bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnitude and associated factors of acute kidney injury among preterm neonates admitted to public hospitals in Bahir Dar city, Ethiopia 2022: cross-sectional study
Authors: Mehari Sayih , Muluken Silenat , Getie Asmare , Belachew Amare
Published: June 2023

Background

Acute kidney injury is an independent risk factor for morbidity and mortality in critically ill neonates. Although the magnitude of preterm neonates is high and a major risk for acute kidney injury, there is a paucity of information regarding the magnitude and associated factors of acute kidney injury among preterm neonates in the study area. Therefore, the aim of this study was to assess magnitude and associated factors of acute kidney injury among preterm neonates admitted to public hospitals in Bahir Dar city, Ethiopia, 2022.

Methods

An institutional-based cross-sectional study was conducted among 423 preterm neonates admitted to public hospitals in Bahir Dar city from May 27 to June 27, 2022. Data were entered into Epi Data Version 4.6.0.2 transferred to Statistical Package and Service Solution version 26 for analysis. Descriptive and inferential statistics were employed. A binary logistic regression analysis was done to identify factors associated with acute kidney injury. Model fitness was checked through Hosmer-Lemeshow goodness of fit test. Variables with a p-value < 0.05 were considered as statistically significant in the multiple binary logistic regression analysis.

Result

Out of 423 eligible, 416 neonatal charts were reviewed with a response rate of 98.3%.This study revealed that the magnitude of acute kidney injury was 18.27% (95% CI = 15–22). Very low birth weight (AOR = 3.26; 95% CI = 1.18–9.05), perinatal asphyxia (AOR = 2.84; 95%CI = 1.55–5.19), dehydration (AOR = 2.30; 95%CI = 1.29–4.09), chest compression (AOR = 3.79; 95%CI = 1.97–7.13), and pregnancy-induced hypertension (AOR = 2.17; 95%CI = 1.20–3.93) were factors significantly associated with the development of neonatal acute kidney injury.

Conclusion

Almost one in five admitted preterm neonates developed acute kidney injury. The odds of acute kidney injury were high among neonates who were very low birth weight, perinataly asphyxiated, dehydrated, recipients of chest compression, and born to pregnancy-induced hypertensive mothers. Therefore, clinicians have to be extremely cautious and actively monitor renal function in those neonatal population in order to detect and treat acute kidney injury as early as possible.
Children born preterm admitted to paediatric intensive care for bronchiolitis: a systematic review and meta-analysis
Authors: van Hasselt Tim J. , Webster Kirstin , Gale Chris , Draper Elizabeth S. , Seaton Sarah E.
Published: June 2023

Background

To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus (RSV) and/or bronchiolitis who were born preterm, and compare their outcomes in PICU with children born at term.

Methods

We searched Medline, Embase and Scopus. Citations and references of included articles were searched. We included studies published from the year 2000 onwards, from high-income countries, that examined children 0–18 years of age, admitted to PICU from the year 2000 onwards for RSV and/or bronchiolitis.

The primary outcome was the percentage of PICU admissions born preterm, and secondary outcomes were observed relative risks of invasive mechanical ventilation and mortality within PICU.

We used the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies to assess risk of bias.

Results

We included 31 studies, from 16 countries, including a total of 18,331 children.

Following meta-analysis, the pooled estimate for percentage of PICU admissions for RSV/bronchiolitis who were born preterm was 31% (95% confidence interval: 27% to 35%). Children born preterm had a greater risk of requiring invasive ventilation compared to children born at term (relative risk 1.57, 95% confidence interval 1.25 to 1.97, I2 = 38%). However, we did not observe a significant increase in the relative risk for mortality within PICU for preterm-born children (relative risk 1.10, 95% confidence interval: 0.70 to 1.72, I2 = 0%), although the mortality rate was low across both groups.

The majority of studies (n = 26, 84%) were at high risk of bias.

Conclusions

Among PICU admissions for bronchiolitis, preterm-born children are over-represented compared with the preterm birth rate (preterm birth rate 4.4% to 14.4% across countries included in review). Preterm-born children are at higher risk of mechanical ventilation compared to those born at term.
Physical Literacy for Communities (PL4C): physical literacy, physical activity and associations with wellbeing
Authors: Tang Yiling , Algurén Beatrix , Pelletier Chelsea , Naylor Patti-Jean , Faulkner Guy
Published: June 2023

Background

Physical literacy (PL) is considered an important determinant of children's physical activity through which health benefits may be derived. The purpose of this study is to describe a sample of Canadian children’s baseline levels of PL and movement behaviors, and explore whether the associations between PL and their mental wellbeing, if any, are mediated by moderate-to-vigorous physical activity (MVPA).

Methods

All grade two children in 14 elementary schools in the West Vancouver School District, Canada were invited to participate in a two-year longitudinal project. PL was assessed through PLAYfun and PLAYself tools. Physical activity was measured by wrist-worn accelerometers (GT3X + BT) for seven days. Children's mental well-being was assessed using the Strengths and Difficulties Questionnaire (SDQ). A score of total difficulties was aggregated for internalizing and externalizing problems.

Results

A total of 355 children aged 7–9 (183 boys, 166 girls, 6 non-binary) participated with 258 children providing valid accelerometer data. Children exhibited an average of 111.1 min of MVPA per day, with 97.3% meeting the physical activity guidelines. Approximately 43% (108/250) of participants were meeting the Canadian 24-h movement guidelines. Children were at an ‘emerging’ level of overall physical competence (45.8 ± 5.6) and reported a mean score of 68.9 (SD = 12.3) for self-perceived PL, with no significant differences between boys and girls. PL was significantly associated with MVPA (r = .27) and all SDQ variables (rs = -.26—.13) except for externalizing problems. Mediation analyses showed PL was negatively associated with internalizing problems and total difficulties when the association with MVPA was considered. However, the mediating role of MVPA was found only between PL and internalizing problems, β = -.06, 95%CI [-.12, -.01].

Conclusions

Although most of our sample was physically active and showed higher adherence to 24-H movement guidelines than comparable population data, the motor competence and self-perceived PL of our sample were similar to those of previous studies. PL has an independent association with children’s internalizing problems and total difficulties. Ongoing assessment will investigate the relationships between PL and children’s mental health from a longitudinal perspective.
Participatory prioritisation of interventions to improve primary school food environments in Gauteng, South Africa
Authors: Erzse Agnes , Karim Safura Abdool , Rwafa-Ponela Teurai , Kruger Petronell , Hofman Karen , Foley Louise , Oni Tolu , Goldstein Susan
Published: June 2023

Background

In South Africa, overweight and obesity affect 17% of children aged 15–18. School food environments play a vital role in children’s health, influencing dietary behaviours and resulting in high obesity rates. Interventions targeting schools can contribute to obesity prevention if evidence-based and context-specific. Evidence suggests that current government strategies are inadequate to ensure healthy school food environments. The aim of this study was to identify priority interventions to improve school food environments in urban South Africa using the Behaviour Change Wheel model.

Methods

A three-phased iterative study design was implemented. First, we identified contextual drivers of unhealthy school food environments through a secondary framework analysis of 26 interviews with primary school staff. Transcripts were deductively coded in MAXQDA software using the Behaviour Change Wheel and the Theoretical Domains Framework. Second, to identify evidence-based interventions, we utilised the NOURISHING framework and matched interventions to identified drivers. Third, interventions were prioritised using a Delphi survey administered to stakeholders (n = 38). Consensus for priority interventions was defined as an intervention identified as being 'somewhat' or ‘very' important and feasible with a high level of agreement (quartile deviation ≤ 0.5).

Results

We identified 31 unique contextual drivers that school staff perceived to limit or facilitate a healthy school food environment. Intervention mapping yielded 21 interventions to improve school food environments; seven were considered important and feasible. Of these, the top priority interventions were to: 1) “regulate what kinds of foods can be sold at schools”, 2) “train school staff through workshops and discussions to improve school food environment”, and affix 3) “compulsory, child-friendly warning labels on unhealthy foods”.

Conclusion

Prioritising evidence-based, feasible and important interventions underpinned by behaviour change theories is an important step towards enhanced policy making and resource allocation to tackle South Africa’s childhood obesity epidemic effectively.
Does the accelerometer-based navigation system reduce blood loss and transfusion in one-stage sequential bilateral total knee arthroplasty? A randomized double-blind controlled trial
Authors: Jarusriwanna Atthakorn , Pornrattanamaneewong Chaturong , Narkbunnam Rapeepat , Ruangsomboon Pakpoom , Thitithapana Paweena , Chareancholvanich Keerati
Published: June 2023

Background

Total knee arthroplasty (TKA) is associated with significant blood loss and postoperative transfusion. The accelerometer-based navigation (ABN) system guides the bone cutting plane without breaching the intramedullary canal, which may reduce bleeding. This study aimed to investigate blood loss and transfusion compared between the ABN system and the conventional procedure in patients undergoing one-stage sequential bilateral TKA (SBTKA).

Methods

A total of 66 patients scheduled for SBTKA were randomly allocated to either the ABN or conventional group. Postoperative hematocrit (Hct) level, drainage blood loss, transfusion rate, and amount of packed red cell transfusion were collected. Total red blood cell (RBC) loss was then calculated for the primary outcome.

Results

The mean calculated total RBC loss in the ABN and conventional group was 669.7 and 630.0 mL, respectively (p = 0.572). There was no significant difference between groups for other evaluated outcome parameters, including postoperative Hct level, drainage blood loss, or packed red cell transfusion volume. All patients in the conventional group required postoperative blood transfusion while 96.8% of patients in the ABN group were transfused.

Conclusions

The total RBC loss and volume of packed red cells transfusion were not significant difference between interventions, which suggest no benefit of the ABN system in reducing blood loss and transfusion in patients undergoing SBTKA.

Trial registration

The protocol of this study was registered in the Thai Clinical Trials Registry database no. TCTR20201126002 on 26/11/2020.
No major difference in perceived quality of care in patients with hip or knee osteoarthritis assessed in a physical therapy-led triage compared with standard care: a randomized controlled trial
Authors: Gustavsson Linnea , Mohaddes Maziar , Samsson Karin , Beischer Susanne
Published: June 2023

Background

Physical therapy-led orthopedic triage is a care model used to optimize pathways for patients with hip or knee osteoarthritis. However, scientific evidence of the effectiveness of this model of care is still limited and only a few studies report patients’ perception of it. The aim of this study was to compare patients’ perceived quality of care after physical therapy-led triage with standard practice in a secondary care setting for patients with primary hip or knee osteoarthritis.

Methods

In this randomized study, patients with hip or knee osteoarthritis referred for an orthopedic consultation received either physical therapy-led triage (n = 344) or a standard care assessment by an orthopedic surgeon (n = 294). To evaluate the patients’ perceived quality of care, a short version of the Quality from the Patient’s Perspective (QPP) questionnaire was sent to the patients within a week after their assessment. The primary outcome was the statement “I received the best examination and treatment” on QPP.

Results

A total of 348 patients (70%, physical therapy-led triage: n = 249, standard care: n = 199) answered the questionnaire. No significant difference was found in the primary outcome between the groups (p = 0.6). Participants in the triage group perceived themselves to have received significantly better information about how to take care of their osteoarthritis (p = 0.017) compared with the standard care group. The standard care group reported that they participated in the decision-making process to a greater extent (p = 0.005), that their expectations were met to a greater degree (p = 0.013), and that their care depended more on their need for care rather than the caregivers’ routines (0.007).

Conclusion

Both groups report high perceived quality of care. Significant differences were found in four of 14 questions, one in favor of the physical therapist and three in favor of the standard care group. The findings of this study are in line with previous research and support the use of this care model for patients with hip or knee OA in secondary care. However, due to the dropout size, the results should be interpreted with caution.

Trial registration

Clinical Trials NCT04665908, registered 14/12/2020.
Preference of musculoskeletal pain treatment in middle-aged and elderly chinese people: a machine learning analysis of the China health and retirement longitudinal study
Authors: Mei Fengyao , Dong Shengjie , Li Jiaojiao , Xing Dan , Lin Jianhao
Published: June 2023

Background

Musculoskeletal pain is a major cause of physical disability, associated with huge socioeconomic burden. Patient preference for treatment is an important factor contributing to the choice of treatment strategies. However, effective measurements for evaluating the ongoing management of musculoskeletal pain are lacking. To help improve clinical decision making, it’s important to estimate the current state of musculoskeletal pain management and analyze the contribution of patient treatment preference.

Methods

A nationally representative sample for the Chinese population was derived from the China Health and Retirement Longitudinal Study (CHARLS). Information on the patients’ demographic characteristics, socioeconomic status, other health-related behavior, as well as history on musculoskeletal pain and treatment data were obtained. The data was used to estimate the status of musculoskeletal pain treatment in China in the year 2018. Univariate analysis and multivariate analysis were used to find the effect factors of treatment preference. XGBoost model and Shapley Additive exPlanations (SHAP) method were performed to analyze the contribution of each variable to different treatment preferences.

Results

Among 18,814 respondents, 10,346 respondents suffered from musculoskeletal pain. Approximately 50% of musculoskeletal pain patients preferred modern medicine, while about 20% chose traditional Chinese medicine and another 15% chose acupuncture or massage therapy. Differing preferences for musculoskeletal pain treatment was related to the respondents’ gender, age, place of residence, education level, insurance status, and health-related behavior such as smoking and drinking. Compared with upper or lower limb pain, neck pain and lower back pain were more likely to make respondents choose massage therapy (P < 0.05). A greater number of pain sites was associated with an increasing preference for respondents to seek medical care for musculoskeletal pain (P < 0.05), while different pain sites did not affect treatment preference.

Conclusion

Factors including gender, age, socioeconomic status, and health-related behavior may have potential effects on people’ s choice of treatment for musculoskeletal pain. The information derived from this study may be useful for helping to inform clinical decisions for orthopedic surgeons when devising treatment strategies for musculoskeletal pain.
Construction and validation of a nomogram model for predicting the overall survival of colorectal cancer patients
Authors: Peiyuan Guo , xuhua Hu , Ganlin Guo , Xu Yin , Zining Liu , Jiachao Han , Bin Yu , Guiying Wang
Published: June 2023

Background

Colorectal cancer (CRC) is a frequent cancer worldwide with varied survival outcomes.

Objective

We aimed to develop a nomogram model to predict the overall survival (OS) of CRC patients after surgery.

Design

This is a retrospective study.

Setting

This study was conducted from 2015 to 2016 in a single tertiary center for CRC.

Patients

CRC patients who underwent surgery between 2015 and 2016 were enrolled and randomly assigned into the training (n = 480) and validation (n = 206) groups. The risk score of each subject was calculated based on the nomogram. All participants were categorized into two subgroups according to the median value of the score.

Main outcome measures

The clinical characteristics of all patients were collected, significant prognostic variables were determined by univariate analysis. Least absolute shrinkage and selection operator (LASSO) regression was applied for variable selection. The tuning parameter (λ) for LASSO regression was determined by cross-validation. Independent prognostic variables determined by multivariable analysis were used to establish the nomogram. The predictive capacity of the model was assessed by risk group stratification.

Results

Infiltration depth, macroscopic classification, BRAF, carbohydrate antigen 19 − 9 (CA-199) levels, N stage, M stage, TNM stage, carcinoembryonic antigen levels, number of positive lymph nodes, vascular tumor thrombus, and lymph node metastasis were independent prognostic factors. The nomogram established based on these factors exhibited good discriminatory capacity. The concordance indices for the training and validation groups were 0.796 and 0.786, respectively. The calibration curve suggested favorable agreement between predictions and observations. Moreover, the OS of different risk subgroups was significantly different.

Limitations

The limitations of this work included small sample size and single-center design. Also, some prognostic factors could not be included due to the retrospective design.

Conclusions

A prognostic nomogram for predicting the OS of CRC patients after surgery was developed, which might be helpful for evaluating the prognosis of CRC patients.
Assessing the cost-effectiveness of integrated case management of Neglected Tropical Diseases in Liberia
Authors: Godwin-Akpan Tiawanlyn G. , Diaconu Karin , Edmiston Melissa , Smith John Solunta , Sosu Fred , Weiland Stefanie , Kollie Karsor K.
Published: June 2023

Background

In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems.

Methods

This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness.

Results

The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9–10 times more patients were diagnosed and treated.

Conclusions

The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.
Help-seeking challenges for female sexual concerns: a qualitative study from Iran
Authors: Maasoumi Raziyeh , Sabetghadam Shadi , Keramat Afsaneh , Aghayan Seyed Shahrokh
Published: June 2023

Background

To effectively manage sexual health, people must have access to sexual health services. A small percentage of women with sexual concerns seek professional help. Hence, the need to explain the help-seeking challenges is felt from the perspective of women and health care providers.

Methods

This study explored Iranian women’s challenges when seeking help for sexual concerns. Using a purposive sampling method, 26 in-depth interviews were conducted in Rasht in 2019–2020. The participants included sexually active women of reproductive age over 18 years old and 8 health care providers. The recorded interviews were transcribed and analyzed through content analysis.

Results

From the description of 17 subthemes provided by the participants, two main themes were achieved, “Unfavorable sexuality development context” and “Inefficient sexual health services.”

Conclusions

According to the results, it is suggested that policymakers pay more attention to the challenges women and health care providers face in help-seeking and promote sexuality education and sexual health services to achieve a higher level of help-seeking among women.
Cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with relapsed or refractory metastatic triple-negative breast cancer
Authors: Xie Jiao , Li SiNi , Li YaMin , Li JianHe
Published: June 2023

Background

The effectiveness of sacituzumab govitecan for metastatic triple-negative breast cancer (TNBC) has been reported in recent research, however, the value of the effectiveness and cost of sacituzumab govitecan is still unclear.

Methods

A microsimulation model was developed using data from the ASCENT trial to assess the cost-effectiveness of sacituzumab govitecan for patients with relapsed or refractory metastatic TNBC over a lifetime. Model inputs, including clinical data, patient characteristics, and direct medical costs, were based on the ASCENT trial, public databases, and published literature. The primary outcomes of the model were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) and multiple scenario analyses were performed to address the uncertainty of the model.

Results

Our results revealed that sacituzumab govitecan versus chemotherapy costs $293,037 and yielded an additional 0.2340 of QALYs in the whole population with metastatic TNBC, leading to an ICER of $1,252,295 gained. And in the population with metastatic TNBC without brain metastasis, the sacituzumab govitecan versus chemotherapy costs $309,949 and obtained an extra 0.2633 of QALYs, which resulted in an ICER of $1,177,171/QALYs. Univariate analyses indicated that the model outcomes were most sensitive to the drug cost of sacituzumab govitecan, the utility of progression-free disease, and the utility of progressed disease.

Conclusion

From the US payer perspective, sacituzumab govitecan is unlikely to be a cost-effective option for patients with relapsed or refractory metastatic TNBC compared with chemotherapy. Based on the value standpoint, a price decrease of sacituzumab govitecan is expected to increase the cost-effectiveness of sacituzumab govitecan in patients with metastatic TNBC.
Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis
Authors: Farooqi Raabia , Kooner Jaspal S. , Zhang Weihua
Published: June 2023

Background

COVID-19 manifests with huge heterogeneity in susceptibility and severity outcomes. UK Black Asian and Minority Ethnic (BAME) groups have demonstrated disproportionate burdens. Some variability remains unexplained, suggesting potential genetic contribution. Polygenic Risk Scores (PRS) can determine genetic predisposition to disease based on Single Nucleotide Polymorphisms (SNPs) within the genome. COVID-19 PRS analyses within non-European samples are extremely limited. We applied a multi-ethnic PRS to a UK-based cohort to understand genetic contribution to COVID-19 variability.

Methods

We constructed two PRS for susceptibility and severity outcomes based on leading risk-variants from the COVID-19 Host Genetics Initiative. Scores were applied to 447,382 participants from the UK-Biobank. Associations with COVID-19 outcomes were assessed using binary logistic regression and discriminative power was validated using incremental area under receiver operating curve (ΔAUC). Variance explained was compared between ethnic groups via incremental pseudo-R2 (ΔR2).

Results

Compared to those at low genetic risk, those at high risk had a significantly greater risk of severe COVID-19 for White (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42–1.74), Asian (OR 2.88, 95% CI 1.63–5.09) and Black (OR 1.98, 95% CI 1.11–3.53) ethnic groups. Severity PRS performed best within Asian (ΔAUC 0.9%, ΔR2 0.98%) and Black (ΔAUC 0.6%, ΔR2 0.61%) cohorts. For susceptibility, higher genetic risk was significantly associated with COVID-19 infection risk for the White cohort (OR 1.31, 95% CI 1.26–1.36), but not for Black or Asian groups.

Conclusions

Significant associations between PRS and COVID-19 outcomes were elicited, establishing a genetic basis for variability in COVID-19. PRS showed utility in identifying high-risk individuals. The multi-ethnic approach allowed applicability of PRS to diverse populations, with the severity model performing well within Black and Asian cohorts. Further studies with larger sample sizes of non-White samples are required to increase statistical power and better assess impacts within BAME populations.
Decreased level of serum NT-proCNP associates with disease severity in COVID-19
Authors: Bojti Istvan , Przewosnik Anne-Sophie , Luxenburger Hendrik , Hofmann Maike , Neumann-Haefelin Christoph , Esser Jennifer S. , Siegel Patrick M. , Maier Alexander , Kovacs Sarolta Bojtine , Kardos Laszlo , Csanádi Zoltan , Rieder Marina , Duerschmied Daniel , Lother Achim , Bode Christoph , Szabó Gabor Tamas , Czuriga Daniel
Published: June 2023

Background

C-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the current study, we aimed to determine possible changes in the NT-proCNP levels of patients with coronavirus disease 2019 (COVID-19), with special regard to disease severity and outcome.

Methods

In this retrospective analysis, we determined the serum level of NT-proCNP in hospitalized patients with symptoms of upper respiratory tract infection, using their blood samples taken on admission, stored in a biobank. The NT-proCNP levels of 32 SARS-CoV-2 positive and 35 SARS-CoV-2 negative patients were measured to investigate possible correlation with disease outcome. SARS-CoV-2 positive patients were then divided into two groups based on their need for intensive care unit treatment (severe and mild COVID-19).

Results

The NT-proCNP was significantly different in the study groups (e.g. severe and mild COVID-19 and non-COVID-19 patients), but showed inverse changes compared to previous observations in septic patients: lowest levels were detected in critically ill COVID-19 patients, while highest levels in the non-COVID-19 group. A low level of NT-proCNP on admission was significantly associated with severe disease outcome.

Conclusions

Low-level NT-proCNP on hospital admission is associated with a severe COVID-19 disease course. The pathomechanism underlying this observation remains to be elucidated, while future studies in larger patient cohorts are necessary to confirm these observations and reveal therapeutic importance.

Trial registration DRKS00026655 Registered 26. November 2021
Non-linear association of atherogenic index of plasma with insulin resistance and type 2 diabetes: a cross-sectional study
Authors: Yin Bei , Wu Zihong , Xia Yaqing , Xiao Shunqiang , Chen Lingling , Li Yousheng
Published: June 2023

Background

Although there is numerous evidence on the epidemiological risk factors for insulin resistance (IR)-related metabolic diseases, there is still insufficient evidence to explore the non-linear association of Atherogenic Index of Plasma (AIP) with IR. Therefore, we aimed to elucidate the non-linear relationship between AIP and IR and type 2 diabetes (T2D).

Methods

This cross-sectional study was conducted in the National Health and Nutrition Survey (NHANES) from 2009 to 2018. A total of 9,245 participants were included in the study. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included IR and T2D defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, subgroup analysis, generalized additive model, smooth fitting curve and two-part logistic regression were adopted to reveal the relationship of AIP with IR and T2D.

Results

After adjustment for age, gender, race, education level, smoking status, alcohol consumption, vigorous/moderate physical activity, body mass index, waist circumference and hypertension, we found that AIP was positively associated with fasting blood glucose (β = 0.08, 95% CI: 0.06, 0.10), glycosylated hemoglobin (β = 0.04, 95% CI: 0.39, 0.58), fasting serum insulin (β = 4.26, 95% CI: 3.73, 4.79), and homeostasis model assessment of insulin resistance (β = 0.22, 95% CI: 0.18, 0.25). Further studies found that AIP was associated with increased risk of IR (OR = 1.29, 95% CI: 1.26–1.32) and T2D (OR = 1.18, 95% CI: 1.15–1.22). However, the positive association between AIP and IR or T2D was more significant in female than in male (IR: P for interaction = 0.0135; T2D: P for interaction = 0.0024). A non-linear and inverse L-shaped association was found between AIP and IR, while a J-shaped association was found between AIP and T2D. In patients with − 0.47 < AIP < 0.45, increased AIP was significantly associated with increased risk of IR and T2D.

Conclusions

AIP showed an inverse L-shaped association with IR and a J-shaped association with T2D, indicating that AIP should be reduced to a certain level to prevent IR and T2D.
Enhanced extracellular production of raw starch-degrading α-amylase in Bacillus subtilis through expression regulatory element modification and fermentation optimization
Authors: Yao Dongbang , Han Xudong , Gao Huanhuan , Wang Bin , Fang Zemin , Li He , Fang Wei , Xiao Yazhong
Published: June 2023

Background

Raw starch-degrading α-amylase (RSDA) can hydrolyze raw starch at moderate temperatures, thus contributing to savings in starch processing costs. However, the low production level of RSDA limits its industrial application. Therefore, improving the extracellular expression of RSDA in Bacillus subtilis, a commonly used industrial expression host, has great value.

Results

In this study, the extracellular production level of Pontibacillus sp. ZY raw starch-degrading α-amylase (AmyZ1) in B. subtilis was enhanced by expression regulatory element modification and fermentation optimization. As an important regulatory element of gene expression, the promoter, signal peptide, and ribosome binding site (RBS) sequences upstream of the amyZ1 gene were sequentially optimized. Initially, based on five single promoters, the dual-promoter Pveg-PylB was constructed by tandem promoter engineering. Afterward, the optimal signal peptide SPNucB was obtained by screening 173 B. subtilis signal peptides. Then, the RBS sequence was optimized using the RBS Calculator to obtain the optimal RBS1. The resulting recombinant strain WBZ-VY-B-R1 showed an extracellular AmyZ1 activity of 4824.2 and 41251.3 U/mL during shake-flask cultivation and 3-L fermenter fermentation, which were 2.6- and 2.5-fold greater than those of the original strain WBZ-Y, respectively. Finally, the extracellular AmyZ1 activity of WBZ-VY-B-R1 was increased to 5733.5 U/mL in shake flask by optimizing the type and concentration of carbon source, nitrogen source, and metal ions in the fermentation medium. On this basis, its extracellular AmyZ1 activity was increased to 49082.1 U/mL in 3-L fermenter by optimizing the basic medium components as well as the ratio of carbon and nitrogen sources in the feed solution. This is the highest production level reported to date for recombinant RSDA production.

Conclusions

This study represents a report on the extracellular production of AmyZ1 using B. subtilis as a host strain, and achieved the current highest expression level. The results of this study will lay a foundation for the industrial application of RSDA. In addition, the strategies employed here also provide a promising way for improving other protein production in B. subtilis.
Carboligation of 5-(hydroxymethyl)furfural via whole-cell catalysis to form C12 furan derivatives and their use for hydrazone formation
Authors: Glaser Sara Jonsdottir , Pyo Sang-Hyun , Rehnberg Nicola , Rother Dörte , Hatti-Kaul Rajni
Published: June 2023

Background

Biobased 5-(hydroxymethyl)furfural (5-HMF) is an important platform that offers numerous possibilities for upgrading to a range of chemical, material and fuel products. One reaction of special interest is the carboligation of 5-HMF into C12 compounds, including 5,5’-bis(hydroxymethyl)furoin (DHMF) and its subsequent oxidation to 5,5’-bis(hydroxymethyl)furil (BHMF), due to their potential applications as building blocks for polymers and hydrocarbon fuels.

Objectives

This study was aimed at evaluating the use of whole cells of Escherichia coli carrying recombinant Pseudomonas fluorescens benzaldehyde lyase as biocatalysts for 5-HMF carboligation, recovery of the C12 derivatives DHMF and BHMF, and testing the reactivity of the carbonyl groups for hydrazone formation for potential use as cross-linking agents in surface coatings. The effects of different parameters on the reaction were investigated to find the conditions for achieving high product yield and productivity.

Results

The reaction with 5 g/L 5-HMF using 2 gCDW/L recombinant cells in 10% dimethyl carbonate, pH 8.0 at 30 °C resulted in DHMF yield of 81.7% (0.41 mol/mol) at 1 h, and BHMF yield of 96.7% (0.49 mol/mol) at 72 h reaction time. Fed-batch biotransformation generated a maximum DHMF concentration of 53.0 g/L (or 26.5 g DHMF/g cell catalyst) with productivity of 10.6 g/L.h, after five feeds of 20 g/L 5-HMF. Both DHMF and BHMF reacted with adipic acid dihydrazide to form hydrazone that was confirmed by Fourier-transform infrared spectroscopy and 1H NMR.

Conclusion

The study demonstrates the potential application of recombinant E. coli cells for cost-effective production of commercially relevant products.
Abundant diversity of accessory genetic elements and associated antimicrobial resistance genes in pseudomonas aeruginosa isolates from a single Chinese hospital
Authors: Mu Xiaofei , Li Xinyue , Yin Zhe , Jing Ying , Chen Fangzhou , Gao Huixia , Zhang Zhi , Tian Yueyang , Guo Huiqian , Lu Xiuhui , He Jiaqi , Zheng Yali , Zhou Dongsheng , Wang Peng , Dai Erhei
Published: June 2023

Objectives

Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital.

Methods

Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates.

Results

From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512−IMP plasmids, and IncpPA7790 plasmids.

Conclusion

This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.
Development and validation of a nomogram for predicting metabolic-associated fatty liver disease in the Chinese physical examination population
Authors: Zhou Bingqian , Gong Ni , Huang Xinjuan , Zhu Jingchi , Qin Chunxiang , He Qingnan
Published: June 2023

Aim

We aim to develop and validate a nomogram including readily available clinical and laboratory indicators to predict the risk of metabolic-associated fatty liver disease (MAFLD) in the Chinese physical examination population.

Methods

The annual physical examination data of Chinese adults from 2016 to 2020 were retrospectively analyzed. We extracted the clinical data of 138 664 subjects and randomized participants to the development and validation groups (7:3). Significant predictors associated with MAFLD were identified by using univariate and random forest analyses, and a nomogram was constructed to predict the risk of MAFLD based on a Lasso logistic model. Receiver operating characteristic curve analysis, calibration curves, and decision curve analysis were used to verify the discrimination, calibration, and clinical practicability of the nomogram, respectively.

Results

Ten variables were selected to establish the nomogram for predicting MAFLD risk: sex, age, waist circumference (WC), uric acid (UA), body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting plasma glucose (FPG), triglycerides (TG), and alanine aminotransferase (ALT). The nomogram built on the nonoverfitting multivariable model showed good prediction of discrimination (AUC 0.914, 95% CI: 0.911–0.917), calibration, and clinical utility.

Conclusions

This nomogram can be used as a quick screening tool to assess MAFLD risk and identify individuals at high risk of MAFLD, thus contributing to the improved management of MAFLD.
Nesfatin-3 possesses divalent metal ion binding properties, which remain hidden in the nucleobindin-2 precursor protein
Authors: Skorupska-Stasiak Anna , Bystranowska Dominika , Tran Józef Ba , Krężel Artur , Ożyhar Andrzej
Published: June 2023

Background

Nucleobindin-2 (Nucb2) is a multidomain protein that, due to its structure, participates in many physiological processes. It was originally identified in several regions of the hypothalamus. However, more recent studies have redefined and extended the function of Nucb2 far beyond its initially observed role as a negative modulator of food intake.

Results

Previously, we described Nucb2 as structurally divided into two parts: the Zn2+-sensitive N-terminal half and the Ca2+-sensitive C-terminal half. Here, we investigated the structural and biochemical properties of its C-terminal half, which, after posttranslational processing, yields the formation of a fully uncharacterized peptide product known as nesfatin-3. Nesfatin-3 likely contains all the key respective structural regions of Nucb2. Hence, we expected that its molecular properties and affinity toward divalent metal ions might resemble those of Nucb2. Surprisingly, the obtained results showed that the molecular properties of nesftain-3 were completely different from those of its precursor protein. Moreover, we designed our work as a comparative analysis of two nesfatin-3 homologs. We noticed that in their apo forms, both proteins had similar shapes and existed in solution as extended molecules. They both interacted with divalent metal ions, and this interaction manifested itself in a compaction of the protein molecules. Despite their similarities, the differences between the homologous nesfatin-3s were even more informative. Each of them favored interaction with a different metal cation and displayed unique binding affinities compared either to each other or to Nucb2.

Conclusions

The observed alterations suggested different from Nucb2 physiological roles of nesfatin-3 and different impacts on the functioning of the tissues and on metabolism and its control. Our results clearly demonstrated that nesfatin-3 possessed divalent metal ion binding properties, which remained hidden in the nucleobindin-2 precursor protein.
Growth hormone reduces aneuploidy and improves oocytes quality by JAK2-MAPK3/1 pathway in aged mice
Authors: Luo Yun-Yao , Zeng Xi , Zhu Ling , Li Chong , Xie Juan , Dong Qiang , Sun Qing-Yuan , Huang Guo-Ning , Li Jing-Yu
Published: June 2023

Background

The global delay in women’s reproductive age has raised concerns about age-related infertility. The decline in oocyte quality is a limiting factor of female fertility, yet there are currently no strategies to preserve oocyte quality in aged women. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aged oocytes.

Methods

For the in vivo experiments, the aged mice (8-month-old) were intraperitoneally injected with GH daily for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aged mice were treated with GH during oocyte maturation. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to assess oocyte quality, aneuploidy and developmental potential characteristics. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aged oocytes.

Results

In this study, we demonstrated that GH supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, we discovered that GH supplementation reduced aneuploidy in aged oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the MAPK3/1 pathway may be involved in the reduction in aneuploidy of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 may also act as a mediator in how GH regulates MAPK3/1.

Conclusions

In conclusion, our research reveals that GH supplementation protects oocytes against aging-related aneuploidy and enhances the quality of aged oocytes, which has clinical significance for aged women undergoing assisted reproduction technology.

Graphical Abstract
Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) in a Middle Eastern patient cohort
Authors: Yavuz Lemis , AlHamdani Sarmad , Alasrawi Samah , Wafadari Deena , Al-Fraihat Ali , Bebars Marwa A. , Nath Jaidev , Arango Diego , Pallavidino Marco , Jain Ruchi , Yavuz Sinan , AlAwadhi Mohamed , Alkhayat Abdulla , Tayoun Ahmad Abou , Abuhammour Walid Mohammad
Published: June 2023

Objective

This is a comprehensive characteristic study of Kawasaki disease (KD) and Multi system inflammatory syndrome in children (MIS-C) in the Middle East that creates a formula to differentiate between the two.

Methods

We conducted a descriptive comparative study of KD and MIS-C in the United Arab Emirates. Retrospective MIS-C and KD cohorts were recruited between January 2017 until August 2021.We compared clinical and laboratory characteristics between both groups. Our data were compared with 87 patients with KD or MIS-C from the literature.

Results

We report on123 patients. Sixty-seven (54%) met the criteria for KD (36 male, 43 Arab), and fifty-six (46%) met the criteria for MIS-C (28 male, 35 Arab). The median age was 2.2 years range (0.15–10.7) in the KD group and 7.3 years (0.7–15.2) in the MIS-C group (P < 0.001). The clinical features on admission showed an increase in gastrointestinal manifestations in MIS-C compared with KD (84% vs. 31%, P < 0.001). Laboratory tests on admission revealed a significant increase in the following tests in KD compared with MIS-C; white blood cells (mean 16.30 10(3) µcL vs. 11.56 10(3) µcL, P < 0.001), absolute neutrophils (mean 10.72 10(3) µcL vs. 8.21 10(3) µcL, P 0.008), absolute lymphocytes (mean 3.92 10(3) µcL vs. 2.59 10(3) µcL, P 0.003), erythrocyte sedimentation rate (mean 73 mm/hr vs. 51 mm/hr, P < 0.001) and platelets (median {390 10(3) µcL vs. 236 10(3) µcL, P < 0.001}). In contrast, procalcitonin and ferritin were increased in the MIS-C group (2.4 )ng/mL, 370 ng/mL; P < 0.001). Cardiac dysfunction and admission to the pediatric intensive care unit were higher in MIS-C than in KD (21% vs. 8% and 33% vs. 7.5%, respectively, P < 0.001).

Conclusion

This study showed vast similarities between KD and MIS-C, suggesting that they lie along the same clinical spectrum. However, there are several differences between the two disease entities suggesting that MIS-C most likely represents a new severe variant of KD. Based on our findings in this study, we created a formula to differentiate between KD and MIS-C.