bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hand Osteoarthritis: investigating Pain Effects of estrogen-containing therapy (HOPE-e): a protocol for a feasibility randomised placebo-controlled trial
Authors: Marian Ioana R. , Goff Megan , Williams Jennifer A. E. , Gulati Malvika , Chester-Jones Mae , Francis Anne , Watson Marion , Vincent Tonia L. , Woollacott Sue , Mackworth-Young Charles , Glover Victoria , Furniss Dominic , Gardiner Matthew , Lamb Sarah E. , Vincent Katy , Barber Vicki S. , Black Joanna , Dutton Susan J. , Watt Fiona E. 
Published: June 2021

Abstract
Background
Hand osteoarthritis (OA) is a common condition, causing pain, stiffness and reduced quality of life. Incidence is higher amongst women, particularly around the age of the menopause. Whilst the relationship between sex hormones and OA has been studied in vitro, in epidemiological studies and in clinical trials of hormone replacement therapy (HRT), this study is the first to investigate the effect of estrogen-containing therapy on hand pain in post-menopausal women with symptomatic hand OA in a randomised study design.

Methods
This is a feasibility study of a double-blinded placebo-controlled intervention with 1:1 randomisation to either a combination of conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg (Duavive) or placebo. The target population is post-menopausal women with symptomatic hand OA, aiming to recruit 60–90 study participants. The primary objective is to assess the feasibility of a future fully powered randomised controlled trial (RCT). Participants will take the study medication for 24 weeks and be followed up for 28 weeks after randomisation. The primary outcomes used to determine feasibility are eligible participant identification rates and routes; recruitment, randomisation and retention rates of eligible participants; study medication compliance; and the likelihood of unintentional unblinding. Secondary outcomes include measures of hand pain, function, appearance and menopausal symptoms. An end of study questionnaire and focus groups will help to refine the final protocol for a full study.

Discussion
Identifying new treatments for symptomatic hand OA is a recognised research priority. The study will help us to understand whether there are sufficient interested and eligible individuals in this target population who would consider HRT for their hand symptoms. It will provide proof-of-concept RCT data on the effects of HRT on hand pain and other clinically relevant outcomes in this population. The study will gain valuable information on the feasibility of a full RCT and how best to run this. The findings will be published in a peer-reviewed journal and presented at a relevant conference.

Trial registration
ISRCTN12196200 registered on 15 January 2019.
Business ecosystem architecture development: a case study of Electric Vehicle home charging
Authors: Ma Zheng , Christensen Kristoffer , Jørgensen Bo Nørregaard 
Published: June 2021

AbstractDue to the complexity of business ecosystems, the architecture of business ecosystems has not been well discussed in the literature, and modeling or simulation of business ecosystems has been rarely focused. Therefore, this paper proposes a business ecosystem ontology and introduces a methodology for business ecosystem architecture design. The proposed methodology includes five stages: 1) Boundary identification of a business ecosystem; 2) Identification of actors and their roles in the business ecosystem; 3) Identification of actors’ value propositions; 4) Identification of interaction between actors; 5) Verification of business ecosystem architecture design. This paper uses the Danish electricity system as an example to introduce the methodology, and use Electric Vehicle home charging as a case study to demonstrate the application of the developed methodology. The case study demonstrates that the proposed methodology is a systematic approach and can be easily applied to any ecosystem architecture design with the five stages, and the designed ecosystem architecture can represent the physical system and business. Several definitions are clarified in the paper, e.g., actor, role, interaction, ecosystem roadmap and expanded/shifted ecosystem, etc. With clear definitions, the proposed methodology provides a visualized, clear structure of behaviors and specifications for a given business ecosystem.
Chronology of cardiac dysfunction after permanent pacemaker implantation: an observational 2 year prospective study in North India
Authors: Gupta Harshit , Showkat Hakim Irfan , Aslam Naved , Tandon Rohit , Wander G. S. , Gupta Shweta , Anwar Sadaf , Sohil Mohd Maqbool 
Published: June 2021

Abstract
Background
The purpose of this study is to evaluate cardiac functions using transthoracic echocardiography, change in lead parameters and electrocardiogram (ECG) morphology in patients undergoing permanent pacemaker implantation over a follow-up period of 6 months.

Methods
This is a prospective study in patients undergoing permanent pacemaker implantation in a tertiary care hospital. Patients undergoing permanent pacemaker implantation were enrolled for up to one year and Echocardiographic parameters (by 2 blind operators) and ECG parameters were recorded at admission (within 24 h), before discharge (within 7 days of pacemaker implantation), after 1 month (± 7 days) and after 6 months (± 7 days) of follow-up.

Results
A total of 96 patients (60.4% males and 39.6% female, mean age 66.65 years) were implanted with permanent pacemaker. The mean QRS duration was 133.18 ms and increased significantly to 146.03 ms by 6 months despite septal lead placement in majority (92%) of patients. The mean baseline ejection fraction of 51.47 decreased significantly to 47.83 by 6 months. Diastolic parameters like left atrial volume index, early to late diastolic transmitral flow velocity (E/A) and early diastolic mitral annular tissue velocity (E/e′) showed a significant increase (> 5%) from baseline by the end of first week. By the end of first month, systolic dysfunction of RV sets in with significant (> 5%) change from baseline in parameters like Right ventricle myocardial performance index, transannular plane systolic excursion and right ventricle systolic excursion velocity (RVS′).

Conclusion
We have observed that pacemaker recipients with baseline reduced left ventricle (LV) systolic functions perform significantly worse compared to those with baseline normal cardiac functions and had a higher rate of deterioration of LV function. RV dysfunction is the first abnormality that occurs, by 1 week followed by LV dysfunction which starts by 1 month and the diastolic dysfunctions precede the systolic dysfunction. QRS duration also showed a gradual increase despite septal lead placement in majority (92%) and lead parameters showed no significant change over 6 months.
Behavior-dependent critical dynamics in collective states of active particles
Authors: Löffler Robert C. , Bäuerle Tobias , Kardar Mehran , Rohwer Christian M. , Bechinger Clemens 
Published: June 2021

Abstract
We experimentally demonstrate critical collective behavior in a system of active colloidal particles (APs), achieved through variations of their mutual interactions using feedback control. At the transition between a swarm and a swirl we observe an explicit bifurcation dynamics of the rotational order parameter and a critical slowing down, i.e., a growth of the relaxation time by almost one order of magnitude. Additional signatures of critical dynamics, including hysteresis in presence of symmetry-breaking particle interactions, and a maximum of the susceptibility, are measured and characterized in terms of a theoretical model which is based purely on the time-reversal symmetry of the order parameter.
Contesting Militarized Violence in “Northeast India”
Authors: Mehta Brinda J. 
Published: June 2021

Abstract
The northeastern states of India have been positioned as India’s postcolonial other in mainstream politics with the aim to create xenophobic binaries between insider and outsider groups. Comprising the eight “sister” states of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, and Tripura, this region represents India’s amorphous shadowlands in arbitrary political markings between the mainland and the off-centered northeastern periphery. These satellite states have been subjected to the neocolonial governance of the Indian government and its implementation of political terror through abusive laws, militarized violence, protracted wars against civilians and insurgents alike, and gender abuse. Women poets from the region, such as Monalisa Changkija, Temsüla Ao, Mamang Dai, and others, have played a leading role in exposing and denouncing this violence. This essay examines the importance of women’s poetry as a gendered documentation of conflict, a peace narrative, a poet’s reading of history, and a site of memory. Can poetry express the particularized “sorrow of women” (Mamang Dai) without sentimentality and concession? How do these poetic contestations of conflict represent complex interrogations of identity, eco-devastation, and militarization to invalidate an elitist “poetry for poetry’s sake” ethic?
The Mythical Courtesan
Authors: Putcha Rumya S. 
Published: June 2021

Abstract
This article interrogates how and why courtesan identities are simultaneously embraced and disavowed by Brahman dancers. Using a combination of ethnographic and critical feminist methods, which allow the author to toggle between the past and the present, between India and the United States, and between film analysis and the dance studio, the author examines the cultural politics of the romanticized and historical Indian dancer—the mythical courtesan. The author argues that the mythical courtesan was called into existence through film cultures in the early twentieth century to provide a counterpoint against which a modern and national Brahmanical womanhood could be articulated. The author brings together a constellation of events that participated in the construction of Indian womanhood, especially the rise of sound film against the backdrop of growing anticolonial and nationalist sentiments in early twentieth-century South India. The author focuses on films that featured an early twentieth-century dancer-singer-actress, Sundaramma. In following her career through Telugu film and connecting it to broader conversations about Indian womanhood in the 1930s and 1940s, the author traces the contours of an affective triangle between three mutually constituting emotional points: pleasure, shame, and disgust.
Cell cycle control during early embryogenesis
Authors: Brantley Susanna E. , Di Talia Stefano 
Published: June 2021

ABSTRACT
Understanding the mechanisms of embryonic cell cycles is a central goal of developmental biology, as the regulation of the cell cycle must be closely coordinated with other events during early embryogenesis. Quantitative imaging approaches have recently begun to reveal how the cell cycle oscillator is controlled in space and time, and how it is integrated with mechanical signals to drive morphogenesis. Here, we discuss how the Drosophila embryo has served as an excellent model for addressing the molecular and physical mechanisms of embryonic cell cycles, with comparisons to other model systems to highlight conserved and species-specific mechanisms. We describe how the rapid cleavage divisions characteristic of most metazoan embryos require chemical waves and cytoplasmic flows to coordinate morphogenesis across the large expanse of the embryo. We also outline how, in the late cleavage divisions, the cell cycle is inter-regulated with the activation of gene expression to ensure a reliable maternal-to-zygotic transition. Finally, we discuss how precise transcriptional regulation of the timing of mitosis ensures that tissue morphogenesis and cell proliferation are tightly controlled during gastrulation.
Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice
Authors: Nie Yu , Xu Shang-Fu , Lu Yan-Liu , Zhao Xiu-Rong , Li Cen , Wei Li-Xin , Liu Jie 
Published: June 2021

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.
Focused ultrasound in out-of-hospital cardiac arrest by advanced paramedics
Authors: Brown Nick , Fothergill Rachael , McIntyre Ian , Faulkner Mark , Quinn Tom 
Published: June 2021

Background: This study describes and evaluates advanced paramedic practitioner (APP) use of focused cardiac ultrasound (FoCUS) in out-of-hospital cardiac arrest (OHCA), and relates ultrasound findings with decisions to terminate resuscitation. The authors report characteristics of patients who do/do not undergo a FoCUS examination by APPs, ultrasound probe positions used and whether FoCUS findings were associated with decisions to terminate resuscitation or to convey patients to an emergency department (ED) with ongoing resuscitation. Method: A retrospective, observational cohort study of all adult medical OHCA patients attended by APPs in Greater London during 2018 was carried out using data from EMS and APP databases. Results: Twenty-eight APPs attended 1444 OHCA patients in 2018, of whom 744 underwent FoCUS. The subcostal probe position was used most frequently (74%), followed by the parasternal long axis (19%), with significantly smaller use of the parasternal short axis and apical windows. Absence of spontaneous cardiac motion (SCM) was associated with resuscitation being terminated (333 out of 391; 85%) and the presence of SCM was associated with conveyance to the emergency department (213 out of 264 patients; 80%). All decisions to terminate resuscitation were within the APP scope of practice. Conclusion: The authors believe this is the largest prehospital study involving FoCUS in OHCA. An association between FoCUS findings and decisions made to either convey patients to hospital or terminate resuscitation was found. The SC window was most used and ROLE decisions were deemed to be in accordance with local guidance and practice.
Undernutrition, food insecurity, and leprosy in North Gondar Zone, Ethiopia: A case-control study to identify infection risk factors associated with poverty
Authors: Anantharam Puneet , Emerson Lisa E. , Bilcha Kassahun D. , Fairley Jessica K. , Tesfaye Annisa B. 
Published: June 2021

Background
Ethiopia has over 3,200 new cases of leprosy diagnosed every year. Prevention remains a challenge as transmission pathways are poorly understood. Susceptibility and disease manifestations are highly dependent on individual host-immune response. Nutritional deficiencies, such as protein-energy malnutrition, have been linked to reduced cell-mediated immunity, which in the case of leprosy, could lead to a higher chance of active leprosy and thus an increased reservoir of transmissible infection.

Methodology/Principal findings
Between June and August 2018, recently diagnosed patients with leprosy and individuals without known contact with cases were enrolled as controls in North Gondar regional health centers. Participants answered survey questions on biometric data, demographics, socioeconomic situation, and dietary habits. Descriptive statistics, univariate, and multivariate logisitic regression examined associations between undernutrition, specifically body mass index (BMI), middle upper arm circumference (MUAC), and leprosy. Eighty-one participants (40 cases of leprosy, 41 controls) were enrolled (75% male) with an average age of 38.6 years (SD 18.3). The majority of cases were multibacillary (MB) (90%). There was a high prevalence of undernutrition with 24 (29.6%) participants underweight (BMI <18.5) and 17 (21%) having a low MUAC. On multivariate analysis, underweight was significantly associated with leprosy (aOR = 9.25, 95% CI 2.77, 30.81). Also found to be associated with leprosy was cutting the size of meals/skipping meals (OR = 2.9, 95% CI 1.0, 8.32) or not having enough money for food (OR = 10, 95% CI 3.44 29.06).

Conclusions/Significance
The results suggest a strong association between leprosy and undernutrition, while also supporting the framework that food insecurity may lead to undernutrition that then could increase susceptibility to leprosy. In conclusion, this study highlights the need to study the interplay of undernutrition, food insecurity, and the manifestations of leprosy.
Evaluation of leukopenia during sepsis as a marker of sepsis-defining organ dysfunction
Authors: Belok Samuel H. , Bosch Nicholas A. , Klings Elizabeth S. , Walkey Allan J. 
Published: June 2021

Background
Although both leukocytosis and leukopenia have been considered Systemic Inflammatory Response Syndrome criteria, leukopenia is not generally considered a normal response to infection. We sought to evaluate the prognostic validity of leukopenia as a sign of sepsis-defining hematological organ dysfunction within the Sepsis-3 framework. We hypothesized that leukopenia is associated with higher risk of mortality than leukocytosis among patients with suspected infection.

Methods
We performed a retrospective cohort study using the Medical Information Mart v1.4 in Intensive Care-III database. Multivariable regression models were used to evaluate the association between leukopenia and mortality in patients with suspected infection defined by Sepsis-3.

Results
We identified 5,909 ICU patients with suspected infection; 250 (4.2%) had leukopenia. Leukopenia was associated with increased in-hospital mortality compared with leukocytosis (OR, 1.5; 95% CI 1.1–1.9). After adjusting for demographics and comorbidities in the Sepsis-3 consensus model, leukopenia remained associated with increased risk of mortality compared with leukocytosis (OR 1.6, 95% CI 1.2–2.2). Further adjustment for the platelet component of the SOFA attenuated the association between leukopenia and mortality (OR decreased from 1.5 to 1.1). However, 83 (1.4%) of patients had leukopenia without thrombocytopenia and 14 had leukopenia prior to thrombocytopenia.

Conclusions
Among ICU patients with suspected infection, leukopenia was associated with increased risk of death compared with leukocytosis. Due to correlation with thrombocytopenia, leukopenia did not independently improve the prognostic validity of SOFA; however, leukopenia may present as a sign of sepsis prior to thrombocytopenia in a small subset of patients.
Machine learning-based glucose prediction with use of continuous glucose and physical activity monitoring data: The Maastricht Study
Authors: van Doorn William P. T. M. , Foreman Yuri D. , Schaper Nicolaas C. , Savelberg Hans H. C. M. , Koster Annemarie , van der Kallen Carla J. H. , Wesselius Anke , Schram Miranda T. , Henry Ronald M. A. , Dagnelie Pieter C. , de Galan Bastiaan E. , Bekers Otto , Stehouwer Coen D. A. , Meex Steven J. R. , Brouwers Martijn C. G. J. 
Published: June 2021

Background
Closed-loop insulin delivery systems, which integrate continuous glucose monitoring (CGM) and algorithms that continuously guide insulin dosing, have been shown to improve glycaemic control. The ability to predict future glucose values can further optimize such devices. In this study, we used machine learning to train models in predicting future glucose levels based on prior CGM and accelerometry data.

Methods
We used data from The Maastricht Study, an observational population‐based cohort that comprises individuals with normal glucose metabolism, prediabetes, or type 2 diabetes. We included individuals who underwent >48h of CGM (n = 851), most of whom (n = 540) simultaneously wore an accelerometer to assess physical activity. A random subset of individuals was used to train models in predicting glucose levels at 15- and 60-minute intervals based on either CGM data or both CGM and accelerometer data. In the remaining individuals, model performance was evaluated with root-mean-square error (RMSE), Spearman’s correlation coefficient (rho) and surveillance error grid. For a proof-of-concept translation, CGM-based prediction models were optimized and validated with the use of data from individuals with type 1 diabetes (OhioT1DM Dataset, n = 6).

Results
Models trained with CGM data were able to accurately predict glucose values at 15 (RMSE: 0.19mmol/L; rho: 0.96) and 60 minutes (RMSE: 0.59mmol/L, rho: 0.72). Model performance was comparable in individuals with type 2 diabetes. Incorporation of accelerometer data only slightly improved prediction. The error grid results indicated that model predictions were clinically safe (15 min: >99%, 60 min >98%). Our prediction models translated well to individuals with type 1 diabetes, which is reflected by high accuracy (RMSEs for 15 and 60 minutes of 0.43 and 1.73 mmol/L, respectively) and clinical safety (15 min: >99%, 60 min: >91%).

Conclusions
Machine learning-based models are able to accurately and safely predict glucose values at 15- and 60-minute intervals based on CGM data only. Future research should further optimize the models for implementation in closed-loop insulin delivery systems.