bluuebunny/crossref_metadata_2025 huggingface dataset:
The BioCyc Metabolic Network Explorer
Authors: Paley Suzanne , Karp Peter D.
Published: April 2021

Background

The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show only a subset of all possible metabolite connections, or the results will be visually overwhelming. Existing tools, even those that purport to show an organism’s full metabolic network, limit the set of displayed connections based on predefined pathways or other preselected criteria. We sought instead to provide a tool that would give the user dynamic control over which connections to follow.

Results

The Metabolic Network Explorer is an easy-to-use, web-based software tool that allows the user to specify a starting metabolite of interest and interactively explore its immediate metabolic neighborhood in either or both directions to any desired depth, letting the user select from the full set of connected reactions. Although, as for other tools, only a small portion of the metabolic network is visible at a time, that portion is selected by the user, based on the full reaction complement, and it is easy to switch among alternate paths of interest. The display is intuitive, customizable, and provides copious links to more detailed information pages.

Conclusions

The Metabolic Network Explorer fills a gap in the set of metabolic network visualization tools and complements other modes of exploration. Its primary strengths are its ease of use, diagrams that are intuitive to biologists, and its integration with the broader corpus of data provided by a BioCyc Pathway/Genome Database.
Using CPAP in COVID-19 patients outside of the intensive care setting: a comparison of survival and outcomes between dialysis and non-dialysis dependent patients
Authors: Floyd Lauren , Stauss Madelena , Storrar Joshua , Vanalia Parthvi , France Anna , Dhaygude Ajay
Published: April 2021

Background

SARS-CoV-2 (COVID-19) is a novel coronavirus associated with high mortality rates. The use of Continuous Positive Airway Pressure (CPAP) has been recognised as a management option for severe COVID-19 (NHS, Specialty guides for patient management during the coronavirus pandemic Guidance for the role and use of non-invasive respiratory support in adult patients with coronavirus (confirmed or suspected), https://www.nice.org.uk/guidance/ng159). We offered ward-based CPAP to COVID-19, dialysis patients not suitable for escalation to ICU. The aim of the study was to evaluate the use of CPAP for COVID-19 dialysis patients compared to non-dialysis COVID-19 patients outside of the intensive care setting. We further aimed to investigate factors associated with improved outcomes.

Methods

Data was collected from a single centre (Royal Preston Hospital, UK), from March to June 2020. Treatment outcomes were compared for dialysis and non-dialysis dependent patients who received CPAP with limitations on their escalation and resuscitation status. Kaplan-Meier survival curves and Cox regression models were used to compare outcomes. The primary study outcome was 30 day mortality. Confounders including length of admission, systemic anticoagulation and ultrafiltration volumes on dialysis were also analysed.

Results

Over the study period, 40 dialysis patients tested positive for COVID-19, with 30 requiring hospital admission. 93% (n = 28) required supplementary oxygen and 12% (n = 9) required CPAP on the ward. These patients were compared to a serial selection of 14 non-dialysis patients treated with CPAP during the same period. Results showed a significant difference in 30 day survival rates between the two groups: 88.9% in the dialysis group vs. 21.4% in the non-dialysis group. Statistical modelling showed that anticoagulation was also an important factor and correlated with better outcomes.

Conclusion

This is to the best of our knowledge, the largest series of COVID-19 dialysis patients treated with CPAP in a ward-based setting. In general, dialysis dependent patients have multiple co-morbidities including cardiovascular disease and diabetes mellitus making them vulnerable to COVID-19 and not always suitable for treatment in ICU. We showed a significantly lower 30 day mortality rate with the use of CPAP in the dialysis group (11.1%) compared to the non-dialysis group (78.6%). Despite a small sample size, we believe this study provides impetus for further work clarifying the role of CPAP in treating COVID-19 dialysis dependent patients.
Aging-associated inflammation and fibrosis in arachnoid membrane
Authors: Suzuki Hime , Mikami Takeshi , Iwahara Naotoshi , Akiyama Yukinori , Wanibuchi Masahiko , Komatsu Katsuya , Yokoyama Rintaro , Hirano Tsukasa , Hosoda Ryusuke , Horio Yoshiyuki , Kuno Atsushi , Mikuni Nobuhiro
Published: April 2021

Background

The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis.

Methods

Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 μm) and the non-hyperplastic AM group (< 50 μm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFβ, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated.

Results

The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFβ and TNFα.

Conclusions

The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.
Effect of the CRADLE vital signs alert device intervention on referrals for obstetric haemorrhage in low-middle income countries: a secondary analysis of a stepped- wedge cluster-randomised control trial
Authors: Giblin Lucie , Vousden Nicola , Nathan Hannah , Gidiri Francis , Goudar Shivaprasad , Charantimath Umesh , Sandall Jane , Seed Paul T. , Chappell Lucy C. , Shennan Andrew H.
Published: April 2021

Background

Obstetric haemorrhage is the leading cause of maternal death worldwide, 99% of which occur in low and middle income countries. The majority of deaths and adverse events are associated with delays in identifying compromise and escalating care. Management of severely compromised pregnant women may require transfer to tertiary centres for specialised treatment, therefore early recognition is vital for efficient management. The CRADLE vital signs alert device accurately measures blood pressure and heart rate, calculates the shock index (heart rate divided by systolic blood pressure) and alerts the user to compromise through a traffic light system reflecting previously validated shock index thresholds.

Methods

This is a planned secondary analysis of data from the CRADLE-3 trial from ten clusters across Africa, India and Haiti where the device and training package were randomly introduced. Referral data were prospectively collected for a 4-week period before, and a 4-week period 3 months after implementation. Referrals from primary or secondary care facilities to higher level care for any cause were recorded. The denominator was the number of women seen for maternity care in these facilities.

Results

Between April 1 2016 and Nov 30th, 2017 536,223 women attended maternity care facilities. Overall, 3.7% (n = 2784/74,828) of women seen in peripheral maternity facilities were referred to higher level care in the control period compared to 4.4% (n = 3212/73,371) in the intervention period (OR 0.89; 0.39–2.05) (data for nine sites that were able to collect denominator). Of these 0.29% (n = 212) pre-intervention and 0.16% (n = 120) post-intervention were referred to higher-level facilities for maternal haemorrhage. Although overall referrals did not significantly reduce there was a significant reduction in referrals for obstetric haemorrhage (OR 0.56 (0.39–0.65) following introduction of the device with homogeneity (i-squared 26.1) between sites. There was no increase in any bleeding-related morbidity (maternal death or emergency hysterectomy).

Conclusions

Referrals for obstetric haemorrhage reduced following implementation of the CRADLE Vital Signs Alert Device, occurring without an increase in maternal death or emergency hysterectomy. This demonstrates the potential benefit of shock index in management pathways for obstetric haemorrhage and targeting limited resources in low- middle- income settings.

Trial registration

This study is registered with the ISRCTN registry, number ISRCTN41244132 (02/02/2016).
Clinical outcomes observation in stage IIB–IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy
Authors: Li Yong , Chen Zhiying , Wang Xiang , Li Xiumei , Zhou Jie , Zhang Yongchun
Published: April 2021

Background

To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB–IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery.

Methods

Forty-nine patients diagnosed with stage IIB–IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed.

Results

Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 andP = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 andP = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 andP = 0.044, respectively).

Conclusion

CCRT combined with surgery for stage IIB–IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.
Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment
Authors: Al-Aamri Hussain Mubarak , Irving Helen R. , Bradley Christopher , Meehan-Andrews Terri
Published: April 2021

Background

Daunorubicin is used clinically in the treatment of myeloma, acute lymphatic and myelocytic leukaemia. The toxic lesions caused by daunorubicin induce various modes of cell death, including apoptosis. Apoptosis is highly regulated programmed cell death that can be initiated mainly via two pathways, through death receptors (extrinsic) or involvement of the mitochondria (intrinsic). Induction of apoptosis via these pathways has been alluded following treatment with daunorubicin, but never compared in acute lymphoblastic leukaemia over a time course.

Methods

This study investigated the mechanisms of daunorubicin induced apoptosis in the treatment of CCRF-CEM, MOLT-4 (acute T-lymphoblastic leukaemia) and SUP-B15 (acute B-lymphoblastic leukaemia) cells. Cells were treated with daunorubicin for 4 h, and then placed in recovery medium (without daunorubicin) for 4 h, 12 h and 24 h. Apoptotic response was analysing using annexin-V expression, caspase activity, mitochondrial membrane potential change and an array to detect 43 apoptotic proteins.

Results

Daunorubicin induced apoptosis in all leukemic cell lines, but with different levels and duration of response. Both apoptosis levels and caspase activity increased after four hours recovery then declined in CCRF-CEM and MOLT-4 cells. However, SUP-B15 cells displayed initially comparable levels but remained elevated over the 24 h assessment period. Changes in mitochondrial membrane potential occurred in both MOLT-4 and CCRF-CEM cells but not in SUP-B15 cells. Expression of apoptotic proteins, including Bcl-2, Bax, caspase 3 and FADD, indicated that daunorubicin potentially induced both extrinsic and intrinsic apoptosis in both CCRF-CEM and MOLT-4 cells, but only extrinsic apoptosis in SUP-B15 cells.

Conclusions

This study describes variations in sensitivities and timing of apoptotic responses in different leukaemia cell lines. These differences could be attributed to the lack of functional p53 in coordinating the cells response following cytotoxic treatment with daunorubicin, which appears to delay apoptosis and utilises alternative signalling mechanisms that need to be further explored.
Improving knowledge, attitudes and practice to prevent COVID-19 transmission in healthcare workers and the public in Thailand
Authors: Maude Rapeephan R. , Jongdeepaisal Monnaphat , Skuntaniyom Sumawadee , Muntajit Thanomvong , Blacksell Stuart D. , Khuenpetch Worarat , Pan-Ngum Wirichada , Taleangkaphan Keetakarn , Malathum Kumtorn , Maude Richard James
Published: April 2021

Background

Key infection prevention and control measures to limit transmission of COVID-19 include social distancing, hand hygiene, use of facemasks and personal protective equipment. However, these have limited or no impact if not applied correctly through lack of knowledge, inappropriate attitude or incorrect practice. In order to maximise the impact of infection prevention and control measures on COVID-19 spread, we undertook a study to assess and improve knowledge, attitudes and practice among 119 healthcare workers and 100 general public in Thailand. The study setting was two inpatient hospitals providing COVID-19 testing and treatment. Detailed information on knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations.

Results

Knowledge of the main transmission routes, commonest symptoms and recommended prevention methods was mostly very high (> 80%) in both groups. There was lower awareness of aerosols, food and drink and pets as sources of transmission; of the correct duration for handwashing; recommended distance for social/physical distancing; and about recommended types of face coverings. Information sources most used and most trusted were the workplace, work colleagues, health workers and television. The results were used to produce a set of targeted educational videos which addressed many of these gaps with subsequent improvements on retesting in a number of areas. This included improvements in handwashing practice with an increase in the number of areas correctly washed in 65.5% of the public, and 57.9% of healthcare workers. The videos were then further optimized with feedback from participants followed by another round of retesting.

Conclusions

Detailed information on gaps in knowledge, attitudes and practice among the general public and healthcare workers regarding COVID-19 transmission and its prevention were obtained from a combination of questionnaires and observations. This was used to produce targeted educational videos which addressed these gaps with subsequent improvements on retesting. The resulting videos were then disseminated as a resource to aid in efforts to fight COVID-19 in Thailand and worldwide.
A cross-sectional study of opioid involvement in non-poisoning suicide – risks and prevention opportunities
Authors: Mason Maryann , Welch Sarah B. , McLone Suzanne , Bartell Tami , Lank Patrick M. , Sheehan Karen , Post Lori Ann
Published: April 2021

Objective

To examine prevalence, demographic, and incident factors associated with opioid-positivity in Illinois suicide decedents who died by causes other than poisoning.

Method

Cross-sectional study of Illinois’ suicide decedents occurring between January 2015 and December 2017. Data come from the National Violent Death Reporting System. We used Chi-square tests to compare decedent and incident circumstance characteristics by opioid toxicology screen status. Incident narratives were analyzed to obtain physical and mental health histories and circumstances related to fatal injury events.

Results

Of 1007 non-poisoning suicide decedents screened for opioids, 16.4% were opioid-positive. White race, age 75 and over, and widowed or unknown marital status were associated with opioid-positivity. Among opioid-positive decedents, 25% had a history of substance use disorder (SUD), 61% depression, and 19% anxiety. The majority (52%) of opioid-positive decedents died by firearm, a higher percentage than opioid-negative decedents.

Conclusion

The opioid overdose crisis largely has not overlapped with non-poisoning suicide in this study. Overall, our analyses have not identified additional risk factors for suicide among opioid-positive suicide decedents. However, the overlap between opioid-positivity, SUD, and physical and mental health problems found among decedents in our data suggest several suicide prevention opportunities. These include medication assisted treatment for SUD which has been shown to reduce suicide, screening for opioid/benzodiazepine overlap, and limiting access to lethal means during opioid use. Improved death scene investigations for substances and use of the Prescription Drug Monitoring Program to document prescriptions are needed to further understanding of the role of substances in non-poisoning suicide.
Empathy and attitude toward communication skill learning as a predictor of patient-centered attitude: a cross-sectional study of dental students in Korea
Authors: Lee Minjung , Ihm Jungjoon
Published: April 2021

Background

Enhancing medical students’ practice of patient-centered care is a goal of medical schools. In addition to exploring the demographic and academic factors of the students, it is necessary to identify other attitudes and perceptions that may influence the student’s patient-centered attitude and inclination toward communication skill learning. This study aimed to assess patient-centered attitudes among dental students in Korea and identify the association between the students’ characteristics and empathy, communication skill learning attitude, and patient-centered attitude.

Methods

Data were collected via a cross-sectional online survey, and 312 dental students were included in the analyses. The study participants completed the Patient–Practitioner Orientation Scale (PPOS), the Interpersonal Reactivity Index (IRI), and the Communication Skills Attitude Scale (CSAS). Analyses were performed using independent samples’ t-tests, hierarchical multi-variable regression, and ANOVA with a post-hoc Tukey test.

Results

The students tend to be moderately patient-oriented toward the sharing subscale of PPOS score (M = 3.78, standard deviation [SD] = 0.54) and slightly more patient-centered toward the caring subscale of PPOS score (M = 4.41, SD = 0.52) of patient-centered attitudes. Being a female and a shorter academic period in dentistry were associated with attitudes toward patient-centered care. Empathy and positive attitude toward learning communication skills were also related to a patient-centered attitude, and among aspects of empathy, “empathic concern” had the greatest significant impact on patient-centered attitude.

Conclusions

Gender, academic period, empathy, and attitudes on learning communication skills were important influencing factors of patient-centered attitudes. Patient-centered attitude can and must be taught. Education programs should focus on enhancing empathy, emphasizing positive attitudes on learning communication skills, and conducting follow-up educational sessions to prevent students from becoming less patient-centered with an increase in duration of their academic period.
Statistical models for analyzing count data: predictors of length of stay among HIV patients in Portugal using a multilevel model
Authors: Shaaban Ahmed Nabil , Peleteiro Bárbara , Martins Maria Rosario O.
Published: April 2021

Background

This study offers a comprehensive approach to precisely analyze the complexly distributed length of stay among HIV admissions in Portugal.

Objective

To provide an illustration of statistical techniques for analysing count data using longitudinal predictors of length of stay among HIV hospitalizations in Portugal.

Method

Registered discharges in the Portuguese National Health Service (NHS) facilities Between January 2009 and December 2017, a total of 26,505 classified under Major Diagnostic Category (MDC) created for patients with HIV infection, with HIV/AIDS as a main or secondary cause of admission, were used to predict length of stay among HIV hospitalizations in Portugal. Several strategies were applied to select the best count fit model that includes the Poisson regression model, zero-inflated Poisson, the negative binomial regression model, and zero-inflated negative binomial regression model. A random hospital effects term has been incorporated into the negative binomial model to examine the dependence between observations within the same hospital. A multivariable analysis has been performed to assess the effect of covariates on length of stay.

Results

The median length of stay in our study was 11 days (interquartile range: 6–22). Statistical comparisons among the count models revealed that the random-effects negative binomial models provided the best fit with observed data. Admissions among males or admissions associated with TB infection, pneumocystis, cytomegalovirus, candidiasis, toxoplasmosis, or mycobacterium disease exhibit a highly significant increase in length of stay. Perfect trends were observed in which a higher number of diagnoses or procedures lead to significantly higher length of stay. The random-effects term included in our model and refers to unexplained factors specific to each hospital revealed obvious differences in quality among the hospitals included in our study.

Conclusions

This study provides a comprehensive approach to address unique problems associated with the prediction of length of stay among HIV patients in Portugal.
Dysphagia symptoms in obstructive sleep apnea: prevalence and clinical correlates
Authors: Pizzorni Nicole , Radovanovic Dejan , Pecis Marica , Lorusso Rosaria , Annoni Federica , Bartorelli Alice , Rizzi Maurizio , Schindler Antonio , Santus Pierachille
Published: April 2021

Background

Epidemiology of dysphagia and its drivers in obstructive sleep apnea (OSA) are poorly understood. The study aims to investigate the prevalence of dysphagia symptoms and their association with demographic and clinical factors in patients with OSA.

Methods

Patients with OSA referring to an Academic Sleep Outpatient Clinic were enrolled in a prospective study. Demographic, clinical characteristics, and OSA symptoms were collected. All patients underwent home sleep cardiorespiratory polygraphy and the Eating-Assessment Tool questionnaire (EAT-10) to investigate dysphagia symptoms. Patients with a positive EAT-10 were offered to undergo a fiberoptic endoscopic evaluation of swallowing (FEES) to confirm the presence of dysphagia. FEES findings were compared with a healthy control group. Univariate and multivariate analyses were performed to assess predictors of dysphagia.

Results

951 patients with OSA (70% males, age 62 IQR51-71) completed the EAT-10, and 141 (15%) reported symptoms of dysphagia. Female gender (OR = 2.31), excessive daily sleepiness (OR = 2.24), number of OSA symptoms (OR = 1.25), anxiety/depression (OR = 1.89), and symptoms of gastroesophageal reflux (OR = 2.75) were significantly (p < 0.05) associated with dysphagia symptoms. Dysphagia was confirmed in 34 out of 35 symptomatic patients that accepted to undergo FEES. Patients with OSA exhibited lower bolus location at swallow onset, greater pharyngeal residue, and higher frequency and severity of penetration and aspiration events than healthy subjects (p < 0.05).

Conclusion

A consistent number of patients with OSA show symptoms of dysphagia, which are increased in females and patients with a greater OSA symptomatology, anxiety and depression, and gastroesophageal reflux. The EAT-10 appears a useful tool to guide the selection of patients at high risk of dysphagia. In clinical practice, the integration of screening for dysphagia in patients with OSA appears advisable.
Engineering the acyltransferase domain of epothilone polyketide synthase to alter the substrate specificity
Authors: Wang Huimin , Liang Junheng , Yue Qianwen , Li Long , Shi Yan , Chen Guosong , Li Yue-zhong , Bian Xiaoying , Zhang Youming , Zhao Guoping , Ding Xiaoming
Published: April 2021

Background

Polyketide synthases (PKSs) include ketone synthase (KS), acyltransferase (AT) and acyl carrier protein (ACP) domains to catalyse the elongation of polyketide chains. Some PKSs also contain ketoreductase (KR), dehydratase (DH) and enoylreductase (ER) domains as modification domains. Insertion, deletion or substitution of the catalytic domains may lead to the production of novel polyketide derivatives or to the accumulation of desired products. Epothilones are 16-membered macrolides that have been used as anticancer drugs. The substrate promiscuity of the module 4 AT domain of the epothilone PKS (EPOAT4) results in production of epothilone mixtures; substitution of this domain may change the ratios of epothilones. In addition, there are two dormant domains in module 9 of the epothilone PKS. Removing these redundant domains to generate a simpler and more efficient assembly line is a desirable goal.

Results

The substitution of module 4 drastically diminished the activity of epothilone PKS. However, with careful design of the KS-AT linker and the post-AT linker, replacing EPOAT4 with EPOAT2, EPOAT6, EPOAT7 or EPOAT8 (specifically incorporating methylmalonyl-CoA (MMCoA)) significantly increased the ratio of epothilone D (4) to epothilone C (3) (the highest ratio of 4:3 = 4.6:1), whereas the ratio of 4:3 in the parental strain Schlegelella brevitalea 104-1 was 1.4:1. We also obtained three strains by swapping EPOAT4 with EPOAT3, EPOAT5, or EPOAT9, which specifically incorporate malonyl-CoA (MCoA). These strains produced only epothilone C, and the yield was increased by a factor of 1.8 compared to that of parental strain 104-1. Furthermore, mutations of five residues in the AT domain identified Ser310 as the critical factor for MMCoA recognition in EPOAT4. Then, the mutation of His308 to valine or tyrosine combined with the mutation of Phe310 to serine further altered the product ratios. At the same time, we successfully deleted the inactive module 9 DH and ER domains and fused the ΨKR domain with the KR domain through an ~ 25-residue linker to generate a productive and simplified epothilone PKS.

Conclusions

These results suggested that the substitution and deletion of catalytic domains effectively produces desirable compounds and that selection of the linkers between domains is crucial for maintaining intact PKS catalytic activity.
Identification of heart rate dynamics during treadmill exercise: comparison of first- and second-order models
Authors: Wang Hanjie , Hunt Kenneth J.
Published: April 2021

Background

Characterisation of heart rate (HR) dynamics and their dependence on exercise intensity provides a basis for feedback design of automatic HR control systems. This work aimed to investigate whether the second-order models with separate Phase I and Phase II components of HR response can achieve better fitting performance compared to the first-order models that do not delineate the two phases.

Methods

Eleven participants each performed two open-loop identification tests while running at moderate-to-vigorous intensity on a treadmill. Treadmill speed was changed as a pseudo-random binary sequence (PRBS) to excite both the Phase I and Phase II components. A counterbalanced cross-validation approach was implemented for model parameter estimation and validation.

Results

Comparison of validation outcomes for 22 pairs of first- and second-order models showed that root-mean-square error (RMSE) was significantly lower and fit (normalised RMSE) significantly higher for the second-order models: RMSE was 2.07 bpm ± 0.36 bpm vs. 2.27 bpm ± 0.36 bpm (bpm = beats per min), second order vs. first order, with $$p = 2.8 \times 10^{-10}$$

p
=
2.8
×

10

-
10

; fit was $$54.5\% \pm 5.2$$

54.5
%
±
5.2

% vs. $$50.2\% \pm 4.8$$

50.2
%
±
4.8

%, $$p = 6.8 \times 10^{-10}$$

p
=
6.8
×

10

-
10

.

Conclusion

Second-order models give significantly better goodness-of-fit than first-order models, likely due to the inclusion of both Phase I and Phase II components of heart rate response. Future work should investigate alternative parameterisations of the PRBS excitation, and whether feedback controllers calculated using second-order models give better performance than those based on first-order models.
Relationship between both cardiorespiratory and muscular fitness and health-related quality of life in children and adolescents: a systematic review and meta-analysis of observational studies
Authors: Bermejo-Cantarero Alberto , Álvarez-Bueno Celia , Martínez-Vizcaino Vicente , Redondo-Tébar Andrés , Pozuelo-Carrascosa Diana P. , Sánchez-López Mairena
Published: April 2021

Background

No review to date has evaluated the association between physical fitness and health-related quality of life (HRQoL) in healthy children and adolescents. The aims of this systematic review and meta-analysis were to examine the relationship between both cardiorespiratory fitness (CRF) and muscular fitness (MF) and HRQoL in healthy subjects under 18 years of age and to describe the dimensions of HRQoL in which these relationships are more robust.

Methods

The Medline, Embase, Cochrane Library, SCIELO, SPORTDiscus and PEDro databases were systematically searched to collect observational studies that examined the relationship between CRF and HRQoL and between MF and HRQoL in participants under 18 years of age without any diagnosed medical condition. Pooled effect sizes (ES) were estimated for the associations between both CRF and MF and the various HRQoL dimensions.

Results

The pooled ES (95% CI) estimates for the relationship between CRF and HRQoL were as follows: 0.19 (0.10 to 0.27) for physical well-being, 0.19 (0.07 to 0.32) for psychological well-being, 0.20 (− 0.14 to 0.55) for perceived health status, 0.10 (0.00 to 0.20) for self-perception/self-esteem, 0.07 (− 0.05 to 0.19) for quality of family relationship, 0.14 (0.04 to 0.25) for quality of peer relationship, 0.17 (0.04 to 0.29) for everyday functioning at school and 0.20 (0.12 to 0.28) for total HRQoL score. The pooled ES (95% CI) estimates for the relationship between MF and HRQoL were: 0.25 (0.12 to 0.37) for physical well-being, 0.11 (0.04 to 0.17) for psychological well-being, 0.08 (0.01 to 0.15) for quality of family relationship, 0.14 (0.03 to 0.25) for quality of peer relationship, and 0.09 (0.03 to 0.14) for total HRQoL score.

Conclusions

Our data suggest that both CRF and MF are positively associated with HRQoL, mainly in physical, psychological and peer relationships. Moreover, CRF is positively associated with school dimensions and MF is positively associated with family relationships.

Trail registration Protocol PROSPERO registration number: CRD42015025823.
Typology of changes in quality of life over 12 months among currently or formerly homeless individuals using different housing services in Quebec, Canada
Authors: Kaltsidis Gesthika , Grenier Guy , Cao Zhirong , L’Espérance Nadia , Fleury Marie-Josée
Published: April 2021

Background

In health and social service evaluations, including research on homelessness, quality of Life (QOL) is often used as a key indicator of well-being among service users. However, no typology has been developed on changes in QOL over a 12-month period for a heterogenous sample of homeless individuals.

Methods

Cluster analysis was employed to identify a typology of change in QOL for 270 currently or formerly homeless individuals using emergency shelters, temporary housing (TH) and permanent housing (PH) services in Quebec (Canada). Participant interviews were conducted at baseline and 12 months later. An adapted Gelberg–Andersen Model helped organize QOL-related sociodemographic, clinical, and service use variables into predisposing, needs, and enabling factors, respectively. Comparison analyses were performed to determine group differences.

Results

Four groups emerged from the analyses: (1) young women in stable-PH or improved housing status with moderately high needs and specialized ambulatory care service use, with improved QOL over 12 months; (2) middle-age to older men with stable housing status, few needs and low acute care service use, with most improvement in QOL over 12 months; (3) older individuals residing in stable-PH or improved housing status with very high needs and reduced QOL over 12 months; and (4) men in stable-TH or worse housing status, with high substance use disorder, using few specialized ambulatory care services and showing decline in QOL over 12 months.

Conclusions

Findings suggest that positive change in QOL over 12 months was mainly associated with fewer needs, and stability in housing status more than housing improvement. Specific recommendations, such as assertive community treatment and harm reduction programs, should be prioritized for individuals with high needs or poor housing status, and among those experiencing difficulties related to QOL, whereas individuals with more favourable profiles could be encouraged to maintain stable housing and use services proportional to their needs.
Circ_0055625 knockdown inhibits tumorigenesis and improves radiosensitivity by regulating miR-338-3p/MSI1 axis in colon cancer
Authors: Gao Chao , Zhang Yi , Tian Yanming , Han Chun , Wang Lan , Ding Boyue , Tian Hua , Zhou Chaoxi , Ju Yingchao , Peng Ale , Yu Qiyao
Published: April 2021

Background

Radiotherapy is a main therapeutic method for cancers, including colon cancer. In the current study, we aim to explore the effects of circular RNA (circRNA) circ_0055625 in the progression and radiosensitivity of colon cancer and the underlying mechanism.

Methods

The expression of circ_0055625 and musashi homolog 1 (MSI1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MSI1 protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell survival fraction, apoptosis, and invasion were investigated by colony formation assay, flow cytometry analysis, and transwell invasion assay, respectively. Cell migration was detected by wound-healing and transwell migration assays. The binding relationship between microRNA-338-3p (miR-338-3p) and circ_0055625 or MSI1 was predicted by online databases and identified by Dual-Luciferase Reporter Assay. The effects of circ_0055625 silencing on the tumor formation and radiosensitivity of colon cancer in vivo were explored by in vivo tumor formation assay.

Results

Circ_0055625 and MSI1 were upregulated in colon cancer tissues and cells relative to control groups. Radiation treatment apparently increased the expression of circ_0055625 and MSI1 in colon cancer cells. Circ_0055625 knockdown or MSI1 silencing repressed cell proliferation, migration, and invasion and promoted cell apoptosis and radiosensitivity in colon cancer. Also, circ_0055625 silencing-mediated effects were attenuated by MSI1 overexpression. Additionally, circ_0055625 silencing reduced MSI1 expression, which could be attenuated by miR-338-3p inhibitor. Mechanically, circ_0055625 acted as a sponge for miR-338-3p to regulate MSI1. Furthermore, circ_0055625 knockdown hindered tumor growth and improved radiosensitivity in vivo.

Conclusion

Circ_0055625 repression inhibited the progression and radioresistance of colon cancer by downregulating MSI1 through sponging miR-338-3p. This result might provide a theoretical basis for improving the therapy of colon cancer with radiation.
Pushing occupational rehabilitation – implementation of a therapy diary in the outpatient aftercare of psychosomatic rehabilitation may promote the occupational reintegration process: a survey of therapists and patients
Authors: Thiel Carolin , Richter Cynthia , Samos Franziska-Antonia Zora , Heise Marcus , Frese Thomas , Fankhaenel Thomas
Published: April 2021

Background

Treatment results achieved after fulfilling an inpatient psychosomatic rehabilitation are often not permanent. Additional participation in outpatient rehabilitation aftercare may reduce the risk of recurrent disorders and support a successful reentry to working life. A therapy diary should accompany the aftercare and bring about the self-reflection process of psychosomatic rehabilitates, which could reduce recurrent disease progressions and support the recovery process as a whole. The study focuses on the evaluation of the effectiveness and implementation potentialities of a therapy diary in outpatient rehabilitation aftercare.

Methods

In a qualitative study, seven therapists for outpatient rehabilitation aftercare in Central Germany and eleven outpatient psychosomatic rehabilitation patients were interrogated using partially standardized, guideline-based expert interviews.

The data evaluation is based on the Qualitative Content Analysis according to Mayring.

Results

The results show that an accompanying use of a therapy diary during the outpatient rehabilitation aftercare enables an intense commitment through own thoughts and feelings. By writing down thoughts, emotions, dysfunctional behaviors in problematic situations, great successes are experienced. Through this initiated self-reflection process, the rehabilitant gains a better knowledge of one’s behavior in dealing with oneself and the environment and thereby, whenever necessary, learns to create new ways of acting.

Conclusions

The voluntary use of the therapy diary in the outpatient rehabilitation aftercare could assist the therapy process and henceforward the recovery of the rehabilitants, and also increase the prospect of successful occupational rehabilitation.
Availability, timeliness, documentation and quality of consultations among hospital departments: a prospective, comparative study
Authors: Jarjou’i Amir , Mendlovic Joseph , Dadon Ziv , Sneineh Marwan Abu , Tabi Meir , Kalak George , Jarallah Yousef R. , Yinnon Amos M. , Munter Gabriel
Published: April 2021

Background

Many in-patients require care from practitioners in various disciplines. Consultations most probably have significant implications for hospitalization outcomes.

Purpose

To determine key aspects of consultations provided by various departments to formulate an optimal policy.

Methods

This study comprised two methods: first, a questionnaire was completed in 2019 by 127 physicians interns, residents and senior doctors) from the medical and surgical departments (64 from the surgical wards, 43 from the medical wards and 22 from the emergency room and General ICU) regarding the availability, timeliness and documentation rate of the consultations they received from different disciplines. The investigators rounded through the various departments that were included in the study and they accosted a sample of interns, residents and attending physicians, who were then asked to fill the questionnaire. Overall compliance of filling the questionnaire was 95%. Residents accounted for 72% of the filled questionnaires, seniors and interns accounted for 15 and 13% respectively. Second, a convenience sample of 300 electronic records of hospitalized patients (135 from the surgical wards, 129 from the Medical wards and 36 from the emergency room and General ICU) of actually carried out consultations was reviewed for validated indicators of quality for both the consultation request and response. We used a 5-point Likert scale, ranging from poor (1) to superb (5), to grade the measured parameters.

Results

The availability, timeliness and documentation rate for medical consultations were 4 ± 0.9, 4.1 ± 0.9 and 4.3 ± 0.9 respectively, as compared with surgical consultations 3.2 ± 1.1, 3.4 ± 1.2 and 3.6 ± 1.2 respectively (P < 0.001). The mean time (in hours) from the consultation request till documentation (of the requested consultation) by consultants in the medical and surgical departments was 3.9 ± 5.9 and 10.0 ± 15.6, respectively (P < 0.001). The quality of requests of consultations from the medical and surgical departments was 3.4 ± 1.1 and 2.8 ± 1.2, respectively (P < 0.001). Two different models of consultations are employed: while each medical department adopts several departments for medical consultations, each day’s on-call surgeon provides all the hospital’s surgical consultations.

Conclusion

We detected significant differences in key aspects of consultations provided by the departments. The medical model of consultations, in which each medical department adopts several other wards to which it provides consulting services upon request, should probably be adopted as a major policy decision by hospitals directors to enhance inter-departmental consultations.
Genetic basis of negative heterosis for growth traits in chickens revealed by genome-wide gene expression pattern analysis
Authors: Mai Chunning , Wen Chaoliang , Xu Zhiyuan , Xu Guiyun , Chen Sirui , Zheng Jiangxia , Sun Congjiao , Yang Ning
Published: April 2021

Background

Heterosis is an important biological phenomenon that has been extensively utilized in agricultural breeding. However, negative heterosis is also pervasively observed in nature, which can cause unfavorable impacts on production performance. Compared with systematic studies of positive heterosis, the phenomenon of negative heterosis has been largely ignored in genetic studies and breeding programs, and the genetic mechanism of this phenomenon has not been thoroughly elucidated to date. Here, we used chickens, the most common agricultural animals worldwide, to determine the genetic and molecular mechanisms of negative heterosis.

Results

We performed reciprocal crossing experiments with two distinct chicken lines and found that the body weight presented widely negative heterosis in the early growth of chickens. Negative heterosis of carcass traits was more common than positive heterosis, especially breast muscle mass, which was over − 40% in reciprocal progenies. Genome-wide gene expression pattern analyses of breast muscle tissues revealed that nonadditivity, including dominance and overdominace, was the major gene inheritance pattern. Nonadditive genes, including a substantial number of genes encoding ATPase and NADH dehydrogenase, accounted for more than 68% of differentially expressed genes in reciprocal crosses (4257 of 5587 and 3617 of 5243, respectively). Moreover, nonadditive genes were significantly associated with the biological process of oxidative phosphorylation, which is the major metabolic pathway for energy release and animal growth and development. The detection of ATP content and ATPase activity for purebred and crossbred progenies further confirmed that chickens with lower muscle yield had lower ATP concentrations but higher hydrolysis activity, which supported the important role of oxidative phosphorylation in negative heterosis for growth traits in chickens.

Conclusions

These findings revealed that nonadditive genes and their related oxidative phosphorylation were the major genetic and molecular factors in the negative heterosis of growth in chickens, which would be beneficial to future breeding strategies.
Impacts of a comprehensive tuberculosis control model on the quality of clinical services and the financial burden of treatment for patients with drug-resistant tuberculosis in China: a mixed-methods evaluation
Authors: Jiang Wei-Xi , Li Zhi-Peng , Zhao Qi , Gao Meng-Qiu , Long Qian , Wang Wei-Bing , Huang Fei , Wang Ni , Tang Sheng-Lan
Published: April 2021

Background

The China National Health Commission-Gates TB Project Phase III implemented a comprehensive TB control model including multiple interventions to address the burden of drug-resistant TB (DRTB). This study aims to evaluate the quality of DRTB clinical services and assess the financial burden of DRTB patients during the intervention period.

Methods

A mixed-methods approach was used to evaluate the effectiveness of interventions in the three project provinces: Zhejiang, Jilin and Ningxia Hui Autonomous Region. The quantitative data included de-identified DRTB registry data during 2015–2018 in project provinces from China CDC, medical records of DRTB patients registered in 2018 (n = 106) from designated hospitals, and a structured DRTB patient survey in six sample prefectures in 2019. The quality of clinical services was evaluated using seven indicators across patient screening, diagnosis and treatment. Logistic regression was conducted to explore factors associated with the extremely high financial burden. Semi-structured in-depth interviews with policymakers and focus group discussions with physicians and DRTB patients were conducted to understand the interventions implemented and their impacts.

Results

The percentage of bacterially confirmed patients taking a drug susceptibility test (DST) increased significantly between 2015 and 2018: from 57.4 to 93.6% in Zhejiang, 12.5 to 86.5% in Jilin, and 29.7 to 91.4% in Ningxia. The treatment enrollment rate among diagnosed DRTB patients also increased significantly and varied from 73 to 82% in the three provinces in 2018. Over 90% of patients in Zhejiang and Jilin and 75% in Ningxia remained in treatment by the end of the first six months’ treatment. Among all survey respondents 77.5% incurred extremely high financial burden of treatment. Qualitative results showed that interventions on promoting rapid DST technologies and patient referral were successfully implemented, but the new financing policies for reducing patients’ financial burden were not implemented as planned.

Conclusions

The quality of DRTB related clinical services has been significantly improved following the comprehensive interventions, while the financial burden of DRTB patients remains high due to the delay in implementing financing policies. Stronger political commitment and leadership are required for multi-channel financing to provide additional financial support to DRTB patients.