bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques
Authors: Tsampasian Vasiliki , Swift Andrew J. , Assadi Hosamadin , Chowdhary Amrit , Swoboda Peter , Sammut Eva , Dastidar Amardeep , Cabrero Jordi Broncano , Del Val Javier Royuela , Nair Sunil , Nijveldt Robin , Ryding Alisdair , Sawh Chris , Bucciarelli-Ducci Chiara , Levelt Eylem , Vassiliou Vassilios , Garg Pankaj
Published: November 2021

The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use.
Effect of maternal BMI on labor outcomes in primigravida pregnant women
Authors: Khalifa Eissa , El-Sateh Alaa , Zeeneldin Mohamed , Abdelghany Ahmed M. , Hosni Mahmoud , Abdallah Ameer , Salama Sameh , Abdel-Rasheed Mazen , Mohammad Hashem
Published: November 2021

Background

This study aims to detect the effects of increased BMI on labor outcomes in primigravida pregnant women.

Methods

A cross-sectional study involved 600 full-term singleton primigravida pregnant women who presented in the active phase of labor to the labor ward. They were divided according to BMI into three equals groups; women with normal BMI (group I), overweight women (group II), and women with class I obesity (group III).

Results

We found that high BMI was associated with a significantly increased risk of Caesarean section (C.S.) (13% in group I, 18% in group II and 40% in group III). Women with higher BMI and delivered vaginally had a significantly prolonged first and second stage of labor, consequently increased the need for oxytocin augmentation as well as the oxytocin dose. Regarding the maternal and fetal outcomes, there are significantly increased risks of postpartum sepsis, perineal tears, wound infection, as well as significantly increased birth weight and longer neonatal stay in the neonatal unit (NNU).

Conclusion

Obese primigravida pregnant women were at higher risk of suboptimal outcomes. Besides, prolonged first and second stages of labor and the incidence of C.S. have also been increased.
Characteristics in gut microbiome is associated with chemotherapy-induced pneumonia in pediatric acute lymphoblastic leukemia
Authors: Liu Xiaoming , Zou Yao , Zhang Yingchi , Liu Lipeng , Duan Yongjuan , Zhang Aoli , Zhang Xiaoyan , Zhang Ranran , Zhao Beibei , Li Xiaolan , Wei Tong , He Hongrui , Gan Yu , Wang Kejian , Zhu Xiaofan
Published: November 2021

Background

Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients.

Methods

We conducted a case–control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique.

Results

There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group.

Conclusions

Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.
Body mass index and physical activity in seven-year-old children whose mothers exercised during pregnancy: follow-up of a multicentre randomised controlled trial
Authors: Bjøntegaard Karen Alterhaug , Stafne Signe Nilssen , Mørkved Siv , Salvesen Kjell Åsmund , Evensen Kari Anne I.
Published: November 2021

Background

There are limited data on long-term outcomes of children whose mothers have followed exercise interventions during pregnancy. The aim of this paper was to investigate whether regular moderate intensity exercise during pregnancy affected the children’s body mass index (BMI) and physical activity (PA) at 7 years of age, and determine the relationship between children’s and mothers’ BMI and PA.

Methods

This was a follow-up of a multicentre randomised controlled trial, carried out at St. Olavs Hospital, Trondheim University Hospital, and Stavanger University Hospital, Norway (2007–2009 and 2014–2016). Women were randomised to follow a 12-week structured exercise protocol or standard antenatal care during pregnancy. At the 7-year follow-up, parents reported their child’s height, weight, and PA. The mothers also reported their own weight and PA. Main outcome variables were BMI, frequency and duration of moderate to vigorous PA (MVPA), and intensity of PA.

Results

A total of 855 women were randomised to exercise (n = 429) or standard antenatal care (n = 426) during pregnancy. At follow-up, 164 (38.2%) children and mothers in the intervention group and 117 (27.5%) in the control group participated. We found no group differences in the children’s iso-BMI or PA. Findings were similar when we performed stratified analyses by sex, except boys in the control group spent more time on electrical devices than boys in the intervention group. Subgroup analyses of children of mothers who adhered to the exercise protocol and sensitivity analyses excluding children born preterm, children admitted to the neonatal intensive care unit, and children with diseases or health problems at the 7-year follow-up, did not change the results. Children’s BMI, weekly leisure time MVPA and intensity of PA correlated with mothers’ BMI, daily exercise, and intensity of exercise.

Conclusions

Regular moderate intensity exercise during pregnancy did not affect BMI or PA of the children at 7 years. Good maternal health should be encouraged as it may influence the health of the next generation.

Trial registration

The initial RCT study was registered in ClinicalTrials.govNCT00476567.
Advance directives and end-of-life care preferences among adults in Wuhan, China: a cross-sectional study
Authors: Ni Ping , Wu Bei , Lin Huijing , Mao Jing
Published: November 2021

Background

Little is known about advance directives (ADs) and end-of-life (EOL) care preferences among the general population in Mainland China. This study aimed to describe knowledge and attitudes of ADs and EOL care preferences, and to explore factors related to preferences for ADs among Chinese adults.

Methods

The sample included 1114 adult participants in Wuhan, Mainland China. A brief message including the link to the online survey was sent to local residents who were registered at household registration management centers in Wuhan. The questionnaire included information regarding demographics, self-rated health, views on ADs and EOL care. Bivariate analyses and binary forward logistic regression were conducted to examine factors related to ADs preferences of Chinese adults.

Results

The average age of the sample was 48.0 years and more than half of the sample was female. 81.8% had never heard of ADs, but 86.6% indicated that they might create one after learning what ADs were. 58% would choose hospice care if they were terminally ill whereas 48.7% of the participants wanted to die at home. 92.3% would want to know their diagnosis and prognosis if ill; however, if their family members were diagnosed with an incurable disease, 50.5% would not tell their ill family member the actual diagnosis and prognosis. Those who had heard of ADs (OR = 1.567, p < 0.001), earned an associate’s degree (OR = 2.448, p < 0.001) or a bachelor’s degree or higher (OR = 2.382, p < 0.001), and self-rated their health as very poor/poor (OR = 1.002, p = 0.001) were more likely to be willing to make an AD than their counterparts. However, those who were single (OR = 0.149, p < 0.001) or widowed /divorced/separated (OR = 0.405, p = 0.001) were less likely to be willing to make an AD than the married ones.

Conclusions

Chinese adults showed positive attitudes towards ADs. There is an urgent need to promote more educational initiatives and raise awareness on the importance of ADs. It is important to develop more policies and legislation about ADs to improve the quality of EOL care in Mainland China.
Examining if changes in gender-specific and co-ed intramural programs affect youth physical activity over time: a natural experiment evaluation using school- and student-level data from the COMPASS study
Authors: Burns Kathleen E. , Chaurasia Ashok , Carson Valerie , Leatherdale Scott T.
Published: November 2021

Background

Despite the benefits of physical activity (PA), the majority of Canadian youth are falling short of the recommended 60 min of moderate-to-vigorous physical activity (MVPA) per day. School-based physical activity programs such as intramurals, are important opportunities for youth to be physically active. There is limited evidence available on the impact of gender-specific (e.g., female-only, male-only) and co-ed intramurals on youth PA over time, however, evidence suggests female-only intramurals may be important for female MVPA. This research aims to capitalize on a natural experiment to generate practice-based evidence on the impact of changes in gender-specific and co-ed intramurals on youth MVPA over time.

Methods

This study used linked longitudinal school- and student-level data from Ontario secondary schools in year 5 (Y5:2016–2017), year 6 (Y6: 2017–2018) and year 7 (Y7: 2018–2019) of the COMPASS study. Data on intramurals from 55 schools were used to determine the changes to gender-specific and co-ed intramurals that occurred from Y5 to Y6. Baseline demographic characteristics were measured and data on PA and sport participation were collected in Y5, Y6 and Y7 on a sample of 4417 students. Hierarchical linear mixed regression models were used to estimate how changes in gender-specific and co-ed intramurals were associated with youth MVPA over time.

Results

Participation in intramural, varsity and community sport were all positively and significantly associated with youth MVPA. Changes in gender-specific and co-ed intramurals were not significantly associated with youth MVPA in Y6 or Y7. However, the positive association between maintaining the addition of gender-specific intramurals on female MVPA in Y7 was on par with the significance level of α = 0.05, suggesting that adding gender-specific intramurals may be important for female MVPA.

Conclusions

Adding gender-specific and co-ed intramurals may not be sufficient strategies to increase PA among youth. Further research should explore the effect of gender-specific intramurals on youth PA, as this study may have been underpowered at the school-level. Gender-specific intramurals may promote a supportive PA environment that promotes MVPA, especially among females. These intramurals may be an important component of more comprehensive strategies to increase youth MVPA.
Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial
Authors: Badenes-Bonet Diana , Cejudo Pilar , Rodó-Pin Anna , Martín-Ontiyuelo Clara , Chalela Roberto , Rodríguez-Portal Jose Antonio , Vázquez-Sánchez Rosa , Gea Joaquim , Duran Xavier , Caguana Oswaldo Antonio , Rodriguez-Chiaradia Diego Agustín , Balcells Eva
Published: November 2021

Background

Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT.

Methods

This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms.

Results

Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices.

Conclusions

This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs.
Impact of tourniquet on short-term outcomes in opening wedge high tibial osteotomy with modern tranexamic acid protocols: a retrospective cohort study
Authors: Wang Limin , Zhang Zhen , Xiong Wei , Fang Qian , Tang Yunfeng , Wang Guanglin
Published: November 2021

Background

The use of a tourniquet during high tibial osteotomy (HTO) is a routine procedure, but there is currently no research on the benefits and potential risks of tourniquet use during HTO. The aim of this study was to investigate the impact of tourniquet on perioperative blood loss, early functional recovery and complications in opening wedge HTO with modern tranexamic acid protocols.

Methods

This was a retrospective cohort study of patients who underwent unilateral opening wedge HTO between January 2019 and September 2020. All patients were divided into two groups according to whether a tourniquet was applied during HTO. Patients in both groups received the same surgical procedures, tranexamic acid protocols and other perioperative treatments. Preoperative baseline data, intraoperative data, early postoperative recovery and all complications during the 3-month follow-up were collected and compared between the two groups.

Results

A total of 62 patients were enrolled in this study, including 32 in the tourniquet group and 30 in the non-tourniquet group. There was no significant difference in preoperative baseline data between the two groups (P > 0.05 in all). Intraoperative blood loss in the tourniquet group was significantly lower than that in the non-tourniquet group (80.22 ml versus 94.00 ml, P < 0.001), but there was no difference in total blood loss (187.39 ml versus 193.31 ml, P = 0.714). And no patient in either group required blood transfusion. In terms of early postoperative recovery, tourniquet use significantly increased pain scores and reduced knee range of motion on the first and second postoperative days, but there was no significant difference between the two groups at postoperative third day and third month. Furthermore, there was no significant difference between the two groups in terms of lower limb force line correction, length of stay, Knee Society Score or the incidence of complications during the 3-month follow-up (P > 0.05 in all).

Conclusions

In opening wedge HTO with modern tranexamic acid protocols, not using a tourniquet does not increase perioperative total blood loss or the risk of complications, but facilitates early postoperative recovery by reducing pain and increasing range of motion.
Effectiveness of MTA apical plug in dens evaginatus with open apices
Authors: Van Pham Khoa , Tran Thu Anh
Published: November 2021

Background

The present study aims to evaluate the effectiveness of mineral trioxide aggregate (MTA) application in treating dens evaginatus affected teeth with apical lesions and open apices using haemostatic collagen membrane to prevent the apical extrusion of MTA.

Methods

Twelve patients with 14 dens evaginatus affected teeth with apical lesions and open apices were treated with MTA apical plug and haemostatic collagen membrane. Clinical symptoms of subjective pain, pain of palpation, percussion, sinus tract, and the apical lesions' radiographic parameter were recorded at every 3-month interval up to 9 months after treatment. Paired t-test or Wilcoxon signed-rank test was used for statistical analysis with P < 0.05 as the threshold for considering results to be statistically significant.

Results

No patient experienced clinical symptoms 3 months after endodontic treatment. In addition, there was a significant difference in the dimensions of the apical lesions' before compared to 3 months after endodontic treatment.

Conclusions

The combination of MTA apical plug and haemostatic collagen membrane effectively treated dens evaginatus affected teeth with apical lesions, and open apices.
Reporting violations of European Charter of Patients’ Rights: analysis of patient complaints in Croatia
Authors: Karačić Jasna , Viđak Marin , Marušić Ana
Published: November 2021

Background

The European Charter of Patients' Rights (ECPR) presents basic patients' rights in health care. We analysed the characteristics of patients' complaints about their rights submitted through the official complaints system and to a non-governmental organization in Croatia.

Methods

The official system for patients’complaints in Croatia does not have a common pathway but offers different modes for addressing patient complaints. In this cross-sectional study, we analysed the reports about patients’ complaints from the official regional committees sent to the Ministry of Health. We also analysed the complaints received by the Croatian Association for the Protection of Patient’s Rights (CAPR) and mapped them to the ECPR.

Results

The aggregated official data from the Ministry of Health in 2017 and 2018 covered only 289 individual complaints from 10 out of 21 counties. Complaints were most frequently related to secondary and tertiary healthcare institutions and details were not provided. CAPR received a total of 440 letters, out of which 207 contained 301 complaints about violations of patients’ rights in 2017–2018. The most common complaint was the Right of Access to health care (35.3%) from the ECPR, followed by the Right to Information (29.9%) and the Right to Safety (21.7%). The fewest complaints were about the Right to Complain (1.9%), Right to Innovation (1.4%), Right to Compensation (1.4%), and Right to Preventive Measures (1.0%).

Conclusions

Reporting and dealing with patients’ complaints about violations of their patients’ rights does not appear to be effective in a system with parallel but uncoordinated complaints pathways. Mapping patient's complaints to the ECPR is a useful tool to assess the perception of patients’ rights and to plan actions to improve the complaints system for effective health care.
The effects of genetic polymorphisms of APOE on circulating lipid levels in middle-aged and elderly chinese Fujian Han population: toward age- and sex-personalized management
Authors: Liu Xiaofeng , Lin Qingwen , Fan Kengna , Tang Minjie , Zhang Weiqing , Yang Bin , Ou Qishui
Published: November 2021

Background

Increased evidence has reported the association of genetic polymorphisms of Apolipoprotein E (APOE) with serum lipids. However, few studies have explored the combined effects of APOE, gender, and age.

Methods

A total of 1,419 middle-aged and elderly subjects were randomly selected and studied. The APOE genotypes and the serum lipids were detected. The effects of APOE, gender, and age on serum lipids were preliminarily observed in general. The subjects were then divided into the middle-aged group (40–64 years old) and the elderly group (≥ 65 years old), for both males and females, to explore the combined effects of the APOE, gender, and age on serum lipids. Finally, a multivariate logistic regression model was used to evaluate the associations between the APOE allele carriers and the at-risk levels of dyslipidemia.

Results

The serum TC, LDL-C, and ApoB in the ε2 carriers were lower than the ε3 carriers (all P < 0.05), and there was no significant difference in the ε4 carriers compared to the ε3 carriers in general (all P > 0.05). The serum LDL-C and ApoB of the ε2 carriers were lower than the noncarriers in the middle-aged and elderly males (all P < 0.05). The serum TC in the ε2 carriers was lower than the noncarriers only in middle-aged males (P < 0.05). As to the levels of serum HDL-C and ApoA1, the ε2 carriers were higher than the noncarriers in middle-aged females (all P < 0.05), and the ε4 carriers were lower than noncarriers in middle-aged males (P < 0.05). Especially, the serum TG in the ε4 carriers was significantly higher than the noncarriers in elderly females. The logistic regression analysis indicated that the ε2 carriers were less likely to have at-risk levels of high LDL-C in middle-aged and elderly males (all P < 0.05) versus low HDL-C in middle-aged females (P < 0.05). In contrast, the ε4 carriers were more likely to have at-risk levels of high TG in elderly females (P < 0.05).

Conclusions

The effects of the genetic polymorphisms of APOE on the serum lipids were both gender- and age-dependent in the middle-aged and elderly Chinese Fujian Han population.
Establishment of multiplex RT-PCR to detect fusion genes for the diagnosis of Ewing sarcoma
Authors: Ueno-Yokohata Hitomi , Okita Hajime , Nakasato Keiko , Kiyotani Chikako , Kato Motohiro , Matsumoto Kimikazu , Kiyokawa Nobutaka , Nakazawa Atsuko , Yoshioka Takako
Published: November 2021

Background

Detection of the tumor-specific EWSR1/FUS-ETS fusion gene is essential to diagnose Ewing sarcoma. Reverse transcription–polymerase chain reaction (RT–PCR) and fluorescence in situ hybridization are commonly used to detect the fusion gene, and assays using next-generation sequencing have recently been reported. However, at least 28 fusion transcript variants have been reported, making rapid and accurate detection difficult.

Methods

We constructed two sets of multiplex PCR assays and evaluated their utility using cell lines and clinical samples.

Results

EWSR1/FUS-ETS was detected in five of six tumors by the first set, and in all six tumors by the second set. The fusion gene detected only by the latter was EWSR1-ERG, which completely lacked exon 7 of EWSR1. The fusion had a short N-terminal region of EWSR1 and showed pathologically atypical features.

Conclusions

We developed multiplex RT–PCR assays to detect EWSR1-ETS and FUS-ETS simultaneously. These assays will aid the rapid and accurate diagnosis of Ewing sarcoma. In addition, variants of EWSR1/FUS-ETS with a short N-terminal region that may have been previously missed can be easily detected.
Few-shot cotton leaf spots disease classification based on metric learning
Authors: Liang Xihuizi
Published: November 2021

Background

Cotton diceases seriously affect the yield and quality of cotton. The type of pest or disease suffered by cotton can be determined by the disease spots on the cotton leaves. This paper presents a few-shot learning framework that can be used for cotton leaf disease spot classification task. This can be used in preventing and controlling cotton diseases timely. First, disease spots on cotton leaf’s disease images are segmented by different methods, compared by using support vector machine (SVM) method and threshold segmentation, and discussed the suitable one. Then, with segmented disease spot images as input, a disease spot dataset is established, and the cotton leaf disease spots were classified using a classical convolutional neural network classifier, the structure and framework of convolutional neural network had been designed. At last, the features of two different images are extracted by a parallel two-way convolutional neural network with weight sharing. Then, the network uses a loss function to learn the metric space, in which similar leaf samples are close to each other and different leaf samples are far away from each other. In summary, this work can be regarded as a significang reference and the benchmark comparison for the follow-up studies of few-shot learning tasks in the agricultural field.

Results

To achieve the classification of cotton leaf spots by small sample learning, a metric-based learning method was developed to extract cotton leaf spot features and classify the sick leaves. The threshold segmentation and SVM were compared in the extracting of leaf spot. The results showed that both of these two method can extract the leaf spot in a good performance, SVM expented more time, but the leaf spot which extracted from SVM was much more suitable for classifying, thus SVM method can retain much more information of leaf spot, such as color, shape, textures, ect, which can help classficating the leaf spot. In the process of leaf spot classification, the two-way parallel convolutional neural network was established for building the leaf spot feature extractor, and feature classifier is constructed. After establishing the metric space, KNN was used as the spot classifier, and for the construction of convolutional neural networks, commonly used models were selected for comparison, and a spatial structure optimizer (SSO) is introduced for local optimization of the model, include Vgg, DesenNet, and ResNet. Experimentally, it is demonstrated that the classification accuracy of DenseNet is the highest, compared to the other two networks, and the classification accuracy of S-DenseNet is 7.7% higher then DenseNet on average for different number of steps.

Conclusions

As the step increasing, the accuracy of DesenNet, and ResNet are all improved, and after using SSO, each of these neural networks can achieved better performance. But The extent of increase varies, DesenNet with SSO had been improved the most obviously.
Exploring the perceived challenges and support needs of Indonesian mental health stakeholders: a qualitative study
Authors: Putri Adelia Khrisna , Gustriawanto Nuvi , Rahapsari Satwika , Sholikhah Anna Rusdiyana , Prabaswara Sanidya , Kusumawardhani Annisa Cahya , Kristina Susi Ari
Published: November 2021

Background

Despite the large treatment gap in Indonesia, limited studies have attempted to explore both service users’ and providers’ evaluations of the current mental health system holistically. This study aims to explore the perceived challenges and support needs of Indonesian mental health stakeholders.

Methods

This qualitative study collected data from 17 participants from two mental health stakeholders in Yogyakarta (i.e., health professionals and service users) through a semi-structured interview. Thematic analysis was used to analyze the data.

Results

Findings reveal that service providers and users shared equally strong concerns regarding challenges and needs for improving mental health literacy, accessibility to services, and government support. However, a distinct emphasis was made in several areas—with service providers hinting more towards issues with interprofessional collaboration. In contrast, service users emphasized the negative attitude of health professionals and poor accessibility to service information.

Conclusion

The mental health service system is challenged by the lack of accessibility to service information, the limited spread of mental health practitioners, stigma, and lack of mental health literacy among both the public and professionals. A need for improvement in mental health promotion, accessibility, and quality of mental health workers is highlighted to satisfy the needs of both service users and providers.
TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
Authors: Cheng Yubao , Liu Miao , Hu Mengwei , Wang Siyuan
Published: November 2021

Background

Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing lead to the discovery of cohesin-independent TAD-like structures, also known as single-cell domains, which are highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains.

Results

Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components and transcription mostly do not affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains.

Conclusions

In sum, this study suggests that single-cell domains are genome architecture building blocks independent of the tested major epigenetic components.
A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial
Authors: Dylla Layne , Douin David J. , Anderson Erin L. , Rice John D. , Jackson Conner L. , Bebarta Vikhyat S. , Lindsell Christopher J. , Cheng Alex C. , Schauer Steven G. , Ginde Adit A.
Published: November 2021

Background

Targeted normoxia (SpO2 90–96% or PaO2 60–100 mmHg) may help to conserve oxygen and improve outcomes in critically ill patients by avoiding potentially harmful hyperoxia. However, the role of normoxia for critically ill trauma patients remains uncertain. The objective of this study is to describe the study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients (SAVE-O2) clinical trial.

Methods

Design, setting, and participants: Protocol for a multicenter cluster randomized, stepped wedge implementation trial evaluating the effectiveness of a multimodal intervention to target normoxia in critically ill trauma patients at eight level 1 trauma centers in the USA. Each hospital will contribute pre-implementation (control) and post-implementation (intervention) data. All sites will begin in the control phase with usual care. When sites reach their randomly assigned time to transition, there will be a one-month training period, which does not contribute to data collection. Following the 1-month training period, the site will remain in the intervention phase for the duration of the trial.

Main outcome measures: The primary outcome will be supplemental oxygen-free days, defined as the number of days alive and not on supplemental oxygen. Secondary outcomes include in-hospital mortality to day 90, hospital-free days to day 90, ventilator-free days (VFD) to day 28, time to room air, Glasgow Outcome Score (GOS), and duration of time receiving supplemental oxygen.

Discussion

SAVE-O2 will determine if a multimodal intervention to improve compliance with targeted normoxia will safely reduce the need for concentrated oxygen for critically injured trauma patients. These data will inform military stakeholders regarding oxygen requirements for critically injured warfighters, while reducing logistical burden in prolonged combat casualty care.

Trial registration

ClinicalTrials.govNCT04534959. Registered September 1, 2020.
Use of external evidence for design and Bayesian analysis of clinical trials: a qualitative study of trialists’ views
Authors: Clayton Gemma L. , Elliott Daisy , Higgins Julian P. T. , Jones Hayley E.
Published: November 2021

Background

Evidence from previous studies is often used relatively informally in the design of clinical trials: for example, a systematic review to indicate whether a gap in the current evidence base justifies a new trial. External evidence can be used more formally in both trial design and analysis, by explicitly incorporating a synthesis of it in a Bayesian framework. However, it is unclear how common this is in practice or the extent to which it is considered controversial. In this qualitative study, we explored attitudes towards, and experiences of, trialists in incorporating synthesised external evidence through the Bayesian design or analysis of a trial.

Methods

Semi-structured interviews were conducted with 16 trialists: 13 statisticians and three clinicians. Participants were recruited across several universities and trials units in the United Kingdom using snowball and purposeful sampling. Data were analysed using thematic analysis and techniques of constant comparison.

Results

Trialists used existing evidence in many ways in trial design, for example, to justify a gap in the evidence base and inform parameters in sample size calculations. However, no one in our sample reported using such evidence in a Bayesian framework. Participants tended to equate Bayesian analysis with the incorporation of prior information on the intervention effect and were less aware of the potential to incorporate data on other parameters. When introduced to the concepts, many trialists felt they could be making more use of existing data to inform the design and analysis of a trial in particular scenarios. For example, some felt existing data could be used more formally to inform background adverse event rates, rather than relying on clinical opinion as to whether there are potential safety concerns. However, several barriers to implementing these methods in practice were identified, including concerns about the relevance of external data, acceptability of Bayesian methods, lack of confidence in Bayesian methods and software, and practical issues, such as difficulties accessing relevant data.

Conclusions

Despite trialists recognising that more formal use of external evidence could be advantageous over current approaches in some areas and useful as sensitivity analyses, there are still barriers to such use in practice.
Addressing constraints to informal providers’ involvement in tuberculosis control: a qualitative study of patent medicine dealers and tuberculosis programme managers
Authors: Onah Cosmas Kenan , Azuogu Benedict Ndubueze , Ossai Edmund Ndudi , Agu Adaoha Pearl , Azuogu Victoria Chioma , Alobu Isaac , Ogah Emeka Onwe
Published: November 2021

Background

A major constraint to tuberculosis control is low case finding with under-reporting to national authorities. Evidence shows that Patent Medicine Dealers are first port of call for most people with symptoms of tuberculosis, yet there is poor referral of such clients to tuberculosis treatment facilities for further evaluation. This study investigated constraints to involvement of Patent Medicine Dealers in tuberculosis control.

Methods

This was a cross-sectional qualitative study among Patent Medicine Dealers and Tuberculosis Control Programme Managers in Ebonyi State Nigeria. Sixty-four Patent Medicine Dealers and five Tuberculosis Control Programme Managers were interviewed using Focus Group Discussion and In-Depth Interview respectively. Data was collected with electronic audio-recording device and analyzed using thematic approach.

Results

There are some knowledge gaps about tuberculosis signs, symptoms, free-treatment policy and mode of operation of care service among Patent Medicine Dealers. Patent Medicine Dealers and Tuberculosis Control Programme Managers are willing to collaborate in tuberculosis control effort but constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Control Programme to keep up with such demands are obvious constraints.

Conclusions

Knowledge gaps in tuberculosis, its control, constant demand for incentives by Patent Medicine Dealers and inability of National Tuberculosis Control Programme to satisfy such demands are constraints to involvement of Patent Medicine Dealers in tuberculosis control. More robust engagement of Patent Medicine Dealers in tuberculosis control with clear job description through tuberculosis education and provision of incentives to support them are recommended policy approaches to improve linkage of clients to tuberculosis treatment facilities.
Prescreening to Increase Therapeutic Oncology Trial Enrollment at the Largest Public Hospital in the United States
Authors: Wu Jennifer , Yakubov Amin , Abdul-Hay Maher , Love Erica , Kroening Gianna , Cohen Deirdre , Spalink Christy , Joshi Ankeeta , Balar Arjun , Joseph Kathie-Ann , Ravenell Joseph , Mehnert Janice
Published: November 2021

PURPOSE:

The recruitment of underserved patients into therapeutic oncology trials is imperative. The National Institutes of Health mandates the inclusion of minorities in clinical research, although their participation remains under-represented. Institutions have used data mining to match patients to clinical trials. In a public health care system, such expensive tools are unavailable.

METHODS:

The NYU Clinical Trials Office implemented a quality improvement program at Bellevue Hospital Cancer Center to increase therapeutic trial enrollment. Patients are screened through the electronic medical record, tumor board conferences, and the cancer registry. Our analysis evaluated two variables: number of patients identified and those enrolled into clinical trials.

RESULTS:

Two years before the program, there were 31 patients enrolled. For a period of 24 months (July 2017 to July 2019), we identified 255 patients, of whom 143 (56.1%) were enrolled. Of those enrolled, 121 (84.6%) received treatment, and 22 (15%) were screen failures. Fifty-five (38.5%) were referred to NYU Perlmutter Cancer Center for therapy. Of the total enrollees, 64% were female, 56% were non-White, and overall median age was 55 years (range: 33-88 years). Our participants spoke 16 different languages, and 57% were non–English-speaking. We enrolled patients into eight different disease categories, with 38% recruited to breast cancer trials. Eighty-three percent of our patients reside in low-income areas, with 62% in both low-income and Health Professional Shortage Areas.

CONCLUSION:

Prescreening at Bellevue has led to a 4.6-fold increase in patient enrollment to clinical trials. Future research into using prescreening programs at public institutions may improve access to clinical trials for underserved populations.
Physical Fitness and Cardiovascular Risk Factors in Novel Diabetes Subgroups
Authors: Saatmann Nina , Zaharia Oana-Patricia , Strassburger Klaus , Pesta Dominik Hans , Burkart Volker , Szendroedi Julia , Gerdes Norbert , Kelm Malte , Roden Michael
Published: November 2021

Context

Physical inactivity promotes insulin resistance and increases the risk of diabetes and cardiovascular disease. Recently introduced clustering based on simple clinical measures identified diabetes subgroups (clusters) with different risks of diabetes-related comorbidities and complications.

Objective

This study aims to determine differences in physical fitness and cardiovascular risk between diabetes subgroups and a glucose-tolerant control group (CON). We hypothesized that the severe insulin-resistant diabetes (SIRD) subgroup would be associated with lower physical fitness and increased cardiovascular risk.

Methods

The physical fitness and cardiovascular risk of 746 participants with recent-onset diabetes (diabetes duration of < 12 months, aged 18-69 years) and 74 CONs of the German Diabetes Study (GDS), a prospective longitudinal cohort study, were analyzed. Main outcome measures included physical fitness (VO2max from spiroerogometry), endothelial function (flow- and nitroglycerin-mediated dilation), and cardiovascular risk scores (Framingham Risk Scores for Coronary Heart Disease [FRS-CHD] and Atherosclerotic CardioVascular Disease [ASCVD] risk score).

Results

VO2max was lower in SIRD than in CON, severe autoimmune diabetes (SAID) (both P < .001), and mild age-related diabetes (MARD) (P < .01) subgroups, but not different compared to severe insulin-deficient diabetes (SIDD) (P = .98) and moderate obesity-related diabetes (MOD) subgroups (P = .07) after adjustment for age, sex, and body mass index. Endothelial function was similar among all groups, whereas SAID had lower FRS-CHD and ASCVD than SIRD, MOD, and MARD (all P < .001).

Conclusion

Despite comparable endothelial function across all groups, SIRD showed the lowest physical fitness. Of note, SAID had the lowest cardiovascular risk within the first year after diabetes diagnosis compared to the other diabetes subgroups.
Association Between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients With Type 2 Diabetes
Authors: Au Philip C M , Tan Kathryn C B , Cheung Bernard M Y , Wong Ian C K , Wong Ying , Cheung Ching-Lung
Published: November 2021

Context

Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown.

Objective

To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared with dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong.

Design

A retrospective cohort study. The “prevalent new-user” design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the 2 groups.

Setting and participants

Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System.

Main Outcome Measures

Pneumonia incidence and mortality.

Results

The PS-matched cohort consisted of 6664 users of SGLT2is and 26 656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared with DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI, 2.61-5.51). The corresponding incidence rate ratio was 0.71 (95% CI, 0.62-0.81). Similar reduction in risk of pneumonia death was observed (hazard ratio 0.57; 95% CI, 0.42-0.77).

Conclusion

Compared with DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting.
Ιικότητα: Ενάντια σε μια Τυπική Μονάδα Ζωής
Authors: Gupta Sonali , Bolin Hunter
Published: November 2021

Ο ιός υπάρχει στον μεθοριακό χώρο μεταξύ ζωής και μη ζωής. Μια μικρή ποσότητα γενετικού υλικού εσωκλειόμενη σε ένα τέλεια γεωμετρικό μοριακό περίβλημα, είναι με κάποιο τρόπο ικανή να αυτο-αναπαραχθεί, να χειριστεί το περιβάλλον της, να προσαρμοστεί και εξελιχθεί – όλα χαρακτηριστικά που θα θεωρούσαμε ενδεικτικά της ζωής. Και όμως, ένας ιός δεν αναπνέει. Είτε την αποκαλέσουμε πράνα, τσι είτε βασική βιοχημεία, η αναπνοή είναι απλώς μια μεταβολική διαδικασία για την μεταγωγή ενέργειας. Η μικρότερη οντότητα ικανή να αναπνεύσει είναι το κύτταρο – ίσως ο λόγος που το χαρακτηρίζουμε ως «θεμελιώδη μονάδα ζωής». Τα τελευταία λόγια των Έρικ Γκάρνερ και Τζωρτζ Φλόιντ, «Δε μπορώ να αναπνεύσω,» αντανακλούν την ιδιαίτερη εμπειρία του να είσαι μαύρος στην Αμερική. Όμως, οι ίδιες αυτές λέξεις αντηχούν και σα φαντασ(μα)τικός πόνος όταν μια παγκόσμια πανδημία αφαιρεί τις ζωές εκατομμυρίων, και ανεξέλεγκτες πυρκαγιές αποδεκατίζουν τα δάση – τους πνεύμονες της γης. Σε αυτή την πλανητική ασφυξία, εξετάζουμε αυτό που δεν αναπνέει αλλά παραμένει έμβιο – τον ιό.
Τεχνητά Συστήματα Εικαστικής Παραγωγής: Συναρμογή, Αυτονομία και Δημιουργικότητα
Authors: Σοφοκλέους Στέλλα
Published: November 2021

Τις τελευταίες δεκαετίες, στο πεδίο της θεωρίας της τέχνης, γίνεται προσπάθειααφομοίωσης και χαρτογράφησης μιας αναδυόμενης τάσης καλλιτεχνικής παραγωγής, η οποία σχετίζεται με την ικανότητα τεχνητών συστημάτων και αλγορίθμων να δημιουργούν έργα τέχνης με μια σχετική αυτονομία. Στην προοπτική ύπαρξης εξ ολοκλήρου αυτόνομων συστημάτων καλλιτεχνικής δημιουργίας στο εγγύς μέλλον, η παρούσα εργασία επιχειρεί να θέσει υπό αμφισβήτηση την εξήγηση της τεχνητής δημιουργικότητας της παραγωγικής τέχνης (generative art) μέσω του ανθρωποκεντρικού παραδείγματος. Μέσω της παρατήρησης μεταμοντέρνων και σύγχρονων εικαστικών projects, η ανάλυση φανερώνει πως η φύση της αλληλεπίδρασης των καλλιτεχνών/προγραμματιστών με τα τεχνητά συστήματα εικαστικής παραγωγής, οδηγεί σε μια γόνιμη κατανόηση έμβιων και άβιων δημιουργικών δρώντων στο πλαίσιο μιας συναρμογής (assemblage), με στόχο την από κοινού εξερεύνηση νέων δυνατοτήτων καλλιτεχνικής δημιουργίας. Το δεύτερο μέρος, διερευνά κατά πόσο η ακαμψία που χαρακτηρίζει του αλγόριθμους μετριάζεται μέσω της ανάδειξης των λιγότερο γνωστών πτυχών της συμπεριφοράς τους και εάν οι πτυχές αυτές δύνανται να αποτελέσουν δίοδο προς την οντολογική εξερεύνηση της τεχνητής δημιουργικότητας. Υπό ένα μεθοδολογικό πρίσμα, η συζήτηση καταδεικνύει την ανάγκη συγκρότησης ενός θεωρητικού πλαισίου το οποίο θα απομακρύνει την εν λόγω τάση από την τεχνολογική μεθόριο στην οποία βρισκόταν καθηλωμένη για χρόνια και θα επιτρέψει την ένταξή της στην εξελικτική αλυσίδα του τεχνοϊστορικού αφηγήματος.