sebastian , Hassan Heba , Lucyk Bryanna , Booth Richard
Published: February 2023

Background

Recovery-oriented programs provide individuals with opportunities for well-being through community integration processes that enhance the degree to which individuals could live, work, and recreate in their community. The current evaluation assessed how tenants experience their home environment after the modernization of Homes for Special Care (HSC) to Community Homes for Opportunity (CHO) in Southwest Ontario, Canada. Our study identifies existing policies and practices that could interfere with or promote the modernization process.

Methods

We applied ethnographic qualitative techniques to purposefully recruit 188 participants with severe mental illness from 28 group homes. Focus groups were conducted at three time points, i.e., at pre-implementation/Baseline/Time I – spring 2018; Transition/Time II – fall 2018, and Final/Time III – winter 2019.

Results

Study findings suggest that the transition of HSC to CHO supports activities that empower tenants towards personal growth and development. Participants were largely satisfied with the support they were getting in relation to the program-related services. Tenants disclosed that their quality of life and well-being had been enhanced through participating in the program, and that their social interaction and support for each other had also improved. Most tenants demonstrated autonomy in terms of personal and financial independence. The enhanced financial support for tenants did not only improve their quality of life, but also helped to raise their purchasing power, decision making, sense of responsibility and accountability towards healthy spending of their resources. Despite tenants’ good impression about the CHO, some still encountered problems and provided suggestions to further improve the program.

Conclusion

It is expected that a more effective and expanded CHO will lead to tenant empowerment and successful social integration.
Effects of 2018 Japan floods on healthcare costs and service utilization in Japan: a retrospective cohort study
Authors: Yoshida Shuhei , Kashima Saori , Okazaki Yuji , Matsumoto Masatoshi
Published: February 2023

Background

Floods and torrential rains are natural disasters caused by climate change. Unfortunately, such events are more frequent and are increasingly severe in recent times. The 2018 Japan Floods in western Japan were one of the largest such disasters. This study aimed to evaluate the effect of the 2018 Japan Floods on healthcare costs and service utilization.

Methods

This retrospective cohort study included all patients whose receipts accrued between July 2017 and June 2019 in Hiroshima, Okayama, and Ehime prefectures using the National Database of Health Insurance Claims. We used Generalized Estimating Equations (GEEs) to investigate yearly healthcare costs during the pre-and post-disaster periods, quarterly high-cost patients (top 10%), and service utilization (outpatient care, inpatient care, and dispensing pharmacy) during the post-disaster period. After the GEEs, we estimated the average marginal effects as the attributable disaster effect.

Results

The total number of participants was 5,534,276. Victims accounted for 0.65% of the total number of participants (n = 36,032). Although there was no significant difference in pre-disaster healthcare costs (p = 0.63), post-disaster costs were $3,382 (95% CI: 3,254–3,510) for victims and $3,027 (95% CI: 3,015–3,038) for non-victims (p < 0.001). The highest risk difference among high-cost patients was 0.8% (95% CI: 0.6–1.1) in the fourth quarter. In contrast, the highest risk difference of service utilization was in the first quarter (outpatient care: 7.0% (95% CI: 6.7–7.4), inpatient care: 1.3% (95% CI: 1.1–1.5), and dispensing pharmacy: 5.9% (95% CI: 5.5–6.4)).

Conclusion

Victims of the 2018 Japan Floods had higher medical costs and used more healthcare services than non-victims. In addition, the risk of higher medical costs was highest at the end of the observation period. It is necessary to estimate the increase in healthcare costs according to the disaster scale and plan for appropriate post-disaster healthcare service delivery.
Disparities in the first-ever diagnosed liver cancers between the emergency department and outpatient department in Taiwan: a population-based study
Authors: Hsu Tai-Yi , Ye Jhu-Jing , Ye Sih-Yun , Tseng Hsiao-Yuan , Chou Wen-Yu , Kung Pei-Tseng , Tsai Wen-Chen
Published: February 2023

Background

Liver cancer is ranked fifth in incidence and second in mortality among cancers in Taiwan. Nevertheless, the Taiwan government does not screen for liver cancer in its free cancer screening and preventive health examination service. This study compared the differences in cancer stage and survival between patients who received an initial liver cancer diagnosis in outpatient departments (OPDs) and those who received such a diagnosis in emergency departments (EDs).

Methods

This retrospective cohort study used the 2000–2016 National Health Insurance Database to obtain a sample from 2 million Taiwanese residents. To evaluate the effect of the utilization of the adult health examination offered to people aged ≥ 40 years, patients aged ≥ 40 years who received an initial liver cancer diagnosis between 2003 and 2015 were followed up until December 31, 2016.

Results

In total, 2,881 patients were included in this study. A greater proportion of cancer cases in the OPD group were non-advanced than those in the ED group (75.26% vs. 54.23%). Having stage C or D cancer, having a low monthly salary, and a Charlson comorbidity index score ≥ 8, not having hepatitis B, being divorced, and attending a non-public hospital as the primary care institution were risk factors for initial ED diagnosis. The risk of liver cancer-specific death among the ED group patients was 1.38 times that among the OPD group patients (adjusted hazard ratio = 1.38, 95% confidence interval [CI] = 1.14–1.68, P < 0.001). However, the use of health examination did not exert a significant effect on the likelihood of liver cancer diagnosis in an ED (adjusted odds ratio = 0.86, 95% CI = 0.61–1.21, P = 0.381).

Conclusion

Government-subsidized health examinations are insufficient to prevent first-ever diagnosed liver cancers in EDs. Patients with liver cancers diagnosed in EDs had a higher risk of advanced stage and mortality. For early detection and treatment, the government may consider implementing liver cancer screening for high-risk and low-socioeconomic people.
In vitro culture of bovine fibroblasts using select serum-free media supplemented with Chlorella vulgaris extract
Authors: Defendi-Cho Galileo , Gould Timothy M.
Published: February 2023

Standard cell culture practices require the addition of animal-derived serum to culture media to achieve adequate cell growth. Typically, 5–10% by volume of fetal bovine serum (FBS) is used, which accounts for a vast majority of the media cost while also imposing environmental and ethical concerns associated with the use of animal serum. Here we tested the efficacy of culturing cells by replacing serum in the media with algae extract and select additives. Using LC–MS, we compared molecular signatures of FBS to Chlorella algae extracts and identified NAD(H)/NADP(H) as common and relatively abundant features in their characteristic profiles. Bovine fibroblasts, cultured in serum-free media supplemented with C. vulgaris extract and just two growth factors plus insulin, showed significant growth with enhanced viability compared to control cells cultured without serum, albeit still lower than that of controls cultured with 10% FBS. Moreover, C. vulgaris extract enhanced cell viability beyond that of cells cultured with the two growth factors and insulin alone. These results suggest that key components in serum which are essential for cell growth may also be present in C. vulgaris extract, demonstrating that it may be used at least as a partial alternative to serum for cell culture applications.
Antibacterial efficacy of indigenous Pakistani honey against extensively drug-resistant clinical isolates of Salmonella enterica serovar Typhi: an alternative option to combat antimicrobial resistance
Authors: Ejaz Hasan , Sultan Mamoona , Qamar Muhammad Usman , Junaid Kashaf , Rasool Nasir , Alanazi Awadh , Alruways Mashael W. , Mazhari Bi Bi Zainab , Alruwaili Yasir , Bukhari Syed Nasir Abbas , Younas Sonia
Published: February 2023

Background

Extensively drug-resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) poses a grave threat to public health due to increased mortality and morbidity caused by typhoid fever. Honey is a promising antibacterial agent, and we aimed to determine the antibacterial activity of honey against XDR S. Typhi.

Methods

We isolated 20 clinical isolates of XDR S. Typhi from pediatric septicemic patients and determined the minimum inhibitory concentrations (MICs) of different antibiotics against the pathogens using the VITEK 2 Compact system. Antimicrobial-resistant genes carried by the isolates were identified using PCR. The antibacterial efficacy of five Pakistani honeys was examined using agar well diffusion assay, and their MICs and minimum bactericidal concentrations (MBCs) were determined with the broth microdilution method.

Results

All 20 isolates were confirmed as S. Typhi. The antibiogram phenotype was confirmed as XDR S. Typhi with resistance to ampicillin (≥ 32 µg/mL), ciprofloxacin (≥ 4 µg/mL), and ceftriaxone (≥ 4 µg/mL) and sensitivity to azithromycin (≤ 16 µg/mL) and carbapenems (≤ 1 µg/mL). Molecular conformation revealed the presence of blaTM-1, Sul1, qnrS, gyrA, gyrB, and blaCTX-M-15 genes in all isolates. Among the five honeys, beri honey had the highest zone of inhibition of 7–15 mm and neem honey had a zone of inhibition of 7–12 mm. The MIC and MBC of beri honey against 3/20 (15%) XDR S. Typhi isolates were 3.125 and 6.25%, respectively, while the MIC and MBC of neem were 3.125 and 6.25%, respectively, against 3/20 (15%) isolates and 6.25 and 12.5%, respectively, against 7/20 (35%) isolates.

Conclusion

Indigenous honeys have an effective role in combating XDR S. Typhi. They are potential candidates for clinical trials as alternative therapeutic options against XDR S. Typhi isolates.
Use of a two-handed model to improve comprehension of ventricular outflow tract anatomy
Authors: Xue Xiang , Luo Xianyuan , Liu Zhaoyang , Jin Yun
Published: February 2023

Background

Mastering cardiac anatomy is a formidable obstacle in the learning process for cardiac electrophysiology trainees. The complex three-dimensional characteristics and contiguous relationship of the ventricular outflow tract are particularly difficult to visualize with the limited study methods available. The hands can recreate a morphology similar to the ventricular outflow tract; this study explored whether a two-handed model of the heart helps electrophysiology trainees improve their understanding of ventricular outflow tract anatomy.

Methods

After an initial assessment, trainees were randomly placed into variable and control groups. Subsequently, all trainees learned the outflow tract anatomy using routine methods, with the variable group receiving additional instruction using the two-handed model. One day and one week after the course conclusion, knowledge of the ventricular outflow tract anatomy was assessed for the participants in both groups.

Results

Thirty-eight trainees participated (19 in each group). The median scores obtained for the first, second, and third tests were 38 (24,55), 80 (70,86), and 75 (70,81) points, respectively. In the second test, trainees in the variable group had a mean score 6.8 points higher than those in the control group (p = 0.103); in the last test, the mean score was 9.7 points higher in the variable group than in the control group (p = 0.003).

Conclusions

It is convenient to use hands to create a model representing the ventricular outflow tract. Trainees using this model had a better understanding and retention of the ventricular outflow tract anatomy compared to those of the control group.
Factors that influence the satisfaction of people living with HIV with differentiated antiretroviral therapy delivery models in East Central Uganda: a cross-sectional study
Authors: Baleeta Keith , Muhwezi Augustin , Tumwesigye Nathan , Kintu Betty Nsangi , Riese Sara , Byonanebye Dathan , Mbonye Martin , Mwehire Daniel , Iriso Robert , Ayebazibwe Bernard , Bailey Lauren , Lopez Deborah , McGough Laura , Etukoit Michael , Nantamu Dyogo , Nakitende Louisa , Tibengana Baker , Wasswa Jacob
Published: February 2023

Background

The World Health Organization (WHO) and the Uganda Ministry of Health recommend differentiated service delivery models (DSDMs) as patient-centered antiretroviral therapy (ART) mechanisms for people living with HIV/AIDS (PLHIV) with undetectable viral loads. We studied patient satisfaction with ART services, and its associated factors amongst PLHIV enrolled in DSDMs in Uganda.

Methods

This cross-sectional study involved a random sample of PLHIV accessing DSDM-related ART at nine facilities in East Central Uganda. Eligible patients were adult PLHIV (≥18 years), on ART, and enrolled for at least 12 months in one of three DSDMs: Community Client-Led ART Delivery (CCLAD), Community Drug Distribution Points (CDDP), or Fast-Track Drug Refill (FTDR). We collected data from June to July 2019. A validated tool measured satisfaction. General Estimating Equations with modified Poisson regression and exchangeable correlation structures accounted for clustering at health facilities and identified DSDM-related satisfaction factors.

Results

Of 842 participants enrolled, 530 (63.5%) accessed HIV care through CDDP, 166 (20.1%) through CCLAD, and 146 (16.3%) through FTDR; 541 (64.2%) were satisfied with DSDM services: 78.7% in CDDP, 42.8% in CCLAD, and 36.3% in FTDR. The delivery and treatment factors positively associated with satisfaction included: being enrolled on CDDP [adjusted prevalence ratio (aPR) = 1.51, 95% CI:1.47–1.56] or FTDR [aPR = 1.47, 95% CI:1.26–1.71] relative to CCLAD and being enrolled in a DSDM for more than 3 years [aPR = 1.28, 95% CI:1.11–1.48]. Poor ART adherence [aPR = 0.33, 95% CI:0.19–0.56] and having a baseline WHO HIV stage of 3 or 4 [aPR = 0.36, 95% CI:0.20–0.64] relative to stages 1 and 2 were negatively associated. Among socioeconomic factors, having lower transport costs (< $1.35) per clinic visit [aPR = 1.34, 95% CI:1.17–1.53], being employed [aPR = 1.61, 95% CI:1.38–1.87], and being single [aPR = 1.10, 95% CI:1.08–1.13] were positively associated with satisfaction; drinking alcohol at least once a week [aPR = 0.77, 95% CI:0.63–0.93] was negatively associated with patient satisfaction.

Conclusions

Results showed that 64.2% of patients were satisfied with DSDM services. HIV service delivery and treatment factors (DSDM type, time in DSDM, WHO stage, ART adherence), plus social factors (employment and marital status, transport costs, alcohol consumption), were associated with patient satisfaction. DSDM implementers should tailor services to address these factors to improve patient satisfaction.
The broad use of the Pm8 resistance gene in wheat resulted in hypermutation of the AvrPm8 gene in the powdery mildew pathogen
Authors: Kunz Lukas , Sotiropoulos Alexandros G. , Graf Johannes , Razavi Mohammad , Keller Beat , Müller Marion C.
Published: February 2023

Background

Worldwide wheat production is under constant threat by fast-evolving fungal pathogens. In the last decades, wheat breeding for disease resistance heavily relied on the introgression of chromosomal segments from related species as genetic sources of new resistance. The Pm8 resistance gene against the powdery mildew disease has been introgressed from rye into wheat as part of a large 1BL.1RS chromosomal translocation encompassing multiple disease resistance genes and yield components. Due to its high agronomic value, this translocation has seen continuous global use since the 1960s on large growth areas, even after Pm8 resistance was overcome by the powdery mildew pathogen. The long-term use of Pm8 at a global scale provided the unique opportunity to study the consequences of such extensive resistance gene application on pathogen evolution.

Results

Using genome-wide association studies in a population of wheat mildew isolates, we identified the avirulence effector AvrPm8 specifically recognized by Pm8. Haplovariant mining in a global mildew population covering all major wheat growing areas of the world revealed 17 virulent haplotypes of the AvrPm8 gene that grouped into two functional categories. The first one comprised amino acid polymorphisms at a single position along the AvrPm8 protein, which we confirmed to be crucial for the recognition by Pm8. The second category consisted of numerous destructive mutations to the AvrPm8 open reading frame such as disruptions of the start codon, gene truncations, gene deletions, and interference with mRNA splicing. With the exception of a single, likely ancient, gain-of-virulence mutation found in mildew isolates around the world, all AvrPm8 virulence haplotypes were found in geographically restricted regions, indicating that they occurred recently as a consequence of the frequent Pm8 use.

Conclusions

In this study, we show that the broad and prolonged use of the Pm8 gene in wheat production worldwide resulted in a multitude of gain-of-virulence mechanisms affecting the AvrPm8 gene in the wheat powdery mildew pathogen. Based on our findings, we conclude that both standing genetic variation as well as locally occurring new mutations contributed to the global breakdown of the Pm8 resistance gene introgression.
Cold exposure alters lipid metabolism of skeletal muscle through HIF-1α-induced mitophagy
Authors: Chen Wentao , Xu Ziye , You Wenjing , Zhou Yanbing , Wang Liyi , Huang Yuqin , Shan Tizhong
Published: February 2023

Background

In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment.

Results

Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment.

Conclusions

Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.
Association between the stress hyperglycemia ratio and severity of coronary artery disease under different glucose metabolic states
Authors: Zhang Yu , Song Haiyan , Bai Jing , Xiu Jiahui , Wu Ganggang , Zhang Liao , Wu Yunhe , Qu Ying
Published: February 2023

Background

Stress hyperglycemia ratio (SHR) is significantly related to adverse cardiovascular clinical outcomes and increased in-hospital mortality. However, the relationship between SHR and coronary artery disease (CAD) severity has hitherto not been reported. This study sought to clarify the relationship between the SHR and CAD severity of individuals with different glucose metabolic statuses.

Methods

A retrospective analysis was performed on 987 patients who underwent coronary angiography (CAG) from October 2020 to May 2022. Based on CAG results, patients were divided into single-vessel CAD and multi-vessel CAD groups. All subjects were stratified into three groups according to the tertiles of the SHR (T1 group: SHR < 0.930; T2 group: 0.930 ≤ SHR < 1.154; T3 group: 1.154 ≤ SHR). Moreover, according to glucose metabolism status, study subjects were divided into normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM) and diabetes mellitus (DM) groups. Finally, the correlation between SHR and CAD severity was analyzed by logistic regression analysis and receiver operating characteristic (ROC) curve.

Results

The results showed significantly higher SHR in the multi-vessel CAD group than in the single-vessel group. Logistic regression analysis showed that SHR was an independent risk factor for multi-vessel CAD when used as a continuous variable (OR, 4.047; 95% CI 2.137–7.663; P < 0.001). After adjusting for risk factors, the risk of multi-vessel CAD in the T2 and T3 groups was 1.939-fold (95% CI 1.341–2.804; P < 0.001) and 1.860-fold (95% CI 1.272–2.719; P = 0.001) higher than in the T1 group, respectively. The area under the curve (AUC) of ROC plots was 0.613 for SHR. In addition, SHR was significantly correlated with an increased risk of multi-vessel CAD in the pre-DM and DM groups.

Conclusions

Our study indicated that SHR was significantly correlated with the risk of multi-vessel CAD and predicted CAD severity, especially in pre-DM and DM patients.
Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling
Authors: Liu Xiao , Guo Qingdong , Gao Guangxun , Cao Zhengcong , Guan Zhihao , Jia Bo , Wang Weizhong , Zhang Kuo , Zhang Wangqian , Wang Shuning , Li Weina , Hao Qiang , Zhang Yingqi , Li Meng , Zhang Wei , Gu Jintao
Published: February 2023

Although temozolomide (TMZ) provides significant clinical benefit for glioblastoma (GBM), responses are limited by the emergence of acquired resistance. Here, we demonstrate that exosomal circCABIN1 secreted from TMZ-resistant cells was packaged into exosomes and then disseminated TMZ resistance of receipt cells. CircCABIN1 could be cyclized by eukaryotic translation initiation factor 4A3 (EIF4A3) and is highly expressed in GBM tissues and glioma stem cells (GSCs). CircCABIN1 is required for the self-renewal maintenance of GSCs to initiate acquired resistance. Mechanistically, circCABIN1 regulated the expression of olfactomedin-like 3 (OLFML3) by sponging miR-637. Moreover, upregulation of OLFML3 activating the ErbB signaling pathway and ultimately contributing to stemness reprogramming and TMZ resistance. Treatment of GBM orthotopic mice xenografts with engineered exosomes targeting circCABIN1 and OLFML3 provided prominent targetability and had significantly improved antitumor activity of TMZ. In summary, our work proposed a novel mechanism for drug resistance transmission in GBM and provided evidence that engineered exosomes are a promising clinical tool for cancer prevention and therapy.

Graphical Abstract
Prevalence and predictors of workplace violence against emergency physicians in China: a cross-sectional study
Authors: Yan Shijiao , Feng Jing , Gan Yong , Wang Rixing , Song Xingyue , Luo Zhiqian , Han Xiaotong , Lv Chuanzhu
Published: February 2023

Background

Workplace violence (WPV) is considered a global problem, particularly in the health sector; however, no studies have assessed the national prevalence of WPV against emergency physicians and the associated factors in China.

Methods

A national cross-sectional survey was conducted in 31 provinces/autonomous regions/municipalities across China between July 2019 and September 2019. A total of 15 455 emergency physicians were selected using a multistage stratified random sampling method. A structured self-administered questionnaire was used to collect information on WPV and potential associated factors among emergency physicians. Descriptive and multivariable logistic regression analyses were used to identify the predictors of WPV.

Results

A total of 14 848 emergency physicians responded effectively (effective response rate: 96.07%). Of the respondents, 90.40%, 51.45%, and 90.00% reported exposure to any type of WPV, physical or nonphysical violence in the preceding year, respectively. Verbal aggression (87.25%) was the most common form of violence, followed by threat (71.09%), physical assault (48.24%), verbal sexual harassment (38.13%), and sexual assault (19.37%). Patients’ families were the main perpetrators of these incidents. Unmet patient needs, taking drugs or drinking, and long waiting times were the main contributors to WPV. Physicians who were from low-developed regions, female, and without shift work were less likely to have experienced any type of WPV. Chinese emergency physicians who were from medium-developed regions, had a bachelor’s degree, worked in a higher level hospital, had a higher professional title, with lower incomes, had a history of hypertension or coronary heart disease, were smokers or drinkers, and worked in hospitals without preventive measures or training for WPV and not encouraging to report WPV were more likely to have experienced any type of WPV. The predictors of WPV varied in different types of WPV.

Conclusions

This study shows that the prevalence of WPV against emergency physicians is high in China. Measures should be taken at the physicians, patients, hospital, and national levels to protect GPs from WPV; for example, improving physicians’ level of service and hospital’ reporting procedures. Creating a prevention strategy and providing a safer workplace environment for emergency physicians should be prioritized.
Economic costs, health-related quality of life outcomes and cost-utility of a physical and psychological group intervention targeted at older adults with neurogenic claudication
Authors: Maredza Mandy , Khan Kamran , Marian Ioana R. , Dutton Susan J. , Williamson Esther , Lamb Sarah E. , Petrou Stavros
Published: February 2023

Background

Emerging evidence suggests that structured and progressive exercise underpinned by a cognitive behavioural approach can improve functional outcomes in patients with neurogenic claudication (NC). However, evidence surrounding its economic benefits is lacking.

Objectives

To estimate the economic costs, health-related quality of life outcomes and cost-effectiveness of a physical and psychological group intervention (BOOST programme) versus best practice advice (BPA) in older adults with NC.

Methods

An economic evaluation was conducted based on data from a pragmatic, multicentre, superiority, randomised controlled trial. The base-case economic evaluation took the form of an intention-to-treat analysis conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective and separately from a societal perspective. Costs (£ 2018–2019 prices) were collected prospectively over a 12 month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of the BOOST programme in comparison to BPA. Sensitivity and pre-specified subgroup analyses explored uncertainty and heterogeneity in cost-effectiveness estimates.

Results

Participants (N = 435) were randomised to the BOOST programme (n = 292) or BPA (n = 143). Mean (standard error [SE]) NHS and PSS costs over 12 months were £1,974 (£118) in the BOOST arm versus £1,827 (£169) in the BPA arm (p = 0.474). Mean (SE) QALY estimates were 0.620 (0.009) versus 0.599 (0.006), respectively (p = 0.093). The probability that the BOOST programme is cost-effective ranged between 67 and 83% (NHS and PSS perspective) and 79–89% (societal perspective) at cost-effectiveness thresholds between £15,000 and £30,000 per QALY gained. INMBs ranged between £145 and £464 at similar cost-effectiveness thresholds. The cost-effectiveness results remained robust to sensitivity analyses.

Conclusions

The BOOST programme resulted in modest QALY gains over the 12 month follow-up period. Future studies with longer intervention and follow-up periods are needed to address uncertainty around the health-related quality of life impacts and cost-effectiveness of such programmes.

Trial registration This study has been registered in the International Standard Randomised Controlled Trial Number registry, reference number ISRCTN12698674. Registered on 10 November 2015.
Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker
Authors: Augustin Sebastien , Lam Marion , Lavalette Sophie , Verschueren Anna , Blond Frédéric , Forster Valérie , Przegralek Lauriane , He Zhiguo , Lewandowski Daniel , Bemelmans Alexis-Pierre , Picaud Serge , Sahel José-Alain , Mathis Thibaud , Paques Michel , Thuret Gilles , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian
Published: February 2023

Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the “don’t eat me” signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47−/−-mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.
Heterogeneous effects of individual high-fat diet compositions on phenotype, metabolic outcome, and hepatic proteome signature in BL/6 male mice
Authors: Janoschek Ruth , Handwerk Marion , Hucklenbruch-Rother Eva , Schmitz Lisa , Bae-Gartz Inga , Kasper Philipp , Lackmann Jan-Wilm , Kretschmer Tobias , Vohlen Christina , Mesaros Andrea , Purrio Martin , Quaas Alexander , Dötsch Jörg , Appel Sarah
Published: February 2023

The multitude of obesogenic diets used in rodent studies can hardly be overviewed. Since standardization is missing and assuming that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the individual effects of three commonly used obesogenic diets, mainly differing in sugar and fat content. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research. In conclusion, we strongly recommend a careful selection of the appropriate diet in advance of a new experiment, taking into account the specific research question.