bluuebunny/crossref_metadata_2025 huggingface dataset:
Wide-field swept-source OCTA in the assessment of retinal microvasculature in early-stage diabetic retinopathy
Authors: Wang Xiang-ning , Cai Xuan , Li Shi-wei , Li Tingting , Long Da , Wu Qiang
Published: December 2022

Background

To perform a quantitative analysis of retinal microvasculature in patients with early-stage diabetic retinopathy (DR) using wide-field swept-source optical coherence tomography angiography (SS-OCTA). 

Methods

One hundred nineteen eyes of 119 patents (67 eyes with no DR and 52 eyes with mild-moderate nonproliferative diabetic retinopathy (NPDR)) were enrolled in this observational and cross-sectional cohort study, and an age-matched group consisting of 39 eyes of 39 non-diabetic subjects were set as the control. Each participant underwent a full ophthalmic examination, including wide-field SS-OCTA imaging. On OCTA scans (12 mm * 12 mm), the mean perfusion area (PA) and vessel density (VD) were independently measured in all 16 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Linear regression analyses were conducted to evaluate the influences of PA.

Results

In the central ring, there were no significant differences in the average PA and VD among the groups. In the 3 mm radius, the PA and VD of the no DR and mild-moderate NPDR were significantly decreased compared with the control group in superior and inferior quadrants. In the wide-field scans (9 and 12 mm radius), there was no significant difference in average PA and VD between the groups in each sectors (p > 0.05). Regression analysis found that the effect of VD on PA was statistically different (b = 1.311, p < 0.001).

Conclusion

Wide-field OCTA imaging is useful for evaluating peripheral capillary perfusion in eyes with early-stage DR. Decrease in PA and VD was greater in the S3 and I3 sectors, and reductions in PA and VD were uneven in wide-filed sectors (9 and 12 mm radius).
Evaluation of factors associated the expression of anti-HBs in children in Hunan Province, China
Authors: Tan Shan , Li Shizhou , Dong Jianxiang , Dai Hongmei , Yang Minghua , Sun Fang , Yang Yang , Jiang Jie , Zhu Shan , Zhao Mingyi , Chen Zhiheng
Published: December 2022

Background and objectives

Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically.

Methods

The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P < 0.10) in chi-square test or T test were further assessed with collinearity and chosen for univariate and multivariate logistic regression analysis by the stepwise backward maximum likelihood method (αin = 0.05, αout = 0.10).

Results

A total of 5838 samples (3362 males, 57.6%) were enrolled. In total, the incidence of negative anti-HBs increased with age[OR = 1.037(1.022–1.051)]. Multivariate logistic regression analysis illustrated that anemia[OR = 0.392(0.185–0.835)], age[OR = 2.542(1.961–3.295)] and Vit D[OR = 0.977(0.969–0.984)] in 0.5–2.99 years subgroup, Zinc deficiency[OR = 0.713(0.551–0.923] and age[OR = 1.151(1.028–1.289)] in 3–5.99 years subgroup, Vit D[OR = 0.983(0.971–0.995)] in 12–18 years subgroup had significant association with anti-HBs.

Conclusions

This retrospective study illustrated that age, anemia status, zinc deficiency and vitamin D were associated with anti-HBs expression in specific age groups of children, which could serve as a reference for the prevention of HBV.
Digital cognitive behavior therapy for insomnia improving sleep quality: a real-world study
Authors: Liang Sugai , Mao Hongjing , Yang Jingyun , Deng Wei , Cao Bo , Yu Zhenghe , Yang Lili , Xu You , Hu Nannan , Liu Wenjuan , Greenshaw Andrew J. , Li Tao
Published: December 2022

Background

Digital cognitive behavior therapy for insomnia (dCBT-I) is an effective treatment in alleviating insomnia. This study examined the effect of dCBT-I for improving sleep quality in patients with insomnia complaints from a clinical population in a real-world setting.

Methods

The study included 6,002 patients aged 18 years and above with primary complaints of dissatisfying sleep from a sleep clinic in a psychiatric hospital from November 2016 to April 2021. Patients were diagnosed with insomnia, anxiety disorders, or anxiety comorbid with insomnia or depression according to ICD-10. A mobile app was developed for self-reported assessment and delivering dCBT-I interventions and treatment prescriptions to participants. The primary outcome was change in global sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). At 8- and 12-week follow-up, 509 patients were reassessed. Data were analyzed with non-parametric tests for repeated measures.

Results

Patients treated with dCBT-I monotherapy were younger, with a more frequent family history of insomnia compared to those with medication monotherapy and those with combined dCBT-I and medication therapy. Improvements of sleep quality from baseline to 8-week follow-up were significant in each treatment type. Compared to 8-week follow-up, PSQI scores at 12-week were significantly decreased in the depression group receiving combined therapy and in the anxiety group treated with dCBT-I monotherapy and with combined therapy. A time-by-treatment interaction was detected in anxiety patients indicating differential reduction in PSQI scores over time between different treatment options.

Conclusion

The current findings suggest dCBT-I is a practical and effective approach for lessening insomnia symptoms, especially for patients with anxiety symptoms suggesting with a more extended intervention period (i.e., 12 weeks).

Trial registration

Chinese Clinical Trial Registry (ChiCTR1900022699).
Exploring arts-based interventions for youth substance use prevention: a scoping review of literature
Authors: Maina Geoffrey , Li Yiyan , Fang Yiting , Amoyaw Jonathan , Pandey Mamata , Herzog Thea , Nkrumah Daniel , Sherstobitoff Jordan , Mousavian Ghazal
Published: December 2022

Introduction

There is a rise in problematic substance use among Canadian youth, which is precipitating a public health crisis. Interventions are needed to empower youth to mitigate substance use risks. Active youth involvement in substance use prevention is urgently needed to increase uptake and ownership of the process and outcome of the intervention. Arts-based interventions are ideal participatory action approaches that can empower young people to be active agents in substance use prevention. These approaches can help promote health, reduce harm, and change behaviours. Scoping reviews are a vital tool that can help the research team identify relevant interventions that can be adapted to a community.

Methods

This scoping review explores various arts-based substance use prevention interventions for youth. The scoping review used the iterative stages of Arksey and O’Malley to search Portal ERIC, Ovid MEDLINE, C.I.N.A.H.L., E.M.B.A.S.E., Web of Science, and A.P.A. PsycInfo and grey literature from Canadian Centre on Substance Use and Addiction and websites suggested by the Canadian Agency for Drugs and Technologies in Health. Inclusion criteria are a) articles utilizing arts-based intervention on substance use prevention; b) studies with a clearly defined intervention; c) intervention targeting the youth (age 12–17) and d) publications written in English. Thematic analysis was used to identify the main themes from the included articles.

Results and discussion

Themes identified in a thematic synthesis of these studies included a) the intent of the intervention; b) intervention characteristics; and c) the perceived effectiveness of interventions. Art-based interventions increased knowledge and changed attitudes and practices on substance use among youth. Making the interventions aesthetically appealing and engaging, active youth involvement in the development of the intervention and developing youth-centred interventions which attended to the realities they faced were central to the success of these interventions.
Milligan–Morgan hemorrhoidectomy vs. hemorrhoid artery ligation and recto-anal repair: a comparative study
Authors: Symeonidis Dimitrios , Spyridakis Michail , Zacharoulis Dimitrios , Tzovaras George , Samara Athina A. , Valaroutsos Alexandros , Diamantis Alexandros , Tepetes Konstantinos
Published: December 2022

Background

Several surgical techniques for the treatment of hemorrhoidal disease (HD) have been proposed. However, the selection of the most proper technique for each individual case scenario is still a matter of debate. The purpose of the present study was to compare the Milligan–Morgan (MM) hemorrhoidectomy and the hemorrhoidal artery ligation and rectoanal repair (HAL–RAR) technique.

Methods

A retrospective analysis of the prospectively collected database of patients submitted to HD surgery in our department was conducted. Patients were divided into two groups, the MM group and the HAL–RAR group. Primary end points were recurrence rates and patients’ satisfaction rates. The Unpaired t test was used to compare numerical variables while the x2 test for categorical variables.

Results

A total of 124 patients were identified, submitted either to HAL–RAR or MM hemorrhoidectomy. Eight (8) patients were lost to follow up and were excluded from the analysis. Of the remaining 116 patients, 69 patients (54 males and 15 females–male / female ratio: 3.6) with a median age of 47 years old (range 18–69) were included in the HAL–RAR group while 47 patients (40 males and 7 females–male / female ratio: 5.7) with a median age of 52 years old (range 32–71) comprised the MM group. At a median follow up of 41 months (minimum 24 months–maximum 72 months), we recorded 20 recurrences (28.9%) in the HAL–RAR group and 9 recurrences in the MM group (19.1%) (p 0.229). The mean time from the procedure to the recurrence was 14.1 ± 9.74 months in the HAL–RAR group and 21 ± 13.34 months in the MM group. Patients with itching, pain or discomfort as the presenting symptoms of HD experienced statistically significantly lower recurrences (p 0.0354) and reported statistically significantly better satisfaction rates (6.72 ± 2.15 vs. 8.11 ± 1.99—p 0.0111) when submitted to MM. In the subgroup of patients with bleeding as the presenting symptom, patients satisfaction rates were significantly better (8.59 ± 1.88 vs. 6.45 ± 2.70—p 0.0013) in the HAL–RAR group.

Conclusions

In patients with pain, itching or discomfort as the presenting symptoms of HD, MM was associated with less recurrences and better patients satisfaction rates compared to HAL–RAR. In patients with bleeding as the main presenting symptom of HD, HAL–RAR was associated with better patients’ satisfaction rates and similar recurrence rates compared to MM.
Application of hepatic lobe hyperplasia techniques in the treatment of advanced hepatic alveolar echinococcosis: a single-centre experience
Authors: Guo Qiang , Wang Maolin , Zhong Kai , Li Jialong , Jiang Tiemin , Ran Bo , Shalayiadang Paizula , Zhang Ruiqing , Tuergan Talaiti , Aji Tuerganaili , Shao Yingmei
Published: December 2022

Background

This study was designed to investigate clinical efficiency and application indications of hepatic lobe hyperplasia techniques for advanced hepatic alveolar echinococcosis (AE) patients.

Methods

A retrospective case series covering 19 advanced hepatic AE patients admitted to the First Affiliated Hospital of Xinjiang Medical University from September 2014 to December 2021 and undergoing hepatic lobe hyperplasia techniques due to insufficient remnant liver volume were analyzed. Changes of liver function, lesions volume, remnant liver volume, total liver volume before and after operation have been observed.

Results

Among the patients, 15 underwent portal vein embolization (PVE). There was no statistical difference in total liver volume and lesions volume before and after PVE (P > 0.05). However, the remnant liver volume was significantly increased after PVE (P < 0.05). The median monthly increase rate in future liver remnant volume (FLRV) after PVE stood at 4.49% (IQR 3.55–7.06). Among the four patients undergoing two-stage hepatectomy (TSH), FLRV was larger than that before the first stage surgery, and the median monthly increase rate in FLRV after it stood at 3.34% (IQR 2.17–4.61). Despite no statistical difference in total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) in all patients with PVE, four patients who underwent TSH showed a decrease in ALT, AST and GGT. During the waiting process before the second stage operation, no serious complications occurred in all patients.

Conclusions

For patients suffering from advanced hepatic AE with insufficient FLRV, PVE and TSH are safe and feasible in promoting hepatic lobe hyperplasia.
The correlation of the fecal microbiome with the biochemical profile during menopause: a Brazilian cohort study
Authors: da Silva Thayane Christine Alves , dos Santos Gonçalves Jennefer Aparecida , Souza Laura Alves Cota e , Lima Angélica Alves , Guerra-Sá R.
Published: December 2022

Background

Hormonal, biochemical, and metabolic changes after menopause may alter the quality of life of women, leading to vasomotor, psychological, and genitourinary symptoms, and changes in their gut microbiota, which regulates estrogen levels through the estroboloma. Fecal samples were used to investigate the changes in the gut microbiota during aging and hormonal changes in women. A balanced gut microbiota has been associated with health or disease conditions and remains poorly understood after menopause. This study identified the fecal microbiota, and their association with biochemical and hormonal parameters of a cohort of women in the climacteric in the city of Ouro Preto—MG, Brazil.

Methods

A total of 102 women aged 40 to 65 years old were recruited and distributed into three groups according to the STRAW criteria for reproductive stage: reproductive (n = 18), premenopausal (n = 26), and postmenopausal (n = 58). Blood samples were collected to measure their serum biochemical and hormone levels, and the participants answered a questionnaire. The gut microbiota was analyzed from fecal samples by qPCR using the genera Bifidobacterium, Bacteroides, Lactobacillus, and Clostridium.

Results

The following parameters showed differences among the groups: total cholesterol, triglycerides, VLDL, ApoB, urea, calcium, uric acid, and alkaline phosphatase (p < 0.05). qPCR revealed the genus Clostridium to be the most abundant in all three groups. In the reproductive age group, the significant correlations were: Bacteroides with glucose (r = -0.573 p = 0.0129), and SDHEA (r = -0.583 p = 0.0111). For the premenopausal group, they were: Bifidobacteria with total cholesterol (r = 0.396 p = 0.0451), LDL (r = 0.393 p = 0.0468), ApoB (r = 0.411 p = 0.0368); Lactobacillus and calcium (r = 0.443 p = 0.0232), ALP (r = 0.543 p = 0.0041), LPa (r =-0.442 p = 0.02336); and Bacteroides and urea (r =-0.461 p = 0.0176). In the postmenopausal group, they were Bifidobacterium and ALP (r =-0.315 p = 0.0159), Lactobacillus and urea (r =-0.276 p = 0.0356), and Clostridium and beta estradiol (r =-0.355 p = 0.0062).

Conclusion

In conclusion, the hormonal and metabolic changes during menopause in the population studied were accompanied by a significant change in the fecal microbiota, especially of the genus Clostridium.
Predictive models for overall survival in breast cancer patients with a second primary malignancy: a real-world study in Shanghai, China
Authors: Yuan Ling , Chen Yichen , Li Xiaopan , Jin Hua , Shi Jianwei
Published: December 2022

Background

The incidents of second primary malignancy (SPM) is increasing among breast cancer (BC) patients with long-term progression, adversely affecting survival. The purpose of this study was to screen independent overall survival (OS) risk factors and establish nomograms to predict the survival probabilities of BC patients with SPM.

Method

A total of 163 BC patients with SPM were recruited during 2002–2015 from a total of 50 hospitals in Shanghai, China. Two nomograms to predict survival from primary BC and SPM diagnosis were constructed based on independent factors screened from multivariable analysis. The calibration and discrimination of nomograms were calculated in the training and validation cohorts.

Results

The overall survival rates of BC patients with SPM were 88.34%, 64.42% and 54.66% at 5, 10 and 15 years, respectively. Factors of late TNM stage of SPM (HR = 4.68, 95% CI 2.14–10.25), surgery for SPM (HR = 0.60, 95% CI 0.36–1.00), SPM in the colon and rectum (HR = 0.49, 95% CI 0.25–0.98) and thyroid (HR = 0.08, 95% CI 0.01–0.61) independently affected the OS of BC patients with SPM (p < 0.05). In addition, a longer latency (≥ 5 years) was associated with better OS from BC diagnosis (p < 0.001). Older age (≥ 56) was associated with poor OS from SPM diagnosis (p = 0.019). Two nomograms established based on the above factors had better calibration and discrimination.

Conclusion

The TNM stage of SPM, surgery for SPM, SPM sites, latency and age at BC diagnosis are independent factors for survival and the two nomograms may provide more personalized management for BC patients with SPM.
Patients’ preference approach to overcome the moral implications of family-centred decisions in Saudi medical settings
Authors: Alfahmi Manal Z.
Published: December 2022

Background

In Saudi clinical settings, cultural influences can give a patient’s family authority to override the patient’s autonomous right to make informed health-related decisions. Cultural values should not prevent patients from exercising their genuine preferences when making medical decisions in their own best interests.

Discussion

This article discusses the moral implications of family-centred medical decisions for autonomous patients who are competent and capable of making decisions. The author argues that socio-cultural values do not justify the decision to override patient autonomy when patients express a preference for making their own choices.

Conclusion

The author recommends the use of a model of shared decision-making that accounts for both individual and relational conceptions of autonomy, approaching patients’ preferences in all medical encounters with the aim of minimising the potential for socio-cultural values to undermine patient autonomy. Although this approach is a safeguard against both family and medical paternalism, allowance is made for clinicians to act in weakly paternalistic ways when patients at high risk of exacerbating existing medical conditions are likely to benefit from delaying or limiting the disclosure of potentially distressing but non-fatal diagnoses and prognoses. Thus, the author argues that even in a culture that supports family involvement in management decisions, physicians should respect patient autonomy by asking patients for their preferences in the disclosure of their medical diagnoses, prognoses and management options and verifying patients’ preferences about the roles they wish their families to play (if any) in health-related decisions.
The prevalence of chronic medication therapy problems and pharmacists’ interventions among hospitalized perioperative patients: a retrospective observational study
Authors: Cheng Hai-Ting , Zhao Ming , Liu Hong-Tao , Shen Guo-Liang , Zhao Ting , Feng Zhi-En
Published: December 2022

Background

Inadequate preoperative management of chronic medications can place perioperative patients at risk and cause unnecessary delays in surgical procedures. This study aims to investigate the prevalence of chronic medication therapy problems (CMTPs) in hospitalized perioperative patients and assess the relevance of pharmacists’ interventions.

Methods

We conducted a retrospective study of pharmacist-led preoperative management of chronic medications in hospitalized adult patients from November 2018 to April 2019. The recorded drug-related problems (DRPs) were retrospectively reviewed and categorized according to the Pharmaceutical Care Network Europe classification V9.1 and were analyzed with a multinomial regression model to identify risk factors.

Results

A total of 254 DRPs were recorded, with an average of 0.52 DRPs per patient. Treatment safety (66.9%) was the most common DRP. The most frequent causes of perioperative DRPs and nonperioperative DRPs were drug selection (72.9%) and patient related (50.8%), respectively. Of the 292 documented interventions, 71.6% were fully accepted by the clinicians and patients. The majority (68.9%) of the recorded problems were completely resolved. The number of comorbidities (OR = 3.815) and the number of chronic medications taken (OR = 1.539) were risk factors for the occurrence of DRPs.

Conclusion

The findings of this study suggest that pharmacist-led chronic medication therapy management in surgical wards may be an effective method to help reduce medication-related surgical risks and optimize the medication therapies used for the long-term treatment of chronic diseases.
Dietary carbon loaded with nano-ZnO alters the gut microbiota community to mediate bile acid metabolism and potentiate intestinal immune function in fattening beef cattle
Authors: Zhang Haibo , Guan Weikun , Li Lizhi , Guo Dongsheng , Zhang Xiangfei , Guan Jiuqiang , Luo Runxiao , Zheng Siying , Fu Jiangwen , Cheng Yingying , He Qin
Published: December 2022

Background

To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively.

Results

The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1β were significantly decreased.

Conclusions

In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.
Prevalence and detection of Tropheryma whipplei in the stools of Korean patients with diarrhea using real-time PCRs
Authors: Yoon Sumi , Choi Yoo Jeong , Lim Yong Kwan , Kweon Oh Joo , Kim Hye Ryoun , Kim Tae-Hyoung , Lee Mi-Kyung
Published: December 2022

Background

The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15.

Methods

A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S–23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs.

Results

T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6–19 than in those aged 1–5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively.

Conclusions

This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.
Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
Authors: Jo Yong Suk , Rhee Chin Kook , Yoon Hyoung Kyu , Park Chan Kwon , Lim Jeong Uk , An Tai Joon , Hur Jung
Published: December 2022

Background

Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO.

Methods

We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system.

Results

Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model.

Conclusion

We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.
Smooth muscle cell fate decisions decipher a high-resolution heterogeneity within atherosclerosis molecular subtypes
Authors: Zhang Ge , Liu Zaoqu , Deng Jinhai , Liu Long , Li Yu , Weng Siyuan , Guo Chunguang , Zhou Zhaokai , Zhang Li , Wang Xiaofang , Liu Gangqiong , Guo Jiacheng , Bai Jing , Wang Yunzhe , Du Youyou , Li Tao-Sheng , Tang Junnan , Zhang Jinying
Published: December 2022

Background

Mounting evidence has revealed the dynamic variations in the cellular status and phenotype of the smooth muscle cell (SMC) are vital for shaping the atherosclerotic plaque microenvironment and ultimately mapping onto heterogeneous clinical outcomes in coronary artery disease. Currently, the underlying clinical significance of SMC evolutions remains unexplored in atherosclerosis.

Methods

The dissociated cells from diseased segments within the right coronary artery of four cardiac transplant recipients and 1070 bulk samples with atherosclerosis from six bulk cohorts were retrieved. Following the SMC fate trajectory reconstruction, the MOVICS algorithm integrating the nearest template prediction was used to develop a stable and robust molecular classification. Subsequently, multi-dimensional potential biological implications, molecular features, and cell landscape heterogeneity among distinct clusters were decoded.

Results

We proposed an SMC cell fate decision signature (SCFDS)-based atherosclerosis stratification system and identified three SCFDS subtypes (C1–C3) with distinguishing features: (i) C1 (DNA-damage repair type), elevated base excision repair (BER), DNA replication, as well as oxidative phosphorylation status. (ii) C2 (immune-activated type), stronger immune activation, hyper-inflammatory state, the complex as well as varied lesion microenvironment, advanced stage, the most severe degree of coronary stenosis severity. (iii) C3 (stromal-rich type), abundant fibrous content, stronger ECM metabolism, immune-suppressed microenvironment.

Conclusions

This study uncovered atherosclerosis complex cellular heterogeneity and a differentiated hierarchy of cell populations underlying SMC. The novel high-resolution stratification system could improve clinical outcomes and facilitate individualized management.
A functional loop between YTH domain family protein YTHDF3 mediated m6A modification and phosphofructokinase PFKL in glycolysis of hepatocellular carcinoma
Authors: Zhou Rong , Ni Wen , Qin Chao , Zhou Yunxia , Li Yuqing , Huo Jianping , Bian Lijuan , Zhou Aijun , Li Jianming
Published: December 2022

Background & aims

N6-methyladenosine (m6A) modification plays a critical role in progression of hepatocellular carcinoma (HCC), and aerobic glycolysis is a hallmark of cancer including HCC. However, the role of YTHDF3, one member of the core readers of the m6A pathway, in aerobic glycolysis and progression of HCC is still unclear.

Methods

Expression levels of YTHDF3 in carcinoma and surrounding tissues of HCC patients were evaluated by immunohistochemistry. Loss and gain-of-function experiments in vitro and in vivo were used to assess the effects of YTHDF3 on HCC cell proliferation, migration and invasion. The role of YTHDF3 in hepatocarcinogenesis was observed in a chemically induced HCC model with Ythdf3−/− mice. Untargeted metabolomics and glucose metabolism phenotype assays were performed to evaluate relationship between YTHDF3 and glucose metabolism. The effect of YTHDF3 on PFKL was assessed by methylated RNA immunoprecipitation assays (MeRIP). Co-immunoprecipitation and immunofluorescence assays were performed to investigate the connection between YTHDF3 and PFKL.

Results

We found YTHDF3 expression was greatly upregulated in carcinoma tissues and it was correlated with poor prognosis of HCC patients. Gain-of-function and loss-of-function assays demonstrated YTHDF3 promoted proliferation, migration and invasion of HCC cells in vitro, and YTHDF3 knockdown inhibited xenograft tumor growth and lung metastasis of HCC cells in vivo. YTHDF3 knockout significantly suppressed hepatocarcinogenesis in chemically induced mice model. Mechanistically, YTHDF3 promoted aerobic glycolysis by promoting phosphofructokinase PFKL expression at both mRNA and protein levels. MeRIP assays showed YTHDF3 suppressed PFKL mRNA degradation via m6A modification. Surprisingly, PFKL positively regulated YTHDF3 protein expression, not as a glycolysis rate-limited enzyme, and PFKL knockdown effectively rescued the effects of YTHDF3 overexpression on proliferation, migration and invasion ability of Sk-Hep-1 and HepG2 cells. Notably, co-immunoprecipitation assays demonstrated PFKL interacted with YTHDF3 via EFTUD2, a core subunit of spliceosome involved in pre-mRNA splicing process, and ubiquitination assays showed PFKL could positively regulate YTHDF3 protein expression via inhibiting ubiquitination of YTHDF3 protein by EFTUD2.

Conclusions

our study uncovers the key role of YTHDF3 in HCC, characterizes a positive functional loop between YTHDF3 and phosphofructokinase PFKL in glucose metabolism of HCC, and suggests the connection between pre-mRNA splicing process and m6A modification.
Association between cholinesterase activity and critical illness brain dysfunction
Authors: Hughes Christopher G. , Boncyk Christina S. , Fedeles Benjamin , Pandharipande Pratik P. , Chen Wencong , Patel Mayur B. , Brummel Nathan E. , Jackson James C. , Raman Rameela , Ely E. Wesley , Girard Timothy D.
Published: December 2022

Background

Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge.

Methods

We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates.

Results

We included 272 critically ill patients who were a median (IQR) age 56 (39–67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5–11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge.

Conclusion

Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction.

Trial Registration: NCT03098472. Registered 31 March 2017.
Activation of primary hepatic stellate cells and liver fibrosis induced by targeting TGF-β1/Smad signaling in schistosomiasis in mice
Authors: Huang Ping , Ma Huihui , Cao Yun , Zhan Tingzheng , Zhang Tingting , Wang Xinyi , Zhang Yanan , Xu Jing , Xia Chaoming
Published: December 2022

Background

In mice, liver fibrosis is the most serious pathologic change during Schistosoma japonicum (S. japonicum) infection. Schistosomiasis is mainly characterized by schistosome egg-induced granulomatous fibrosis. Hepatic stellate cells (HSCs) are mainly responsible for the net accumulation of collagens and fibrosis formation in the liver. Activated HSCs regulated by transforming growth factor-β1 (TGF-β1)/Smad signaling have emerged as the critical regulatory pathway in hepatitis virus or carbon tetrachloride-induced liver fibrosis. However, the detailed mechanism of HSC activation in schistosome-induced liver fibrosis is poorly understood.

Methods

Schistosoma japonicum-induced murine models and a control group were generated by abdominal infection with 15 (± 1) cercariae. The purity of cultured primary HSCs was evaluated by immunocytochemistry. The histopathological changes in the livers of infected mice were estimated by hematoxylin–eosin and Masson staining. Dynamic expression of pro-fibrotic molecules and microRNAs was detected by real-time quantitative PCR (RT-qPCR). Mainly members involved in the TGF-β1/Smad signaling pathway were examined via RT-qPCR and Western blot.

Results

The egg-induced granulomatous inflammation formed at 4 weeks post-infection (wpi) and developed progressively. Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, TGF-β1, Smad2, Smad3, and Smad4 showed a significant increase in mitochondrial RNA (mRNA) and protein expression compared with the control group at 7 and 9 weeks post-infection (wpi), while an opposite effect on Smad7 was observed. In addition, the mRNA expression of microRNA-21 (miRNA-21) was significantly increased at 7 wpi, and the mRNA expression of miRNA-454 was decreased starting from 4 wpi.

Conclusion

Our present findings revealed that HSCs regulated by the TGF-β1/Smad signaling pathway play an important role in liver fibrosis in S. japonicum-infected mice, which may provide proof of concept for liver fibrosis in schistosomiasis.

Graphical Abstract
Cerebrovascular accident in a child with precursor B-cell acute lymphoblastic leukemia and coronavirus disease 2019: a case report
Authors: Karimi Hanie , Sarmadian Roham , Gilani Abolfazl , salajegheh Poorya , Nejad Biglari Habibe , Gholizadeh Mahsa
Published: December 2022

Background

Coronavirus disease 2019 can lead to rare but severe and life-threatening diseases in susceptible high-risk populations, including patients with immunodeficiency. A rare event in this report is stroke following COVID-19 disease in a patient with an immunocompromised background due to leukemia and anti-cancer treatments.

Case presentation

A 6-year-old iranian girl with precursor B-cell leukemia receiving vincristine therapy presented with fever and absolute neutrophil count < 500. Her severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test was positive. During hospitalization, she had abrupt onset tachypnea, reduced O2 saturation, and generalized tonic–clonic seizures treated with phenytoin and levetiracetam. Right parietal lobe ischemia was found on a brain computed tomography scan, and the cerebrospinal fluid polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus 2. Several days later, she developed lower extremity paralysis and speech impairment, so speech therapy and physiotherapy were initiated. The patient also received dexamethasone, mannitol, heparin, and remdesivir. She was discharged with enoxaparin and levetiracetam. Chemotherapy resumed 2 weeks following discharge. Her speech and walking improved after 10 months of follow-up, and bone marrow aspiration showed total remission.

Conclusion

Owing to the link between coronavirus disease 2019 and hematologic cancers with hypercoagulopathy and the tendency of patients with leukemia to have coronavirus disease 2019 complications, children with leukemia as well as suspected coronavirus disease 2019 must be hospitalized to prevent blood clot formation.
Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France
Authors: Dormoy Alexandre , Haissaguerre Magalie , Vitellius Géraldine , Do Cao Christine , Geslot Aurore , Drui Delphine , Lasolle Hélène , Vieira-Pinto Oceana , Salenave Sylvie , François Maud , Puerto Marie , Boullay Hélène Du , Mayer Anne , Rod Anne , Laurent Claire , Chanson Philippe , Reznik Yves , Castinetti Frédéric , Chabre Olivier , Baudin Eric , Raverot Gérald , Tabarin Antoine , Young Jacques
Published: December 2022

Context

Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS).

Objective

This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS.

Methods

A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11).

Results

In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients.

Conclusion

Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.
Glyphosate and the Swirl
Authors: Adams Vincanne
Published: December 2022

In Glyphosate and the Swirl Vincanne Adams explores the chemical glyphosate—the active ingredient in Roundup and a pervasive agricultural herbicide—as a predicament of contested science and chemically saturated life. Adams traces the history of glyphosate’s invention and its multiple uses as activists, regulators, scientists, clinicians, consumers, and sick people try to determine its safety and harm. Scientific and political debates over glyphosate’s toxicity are agitated into a swirl—a condition in which certainty is continually contested, divided, and multiplied. This movement replicates the chemical’s movement in soils, foods, bodies, archives, labs, and legislative bodies, settling in some places here and in other places there, its potencies changing and altering what it touches with different scales and kinds of impact. The swirl is both an artifact of academic capitalism, activist tactics, and contested scientific facts and a way to capture the complexity of contemporary life with chemicals.
Vorwort und Impressionen
Authors: Lassau Guido
Published: December 2022

Vorwort des Kantonsarchäologen Guido Lassau und Impressionen aus dem Berichtsjahr 2021.
Fundchronik: Ausgrabungen und Funde im Jahr 2021
Authors: Allemann Martin , Bernasconi Marco , Billo Sven , Colomb Livia , Graber Simon , Hodel Corinne , Ketzler Michael , Leistner Verena , Savary Johann , Schmidig Roman , Steiner Susan , Weidkuhn Delia
Published: December 2022

Berichte zu den archäologischen Untersuchungen der Archäologischen Bodenforschung Basel-Stadt im Jahr 2021.
Latrinen auf dem Areal des Augustinerklosters
Authors: Kamber Pia
Published: December 2022

Im Innenhof des Naturhistorischen Museums (ehemaliges Areal des Augustinerklosters) wurden fünf Latrinengruben ausgegraben. Die Kleinlatrinen 1,2 (und 5) stammen aus vorklösterlicher Zeit (vor 1276). Die grossen Abortgruben 3 und 4 weisen auf eine Benutzung in klösterlicher Zeit hin und wurden spätestens 1290/1300 zugeschüttet. Neben der umfangreichen Geschirr- und Ofenkeramik enthielten die Abortgruben auch ein breites Spektrum an Gläsern. Dank der schriftlichen Quellenlage konnte die Keramik zeitlich gut eingegrenzt werden. Vergleichsfunde aus der Verfüllung des Klosterkellers (zugeschüttet um 1320/40) zeigten markante Unterschiede in den Ensembles sowie in den Techniken. Kurze Exkurse zur Archäobotanik, Sedimentologie, Archäozoologie und Archäometrie ergänzen die Aussagen der Archäologin.
Sedimentanalyse von drei Erdproben aus Latrine 3 von der Augustinergasse 2 in Basel (1968)
Authors: Joos Marcel
Published: December 2022

Von drei analysierten Kalkproben können zwei als Desinfektionsmittel gedeutet werden, so dass alles in allem aus sedimentologischer Sicht die Uminterpretation des mittelalterlichen Kellers 3 in eine Latrine einen hohen Grad an Wahrscheinlichkeit für sich beanspruchen kann.
Überlegungen zur Pfostenreihe 7d-7h in Bezug auf ihre topographische Ausrichtung
Authors: Maurer François
Published: December 2022

Vier über eine Länge von etwa vierzehn Metern gereihte rundliche Gruben können Achse und Angelpunkte für die Anfänge des Augustinerklosters und die Zeit unmittelbar davor sein.
Versuch einer Baugeschichte des Klosters der Augustiner-Eremiten
Authors: Maurer François
Published: December 2022

Die architektonischen Befunde der Grabung von 1968 sowie weitere Einzelbeobachtungen der Jahre 1963, 1972 und 1978, ferner neuere kunsthistorische Überlegungen haben vieles der zuvor postulierten Chronologie bestätigt, manches verfeinert sowie neue Erkenntnisse samt neuen Fragen auch zur Klosterzeit erbracht. Der Beitrag bietet eine Übersicht über die aktuellen Erkenntnisse.
Methodology of sociological research of characteristics and level of sociopolitical stability of student youth as a factor of sustainable development of Russian statehood in the context of modern global challenges
Authors: Kokurina O. , Burov A.
Published: December 2022

Methodology defines and describes the hypothesis, methodological tools, goal, objectives, and the result of empirical research, which is carried out in the form of a sociological survey. The Methodology also defines the general population of respondents, their gender, age and level of education. The specified result of intellectual activity reflects in detail the program of empirical research and its structural stages. The Methodology includes a sample questionnaire of sociological research, information about the content and nature of the questions, and a description of its conceptual parts. The methodology provides for the preparation of an independent result of intellectual activity - a detailed Аnalytical report containing proposals aimed at improving the sociopolitical stability of students as a factor in strengthening the Russian statehood and the viability of the state.