bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining therapeutic equivalence between branded and generic warfarin in Brazil: The WARFA crossover randomized controlled trial
Authors: Gomes Freitas Carolina , Walsh Michael , Coutinho Enia Lucia , Vincenzo de Paola Angelo Amato , Atallah Álvaro Nagib
Published: April 2021

Objectives

To determine whether the generic and branded warfarins used as anticoagulants in Brazil are therapeutic equivalents based on their international normalized ratio (INR) results.

Methods

This crossover randomized controlled trial had four periods. We used the branded Marevan and two generic versions of warfarin sodium tablets, manufactured by União Química and Teuto laboratories, all purchased from retail drugstores. Eligible participants were outpatients from an anticoagulation clinic at a university hospital in São Paulo, Brazil. They had atrial fibrillation or flutter and had been using warfarin for at least 2 months with an INR therapeutic range of 2.0–3.0. Randomization was by numbered, opaque, sealed envelopes. Healthcare personnel and outcome assessors were blinded to treatments, but patients were not. The primary outcome was the variability in the INR (ΔINR) and secondary outcomes included mean INR. We accepted formulations as equivalent if the 95% confidence interval (CI) of the comparison of ΔINR between branded and generic formulations was within the limit of ±0.49.

Results

One hundred patients were recruited and randomized to six sequences of treatment (four sequences with n = 17 and two sequences with n = 16). União Química generic warfarin had equivalent variability in the INR to Marevan (ΔINR +0.09 [95% CI -0.29 to +0.46], n = 84). Comparison between Teuto generic warfarin and Marevan was inconclusive (ΔINR +0.29 [95% CI -0.09 to +0.68], n = 84).

Conclusions

Marevan and União Química warfarin had equivalent therapeutic effectiveness and both could be confidently used for anticoagulation. The comparison between Marevan and TW was inconclusive and does not warrant a statement of equivalence. Our methods are especially important for comparing generic and branded drugs that raise concerns and may be subject of future investigations by regulatory agents.

Trial registration

ClinicalTrials.govNCT02017197.
Factors that influence market participation among traditional beef cattle farmers in the Meatu District of Simiyu Region, Tanzania
Authors: Kibona Cornel Anyisile , Yuejie Zhang
Published: April 2021

Market participation among beef cattle farmers is key to ensuring better income, food security, and sustainable beef supply. Farmers in the traditional beef cattle sector, nevertheless, are well known for their low market participation. This study, thus, sought to examine factors that influenced market participation among beef cattle farmers in the Meatu district of Simiyu region, Tanzania. The study randomly selected a sample size of 393 farmers. The cross-sectional data collected through interviews and questionnaires were analyzed using descriptive statistics and ordinary least squares (OLS) regression models. The descriptive analyses showed that the average age of the interviewees was 53.73 years with a family size of 13.11. On average, the respondents had about 24.14 years of farming experience. Most of the respondents (67.9%) had primary education. Among the respondents, about 61.3%, 4.6%, and 32.6% had access to market information, farm credits, and veterinary services, respectively. The average cattle herd size was 53.46 heads. About 90.1% of farmers had participated in the markets by selling an average of 5 heads each, per year. This study has revealed low volume of sales, low education levels, and poor access to credits and veterinary services as the major factors that limit market participation. Furthermore, econometric results show that the key factors that significantly influenced farmers to increase the volume of beef cattle sales in the market at P < 0.05 included price, herd size, off-farm income, distance to market, age of the farmer, and cattle fattening. Moreover, membership in cooperatives, access to market information, and farming experience also had significant influence at P < 0.05. This study recommends establishment of strategic cooperatives to function not only as a communication channel for farm credits, price, market information, and training on commercial farming, but also to assist farmers in selection of profitable markets.
Moringa isothiocyanate-1 regulates Nrf2 and NF-κB pathway in response to LPS-driven sepsis and inflammation
Authors: Sailaja Badi Sri , Aita Rohit , Maledatu Shane , Ribnicky David , Verzi Michael P. , Raskin Ilya
Published: April 2021

This study aims to document the dual mode of pharmacological action of moringa isothiocyanate-1 (MIC-1) derived from seeds of Moringa oleifera Lam. Oral administration of chemically stable MIC-1 (80 mg/kg) significantly reduced the expression of inflammatory markers (Tnf-α, Ifn-α, IL-1β, IL-6) in the liver, kidney, spleen, and colon and decreased spleen weight in the lipopolysaccharide (LPS)-induced sepsis / acute inflammation model in mice. Transcriptomic analysis of the effect of MIC-1 on the liver and in the LPS-induced RAW264.7 murine macrophage showed that MIC-1 decreases inflammation via inflammation, immunity, and oxidative stress pathways. These results are supported by the immunocytochemical observations that MIC-1 increased the nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor and decreased the nuclear accumulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the LPS-induced macrophages. Transcriptional activation of antioxidant genes by MIC-1 translated into a reduction of reactive oxygen species (ROS) in the cytoplasm, decrease of mitochondrial superoxide content, and restoration of the mitochondrial membrane potential in the LPS-induced macrophages. Our data indicate that MIC-1 affects inflammation and oxidative stress, two key processes involved in the etiology of many chronic diseases. These effects involve upstream regulation of two key transcriptional factors regulating responses to these processes at a gene expression level.
Neurocognitive impairment and health-related quality of life among people living with Human Immunodeficiency Virus (HIV)
Authors: Amara Philip S. , Naveed Zaeema , Wichman Christopher S. , Fox Howard S. , Baccaglini Lorena
Published: April 2021

The association between HIV-associated neurocognitive impairment (NCI) and health-related quality of life (HRQoL) is not well known. We investigated this association among the CNS (Central Nervous System) HIV Antiretroviral Therapy Effects Research (CHARTER) study participants. We performed factor analysis to distinguish physical and mental HRQoL, followed by general linear models. We analyzed 1,340 HIV participants, including 35.6% with NCI, 77.2% males, 70.5% unemployed, and 42.2% with depression. Impaired participants had lower (worse) mental and physical HRQoL mean scores compared to unimpaired participants. NCI was negatively associated with mental HRQoL in crude (mean difference: -4.38; 95% CI: -6.70 to -2.06) and adjusted analysis (-2.56, -4.83 to -0.30). NCI was also negatively associated with physical HRQoL in unadjusted analysis (-4.62, -7.45 to -1.78), though the association weakened in the adjusted analysis (-2.20, -4.81 to 0.40). The association between NCI and HRQoL was confounded mainly by employment and was partially mediated by depression. These findings suggest that future strategies aimed at improving HRQoL among HIV-infected patients with NCI might benefit from concurrent management of depression.
Prolonged grief and posttraumatic stress disorder following the loss of a significant other: An investigation of cognitive and behavioural differences
Authors: Smith Kirsten V. , Ehlers Anke
Published: April 2021

Background

Cognitive behavioural correlates to bereavement-related mental health problems such a Prolonged Grief Disorder (PGD) and Posttraumatic Stress Disorder (PTSD) are of theoretical and clinical importance.

Methods

Individuals bereaved at least six months (N = 647) completed measures of loss-related cognitions and behaviours (i.e., loss-related memory characteristics, negative appraisals, coping strategies, grief resilience, and perceived social disconnection) and measures of PGD and PTSD symptoms. Individuals were assigned to one of four groups depending on probable clinical diagnoses (No-PGD/PTSD, PTSD, PGD, PGD+PTSD).

Results

Results indicated that higher loss-related memory characteristics and lower grief resilience increased the likelihood of a clinical problem. The PGD and PGD+PTSD groups reported significantly higher loss-related memory characteristics and appraisals compared to the PTSD group. Social disconnection increased the likelihood of comorbid PGD+PTSD in comparison to any other group.

Conclusions

Results indicate cognitive differences between loss-related cognitions, memory characteristics and coping strategies between PGD and PTSD, and points to distinct cognitive correlates to psychopathology following loss.
An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells
Authors: Lee Young Shin , Heo Woong , Choi Ho-Jung , Cho Hae-Ryung , Nam Ji Ho , Ki Yong Gan , Lee Hong-Rae , Son Woo-Chang , Park You-Soo , Kang Chi-Dug , Bae Jaeho
Published: April 2021

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.
Trends in US pediatric mental health clinical trials: An analysis of ClinicalTrials.gov from 2007–2018
Authors: Wortzel Joshua R. , Turner Brandon E. , Weeks Brannon T. , Fragassi Christopher , Ramos Virginia , Truong Thanh , Li Desiree , Sahak Omar , O’Connor Thomas G.
Published: April 2021

Whereas time trends in the epidemiologic burden of US pediatric mental health disorders are well described, little is known about trends in how these disorders are studied through clinical research. We identified how funding source, disorders studied, treatments studied, and trial design changed over the past decade in US pediatric mental health clinical trials. We identified all US pediatric interventional mental health trials submitted to ClinicalTrials.gov between October 1, 2007 and April 30, 2018 (n = 1,019) and manually characterized disorders and treatments studied. We assessed trial growth and design characteristics by funding source, treatments, and disorders. US pediatric mental health trials grew over the past decade (compound annual growth rate [CAGR] 4.1%). The number of studies funded by industry and US government remained unchanged, whereas studies funded by other sources (e.g., academic medical centers) grew (CAGR 11.3%). Neurodevelopmental disorders comprised the largest proportion of disorders studied, and Non-DSM-5(Diagnostic and Statistical Manual-5) conditions was the only disorder category to grow (14.5% to 24.6%; first half to second half of decade). There was significant growth of trials studying non-psycho/pharmacotherapy treatments (33.8% to 49.0%) and a decline in trials studying pharmacotherapies (31.7% to 20.6%), though these trends differed by funding source. There were also notable differences in funding sources and treatments studied within each disorder category. Trials using double blinding declined (26.2% to 18.0%). Limitations include that ClinicalTrials.gov is not an exhaustive list of US clinical trials, and trends identified may in part reflect changes in trial registration rather than changes in clinical research. Nevertheless, ClinicalTrials.gov is among the largest databases available for evaluating trends and patterns in pediatric mental health research that might otherwise remain unassessable. Understanding these trends can guide researchers and funding bodies when considering the trajectory of the field.
Risk prediction models for acute kidney injury in adults: An overview of systematic reviews
Authors: Van Acker Paulien , Van Biesen Wim , Nagler Evi V. , Koobasi Muguet , Veys Nic , Vanmassenhove Jill
Published: April 2021

Background

The incidence of Acute Kidney Injury (AKI) and its human and economic cost is increasing steadily. One way to reduce the burden associated with AKI is to prevent the event altogether. An important step in prevention lies in AKI risk prediction. Due to the increasing number of available risk prediction models (RPMs) clinicians need to be able to rely on systematic reviews (SRs) to provide an objective assessment on which RPM can be used in a specific setting. Our aim was to assess the quality of SRs of RPMs in AKI.

Methods

The protocol for this overview was registered in PROSPERO. MEDLINE and Embase were searched for SRs of RPMs of AKI in any setting from 2003 till August 2020. We used the ROBIS tool to assess the methodological quality of the retrieved SRs.

Results

Eight SRs were retrieved. All studies were assessed as being at high risk for bias using the ROBIS tool. Eight reviews had a high risk of bias in study eligibility criteria (domain 1), five for study identification and selection (domain 2), seven for data collection and appraisal (domain 3) and seven for synthesis and findings (domain 4). Five reviews were scored at high risk of bias across all four domains. Risk of bias assessment with a formal risk of bias tool was only performed in five reviews. Primary studies were heterogeneous and used a wide range of AKI definitions. Only 19 unique RPM were externally validated, of which 11 had only 1 external validation report.

Conclusion

The methodological quality of SRs of RPMs of AKI is inconsistent. Most SRs lack a formal risk of bias assessment. SRs ought to adhere to certain standard quality criteria so that clinicians can rely on them to select a RPM for use in an individual patient.

Trial registration

PROSPERO registration number is CRD 42020204236, available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=204236.
Prospect theory, constant relative risk aversion, and the investment horizon
Authors: Levy Haim , Levy Moshe
Published: April 2021

Prospect Theory (PT) and Constant-Relative-Risk-Aversion (CRRA) preferences have clear-cut and very different implications for the optimal asset allocation between a riskless asset and a risky stock as a function of the investment horizon. While CRRA implies that the optimal allocation is independent of the horizon, we show that PT implies a dramatic and discontinuous “jump” in the optimal allocation as the horizon increases. We experimentally test these predictions at the individual level. We find rather strong support for CRRA, but very little support for PT.
DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis
Authors: Taman Hagar , Fenton Christopher G. , Anderssen Endre , Florholmen Jon , Paulssen Ruth H.
Published: April 2021

Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.
Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
Authors: Kim Jun-dae , Zhu Lingping , Sun Quan , Fang Longhou
Published: April 2021

Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients.
Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study
Authors: Mancini Antonio , Guidi Francesco , Bruno Carmine , Angelini Flavia , Vergani Edoardo , Lanza Paola , Mordente Alvaro , Meucci Elisabetta , Silvestrini Andrea
Published: April 2021

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50μg iv+arginine 0,5 g/Kg test, with peak GH response <9 μg/L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.
State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity
Authors: Mirzazadeh Ali , Kahn James G. , Haddad Maryam B. , Hill Andrew N. , Marks Suzanne M. , Readhead Adam , Barry Pennan M. , Flood Jennifer , Mermin Jonathan H. , Shete Priya B.
Published: April 2021

Introduction

Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity.

Methods

We created a mathematical model using all incident TB disease cases during 2013–2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015.

Results

We estimated that 2.7% (CI: 2.6%–2.8%) of the U.S. population, or 8.6 (CI: 8.3–8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%–1.1%) and among non-US-born persons was 13.9% (CI: 13.5%–14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45–64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%).

Conclusions

Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.
Predicting innovative firms using web mining and deep learning
Authors: Kinne Jan , Lenz David
Published: April 2021

Evidence-based STI (science, technology, and innovation) policy making requires accurate indicators of innovation in order to promote economic growth. However, traditional indicators from patents and questionnaire-based surveys often lack coverage, granularity as well as timeliness and may involve high data collection costs, especially when conducted at a large scale. Consequently, they struggle to provide policy makers and scientists with the full picture of the current state of the innovation system. In this paper, we propose a first approach on generating web-based innovation indicators which may have the potential to overcome some of the shortcomings of traditional indicators. Specifically, we develop a method to identify product innovator firms at a large scale and very low costs. We use traditional firm-level indicators from a questionnaire-based innovation survey (German Community Innovation Survey) to train an artificial neural network classification model on labelled (product innovator/no product innovator) web texts of surveyed firms. Subsequently, we apply this classification model to the web texts of hundreds of thousands of firms in Germany to predict whether they are product innovators or not. We then compare these predictions to firm-level patent statistics, survey extrapolation benchmark data, and regional innovation indicators. The results show that our approach produces reliable predictions and has the potential to be a valuable and highly cost-efficient addition to the existing set of innovation indicators, especially due to its coverage and regional granularity.
“I have never seen something like that”: Discrepancies between lived experiences and the global health concept of child marriage in northern Tanzania
Authors: Schaffnit Susan B. , Urassa Mark , Wamoyi Joyce , Dardoumpa Maria , Lawson David W.
Published: April 2021

Background

The concept of ‘child marriage’ in global health distinguishes ostensibly harmful from healthy ages to marry at a universally-applied threshold of 18-years. With intensifying efforts to end child marriage, targeted communities are increasingly asked to change their perception of such marriages from relatively benign to profoundly problematic. The objective of this study is to understand how this shift in perception is navigated by adolescent girls and young women (AGYW).

Methods

Using qualitative data collected in 2019 from a semi-urban community in Tanzania where marriage under 18-years is common and campaigns to end child marriage ongoing, we contrast reports of lived experiences of marriage under 18-years among AGYW to views of child marriage as an abstract concept. Thirteen in-depth interviews with AGYW, as part of a wider qualitative study, were recorded, transcribed, and analyzed using a framework analysis approach.

Results

While many AGYW had heard of child marriage, the concept was routinely conflated with forced marriage, which is rare in the community, and non-marital teenage sex and pregnancy, which are common. As a likely consequence, participants disagreed on whether or not child marriage occurs locally. Furthermore, accounts of real-life marriages under 18 sometimes aligned with, but often departed from, common narratives about the purported causes and harmful consequences inherent to the global health concept of child marriage.

Conclusions

We argue that engaging with diverse local views and experiences of marrying young is essential to producing culturally-sensitive, effective initiatives addressing the vulnerabilities of female adolescence.
Fracture strength analysis of titanium insert-reinforced zirconia abutments according to the axial height of the titanium insert with an internal connection
Authors: Song Seung-rye , Park Kyeong-Mee , Jung Bock-Young
Published: April 2021

This study aimed to analyze fracture strength in vitro by varying the axial height of the titanium insert and the labial height of the zirconia abutment in an internal connection implant to identify the titanium insert axial height with optimal mechanical stability. Sixty implants with an internal connection system were used. Two-piece zirconia abutments were used with the titanium inserts. Combinations of different titanium insert axial heights (mm) and zirconia abutment labial heights (mm) constituted five groups: Gr1 (1–3), Gr2 (3–3), Gr3 (3–5), Gr4 (5–3), and Gr5 (5–5). After thermocycling, a fracture load test was performed with a universal testing machine. The initial deformation load and the fracture load were measured and analyzed. The fractured surface and cross-section of the specimens were examined by scanning electron microscopy (SEM). The groups of titanium inserts with axial heights of 3 mm and 5 mm showed significantly greater initial deformation load and fracture load than the group with an axial height of 1 mm (p < 0.05), but there was no significant difference between the two groups with axial heights of 3 mm and 5 mm. The labial height of the zirconia abutment had no significant influence on the initial deformation load and fracture load. In some specimens in Gr4 and Gr5, cracking or bending of the titanium insert and abutment screw was observed on SEM. The axial height of the titanium insert should be designed to not be less than 3 mm to increase the fracture strength and promote the long-term stability of implants.
Characterizing and quantifying the temporal relationship between structural and functional change in glaucoma
Authors: Chu Fang-I , Racette Lyne
Published: April 2021

Purpose

To characterize and quantify the temporal relationship between structural and functional change in glaucoma.

Methods

120 eyes of 120 patients with ocular hypertension or primary open-angle glaucoma were selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. Patients had 11 visits, separated by at least 3 months over 5 to 10 years. Each visit had rim area (RA) and mean sensitivity (MS) measurements taken within a 30-day period. The structure-function (SF) relationship was summarized using conventional and modified cross-correlation functions (CCFs), which identified the strongest absolute and positive correlation, respectively. Patients were categorized in one of the following three groups: RA and MS evolved simultaneously (lag = 0), RA preceded MS (lag<0), and MS preceded RA (lag>0). Lagging regression analysis was used to examine the variations of the SF relationship within groups.

Results

The number of participants, mean visit lag, and mean correlation (standard deviation) were, for the conventional and modified CCFs, respectively: lag = 0 [16, 0, 0.53 (0.10) and 16, 0, 0.46 (0.11)]; lag<0 [50, −2.94, 0.51 (0.11) and 55, −3.45, 0.44 (0.12)], and lag>0 [54, 3.35, 0.53 (0.13) and 49, 3.78, 0.45 (0.12)]. A significant difference of the visit lag relation within groups was identified using lagging regression analysis (p<0.0001).

Conclusions

The strongest relationship between structure and function was obtained at different visit lags in different patients. This finding also suggests that the SF relationship should be addressed at the subject level when using both measurements jointly to model glaucoma progression.
Are neuromuscular adaptations present in people with recurrent spinal pain during a period of remission? a systematic review
Authors: Devecchi Valter , Rushton Alison B. , Gallina Alessio , Heneghan Nicola R. , Falla Deborah
Published: April 2021

A plethora of evidence supports the existence of neuromuscular changes in people with chronic spinal pain (neck and low back pain), yet it is unclear whether neuromuscular adaptations persist for people with recurrent spinal pain when in a period of remission. This systematic review aimed to synthesise the evidence on neuromuscular adaptations in people with recurrent spinal pain during a period of remission. Electronic databases, grey literature, and key journals were searched from inception up to the 4th of September 2020. Eligibility criteria included observational studies investigating muscle activity, spine kinematics, muscle properties, sensorimotor control, and neuromuscular performance in adults (≥ 18 years) with recurrent spinal pain during a period of remission. Screening, data extraction, and quality assessment (Newcastle-Ottawa Scale) were conducted independently by two reviewers. Data synthesis was conducted per outcome domain. A meta-analysis with a random-effects model was performed where possible. The overall strength of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation guidelines (GRADE). From 8292 records, 27 and five studies were included in a qualitative and quantitative synthesis, respectively. Very low level of evidence supports muscle activity changes in people with recurrent low back pain, especially greater co-contraction, redistribution of muscle activity, and delayed postural control of deeper trunk muscles. Reduced range of motion of the lumbar spine was also found. Meaningful conclusions regarding other outcome domains or people with recurrent neck pain could not be drawn. In conclusion, people with recurrent low back pain during a period of remission show muscle activity and spine kinematics adaptations. Future research should investigate the long-term impact of these changes, as well as adaptations in people with recurrent neck pain.
Assessment of the association between body composition and risk of non-alcoholic fatty liver
Authors: Ariya Mohammad , Koohpayeh Farbod , Ghaemi Alireza , Osati Saeed , Davoodi Sayed Hossain , Razzaz Jalaledin Mirzay , Javedan Gholamali , Ehrampoush Elham , Homayounfar Reza
Published: April 2021

Non-alcoholic fatty liver disease (NAFLD) is defined as the condition of fat accumulation in the liver. This cross-sectional study aimed to investigate the relationship between body composition and fatty liver and determine of cut-off point for predicting NAFLD. Samples were selected from the nutrition clinic from 2016 to 2017 in Tehran, Iran. The liver steatosis was calculated using the CAP score through the FiroScan™and body composition was measured using the dual-energy X-ray absorptiometry scan method. A total of 2160 patients participated in this study, 745 (34.5%) subjects had NAFLD. We found that fat-free tissue was inversely and fat tissue was directly correlated with the risk of NAFLD in almost all factors and the risk of developing NAFLD increases if the total fat exceeds 32.23% and 26.73% in women and men and abdominal fat exceeds 21.42% and 13.76% in women and men, respectively. Finally, we realized that the total fat percent had the highest AUC (0.932 for men and 0.917 for women) to predict the risk of NAFLD. Overall, the likelihood of NAFLD development rose significantly with increasing the amount of total fat and abdominal fat from the cut-off point level.
Understanding the impact of lumbar disc degeneration and chronic low back pain: A cross-sectional electromyographic analysis of postural strategy during predicted and unpredicted postural perturbations
Authors: Deane Janet A. , Lim Adrian K. P. , McGregor Alison H. , Strutton Paul H.
Published: April 2021

People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007–0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004–0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation.
How does engagement in society in adolescence affect educational attainment and employment in early adulthood: A prospective cohort study
Authors: Just-Noerregaard Vivi , Andersen Johan Hviid , Nohr Ellen Aagaard , Vestergaard Jesper Medom , Winding Trine Nohr
Published: April 2021

Introduction

Educational attainment and employment are essential for young people to develop the skills needed to participate in society and maintain a stable connection to the labour market in adult life. The objective of this study was to examine associations between engagement in society, measured by leisure time activities and part-time work in mid and late adolescence and educational attainment and employment in early adulthood.

Method

A cohort of Danish young people born in 1989 was followed in a prospective study with questionnaires in 2004 (n = 3,054) and 2007 (n = 2,400) where information on leisure time activities and part-time work was collected. Information on connection to education and work was collected from a register of social benefits when participants were 25–29 years old and divided into high and low connection. The associations were examined using logistic regression and stratified by gender and childhood socioeconomic groups.

Results

Part-time work was, both in mid (OR: 1.7 [95% CI 1.3; 2.2]) and late (1.9 [1.4;2.6]) adolescence, positively associated with connection to education and work. Leisure time activities in mid adolescence were associated with connection to education and work (OR:1.6 [1.2;2.1]). Among men engagement in society showed strongest associations with later connection to education or work in mid adolescence (ORs up to 2.2), whereas the associations for women seemed strongest in late adolescence (ORs up to 2.8).

Conclusion

The study showed that adolescent engagement in society had positive associations with later educational attainment and employment, with stronger impact of part-time work compared to leisure time activities. The study identified differences between genders and the timing of engagement. Associations were consistent across socioeconomic groups.
Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice
Authors: Nagasawa Yosuke , Takei Masami , Iwata Mitsuhiro , Nagatsuka Yasuko , Tsuzuki Hiroshi , Imai Kenichi , Imadome Ken-Ichi , Fujiwara Shigeyoshi , Kitamura Noboru
Published: April 2021

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull(hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.
Applicability and safety of discontinuous ADVanced Organ Support (ADVOS) in the treatment of patients with acute-on-chronic liver failure (ACLF) outside of intensive care
Authors: Kaps L. , Ahlbrand C. J. , Gadban R. , Nagel M. , Labenz C. , Klimpke P. , Holtz S. , Boedecker S. , Michel M. , Kremer W. M. , Hilscher M. , Galle P. R. , Kraus D. , Schattenberg J. M. , Weinmann-Menke J.
Published: April 2021

Background

ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis and holds promise to sustain liver function and recovery of patients with acute-on-chronic liver failure (ACLF). Previously, ADVOS was tested as continuous treatment for intensive care patients with liver failure. Data related to the applicability and safety as discontinuous treatment outside of ICU is not available.

Aim

Evaluation of ADVOS as discontinuous treatment for patients with ACLF outside intensive care unit and comparison with a matched historic cohort.

Methods and results

In this retrospective study, 26 patients with ACLF and the indication for renal replacement therapy related to HRS-AKI were included. Majority of patients were male (65%) with alcoholic cirrhosis in 88% and infections as a trigger of ACLF in 96%. Liver function was severely compromised reflected by high median MELD and CLIF-C ACLF scores of 37 (IQR 32;40) and 56.5 (IQR 51;60), respectively. Patients were treated discontinuously with ADVOS over a median time of 12 days (IQR 8.25;17) and received 8 (IQR 4.25;9.75) treatment cycles on average. No treatment related adverse events were recorded, and safety laboratory parameters remained constant during the observation time. After 16 h cumulative dialysis therapy, ADVOS significantly reduced protein-bound bilirubin (14%), creatinine (11.8%) and blood urea nitrogen (BUN, 33%). Using a matched cohort with ACLF treated with hemodialysis, ADVOS achieved a stronger decrease in bilirubin (p = 0.01), while detoxification of water-soluble catabolites’ including creatinine and BUN was comparable. The 28-days mortality in the ADVOS group was 56% (14/26) and was not inferior to predicted survival (predicted median 28-days mortality was 44%, IQR 30; 59).

Conclusion

Discontinuous ADVOS treatment was safe and effective in patients with ACLF outside intensive care and outperformed hemodialysis in reducing protein-bound metabolites.
Effect of prolactin on normal and keratoconus human corneal stromal fibroblasts in vitro
Authors: Anders Philipp , Song Xuefei , György Bence , Szentmary Nora , Seitz Berthold , Gatzioufas Zisis
Published: April 2021

Purpose

To examine the effect of prolactin (PRL) on human corneal stromal fibroblasts (CSFs), derived from healthy individuals and from keratoconus (KC) patients, in vitro, specifically assessing physiological and elevated PRL concentrations as apparent during pregnancy.

Methods

Eye bank corneas of 3 female and 3 male healthy individuals as well as the corneal buttons of 3 female and 3 male KC patients were utilized for this study. The endothelium of the cornea was removed with sterile surgical scalpels, the probes were washed repeatedly with Dulbecco’s PBS and corneoscleral rims were trimmed off. Subsequently the corneal stroma was digested with collagenase type I and the harvested CSFs were cultured. We then examined (1) cell proliferation, (2) cell viability and (3) cytokine release of CSFs upon exposure to prolactin in vitro.

Results

With respect to viability and proliferation our experiments did not show significant differences between CSFs exposed to different PRL concentrations. Our data show a significantly lower IL-8 concentration in normal CSFs exposed to 10ng/ml PRL compared to 0ng/ml and 1000ng/ml at 5 hours post exposition. Moreover, we can report significantly lower secretion of IL-8, IL-6, HGF, VEGF and FGFb in KC CSFs compared to normal CSFs, independent of PRL exposure, as determined by cytokine ELISA.

Conclusion

Our data in part points towards corneal cytokine secretion as a possible link between altered stromal PRL concentrations and KC progression. However, in our small dataset a significant influence of PRL concentration on cytokine secretion can only be described for IL-8 in normal CSFs. Further our results contribute to existing reports on the importance of cytokines in KC development, with an emphasis on significantly lower cytokine secretion in KC CSFs compared to normal controls.
Partial DnaK protein expression from Coxiella-like endosymbiont of Rhipicephalus annulatus tick
Authors: Nooroong Pornpiroon , Trinachartvanit Wachareeporn , Baimai Visut , Anuracpreeda Panat , Ahantarig Arunee
Published: April 2021

Q fever is one of the most important zoonotic diseases caused by the obligate intracellular bacteria,Coxiella burnetii. This bacterial infection has been frequently reported in both humans and animals, especially ruminants. Ticks are important ectoparasite and serve as reservoir hosts ofCoxiella-like endosymbionts (CLEs). In this study, we have attempted to express chaperone-coding genes from CLEs ofRhipicephalus annulatusticks collected fromcow path. The partial DnaK coding sequence has been amplified and expressed byEscherichia coli. Amino acid sequences have been analyzed by MS-MS spectrometry and the UniProt database. Despites nucleotide sequences indicating high nucleotide variation and diversity, many nucleotide substitutions are synonymous. In addition, amino acid substitutions compensate for the physicochemical properties of the original amino acids. Immune Epitope Database and Analysis Resource (IEDB-AR) was employed to indicate the antigenicity of the partial DnaK protein and predict the epitopes of B-and T-cells. Interestingly, some predicted HLA-A and B alleles of the MHC-I and HLA-DR alleles belonging to MHC-II were similar to T-cell responses toC.burnetiiin Q fever patients. Therefore, the partial DnaK protein of CLE fromR.annulatuscould be considered a vaccine candidate and immunogenic marker with future prospects.