bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a Relational Theory of Employee Engagement: Understanding Authenticity, Transparency, and Employee Behaviors
Authors: Jiang Hua , Shen Hongmei
Published: September 2020

Based on the relationship management paradigm and the job demands-resources model, we proposed a relational theory of employee engagement integrating employees’ immediate supervisors’ authentic leadership behaviors and perceived transparent organizational communication as antecedents of employee engagement and contextual performance behavior and turnover intention as behavioral outcomes that engagement leads to. Employee survey ( N = 727) results identified perceived transparent communication and employee engagement as key mediators between perceived authentic leadership and individual employee behavioral outcomes. Our study provided a fresh, interdisciplinary perspective to revisiting relationship management function, testing immediate supervisors’ leadership exchange and an overall transparent organizational communication climate as both relationship cultivation strategies and supportive workplace resources. Our findings also reinforced the value of transparent organizational communication in cultivating relationships with and fostering engagement of an organization’s stakeholders that prior literature called for more research about. In addition, it added more into the relatively limited but growing body of research on authentic leadership in association with organizational communication, engagement and other employee behavioral and organizational outcomes. We also discussed theoretical and practical implications of the study.
(2S,6S)- and (2R,6R)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice
Authors: Kang Heather , Park Pojeong , Han Muchun , Tidball Patrick , Georgiou John , Bortolotto Zuner A. , Lodge David , Kaang Bong-Kiun , Collingridge Graham L.
Published: September 2020

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.
Patient–Physician Alignment in Satisfaction With Psoriatic Arthritis Treatment: Analysis From a Cross-Sectional Survey in the United States and Europe
Authors: Gossec Laure , Orbai Ana-Maria , Lobosco Steve , Moon Rachel , Massey Olivia , Piercy James , Cappelleri Joseph C. , Fallon Lara , Young Pamela , Romero Ana-Belen , Hsu Ming-Ann
Published: September 2020

Background:

There is evidence that patients and physicians are frequently misaligned in their perspectives on psoriatic arthritis (PsA) treatment priorities, which may be associated with increased disease activity, greater disability, and poorer health-related quality of life of PsA patients.

Objective:

To identify factors associated with patient–physician misalignment in satisfaction with PsA disease control.

Methods:

In a cross-sectional survey of physicians and their patients with PsA from the United States and Europe, satisfaction with disease control was examined and classified as satisfied, neutral, or dissatisfied. Bivariate and multivariate regression analyses explored alignment in satisfaction between physicians and patients.

Results:

There were 656 PsA patient–physician pairs included in the analysis. Misalignment occurred in 20.6% of cases. Greater disease impact, worse physician-reported disease severity, and lower patient-reported involvement in treatment decisions were associated with misalignment.

Conclusion:

Greater patient–physician engagement may improve satisfaction, alignment, and outcomes in PsA disease control.
Indianness and Organisation Development
Authors: Malhotra Ashok
Published: September 2020

Anglo-Saxon notions, when deployed in societies like those in India, often become a source of stress and tension, causing waste of human energy and potential. This article traces Indian civilisational predispositions and their uneasy relationship with the prevailing corporate imperatives, exploring these as problematics in the action world of organisations and also as opportunities that need managerial attention in such a context. The author acknowledges the nuances that stem from civilisational uniqueness and underpins it in Indian diversity of contexts and major discontinuities in its geopolitical history. Implications for the organisation development (OD) practitioner in Indian context follow from this unique analytical frame.
The Unique Aspects of Organisation Development in the Social Sector
Authors: Moochhala Mustafa , Bhogal Tejinder Singh
Published: September 2020

At its best, the work of the social sector is about changing society—the underlying norms, attitudes and power relations—and at the very least, ameliorating some of the ills present, for example, paucity of access to health or food. It is this desire for change or amelioration that provides the motive force for organisational members. To build this motive force, organisation development (OD) interventions need to work on some or all of the following: building greater ownership of organisational staff through tweaking governance methods and organisational structures, (founder-led or an institutionalised structure); mirroring expected norms within community with those observed in the organisation; having clarity about the vision of the community; working with organisational dilemmas; and having a clear theory of change. The last implies building and understanding the complex nature of society and social change and interventions therein; and as a corollary, a culture of debate and thoughtfulness.
Embrace the Organisation Unconscious: The Next Steps for Change Leaders and Organisation Development Practitioners
Authors: Kartikeyan V.
Published: September 2020

The move from an ‘A-rational’ world to the rational can be traced to the seventeenth century, in particular to the contribution of Rene Descartes, who advocated what is now known as the Cartesian view, which deifies the rational, the objective and the measurable. The problem with this advocacy was that all aspects of what did not seem rational got marginalised. This marginalisation has led, over the last couple of centuries, to a sense of disenchantment, fragmentation and ‘exclusionary processes’ in society, organisations and in general all human systems.

Carl Jung’s pioneering work on the unconscious offers us a way out of this by beckoning us to revisit and reimagine the ‘A-rational’ in a way that brings vibrancy and aliveness to organisations. By envisaging the ‘Organisation Psyche’ and by learning to work with aspects of the ‘Organisation Unconscious’, such as the ‘Organisation Shadow’ and ‘Symbolic Complexes’, it may be possible to discover new integrative paths for change leaders and organisation development (OD) practitioners alike, to adopt to bring in a new sense of endeavour, volition and adventure for organisations and their agents.
Monteneroite, Cu2+Mn2+2(AsO4)2⋅8H2O, a new vivianite-structure mineral with ordered cations from the Monte Nero mine, Liguria, Italy
Authors: Kampf Anthony R. , Plášil Jakub , Nash Barbara P. , Ciriotti Marco E. , Castellaro Fabrizio , Chiappino Luigi
Published: September 2020

Monteneroite (IMA2020-028), Cu2+Mn2+2(AsO4)2⋅8H2O, is a new vivianite-structure mineral from the Monte Nero mine, Rocchetta di Vara, La Spezia, Liguria, Italy. It is a secondary mineral that crystallised from As-, Cu- and Mn-rich fluids and it is associated with braunite, copper, cuprite, rhodochrosite and strashimirite. Monteneroite occurs as light green, thick blades up to ~2.5 mm long. The streak is white. Crystals are transparent with vitreous lustre. The mineral has Mohs hardness of 2, is somewhat sectile, exhibits two cleavages ({010} perfect and {001} fair) and has irregular stepped fracture. The measured density is 2.97(2) g cm–3. Monteneroite is optically biaxial (+), with α = 1.604(2), β = 1.637(2) and γ = 1.688(2), determined in white light; 2V = 80(1)°; slight dispersion is r < v, orientation: X = b; Z ^ c = 52° in obtuse β. Electron microprobe analyses provided the empirical formula (Cu2+0.88Mn2+0.11)Σ0.99Mn2+2.00(As1.00O4)2⋅8H2O. Monteneroite is monoclinic, C2/m, a = 10.3673(14), b = 13.713(2), c = 4.8420(8) Å, β = 105.992(8)°, V = 661.72(18) Å3 and Z = 2. Monteneroite has a vivianite-type structure (R1 = 0.0535 for 534 I > 2σI reflections). It is the first mineral with this structure type to be defined with ordered octahedral cation sites.
Inverse relationship between oligoclonal expanded CD69− TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients
Authors: Vuckovic Slavica , Bryant Christian E. , Lau Ka Hei Aleks , Yang Shihong , Favaloro James , McGuire Helen M. , Clark Georgina , de St. Groth Barbara Fazekas , Marsh-Wakefield Felix , Nassif Najah , Abadir Edward , Vanguru Vinay , McCulloch Derek , Brown Christina , Larsen Stephen , Dunkley Scott , Khoo Liane , Gibson John , Boyle Richard , Joshua Douglas , Ho P. Joy
Published: September 2020

CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69− and CD69+ subsets, while only CD69− cells are found in PB. Within the BM-TTE compartment, CD69− and CD69+ cells are found in comparable proportions in controls, while CD69− cells are dominant in MGUS and SMM and predominantly either CD69− or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69−TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69−TTE cells include multiple oligoclonal expansions of T-cell receptor/Vβ families shared between BM and PB of NDMM. Oligoclonal expanded CD69−TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69−TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69−TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69− and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease.
Lung function changes over 8 years and testosterone markers in both sexes: UK Biobank
Authors: Lenoir Alexandra , Fuertes Elaine , Gómez-Real Francisco , Leynaert Benedicte , van der Plaat Diana A. , Jarvis Debbie
Published: September 2020

Higher levels of testosterone have been associated with better lung function in cross-sectional population-based studies. The role of testosterone in lung function in women and in lung function decline in men or women is unclear.

We studied 5114 men and 5467 women in the UK Biobank with high-quality spirometry at baseline (2006–2010) and 8.4 years later. We studied cross-sectional associations of total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI) and sex hormone-binding globulin (SHBG) with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using linear regression and associations of baseline markers with lung function decline using linear mixed-effects regression.

Men with higher levels of TT had higher FEV1(27.56 mL per interquartile range increase TT, 95% CI 5.43–49.68) and FVC (48.06 mL, 95% CI 22.07–74.06) at baseline. Higher cFT levels were associated with higher FEV1and FVC among physically active men only. In women, higher FAI and cFT levels were associated with lower lung function at baseline and higher levels of TT, cFT and FAI were associated with slightly attenuated FEV1and FVC decline. Higher levels of SHBG were associated with better lung function in both sexes but slightly accelerated decline in men.

In this population-based sample, higher levels of TT were associated with better lung function in men and higher levels of cFT with better lung function in physically active men. A small attenuation of lung function decline with higher levels of TT, cFT and FAI was seen in women only.
Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy
Authors: Conti Sara , Ferrara Pietro , Mazzaglia Giampiero , D'Orso Marco I. , Ciampichini Roberta , Fornari Carla , Madotto Fabiana , Magoni Michele , Sampietro Giuseppe , Silenzi Andrea , Sileo Claudio V. , Zucchi Alberto , Cesana Giancarlo , Manzoli Lamberto , Mantovani Lorenzo G.
Published: September 2020

Background

The real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on overall mortality remains uncertain as surveillance reports have attributed a limited number of deaths to novel coronavirus disease 2019 (COVID-19) during the outbreak. The aim of this study was to assess the excess mortality during the COVID-19 outbreak in highly impacted areas of northern Italy.

Methods

We analysed data on deaths that occurred in the first 4 months of 2020 provided by the health protection agencies (HPAs) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardised mortality ratio (SMR) and cumulative number of excess deaths through a Poisson generalised additive model of the observed counts in 2020, using 2019 data as a reference.

Results

We estimated that there were 5740 (95% credible set (CS) 5552–5936) excess deaths in the HPA of Bergamo and 3703 (95% CS 3535–3877) in Brescia, corresponding to a 2.55-fold (95% CS 2.50–2.61) and 1.93 (95% CS 1.89–1.98) increase in the number of deaths. The excess death wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly 2 weeks after the introduction of lockdown measures, with significantly higher estimates in Bergamo (9.4, 95% CI 9.1–9.7).

Conclusion

Excess mortality was significantly higher than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on the health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower excess mortality in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.
Landmark-guided versus modified ultrasound-assisted Paramedian techniques in combined spinal-epidural anesthesia for elderly patients with hip fractures: a randomized controlled trial
Authors: Qu Bo , Chen Luying , Zhang Yuling , Jiang Mengting , Wu Caineng , Ma Wuhua , Li Yuhui
Published: September 2020

Background

Combined spinal-epidural (CSE) anesthesia is considerably challenging for elderly patients with hip fractures due to spine degeneration and limitations in positioning. This study aimed to investigate the ability of a modified preprocedural ultrasound-guided technique to improve the success rate and efficacy of CSE anesthesia for elderly patients with hip fractures.

Methods

This prospective, single-blinded, parallel-group randomized controlled trial included 80 patients (aged ≥65 years) who were scheduled for elective hip fracture surgery with CSE anesthesia. Patients were randomly allocated into landmark group (n = 40) or the ultrasound group (n = 40). The primary outcome was first-pass success rate. Secondary outcomes included first-attempt success rate; number of needle insertion attempts; number of needle passes; locating, puncture, and total time; level of block; procedural adverse reactions and postoperative complications; and patient satisfaction score. Patients were blinded to group allocation.

Results

Eighty patients completed the study and were included in the final analysis. The first-pass success rates for the landmark and ultrasound groups were 20 and 70%, respectively (P < 0.001). The first-attempt success rates in the landmark and ultrasound groups were 42.5 and 85%, respectively (P < 0.001). The median number of attempts was lower in ultrasound-assisted group (1 [1, 1]) than landmark-guided group (2 [1, 2]), P < 0.001). The median number of needle passes was lower in ultrasound group (1 [1, 2]) than in landmark-guided group (3 [2, 4], P < 0.001). The locating time (P < 0.001) and total time (P = 0.001) were longer in the ultrasound group, while puncture time was shorter (P = 0.003). No significant difference was found regarding the incidence of adverse reactions and complications. More patients in the ultrasound group had a high satisfaction score of 4–5 (P = 0.007). Interestingly, subgroup analysis demonstrated benefits for ultrasound in patients with scoliosis.

Conclusions

Modified ultrasound-assisted CSE anesthesia increases first-pass and first-attempt success rates, and reduces needle insertion attempts, passes, and puncture time for elderly patients with hip fracture, especially those with scoliosis. This technique improves patient satisfaction and warrants consideration for application in clinical practice.

Trial registration

Chinese Clinical Trial Register (identifier, ChiCTR1900020819; date of registration, January 20, 2019).
Perception of service users and their caregivers on primary care-based mental health services: a qualitative study in Nepal
Authors: Luitel N. P. , Jordans M. J. D. , Subba P. , Komproe I. H.
Published: September 2020

Background

Integration of mental health services into primary health care systems has been advocated as a strategy to minimize the tremendous mental health treatment gap, particularly in low- and middle-income countries. Barriers to integration of mental health into primary health care have been widely documented; however, very little is known about the perception of service users and their caregivers on primary care-based mental health services. This study assessed service users’ and caregivers’ perceptions of mental health services provided by trained primary health care workers in Nepal.

Methods

A qualitative study was conducted among people with depression, psychosis, alcohol use disorder and epilepsy, and their caregivers in Chitwan, a district in southern Nepal. Semi-structured interviews were conducted with 43 service users and 38 caregivers to assess their perceptions about the accessibility of the services, types of services they received, skills and competencies of health care providers, satisfaction and barriers to receiving services.

Results

Overall, both service users and caregivers were satisfied with the mental health services provided by primary health care providers. They also perceived health workers to be competent and skillful because the services they received were effective in reducing their mental health problems. Both psychological and pharmacological services were made available free of cost, however, they considered psychological services more effective than pharmacological treatment. Major challenges and difficulties accessing services were associated with frequent transfer of trained health workers, non-availability of the same health care provider at follow-ups, frequent stock-out of medicines or non-availability of required medicines, lack of a confidential space for consultation in health facilities, and stigmatizing and negative behavior of some health workers.

Conclusion

The results demonstrated that both service users and caregivers perceived primary care-based mental health services to be accessible, acceptable and effective. The key recommendations emerging from this study for improving mental health services in primary care include the provision of a separate cadre of psychosocial workers to provide psychological interventions, developing quick and efficient mechanisms for the procurement and supply of psychotropic medicines, establishing a confidential place within health facilities for consultation, and further training of health workers to reduce stigma.
Does zinc with and without iron co-supplementation have effect on motor and mental development of children? A systematic review and meta-analysis
Authors: Sajedi Firoozeh , Shahshahani Soheila , Ghiasvand Hesam , Mosallanezhad Zahra , Fatollahierad Shiva
Published: September 2020

Background

Effects of zinc with and without iron co-supplementation on child development are uncertain therefore the aims of this systematic review were to explore whether supplementation with zinc alone and zinc with iron in children aged 0–5 years old have beneficial or adverse effects on their mental and motor development.

Method

We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science and Scopus until July 2020 and included randomized controlled trials, which assessed effects of zinc supplementation with and without iron in children less than 5 years old on mental and motor development. Data were pooled by random effects model and the Standardized Mean Differences (SMDs) with 95% confidence interval were estimated. The heterogeneity was assessed by I2.

Results

Twenty-five studies with 11,559 participants were eligible to be included in this systematic review. Meta-analysis was conducted with eight articles that used Bayley Scales of Infant and Toddler Development II. We concluded that zinc alone and zinc with iron co-supplementation do not have beneficial or adverse effect on child mental and motor development at 6 and 12 months of age with low to moderate quality of the evidence. Furthermore, Zinc supplementation does not have any long term effect on child development in preschool and school age children.

Conclusion

Most included studies did not show the efficacy of zinc with and without iron co-supplementation on child mental and motor development up to 9 years old age. Further Randomized Controlled Trials (RCTs) need to be taken into considerations the context-based differences between countries with special focus on socio-economic differences.
Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach
Authors: Huang Xiaoqi , Chen Zhiwei , Li Minyao , Zhang Yaomin , Xu Shijie , Huang Haiyang , Wu Xiaoli , Zheng Xuebao
Published: September 2020

Background

Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) andPaeonia lactifloraPall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair.

Methods

A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets.

Results

The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2(PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect.

Conclusion

This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.
Effective accreditation in postgraduate medical education: from process to outcomes and back
Authors: Bandiera Glen , Frank Jason , Scheele Fedde , Karpinski Jolanta , Philibert Ingrid
Published: September 2020

Background

The accreditation of medical educational programs is thought to be important in supporting program improvement, ensuring the quality of the education, and promoting diversity, equity, and population health. It has long been recognized that accreditation systems will need to shift their focus from processes to outcomes, particularly those related to the end goals of medical education: the creation of broadly competent, confident professionals and the improvement of health for individuals and populations. An international group of experts in accreditation convened in 2013 to discuss this shift.

Main text

Participants unequivocally supported the inclusion of more outcomes-based criteria in medical education accreditation, specifically those related to the societal accountability of the institutions in which the education occurs. Meaningful and feasible outcome metrics, however, are hard to identify. They are regionally variable, often temporally remote from the educational program, difficult to measure, and susceptible to confounding factors. The group identified the importance of health outcomes of the clinical milieu in which education takes place in influencing outcomes of its graduates. The ability to link clinical data with individual practice over time is becoming feasible with large repositories of assessment data linked to patient outcomes. This was seen as a key opportunity to provide more continuous oversight and monitoring of program impact. The discussants identified several risks that might arise should outcomes measures completely replace process issues. Some outcomes can be measured only by proxy process elements, and some learner experience issues may best be measured by such process elements: in brief, the “how” still matters.

Conclusions

Accrediting bodies are beginning to view the use of practice outcome measures as an important step toward better continuous educational quality improvement. The use of outcomes will present challenges in data collection, aggregation, and interpretation. Large datasets that capture clinical outcomes, experience of care, and health system performance may enable the assessment of multiple dimensions of program quality, assure the public that the social contract is being upheld, and allow identification of exemplary programs such that all may improve. There remains a need to retain some focus on process, particularly those related to the learner experience.
The trace aminergic system: a gender-sensitive therapeutic target for IBS?
Authors: Pretorius Lesha , Smith Carine
Published: September 2020

Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a “missing link” that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.
Correction to: Melatonin and urological cancers: a new therapeutic approach
Authors: Pourhanifeh Mohammad Hossein , Hosseinzadeh Azam , Juybari Kobra Bahrampour , Mehrzadi Saeed
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study
Authors: Hejazi Jalal , Ghanavati Matin , Hejazi Ehsan , Poustchi Hossein , Sepanlou Sadaf G. , Khoshnia Masoud , Gharavi Abdolsamad , Sohrabpour Amir Ali , Sotoudeh Masoud , Dawsey Sanford M. , Boffetta Paolo , Abnet Christian C. , Kamangar Farin , Etemadi Arash , Pourshams Akram , FazeltabarMalekshah Akbar , Brennan Paul , Malekzadeh Reza , Hekmatdoost Azita
Published: September 2020

Background and objectives

Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country.

Methods

A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models.

Results

During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73–0.89), 0.83(0.76–0.92), 0.88(0.80–0.96) and 0.83(0.77–0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73–1.00) and 0.85(0.72–1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68–0.98)].

Conclusion

The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.
Expression of angiopoietin-like protein 2 in ovarian tissue of rat polycystic ovarian syndrome model and its correlation study
Authors: Wang Dandan , Guo Yihong , Chai Shujuan , Shen Ke , Li Yanchun , Zhao Ruiqin
Published: September 2020

Background

This study investigated the expression of angiopoietin-like protein 2 (ANGPTL2) in the tissues of rat models of polycystic ovary syndrome (PCOS) and its correlation with PCOS.

Methods

Six-weeks-old female specific pathogen-free rats (n = 60) were divided into blank control, PCOS model, and metformin groups (n = 20/group). After 21 days of metformin intervention, the serum sex hormones, fasting blood glucose, fasting insulin, and insulin resistance (IR) of rats in each group were measured. The mRNA levels of ANGPTL2, Foxol, and Akt in the ovarian tissues were monitored by real-time fluorescence quantitative PCR.

Results

Compared with the control group, the levels of serum sex hormones, fasting blood glucose, fasting insulin, and IR in the model group showed significant increases, and the levels of ANGPTL2, Foxol, and Akt in the ovarian tissue also showed significant increases. Compared with the PCOS group, the serum sex hormones, fasting blood glucose, fasting insulin, and IR of rats in the metformin group were significantly decreased, and the levels of ANGPTL2, Foxol, and Akt in ovarian tissues also showed significant decreases.

Conclusions

These findings suggest that ANGPTL2 might participate in the development of PCOS through the PI3K/Akt signaling pathway. Metformin improves IR by reducing the expression of ANGPTL2, thus improving the endocrine environment of PCOS and might change the disease outcome.
Tissue-specific usage of transposable element-derived promoters in mouse development
Authors: Miao Benpeng , Fu Shuhua , Lyu Cheng , Gontarz Paul , Wang Ting , Zhang Bo
Published: September 2020

Background

Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology.

Results

We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution.

Conclusion

Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development.
Identification of new driver and passenger mutations within APOBEC-induced hotspot mutations in bladder cancer
Authors: Shi Ming-Jun , Meng Xiang-Yu , Fontugne Jacqueline , Chen Chun-Long , Radvanyi François , Bernard-Pierrot Isabelle
Published: September 2020

Background

APOBEC-driven mutagenesis and functional positive selection of mutated genes may synergistically drive the higher frequency of some hotspot driver mutations compared to other mutations within the same gene, as we reported forFGFR3S249C. Only a few APOBEC-associated driver hotspot mutations have been identified in bladder cancer (BCa). Here, we systematically looked for and characterised APOBEC-associated hotspots in BCa.

Methods

We analysed 602 published exome-sequenced BCas, for part of which gene expression data were also available. APOBEC-associated hotspots were identified by motif-mapping, mutation signature fitting and APOBEC-mediated mutagenesis comparison. Joint analysis of DNA hairpin stability and gene expression was performed to predict driver or passenger hotspots. Aryl hydrocarbon receptor (AhR) activity was calculated based on its target genes expression. Effects of AhR knockout/inhibition on BCa cell viability were analysed.

Results

We established a panel of 44 APOBEC-associated hotspot mutations in BCa, which accounted for about half of the hotspot mutations. Fourteen of them overlapped with the hotspots found in other cancer types with high APOBEC activity. They mostly occurred in the DNA lagging-strand templates and the loop of DNA hairpins. APOBEC-associated hotspots presented systematically a higher prevalence than the other mutations within each APOBEC-target gene, independently of their functional impact. A combined analysis of DNA loop stability and gene expression allowed to distinguish known passenger from known driver hotspot mutations in BCa, including loss-of-function mutations affecting tumour suppressor genes, and to predict new candidate drivers, such asAHRQ383H. We further characterisedAHRQ383H as an activating driver mutation associated with high AhR activity in luminal tumours. High AhR activity was also found in tumours presenting amplifications ofAHRand its co-receptorARNT. We finally showed that BCa cells presenting those different genetic alterations were sensitive to AhR inhibition.

Conclusions

Our study identified novel potential drivers within APOBEC-associated hotspot mutations in BCa reinforcing the importance of APOBEC mutagenesis in BCa. It could allow a better understanding of BCa biology and aetiology and have clinical implications such as AhR as a potential therapeutic target. Our results also challenge the dogma that all hotspot mutations are drivers and mostly gain-of-function mutations affecting oncogenes.
Understanding the impact of antibiotic perturbation on the human microbiome
Authors: Schwartz Drew J. , Langdon Amy E. , Dantas Gautam
Published: September 2020

The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome’s ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.
From invention to industry from a social movement perspective: the emergence of the 3D printing industry
Authors: Lechner Christian , Pervaiz Abeer
Published: September 2020

In the entrepreneurship literature, the phenomenon of industry emergence has been largely investigated from an institutional perspective. Appropriate institutions would allow then a group of individual entrepreneurs (“the heroes”) to create an industry through innovative ventures. New ventures create new industries and firm entry, survival, and exit drive industry evolution. Our research, however, explores what creates the favorable set of circumstances for new ventures to emerge and focuses on the pre-emergence phase and we propose that the patterns of emergence resemble those of social movements. Through an actor perspective, this research highlights the existence of diverse actors, not necessarily entrepreneurs, who are necessary to trigger a collective action during the pre-emergence phase of industries. This research is also distinct from entrepreneurial ecosystems as its development already requires some successful entrepreneurial action. The 3D printing industry was chosen as a single longitudinal case study, where the actors are the embedded units of analysis. The findings of the study lead to the identification of three aggregate dimensions—“Social Movement Composition,” Temporal Engagement,” and “Coalitions Development”—that were prevalent during the pre-emergence phase of the 3D printing industry. Our propositions emphasize the importance of large collective action and the role of multiple actors in order to create the conditions for, first, firm emergence and, the second, to the process of industry emergence.
FibroBox: a novel noninvasive tool for predicting significant liver fibrosis and cirrhosis in HBV infected patients
Authors: Lu Xiao-Jie , Yang Xiao-Jun , Sun Jing-Yu , Zhang Xin , Yuan Zhao-Xin , Li Xiu-Hui
Published: September 2020

Background

China is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort.

Methods

Using liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets).

Results

Of 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis.

Conclusions

FibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.
Acupuncture for knee osteoarthritis with sensitized acupoints: results from a pilot, feasibility randomized controlled trial
Authors: Jia Pengli , Liu Jiali , Li Ling , Luo Yanan , Li Ying , Zhao Ling , Liang Fanrong , Liu Zhibin , Zou Kang , Tang Li , Sun Xin
Published: September 2020

Background

Although previous clinical studies suggest possible benefits of acupuncture for knee osteoarthritis (KOA), the value of acupuncture at sensitized points is uncertain. We aimed to preliminarily assess the feasibility of performing a definitive randomized controlled trial to explore the effectiveness of acupuncture for KOA with highly sensitized acupoints.

Methods

In this randomized, single-blind, parallel, pilot trial, 36 participants with KOA were randomly assigned to receive acupuncture at highly sensitized acupoints (high-sensitization group) or at low/non-sensitized points (low/non-sensitization group) by a computer-generated random sequence. Both groups received three treatment sessions per week for four consecutive weeks (12 sessions in total). Assessments were performed at screening and at 4, 8, 12, and 16 weeks after randomization. Primary feasibility outcomes were patient recruitment, retention rate, and adherence to group treatment. Secondary outcomes included the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score from baseline to 16 weeks, the change of Short Form (SF)-12 health survey score, and safety outcomes.

Results

Patient recruitment of 36 patients took 2 months, achieving the recruitment target. Retention rates were similar between the treatment groups, 14 (77.8%) patients in the high-sensitization group completed the 16-week follow-up and compared to 14 (77.8%) patients in low/non-sensitization group, but the result was lower than expected. All patients received at least ten treatment sessions in total. The WOMAC total score and the pain, stiffness, and physical function score in the high-sensitization group were lower or very close to those in the control group at each assessment point. Similar results were observed on quality of life. No adverse events occurred.

Conclusion

This trial has presented preliminary data on the feasibility of conducting a large trial to test the effectiveness of acupuncture at sensitized points in KOA patients.

Trial registration

ClinicalTrials.gov, NCT03008668. Registered on 26 December 2016—retrospectively registered.
Single arm prospective multicenter case series on the use of burst stimulation to improve pain and motor symptoms in Parkinson’s disease
Authors: Chakravarthy Krishnan V. , Chaturvedi Rahul , Agari Takashi , Iwamuro Hirokazu , Reddy Rajiv , Matsui Ayano
Published: September 2020

Background

In this study we analyze new clinical data in the use of spinal cord stimulation (SCS) for the treatment of pain and motor symptoms in patients with Parkinson’s Disease (PD), as both a singular bioelectric therapy and as a salvage therapy after deep brain stimulation (DBS).

Methods

Fifteen patients were recruited and had percutaneous electrodes implanted at the level of the thoracic or cervical spine. Participants were set to one of three stimulation modes: continuous tonic stimulation, continuous Burst stimulation (40 Hz, 500 Hz, 1000 μs), or cycle mode (on time of 10–15 s, off time of 15–30 s) with Burst (40 Hz, 500 Hz, 1000 μs). Patients completed the Visual Analogue Scale (VAS), Unified Parkinson’s Disease Rating Scale, Self-Rating Depression Scale, Hamilton Depression Rating Scale, Profile of Mood State, 10-meter walking test, and the Timed Up and Go (TUG).

Results

All patients experienced significant improvement in VAS scores with a mean reduction of 59% across all patients. Patients who chose the cycling burst stimulation parameter had an average 67% reduction in VAS scores, as compared to the continuous burst parameter group, which had an average 48% reduction in VAS scores. Seventy-three percent of patients experienced improvement in the 10-meter walk, with an average improvement of 12%. Sixty-four percent of patients experienced clinically relevant improvements in the TUG, with an average improvement of 21%.

Conclusions

This study points to the potential utility of SCS to address both pain and certain aspects of motor symptoms in PD patients who have and have not received DBS therapy.