bluuebunny/crossref_metadata_2025 huggingface dataset:
“Worlds. . .[of] Contingent Possibilities”: Genderqueer and Trans Adolescents Reading Fan Fiction
Authors: Duggan Jennifer
Published: May 2021

Cultural studies scholars have long been interested in the nexus between people’s online activities and their identities. One activity that has drawn attention is reading/writing fan fiction (fictions written by and for fans that build upon the characters and worlds depicted in commercial texts). While fan fiction and its surrounding communities have long been understood as resistant to heteronormativity, previous work exploring the fans who produce and consume fan fiction has largely insisted that most of these fans are adult ciswomen. Little has been written about the experiences of trans and genderqueer fans. To remedy this elision, this article explores two trans and genderqueer individuals’ experiences with fan fiction. It closely examines the roles reading, and especially reading fan fiction, has or has not played in their understandings of themselves, their identities, and their places in the world.
Using Data Mining for Rapid Complex Case Study Descriptions: Example of Public Health Briefings During the Onset of the COVID-19 Pandemic
Authors: Poth Cheryl N. , Bulut Okan , Aquilina Alexandra M. , Otto Simon J. G.
Published: May 2021

The methodological purpose of this article is to demonstrate how data mining contributes to rapid complex case study descriptions. Our complexity-informed design draws on freely accessible datasets reporting the public health response surrounding the onset of the COVID-19 pandemic in Alberta (Canada) and involves the cross analysis of integrated findings across six periods of fluctuation identified in the initial quantitative phase of a convergent sequential approach. We discuss how our case meta-inferences, informing how public health briefings can build credibility and trust, were derived by attending to three key concepts of complex adaptive systems: emergence, interdependence, and adaptation. This article serves as an essential reference for using data mining within a case study–mixed methods design for studying complex phenomena.
Accelerated Recovery After Renal Cell Carcinoma and Partial Nephrectomy With Lifestyle Modifications
Authors: Moore Scott
Published: May 2021

Objective and subjective recovery times following a partial nephrectomy may exceed 1 year if patients adhere to the current Western lifestyle. This case demonstrates the rapid recovery of a 59-year-old female who underwent a robotic partial nephrectomy and utilized lifestyle modifications as an adjunct to the treatment of a Stage T1a clear cell renal cell carcinoma. All 6 pillars of lifestyle medicine are incorporated into this patient’s recovery plan, which successfully reduced her time to recovery after a partial nephrectomy. This case illustrates how modifications in diet, activity, sleep, stress management, social connectedness, and avoidance of risky substances may shorten recovery time after a partial nephrectomy and may serve as an example that providers can prescribe for patients recovering from other surgeries.
Research on the inverse kinematics of manipulator using an improved self-adaptive mutation differential evolution algorithm
Authors: Zhang Qianqian , Wang Daqing , Gao Lifu
Published: May 2021

To assess the inverse kinematics (IK) of multiple degree-of-freedom (DOF) serial manipulators, this article proposes a method for solving the IK of manipulators using an improved self-adaptive mutation differential evolution (DE) algorithm. First, based on the self-adaptive DE algorithm, a new adaptive mutation operator and adaptive scaling factor are proposed to change the control parameters and differential strategy of the DE algorithm. Then, an error-related weight coefficient of the objective function is proposed to balance the weight of the position error and orientation error in the objective function. Finally, the proposed method is verified by the benchmark function, the 6-DOF and 7-DOF serial manipulator model. Experimental results show that the improvement of the algorithm and improved objective function can significantly improve the accuracy of the IK. For the specified points and random points in the feasible region, the proportion of accuracy meeting the specified requirements is increased by 22.5% and 28.7%, respectively.
Remotely Delivered Monitoring and Management of Diabetes-Related Foot Disease: An Overview of Systematic Reviews
Authors: Drovandi Aaron , Wong Shannon , Seng Leonard , Crowley Benjamin , Alahakoon Chanika , Banwait Jasmin , Fernando Malindu E. , Golledge Jonathan
Published: May 2021

Background:

Diabetes-related foot disease (DFD) management requires input from multiple healthcare professionals, and has worse outcomes for people living in remote localities by comparison to urban areas. Remotely delivered healthcare may reduce this disparity. This overview summarizes current evidence on the effectiveness, stakeholder perceptions, and cost-effectiveness of remotely delivered healthcare for DFD.

Methods:

A search of 5 databases was conducted to identify systematic reviews published between January 2000 and June 2020. Eligible reviews were those evaluating remotely delivered monitoring or management of patients at risk of or with active DFD, or clinicians managing these patients. Risk of bias was assessed using the AMSTAR-2 tool.

Results:

Eight reviews were eligible for inclusion, including 88 primary studies and 8509 participants, of which 36 studies involving 4357 participants evaluated remotely delivered monitoring or management of DFD. Only one review had a low risk of bias, with most reviews demonstrating limited search strategies and poor reporting of participants. Evidence on effectiveness was mixed, with meta-analyses demonstrating long-term ulcer healing and mortality were not significantly different between telehealth and standard care groups, although the lower-limb amputation rate was significantly decreased in one meta-analysis. Perceptions of telehealth by patients and clinicians were generally positive, whilst acknowledging limitations relating to access and use. Cost-effectiveness data were limited, with poor reporting preventing clear conclusions.

Conclusions:

Remotely delivered healthcare of DFD is well received by patients and clinicians, but its effectiveness is unclear. High quality trials are needed to evaluate the risks and benefits of remotely delivered DFD management.
Comparing Patch vs Pen Bolus Insulin Delivery in Type 2 Diabetes Using Continuous Glucose Monitoring Metrics and Profiles
Authors: Bergenstal Richard M. , Johnson Mary L. , Aroda Vanita R. , Brazg Ronald L. , Dreon Darlene M. , Frias Juan P. , Kruger Davida F. , Molitch Mark E. , Mullen Deborah M. , Peyrot Mark , Richter Sara , Rosenstock Julio , Serusclat Pierre , Vance Carl , Weinstock Ruth S. , Levy Brian L.
Published: May 2021

Objective:

CeQur Simplicity™ (CeQur, Marlborough, MA) is a 3-day insulin delivery patch designed to meet mealtime insulin requirements. A recently reported 48-week, randomized, multicenter, interventional trial compared efficacy, safety and self-reported outcomes in 278 adults with type 2 diabetes (T2D) on basal insulin therapy who initiated and managed mealtime insulin therapy with a patch pump versus insulin pen. We assessed changes in key glycemic metrics among a subset of patients who wore a continuous glucose monitoring (CGM) device.

Methods:

Study participants (patch, n = 49; pen, n = 48) wore a CGM device in masked setting during the baseline period and prior to week 24. Glycemic control was assessed using international consensus guidelines for percentage of Time In Range (%TIR: >70% at 70-180 mg/dL), Time Below Range (%TBR: <4% at <70 mg/dL; <1% at <54 mg/dL), and Time Above Range (%TAR: <25% at >180 mg/dL; <5% at >250 mg/dL).

Results:

Both the patch and pen groups achieved recommended targets in %TIR (74.1% ± 18.7%, 75.2 ± 16.1%, respectively) and marked reductions in %TAR >180 mg/dL (21.1% ± 19.9%, 19.7% ± 17.5%, respectively) but with increased %TBR <70 mg/dL (4.7% ± 5.2%, 5.1 ± 5.8, respectively), all P < .0001. No significant between-group differences in glycemic improvements or adverse events were observed.

Conclusions:

CGM confirmed that the patch or pen can be used to safely initiate and optimize basal-bolus therapy using a simple insulin adjustment algorithm with SMBG. Preference data suggest that use of the patch vs pen may enhance treatment adherence.
Mechanism of Compound Houttuynia Mixture as an Anti-COVID-19 Drug Based on Network Pharmacology and Molecular Docking
Authors: Wu Xing-Pan , Wang Tian-Shun , Yuan Zi-Xin , Yang Yan-Fang , Wu He-Zhen
Published: May 2021

Objective

To explore the anti-COVID-19 active components and mechanism of Compound Houttuynia mixture by using network pharmacology and molecular docking.

Methods

First, the main chemical components of Compound Houttuynia mixture were obtained by using the TCMSP database and referring to relevant chemical composition literature. The components were screened for OB ≥30% and DL ≥0.18 as the threshold values. Then Swiss Target Prediction database was used to predict the target of the active components and map the targets of COVID-19 obtained through GeneCards database to obtain the gene pool of the potential target of COVID-19 resistance of the active components of Compound Houttuynia mixture. Next, DAVID database was used for GO enrichment and KEGG pathway annotation of targets function. Cytoscape 3.8.0 software was used to construct a “components-targets-pathways” network. Then String database was used to construct a “protein-protein interaction” network. Finally, the core targets, SARS-COV-2 3 Cl, ACE2 and the core active components of Compound Houttuyna Mixture were imported into the Discovery Studio 2016 Client database for molecular docking verification.

Results

Eighty-two active compounds, including Xylostosidine, Arctiin, ZINC12153652 and ZINC338038, were screened from Compound Houttuyniae mixture. The key targets involved 128 targets, including MAPK1, MAPK3, MAPK8, MAPK14, TP53, TNF, and IL6. The HIF-1 signaling, VEGF signaling, TNF signaling and another 127 signaling pathways associated with COVID-19 were affected ( P < 0.05). From the results of molecular docking, the binding ability between the selected active components and the core targets was strong.

Conclusion

Through the combination of network pharmacology and molecular docking technology, this study revealed that the therapeutic effect of Compound Houttuynia mixture on COVID-19 was realized through multiple components, multiple targets and multiple pathways, which provided a certain scientific basis of the clinical application of Compound Houttuynia mixture.
Oroxylum indicum Extract, at a Physiologically Relevant Dosage, Does Not Induce Hepatotoxicity in C57BL/6J Mice
Authors: Pondugula Satyanarayana R. , Salamat Julia M. , Abbott Kodye L. , Flannery Patrick C. , Majrashi Mohammed , Almaghrabi Mohammed , Govindarajulu Manoj , Ramesh Sindhu , Onteru Suneel K. , Sandey Maninder , Haung Chen-Che J. , Gill Kristina , Narayanan Natasha , McElroy Edwin , Desai Darshini , Nadar Rishi , Moore Timothy , Kalyanam Nagabhushanam , Majeed Muhammed , Dhanasekaran Muralikrishnan
Published: May 2021

Background

Botanical supplements have been proven to provide beneficial health effects. However, they can induce unintended adverse events such as hepatotoxicity. Oroxylum indicum extract (OIE, Sabroxy®) has several health benefits including anti-inflammatory, anti-arthritic, antifungal, antibacterial, and neuroprotective effects. It is currently unknown whether OIE has the potential to induce hepatotoxicity.

Purpose

In the current study, we sought to determine whether OIE can induce hepatotoxicity in C57BL/6J mouse model.

Methods

The male mice were fed powdered rodent food (control group) or powdered rodent food mixed with OIE (Sabroxy®, 500 mg/kg) daily for 4 weeks. Following the treatment, we assessed liver histology and serum levels of biomarkers commonly associated with liver damage, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP).

Results

No significant alterations were observed in liver histology, and serum levels of ALT, AST, ALP, bilirubin, albumin, globulin, and total protein in the OIE fed mice compared to the control mice.

Conclusion

Taken together, our results suggest that OIE, when fed at its physiologically relevant dosage, does not induce hepatotoxicity in C57BL/6J mice.
Effect of Phlorotannins Isolated From Eisenia bicyclis on Melanogenesis in Mouse B16 Melanoma Cells
Authors: Ohno Yuki , Kondo Shiori , Tajima Kiho , Shibata Toshiyuki , Itoh Tomohiro
Published: May 2021

Phlorotannins isolated from brown algae, such as Eisena bicyclis, have positive physiological effects, including anti-cancer, anti-inflammatory, and anti-Alzheimer’s disease. Although phlorotannins have been shown to inhibit tyrosinase, an enzyme essential for melanogenesis, their effect on melanogenesis remains unexplored. Thus, we isolated phlorotannins from E. bicyclis and examined their effects on α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in murine B16 melanoma cells. Both fucofuroeckol-A (FF-A) and phlorofucofuroeckol-A (PFF-A) suppressed α-MSH-induced melanogenesis. Neither inhibited human tyrosinase (TYR) activity, but both inhibited tyrosinase-related protein-2 activity. FF-A downregulated the expression of microphthalmia-associated transcription factor and TYR, which subsequently suppressed melanin production. These results suggest that phlorotannins could be beneficial as melanin control drugs for hyperpigmentation disorders.
Iron deficiency in pulmonary arterial hypertension: perspectives
Authors: Quatredeniers Marceau , Montani David , Cohen‐Solal Alain , Perros Frédéric
Published: May 2021

In left heart failure, iron supplementation (IS) is a first‐line treatment option, regardless of anemia. Pulmonary arterial hypertension (PAH), a rare disease leading to right heart failure, is also associated with iron deficiency. While it is a much debated topic, recent evidence demonstrate that restoration of iron stores results in improved right ventricular function and exercise tolerance. Hence, IS may also be considered as an option in the treatment of PAH.
Nutrition Care for Poorly Nourished Outpatients Reduces Resource Use and Lowers Costs
Authors: Hong Kurt , Sulo Suela , Wang William , Kim Susan , Huettner Laura , Taroyan Rose , Kerr Kirk W. , Kaloostian Carolyn
Published: May 2021

Background and Objectives:

Over 25% of United States (US) community-dwelling, older adults are at nutritional risk. Health and cost burdens of poor nutrition can be lowered by nutrition programs for hospital inpatients, but few studies have looked at the impact on outpatients. The objective of our study was to assess outcomes of a nutrition focused quality improvement program (QIP) on healthcare resource use and costs in poorly nourished outpatients.

Methods:

This pre-post QIP study was implemented at 3 US healthcare system clinics. Included patients (n = 600) were ≥45 years old, had ≥2 chronic conditions, and were enrolled over a 15-month interval. For comparison, historical (n = 600) and concurrent control (n = 600) groups were used. Assessment of poor nutritional status was performed during each patient’s baseline visit. Healthcare resource use (hospitalizations, emergency department visits, and outpatient clinic visits), medication use, and costs were determined for a 90-day interval.

Results:

QIP patients (mean age 61.6 years) were predominantly female (62.5%) and overweight/obese (81.7%). The proportion of QIP outpatients presenting for healthcare services was significantly reduced compared to both historical and concurrent controls—relative risk reduction (RRR) versus historical (11.6%, P < .001) and versus concurrent (8.9%, P = .003). Of those who presented, RRR for healthcare resource use by QIP was significant in comparison with historical (12.9%, P = .022) but not concurrent controls. No significant differences were observed for medication usage. Lower resource use among QIP patients yielded total cost savings of $290 923 or per-patient savings of $485.

Conclusions:

Nutrition QIPs in outpatient clinics are feasible and can reduce healthcare resource use and cut costs. Such findings underscore benefits of nutritional interventions for community-dwelling outpatients with poor nutritional status.
Effects of Individual and Neighborhood Characteristics on Childhood Blood Lead Testing and Elevated Blood Lead Levels, A Pennsylvania Birth Cohort Analysis
Authors: Chen Yeh-Hsin , Ma Zhen-Qiang , Watkins Sharon M.
Published: May 2021

Background:

Despite declining lead exposure among U.S. children, childhood blood lead level (BLL) undertesting and elevation remains a public health issue. This study explores the impacts of maternal, infant, and neighborhood characteristics on the receipt of lead testing and having elevated BLLs (EBLLs) among children under age two.

Methods:

Pennsylvania infants born in 2015 and 2016 were followed to 24 months. Birth certificate data were linked to 2015 through 2018 blood lead surveillance data and neighborhood data on household income, poverty, and the burden of houses built before 1970. Generalized linear mixed models were used to examine the individual and neighborhood characteristics independently and/or interactively affecting the likelihood of lead testing and of having EBLLs.

Results:

A total of 48.6% of children were tested for BLLs, and 2.6% of them had confirmed EBLLs. The likelihood of lead testing and of having EBLLs among non-Hispanic black children was respectively 7% and 18% higher than white children. Children born to mothers with the lowest educational attainment (<high school), with self-payment as a payment source for delivery, and without WIC enrollment were at higher risk of undertesting. Children living in neighborhoods of the lowest quartile of household income and the highest quartile of poverty and old housing were more likely to have EBLLs. Different neighborhood characteristics modified the associations between some individual factors (such as race/ethnicity, payment source for delivery, and WIC enrollment) and the odds of undertesting and of having EBLLs.

Conclusion:

This cohort analysis provides more accurate estimates of lead screening rates and the percentages of EBLLs than cross-sectional analysis. Some maternal and infant demographics significantly impact the risk of undertesting and of having EBLLs, and some of the effects vary across different neighborhood characteristics. These findings can help lead prevention programs to target screening and treatment resources to children with specific characteristics.
Assessing Biomarkers of Breast Cancer Risk in Underserved Women in a Midwestern County
Authors: DeWitt Marla A. , Croghan Ivana T. , Vachon Celine M. , Thacher Thomas D. , Venegas Pont Marcia R. , Neal Lonzetta , Stan Daniela L. , Jenkins Sarah M. , Pruthi Sandhya
Published: May 2021

Objective:

The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density.

Methods:

Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up.

Results:

Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status ( P = .06).

Conclusions:

On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.
Hand Hygiene Habits and Prevalence of Hand Eczema During the COVID-19 Pandemic
Authors: Techasatian Leelawadee , Thaowandee Wilairat , Chaiyarit Jitjira , Uppala Rattapon , Sitthikarnkha Phanthila , Paibool Watuhatai , Charoenwat Busara , Wongmast Piyathida , Laoaroon Napat , Suphakunpinyo Chanyut , Kiatchoosakun Pakaphan , Kosalaraksa Pope
Published: May 2021

Purpose:

This study aimed to explore the prevalence of and possible risk factors for hand eczema with respect to the dissemination of information about new hand hygiene habits to protect against ongoing COVID-19 cross-transmission. The authors conducted a survey among health care workers (HCWs) and non-HCW populations in Khon Kaen, Thailand.

Results:

A total of 805 participants participated. The prevalence of hand eczema in the study population was 20.87%. There were several risk factors, including working as a HCW, having a history of previous hand eczema, having underlying atopic dermatitis, wearing gloves in everyday life, and washing hands frequently (more than 10 times/day). Hand hygiene with alcohol-based products was shown to be a risk factor for hand eczema, (OR (95% CI) 1.86 (1.03-3.35), P = .04).

Conclusion:

In terms of hand eczema prevention, we suggest that the use of alcohol-based products should be discontinued if other handwashing methods are available. The following factors increase the risk of hand eczema: being a HCW, having previous hand eczema, and having underlying atopic dermatitis. Proper strategies in terms of hand eczema prevention should be addressed, especially in this group, since we need to continue performing hand hygiene during the ongoing COVID-19 pandemic.
Effect of the Incorporation of Chitosan and TiO2 Nanoparticles on the Shear Bond Strength of an Orthodontic Adhesive: An In Vitro Study
Authors: Farzanegan Fahimeh , Shafaee Hooman , Darroudi Majid , Rangrazi Abdolrasoul
Published: May 2021

Aim:

This in vitro study was aimed to evaluate the effect of adding different concentrations of chitosan nanoparticles (NPs) and TiO2 NPs on the shear bond strength (SBS) of an orthodontic adhesive.

Materials and Methods:

In this in vitro study, 72 extracted human premolars were embedded in an acrylic resin and randomly allocated into four groups of 18 specimens. In group 1 (control), brackets were bonded to the tooth with the Transbond XT orthodontic adhesive. In groups 2, 3, and 4, 0.5% chitosan NPs and 0.5% TiO2 NPs, 1% chitosan NPs and 1% TiO2 NPs, and 1.5% chitosan NPs and 1.5% TiO2 NPs were added to Transbond XT, respectively. Then, the brackets were bonded by the modified adhesive. The SBS and adhesive remnant index (ARI) of each group were assessed with a universal testing machine. The SBS test results were analyzed using one-way analysis of variance followed by the posthoc Tukey’s honestly significant difference (HSD) test. The Kruskal–Wallis test was also applied to evaluate the ARI scores.

Results:

The results showed no statistically significant difference between groups 1, 2, and 3, but SBS decreased significantly in group 4. With increasing the concentration of NPs up to 1% chitosan NPs and 1% TiO2 NPs, SBS did not change significantly. However, in 1.5% chitosan NPs and 1.5% TiO2 NPs, SBS decreased compared to the other three groups. No significant differences were found between the groups in terms of ARI scores.

Conclusion:

It is concluded that the orthodontic composite containing 1% chitosan NPs and 1% TiO2 NPs has adequate SBS for use in the clinical setting.
Men’s Lacrosse Injuries in the 2018 International World Championship Play
Authors: Cheney Sarah , Casey Ellen , Abutalib Zafir , Tepper Kenneth B. , Dressler Reuven , Sutton Karen Michelle
Published: May 2021

Background:

Limited data exist on injuries in men’s lacrosse at the international level. As lacrosse’s popularity grows rapidly across the globe, health care providers must understand how to treat lacrosse athletes.

Purpose:

To analyze injury data from the 2018 Men’s World Lacrosse Championship.

Study Design:

Descriptive epidemiology study.

Methods:

This study prospectively observed injuries that occurred during the 2018 Men’s World Lacrosse Championship. The medical staff of each team completed injury report forms, and data were categorized into body part injury, type, mechanism, time, and location of injury.

Results:

Over 11 days, 1019 athletes competed in 170 games, resulting in a total of 7147 athlete-exposures (AEs). A total of 140 injuries were recorded during the tournament for an injury rate of 19.6 per 1000 AEs (95% CI, 16.4-22.7). Overall, there were more contact injuries (n = 99; 70.7%) than noncontact injuries (n = 41; 29.3%) ( P < .0001). Contact injuries most commonly affected the upper extremity, while noncontact injuries most commonly affected the lower extremity. Contusions were the most commonly reported injury type in the tournament (n = 41; 29.3%), followed by ligament sprains (n = 32; 22.9%) and muscle strains (n = 21; 15.0%). Although there was no difference between the first and second half of gameplay, the injury rate increased in the latter portion of each half (the first and third quarters vs the second and fourth quarters) ( P < .0001). A total of 4 injuries required trips to the hospital.

Conclusion:

Lacrosse has a unique injury profile, as it includes both overhead and collision activity as well as multidirectional, cutting movements. Understanding common injury patterns may help with treatment and prevention. Fatigue may play a role in injury rate, and future research of within-game and within-tournament fatigue should explore this relationship.
An Ethnomethodological Study of Abductive Reasoning While Tinkering
Authors: Kim ChanMin , Belland Brian R. , Baabdullah Afaf , Lee Eunseo , Dinç Emre , Zhang Anna Y.
Published: May 2021

Tinkering is often viewed as arbitrary practice that should be avoided. However, tinkering can be performed as part of a sound reasoning process. In this ethnomethodological study, we investigated tinkering as a reasoning process that construes logical inferences. This is a new asset-based approach that can be applied in computer science education. We analyzed artifact-based interviews, video observations, reflections, and scaffolding entries from three pairs of early childhood teacher candidates to document how they engaged in reasoning while tinkering. Abductive reasoning observed during tinkering is discussed in detail.
Precise Answers to Vague Questions: Issues With Interactions
Authors: Rohrer Julia M. , Arslan Ruben C.
Published: May 2021

Psychological theories often invoke interactions but remain vague regarding the details. As a consequence, researchers may not know how to properly test them and may potentially run analyses that reliably return the wrong answer to their research question. We discuss three major issues regarding the prediction and interpretation of interactions. First, interactions can be removable in the sense that they appear or disappear depending on scaling decisions, with consequences for a variety of situations (e.g., binary or categorical outcomes, bounded scales with floor and ceiling effects). Second, interactions may be conceptualized as changes in slope or changes in correlations, and because these two phenomena do not necessarily coincide, researchers might draw wrong conclusions. Third, interactions may or may not be causally identified, and this determines which interpretations are valid. Researchers who remain unaware of these distinctions might accidentally analyze their data in a manner that returns the technically correct answer to the wrong question. We illustrate all issues with examples from psychology and issue recommendations for how to best address them in a productive manner.
Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis
Authors: Wang Jia-feng , Wang Yun-peng , Xie Jian , Zhao Zhen-zhen , Gupta Sahil , Guo Yu , Jia Song-hui , Parodo Jean , Marshall John C. , Deng Xiao-ming
Published: May 2021

PD-L1 is a ligand for PD-1, and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. In this study, PD-L1 expression correlated negatively with rates of apoptosis in human neutrophils harvested from patients with sepsis. Coimmunoprecipitation assays on control neutrophils challenged with interferon-γ and LPS showed that PD-L1 complexes with the p85 subunit of phosphatidyl 3-kinase (PI3K) to activate AKT-dependent survival signaling. Conditional CRE/LoxP deletion of neutrophil PD-L1 in vivo further protected against lung injury and reduced neutrophil lung infiltration in a cecal ligation and puncture (CLP) experimental sepsis animal model. Compared with wild-type animals, PD-L1–deficient animals presented lower levels of plasma tumor necrosis factor-α and interleukin-6 (IL-6) and higher levels of IL-10 after CLP, and reduced 7-day mortality in CLP PD-L1–knockout animals. Taken together, our data suggest that increased PD-L1 expression on human neutrophils delays cellular apoptosis by triggering PI3K–dependent AKT phosphorylation to drive lung injury and increase mortality during clinical and experimental sepsis.
CALR mutant protein rescues the response of MPL p.R464G variant associated with CAMT to eltrombopag
Authors: Basso-Valentina Francesca , Levy Gabriel , Varghese Leila N. , Oufadem Myriam , Neven Benedicte , Boussard Charlotte , Balayn Nathalie , Marty Caroline , Vainchenker William , Plo Isabelle , Ballerini Paola , Constantinescu Stefan N. , Favier Remi , Raslova Hana
Published: May 2021

Congenital amegakaryocytic thrombocytopenia (CAMT) is a severe inherited thrombocytopenia due to loss-of-function mutations affecting the thrombopoietin (TPO) receptor, MPL. Here, we report a new homozygous MPL variant responsible for CAMT in 1 consanguineous family. The propositus and her sister presented with severe thrombocytopenia associated with mild anemia. Next-generation sequencing revealed the presence of a homozygous MPLR464G mutation resulting in a weak cell-surface expression of the receptor in platelets. In cell lines, we observed a defect in MPLR464G maturation associated with its retention in the endoplasmic reticulum. The low cell-surface expression of MPLR464G induced very limited signaling with TPO stimulation, leading to survival and reduced proliferation of cells. Overexpression of a myeloproliferative neoplasm–associated calreticulin (CALR) mutant did not rescue trafficking of MPLR464G to the cell surface and did not induce constitutive signaling. However, it unexpectedly restored a normal response to eltrombopag (ELT), but not to TPO. This effect was only partially mimicked by the purified recombinant CALR mutant protein. Finally, the endogenous CALR mutant was able to restore the megakaryocyte differentiation of patient CD34+ cells carrying MPLR464G in response to ELT.
Profile hidden Markov model sequence analysis can help remove putative pseudogenes from DNA barcoding and metabarcoding datasets
Authors: Porter T. M. , Hajibabaei M.
Published: May 2021

Background

Pseudogenes are non-functional copies of protein coding genes that typically follow a different molecular evolutionary path as compared to functional genes. The inclusion of pseudogene sequences in DNA barcoding and metabarcoding analysis can lead to misleading results. None of the most widely used bioinformatic pipelines used to process marker gene (metabarcode) high throughput sequencing data specifically accounts for the presence of pseudogenes in protein-coding marker genes. The purpose of this study is to develop a method to screen for nuclear mitochondrial DNA segments (nuMTs) in large COI datasets. We do this by: (1) describing gene and nuMT characteristics from an artificial COI barcode dataset, (2) show the impact of two different pseudogene removal methods on perturbed community datasets with simulated nuMTs, and (3) incorporate a pseudogene filtering step in a bioinformatic pipeline that can be used to process Illumina paired-end COI metabarcode sequences. Open reading frame length and sequence bit scores from hidden Markov model (HMM) profile analysis were used to detect pseudogenes.

Results

Our simulations showed that it was more difficult to identify nuMTs from shorter amplicon sequences such as those typically used in metabarcoding compared with full length DNA barcodes that are used in the construction of barcode libraries. It was also more difficult to identify nuMTs in datasets where there is a high percentage of nuMTs. Existing bioinformatic pipelines used to process metabarcode sequences already remove some nuMTs, especially in the rare sequence removal step, but the addition of a pseudogene filtering step can remove up to 5% of sequences even when other filtering steps are in place.

Conclusions

Open reading frame length filtering alone or combined with hidden Markov model profile analysis can be used to effectively screen out apparent pseudogenes from large datasets. There is more to learn from COI nuMTs such as their frequency in DNA barcoding and metabarcoding studies, their taxonomic distribution, and evolution. Thus, we encourage the submission of verified COI nuMTs to public databases to facilitate future studies.
Historical biogeography, systematics, and integrative taxonomy of the non-Ethiopian speckled pelage brush-furred rats (Lophuromys flavopunctatus group)
Authors: Onditi Kenneth Otieno , Demos Terrence C. , Kerbis Peterhans Julian , Chen Zhong-Zheng , Bryja Josef , Lavrenchenko Leonid A. , Musila Simon , Verheyen Erik , Van de Perre Frederik , Akaibe Benjamin Dudu , de la Sancha Noé U. , Jiang Xue-Long
Published: May 2021

Background

The speckled-pelage brush-furred rats (Lophuromys flavopunctatus group) have been difficult to define given conflicting genetic, morphological, and distributional records that combine to obscure meaningful accounts of its taxonomic diversity and evolution. In this study, we inferred the systematics, phylogeography, and evolutionary history of the L. flavopunctatus group using maximum likelihood and Bayesian phylogenetic inference, divergence times, historical biogeographic reconstruction, and morphometric discriminant tests. We compiled comprehensive datasets of three loci (two mitochondrial [mtDNA] and one nuclear) and two morphometric datasets (linear and geometric) from across the known range of the genus Lophuromys.

Results

The mtDNA phylogeny supported the division of the genus Lophuromys into three primary groups with nearly equidistant pairwise differentiation: one group corresponding to the subgenus Kivumys (Kivumys group) and two groups corresponding to the subgenus Lophuromys (L. sikapusi group and L. flavopunctatus group). The L. flavopunctatus group comprised the speckled-pelage brush-furred Lophuromys endemic to Ethiopia (Ethiopian L. flavopunctatus members [ETHFLAVO]) and the non-Ethiopian ones (non-Ethiopian L. flavopunctatus members [NONETHFLAVO]) in deeply nested relationships. There were distinctly geographically structured mtDNA clades among the NONETHFLAVO, which were incongruous with the nuclear tree where several clades were unresolved. The morphometric datasets did not systematically assign samples to meaningful taxonomic units or agree with the mtDNA clades. The divergence dating and ancestral range reconstructions showed the NONETHFLAVO colonized the current ranges over two independent dispersal events out of Ethiopia in the early Pleistocene.

Conclusion

The phylogenetic associations and divergence times of the L. flavopunctatus group support the hypothesis that paleoclimatic impacts and ecosystem refugia during the Pleistocene impacted the evolutionary radiation of these rodents. The overlap in craniodental variation between distinct mtDNA clades among the NONETHFLAVO suggests unraveling underlying ecomorphological drivers is key to reconciling taxonomically informative morphological characters. The genus Lophuromys requires a taxonomic reassessment based on extensive genomic evidence to elucidate the patterns and impacts of genetic isolation at clade contact zones.
The symbiotic relationship between Caenorhabditis elegans and members of its microbiome contributes to worm fitness and lifespan extension
Authors: Haçariz Orçun , Viau Charles , Karimian Farial , Xia Jianguo
Published: May 2021

Background

A healthy microbiome influences host physiology through a mutualistic relationship, which can be important for the host to cope with cellular stress by promoting fitness and survival. The mammalian microbiome is highly complex and attributing host phenotypes to a specific member of the microbiome can be difficult. The model organism Caenorhabditis elegans and its native microbiome, discovered recently, can serve as a more tractable, experimental model system to study host-microbiome interactions. In this study, we investigated whether certain members of C. elegans native microbiome would offer a benefit to their host and putative molecular mechanisms using a combination of phenotype screening, omics profiling and functional validation.

Results

A total of 16 members of C. elegans microbiome were screened under chemically-induced toxicity. Worms grown with Chryseobacterium sp. CHNTR56 MYb120 or Comamonas sp. 12022 MYb131, were most resistant to oxidative chemical stress (SiO2 nanoparticles and juglone), as measured by progeny output. Further investigation showed that Chryseobacterium sp. CHNTR56 positively influenced the worm’s lifespan, whereas the combination of both isolates had a synergistic effect. RNAseq analysis of young adult worms, grown with either isolate, revealed the enrichment of cellular detoxification mechanisms (glutathione metabolism, drug metabolism and metabolism of xenobiotics) and signaling pathways (TGF-beta and Wnt signaling pathways). Upregulation of cysteine synthases (cysl genes) in the worms, associated with glutathione metabolism, was also observed. Nanopore sequencing uncovered that the genomes of the two isolates have evolved to favor the specific route of the de novo synthesis pathway of vitamin B6 (cofactor of cysl enzymes) through serC or pdxA2 homologs. Finally, co-culture with vitamin B6 extended worm lifespan.

Conclusions

In summary, our study indicates that certain colonizing members of C. elegans have genomic diversity in vitamin B6 synthesis and promote host fitness and lifespan extension. The regulation of host cellular detoxification genes (i.e. gst) along with cysl genes at the transcriptome level and the bacterium-specific vitamin B6 synthesis mechanism at the genome level are in an agreement with enhanced host glutathione-based cellular detoxification due to this interspecies relationship. C. elegans is therefore a promising alternative model to study host-microbiome interactions in host fitness and lifespan.
Comparative transcriptomic analysis of candidate effectors to explore the infection and survival strategy of Bursaphelenchus xylophilus during different interaction stages with pine trees
Authors: Hu Long-Jiao , Wu Xiao-Qin , Ding Xiao-Lei , Ye Jian-Ren
Published: May 2021

Background

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is a devastating pathogen of many Pinus species in China. The aim of this study was to understand the interactive molecular mechanism of PWN and its host by comparing differentially expressed genes and candidate effectors from three transcriptomes of B. xylophilus at different infection stages.

Results

In total, 62, 69 and 46 candidate effectors were identified in three transcriptomes (2.5 h postinfection, 6, 12 and 24 h postinoculation and 6 and 15 d postinfection, respectively). In addition to uncharacterized pioneers, other candidate effectors were involved in the degradation of host tissues, suppression of host defenses, targeting plant signaling pathways, feeding and detoxification, which helped B. xylophilus survive successfully in the host. Seven candidate effectors were identified in both our study and the B. xylophilus transcriptome at 2.5 h postinfection, and one candidate effector was identified in all three transcriptomes. These common candidate effectors were upregulated at infection stages, and one of them suppressed pathogen-associated molecular pattern (PAMP) PsXEG1-triggered cell death in Nicotiana benthamiana.

Conclusions

The results indicated that B. xylophilus secreted various candidate effectors, and some of them continued to function throughout all infection stages. These various candidate effectors were important to B. xylophilus infection and survival, and they functioned in different ways (such as breaking down host cell walls, suppressing host defenses, promoting feeding efficiency, promoting detoxification and playing virulence functions). The present results provide valuable resources for in-depth research on the pathogenesis of B. xylophilus from the perspective of effectors.
The relationship between the atherogenic index of plasma and arterial stiffness in essential hypertensive patients from China: a cross-sectional study
Authors: Yin Juan , Li Minghui , Yu Lingling , Hu Feng , Yu Yu , Hu Longlong , Bao Huihui , Cheng Xiaoshu
Published: May 2021

Background

The atherogenic index of plasma (AIP) always remains in a potential association with arterial stiffness, however, this association has not been fully discovered and needs to be studied in depth in large hypertensive patient populations. The present analysis thus sought to further explore the association that exists between AIP and arterial stiffness in Chinese patients diagnosed with arterial hypertension.

Methods

This cross-sectional study analyzed 4744 Chinese individuals with essential hypertension. AIP was defined as the base 10 logarithm of the ratio of plasma of triglycerides to high-density lipoprotein cholesterol levels indicated in molar concentrations. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV).

Results

Data were adjusted for potential confounding variables, and multivariate linear regression analysis revealed AIP to be positively correlated with baPWV (β = 1.34, 95% CI: 0.96 to 1.72, P < 0.001). When AIP was instead treated as a categorical variable divided into quartiles, the same relationship was observed (P for trend < 0.001). We additionally found AIP and baPWV had a stronger positive association in individuals with a body mass index (BMI) < 24 kg/m2 (P for interaction < 0.05).

Conclusion

AIP and arterial stiffness were positively correlated in essential hypertension patients in China, especially in those with a BMI < 24 kg/m2.

Clinical trial registration ChiCTR1800017274.
The influence of the interval between percutaneous transhepatic gallbladder drainage and cholecystectomy on perioperative outcomes: a retrospective study
Authors: Kimura Koichi , Adachi Eisuke , Omori Sachie , Toyohara Ayako , Higashi Takahiro , Ohgaki Kippei , Ito Shuhei , Maehara Shin-ichiro , Nakamura Toshihiko , Ikeda Yoichi , Maehara Yoshihiko
Published: May 2021

Background

Percutaneous transhepatic gallbladder drainage (PTGBD) is recommended for acute cholecystitis patients at high risk for surgical treatment. However, there is no evidence about the best timing of surgery after PTGBD. Here, we retrospectively investigated the influence of the interval between PTGBD and surgery on perioperative outcomes and examined the optimal timing of surgery after PTGBD.

Methods

We performed a retrospective analysis of 22 patients who underwent cholecystectomy after PTGBD from January 2008 to August 2019. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). Moreover, we also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 10) and those with an interval of ≥ 15 days (≥ 15-day group; n = 12).

Results

Of the 22 patients, 9 had Grade I cholecystitis, 12 had Grade II cholecystitis, and 2 had Grade III cholecystitis. Nine patients had high-grade cholecystitis before PTGBD and 13 had a poor general condition. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). The C-reactive protein (CRP) level before surgery was significantly higher (12.70 ± 1.95 mg/dL vs. 1.13 ± 2.13 mg/dL, p = 0.0007) and the total hospitalization was shorter (17.6 ± 8.0 days vs. 54.1 ± 8.8 days, p = 0.0060) in the ≤ 7-day group than in the ≥ 8-day group. We also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 14) and those with an interval of ≥ 15 days (≥ 15-day group; n = 8). The CRP level before surgery was significantly higher (11.13 ± 2.00 mg/dL vs. 0.99 ± 2.64 mg/dL, p = 0.0062) and the total hospitalization was shorter (19.5 ± 7.2 days vs. 59.9 ± 9.5 days, p = 0.0029) in the ≤ 14-day group than in the ≥ 15-day group. However, there were no significant differences between the ≤ 14-day group and the ≥ 15-day group in the levels of hepatic enzymes before surgery, adhesion grade, amount of bleeding during surgery, operative duration, frequency of surgical complications, or length of hospitalization after surgery.

Conclusions

The interval between PTGBD and surgery has little influence on perioperative outcomes.
Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations – a registry-based analysis
Authors: Bramlage Peter , Lanzinger Stefanie , Tittel Sascha R. , Hess Eva , Fahrner Simon , Heyer Christoph H. J. , Friebe Mathias , Buschmann Ivo , Danne Thomas , Seufert Jochen , Holl Reinhard W.
Published: May 2021

Background

Recent European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) guidelines provide recommendations for detecting and treating chronic kidney disease (CKD) in diabetic patients. We compared clinical practice with guidelines to determine areas for improvement.

Methods

German database analysis of 675,628 patients with type 1 or type 2 diabetes, with 134,395 included in this analysis. Data were compared with ESC/EASD recommendations.

Results

This analysis included 17,649 and 116,747 patients with type 1 and type 2 diabetes, respectively. The analysis showed that 44.1 and 49.1 % patients with type 1 and type 2 diabetes, respectively, were annually screened for CKD. Despite anti-diabetic treatment, only 27.2 % patients with type 1 and 43.5 % patients with type 2 achieved a target HbA1c of < 7.0 %. Use of sodium-glucose transport protein 2 inhibitors (1.5 % type 1/8.7 % type 2 diabetes) and glucagon-like peptide-1 receptor agonists (0.6 % type 1/5.2 % type 2 diabetes) was limited. Hypertension was controlled according to guidelines in 41.1 and 67.7 % patients aged 18–65 years with type 1 and 2 diabetes, respectively, (62.4 vs. 68.4 % in patients > 65 years). Renin angiotensin aldosterone inhibitors were used in 24.0 and 40.9 % patients with type 1 diabetes (micro- vs. macroalbuminuria) and 39.9 and 47.7 %, respectively, in type 2 diabetes.

Conclusions

Data indicate there is room for improvement in caring for diabetic patients with respect to renal disease diagnosis and treatment. While specific and potentially clinically justified reasons for non-compliance exist, the data may serve well for a critical appraisal of clinical practice decisions.