bluuebunny/crossref_metadata_2025 huggingface dataset:
Saccadic Eye-Movements Suppress Visual Mental Imagery and Partly Reduce Emotional Response During Music Listening
Authors: Hashim Sarah , Stewart Lauren , Küssner Mats B.
Published: December 2020

Visual mental imagery has been proposed to be an underlying mechanism of music-induced emotion, yet very little is known about the phenomenon due to its ephemeral nature. The present study utilised a saccadic eye-movement task designed to suppress visual imagery during music listening. Thirty-five participants took part in Distractor (eye-movement) and Control (blank screen) conditions, and reported the prevalence, control, and vividness of their visual imagery, and felt emotion ratings using the GEMS-9 in response to short excerpts of film music. The results show that the eye-movement task was highly effective in reducing ratings for prevalence and vividness of visual imagery, and for one GEMS item, Nostalgia, but was not successful in reducing control of imagery or the remaining GEMS items in response to the music. This represents a novel approach to understanding the potentially causal role of visual imagery on music-induced emotion, on which future research can build by considering the attentional mechanisms that a distraction task may pose during music-induced visual imagery formation.
Autobiographical Significance of Meaningful Musical Experiences: Reflections on Youth and Identity
Authors: Peck Landon S. L. , Grealey Patrick
Published: December 2020

Meaningful musical experiences during youth can leave a lasting impression on an individual by shaping their identity and place in the world. This study examines such experiences in relation to autobiography and self-identity. An online questionnaire ( N = 50) was distributed to establish how individuals understood musical experiences from their youth as important to their past and present self-identities. Following the online study, 10 questionnaire participants were selected to be interviewed to further examine the meanings created within their nominated experiences, and how these meanings had been autobiographically contextualised against the backdrop of the memory of these experiences. Questionnaire data was analysed using Thematic Analysis to establish shared autobiographical- and identity-related concepts. Interpretative Phenomenological Analysis served as the methodological framework for analysing the participant interviews to support a more individualised interpretation of each participant’s experience. Data from the online questionnaire were analysed to reveal a network of identity- and autobiography-relevant themes, which were organised under three wider thematic categories: the self, the social, and the musical. Analysis of the interviews, guided by Identity Theory, revealed individual differences in participants’ processes of identity formation, relationships with music, and attitudes towards their past selves. In both sets of data, prominent themes emerged around ideas of personal transformation and pivoting to a new path in life. These findings frame autobiographically significant musical experiences as powerful in their potential to contribute to identity formation, although their impact varies for each individual. We assessed this autobiographical significance through the enduring salience over time of the identity the experience affected, enabled by our respondents’ reflections on both their past and their present self-identities. Our results illustrate that music can support a wide range of self-identity-relevant meanings, and fundamentally transform our sense of who we are.
Dimensions of Identification in the Workgroup and Employees’ Contributions to Collaborative Activities
Authors: Sidorenkov Andrey V. , Salnikova Ekaterina S. , Vorontsov Dmitry V. , Klimov Alexey A.
Published: December 2020

The aim of this research is to find out connections of identifications with the work group (group identification), informal subgroups (micro-group identification), and other members in the work group (interpersonal identification), considering cognitive, affective, and behavioral components, with an employee’s contribution to cooperative activities. The sample includes 302 fellows of 35 workgroups in Russian commercial companies and public organizations. Empirical data were collected with the Questionnaire of Interpersonal Identification, the Questionnaire of Micro-group and Group Identification, and the Collaborative Group Activity Scale from the Leadership, Contribution, and Interpersonal Style Questionnaire. All the tools were assembled into the computer-based assessment program “Group Profile” (GP) to conduct the survey individually on PC. It was found that all three dimensions of group identification and affective measures of interpersonal and micro-group identification predict individual contribution to collaborative activities in groups. Employee involvement in the informal subgroup within the work group mediates relations between identification dimensions at different levels and contribution to collaborative activities. The ties of additional characteristics (gender, age, tenure with the organization) with cooperative activities have been described. The multivariate model of identification makes it possible to extend the research scope and enhance the understanding of causes and effects of employee identification in the group.
Women in Braj Bhūm (Mathura region): Glimpses through Mughal-period documents
Authors: Habib Irfan
Published: December 2020

The article explores documents in the so-called Vrindavan archives from Mughal times to extract information about individual women who appear there as complainants, sellers and donors. It seeks to establish what we can learn about women’s limited rights to inheritance and notes their total exclusion from peasant holdings. An appendix furnishes recorded descriptions (ḥuliya) of women who appeared before the local qāẓī (judge).
Review article: Francine R. Frankel, When Nehru Looked East: Origins of India–US Suspicion and India–China Rivalry
Authors: Batabyal Rakesh
Published: December 2020

Francine R. Frankel, When Nehru Looked East: Origins of India–US Suspicion and India–China Rivalry (New Delhi: Oxford University Press), 2020, xx + 339 pp., ₹995 (Hb).
Book review: R. Mahalakshmi, ed., Art and History: Texts, Contexts and Visual Representations in Ancient and Early Medieval India
Authors: Jha D.N.
Published: December 2020

R. Mahalakshmi, ed., Art and History: Texts, Contexts and Visual Representations in Ancient and Early Medieval India (New Delhi: Bloomsbury India), 2019, xlvi + 352 pp., ₹1,321 (Hb).
Book review: Kunal Chakrabarti and Kanad Sinha, eds., State, Power and Legitimacy: The Gupta Kingdom
Authors: Sahu Bhairabi Prasad
Published: December 2020

Kunal Chakrabarti and Kanad Sinha, eds., State, Power and Legitimacy: The Gupta Kingdom (New Delhi: Primus Books), 2019, 951 pp., ₹1,195 (Pb).
Book review: Mathew S. Gordon and Kathryn A. Hain, eds., Concubines and Courtesans: Women and Slavery in Islamic History
Authors: Rezavi Syed Ali Nadeem
Published: December 2020

Mathew S. Gordon and Kathryn A. Hain, eds., Concubines and Courtesans: Women and Slavery in Islamic History (New York: Oxford University Press), 2017, ix + 354 pp., ISBN 9780190622183 (Hb.), ISBN 9780190622206 (e.pub), ₹1,969.97 (Kindle).
The social reproduction of labour in the context of the work of women: Past and present
Authors: Patnaik Utsa
Published: December 2020

After the primary role that Gordon Childe assigned to women in prehistory in both the beginnings of agriculture and cattle-domestication, women have been placed at an inferior position in both the realms of production and consumption. Even when they were employed in factories after the Industrial Revolution, they were paid much lower wages than men workers. As Marx pointed out, however, wages have to cover the entire family expenses, and, on this count, wage-levels in colonial countries, even after ‘decolonisation’, have not reached appropriate levels. In colonial India, owing both to tribute and free trade, Indian labouring women, for example, spinners, suffered very grievous hardship. Today it is essential that poverty-lines should be raised and minimum wages adjusted to subsistence needs.
Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3-mimetic resistance in lymphomas
Authors: Boiko Scott , Proia Theresa , San Martin Maryann , Gregory Gareth P. , Wu Michelle Min , Aryal Neeraj , Hattersley Maureen , Shao Wenlin , Saeh Jamal C. , Fawell Stephen E. , Johnstone Ricky W. , Drew Lisa , Cidado Justin
Published: December 2020

BH3 mimetics like venetoclax target prosurvival Bcl-2 family proteins and are important therapeutics in the treatment of hematological malignancies. We demonstrate that endogenous Bfl-1 expression can render preclinical lymphoma tumor models insensitive to Mcl-1 and Bcl-2 inhibitors. However, suppression of Bfl-1 alone was insufficient to fully induce apoptosis in Bfl-1–expressing lymphomas, highlighting the need for targeting additional prosurvival proteins in this context. Importantly, we demonstrated that cyclin-dependent kinase 9 (CDK9) inhibitors rapidly downregulate both Bfl-1 and Mcl-1, inducing apoptosis in BH3-mimetic–resistant lymphoma cell lines in vitro and driving in vivo tumor regressions in diffuse large B-cell lymphoma patient-derived xenograft models expressing Bfl-1. These data underscore the need to clinically develop CDK9 inhibitors, like AZD4573, for the treatment of lymphomas using Bfl-1 as a selection biomarker.
Comparative genomics in “Candidatus Kuenenia stuttgartiensis” reveal high genomic plasticity in the overall genome structure, CRISPR loci and surface proteins
Authors: Ding Chang , Adrian Lorenz
Published: December 2020

Background

Anaerobic ammonium oxidizing bacteria (anammox bacteria) are contributing significantly to the nitrogen cycle and are successfully used in wastewater treatment. Due to the lack of complete genomes in the databases, little is known about the stability and variability of their genomes and how the genomes evolve in response to changing environments.

Results

Here we report the complete genome of the anammox bacterium “Candidatus Kuenenia stuttgartiensis” strain CSTR1 which was enriched planktonically in a semi-continuous stirred-tank reactor. A comparison of the genome of strain CSTR1 with the genome of “Ca. Kuenenia stuttgartiensis” MBR1 and the draft genome of KUST showed > 99% average nucleotide identity among all. Rearrangements of large genomic regions were observed, most of which were associated with transposase genes. Phylogenetic analysis suggests that strain MBR1 is more distantly related to the other two strains. Proteomic analysis of actively growing cells of strain CSTR1 (growth rate ~ 0.33 d− 1) failed to detect the annotated cytochrome cd1-type nitrite reductase (NirS) although in total 1189 proteins were found in the proteome. Yet, this NirS was expressed when strain CSTR1 was under stress or starvation (growth rate < 0.06 d− 1). We also observed large sequence shifts in the strongly expressed S-layer protein compared to other “Ca. Kuenenia” strains, indicating the formation of hybrids of genes encoding the surface proteins.

Conclusions

“Ca. Kuenenia” strains appear to be relatively stable in their basic physiological traits, but show high variability in overall genome structure and surface proteins.
Genome-wide identification and characterization of long non-coding RNAs related to grain yield in foxtail millet [Setaria italica (L.) P. Beauv.]
Authors: Zhao Zilong , Liu Dan , Cui Yanjiao , Li Suying , Liang Dan , Sun Daizhen , Wang Jianhe , Liu Zhengli
Published: December 2020

Background

Long noncoding RNAs (lncRNAs) have been reported to play critical roles in diverse growth and development processes in plants. However, the systematic identification and characterization of lncRNAs in foxtail millet is nearly blank.

Results

In this study, we performed high-throughput sequencing of young spikelets from four foxtail millet varieties in different yield levels at booting stage. As a result, a total of 12,378 novel lncRNAs were identified, and 70 were commonly significantly differentially expressed in comparisons between high-yield varieties and conventional varieties, suggesting that they involved in yield formation and regulation in foxtail millet. Functional analysis revealed that among the 70 significantly differentially expressed lncRNAs, 67 could transcriptionally modulate target genes in cis and in trans. Moreover, 18 lncRNAs related to grain yield in foxtail millet were predicted to function as miRNA target mimics and regulate gene expression by competing for the interaction between miRNAs and their target mRNAs.

Conclusion

Our results will provide materials for elucidation of the molecular mechanisms of lncRNAs participate in yield regulation, and will contribute to high yield foxtail millet breeding.
Outcome of community- versus hospital-acquired intra-abdominal infections in intensive care unit: a retrospective study
Authors: Abaziou Timothée , Vardon-Bounes Fanny , Conil Jean-Marie , Rouget Antoine , Ruiz Stéphanie , Grare Marion , Fourcade Olivier , Suc Bertrand , Leone Marc , Minville Vincent , Georges Bernard
Published: December 2020

Background

To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications.

Methods

Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis.

Results

Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15–25] vs. 21 [15–24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7–36] vs. 6[3–12] days, p < 0.001 and 41 [24–66] vs. 17 [7–32] days, p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI.

Conclusion

CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.
Controlled direct effect of psychiatric disorders on cardiovascular disease: evidence from a large Kurdish cohort
Authors: Darabi Zahra , Najafi Farid , Safari-Faramani Roya , Salimi Yahya
Published: December 2020

Background

Psychiatric disorders are significantly associated with the incidence and prevalence of cardiovascular diseases, mortality, hospital readmissionn. Oral and dental hygiene may play a role in such association. This study aimed to evaluate the controlled direct effect of psychiatric disorders on cardiovascular diseases by controlling the mediating effect of oral and dental hygiene.

Methods

The data used for this study came from the baseline phase of Ravansar Non-communicable Disease (RaNCD) cohort study. RaNCD cohort study is including a representative sample of 10,065 adults (35–65 years old) living in Ravansar, a city in the west of Iran. The marginal structural model with stabilized inverse probability weights accounted for potential confounders was used to estimate the controlled direct effect of psychiatric disorders on cardiovascular diseases. Three different models using three mediators including oral and dental hygiene behaviors, oral ulcer and lesions, and decayed, missing, and filled tooth, were used.

Results

Psychiatric disorders increase the odds of cardiovascular diseases by 83% (OR = 1.83, CI 1.27, 2.61) and about two times (OR = 2.14, 95% CI 1.74, 2.63) when controlled for oral and dental hygiene behaviors, and oral ulcer and lesions as mediators, respectively. When decayed, missing, and filled tooth, as a mediator, was set at ≤ 8, there was no statistically significant controlled direct effect of psychiatric disorders on cardiovascular diseases (OR = 0.90, 95% CI 0.62, 1.30).

Conclusion

Our results suggested that psychiatric disorder was directly related to cardiovascular diseases even if it was possible to have good oral and dental hygiene. The results suggested that interventions targeting people with psychiatric disorders could reduce prevalence of the cardiovascular diseases.
DGAT1 mutations leading to delayed chronic diarrhoea: a case report
Authors: Xu Luojia , Gu Weizhong , Luo Youyou , Lou Jingan , Chen Jie
Published: December 2020

Background

Early-onset chronic diarrhoea often indicates a congenital disorder. Mutation in diacylglycerol o-acyltransferase 1 (DGAT1) has recently been linked to early-onset chronic diarrhoea. To date, only a few cases of DGAT1 deficiency have been reported. Diarrhoea in those cases was severe and developed in the neonatal period or within 2 months after birth.

Case presentation

Here, we report a female patient with DGAT1 mutations with delayed-onset chronic diarrhoea. The patient had vomiting, hypoalbuminemia, hypertriglyceridemia, and failure to thrive at early infancy. Her intractable chronic diarrhoea occurred until she was 8 months of age. A compound heterozygous DGAT1 mutation was found in the patient, which was first found in the Chinese population. Her symptoms and nutrition status improved after nutritional therapy, including a fat restriction diet.

Conclusions

This case expanded our knowledge of the clinical features of patients with DGAT1 mutations. Intractable diarrhoea with delayed onset could also be a congenital disorder.
Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study
Authors: Majoni Sandawana William , Barzi Federica , Hoy Wendy , MacIsaac Richard J. , Cass Alan , Maple-Brown Louise , Hughes Jaquelyne T.
Published: December 2020

Background

Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities.

Methods

Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs.

Results

Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8–3.6) years. Annual decline in eGFR was associated with low serum albumin (p < 0.001) and haemoglobin (p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p < 0.001), haemoglobin (p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR.

Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes.

Conclusions

GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.
Breast cancer mortality trends in Peruvian women
Authors: Torres-Roman J. Smith , Martinez-Herrera Jose Fabian , Carioli Greta , Ybaseta-Medina Jorge , Valcarcel Bryan , Pinto Joseph A. , Aguilar Alfredo , McGlynn Katherine A. , La Vecchia Carlo
Published: December 2020

Background

Breast cancer (BC) is the most common malignancy in Latin American women, but with a wide variability with respect to their mortality. This study aims to estimate the mortality rates from BC in Peruvian women and to assess mortality trends over 15 years.

Methods

We calculated BC age-standardized mortality rate (ASMR) per 100,000 women-years using the world standard SEGI population. We estimated joinpoint regression models for BC in Peru and its geographical areas. The spatial analysis was performed using the Moran’s I statistic.

Results

In a 15-year period, Peru had a mortality rate of 9.97 per 100,000 women-years. The coastal region had the highest mortality rate (12.15 per 100,000 women-years), followed by the highlands region (4.71 per 100,000 women-years). In 2003, the highest ASMR for BC were in the provinces of Lima, Arequipa, and La Libertad (above 8.0 per 100,000 women-years), whereas in 2017, the highest ASMR were in Tumbes, Callao, and Moquegua (above 13.0 per women-years). The mortality trend for BC has been declining in the coastal region since 2005 (APC = − 1.35, p < 0.05), whereas the highlands region experienced an upward trend throughout the study period (APC = 4.26, p < 0.05). The rainforest region had a stable trend. Spatial analysis showed a Local Indicator of Spatial Association of 0.26 (p < 0.05).

Conclusion

We found regional differences in the mortality trends over 15 years. Although the coastal region experienced a downward trend, the highlands had an upward mortality trend in the entire study period. It is necessary to implement tailored public health interventions to reduce BC mortality in Peru.
Preloaded vs manually loaded IOL delivery systems in cataract surgery in the largest ambulatory surgery center of northwestern China: an efficiency analysis
Authors: Wu Yazhen , Yan Hong , Yan Weijia
Published: December 2020

Background

To compare the efficiency of preloaded vs manually loaded IOL (P-IOL vs M-IOL, respectively) delivery systems in cataract surgery in the largest ambulatory surgery center of Northwestern China.

Methods

A total of 200 cases were included in this prospective, observational study. Time and motion data were collected in a one- or two-operating room (1-OR or 2-OR, respectively) scenario. A model of the efficiency and revenue implications of introducing a preloaded delivery system for IOLs in cataract surgery was used to estimate the changes in cataract throughput and hospital revenue through transitioning from the M-IOL delivery system to the P-IOL system.

Results

In the 1-OR scenario, the mean total case time was 16.9 min using P-IOL, which was a 7.7% reduction compared with M-IOL (P < 0.01). In the 2-OR scenario, the mean total surgeon time was 10.8 min using P-IOL, which was a 7.8% reduction compared with M-IOL (P < 0.05). By switching from M-IOL to P-IOL, annual throughput will increase by 5.2% (960 cases) in the 1-OR scenario and 7.7% (1440 cases) in the 2-OR scenario, accompany by an increase in revenue of approx. 284,352 USD in the 1-OR scenario and approx. 426,528 USD in the 2-OR scenario.

Conclusion

This report is the first of a comparison of two IOL delivery systems in China using different settings in the scenario. IOL delivery with preloaded systems is time saving in both the 1-OR scenario and the 2-OR scenario. Moreover, switching from the M-IOL delivery system to the P-IOL system holds potential to increase cataract throughput and hospital revenue.
Proliferative retinopathy as a feature of Vogt Koyanagi Harada Disease: a report of two cases
Authors: Magliyah Moustafa S. , Al-Fakhri Abdulmajeed S. , Al-Dhibi Hassan A.
Published: December 2020

Background

Proliferative retinopathy is an uncommon feature of Vogt Koyanagi Harada (VKH) disease which might indicate poor uveitis control in these patients. We aim to describe the clinical features and outcome of management of proliferative retinopathy in 2 patients with VKH.

Case Presentation

19 and 33 years old females with VKH presented with unilateral proliferative retinopathy. Both patients had neovascularization of the optic disc (NVDs) and one patient had neovascularizations elsewhere (NVEs) and preretinal hemorrhage. Both patients had exudative retinal detachments (ERD). Systemic steroids and immunomodulatory agents were successfully used to control inflammation and achieve regression. One patient developed fibrous tissue formation at the disc area as well as an epiretinal membrane formation, for which she had pars plana vitrectomy with membrane peeling. Both patients had controlled inflammation with stable vision.

Conclusions

Proliferative retinopathy can present variably in VKH patients and indicates persistent inflammation which is incompletely controlled. Proper uveitis control is sufficient to achieve regression of retinal neovascularization.
Design and protocol of the multimorbidity and mental health cohort study in frailty and aging (MiMiCS-FRAIL): unraveling the clinical and molecular associations between frailty, somatic disease burden and late life depression
Authors: Aprahamian Ivan , Mamoni Ronei Luciano , Cervigne Nilva Karla , Augusto Taize Machado , Romanini Carla Vasconcelos , Petrella Marina , da Costa Daniele Lima , Lima Natalia Almeida , Borges Marcus K. , Oude Voshaar Richard C.
Published: December 2020

Background

To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness.

Methods

MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R2 between the predictor (death) and all covariates of 0.20. Local ethical board approved this study.

Discussion

Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.
The impact of COL1A1 and COL6A1 expression on hypospadias and penile curvature severity
Authors: Yuri Prahara , Gunadi  , Lestari Rahmadani Puji , Fardilla Firly Putri , Setyaningsih Wiwit Ananda Wahyu , Arfian Nur , Dachlan Ishandono
Published: December 2020

Background

Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penis, i.e. chordee. Abnormality of darto tissue has been suggested as the pathophysiology of chordees. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expression of collagen 1 (COL1A1) and COL6A1 in patients with hypospadias and associated them with the severity of penile curvature.

Methods

We included 60 children < 18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 controls in our institution from 2017 – 2020. The expression of COL1A1 and COL6A1 in darto tissue was determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (< 30 degrees), moderate (30–60 degrees), and severe (> 60 degrees).

Results

qPCR showed that COL1A1 and COL6A1 expression was significantly downregulated in the distal (0.88 (0.38–2.53) and 0.54 (0.16–4.35), respectively) and proximal 0.76 (0.33–2.57) and 0.57 (0.18–1.38), respectively) hypospadias groups compared to controls (1.85 (0.24–4.61) and 0.93 (0.17–4.06), respectively) with p-values of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expression (r = 0.458, p < 0.0001). Interestingly, COL1A1 and COL6A1 were also significantly downregulated in the moderate and severe chordee groups compared to the mild chordee groups, with p-values of 0.003 and 0.037, respectively.

Conclusions

Aberrant COL1A1 and COL6A1 expression might affect abnormalities in darto tissue and penile curvature severity in hypospadias patients.
Google analytics of a pilot study to characterize the visitor website statistics and implicate for enrollment strategies in Medical University
Authors: Chen Szu-Chieh , Tsao Thomas Chang-Yao , Lue Ko-Huang , Tsai Yafang
Published: December 2020

Background

Taiwan’s colleges and universities are struggling to maintain their student enrollment rates owing to the declining fertility rate. Focusing on students in higher education programs, this study aims to analyze online behavioral patterns for university departmental websites and accordingly, suggests response strategies to increase the rate of enrollment.

Methods

We use Google Analytics to examine the websites of two departments in a medical university between February 1 and July 30, 2018. We study website patterns during the study periods for three college admission routes: STARS program, personal applications, and admission through examination and placement.

Results

Most website visitors during the three visiting date ranges for the two departments are 18–24 years. The visitor groups are mainly freshmen at the university and their parents. The homepage and Subject Credits, Course Planning, Teacher Lineup, and Certificate of Subjects were the most visited webpages. The overall number of daily page views varied by academic event.

Conclusions

University departments should enhance the presentation of featured courses on their webpage or distinguish course characteristics from those of competing departments in the curriculum to ensure clear market segmentation. In addition, departments should consider examining online data to identify suitable high schools that can be visited to attract potential students and to improve students’ willingness to choose their university.
The extended lipid panel assay: a clinically-deployed high-throughput nuclear magnetic resonance method for the simultaneous measurement of lipids and Apolipoprotein B
Authors: Garcia Erwin , Bennett Dennis W. , Connelly Margery A. , Jeyarajah Elias J. , Warf Franklin C. , Shalaurova Irina , Matyus Steven P. , Wolak-Dinsmore Justyna , Oskardmay David N. , Young Randolph M. , Sampson Maureen , Remaley Alan T. , Otvos James D.
Published: December 2020

Background

Standard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing.

Methods

Partial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n > ~ 1000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated.

Results

Excellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested.

Conclusions

Extensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.
NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice
Authors: Wang Miao , Ye Xinchun , Hu Jinxia , Zhao Qiuchen , Lv Bingchen , Ma Weijing , Wang Weiwei , Yin Hanhan , Hao Qi , Zhou Chao , Zhang Tao , Wu Weifeng , Wang Yan , Zhou Mingyue , Zhang Cong-hui , Cui Guiyun
Published: December 2020

Background

Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin.

Methods

Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2.

Results

The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study.

Conclusion

NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1β/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.
Prophylactic inhibition of NF-κB expression in microglia leads to attenuation of hypoxic ischemic injury of the immature brain
Authors: Zaghloul Nahla , Kurepa Dalibor , Bader Mohammad Y. , Nagy Nadia , Ahmed Mohamed N.
Published: December 2020

Background

Periventricular leukomalacia (PVL), a devastating brain injury affecting premature infants, is the most common cause of cerebral palsy. PVL is caused by hypoxia ischemia (HI) and is characterized by white matter necrotic lesions, microglial activation, upregulation of NF-κB, and neuronal death. The microglia is the main cell involved in PVL pathogenesis. The goal of this study was to investigate the role of microglial NF-κB activity and its prophylactic inhibition in a neonate mouse model of HI.

Methods

Transgenic mice with specific knockout NF-κB in microglia and colony stimulating factor 1 receptor Cre with floxed IKKβ (CSF-1R Cre + IKKβflox/wt) were used. Postnatal day 5 (P5) mice underwent sham or bilateral temporary carotid artery ligation followed by hypoxia. After HI insult, inflammatory cytokines, volumetric MRI, histopathology, and immunohistochemistry for oligodendroglia and microglial activation markers were analyzed. Long-term neurobehavioral assessment, including grip strength, rotarod, and open field testing, was performed at P60.

Results

We demonstrate that selective inhibition of NF-κB in microglia decreases HI-induced brain injury by decreasing microglial activation, proinflammatory cytokines, and nitrative stress. Rescue of oligodendroglia is evidenced by immunohistochemistry, decreased ventriculomegaly on MRI, and histopathology. This selective inhibition leads to attenuation of paresis, incoordination, and improved grip strength, gait, and locomotion.

Conclusion

We conclude that NF-κb activation in microglia plays a major role in the pathogenesis of hypoxic ischemic injury of the immature brain, and its prophylactic inhibition offers significant neuroprotection. Using a specific inhibitor of microglial NF-κB may offer a new prophylactic or therapeutic alternative in preterm infants affected by HI and possibly other neurological diseases in which microglial activation plays a role.
Deficiency of Nrf2 exacerbates white matter damage and microglia/macrophage levels in a mouse model of vascular cognitive impairment
Authors: Sigfridsson Emma , Marangoni Martina , Hardingham Giles E. , Horsburgh Karen , Fowler Jill H.
Published: December 2020

Background

Chronic cerebral hypoperfusion causes damage to the brain’s white matter underpinning vascular cognitive impairment. Inflammation and oxidative stress have been proposed as key pathophysiological mechanisms of which the transcription factor Nrf2 is a master regulator. We hypothesised that white matter pathology, microgliosis, blood-brain barrier breakdown and behavioural deficits induced by chronic hypoperfusion would be exacerbated in mice deficient in the transcription factor Nrf2.

Methods

Mice deficient in Nrf2 (male heterozygote or homozygous for Nrf2 knockout) or wild-type littermates on a C57Bl6/J background underwent bilateral carotid artery stenosis (BCAS) to induce chronic cerebral hypoperfusion or sham surgery and survived for a further 6 weeks. White matter pathology was assessed with MAG immunohistochemistry as a marker of altered axon-glial integrity; alterations to astrocytes and microglia/macrophages were assessed with GFAP and Iba1 immunohistochemistry, and blood-brain barrier breakdown was assessed with IgG immunohistochemistry. Behavioural alterations were assessed using 8-arm radial arm maze, and alterations to Nrf2-related and inflammatory-related genes were assessed with qRT-PCR.

Results

Chronic cerebral hypoperfusion induced white matter pathology, elevated microglial/macrophage levels and blood-brain barrier breakdown in white matter tracts that were increased in Nrf2+/− mice and further exacerbated by the complete absence of Nrf2. Chronic hypoperfusion induced white matter astrogliosis and induced an impairment in behaviour assessed with radial arm maze; however, these measures were not affected by Nrf2 deficiency. Although Nrf2-related antioxidant gene expression was not altered by chronic cerebral hypoperfusion, there was evidence for elevated pro-inflammatory related gene expression following chronic hypoperfusion that was not affected by Nrf2 deficiency.

Conclusions

The results demonstrate that the absence of Nrf2 exacerbates white matter pathology and microgliosis following cerebral hypoperfusion but does not affect behavioural impairment.
Laboratory versus daily life gait characteristics in patients with multiple sclerosis, Parkinson’s disease, and matched controls
Authors: Shah Vrutangkumar V. , McNames James , Mancini Martina , Carlson-Kuhta Patricia , Spain Rebecca I. , Nutt John G. , El-Gohary Mahmoud , Curtze Carolin , Horak Fay B.
Published: December 2020

Background and purpose

 Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinson’s Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring.

Methods

 We recruited 15 people with MS (age mean ± SD: 49 ± 10 years), 16 MS-Ctl (45 ± 11 years), 16 people with idiopathic PD (71 ± 5 years), and 15 PD-Ctl (69 ± 7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. Mann–Whitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life.

Results

 Participants wore sensors for 60–68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI] = 0.80 [0.63–0.96]) whereas gait speed in daily life (AUC = 0.84 [0.69–1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUC = 0.78 [0.59–0.96]) whereas foot-strike angle in daily life (AUC = 0.84 [0.70–0.98]). AUCs were larger in daily life compared to the laboratory.

Conclusions

Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures.
Advancing clinical leadership to improve the implementation of evidence-based practice in surgery: a longitudinal mixed-method study protocol
Authors: Grove Amy , Clarke Aileen , Currie Graeme , Metcalfe Andy , Pope Catherine , Seers Kate
Published: December 2020

Background

Clinical leadership is fundamental in facilitating service improvements in healthcare. Few studies have attempted to understand or model the different approaches to leadership which are used when promoting the uptake and implementation of evidence-based interventions. This research aims to uncover and explain how distributed clinical leadership can be developed and improved to enhance the use of evidence in practice. In doing so, this study examines implementation leadership in orthopaedic surgery to explain leadership as a collective endeavour which cannot be separated from the organisational context.

Methods

A mixed-method study consisting of longitudinal and cross-sectional interviews and an embedded social network analysis will be performed in six NHS hospitals. A social network analysis will be undertaken in each hospital to uncover the organisational networks, the focal leadership actors and information flows in each organisation. This will be followed by a series of repeated semi-structured interviews, conducted over 4 years, with orthopaedic surgeons and their professional networks. These longitudinal interviews will be supplemented by cross-sectional interviews with the national established surgical leaders. All qualitative data will be analysed using a constructivist grounded theory approach and integrated with the quantitative data. The participant narratives will enrich the social network to uncover the leadership configurations which exist, and how different configurations of leadership are functioning in practice to influence implementation processes and outcomes.

Discussion

The study findings will facilitate understanding about how and why different configurations of leadership develop and under what organisational conditions and circumstances they are able to flourish. The study will guide the development of leadership interventions that are grounded in the data and aimed at advancing leadership for service improvement in orthopaedics. The strength of the study lies in the combination of multi-component, multi-site, multi-agent methods to examine leadership processes in surgery. The findings may be limited by the practical challenges of longitudinal qualitative data collection, such as ensuring participant retention, which need to be balanced against the theoretical and empirical insights generated through this comprehensive exploration of leadership across and within a range of healthcare organisations.