bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid Use among Adolescents Undergoing Surgical Repair of Facial Trauma
Authors: Som Avira , Santosa Katherine B. , Skolnick Gary B. , Lapidus Jodi B. , Waljee Jennifer F. , Patel Kamlesh B.
Published: February 2021

Background:

New persistent opioid use has been quantified among adults undergoing surgery; less is known about the risk among adolescents. The authors examine new persistent opioid use in opioid-naive adolescent patients who underwent operative repair of facial fractures.

Methods:

Using the IBM MarketScan Commercial Database, the authors performed a retrospective analysis of patients aged 11 to 17 years who underwent facial fracture repair between 2006 and 2015. The incidences of prolonged opioid use and potentially inappropriate opioid prescriptions were determined.

Results:

Of 4892 patients, 78.5 percent filled a prescription. Among these patients, 7.9 percent had prolonged opioid use. Significant risk factors included older age (i.e., age 15 to 17 years) (OR, 1.579; 95 percent CI, 1.173 to 2.126 compared to younger patients), multiple comorbidities (OR, 3.005; 95 percent CI, 1.193 to 7.568), mandible fracture (OR, 1.614; 95 percent CI, 1.213 to 2.146), and multiple fractures (OR, 1.542; 95 percent CI, 1.002 to 2.372). Overall, 24.1 percent received a potentially inappropriate opioid prescription. Mandible fracture repair was associated with increased risk (OR, 2.753; 95 percent CI, 2.275 to 3.331) of potentially inappropriate opioid prescription.

Conclusions:

Nearly one in 12 adolescents met criteria for prolonged opioid use; nearly one in four received a potentially inappropriate opioid prescription. Significant risk factors included mandible fracture, older age, multiple comorbidities, and multiple fractures. Like adults, many adolescents are at high risk for potentially inappropriate opioid prescriptions and prolonged opioid use following surgical repair.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Amputation versus Free Flap: Long-Term Outcomes of Microsurgical Limb Salvage and Risk Factors for Amputation in the Diabetic Population
Authors: Kotha Vikas S. , Fan Kenneth L. , Schwitzer Jonathan A. , Youn Richard , Black Cara K. , Attinger Christopher E. , Evans Karen K.
Published: February 2021

Background:

Reconstructive microsurgery is an effective limb-saving option for nonhealing lower extremity wounds in diabetic patients. However, the ability to predict the future need for amputation is unclear. This article seeks to identify risk factors for amputation following microsurgical free tissue transfer in the diabetic lower extremity.

Methods:

Diabetic patients undergoing lower extremity free flap surgery between August of 2011 and January of 2018 performed by a single surgeon were identified retrospectively. Patient comorbidities, reconstructive conditions and flap traits, microsurgical outcomes, and long-term outcomes were examined. Variables conferring risk for future amputation were examined by means of regression analysis.

Results:

Sixty-four patients met the criteria. The overall immediate flap success rate was 94 percent (60 of 64). Long term, 50 patients (78.1 percent) underwent successful salvage, and 14 patients (21.9 percent) required major amputation. Acute flap loss resulted in four amputations, and delayed complications (hematoma, infection, recurrent nonhealing) resulted in 10 amputations. The average time to amputation was 5.6 months. Risk factors for amputation were end-stage renal disease (OR, 30.7; p = 0.0087), hindfoot wounds (OR, 4.6; p = 0.020), elevated hemoglobin A1C level greater than 8.4 percent (OR, 1.4; p = 0.05), and positive wound cultures (OR, 6.1; p = 0.003).

Conclusions:

Multiple comorbidities and poor glucose control were identified as risk factors for amputation after free flap limb salvage. However, successful limb preservation is possible.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Salvia miltiorrhiza Injection Promotes the Adipogenic Differentiation of Human Adipose-Derived Stem Cells
Authors: Lin Huaian , Zhang Yifan , Yu Li , Zheng Danning , An Juan
Published: February 2021

Background:

Autologous fat grafting is a commonly used strategy to repair soft-tissue defects that has shown an approximately 40 percent increase in use in the past 5 years. However, the high reabsorption rates (average, 50 percent) often result in an unsatisfactory outcome. Current approaches aimed at increasing the blood supply of grafted fat have little clinical support. Here, we found that Salvia miltiorrhiza could improve fat graft survival by promoting adipogenic differentiation of adipose-derived stem cells by means of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT-enhancer binding protein alpha (C/EBPα) signaling.

Methods:

Adipose tissue was harvested from the thighs of two women. Adipose-derived stem cells were characterized by flow cytometry (CD29, CD90, and CD105). The samples (2 × 104 cells/liter) were incubated with or without S. miltiorrhiza injection (0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, and 5 g/liter) during adipogenic differentiation. Oil Red O staining, triglyceride content, and adipogenic gene expression (PPARγ and C/EBPα) were performed to detect adipogenic differentiation.

Results:

The triglyceride content in the 0.5-g/liter group was increased significantly compared with that in control groups (0.231 ± 0.010, 76.90 percent versus control, p < 0.001, day 9; 0.303 ± 0.010, 91.28 percent versus control, p < 0.001, day 10; 0.361 ± 0.008, 86.65 percent versus control, p < 0.001, day 11). The expression levels of PPARγ and C/EBPα in the 0.5-g/liter group were both increased significantly compared with those in control groups (0.0097 ± 0.0015, 48.1 percent versus control, p < 0.05 for PPARγ; 0.0423 ± 0.003, 112 percent versus control, p < 0.001 for C/EBPα).

Conclusions:

S. miltiorrhiza injection has a positive effect on adipogenesis of adipose-derived stem cells in vitro. The effect of this treatment on improving fat graft survival needs more in vivo research.
A Systematic Review of Health Disparities Research in Plastic Surgery
Authors: Baxter Natalie B. , Howard Julia C. , Chung Kevin C.
Published: February 2021

Background:

In this systematic review, the authors report on the current state of health disparities research in plastic surgery and consider how equity-oriented interventions are taking shape at the patient, provider, and health care system levels.

Methods:

The authors performed a systematic literature search of the PubMed/MEDLINE and Embase databases using search terms related to the social determinants of both health and plastic surgery. Two independent reviewers screened the article titles and abstracts for relevance and identified the plastic surgery focus and study characteristics of the included literature. The articles were then categorized as detecting, understanding, or reducing health disparities according to a conceptual framework. This review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Results:

One hundred forty-seven articles published between 1997 and 2019 met the inclusion criteria. Health disparities research in gender-affirming, craniofacial, cosmetic, and hand surgery was lacking relative to breast reconstruction. Racial/ethnic and socioeconomic disparities were reported across subspecialties. Place of residence was also a large determinant of access to care and quality of surgical outcomes. Half of the included studies were in the detecting phase of research. Meanwhile, 40 and 10 percent were in the understanding and reducing phases, respectively.

Conclusions:

Investigators suggested several avenues for reducing health disparities in plastic surgery, yet there is limited evidence on the actual effectiveness of equity-oriented initiatives. More comprehensive research is needed to disentangle the patient, provider, and system-level factors that underlie inequity across subspecialties.
Cardiovascular Magnetic Resonance Mapping and Strain Assessment for the Diagnosis of Cardiac Involvement in Idiopathic Inflammatory Myopathy Patients With Preserved Left Ventricular Ejection Fraction
Authors: Wang Yue , Wang Qian , Cao Jian , Li Xiao , Lin Lu , Chen Wei , Wang Yi-Ning , Jin Zheng-Yu
Published: February 2021

Purpose:

The aim of the study was to evaluate the role of cardiac magnetic resonance (CMR) mapping and strain analysis in the identification of cardiac involvement in idiopathic inflammatory myopathy (IIM) patients with preserved left ventricular ejection fraction.

Materials and Methods:

In all, 38 IIM patients who underwent CMR examination at our institution were retrospectively included. Twenty-three age-matched healthy individuals served as controls. Mapping parameters including native T1, extracellular volume (ECV), and T2 mapping and strain parameters including global radial strain, global circumferential strain, and global longitudinal strain were measured semiautomatically using a dedicated processing software. All the mapping and strain values were compared between patients and controls.

Results:

Late gadolinium enhancement was only present in IIM patients (n=17, 44.7%). IIM patients showed higher native T1 (1346 vs. 1269 ms, P<0.001), ECV (31.1% vs. 27.4%, P<0.01), and higher T2 (44.4 vs. 39.2 ms, P<0.001) values compared with controls. The global radial strain (36.7% vs. 46.9%, P<0.001), global circumferential strain (−21.2% vs. −24.1%, P<0.01), and global longitudinal strain (−13.6% vs. −15.6%, P<0.05) values were significantly reduced compared with controls.

Conclusions:

Native T1, ECV, T2 values, and global strain values may hold promise for the detection of subclinical myocardial involvement in IIM patients with preserved left ventricular ejection fraction.
Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study
Authors: Barba Thomas , Bachy Emmanuel , Maarek Alizée , Fossard Gaëlle , Genestier Laurent , Anglicheau Dany , Moal Valérie , Dantal Jacques , Rieu Philippe , Chemouny Jonathan , Charrier Manon , Durrbach Antoine , Provot François , Ducloux Didier , Westeel Pierre-François , Heng Anne-Elisabeth , Rerolle Jean-Philippe , Barrou Benoit , Grimbert Philippe , Chatelet Valérie , Mousson Christiane , Janbon Bénédicte , Pernin Vincent , Frimat Luc , Ouali Nacera , Glotz Denis , Thierry Antoine , Mariat Christophe , Büchler Mathias , Gaulard Philippe , Leblond Véronique , Morelon Emmanuel , Dubois Valérie , Salles Gilles , Caillard Sophie , Thaunat Olivier
Published: February 2021

Background.

Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients.

Methods.

All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients.

Results.

T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001).

Conclusions.

This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.
Perioperative Stroke Detected Using Novel SSEP Analysis
Authors: Kelly Michael E. , Peeling Lissa , Norton Jonathan
Published: February 2021

Using a previously described technique that measures the “velocity” of the upswing of the median nerve SSEP, we identified an ischemic event during a carotid surgery that did not meet traditional alarm criteria. Mechanical thrombectomy successfully removed a thrombus, and the patient experienced a good recovery. Analysis of the SSEP waveform may allow for the detection of events missed with traditional alarm criteria.
The periplasmic component of the DctPQM TRAP-transporter is part of the DctS/DctR sensory pathway in Rhodobacter sphaeroides
Authors: Sánchez-Ortiz Veronica Jazmín , Domenzain Clelia , Poggio Sebastian , Dreyfus Georges , Camarena Laura
Published: February 2021

Rhodobacter sphaeroides

can use C4-dicarboxylic acids to grow heterotrophically or photoheterotropically, and it was previously demonstrated in

Rhodobacter capsulatus

that the DctPQM transporter system is essential to support growth using these organic acids under heterotrophic but not under photoheterotrophic conditions. In this work we show that in

R. sphaeroides

this transporter system is essential for photoheterotrophic and heterotrophic growth, when C4-dicarboxylic acids are used as a carbon source. We also found that over-expression of dctPQM is detrimental for photoheterotrophic growth in the presence of succinic acid in the culture medium. In agreement with this, we observed a reduction of the dctPQM promoter activity in cells growing under these conditions, indicating that the amount of DctPQM needs to be reduced under photoheterotrophic growth. It has been reported that the two-component system DctS and DctR activates the expression of dctPQM. Our results demonstrate that in the absence of DctR, dctPQM is still expressed albeit at a low level. In this work, we have found that the periplasmic component of the transporter system, DctP, has a role in both transport and in signalling the DctS/DctR two-component system.
Preservation of neutralizing antibody function in COVID-19 convalescent plasma treated using a riboflavin and ultraviolet light-based pathogen reduction technology
Authors: Yonemura Susan , Hartson Lindsay , Dutt Taru , Henao-Tamayo Marcela , Goodrich Raymond , Marschner Susanne
Published: February 2021

Background and Objective

Convalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19) while other treatments are developed. However, transfusion-transmitted disease is a risk, particularly in regions with high endemic prevalence of transfusion-transmissible diseases. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R+UV) pathogen reduction technology on the functional properties of CCP.

Materials and Methods

CCP units (n = 6) from recovered COVID-19 research donors were treated with R+UV. Pre- and post-treatment samples were tested for coagulation factor and immunoglobulin retention. Antibody binding to spike protein receptor binding domain (RBD), S1, and S2 epitopes of SARS-CoV-2 was assessed by ELISA.

Neutralizing antibody (nAb) function was assessed by pseudovirus reporter viral particle neutralization (RVPN) assay and plaque reduction neutralization test (PRNT).

Results

Mean retention of coagulation factors was ≥ 70% while retention of immunoglobulins was 100%. Starting nAb titers were low, but PRNT50titers did not differ between pre- and post-treatment samples. No statistically significant differences were detected in levels of IgG (P≥ 0.3665) and IgM (P≥ 0.1208) antibodies to RBD, S1, and S2 proteins before and after treatment.

Conclusion

R+UV PRT effects on coagulation factors were similar to previous reports, but no significant effects were observed on immunoglobulin concentration and antibody function. SARS-CoV-2 nAb function in COVID-19 convalescent plasma is conserved following R+UV PRT treatment.
Reported COVID-19 Incidence in Wisconsin High School Athletes During Fall 2020
Authors: Sasser Phillip , McGuine Timothy , Haraldsdottir Kristin , Biese Kevin , Goodavish Leslie , Stevens Bethany , Watson Andrew M.
Published: February 2021

Introduction

The purpose of this study was to describe the reported incidence of COVID-19 in Wisconsin high school athletes in September 2020, and to investigate the relationship of COVID-19 incidence with sport and face mask use.

Methods

Surveys were sent to athletic directors of all Wisconsin high schools regarding sports during September 2020. The association between reported case rates in athletes in each county and the county general population were evaluated with a weighted linear model. Multivariable negative binomial regression models evaluated the associations between COVID-19 incidence and sport type and face mask use by players, adjusting for the county COVID-19 incidence for each school.

Results

207 schools that had reinitiated sport reported 270 COVID-19 cases among 30,074 players, for case and incidence rates of 809 cases per 100,000 players and 32.6 cases per 100,000 player-days, respectively. The case rates for athletes in each county were positively correlated with the case rates for the county’s general population (β =1.14±0.20, r=0.60, p<0.001). One hundred fifteen (55%) of cases were attributed to household contact, 85 (41%) to contact outside sport or school, 5 (2.4%) to school contact, and 1 (0.5%) to sport contact. No difference was identified between team and individual sports (incidence rate ratio (IRR)=1.03 [95% CI=0.49-2.2], p=0.93) or between non-contact and contact sports (IRR=0.53 [0.23-1.3], p=0.14), although the difference between outdoor and indoor sports approached statistical significance (IRR=0.52 [0.26-1.1], p=0.07). 84% of schools required face masks while playing. For those sports with >50 participating schools, there were no significant associations between COVID-19 incidence and face mask use in cross country (IRR=0.71 [0.2-2.2], p=0.52), football (IRR=1.6 [0.6-5.1], p=0.404), boys soccer (IRR=2.3 [0.5-17], p=0.31), or girls volleyball (IRR=1.4 [0.3-6.6], p=0.64).

Conclusions

Incidence of reported COVID-19 among athletes was related to background county incidence and most cases were attributed to household and community contact. Although not statistically significant, reported COVID-19 incidence may be lower in outdoor sports. Face mask use did not have a significant benefit, which may be due to relatively low rates of COVID-19 and the small number of schools that did not report using face masks.
Estimates of the COVID-19 pandemic dynamics in Ukraine based on two data sets
Authors: Nesteruk Igor
Published: February 2021

Background

To simulate how the number of COVID-19 cases increases versus time, various data sets for the number of new cases and different mathematical models can be used. Since there are some differences in statistical data, the results of simulations can be different. Complex mathematical models contain many unknown parameters, the values of which must be determined using a limited number of observations of the disease over time. Even long-term monitoring of the epidemic may not provide reliable estimates of its parameters due to the constant change of testing conditions, isolation of infected and quarantine. Therefore, simpler approaches are necessary. In particular, previous simulations of the COVID-19 epidemic dynamics in Ukraine were based on smoothing of the dependence of the number of cases on time and the generalized SIR (susceptible-infected-removed) model. These approaches allowed to detect the waves of pandemic and to make adequate predictions of the their duration and final sizes. In particular, eight waves of the COVID-19 pandemic in Ukraine were investigated.

Objective

We will compare the results simulation of a new epidemic wave in Ukraine based on national statistics and data reported by Johns Hopkins University (JHU).

Methods

In this study we use the smoothing method for the dependences of the number of cases on time, the generalized SIR model for the dynamics of any epidemic wave, the exact solution of the linear differential equations, and statistical approach developed before.

Results

Ninth epidemic wave in Ukraine was simulated. The optimal values of the SIR model parameters were calculated and compared with the use of two data sets. Both predictions are not very optimistic: new cases will not stop appearing until June-July 2021.

Conclusions

New waves of COVID-19 pandemic can be detected, calculated and predicted with the use of rather simple mathematical models. The results of calculations depend on the data sets for the number of confirmed cases. The expected long duration of the pandemic forces us to be careful and in solidarity. The government and all Ukrainians must strictly adhere to quarantine measures in order to avoid fatal consequences. Probably the presented results could be useful in order to estimate the efficiency of future vaccinations.
Cavernoma in septum pellucidum: descriptive analysis and review of existing literature
Authors: Haque Samiul , Islam Asraful , Rahman Tyfur , Hossain Mohammad D. , Siddik Abu Bakar , Shourav Md Manjurul Islam , Hasan Md Fayad , Ikram Samar , Rahman Masum
Published: February 2021

Background

Cavernomas are rare central nervous system (CNS) lesions that constitute a distinct type of vascular malformation encountered in the brain parenchyma or ventricular system. A cavernoma can be familial or sporadic forms and exhibit a range of presentation from incidental findings to seizures, headaches, hemorrhage. Septum pellucidum cavernoma is exceedingly rare and should be studied for its unique topographical location and clinical course.

Method

We performed a comprehensive literature search and review using multiple databases. the title/abstract and MeSH keywords used included “cavernoma,” “cavernous hemangioma,” “cavernous malformation,” “cavernous angioma,” “CM,” “septum pellucidum” “SP” and “intraventricular,” along with “AND” and “OR” operators. Demographic and clinical data of each patient were collected for qualitative synthesis.

Result

Reported cases were diagnosed at a median age of 42 years; the most frequent symptom was headaches. The incidence of hemorrhage and hydrocephalus was 30%. Gross total resection was performed in 100% of patients and exhibit clinical improvement.

Conclusion

The unique location of the cavernoma exhibits clinical presentations seen and the surgical approach used. Gross total resection conveys the impression of optimum management strategy and leads to a magnificent outcome in most cases.
Impact of environmental temperature on Covid-19 spread: Model and analysis of measurements recorded during the second pandemic in Cyprus
Authors: Livadiotis G.
Published: February 2021

The paper investigates the effect of the environmental temperature on the spread of COVID-19. We study the daily numbers of the cases infected and deaths caused by Covid-19 during the second wave of the pandemic within 2020, and how they were affected by the daily average-high temperature for the districts of the Republic of Cyprus. Among the findings of the paper, we show that (i) the average ratio of the PCR to rapid positive tests is ∼2.57±0.25, as expected from the tests’ responses, indicating that PCR overestimates positivity by ∼2.5 times; (ii) the average age of deaths caused by Covid-19 increases with rate about a year of age per week; (iii) the probability of a person infected by Covid-19 to develop severe symptoms leading to death is strongly depended on the person’s age, while the probability of having a death on the age of ∼67 or younger is less than 1/1000; (iv) the number of infected cases and deaths declined dramatically when the environmental temperature reaches and/or climbs above the critical temperature ofTC=30.1±2.4 C0; (v) the observed negative correlation between the exponential growth rate of the infected cases and the environmental temperature can be described within the framework of chemical kinetics, with at least two competing reactions, the connection of the coronavirus towards the receptor and the dissolution of the coronavirus; the estimated activation energy difference corresponding to the competing chemical reactions, 0.212±0.25 eV, matches the known experimental value; and (vi) the infected cases will decline to zero, when the environmental temperature climbs above the critical temperature within the summery days of 2021, which is expected for the Republic of Cyprus by the 16thof May, 2021.
Losartan Increases Survival of theFbn1mgR/mgRMouse Model of Marfan Syndrome in an Age-Dependent Manner
Authors: Smith Jeffrey D. , Chen Jeff Z. , Phillips Rebecca , Daugherty Alan , Sheppard Mary B.
Published: February 2021

Clinical trials investigating angiotensin receptor blockers (ARB) for attenuation of thoracic aortic aneurysm in people with Marfan syndrome have demonstrated variable efficacy. The primary objective of this study was to determine whether the age of mice at the time of losartan initiation affected mortality in fibrillin-1 hypomorphic (Fbn1mgR/mgR) mice. Male (n=40) and female (n=28) Fbn1mgR/mgR mice were randomized to receive losartan in drinking water (0.6 g/L) starting at either 24 or 50 days of age. Controls included Fbn1mgR/mgR mice (20M, 14F) and wild type (15M, 15F) littermates who were not administered the drug. Mortality of Fbn1mgR/mgR males receiving losartan at postnatal day 24 (P24) was not different from wild type controls (p=0.138). Survival of Fbn1mgR/mgR males administered losartan at P50 was not different compared to Fbn1mgR/mgR males receiving no drug (p=0.194) and decreased compared to wild type mice (p=0.002). Survival analysis after P50 demonstrated increased survival of Fbn1mgR/mgR males administered losartan at P50 compared to Fbn1mgR/mgR mice receiving no drug (p=0.017). Age is a critical variable that affects the therapeutic efficacy of losartan in male Fbn1mgR/mgR mice. Since overall mortality in female Fbn1mgR/mgR mice was lower than in male Fbn1mgR/mgR mice, a survival benefit with losartan was not detected in females.
Unique functions for Notch4 in murine embryonic lymphangiogenesis
Authors: Muley Ajit , Uh Minji Kim , Simone Glicella Salazar-De , Swaminathan Bhairavi , James Jennifer M. , Murtomaki Aino , Youn Seock Won , McCarron Joseph D. , Kitajewski Chris , Buethe Maria Gnarra , Riitano Gloria , Mukoyama Yoh-suke , Kitajewski Jan , Shawber Carrie J.
Published: February 2021

In mice, embryonic dermal lymphatic development is well-understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4 and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulatedDll4transcripts, and differentially and temporally regulated the expression ofNotch1andHes/Heygenes. Mice nullizygous forNotch4had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5, and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. UnlikeNotch4nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increased in LEC proliferation, described for the loss of LECNotch1. Moreover, loss ofNotch4did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.
A conserved paint box underlies color pattern diversity in Estrildid finches
Authors: Hidalgo Magdalena , Curantz Camille , Quenech’Du Nicole , Gluckman Thanh-Lan , Neguer Julia , Beck Samantha , Mohammad Ammara , Manceau Marie
Published: February 2021

Many animals exhibit typical color patterns that have been linked to key adaptive functions, yet the developmental mechanisms establishing these crucial designs remain unclear. Here, we surveyed color distribution in the plumage across a large number of passerine finches. Despite extreme apparent pattern diversity, we identified a small set of conserved color regions whose combinatory association can explain all observed patterns. We found these domains are instructed by early embryonic landmarks, and through profiling and comparative analyses produced a molecular map marking putative color domains in the developing skin. This revealed cryptic pre-patterning common to differently colored species, uncovering a simple molecular landscape underlying extensive color pattern variation.
Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic PrnpZH3/ZH3 mice
Authors: Matamoros-Angles A. , Hervera A. , Soriano J. , Martí E. , Carulla P , Llorens F. , Nuvolone M , Aguzzi A. , Ferrer I. , Gruart A. , Delgado-García JM. , Del Río JA.
Published: February 2021

Background

The cellular prion protein (PrPC) has been associated with numerous cellular processes, such as cell differentiation and neurotransmission. Moreover, it was recently demonstrated that some functions were misattributed to PrPC since results were obtained from mouse models with genetic artifacts. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, like learning and memory, using the new strictly co-isogenic Prnp0/0 mouse (PrnpZH3/ZH3). Behavioral and operant conditioning tests were performed to evaluate memory and learning capabilities. In vivo electrophysiological recordings were carried out at CA3-CA1 synapses in living behaving mice, and spontaneous neuronal firing and network formation were monitored in primary neuronal cultures of PrnpZH3/ZH3 vs. wild-type mice.

Results

Results showed decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures.

Conclusion

In conclusion, PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion might evoke a susceptible epileptogenic brain that would fail to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.
Oxford Nanopore sequencing-based protocol to detect CpG methylation in human mitochondrial DNA
Authors: Bicci Iacopo , Calabrese Claudia , Golder Zoe J. , Gomez-Duran Aurora , Chinnery Patrick F
Published: February 2021

Methylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered major technical issues which introduce a potential bias during methylation quantification. Here, we validate the technical concerns with WGBS, and then develop and assess the accuracy of a protocol for variant-specific methylation identification using long-read Oxford Nanopore Sequencing. Our approach circumvents mtDNA-specific confounders, while enriching for native full-length molecules over nuclear DNA. Variant calling analysis against Illumina deep re-sequencing showed that all expected mtDNA variants can be reliably identified. Methylation calling revealed negligible mtDNA methylation levels in multiple human primary and cancer cell lines. In conclusion, our protocol enables the reliable analysis of epigenetic modifications of mtDNA at single-molecule level at single base resolution, with potential applications beyond methylation.

Motivation

Although whole genome bisulfite sequencing (WGBS) is the gold-standard approach to determine base-level CpG methylation in the nuclear genome, emerging technical issues raise questions about its reliability for evaluating mitochondrial DNA (mtDNA) methylation. Concerns include mtDNA strand asymmetry rendering the C-rich light strand disproportionately vulnerable the chemical modifications introduced with WGBS. Also, short-read sequencing can result in a co-amplification of nuclear sequences originating from ancestral mtDNA with a high nucleotide similarity. Lastly, calling mtDNA alleles with varying proportions (heteroplasmy) is complicated by the C-to-T conversion introduced by WGBS on unmethylated CpGs. Here, we propose an alternative protocol to quantify methyl-CpGs in mtDNA, at single-molecule level, using Oxford Nanopore Sequencing (ONS). By optimizing the standard ONS library preparation, we achieved selective enrichment of native mtDNA and accurate single nucleotide variant and CpG methylation calling, thus overcoming previous limitations.
Intrinsic and growth-mediated cell and matrix specialization during meniscus tissue assembly
Authors: Tsinman Tonia K. , Jiang Xi , Han Lin , Koyama Eiki , Mauck Robert L. , Dyment Nathaniel A.
Published: February 2021

The incredible mechanical strength and durability of mature fibrous tissues and their extremely limited turnover and regenerative capacity underscores the importance of proper matrix assembly during early postnatal growth. In tissues with composite extracellular matrix (ECM) structures, such as the adult knee meniscus, fibrous (Collagen-I rich) and cartilaginous (Collagen-II, proteoglycan-rich) matrix components are regionally segregated to the outer and inner portions of the tissue. While this spatial variation in composition is appreciated to be functionally important for resisting complex mechanical loads associated with gait, the establishment of these specialized zones is poorly understood. To address this issue, the following study tracked the growth of the murine meniscus from its embryonic formation through its first month of growth, encompassing the critical time-window during which animals begin to ambulate and weight bear. Using histological analysis, region specific high-throughput qPCR, and Col-1 and Col-2 fluorescent reporter mice, we found that matrix and cellular features defining specific tissue zones were already present at birth, before continuous weight-bearing had occurred. These differences were further refined with postnatal growth and maturation, resulting in specialization of mature tissue regions. Taken together, this work establishes a detailed timeline of the concurrent spatiotemporal changes that occur at both the cellular and matrix level throughout meniscus maturation. The findings of this study provide a framework for investigating the reciprocal feedback between cells and their evolving microenvironments during assembly of a mechanically robust fibrocartilage tissue, thus providing insight into mechanisms of tissue degeneration and effective regenerative strategies.
A genome-wide circular RNA transcriptome in Rat
Authors: Sharma Disha , Sehgal Paras , Sivasubbu Sridhar , Scaria Vinod
Published: February 2021

Background

Circular RNAs are a novel class of non-coding RNAs that backsplice from 5’ donor site and 3’ acceptor site to form a circular structure. A number of circRNAs have been discovered in model organisms including human, mouse, Drosophila, among other organisms. There are a few candidate-based studies on circular RNAs in rat, a well studied model organism. The availability of a recent dataset of transcriptomes encompassing 11 tissues, 4 developmental stages and 2 genders motivated us to explore the landscape of circular RNAs in the organism.

Methodology

In order to understand the difference among different pipelines, we have used the same bodymap RNA sequencing dataset. A number of pipelines have been published to identify the backsplice junctions for the discovery of circRNAs but studies comparing these tools have suggested that a combination of tools would be a better approach to identify high-confidence circular RNAs. We employed 5 different combinations of tools including tophat_CIRCexplorer2, segemehl_CIRCexplorer2, star_CIRCexplorer, Bowtie2_findcirc and Bowtie2_findcirc (noHisat2) to identify circular RNAs from the dataset.

Results

Our analysis identified a number of tissue-specific, developmental stage specific and gender specific circular RNAs. We further independently validated 16 circRNA junctions out of 24 selected candidates in 5 tissue samples. We additionally estimated the quantitative expression of 5 circRNA candidates using real-time PCR and our analysis suggests 3 candidates as tissue-enriched

Conclusion

This study is one of the most comprehensive studies that provides a circular RNA transcriptome as well as to understand the difference among different computational pipelines in Rat.
Microstates and power envelope hidden Markov modeling probe bursting brain activity at different timescales
Authors: Coquelet N , De Tiège X , Roshchupkina L , Peigneux P , Goldman S , Woolrich M , Wens V
Published: February 2021

State modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. We addressed this issue by using simultaneous MEG/EEG recordings at rest and comparing the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differed both spatially and temporally. Microstates tend to exhibit spatio-temporal locality, whereas power envelope HMM states disclose network-level activity with 100–200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.
Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure
Authors: Niina Toru , Matsunaga Yasuhiro , Takada Shoji
Published: February 2021

Atomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examined four similarity scores via twin-experiments for four test proteins, finding that the cosine similarity score generally worked best, whereas the pixel-RMSD and the correlation coefficient were also useful. We then applied the method to two experimental high-speed-AFM images inferring the probe shape and the molecular placement. The results suggest that the appropriate similarity score can differ between target systems. For an actin filament image, the cosine similarity apparently worked best. For an image of the flagellar protein FlhAC, we found the correlation coefficient gave better results. This difference may partly be attributed to the flexibility in the target molecule, ignored in the rigid-body fitting. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available.

Author Summary

Observation of functional dynamics of individual biomolecules is important to understand molecular mechanisms of cellular phenomena. High-speed (HS) atomic force microscopy (AFM) is a powerful tool that enables us to visualize the real-time dynamics of working biomolecules under near-physiological conditions. However, the information available by the AFM images is limited to the two-dimensional surface shape detected via the force to the probe. While the surface information is affected by the shape of the probe tip, the probe shape itself cannot be directly measured before each AFM measurement. To overcome this problem, we have developed a computational method to simultaneously infer the probe tip shape and the molecular placement from an AFM image. We show that our method successfully estimates the effective AFM tip shape and visualizes a structure with a more accurate placement. The estimation of a molecular placement with the correct probe tip shape enables us to obtain more insights into functional dynamics of the molecule from HS-AFM images.
Young and Undamaged rMSA Improves the Longevity of Mice
Authors: Tang Jiaze , Ju Anji , Li Boya , Zhang Shaosen , Gong Yuanchao , Ma Boyuan , Jiang Yi , Liu Hongyi , Fu Yan , Luo Yongzhang
Published: February 2021

Improvement of longevity is an eternal dream of human beings. Here we report that a single protein recombinant mouse serum albumin (rMSA) improved the lifespan and healthspan of C57BL/6N mice. The median lifespan extensions were 17.6% for female and 20.3% for male, respectively. The grip strength of rMSA-treated female and male mice increased by 29.6% and 17.4%, respectively. Meanwhile, the percentage of successful escape increased 23.0% in rMSA-treated male mice using the Barnes Maze test. The rMSA used in this study is young and almost undamaged. We define the concept “young and undamaged” to any protein without any unnecessary modifications by four parameters: intact free thiol (if any), no advanced glycation end-product, no carbonylation, and no homocysteinylation. Here “young and undamaged” rMSA is much younger and less damaged than the endogenous serum albumin from young mice at 1.5 months of age. We predict that young and undamaged proteins altogether can further improve the longevity.
Gaussian process modeling of nonstationary crop yield distributions with applications to crop insurance
Authors: Wu Wenbin , Wu Ximing , Zhang Yu Yvette , Leatham David
Published: February 2021

Purpose

The purpose of this paper is to bring out the development of a flexible model for nonstationary crop yield distributions and its applications to decision-making in crop insurance.

Design/methodology/approach

The authors design a nonparametric Bayesian approach based on Gaussian process regressions to model crop yields over time. Further flexibility is obtained via Bayesian model averaging that results in mixed Gaussian processes.

Findings

Simulation results on crop insurance premium rates show that the proposed method compares favorably with conventional estimators, especially when the underlying distributions are nonstationary.

Originality/value

Unlike conventional two-stage estimation, the proposed method models nonstationary crop yields in a single stage. The authors further adopt a decision theoretic framework in its empirical application and demonstrate that insurance companies can use the proposed method to effectively identify profitable policies under symmetric or asymmetric loss functions.
Do producers respond to quality information disclosure? The HACCP certification in meat industry
Authors: Zhou Jiehong , Jin Yu , Wang Yu , Liang Qiao
Published: February 2021

Purpose

Food markets are characterized by asymmetric information between suppliers and consumers, which causes inefficiency of market and food safety risks. This paper studies how the food quality and safety information disclosed by the government affects the hazard analysis and critical control point (HACCP) certification decision of meat producers. The heterogeneity of the effects across different regions, provinces with different meat output scales and provinces with different intensities of food safety regulation is evaluated.

Design/methodology/approach

This paper applies a unique database comprising information from multiple sources. Food quality and safety information disclosure is indicated by the number of failure records of food sampling inspections by the government in 2015–2018. Fixed-effect model is used in the analyses.

Findings

The results demonstrate that food quality and safety information disclosure has a significant effect on the HACCP certification adoption by meat producers. The effect is heterogeneous across geographic regions, i.e. this effect is larger in the east and the middle of China than that in the west and the northeast. The heterogeneity across regions may be caused by the variance in meat output scales and fiscal expenditures on food safety among provinces.

Originality/value

This research is one of the preliminary attempts to understand how producers respond in terms of HACCP certification to the amount of food quality and safety information disclosed by the government, based on the case of meat industry in China.
A qualitative exploration of value and waste in a Trinidadian emergency department patient flow process: perspectives of patients and clinicians
Authors: De Freitas Loren , Goodacre Steve , O'Hara Rachel , Thokala Praveen , Hariharan Seetharaman
Published: February 2021

Purpose

A process that does not include the customer's value may not be effective in providing care. This study aimed to identify value and waste in an emergency department (ED) patient flow process from a patient and clinician perspective.

Design/methodology/approach

A qualitative case study was conducted in an ED in Trinidad and Tobago. Observations and informal conversational interviews with clinicians (n = 33) and patients (n = 50) explored patient flow, value and waste. Thematic analysis was used to create a framework on valuable and wasteful aspects in the ED patient flow process.

Findings

Valuable aspects led to direct improvements in the patient's health or an exchange of information in the process. Wasteful aspects were those with no patient activity, no direct ED clinical involvement, or resulted in a perceived inappropriate use of ED resources. However, there was a disparity in responses between clinicians and patients with clinicians identifying more features in the process.

Research limitations/implications

The single case study design limits the generalizability of findings to other settings. This study did not specifically explore the influence of age and gender on what mattered to patients in ED services. Future studies would benefit from exploring whether there are any age and gender differences in patient perspectives of value and waste. Further research is needed to validate the usefulness of the framework in a wider range of settings and consider demographic factors such as age and gender.

Practical implications

The study has produced a framework which may be used to improve patient flow in a way that maximized value to its users. A collaborative approach, with active patient involvement, is needed to develop a process that is valuable to all. The single case study design limits the generalizability of findings to other settings.

Originality/value

Qualitative methods were used to explicitly explore both value and waste in emergency department patient flow, incorporating the patient perspective. This paper provides an approach that decision makers may use to refine the ED patient flow process into one that flows well, improves quality and maximizes value to its users.