bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning from a crisis: a qualitative study of the impact on mothers’ emotional wellbeing of changes to maternity care during the COVID-19 pandemic in England, using the National Maternity Survey 2020
Authors: McLeish Jenny , Harrison Sian , Quigley Maria , Alderdice Fiona
Published: November 2022

Background

Pregnancy and the postnatal period can be times of psychosocial stress and insecurity, but high quality maternity care and social support can help mothers cope with stress and feel more secure. The COVID-19 pandemic and associated social and economic disruption increased rates of antenatal and postnatal stress, anxiety and depression, and also had profound impacts on the organisation of maternity services in England.

Methods

This was a qualitative descriptive study of the impact of pandemic-related changes to maternity care on mothers’ emotional wellbeing, using inductive thematic analysis of open text responses to the National Maternity Survey (NMS) 2020 in England. A random sample of 16,050 mothers who gave birth 11-24th May 2020 were invited to take part in the survey, and 4,611 responded, with 4,384 answering at least one open text question.

Results

There were three themes: ‘Chaos: impact of uncertainty’, ‘Abandoned: impact of reduction in care’, and ‘Alone: impact of loss of social support’. Mothers valued maternity care and many experienced additional stress from chaotic changes and reduction in care during the pandemic; from health professionals’ own uncertainty and anxiety; and from restrictions on essential social support during pregnancy, labour and birth. Others felt that health professionals had communicated and cared for them well despite the changes and restrictions, and these mothers felt psychologically safe.

Conclusions

Planning for future crises should include considering how necessary adaptations to care can be implemented and communicated to minimise distress; ensuring that mothers are not deprived of social support at the time when they are at their most vulnerable; and supporting the psychological welfare of staff at a time of enormous pressure. There are also lessons for maternity care in ‘normal’ times: that care is highly valued, but trust is easily lost; that some mothers come into the maternity system with vulnerabilities that can be ameliorated or intensified by the attitudes of staff; that every effort should be made to welcome a mother’s partner or chosen companion into maternity care; and that high quality postnatal care can make a real difference to mothers’ wellbeing.
The human right to safely give birth: data from 193 countries show that gender equality does affect maternal mortality
Authors: Bagade Tanmay , Chojenta Catherine , Harris Melissa , Oldmeadow Christopher , Loxton Deborah
Published: November 2022

Background

While a reduction in the global maternal mortality ratio (MMR) has slowed, newer strategies are needed to achieve an ongoing and sustainable reduction of the MMR. Previous studies have investigated the association between health system-related factors such as wealth inequalities, healthcare access and use on maternal mortality. However, a women’s rights-based approach to address MMR has not been studied, excluding the health system-related factors. This study aimed to analyse the association between gender equality and MMR globally.

Methods

Using structural equation modelling (SEM), secondary and open access data from the United Nations and other international agencies from 193 countries were analysed using structural equation modelling (SEM). Gender-sensitive variables that represented the theoretical, conceptual framework of the study were selected. The association between latent variable gender equality and the outcome, MMR, was examined in the SEM. A second SEM model (n = 158) was designed to include two variables related to gender-based violence.

Findings

The latent variable, gender equality, was negatively associated with MMR (p < 0‧001, Z = –6‧96, 95% CI: − 6508.98 to − 3141.89 for Model 1 and p < 0‧001, Z = –7‧23, 95% CI: − 6045.356 to − 3467.515 for Model 2).

Interpretation

Gender equality was significantly associated with maternal mortality. Investing in higher education for women, improving their paid employment opportunities, increasing participation in leadership roles and politics, reducing intimate partner violence (IPV) and ending child marriage can significantly reduce maternal mortality.
Exploring the impact of shielding advice on the wellbeing of individuals identified as clinically extremely vulnerable amid the COVID-19 pandemic: a mixed-methods evaluation
Authors: Lasseter Gemma , Compston Polly , Robin Charlotte , Lambert Helen , Hickman Matthew , Denford Sarah , Reynolds Rosy , Zhang Juan , Cai Shenghan , Zhang Tingting , Smith Louise E. , Rubin G James , Yardley Lucy , Amlôt Richard , Oliver Isabel
Published: November 2022

Background

The national shielding programme was introduced by UK Government at the beginning of the COVID-19 pandemic, with individuals identified as clinically extremely vulnerable (CEV) offered advice and support to stay at home and avoid all non-essential contact. This study aimed to explore the impact and responses of “shielding” on the health and wellbeing of CEV individuals in Southwest England during the first COVID-19 lockdown.

Methods

A two-stage mixed methods study, including a structured survey (7 August—23 October 2020) and semi-structured telephone interviews (26 August—30 September 2020) with a sample of individuals who had been identified as CEV and advised to “shield” by Bristol, North Somerset & South Gloucestershire (BNSSG) Clinical Commissioning Group (CCG).

Results

The survey was completed by 203 people (57% female, 54% > 69 years, 94% White British, 64% retired) in Southwest England identified as CEV by BNSSG CCG. Thirteen survey respondents participated in follow-up interviews (53% female, 40% > 69 years, 100% White British, 61% retired). Receipt of ‘official’ communication from NHS England or General Practitioner (GP) was considered by participants as the legitimate start of shielding. 80% of survey responders felt they received all relevant advice needed to shield, yet interviewees criticised the timing of advice and often sought supplementary information. Shielding behaviours were nuanced, adapted to suit personal circumstances, and waned over time. Few interviewees received community support, although food boxes and informal social support were obtained by some. Worrying about COVID-19 was common for survey responders (90%). Since shielding had begun, physical and mental health reportedly worsened for 35% and 42% of survey responders respectively. 21% of survey responders scored ≥ 10 on the PHQ-9 questionnaire indicating possible depression and 15% scored ≥ 10 on the GAD-7 questionnaire indicating possible anxiety.

Conclusions

This research highlights the difficulties in providing generic messaging that is applicable and appropriate given the diversity of individuals identified as CEV and the importance of sharing tailored and timely advice to inform shielding decisions. Providing messages that reinforce self-determined action and assistance from support services could reduce the negative impact of shielding on mental health and feelings of social isolation.
Do we cope similarly with different adversities? COVID-19 versus armed conflict
Authors: Kimhi Shaul , Marciano Hadas , Eshel Yohanan , Adini Bruria
Published: November 2022

Background

Varied populations may react differently to similar crises, depending on their social, cultural, and personal backgrounds; conversely, the same populations may respond differently to varied adversities. The current study aimed to examine three types of resilience (individual, community, and societal resilience) predicting six coping mechanisms (sense of danger, anxiety and depressive symptoms, well-being, hope, and morale) among the same sample of people that faced across two different adversities—COVID-19 and an armed conflict.

Methods

Two repeated measurements of the same Israeli sample (N = 593) were employed, through an internet panel. The research variables were examined through a structured, quantitative questionnaire that consisted of nine scales, based on validated and reliable questionnaires.

Results

Results indicated that: (a) respondents reported more difficulties in coping with the COVID-19 crisis, compared to the armed conflict, in all variables but morale. (b) similar patterns of correlations among the study variables were found in both measurements. (c) path's analysis indicated similar patterns of prediction of distress and well-being by individual and societal resilience. Use of the coping mechanism varied depending on the perception of the threat: COVID -19 is perceived as a less familiar and predictable adversity, which is harder to cope with, compared with the more familiar risk – an armed conflict, which is a recurrent threat in Israel. The correlations between the investigated psychological responses and the impacts of resilience on the coping and distress mechanism were similar in both adversities.

Conclusions

The results indicate that respondents tend to react in a similar pattern of associations among resilience, distress, and well-being across different adversities, such as COVID and armed conflict. However, individuals tend to regard unfamiliar, less predictable adversities as more complex to cope with, compared to better-known crises. Furthermore, respondents tend to underestimate the risks of potential familiar adversities. Healthcare professionals must be aware of and understand the coping mechanisms of individuals during adversities, to appropriately design policies for the provision of medical and psychological care during varied emergencies.
The impact of leadership on employee well-being: on-site compared to working from home
Authors: Lundqvist Daniel , Reineholm Cathrine , Ståhl Christian , Wallo Andreas
Published: November 2022

Background

The Covid-19 pandemic has brought significant changes to the way people work and there are several reasons to believe that working from home will become more common in the future. Yet more knowledge is needed on whether the effectiveness of leadership differs if the work is performed remotely compared to on-site work.

Purpose

The aim of this study is to examine the place of work as a moderator for the effectiveness of leadership on employee well-being.

Method

A survey was answered by 364 white-collar workers, employed by a larger Swedish municipality, who because of the covid-19-pandemic were offered to work from home.

Results

The employees working in their regular office perceived having more sufficient work equipment. No other differences were found in the investigated variables. Supportive leadership was associated with all investigated well-being variables in the hypothesised directions. Place of work did not moderate the relationship between Support leadership and the investigated well-being outcomes (Job satisfaction, Stress, General well-being).

Conclusion

This study shows that there are few differences between employees working from home or working on-site during the Covid-19 pandemic. The supportive leadership of the closest manager seem to be important for well-being regardless of the worksite.
Hepatitis C prevalence in incarcerated settings between 2013–2021: a systematic review and meta-analysis
Authors: Busschots Dana , Kremer Cécile , Bielen Rob , Koc Özgür M. , Heyens Leen , Nevens Frederik , Hens Niel , Robaeys Geert
Published: November 2022

Background

The introduction of highly effective direct-acting antiviral therapy has changed the hepatitis C virus (HCV) treatment paradigm. However, a recent update on HCV epidemiology in incarcerated settings is necessary to accurately determine the extent of the problem, provide information to policymakers and public healthcare, and meet the World Health Organization's goals by 2030. This systematic review and meta-analysis were performed to determine the prevalence of HCV Ab and RNA in incarcerated settings.

Methods

For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and Web of Science for papers published between January 2013 and August 2021. We included studies with information on the prevalence of HCV Ab or RNA in incarcerated settings. A random-effects meta-analysis was done to calculate the pooled prevalence and meta-regression to explore heterogeneity.

Results

Ninety-two unique sources reporting data for 36 countries were included. The estimated prevalence of HCV Ab ranged from 0.3% to 74.4%. HCV RNA prevalence (available in 46 sources) ranged from 0% to 56.3%. Genotypes (available in 19 sources) 1(a) and 3 were most frequently reported in incarcerated settings. HCV/HIV coinfection (available in 36 sources) was highest in Italy, Estonia, Pakistan, and Spain. Statistical analysis revealed that almost all observed heterogeneity reflects real differences in prevalence between studies, considering I2 was very high in the meta-analysis.

Conclusions

HCV in incarcerated settings is still a significant problem with a higher prevalence than in the general population. It is of utmost importance to start screening for HCV (Ab and RNA) in incarcerated settings to give clear, reliable and recent figures to plan further treatment. This is all in the context of meeting the 2030 WHO targets which are only less than a decade away.

Trial registration

PROSPERO: CRD42020162616
Modified gingivoplasty for hereditary gingival fibromatosis: two case reports
Authors: Huang Xin , Zhu Wenjun , Zhang Xinfang , Fu Yun
Published: November 2022

Background

Hereditary gingival fibromatosis (HGF) is characterized by sub-epithelial fibromatosis of keratinized gingiva resulting in a fibrotic enlargement of keratinized gingiva. The treatment choice is gingivectomy, which can be performed with an internal or external bevel incision conventionally. However, both techniques can hardly resume the natural status of gingiva, and have a certain recurrence rate, especially in the cases which have limited width of attached gingiva.

Case description

Two cases of HGF with the chief complaint of difficulty in mastication, pronunciation, and poor esthetics were presented. After the initial periodontal therapy, a novel gingivoplasty modified with a crevicular incision was applied. A full thickness flap above the mucogingival junction and a split flap below the junction were raised. Then, fibrotic connective tissue was completely eliminated and keratinized gingival epithelium was preserved. The fibrotic alveolar bone was shaped by handpiece and bur. Finally, the flap was apically repositioned and sutured. Twelve months after surgery, the gingiva recovered with normal color, contour and consistency.

Conclusions

Compared to traditional gingivectomy, modified gingivoplasty which focuses on eliminating pathological fibrotic connective tissue can completely resume the natural appearance of gingiva and demonstrate no tendency of recurrence.
Evaluation of design, mechanical properties, and torque/force generation of heat-treated NiTi glide path instruments
Authors: Oh Soram , Seo Ji-Yeon , Lee Ji-Eun , Kim Hyun-Jung , Jang Ji-Hyun , Chang Seok Woo
Published: November 2022

Background

Recently, various kinds of heat-treated nickel-titanium (NiTi) glide path instruments have been manufactured. This study aimed to investigate design, phase transformation behavior, mechanical properties of TruNatomy Glider (#17/02), V Taper 2H (#14/03), and HyFlex EDM (#15/03) and compare torque/force generated during simulated glide path preparation with them.

Methods

The designs and phase-transformation behaviors of the instruments were examined via scanning electron microscopy (n = 3) and differential scanning calorimetry (n = 2). Their bending (n = 15), torsional (n = 15), and cyclic fatigue resistances (n = 15) were tested. The ultimate strength and distortion angle were obtained from torsional resistance test. The number of cycles to failure (NCF) was calculated from cyclic fatigue resistance test. The preparation of the glide path was simulated using a double-curved artificial canal (n = 15), and the maximum torque and screw-in forces were measured. Data except NCF was compared between brands with one-way ANOVA with Tukey’s honestly significant difference test. NCF was analyzed via Kruskal–Wallis and Mann–Whitney U tests.

Results

TruNatomy Glider had the greatest number of threads. TruNatomy Glider showed progressive taper, while V Taper 2H and HyFlex EDM had constant taper. The austenitic transformation-finish temperatures of all the instruments were above body temperature. V Taper 2H demonstrated significantly lower ultimate strength, higher distortion angle, and a higher number of cycles to failure compared with HyFlex EDM and TruNatomy Glider (p < 0.05). The maximum torque generated during preparing glide path was lowest for V Taper 2H, and the maximum screw-in force was lowest for HyFlex EDM (p < 0.05). TruNatomy Glider generated the highest torque and screw-in force during the apical preparation.

Conclusions

V Taper 2H #14/03 showed superior cyclic fatigue resistance and lower ultimate strength. TruNatomy Glider generated greater clockwise torque and screw-in force during apical preparation. The mechanical properties, torque, and screw-force was affected by design of heat-treated glide path instruments. Cervical pre-flaring prior to glide path instrument is recommended.
BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells
Authors: Liu C. , Yu J. , Liu B. , Liu M. , Song G. , Zhu L. , Peng B.
Published: November 2022

Background

The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro.

Methods

hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis.BACH1expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability.

Results

BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown ofBACH1greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression ofBACH1increased cell proliferation, ALP activity and the expression of mineralization markers.

Conclusions

Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.
Development and validation of machine learning-based risk prediction models of oral squamous cell carcinoma using salivary autoantibody biomarkers
Authors: Tseng Yi-Ju , Wang Yi-Cheng , Hsueh Pei-Chun , Wu Chih-Ching
Published: November 2022

Introduction

The incidence of oral cavity squamous cell carcinoma (OSCC) continues to rise. OSCC is associated with a low average survival rate, and most patients have a poor disease prognosis because of delayed diagnosis. We used machine learning techniques to predict high-risk cases of OSCC by using salivary autoantibody levels and demographic and behavioral data.

Methods

We collected the salivary samples of patients recruited from a teaching hospital between September 2008 and December 2012. Ten salivary autoantibodies, sex, age, smoking, alcohol consumption, and betel nut chewing were used to build prediction models for identifying patients with a high risk of OSCC. The machine learning algorithms applied in the study were logistic regression, random forest, support vector machine with the radial basis function kernel, eXtreme Gradient Boosting (XGBoost), and a stacking model. We evaluated the performance of the models by using the area under the receiver operating characteristic curve (AUC), with simulations conducted 100 times.

Results

A total of 337 participants were enrolled in this study. The best predictive model was constructed using a stacking algorithm with original forms of age and logarithmic levels of autoantibodies (AUC = 0.795 ± 0.055). Adding autoantibody levels as a data source significantly improved the prediction capability (from 0.698 ± 0.06 to 0.795 ± 0.055,p < 0.001).

Conclusions

We successfully established a prediction model for high-risk cases of OSCC. This model can be applied clinically through an online calculator to provide additional personalized information for OSCC diagnosis, thereby reducing the disease morbidity and mortality rates.
Assessing burnout among Obstetrics & Gynecology residents during night float versus day float in a large academic hospital
Authors: Tarrash Miriam , Nelson David , Gabbur Nagaraj , Goldberg Gary L.
Published: November 2022

Background

The prevalence estimates of burnout among residents vary widely. Resident physicians working overnight have additional stressors and therefore, may be at higher risk of developing burnout.

Objective

To determine the rates of burnout among residents working night rotations versus day rotations.

Methods

This is a prospective, cross sectional, survey-based assessment of the prevalence of burnout among Obstetrics and Gynecology (OBGYN) residents on nights versus days rotations conducted at a large academic residency program that spans two separate hospitals in New York. All residents in the residency program were asked to complete the Maslach Burnout Inventory – Human Services Survey for Medical Personnel (MBI-HSS (MP)) after the first rotation of the academic year in 2018, 2019, and 2020. The results for each of the three aspects of the MBI-HSS (MP): emotional exhaustion, depersonalization, and personal accomplishment, were then compared for those on nights versus day rotations using students t-test.

Results

A total of 76 responses were received, 13 from residents on night rotations and 63 from residents on day rotations with a response rate of 61.8%. Comparing resident responses for a night versus day rotation, the residents averaged a low level of emotional exhaustion (a score of 17 ± 9) on day shift, compared to a moderate level of emotional exhaustion (a score of 18 ± 14) on nights (p = 0.37). Similarly, 55.6% of respondents reports low personal accomplishment on days, compared to 76.9% while on nights.

Conclusions

Emotional exhaustion scores were lower for residents on daytime rotations (mean score 17, SD 9), compared to those on nights rotations (mean 18, SD 14). Although there was no difference in depersonalization when comparing the day and night shift, 45% of the responses indicated high levels of depersonalization regardless of the type of shift. These results highlight the need to continue efforts to minimize burnout in medical training.
Building a knowledge base for colorectal cancer patient care using formal concept analysis
Authors: Xiang Jing , Xu Hanbing , Pokharel Suresh , Li Jiqing , Xue Fuzhong , Zhang Ping
Published: November 2022

Background

Colorectal cancer (CRC) is a heterogeneous disease with different responses to targeted therapies due to various factors, and the treatment effect differs significantly between individuals. Personalize medical treatment (PMT) is a method that takes individual patient characteristics into consideration, making it the most effective way to deal with this issue. Patient similarity and clustering analysis is an important aspect of PMT. This paper describes how to build a knowledge base using formal concept analysis (FCA), which clusters patients based on their similarity and preserves the relations between clusters in hierarchical structural form.

Methods

Prognostic factors (attributes) of 2442 CRC patients, including patient age, cancer cell differentiation, lymphatic invasion and metastasis stages were used to build a formal context in FCA. A concept was defined as a set of patients with their shared attributes. The formal context was formed based on the similarity scores between each concept identified from the dataset, which can be used as a knowledge base.

Results

A hierarchical knowledge base was constructed along with the clinical records of the diagnosed CRC patients. For each new patient, a similarity score to each existing concept in the knowledge base can be retrieved with different similarity calculations. The ranked similarity scores that are associated with the concepts can offer references for treatment plans.

Conclusions

Patients that share the same concept indicates the potential similar effect from same clinical procedures or treatments. In conjunction with a clinician’s ability to undergo flexible analyses and apply appropriate judgement, the knowledge base allows faster and more effective decisions to be made for patient treatment and care.
Identification of clinical factors related to prediction of alcohol use disorder from electronic health records using feature selection methods
Authors: Ebrahimi Ali , Wiil Uffe Kock , Naemi Amin , Mansourvar Marjan , Andersen Kjeld , Nielsen Anette Søgaard
Published: November 2022

Background

High dimensionality in electronic health records (EHR) causes a significant computational problem for any systematic search for predictive, diagnostic, or prognostic patterns. Feature selection (FS) methods have been indicated to be effective in feature reduction as well as in identifying risk factors related to prediction of clinical disorders. This paper examines the prediction of patients with alcohol use disorder (AUD) using machine learning (ML) and attempts to identify risk factors related to the diagnosis of AUD.

Methods

A FS framework consisting of two operational levels, base selectors and ensemble selectors. The first level consists of five FS methods: three filter methods, one wrapper method, and one embedded method. Base selector outputs are aggregated to develop four ensemble FS methods. The outputs of FS method were then fed into three ML algorithms: support vector machine (SVM), K-nearest neighbor (KNN), and random forest (RF) to compare and identify the best feature subset for the prediction of AUD from EHRs.

Results

In terms of feature reduction, the embedded FS method could significantly reduce the number of features from 361 to 131. In terms of classification performance, RF based on 272 features selected by our proposed ensemble method (Union FS) with the highest accuracy in predicting patients with AUD, 96%, outperformed all other models in terms of AUROC, AUPRC, Precision, Recall, and F1-Score. Considering the limitations of embedded and wrapper methods, the best overall performance was achieved by our proposed Union Filter FS, which reduced the number of features to 223 and improved Precision, Recall, and F1-Score in RF from 0.77, 0.65, and 0.71 to 0.87, 0.81, and 0.84, respectively. Our findings indicate that, besides gender, age, and length of stay at the hospital, diagnosis related to digestive organs, bones, muscles and connective tissue, and the nervous systems are important clinical factors related to the prediction of patients with AUD.

Conclusion

Our proposed FS method could improve the classification performance significantly. It could identify clinical factors related to prediction of AUD from EHRs, thereby effectively helping clinical staff to identify and treat AUD patients and improving medical knowledge of the AUD condition. Moreover, the diversity of features among female and male patients as well as gender disparity were investigated using FS methods and ML techniques.
Economic evaluation of COVID-19 rapid antigen screening programs in the workplace
Authors: Vilches Thomas N. , Rafferty Ellen , Wells Chad R. , Galvani Alison P. , Moghadas Seyed M.
Published: November 2022

Background

Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective.

Methods

To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults.

Results

Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening.

Conclusions

Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.
Prognostic models for COVID-19 needed updating to warrant transportability over time and space
Authors: van Klaveren David , Zanos Theodoros P. , Nelson Jason , Levy Todd J. , Park Jinny G. , Retel Helmrich Isabel R. A. , Rietjens Judith A. C. , Basile Melissa J. , Hajizadeh Negin , Lingsma Hester F. , Kent David M.
Published: November 2022

Background

Supporting decisions for patients who present to the emergency department (ED) with COVID-19 requires accurate prognostication. We aimed to evaluate prognostic models for predicting outcomes in hospitalized patients with COVID-19, in different locations and across time.

Methods

We included patients who presented to the ED with suspected COVID-19 and were admitted to 12 hospitals in the New York City (NYC) area and 4 large Dutch hospitals. We used second-wave patients who presented between September and December 2020 (2137 and 3252 in NYC and the Netherlands, respectively) to evaluate models that were developed on first-wave patients who presented between March and August 2020 (12,163 and 5831). We evaluated two prognostic models for in-hospital death: The Northwell COVID-19 Survival (NOCOS) model was developed on NYC data and the COVID Outcome Prediction in the Emergency Department (COPE) model was developed on Dutch data. These models were validated on subsequent second-wave data at the same site (temporal validation) and at the other site (geographic validation). We assessed model performance by the Area Under the receiver operating characteristic Curve (AUC), by the E-statistic, and by net benefit.

Results

Twenty-eight-day mortality was considerably higher in the NYC first-wave data (21.0%), compared to the second-wave (10.1%) and the Dutch data (first wave 10.8%; second wave 10.0%). COPE discriminated well at temporal validation (AUC 0.82), with excellent calibration (E-statistic 0.8%). At geographic validation, discrimination was satisfactory (AUC 0.78), but with moderate over-prediction of mortality risk, particularly in higher-risk patients (E-statistic 2.9%). While discrimination was adequate when NOCOS was tested on second-wave NYC data (AUC 0.77), NOCOS systematically overestimated the mortality risk (E-statistic 5.1%). Discrimination in the Dutch data was good (AUC 0.81), but with over-prediction of risk, particularly in lower-risk patients (E-statistic 4.0%). Recalibration of COPE and NOCOS led to limited net benefit improvement in Dutch data, but to substantial net benefit improvement in NYC data.

Conclusions

NOCOS performed moderately worse than COPE, probably reflecting unique aspects of the early pandemic in NYC. Frequent updating of prognostic models is likely to be required for transportability over time and space during a dynamic pandemic.
Identifying susceptibility of children and adolescents to the Omicron variant (B.1.1.529)
Authors: Chun June Young , Jeong Hwichang , Kim Yongdai
Published: November 2022

Background

The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is a characteristic disease in children. Current coronavirus disease 2019 (COVID-19) cases among children might be higher because (i) school-aged children have higher contact rates and (ii) the COVID-19 vaccination strategy prioritizes the elderly in most countries. However, there have been no reports confirming the age-varying susceptibility to the Omicron variant to date.

Methods

We developed an age-structured compartmental model, combining age-specific contact matrix in South Korea and observed distribution of periods between each stage of infection in the national epidemiological investigation. A Bayesian inference method was used to estimate the age-specific force of infection and, accordingly, age-specific susceptibility, given epidemic data during the third (pre-Delta), fourth (Delta driven), and fifth (Omicron driven) waves in South Korea. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta and Omicron variants, respectively.

Results

A significant difference between the age-specific susceptibility to the Omicron and that to the pre-Omicron variants was found in the younger age group. The rise in susceptibility to the Omicron/pre-Delta variant was highest in the 10–15 years age group (5.28 times [95% CI, 4.94–5.60]), and the rise in susceptibility to the Omicron/Delta variant was highest in the 15–19 years age group (3.21 times [95% CI, 3.12–3.31]), whereas in those aged 50 years or more, the susceptibility to the Omicron/pre-Omicron remained stable at approximately twofold.

Conclusions

Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains.
Optimization of l-malic acid production from acetate with Aspergillus oryzae DSM 1863 using a pH-coupled feeding strategy
Authors: Kövilein Aline , Aschmann Vera , Zadravec Lena , Ochsenreither Katrin
Published: November 2022

Background

Malic acid, a dicarboxylic acid mainly used in the food industry, is currently produced from fossil resources. The utilization of low-cost substrates derived from biomass could render microbial processes economic. Such feedstocks, like lignocellulosic hydrolysates or condensates of fast pyrolysis, can contain high concentrations of acetic acid. Acetate is a suitable substrate for l-malic acid production with the filamentous fungus Aspergillus oryzae DSM 1863, but concentrations obtained so far are low. An advantage of this carbon source is that it can be used for pH control and simultaneous substrate supply in the form of acetic acid. In this study, we therefore aimed to enhance l-malate production from acetate with A. oryzae by applying a pH-coupled feeding strategy.

Results

In 2.5-L bioreactor fermentations, several feeding strategies were evaluated. Using a pH-coupled feed consisting of 10 M acetic acid, the malic acid concentration was increased about 5.3-fold compared to the batch process without pH control, resulting in a maximum titer of 29.53 ± 1.82 g/L after 264 h. However, it was not possible to keep both the pH and the substrate concentration constant during this fermentation. By using 10 M acetic acid set to a pH of 4.5, or with the repeated addition of NaOH, the substrate concentration could be maintained within a constant range, but these strategies did not prove beneficial as lower maximum titers and yields were obtained. Since cessation of malic acid production was observed in later fermentation stages despite carbon availability, a possible product inhibition was evaluated in shake flask cultivations. In these experiments, malate and succinate, which is a major by-product during malic acid production, were added at concentrations of up to 50 g/L, and it was found that A. oryzae is capable of organic acid production even at high product concentrations.

Conclusions

This study demonstrates that a suitable feeding strategy is necessary for efficient malic acid production from acetate. It illustrates the potential of acetate as carbon source for microbial production of the organic acid and provides useful insights which can serve as basis for further optimization.
A novel co-production of cadaverine and succinic acid based on a thermal switch system in recombinant Escherichia coli
Authors: Gao Siyuan , Lu Jiachen , Wang Tongtao , Xu Sheng , Wang Xin , Chen Kequan , Ouyang Pingkai
Published: November 2022

Background

Polyamide (nylon) is an important material, which has aroused plenty of attention from all aspects. PA 5.4 is one kind of nylon with excellent property, which consists of cadaverine and succinic acid. Due to the environmental pollution, bio-production of cadaverine and succinic acid has been more attractive due to the less pollution and environmental friendliness. Microbes, like Escherichia coli, has been employed as cell factory to produce cadaverine and succinic acid. However, the accumulation of cadaverine will cause severe damage on cells resulting in inhibition on cell growth and cadaverine production. Herein, a novel two stage co-production of succinic acid and cadaverine was designed based on an efficient thermos-regulated switch to avoid the inhibitory brought by cadaverine.

Results

The fermentation process was divided into two phase, one for cell growth and lysine production and the other for cadaverine and succinic acid synthesis. The genes of ldhA and ackA were deleted to construct succinic acid pathway in cadaverine producer strain. Then, a thermal switch system based on pR/pL promoter and CI857 was established and optimized. The fermentation conditions were investigated that the optimal temperature for the first stage was determined as 33 ℃ and the optimal temperature for the second stage was 39 ℃. Additionally, the time to shifting temperature was identified as the fermentation anaphase. For further enhance cadaverine and succinic acid production, a scale-up fermentation in 5 L bioreactor was operated. As a result, the titer, yield and productivity of cadaverine was 55.58 g/L, 0.38 g/g glucose and 1.74 g/(L·h), respectively. 28.39 g/L of succinic acid was also obtained with yield of 0.19 g/g glucose.

Conclusion

The succinic acid metabolic pathway was constructed into cadaverine producer strain to realize the co-production of succinic acid and cadaverine. This study provided a novel craft for industrial co-production of cadaverine and succinic acid.
Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?
Authors: Shayan Sara , Arashkia Arash , Azadmanesh Kayhan
Published: November 2022

Viruses are completely dependent on host cell machinery for their reproduction. As a result, factors that influence the state of cells, such as signaling pathways and gene expression, could determine the outcome of viral pathogenicity. One of the important factors influencing cells or the outcome of viral infection is the level of oxygen. Recently, oncolytic virotherapy has attracted attention as a promising approach to improving cancer treatment. However, it was shown that tumor cells are mostly less oxygenated compared with their normal counterparts, which might affect the outcome of oncolytic virotherapy. Therefore, knowing how oncolytic viruses could cope with stressful environments, particularly hypoxic environments, might be essential for improving oncolytic virotherapy.
The role of bone marrow on the mechanical properties of trabecular bone: a systematic review
Authors: Wang Fangxing , Metzner Florian , Osterhoff Georg , Zheng Leyu , Schleifenbaum Stefan
Published: November 2022

Background

Accurate evaluation of the mechanical properties of trabecular bone is important, in which the internal bone marrow plays an important role. The aim of this systematic review is to investigate the roles of bone marrow on the mechanical properties of trabecular bone to better support clinical work and laboratory research.

Methods

A systematic review of the literature published up to June 2022 regarding the role of bone marrow on the mechanical properties of trabecular bone was performed, using PubMed and Web of Science databases. The journal language was limited to English. A total of 431 articles were selected from PubMed (n = 186), Web of Science (n = 244) databases, and other sources (n = 1).

Results

After checking, 38 articles were finally included in this study. Among them, 27 articles discussed the subject regarding the hydraulic stiffening of trabecular bone due to the presence of bone marrow. Nine of them investigated the effects of bone marrow on compression tests with different settings, i.e., in vitro experiments under unconfined and confined conditions, and computer model simulations. Relatively few controlled studies reported the influence of bone marrow on the shear properties of trabecular bone.

Conclusion

Bone marrow plays a non-neglectable role in the mechanical properties of trabecular bone, its contribution varies depending on the different loading types and test settings. To obtain the mechanical properties of trabecular bone comprehensively and accurately, the solid matrix (trabeculae) and fluid-like component (bone marrow) should be considered in parallel rather than tested separately.
Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays
Authors: Abrantes Mafalda , Rodrigues Diana , Domingues Telma , Nemala Siva S. , Monteiro Patricia , Borme Jérôme , Alpuim Pedro , Jacinto Luis
Published: November 2022

Detecting physiological levels of neurotransmitters in biological samples can advance our understanding of brain disorders and lead to improved diagnostics and therapeutics. However, neurotransmitter sensors for real-world applications must reliably detect low concentrations of target analytes from small volume working samples. Herein, a platform for robust and ultrasensitive detection of dopamine, an essential neurotransmitter that underlies several brain disorders, based on graphene multitransistor arrays (gMTAs) functionalized with a selective DNA aptamer is presented. High-yield scalable methodologies optimized at the wafer level were employed to integrate multiple graphene transistors on small-size chips (4.5 × 4.5 mm). The multiple sensor array configuration permits independent and simultaneous replicate measurements of the same sample that produce robust average data, reducing sources of measurement variability. This procedure allowed sensitive and reproducible dopamine detection in ultra-low concentrations from small volume samples across physiological buffers and high ionic strength complex biological samples. The obtained limit-of-detection was 1 aM (10–18) with dynamic detection ranges spanning 10 orders of magnitude up to 100 µM (10–8), and a 22 mV/decade peak sensitivity in artificial cerebral spinal fluid. Dopamine detection in dopamine-depleted brain homogenates spiked with dopamine was also possible with a LOD of 1 aM, overcoming sensitivity losses typically observed in ion-sensitive sensors in complex biological samples. Furthermore, we show that our gMTAs platform can detect minimal changes in dopamine concentrations in small working volume samples (2 µL) of cerebral spinal fluid samples obtained from a mouse model of Parkinson’s Disease. The platform presented in this work can lead the way to graphene-based neurotransmitter sensors suitable for real-world academic and pre-clinical pharmaceutical research as well as clinical diagnosis.
The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors
Authors: Zalpoor Hamidreza , Aziziyan Fatemeh , Liaghat Mahsa , Bakhtiyari Maryam , Akbari Abdullatif , Nabi-Afjadi Mohsen , Forghaniesfidvajani Razieh , Rezaei Nima
Published: November 2022

Innate and adaptive immune cells patrol and survey throughout the human body and sometimes reside in the tumor microenvironment (TME) with a variety of cell types and nutrients that may differ from those in which they developed. The metabolic pathways and metabolites of immune cells are rooted in cell physiology, and not only provide nutrients and energy for cell growth and survival but also influencing cell differentiation and effector functions. Nowadays, there is a growing awareness that metabolic processes occurring in cancer cells can affect immune cell function and lead to tumor immune evasion and angiogenesis. In order to safely treat cancer patients and prevent immune checkpoint blockade-induced toxicities and autoimmunity, we suggest using anti-angiogenic drugs solely or combined with Immune checkpoint blockers (ICBs) to boost the safety and effectiveness of cancer therapy. As a consequence, there is significant and escalating attention to discovering techniques that target metabolism as a new method of cancer therapy. In this review, a summary of immune-metabolic processes and their potential role in the stimulation of intracellular signaling in TME cells that lead to tumor angiogenesis, and therapeutic applications is provided.