bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial colonization of the upper airways of children positive and negative for SARS-CoV-2 during the COVID-19 pandemic
Authors: Ciptaningtyas Vincentia Rizke , Hapsari Rebriarina , Lestari Endang Sri , Farida Helmia , de Mast Quirijn , de Jonge Marinus Isaäk
Published: November 2022

Background

Our understanding of the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bacterial colonization in the children’s upper nasopharyngeal tract during the coronavirus infectious disease (COVID-19) pandemic is limited. This study aimed to determine whether there were any differences in bacterial colonization between asymptomatic children with or without a positive SARS-CoV-2 quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) results in the community setting.

Methods

A cross-sectional community-based exploratory study was conducted from March to May 2021 in Semarang, Central Java Province, Indonesia. Using stored nasopharyngeal swabs collected from children under 18 years as a contact tracing program, we performed a real-time quantitative (qPCR) for the most important bacterial colonizing pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Klebsiella pneumoniae.

Results

Swabs from a total of 440 children were included in this study, of which 228 (51.8%) were RT-qPCR-confirmed SARS-CoV-2 positive. In the 440 children, colonization rates were highest for H. influenzae (61.4%), followed by S. pneumoniae (17.5%), S. aureus (12.0%), and K. pneumoniae (1.8%). The co-occurrence of both S. pneumoniae and H. influenzae in the upper respiratory tract was significantly associated with a SARS-CoV-2 negative RT-qPCR. In contrast, colonization with only S. aureus was more common in SARS-CoV-2-positive children.

Conclusion

Overall, this exploratory study concludes that there is a significant difference in the bacterial nasopharyngeal colonization pattern between SARS-CoV-2 positive and negative in asymptomatic children in the community in Indonesia.
The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review
Authors: Sano Yasuko , Kasai Michi , Shinoda Satoru , Miyagi Etsuko , Aoki Shigeru
Published: November 2022

Background

Placental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases.

Methods

We used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups–blood transfusion and non-transfusion–to compare the maternal characteristics and pregnancy outcomes.

Results

In patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group.

Conclusions

In PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.
The prognostic role of tumor mutation burden on survival of breast cancer: a systematic review and meta-analysis
Authors: Ke Liyuan , Li Su , Cui Hongxia
Published: November 2022

Background

As a potential genetic biomarker, tumor mutation burden (TMB) has made progress in numerous tumors. There are limited data regarding TMB and its prognostic role is controversial in breast cancer. This systematic review and meta-analysis were conducted to assess the prognostic value of TMB on survival of breast cancer.

Methods

The databases PubMed, Embase, Web of Science, and Cochrane Library were searched for articles published through May 31, 2022. Moreover, effective data were extracted from included studies and calculated pooled effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) by STATA 16.0. Heterogeneity was conducted by the I2 statistic and p-value. Using publication bias evaluation, sensitivity analysis, and subgroup analysis, the origin of heterogeneity was further investigated.

Results

They were up to 1,722 patients collected from sixteen cohorts for this analysis. The pooled effects of HR for both OS (HR: 1.14, 95% CI: 0.83,1.58, p > 0.01) and PFS (HR: 0.96, 95% CI: 0.53,1.71, p > 0.01) indicated no statistically significant difference in the high TMB and low TMB group. In immune checkpoint inhibitors (ICIs) subgroup, high TMB patients demonstrated benefit of OS (HR: 0.72, 95% CI: 0.59,0.87, p = 0.001) and PFS (HR: 0.52, 95% CI: 0.35,0.77, p < 0.001), whereas difference was not statistically significant in the non-ICIs subgroup (OS, HR:1.76, 95% CI: 0.97,3.20, p = 0.062; PFS, HR:2.31, 95% CI: 0.89,5.97, p = 0.086). In addition, sensitivity analysis revealed that the pooled effects were stable. The funnel plot and Begg's test suggested the absence of publication bias.

Conclusion

Meta-analysis revealed that the prognostic relevance of TMB in breast cancer is limited in scope. High TMB may be associated with longer survival only in ICIs-based treatment, but the association is not evident in non-ICIs-based treatment.

Trial registration

[https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42022342488.
Retinochoroidal microvascular changes in newly developed obese children: an optical coherence tomography angiography study
Authors: Han Shu , Leng Zhenhua , Li Xiaoxiao , Yan Wen , Shen Shiya , Liu Lei , Zhu Hui , Huang Dan , Liu Hu
Published: November 2022

Background

Childhood obesity was associated with retinochoroidal microvascular changes using optical coherence tomography angiography (OCTA), but obesity duration was neglected. Obesity is chronic and progressive and obesity duration is related to microvascular function. Thus, it is important to identify microvascular changes in obese children timely to allow possible interventions with the increase in the number of obese children. This pilot study aimed to characterize retinochoroidal microvascular changes in newly developed obese children compared to age- and sex-matched controls.

Methods

Forty newly developed obese children and 40 age- and sex-matched controls were recruited. All subjects completed comprehensive eye examinations, including axial length, cycloplegic refraction, optical coherence tomography angiography scans (AngioVue; Optovue Inc), etc.

Results

There were no statistically significant differences between groups in terms of month age (P = 0.927), spherical equivalent refraction (P = 0.753) and axial length (P = 0.196). Newly developed obese children had lower vessel density (VD) in the inferior parafovea (P = 0.026), nasal parafovea (P = 0.038) and temporal perifovea (P = 0.026) of deep vascular complex (DVC), higher VD in the fovea of superficial vascular complex (P = 0.021) and the fovea of DVC (P = 0.016), and smaller foveal avascular zone (P = 0.003) when compared to controls. Also, no apparent differences in any quadrant of total retinal thickness, subfoveal choroidal thickness (SFCT), and choriocapillaries fow voids were detected (all P > 0.05).

Conclusion

Retinochoroidal microvascular changes had already occurred in newly developed obese children, so early screening and close follow-up eye examinations were recommended; Retinal microvascular insult may precede its structural change and that retina may be a better candidate to predict the onset of retinochoroidal microvascular changes than choroid in obese children.
Growth and Nutritional Status of Phenylketonuric Children and Adolescents
Authors: Ahmadzadeh Mina , Sohrab Golbon , Alaei Mohammadreza , Eini-Zinab Hassan , mohammadpour-Ahranjani Behzad , Rastgoo Samira , Namkhah Zahra
Published: November 2022

Background

The goal of this study was to assess the anthropometric and biochemical parameters of children and adolescents with phenylketonuria (PKU).

Methods

The participants in this cross-sectional study ranged in age from four to 18 years old. Biochemical markers such as vitamin B12, folic acid, iron, ferritin, calcium, 25-hydroxy vitamin D3, zinc, plasma phenylalanine (Phe) and tyrosine (Tyr) levels in blood were evaluated, as well as demographics and anthropometric measurements. A three-day dietary recall questionnaire was completed by all individuals.

Results

80% (64) of the 80 patients (42 females, 52.5%) had typical PKU. Consanguineous marriages were found in 57.5% (46) of the patients’ parents. According to the height for age index, 17.5% of the study group (n = 14) were short or very short. According to age-related weight and body mass index (BMI), 37.5% (n = 30) and 43.8% (n = 35) of people are obese or overweight, respectively. Biochemical tests revealed increased vitamin B12 levels and 25-hydroxy vitamin D3 deficiency in 35% (n = 28) of the patients, insufficient folic acid in 12.5% (n = 10), and elevated phenylalanine levels in 70.3% (n = 45) of children under 12 years old, and adolescents 62.5% (n = 10). A high Phe intake (OR = 4.44, CI %95 = 1.27–15.57) is a risk factor for obesity and overweight.

Conclusion

Patients with PKU had a high rate of overweight and obesity. PKU patients who are overweight or obese do not differ from normal-weight patients in terms of dietary intake or laboratory findings (except for serum iron levels). One-third of patients with phenylketonuria were vitamin D deficient and had a BMI/A index of overweight/obese. It is recommended to use special medical food to help solve energy and nutrient deficiencies.
Mothers’ knowledge and self-reported performance regarding the management of traumatic dental injuries and associated factors: a cross-sectional study
Authors: Momeni Zahra , Afzalsoltani Sanaz , Moslemzadehasl Mahmoudreza
Published: November 2022

Background

Dental trauma is common among children. It has negative effects on a child’s quality of life. Parental knowledge, especially among mothers is an important factor for the long-term success of this emergency. This study aimed to investigate mothers’ knowledge and self-reported performance regarding the management of traumatic dental injuries and associated socio-demographic factors.

Methods

In this cross-sectional study, 277 mothers of children (8–12 years) attending the pediatrics department of Alborz dental school were studied by convenience sampling. The participants completed a valid reliable questionnaire about the management of traumatic dental injuries. The predictor variables were the child’s gender, maternal education and employment status, economic status, and accommodation status. The outcome variables were the mothers’ knowledge about the management of traumatic dental injuries (Eight statements with 10 scores) and self-reported performance including four case scenarios of traumatic dental injury (Five questions with 7 scores). Data were analyzed by T-test or One-way ANOVA to test the within-group changes, Pearson’s correlation coefficient and Linear multiple regression to examine the effect of predictor variables on maternal knowledge and self-reported performance.

Results

The mean score of mothers’ knowledge was 3.43; SD = 1.58 (total score ranged from 0 to 10). The mean score of mothers’ performance was 3.38; SD = 1.2 (total score ranged from 0 to 7). Mothers who work (p < 0.001) and mothers with high qualifications (p < 0.001) had higher knowledge. Furthermore, mothers who work (p = 0.011), mothers with high qualifications (p < 0.001), and those who have had previous experience with traumatic dental injuries (p < 0.001) had higher self-reported performance. The results of multiple linear regression analysis demonstrated the association between mothers’ knowledge with mothers’ education (β = 0.22,p = 0.001) and mothers’ employment status (β = 0.15,p = 0.017), while there is a relationship between mothers’ self-reported performance and mothers’ education (β = 0.27,p < 0.001).

Conclusion

Since the means of mothers’ knowledge and performance scores regarding dental trauma management, were less than half of the obtainable scores as well as mothers have a crucial role in the children’s oral health, it is important to increase the mothers’ knowledge and improve their performance in this context. Therefore, running educational programs is necessary for this respect.
Model-informed COVID-19 exit strategy with projections of SARS-CoV-2 infections generated by variants in the Republic of Korea
Authors: Jung Sung-mok , Huh Kyungmin , Radnaabaatar Munkhzul , Jung Jaehun
Published: November 2022

Background

With the prompt administration of coronavirus disease 2019 (COVID-19) vaccines, highly vaccinated countries have begun to lift their stringent control measures. However, considering the spread of highly transmissible new variants, resuming socio-economic activities may lead to the resurgence of incidence, particularly in nations with a low proportion of individuals who have natural immunity. Here, we aimed to quantitatively assess an optimal COVID-19 exit strategy in the Republic of Korea, where only a small number of cumulative incidences have been recorded as of September 2021, comparing epidemiological outcomes via scenario analysis.

Methods

A discrete-time deterministic compartmental model structured by age group was used, accounting for the variant-specific transmission dynamics and the currently planned nationwide vaccination. All parameters were calibrated using comprehensive empirical data obtained from the Korea Disease Control and Prevention Agency.

Results

Our projection suggests that tapering the level of social distancing countermeasures to the minimum level from November 2021 can efficiently suppress a resurgence of incidence given the currently planned nationwide vaccine roll-out. In addition, considering the spread of the Delta variant, our model suggested that gradual easing of countermeasures for more than 4 months can efficiently withstand the prevalence of severe COVID-19 cases until the end of 2022.

Conclusions

Our model-based projections provide evidence-based guidance for an exit strategy that allows society to resume normal life while sustaining the suppression of the COVID-19 epidemic in countries where the spread of COVID-19 has been well controlled.
Application of online teaching mode combining case studies and the MOOC platform in obstetrics and gynecology probation teaching
Authors: Li Yi , Yang Chunfen , Liao Wenyan , Yang Shuangjian , Tong Wenjuan , Li Li , Lan Hui , Yang Dong
Published: November 2022

Objective

To explore the application effect of the clinical basic integration teaching mode constructed by case studies and the MOOC platform in obstetrics and gynecology internship teaching in the face of public health emergencies.

Methods

One hundred ten clinical medical students of grade 2020 were selected as the experimental group, and 110 clinical medical students of grade 2021 were selected as the control group. The experimental group adopted the online teaching mode combined with case studies and the MOOC platform, while the control group adopted the offline traditional probation teaching method. Comprehensive test and questionnaire were used to evaluate and compare the teaching effect of the two groups of students.

Results

The experimental group was found to be superior to the control group in the quality assessment of complete medical record writing and the ability assessment of diagnosis and analysis of typical obstetrics and gynecology cases (P < 0. 05). However, the score of professional knowledge was lower than that of the control group (P < 0. 05). The results of questionnaire survey showed that the satisfaction of the experimental group in stimulating learning interest, enhancing problem solving ability, enhancing communication and clinical thinking ability, enhancing team cooperation awareness and independent innovation ability was higher than that of the control group (P < 0.01). The satisfaction of teacher-student interaction was also better (P < 0.05). However, in terms of strengthening theoretical understanding, the satisfaction of the experimental group was lower than that of the control group, but with no significant difference (P > 0.05).

Conclusion

During the epidemic period, we designed a new online teaching mode, which can be applied to the probation teaching of obstetrics and gynecology. In our study, compared with traditional offline teaching, the new online teaching mode could improve students’ ability of case writing and case analysis. However, more teaching practice is needed to complete this online teaching mode.
Microglia dynamics in aging-related neurobehavioral and neuroinflammatory diseases
Authors: Javanmehr Nima , Saleki Kiarash , Alijanizadeh Parsa , Rezaei Nima
Published: November 2022

Microglia represent the first line of immune feedback in the brain. Beyond immune surveillance, they are essential for maintaining brain homeostasis. Recent research has revealed the microglial cells' spatiotemporal heterogeneity based on their local and time-based functions in brain trauma or disease when homeostasis is disrupted. Distinct "microglial signatures" have been recorded in physiological states and brain injuries, with discrete or sometimes overlapping pro- and anti-inflammatory functions. Microglia are involved in the neurological repair processes, such as neurovascular unit restoration and synaptic plasticity, and manage the extent of the damage due to their phenotype switching. The versatility of cellular phenotypes beyond the classical M1/M2 classification, as well as the double-edge actions of microglia in neurodegeneration, indicate the need for further exploration of microglial cell dynamics and their contribution to neurodegenerative processes. This review discusses the homeostatic functions of different microglial subsets focusing on neuropathological conditions. Also, we address the feasibility of targeting microglia as a therapeutic strategy in neurodegenerative diseases.
Re-evaluating our language when reducing risk of SARS-CoV-2 transmission to healthcare workers: Time to rethink the term, “aerosol-generating procedures”
Authors: Silvers Andrew , Brewster David J. , Ford Alister , Licina Ana , Andrews Cassandra , Adams Mark
Published: November 2022

The term, "aerosol-generating procedures” (AGPs), was proposed during the prior SARS-CoV-1 epidemic in order to maximise healthcare worker and patient protection. The concept of AGPs has since expanded to include routine therapeutic processes such as various modes of oxygen delivery and non-invasive ventilation modalities. Evidence gained during the SARS-CoV-2 pandemic has brought into question the concept of AGPs with regard to intubation, airway management, non-invasive ventilation and high flow nasal oxygen delivery. Although encounters where these procedures occur may still be associated with increased risk of infectious transmission, this is a function of the clinical context and not because the procedure itself is aerosol-generating.
Artificial intelligence-informed mobile mental health apps for young people: a mixed-methods approach on users’ and stakeholders’ perspectives
Authors: Götzl Christian , Hiller Selina , Rauschenberg Christian , Schick Anita , Fechtelpeter Janik , Fischer Abaigar Unai , Koppe Georgia , Durstewitz Daniel , Reininghaus Ulrich , Krumm Silvia
Published: November 2022

Background

Novel approaches in mobile mental health (mHealth) apps that make use of Artificial Intelligence (AI), Ecological Momentary Assessments, and Ecological Momentary Interventions have the potential to support young people in the achievement of mental health and wellbeing goals. However, little is known on the perspectives of young people and mental health experts on this rapidly advancing technology. This study aims to investigate the subjective needs, attitudes, and preferences of key stakeholders towards an AI–informed mHealth app, including young people and experts on mHealth promotion and prevention in youth.

Methods

We used a convergent parallel mixed–method study design. Two semi–structured online focus groups (n = 8) and expert interviews (n = 5) to explore users and stakeholders perspectives were conducted. Furthermore a representative online survey was completed by young people (n = 666) to investigate attitudes, current use and preferences towards apps for mental health promotion and prevention.

Results

Survey results show that more than two-thirds of young people have experience with mHealth apps, and 60% make regular use of 1–2 apps. A minority (17%) reported to feel negative about the application of AI in general, and 19% were negative about the embedding of AI in mHealth apps. This is in line with qualitative findings, where young people displayed rather positive attitudes towards AI and its integration into mHealth apps. Participants reported pragmatic attitudes towards data sharing and safety practices, implying openness to share data if it adds value for users and if the data request is not too intimate, however demanded transparency of data usage and control over personalization. Experts perceived AI-informed mHealth apps as a complementary solution to on–site delivered interventions in future health promotion among young people. Experts emphasized opportunities in regard with low-threshold access through the use of smartphones, and the chance to reach young people in risk situations.

Conclusions

The findings of this exploratory study highlight the importance of further participatory development of training components prior to implementation of a digital mHealth training in routine practice of mental health promotion and prevention. Our results may help to guide developments based on stakeholders’ first recommendations for an AI-informed mHealth app.
Increased CO2 levels in the operating room correlate with the number of healthcare workers present: an imperative for intentional crowd control
Authors: Carroll Gregory T. , Kirschman David L. , Mammana Angela
Published: November 2022

The air in an operating room becomes more contaminated as the occupancy of the room increases. Individuals residing in a room can potentially emit infectious agents. In order to inhibit and better understand the epidemiology of surgical site infections, it is important to develop procedures to track room occupancy level and respiration. Exhaled CO2 provides a respiratory byproduct that can be tracked with IR light and is associated with human occupancy. Exhaled CO2 can also be used as an indirect measure of the potential release and level of infectious airborne agents. We show that non-dispersive infrared CO2 sensors can be used to detect CO2 in operating room air flow conditions of 20 air changes per hour and a positive pressure of 0.03 in. H2O. The CO2 concentration increased consecutively for occupation levels of one to four individuals, from approximately 65 ppm above the background level when one individual occupied the operating room for twenty minutes to approximately 300 ppm above the background when four individuals were present for twenty minutes. The amount of CO2 detected increases as the number of occupants increase, the activity level increases, the residency time increases and when the ventilation level is reduced.
Human and vector behaviors determine exposure to Anopheles in Namibia
Authors: Mwema Tabeth , Lukubwe Ophilia , Joseph Rosalia , Maliti Deodatus , Iitula Iitula , Katokele Stark , Uusiku Petrina , Walusimbi Dennis , Ogoma Sheila Barasa , Tambo Munya , Gueye Cara Smith , Williams Yasmin A. , Vajda Elodie , Tatarsky Allison , Eiseb Seth J. , Mumbengegwi Davis R. , Lobo Neil F.
Published: November 2022

Background

Although the Republic of Namibia has significantly reduced malaria transmission, regular outbreaks and persistent transmission impede progress towards elimination. Towards an understanding of the protective efficacy, as well as gaps in protection, associated with long-lasting insecticidal nets (LLINs), human and Anopheles behaviors were evaluated in parallel in three malaria endemic regions, Kavango East, Ohangwena and Zambezi, using the Entomological Surveillance Planning Tool to answer the question: where and when are humans being exposed to bites of Anopheles mosquitoes?

Methods

Surveillance activities were conducted during the malaria transmission season in March 2018 for eight consecutive nights. Four sentinel structures per site were selected, and human landing catches and human behavior observations were consented to for a total of 32 collection nights per site. The selected structures were representative of local constructions (with respect to building materials and size) and were at least 100 m from each other. For each house where human landing catches were undertaken, a two-person team collected mosquitoes from 1800 to 0600 hours.

Results

Surveillance revealed the presence of the primary vectors Anopheles arabiensis, Anopheles gambiae sensu stricto (s.s.) and Anopheles funestus s.s., along with secondary vectors (Anopheles coustani sensu lato and Anopheles squamosus), with both indoor and outdoor biting behaviors based on the site. Site-specific human behaviors considerably increased human exposure to vector biting. The interaction between local human behaviors (spatial and temporal presence alongside LLIN use) and vector behaviors (spatial and temporal host seeking), and also species composition, dictated where and when exposure to infectious bites occurred, and showed that exposure was primarily indoors in Kavango East (78.6%) and outdoors in Ohangwena (66.7%) and Zambezi (81.4%). Human behavior-adjusted exposure was significantly different from raw vector biting rate.

Conclusions

Increased LLIN use may significantly increase protection and reduce exposure to malaria, but may not be enough to eliminate the disease, as gaps in protection will remain both indoors (when people are awake and not using LLINs) and outdoors. Alternative interventions are required to address these exposure gaps. Focused and question-based operational entomological surveillance together with human behavioral observations may considerably improve our understanding of transmission dynamics as well as intervention efficacy and gaps in protection.

Graphical Abstract
Accrual of organ damage in Behçet’s syndrome: trajectory, associated factors, and impact on patients’ quality of life over a 2-year prospective follow-up study
Authors: Floris Alberto , Piga Matteo , Laconi Riccardo , Espinosa Gerard , Lopalco Giuseppe , Serpa Pinto Luisa , Kougkas Nikolaos , Sota Jurgen , Lo Monaco Andrea , Govoni Marcello , Cantarini Luca , Bertsias George , Correia João , Iannone Florenzo , Cervera Ricard , Vasconcelos Carlos , Mathieu Alessandro , Cauli Alberto
Published: November 2022

Background

This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up.

Methods

Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains.

Results

During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p <0.001). The incidence rate of damage accrual was stable over time, regardless of the disease duration. Out of 61 new BODI items, 25 (41.0%) were considered related to glucocorticoid (GC) use. In multivariate analysis, duration of GC therapy (OR per 1-year 1.15, 95% CI 1.07–1.23; p <0.001) and occurrence of ≥1 disease relapse (OR 3.15, 95% CI 1.09–9.12; p 0.038) were identified as predictors of damage accrual, whereas the use of immunosuppressants showed a protective effect (OR 0.20, 95% CI 0.08–0.54, p<0.001). Damage accrual was independently associated with the impairment of different physical domains and, to a greater extent, in emotional domains of the SF-36 questionnaire. Female sex, higher disease activity, and fibromyalgia were also significantly associated with impairment in HR-QoL.

Conclusion

In BS, organ damage accrues over time, also in long-standing disease, resulting in an impairment of the perceived physical and mental health. Adequate immunosuppressive treatment, preventing disease flares and minimizing exposure to GCs have a crucial role in lowering the risk of damage accrual.
Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?
Authors: Wang Yi-Feng , Liang Feng-Ming , Liu Min , Ding Li-Cheng , Hui Jiao-Jie , Xu Hong-Yang , Liu Li-Jun
Published: November 2022

Background

Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia.

Methods

This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups.

Results

A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group.

Conclusions

Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia.
Recent progress in epigenetics of obesity
Authors: Wu Feng-Yao , Yin Rui-Xing
Published: November 2022

Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.
Effects of fetal famine exposure on the cardiovascular disease risk in the metabolic syndrome individuals
Authors: Shu Zhe , Ding Xiong , Yue Qing , Ma XiaoXu , Liu MinHong , Wu YunTao , Yang Peng , Wu Ying , Li Yun , Wu Shouling
Published: November 2022

Background

Patients with metabolic syndrome (MS) have a higher incidence of cardiovascular disease (CVD), but the possible mechanisms are not fully understood and further exploration of the possible factors influencing the high incidence of CVD in patients with MS is still needed.

Objectives

This study aims to examine the association between fetal famine exposure and the risk of CVD in adulthood with MS.

Methods

Of 13,744 MS patients free of CVD selected from the Kailuan Study in 2006 (referred as the baseline survey) were included in the study. China suffered a severe famine from 1959 to 1962, so the participants born during this period were classified as the uterine famine exposed group. All patients were born between January 1, 1949, and December 31, 1974. Based on the date of birth, all patients were divided into the no-exposed group (born between January 1, 1963, and December 31, 1974), uterine famine exposed group (born between January 1, 1959 and December 31, 1962), and childhood famine exposed group (born between January 1, 1949 and December 31, 1958). After following up to December 31, 2019, the weighted Cox regression analysis model was used to calculate the effect of early life famine exposure in MS individuals on the risk of CVD in adulthood.

Results

During the 12.12 years of follow-up, the incidence of CVD was 5.87%, 10.13%, and 10.90% in the no-exposed group, uterine famine exposed group, and childhood famine exposed group, respectively. Compared with participants in the no-exposed group, the CVD risk and stroke risk increased in participants in the uterine famine exposed group (for CVD, HR: 1.32, 95% CI 1.04–1.67; for stroke, HR:1.37, 95% CI 1.05–1.79), but not in childhood famine exposed group. However, the increased CVD risks were only observed in females or smokers. No increased MI risks were observed for participants in the uterine famine exposed group or childhood famine exposed group.

Conclusions

Our findings suggested that exposure to famine during uterine life might increase the risk of CVD in adulthood in participants with MS.
The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial
Authors: Gohari Sepehr , Reshadmanesh Tara , Khodabandehloo Hadi , Karbalaee-Hasani Amir , Ahangar Hassan , Arsang-Jang Shahram , Ismail-Beigi Faramarz , Dadashi Mohsen , Ghanbari Samin , Taheri Homa , Fathi Mojtaba , Muhammadi Muhammad Javad , Mahmoodian Reyhaneh , Asgari Atieh , Tayaranian Mohammadreza , Moharrami Mehdi , Mahjani Mahsa , Ghobadian Bijan , Chiti Hossein , Gohari Sheida
Published: November 2022

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): − 1.06 pg/mL, 95% CI − 1.80; − 0.32, P = 0.006), interleukin 1β (IL-1β) and high-sensitive C-reactive protein (Hs-CRP) (adiff: − 4.58 pg/mL and − 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: − 342.51, 95% CI − 474.23; − 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: − 8.81, 95% CI − 14.87; − 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA1c, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.

Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective
DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets
Authors: Cai Chunyang , Meng Chunren , He Shuai , Gu Chufeng , Lhamo Thashi , Draga Deji , Luo Dawei , Qiu Qinghua
Published: November 2022

Background

Diabetic retinopathy (DR), a specific neuron-vascular complication of diabetes, is a major cause of vision loss among middle-aged people worldwide, and the number of DR patients will increase with the increasing incidence of diabetes. At present, it is limited in difficult detection in the early stages, limited treatment and unsatisfactory treatment effects in the advanced stages.

Main body

The pathogenesis of DR is complicated and involves epigenetic modifications, oxidative stress, inflammation and neovascularization. These factors influence each other and jointly promote the development of DR. DNA methylation is the most studied epigenetic modification, which has been a key role in the regulation of gene expression and the occurrence and development of DR. Thus, this review investigates the relationship between DNA methylation and other complex pathological processes in the development of DR. From the perspective of DNA methylation, this review provides basic insights into potential biomarkers for diagnosis, preventable risk factors, and novel targets for treatment.

Conclusion

DNA methylation plays an indispensable role in DR and may serve as a prospective biomarker of this blinding disease in its relatively early stages. In combination with inhibitors of DNA methyltransferases can be a potential approach to delay or even prevent patients from getting advanced stages of DR.
A systematic review and meta-analysis assessing antiretroviral therapy for treatment-experienced HIV adult patients using an optimized background therapy approach: is there evidence enough for a standardized third-line strategy?
Authors: Mocellin Lucas Pitrez , Ziegelmann Patricia Klarmann , Kuchenbecker Ricardo
Published: November 2022

Background

The World Health Organization (WHO) has identified the need for evidence on third-line antiretroviral therapy (ART) for adults living with HIV/AIDS, given that some controversy remains as to the best combinations of ART for experienced HIV-1-infected patients. Therefore, we conducted a systematic review and meta-analysis to (i) assess the efficacy of third-line therapy for adults with HIV/AIDS based on randomized controlled trials (RCT) that adopted the “new antiretroviral (ARV) + optimized background therapy (OBT)” approach and (ii) address the key issues identified in WHO’s guidelines on the use of third-line therapy.

Methods

MEDLINE, EMBASE, LILACS, ISI Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for RCTs assessing third-line ARV therapy that used an OBT approach between 1966 and 2015. Data was extracted using an Excel-structured datasheet based on the Consolidated Standards of Reporting Trials (CONSORT) recommendations. The primary outcome of this meta-analysis was the proportion of patients reaching undetectable HIV RNA levels (< 50 copies/mL) at 48 weeks of follow-up. Included studies were evaluated using the Cochrane’s Risk of Bias assessment tool. Summarized evidence was rated according to the GRADE approach.

Results

Eighteen trials assessing 9 new ARV + OBT combinations defined as third-line HIV therapy provided the efficacy data: 7 phase IIb trials and 11 phase III trials. Four of the 18 trials provided extension data, thus resulting in 14 trials providing 48-week efficacy data. In the meta-analysis, considering the outcome regarding the proportion of patients with a viral load below 50 copies/ml at 48 weeks, 9 out of 14 trials demonstrated the superiority of the new combination being studied (risk difference = 0.18, 95% CI 0.13–0.23). The same analysis stratified by the number of fully active ARVs demonstrated a risk difference of 0.29 (95% CI 0.12–0.46), 0.28 (95% CI 0.17–0.38) and 0.17 (95% CI 0.10–0.24) respectively from zero, one, and two or more active drugs strata. Nine of the 18 trials were considered to have a high risk of bias.

Conclusions

Efficacy results demonstrated that the groups of HIV-experienced patients receiving the new ARV + OBT were more likely to achieve viral suppression when compared to the control groups. However, most of these trials may be at a high risk of bias. Thus, there is still not enough evidence to stipulate which combinations are the most effective for therapeutic regimens that are to be used sequentially due to documented multi-resistance.
Prevalence of hypertension and associated risks in hospitalized patients with COVID-19: a meta-analysis of meta-analyses with 1468 studies and 1,281,510 patients
Authors: Khairy Yousof , Naghibi Deniz , Moosavi Ahmad , Sardareh Mehran , Azami-Aghdash Saber
Published: November 2022

Background

Since the COVID-19 outbreak, preliminary research has shown that some risk-associated conditions increase death and severe complications of the disease, hypertension being one of them. Thus, numerous meta-analyses have been conducted to explore this issue. Therefore, this umbrella review aims to perform a meta-analysis of the meta-analyses to estimate the prevalence and associated risks of hypertension in patients with COVID-19.

Methods

PubMed, Scopus, Web of Knowledge, Embase, and Cochrane databases were searched for the published meta-analyses up to January 1, 2022. Google Scholar, citation check, reference check, and Grey literature were also manually searched. A random-effect model approach was used for analysis.

Results

The overall death rate was estimated at 12%. Hypertension was present in 25% of the patients as a comorbid disease. The overall RR for death, disease severity, and the possibility of ICU admission were estimated at 1.79 [1.68–1.89 with 95% CI], 1.74 [1.66–1.83 with 95% CI], and 1.91 [1.48–2.34 with 95% CI], respectively. The meta-regression results showed that being “male” significantly increases the risk of disease severity and ICU admission.

Conclusions

The results indicated that hypertension is a common comorbid disease in hospitalized patients with COVID-19, which significantly increases mortality risk, the severity of the disease, and the probability of ICU admission.

Systematic review registration

This study has been registered in PROSPERO (CRD42021231844).
The method for solving the extension of general of the split feasibility problem and fixed point problem of the cutter
Authors: Saechou Kanyanee , Kangtunyakarn Atid
Published: November 2022

This paper first introduces a new iterative method for weak and strong convergence theorem to demonstrate the estimation potential for a fixed point of the cutter and the finite general split feasibility problem. Consequently, the set of fixed points of a quasi-nonexpansive mapping and the finite general split feasibility problem, the constrained minimization problem, and the general constrained minimization problems are proved using our main results. Finally, we give two numerical examples to advocate our main results.