bluuebunny/crossref_metadata_2025 huggingface dataset:
The Current Status of Spinal Posttraumatic Deformity: A Systematic Review
Authors: De Gendt Erin E. A. , Vercoulen Timon F. G. , Joaquim Andrei F. , Guo Wei , Vialle Emiliano N. , Schroeder Gregory D. , Schnake Klaus S. , Vaccaro Alexander R. , Benneker Lorin Michael , Muijs Sander P. J. , Oner F. Cumhur
Published: December 2020

Study Design:

Systematic Review.

Objective:

To systematically analyze the definitions and descriptions in literature of “Spinal Posttraumatic Deformity” (SPTD) in order to support the development of a uniform and comprehensive definition of clinically relevant SPTD.

Methods:

A literature search in 11 international databases was performed using “deformity” AND “posttraumatic” and its synonyms. When an original definition or a description of SPTD (Patient factors, Radiological outcomes, Patient Reported Outcome Measurements and Surgical indication) was present the article was included. The retrieved articles were assessed for methodological quality and the presented data was extracted.

Results:

46 articles met the inclusion criteria. “Symptomatic SPTD” was mentioned multiple times as an entity, however any description of “symptomatic SPTD” was not found. Pain was mentioned as a key factor in SPTD. Other patient related parameters were (progression of) neurological deficit, bone quality, age, comorbidities and functional disability. Various ways were used to determine the amount of deformity on radiographs. The amount of deformity ranged from not deviant for normal to >30°. Sagittal balance and spinopelvic parameters such as the Pelvic Incidence, Pelvic Tilt and Sacral Slope were taken into account and were used as surgical indicators and preoperative planning. The Visual Analog Scale for pain and the Oswestry Disability Index were used mostly to evaluate surgical intervention.

Conclusion:

A clear-cut definition or consensus is not available in the literature about clinically relevant SPTD. Our research acts as the basis for international efforts for the development of a definition of SPTD.
BJP’s Ideological Hegemony: Combining Religious Conservatism and Nationalism
Authors: Kumar Sanjay , Gupta Pranav
Published: December 2020

This article explores popular support for two key dimensions of the Bharatiya Janata Party’s recent ideological dominance in Indian politics. We examine public opinion on assertive nationalism and religious conservatism. The article analyses data from an individual-level survey conducted among voters across 12 states across the country in 2018. We find that public opinion is largely sympathetic towards the ideological positions held by the right on these dimensions. Moreover, ideological resonance transcends various socio-economic cleavages, and there is high support even among non-core segments of the BJP’s social coalition. We also find suggestive evidence for the role of nationalism in expanding the BJP’s support base.
Dose and Recovery Response of Patellofemoral Cartilage Deformations to Running
Authors: Heckelman Lauren N. , Riofrio Alexie D. , Vinson Emily N. , Collins Amber T. , Gwynn Olivia R. , Utturkar Gangadhar M. , Goode Adam P. , Spritzer Charles E. , DeFrate Louis E.
Published: December 2020

Background:

Running is a common recreational activity that provides many health benefits. However, it remains unclear how patellofemoral cartilage is affected by varied running distances and how long it takes the cartilage to recover to its baseline state after exercise.

Hypothesis:

We hypothesized that patellofemoral cartilage thickness would decrease immediately after exercise and return to its baseline thickness by the following morning in asymptomatic male runners. We further hypothesized that we would observe a significant distance-related dose response, with larger compressive strains (defined here as the mean change in cartilage thickness measured immediately after exercise, divided by the pre-exercise cartilage thickness) observed immediately after 10-mile runs compared with 3-mile runs.

Study Design:

Descriptive laboratory study.

Methods:

Eight asymptomatic male participants underwent magnetic resonance imaging of their dominant knee before, immediately after, and 24 hours after running 3 and 10 miles at a self-selected pace (on separate visits).

Results:

Mean patellar cartilage thicknesses measured before exercise and after the 24-hour recovery period were significantly greater than the thicknesses measured immediately after both the 3- and 10-mile runs ( P < .001). This relationship was not observed in trochlear cartilage. Mean patellar cartilage compressive strains were significantly greater after 10-mile runs compared with 3-mile runs (8% vs 5%; P = .01).

Conclusion:

Patellar cartilage thickness decreased immediately after running and returned to its baseline thickness within 24 hours of running up to 10 miles. Furthermore, patellar cartilage compressive strains were dose-dependent immediately after exercise.

Clinical Relevance:

These findings provide critical baseline data for understanding patellofemoral cartilage biomechanics in asymptomatic male runners that may be used to optimize exercise protocols and investigations targeting those with running-induced patellofemoral pain.
Characteristics of Lower Limb Muscle Activity in Elderly Persons After Ergometric Exercise
Authors: Kaneko Kenichi , Makabe Hitoshi , Mito Kazuyuki , Sakamoto Kazuyoshi , Kawanori Yoshiya , Yonemoto Kiyoshi
Published: December 2020

This study examined the characteristics of lower limb muscle activity in elderly persons after ergometric pedaling exercise for 1 month. To determine the effect of the exercise, surface electromyography (SEMG) of lower limb muscles was subjected to Daubechies-4 wavelet transformation, and mean wavelet coefficients were compared with the pre-exercise coefficients and the post-exercise coefficients in each wavelet level. The characteristics of muscle activity after pedaling exercise were also compared between the elderly subjects and young subjects. For the elderly subjects, the mean wavelet coefficients were significantly decreased in the tibialis anterior and the gastrocnemius medialis at wavelet levels of 3, 4, and 5 (125–62.5, 62.5–31.25, and 31.25–15.625 Hz, respectively), by pedaling exercise. However, the mean power of wavelet levels of 2 and 3 (250–125 and 125–62.5 Hz) within the rectus femoris and the biceps femoris were significantly increased in the young subjects. The effect of pedaling exercise is different from the effects of heavy-resistance training. It was suggested that the muscle coordination, motor unit (MU) firing frequency, and firing fiber type of lower limb muscles are changed with the different characteristics between elderly and young persons by pedaling exercise for 1 month.
Social Determinants of Health Associated With Michigan Residents 50 Years and Older Health-Related Quality of Life and Cardiovascular Health
Authors: Dean Caress A.
Published: December 2020

Objective: Studies show perceived health-related quality of life (HRQL) is associated with cardiovascular health (CVH) status; however, there is a limited understanding of underlying determinants of the CVH and HRQL of adults ≥50 years. Therefore, this study’s objective was to examine social determinants of health (SDOH) associated with Michigan residents ≥50 years HRQL measures and CVH status. Methods: Michigan-level data was extracted from the 2017 Behavioral Risk Factor Surveillance System to complete the study’s objective. The data were weighted to obtain state-level estimates. Multinomial and binary logistic regression analyses identified SDOH significantly associated with Michiganders ≥50 years CVH status and HRQL measures. Results: The sample consisted of 10,889 participants. Compared to residents with a moderate CVH and mental health status, residents who reported unable to visit a doctor due to costs were two times more likely than those who were able to visit a provider to have a non-ideal CVH and mental health status (OR = 2.65; 95% CI: 1.39–5.07). Discussion: SDOH were significantly associated with non-ideal CVH and HRQL measures. Interventions that seek to address the CVH and perceive HRQL of residents ≥50 years should also address their underlying SDOH. Research should be performed to determine the generalizability of these findings.
Amplified Decoupling in the Global Economy: The Case of Bilateral Investment Treaties
Authors: Bandelj Nina , Tester Aaron
Published: December 2020

Developing countries adopt global policies in their quest for economic development. Studies show that such policies are decoupled from their intended effects, or that over time, they become more effective. But what if the opposite happens and policies, which were initially efficacious, become increasingly decoupled with time? We recognize this phenomenon as amplified decoupling. Combining historical and quantitative analysis, we examine a case of bilateral investment treaties (BITs), established to protect and promote foreign direct investment (FDI). The influence of BITs on FDI is significant in the early periods but becomes weaker over time. Historical analysis reveals the unexpected role of (post)communist countries in using BITs for geopolitical purposes and highlight the impact of international organizations which broker treaty signing among pairs of developing countries engaged in economic diplomacy. We suggest that amplified decoupling can result because of institutional multivalence, whereby practical actors reframe and repurpose policies toward uses that were originally unintended.
Amalgam Phase-Down Part 2: UK-Based Knowledge, Opinions, and Confidence in the Alternatives
Authors: Bailey O. , Vernazza C.R. , Stone S. , Ternent L. , Roche A.-G. , Lynch C.
Published: December 2020

Introduction:

Amalgam use has recently been phased down, and the potential for a phase-out is being investigated.

Objectives:

The study aimed to identify knowledge of the phase-down and opinions of a potential phase-out of amalgam by UK primary care clinicians and assess their confidence in using different materials in different situations.

Methods:

An anonymized, prepiloted cross-sectional e-survey was used to assess primary care clinicians’ knowledge and opinions of the amalgam phase-down and potential phase-out and their confidence in using amalgam and the alternatives in different situations. In total, 11,902 invitations were distributed through British dentist and therapist associations. Prior hypotheses were tested alongside descriptive statistics.

Results:

Response rate was 13% ( n = 1,513). Knowledge of the amalgam phase-down was low, with just 3% clinicians correctly identifying all patient groups in whom amalgam use should be avoided in the United Kingdom. Postgraduate education on posterior composite placement was high (88%), but a large majority had personal and patient-centered concerns over the suitability of the alternatives and lacked confidence when placing composite in comparison to amalgam in difficult situations ( P < 0.0001). Logistic regressions revealed that the best predictors of high confidence in placing mesio-occluso-distal composites and composites in difficult situations were being a private general dentist or being primarily a composite user.

Conclusion:

Primary care clinicians have major personal and patient-centered concerns regarding the amalgam phase-down (of which they have limited knowledge) and potential phase-out. Many lack confidence in using the alternative, composite, to restore posterior teeth in difficult situations, whereas confidence in using amalgam in similar situations is high. Effective education of clinicians and understanding patients’ needs, alongside policy changes, are required to enable a successful amalgam phase-down and potential phase-out.

Knowledge Transfer Statement:

This study shows that UK primary care clinicians are worried about the phase-down of amalgam for themselves and their patients. Many lack confidence in the alternative, composite, when used in difficult situations, which is in stark contrast to amalgam. Knowledge of the phase-down is limited. There is a need for more effective education of clinicians, an understanding of patients’ values, and policy changes to ensure the success of the phase-down and potential phase-out of amalgam.
Further exploring the links between high-performance work practices and firm performance: A multiple-mediation model in the German context
Authors: Hauff Sven , Alewell Dorothea , Hansen Nina Katrin
Published: December 2020

In order to improve our understanding of the relationships between high-performance work systems and firm performance, several studies have analysed the mediating effects of motivation-related or human capital-related variables. However, most of these have concentrated on single aspects and are US-focused. We extend previous human resource management research by simultaneously analysing the relevance of four general mediating mechanisms: human capital, employee attitudes, employee performance and operational performance. We apply structural equation modelling with formative constructs to data of 1099 German firms. While our findings support the assumption of positive relationships between high-performance work practices, the four mediating mechanisms and firm performance, they also reveal some peculiarities attributable to the German context. Using formative constructs, we were also able to show that single high-performance work practices have different effects on firm performance.
Sustainable and inclusive – Evaluating urban sustainability indicators’ suitability for measuring progress towards SDG-11
Authors: Thomas Ryan , Hsu Angel , Weinfurter Amy
Published: December 2020

The adoption of the sustainable development goals marks a transition in the global sustainability discourse to a growing focus on equity, with urban areas’ role in achieving sustainable and inclusive growth more explicit in sustainable development goal-11. Within this discourse, urban sustainability indicators could be used to monitor environmental quality and equity within individual cities, while promising to deepen our understanding of how urban areas contribute to global environmental sustainability. We examine 484 indicators of urban and regional environmental sustainability sourced from 40 indexes and online data repositories to determine their suitability for measuring both urban environmental performance and equity. Despite the large number of existing indicators related to urban environmental monitoring, we find that they are inadequate as tools for evaluating progress towards sustainable development goal-11’s integrated goal of sustainable and inclusive (i.e. equitable) urban areas, due to a lack of benchmarks, targets, and explicit measurement of equity considerations. Future research should emphasize data collection that can be disaggregated geographically to make it possible to measure distributional equity and establish locally appropriate benchmarks and realistic targets for urban sustainability indicators. Lastly, we argue that utilizing large-scale, high-resolution datasets has the potential to help overcome these data collection challenges.
CD11c regulates hematopoietic stem and progenitor cells under stress
Authors: Hou Lifei , Voit Richard A. , Sankaran Vijay G. , Springer Timothy A. , Yuki Koichi
Published: December 2020

β2 integrins are well-known leukocyte adhesion molecules consisting of 4 members: CD11a-d. Their known biological functions range widely from leukocyte recruitment, phagocytosis, to immunological synapse formation, but the studies have been primarily focused on CD11a and CD11b. CD11c is 1 of the 4 members and is extremely homologous to CD11b. It has been well known as a dendritic cell marker, but the characterization of its function has been limited. We found that CD11c was expressed on the short-term hematopoietic stem cells and multipotent progenitor cells. The lack of CD11c did not affect the number of hematopoietic stem and progenitor cells (HSPCs) in healthy CD11c knockout mice. Different from other β2 integrin members, however, CD11c deficiency was associated with increased apoptosis and significant loss of HSPCs in sepsis and bone marrow transplantation. Although integrins are generally known for their overlapping and redundant roles, we showed that CD11c had a distinct role of regulating the expansion of HSPCs under stress. This study shows that CD11c, a well-known dendritic cell marker, is expressed on HSPCs and serves as their functional regulator. CD11c deficiency leads to the loss of HSPCs via apoptosis in sepsis and bone marrow transplantation.
Inflammatory myofibroblastic tumour of the central airways: treatment and molecular analysis
Authors: Iyer Aparna , Radonic Teodora , Heukamp Lukas C. , Thunnissen Erik , Daniels Johannes M.A.
Published: December 2020

Inflammatory myofibroblastic tumours (IMT) are a rare cause of endobronchial masses in adults. Surgery has been the mainstay of treatment of endobronchial IMTs, based on the potential for recurrence. Interventional pulmonology has emerged as a minimally invasive and lung function preserving modality in management of airway obstruction due to tumours. We present a series of three adult patients with IMT treated endobronchially with a short discussion on its potential role. We also discuss how molecular analysis of IMTs for mutations in genes such asALKandROS1might provide insights into clinical behaviour and potential targetable therapy in advanced, unresectable and metastatic cases.
Cost-effectiveness analysis of a single-inhaler triple therapy for COPD in the UK
Authors: Fenwick Elisabeth , Martin Alan , Schroeder Melanie , Mealing Stuart J. , Solanke Oyinkansola , Risebrough Nancy , Ismaila Afisi S.
Published: December 2020

UK management costs for COPD, estimated at £1.9 billion/year, are rising. In the FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) study, single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (100/62.5/25 µg) improved clinical outcomesversusbudesonide/formoterol (400/12 µg) in patients with symptomatic COPD at risk of exacerbations. We assessed the cost-effectiveness of fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol for treating COPD from a UK National Health Service perspective.

A model was developed combining a trial-based and Markov component and populated with baseline and treatment effect data from FULFIL, together with UK healthcare resource costs and disease-related utilities. Costs per life year and per quality-adjusted life year gained (costing year 2017) for fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol were calculated for a lifetime horizon. Results were explored using deterministic sensitivity, scenario and probabilistic analyses.

Fluticasone furoate/umeclidinium/vilanterol was associated with gains in life years (0.533) and quality-adjusted life years (0.506)versusbudesonide/formoterol, but at slightly increased total costs (£26 416versus£25 860). This translated to incremental cost-effectiveness ratios of £1042/life year and £1098/quality-adjusted life year for fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol. In scenario analyses, incremental cost-effectiveness ratios ranged from dominant to £1547/quality-adjusted life year gained.

Fluticasone furoate/umeclidinium/vilanterol provides a cost-effective treatment optionversusbudesonide/formoterol for patients with symptomatic COPD in the UK.
Cardiac biomarkers and long-term outcomes of exacerbations of COPD: a long-term follow-up of two cohorts
Authors: Shafuddin Eskandarain , Fairweather Sarah M. , Chang Catherina L. , Tuffery Christine , Hancox Robert J.
Published: December 2020

Background

COPD patients often have cardiac comorbidities. Cardiac involvement at the time of a COPD exacerbation is associated with a high short-term mortality, but whether this influences long-term outcomes is unknown. We explored whether biomarkers of cardiac dysfunction at the time of a COPD exacerbation predict long-term outcomes.

Methods

Two prospective cohorts of patients admitted to Waikato Hospital for exacerbations of COPD were recruited during 2006–2007 and 2012–2013. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured on admission and were used to indicate cardiac stretch and myocardial injury, respectively. 5-year survival after discharge and subsequent admissions for cardiac disease and COPD exacerbations were analysed using Kaplan–Meier and Cox proportional hazards tests.

Results

The overall 5-year mortality was 61%. Patients with high NT-proBNP on admission had higher mortality than those with normal cardiac biomarkers (adjusted hazard ratio (aHR) 1.76, 95% CI 1.18–2.62). High NT-proBNP was also associated with a higher risk of future cardiac admissions (aHR 1.75, 95% CI 1.2–2.55). Troponin T levels were not associated with long-term survival (aHR 0.86, 95% CI 0.40–1.83) or future cardiac admissions (aHR 0.74, 95% CI 0.34–1.57). Neither biomarker predicted future COPD exacerbations.

Conclusion

The long-term prognosis following a hospitalisation for an exacerbation of COPD is poor with less than half of patients surviving for 5 years. Elevated NT-proBNP at the time of a COPD exacerbation is associated with higher long-term mortality and a greater likelihood of future cardiac admissions, but not future COPD exacerbations.
Reliability of maximum oxygen uptake in cardiopulmonary exercise testing with continuous laryngoscopy
Authors: Engan Mette , Hammer Ida Jansrud , Bekken Marianne , Halvorsen Thomas , Fretheim-Kelly Zoe Louise , Vollsæter Maria , Bovim Lars Peder Vatshelle , Røksund Ola Drange , Clemm Hege
Published: December 2020

Aims

A cardiopulmonary exercise test (CPET) is the gold standard to evaluate symptom-limiting exercise intolerance, while continuous laryngoscopy performed during exercise (CLE) is required to diagnose exercise-induced laryngeal obstruction. Combining CPET with CLE would save time and resources; however, the CPET data may be distorted by the extra equipment. We therefore aimed to study whether CPET with CLE influences peak oxygen uptake (V′O2peak) and other gas exchange parameters when compared to a regular CPET.

Methods

Forty healthy athletes without exercise-related breathing problems, 15–35 years of age, performed CPET to peak exercise with and without an added CLE set-up, in randomised order 2–4 days apart, applying an identical computerised treadmill protocol.

Results

At peak exercise, the mean difference (95% confidence interval) between CPET with and without extra CLE set-up forV′O2peak, respiratory exchange ratio (RER), minute ventilation (V′E) and heart rate (HR) was 0.2 (−0.4 to 0.8) mL·kg−1·min−1, 0.01(−0.007 to 0.027) units, 2.6 (−1.3 to 6.5) L·min−1and 1.4 (−0.8 to 3.5) beats·min−1, respectively. Agreement (95% limits of agreement) forV′O2peak, RER andV′Ewas 0.2 (±3.7) mL·kg−1·min−1, 0.01 (±0.10) units and 2.6 (±24.0) L·min−1, respectively. No systematic or proportional bias was found except for the completed distance, which was 49 m (95% CI 16 to 82 m) longer during CPET.

Conclusion

Parameters of gas exchange, includingV′O2peak and RER, obtained from a maximal CPET performed with the extra CLE set-up can be used interchangeably with data obtained from standard CPET, thus preventing unnecessary additional testing.
COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia
Authors: Pedersen Eva S.L. , Collaud Eugénie N.R. , Mozun Rebeca , Ardura-Garcia Cristina , Lam Yin Ting , Harris Amanda , Lucas Jane S. , Copeland Fiona , Manion Michele , Rindlisbacher Bernhard , Silberschmidt Hansruedi , Goutaki Myrofora , Kuehni Claudia E.
Published: December 2020

COVID-PCD is a participatory study initiated by people with primary ciliary dyskinesia (PCD) who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real-time from people with PCD throughout the pandemic to describe incidence of coronavirus disease 2019 (COVID-19), symptoms and course of disease; identify risk factors for prognosis; and assess experiences, wishes and needs.

The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, current symptoms, social contact behaviour and physical activity. Occasional thematic questionnaires are sent out focussing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online.

The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians and researchers.
Glucose-lactose mixture feeds in industry-like conditions: a gene regulatory network analysis on the hyperproducing Trichoderma reesei strain Rut-C30
Authors: Pirayre Aurélie , Duval Laurent , Blugeon Corinne , Firmo Cyril , Perrin Sandrine , Jourdier Etienne , Margeot Antoine , Bidard Frédérique
Published: December 2020

Background

The degradation of cellulose and hemicellulose molecules into simpler sugars such as glucose is part of the second generation biofuel production process. Hydrolysis of lignocellulosic substrates is usually performed by enzymes produced and secreted by the fungusTrichoderma reesei. Studies identifying transcription factors involved in the regulation of cellulase production have been conducted but no overview of the whole regulation network is available. A transcriptomic approach with mixtures of glucose and lactose, used as a substrate for cellulase induction, was used to help us decipher missing parts in the network ofT. reeseiRut-C30.

Results

Experimental results on the Rut-C30 hyperproducing strain confirmed the impact of sugar mixtures on the enzymatic cocktail composition. The transcriptomic study shows a temporal regulation of the main transcription factors and a lactose concentration impact on the transcriptional profile. A gene regulatory network built using BRANE Cut software reveals three sub-networks related toi) a positive correlation between lactose concentration and cellulase production,ii) a particular dependence of the lactose onto theβ-glucosidase regulation andiii) a negative regulation of the development process and growth.

Conclusions

This work is the first investigating a transcriptomic study regarding the effects of pure and mixed carbon sources in a fed-batch mode. Our study expose a co-orchestration ofxyr1,clr2andace3for cellulase and hemicellulase induction and production, a fine regulation of theβ-glucosidase and a decrease of growth in favor of cellulase production. These conclusions provide us with potential targets for further genetic engineering leading to better cellulase-producing strains in industry-like conditions.
Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by Annona muricata L. bark extract and phytochemical, annonacin
Authors: Foster Kimberley , Oyenihi Omolola , Rademan Sunelle , Erhabor Joseph , Matsabisa Motlalepula , Barker James , Langat Moses K. , Kendal-Smith Amy , Asemota Helen , Delgoda Rupika
Published: December 2020

Background

Annona muricataL. was identified as a popular medicinal plant in treatment regimens among cancer patients in Jamaica by a previously conducted structured questionnaire. Ethnomedically used plant parts, were examined in this study against human prostate cancer cells for the first time and mechanisms of action elucidated for the most potent of them, along with the active phytochemical, annonacin.

Methods

Nine extracts of varying polarity from the leaves and bark ofA. muricatawere assessed initially for cytotoxicity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on PC-3 prostate cancer cells and the ethyl acetate bark (EAB) extract was identified as the most potent. EAB extract was then standardized for annonacin content using High-performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) and shown to be effective against a second prostate cancer cell line (DU-145) also. The mode of cell death in DU-145 cells were assessed via several apoptotic assays including induction of increased reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, activation of caspases and annexin V externalization combined with morphological observations using confocal microscopy. In addition, the potential to prevent metastasis was examined via inhibition of cell migration, vascular endothelial growth factor (VEGF) and angiogenesis using the chorioallantoic membrane assay (CAM).

Results

Annonacin and EAB extract displayed selective and potent cytotoxicity against the DU-145 prostate carcinoma cells with IC50values of 0.1 ± 0.07 μM and 55.501 ± 0.55 μg/mL respectively, without impacting RWPE-1 normal prostate cells, in stark contrast to chemotherapeutic docetaxel which lacked such selectivity. Docetaxel’s impact on the cancerous DU-145 was improved by 50% when used in combination with EAB extract. Insignificant levels of intracellular ROS content, depolarization of mitochondrial membrane, Caspase 3/7 activation, annexin V content, along with stained morphological evaluations, pointed to a non-apoptotic mode of cell death. The extract at 50 μg/mL deterred cell migration in the wound-healing assay, while inhibition of angiogenesis was displayed in the CAM and VEGF inhibition assays for both EAB (100 μg /mL) and annonacin (0.5 μM).

Conclusions

Taken together, the standardized EAB extract and annonacin appear to induce selective and potent cell death via a necrotic pathway in DU-145 cells, while also preventing cell migration and angiogenesis, which warrant further examinations for mechanistic insights and validity in-vivo.
Medical students’ self-reported gender discrimination and sexual harassment over time
Authors: Kisiel Marta A. , Kühner Sofia , Stolare Karin , Lampa Erik , Wohlin Martin , Johnston Nina , Rask-Andersen Anna
Published: December 2020

Background

Gender discrimination (GD) and sexual harassment (SH) occur at all academic institutions worldwide. Medical students report high prevalence of GD and SH, which may negatively affect their education and health. There are indications that policies and reforms on reducing GD/SH are insufficient. Swedish medical students’ experiences of GD/SH are monitored by course-evaluations and bi-annual student union evaluations; however, the response rate is usually low. The aim of this study was to compare the exposure to and context of self-reported GD/SH over an 11-year period amongst medical students at a Swedish university.

Methods

In 2002, a questionnaire (n = 622) was mailed to medical students’ home addresses. It was repeated in 2013 and then distributed during mandatory lectures (n = 856). The questions used a behavioristic approach and asked about specific GH/SH experiences. Participation was voluntary and anonymous. The changes in prevalence over time were calculated by sampling weights in order to obtain comparable estimates, representative of both cohorts.

Results

The response frequency was 55% (62% women) in 2002 and 81% (59% women) in 2013. The prevalence of GD tended to decrease for male and clinical students in comparison to female and pre-clinical peers. However, the prevalence of SH increased for female compared to male students. The ratio of SH for female pre-clinical students doubled in many instances; most often, the mistreatment occurred in the clinic. Medical doctors were indicated as perpetrators up to five times more often by all students in 2013.

Conclusion

Our results show a disproportional change in exposure to GD/SH between female and male medical students, resulting in a widening of the gender gap regarding prevalence of GD and SH between 2002 and 2013. In particular, personal experiences of SH increased for both sexes. It is proof that institutional efforts to fight mistreatment might be ineffective.
Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality in the general population: results from the prospective Lifelines-MINUTHE study
Authors: Riphagen Ineke J. , Minović Isidor , Groothof Dion , Post Adrian , Eggersdorfer Manfred L. , Kootstra-Ros Jenny E. , de Borst Martin H. , Navis Gerjan , Muskiet Frits A. J. , Kema Ido P. , Heiner-Fokkema M. Rebecca , Bakker Stephan J. L.
Published: December 2020

Background

Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels are associated with mortality if vitamin B12 and eGFR are taken into account.

Methods

A total of 1533 individuals (aged 60–75 years, 50% male) were included from the Lifelines Cohort and Biobank Study. Individuals were included between 2006 and 2013, and the total follow-up time was 8.5 years.

Results

Median [IQR] age of the study population was 65 [62–69] years, 50% was male. At baseline, median MMA concentration was 170 [138–216] nmol/L, vitamin B12 290 [224–362] pmol/L, and eGFR 84 [74–91] mL/min/1.73 m2. Log2 vitamin B12, log2 eGFR, age, and sex were significantly associated with log2 MMA in multivariable linear regression analyses (model R2 = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log2 MMA levels were significantly associated with mortality (hazard ratio [HR] 1.67 [95% CI 1.25–2.22], P < 0.001). Moreover, we found a significant interaction between MMA and eGFR with respect to mortality (Pinteraction < 0.001).

Conclusions

Only 22% of variation in MMA levels was explained by vitamin B12, eGFR, age, and sex, indicating that a large part of variation in MMA levels is attributable to other factors (e.g., catabolism, dietary components, or gut microbial production). Higher MMA levels are associated with an increased risk for mortality, independent of vitamin B12, eGFR, and sex. This association was more pronounced in individuals with impaired renal function.
Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature
Authors: Zhang Qiang , Qin Zailong , Yi Shang , Wei Hao , Zhou Xun Zhao , Su Jiasun
Published: December 2020

Background

Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13.

Case presentation

A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605_606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed.

Conclusions

This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations.
The C allele of the reactive oxygen species modulator 1 (ROMO1) polymorphism rs6060566 is a biomarker predicting coronary artery stenosis in Slovenian subjects with type 2 diabetes mellitus
Authors: Tibaut Miha , Mankoč Ramuš Sara , Petrovič Daniel
Published: December 2020

Background

We aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (ROMO1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).

Methods

A total of 1072 subjects with T2DM were enrolled in this cross-sectional case–control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). The genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO1 expression according to their genotype.

Results

There were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO1 rs6060566 had a threefold increased likelihood of having 50–75% coronary artery stenosis (Adjusted OR = 3.27, 95% CI 1.16–9.20). Subjects with two affected coronary arteries had a 3.72 fold higher prevalence of MI (OR = 3.72, 95% CI 1.27–10.84). With CAD in LMCA or LAD, MI prevalence was about 3.5-fold higher (p = 0.07 for LMCA and p = 0.01 for LAD). Furthermore, the carriers of the rs6060566 C allele showed higher number of positive cells for ROMO1 expression in endarterectomy samples of coronary arteries.

Conclusions

According to our study, the rs6060566 polymorphism of the ROMO1 gene is not a risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had non-obstructive CAD. Moreover, C allele carriers showed a statistically higher number of cells positive for ROMO1 compared with T allele carriers in coronary endarterectomy samples.
Five novel clinical phenotypes for critically ill patients with mechanical ventilation in intensive care units: a retrospective and multi database study
Authors: Su Longxiang , Zhang Zhongheng , Zheng Fanglan , Pan Pan , Hong Na , Liu Chun , He Jie , Zhu Weiguo , Long Yun , Liu Dawei
Published: December 2020

Background

Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with MV in intensive care units (ICUs).

Methods

A retrospective cohort study was conducted with 5013 patients who had undergone MV and treatment in the Department of Critical Care Medicine, Peking Union Medical College Hospital. Statistical and machine learning methods were used. All the data used in this study, including demographics, vital signs, circulation parameters and mechanical ventilator parameters, etc., were automatically extracted from the electronic health record (EHR) system. An external database, Medical Information Mart for Intensive Care III (MIMIC III), was used for validation.

Results

Phenotypes were derived from a total of 4009 patients who underwent MV using a latent profile analysis of 22 variables. The associations between the phenotypes and disease severity and clinical outcomes were assessed. Another 1004 patients in the database were enrolled for validation. Of the five derived phenotypes, phenotype I was the most common subgroup (n = 2174; 54.2%) and was mostly composed of the postoperative population. Phenotype II (n = 480; 12.0%) led to the most severe conditions. Phenotype III (n = 241; 6.01%) was associated with high positive end-expiratory pressure (PEEP) and low mean airway pressure. Phenotype IV (n = 368; 9.18%) was associated with high driving pressure, and younger patients comprised a large proportion of the phenotype V group (n = 746; 18.6%). In addition, we found that the mortality rate of Phenotype IV was significantly higher than that of the other phenotypes. In this subgroup, the number of patients in the sequential organ failure assessment (SOFA) score segment (9,22] was 198, the number of deaths was 88, and the mortality rate was higher than 44%. However, the cumulative 28-day mortality of Phenotypes IV and II, which were 101 of 368 (27.4%) and 87 of 480 (18.1%) unique patients, respectively, was significantly higher than those of the other phenotypes. There were consistent phenotype distributions and differences in biomarker patterns by phenotype in the validation cohort, and external verification with MIMIC III further generated supportive results.

Conclusions

Five clinical phenotypes were correlated with different disease severities and clinical outcomes, which suggested that these phenotypes may help in understanding heterogeneity in MV treatment effects.
A super-spreader of SARS-CoV-2 in incubation period among health-care workers
Authors: Wei Chaojie , Yuan Yufeng , Cheng Zhenshun
Published: December 2020

Since the coronavirus disease 2019 (COVID-19) identified in Wuhan, Hubei, China in December 2019, it has been characterized as a pandemic by World Health Organization (WHO). It was reported that asymptomatic persons are potential sources of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present an outbreak among health-care workers incited by a doctor who cared a patient with COVID-19 in a Hospital in Wuhan, Hubei, China, which indicates existence of super-spreader even during incubation period.
Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study
Authors: Shi Jie , Zhang Weiwei , Niu Yixin , Lin Ning , Li Xiaoyong , Zhang Hongmei , Hu Renming , Ning Guang , Fan Jiangao , Qin Li , Su Qing , Yang Zhen
Published: December 2020

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals with prediabetes.

Methods

A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis.

Results

During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16–4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects.

Conclusion

Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes.
A systematic scoping review of the habitual dietary costs in low socioeconomic groups compared to high socioeconomic groups in Australia
Authors: Lewis Meron , McNaughton Sarah A. , Rychetnik Lucie , Lee Amanda J.
Published: December 2020

Background

Low socioeconomic groups (SEGs) in Australia are less likely to consume diets consistent with the Australian Dietary Guidelines (ADGs) and suffer poorer health than the broader population. The unaffordability, or perceived high cost, of healthy diets may be a factor. Detailed data on the cost of habitually consumed diets is required in order to inform strategies to alleviate socioeconomic impacts on dietary intake.

This systematic scoping review aims to identify the cost of the habitual dietary intake of low SEGs in Australia, in terms of the whole diet and its composite foods, in comparison to the cost in higher SEGs.

Methods

A systematic search of peer-reviewed literature since 2000 and key government and non-government organisation (NGO) websites was undertaken. Data were extracted, synthesised and analysed in relation to study populations, dietary cost assessment measures, socioeconomic measures, and dietary cost and affordability.

Results

The review identified four studies meeting inclusion criteria. Results confirmed that overall, low SEGs spend a lower amount, yet a higher proportion of household income, on food and drinks than higher SEGs. Quantitative comparison of the dietary costs between included studies was not possible due to difference in populations and study metrics. Costs of the habitual diet in these studies were not reported for ADG food groups, so did not allow for assessment of the healthfulness of the dietary intake or comparison with costs of recommended diets at food group level.

Conclusions

Existing research does not provide sufficiently granular data of the costs of habitual diets of low SEGs in comparison to higher SEGs or data in a form that can inform strategies and interventions to improve dietary intake and diet-related health of low SEGs in Australia. Future empirical health research requires more granular measures of habitual spending on ADG food groups across SEGs.