bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractional exhaled nitric oxide and asthma treatment adherence
Authors: Butler Claire A. , Heaney Liam G.
Published: December 2020

Purpose of review

Despite increased clinician awareness, nonadherence to inhaled corticosteroid treatment presents a major challenge to successful asthma management and risks inappropriate treatment escalation, particularly in severe disease. In patients with Type-2 mediated biology, fractional exhaled nitric oxide (FeNO) has a role in assessment and monitoring of adherence to inhaled corticosteroids.

Recent findings

Asthmatic patients with elevated FeNO are at an increased risk of exacerbation. High FeNO is often secondary to suboptimal adherence to inhaled corticosteroid treatment, whether intentional or nonintentional. FENO-suppression can ‘unmask’ underlying adherence issues and is a useful test in the presence of Type-2 biology in the ‘difficult-to-control’ asthma population. Identification of nonadherence can improve asthma control and prevent inappropriate commencement of costly biologic therapies.

Assessment of adherence and FeNO response to monitored inhaled corticosteroid in Type-2 biomarker high asthmatic individuals may prevent unnecessary escalation to biologic therapy. Establishing an ‘optimised’ FeNO may alert clinicians to the possibility of underlying nonadherence at future clinical assessments.
Safety and Effectiveness of Autologous Fat Grafting after Breast Radiotherapy: A Systematic Review and Meta-Analysis
Authors: Chen Yujie , Li Guangxue
Published: December 2020

Background:

The purpose of this study was to evaluate the safety and effectiveness of autologous fat grafting after radiotherapy.

Methods:

All studies published before December of 2019 were collected by searching on PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. After independently screening the studies and extracting the data, Stata was applied to perform meta-analysis.

Results:

Seventeen qualified articles were eventually included, involving a total of 1658 patients, of which 1555 underwent autologous fat grafting. Overall, empirically from the data, the use of autologous fat grafting after radiotherapy does not increase the incidence of complications or the risk of tumor recurrence. Through statistical analysis, the authors found that 152 patients suffered complications after undergoing autologous fat grafting [152 of 1555 (9.8 percent)]; 72 patients suffered complications after undergoing postradiotherapy autologous fat grafting [72 of 1040 (6.9 percent)], including seven cases of tumor recurrence [seven of 1040 (0.7 percent)]; and 80 patients suffered complications after undergoing autologous fat grafting without radiotherapy [80 of 515 (15.5 percent)], including seven cases of tumor recurrence [seven of 515 (1.4 percent)]. The authors also found that 970 of 1040 patients (93.3 percent) were satisfied with the results of postradiotherapy autologous fat grafting for breast reconstruction.

Conclusions:

This study has provided an evidence-based conclusion supporting the use of autologous fat grafting for breast reconstruction after radiotherapy. Autologous fat grafting can effectively correct breast deformity and contracture caused by breast-conserving therapy and radiotherapy and increase patient satisfaction without increasing the rate of tumor recurrence.
Study Comparing Platform Wound Dressing, a Negative-Pressure Device without a Filler, with Three Conventional Negative-Pressure Wound Therapy Systems in the Treatment of Excisional and Incisional Wounds
Authors: Nuutila Kristo , Broomhead Michael , Proppe Karl , Eriksson Elof
Published: December 2020

Background:

All common negative-pressure wound therapy systems include a material, usually foam or gauze, at the wound/device interface. In this preclinical study, the authors have compared the effects on different wound healing parameters in the three most common negative-pressure wound therapy systems (i.e., V.A.C.VIA, PREVENA, and PICO) with a new device without foam or gauze (i.e., Platform Wound Dressing). A strong effort was made to avoid bias. The study was conducted under good laboratory practice conditions, with the presence of an independent observer.

Methods:

In pigs, three types of wounds were studied: full-thickness excisions, open incisions, and sutured closed incisions. Several macroscopic and microscopic parameters were studied. The pigs were euthanized on day 9 and all wounds were processed for histology and excisions for immunohistochemistry.

Results:

In general, the devices produced similar results, with only a few significant differences. In the excisions, the Platform Wound Dressing reduced wound area more than the V.A.C.VIA and the PICO. In the excisional wounds, reepithelialization was the same. In open incisions, PREVENA was better than the Platform Wound Dressing. Histologic examination showed that, in open incisions, there was less inflammation in the PREVENA-treated in comparison with the Platform Wound Dressing– and the PICO-treated wounds. Immunohistochemical analyses showed that the Platform Wound Dressing–treated excisions had significantly more blood vessels (von Willebrand factor) than the V.A.C.VIA-treated ones and that the PICO caused less T-cell activation (CD3) than the other two.

Conclusion:

The devices—with foam, with gauze, or without either and just an embossed membrane—performed equally in general.
Craniofacial and Long Bone Development in the Context of Distraction Osteogenesis
Authors: Shah Harsh N. , Jones Ruth E. , Borrelli Mimi R. , Robertson Kiana , Salhotra Ankit , Wan Derrick C. , Longaker Michael T.
Published: December 2020

Background:

Bone retains regenerative potential into adulthood, and surgeons harness this plasticity during distraction osteogenesis. The underlying biology governing bone development, repair, and regeneration is divergent between the craniofacial and appendicular skeleton. Each type of bone formation is characterized by unique molecular signaling and cellular behavior. Recent discoveries have elucidated the cellular and genetic processes underlying skeletal development and regeneration, providing an opportunity to couple biological and clinical knowledge to improve patient care.

Methods:

A comprehensive literature review of basic and clinical literature regarding craniofacial and long bone development, regeneration, and distraction osteogenesis was performed.

Results:

The current understanding in craniofacial and long bone development and regeneration is discussed, and clinical considerations for the respective distraction osteogenesis procedures are presented.

Conclusions:

Distraction osteogenesis is a powerful tool to regenerate bone and thus address a number of craniofacial and appendicular skeletal deficiencies. The molecular mechanisms underlying bone regeneration, however, remain elusive. Recent work has determined that embryologic morphogen gradients constitute important signals during regeneration. In addition, striking discoveries have illuminated the cellular processes underlying mandibular regeneration during distraction osteogenesis, showing that skeletal stem cells reactivate embryologic neural crest transcriptomic processes to carry out bone formation during regeneration. Furthermore, innovative adjuvant therapies to complement distraction osteogenesis use biological processes active in embryogenesis and regeneration. Additional research is needed to further characterize the underlying cellular mechanisms responsible for improved bone formation through adjuvant therapies and the role skeletal stem cells play during regeneration.
Holographic Augmented Reality for DIEP Flap Harvest
Authors: Wesselius Tycho S. , Meulstee Jene W. , Luijten Gijs , Xi Tong , Maal Thomas J. J. , Ulrich Dietmar J. O.
Published: December 2020

Background:

During a deep inferior epigastric perforator (DIEP) flap harvest, the identification and localization of the epigastric arteries and its perforators are crucial. Holographic augmented reality is an innovative technique that can be used to visualize this patient-specific anatomy extracted from a computed tomographic scan directly on the patient. This study describes an innovative workflow to achieve this.

Methods:

A software application for the Microsoft HoloLens was developed to visualize the anatomy as a hologram. By using abdominal nevi as natural landmarks, the anatomy hologram is registered to the patient. To ensure that the anatomy hologram remains correctly positioned when the patient or the user moves, real-time patient tracking is obtained with a quick response marker attached to the patient.

Results:

Holographic augmented reality can be used to visualize the epigastric arteries and its perforators in preparation for a deep inferior epigastric perforator flap harvest.

Conclusions:

Potentially, this workflow can be used visualize the vessels intraoperatively. Furthermore, this workflow is intuitive to use and could be applied for other flaps or other types of surgery.
Musculoseptocutaneous Perforator of Anterolateral Thigh Flap: A Clinical Study
Authors: Hsieh Frank , Leow Osbert Qi Yao , Cheong Chon-Fok , Hung Shao-Yu , Tsao Chung-Kan
Published: December 2020

Background:

The anterolateral thigh flap is one of the most useful workhorse flaps for microsurgical reconstruction. However, it can pose a great challenge to surgeons because of its anatomical variability. As the technology advances, not only septocutaneous or musculocutaneous courses of anterolateral thigh perforators but also a hybrid musculoseptocutaneous perforator pattern have been identified on computerized imaging and on cadaveric study. However, there is a paucity of clinical study in the literature. The aim of this investigation was to identify the features of this pattern.

Methods:

All patients undergoing anterolateral thigh flap harvest between September of 2017 and May of 2018 performed by a single surgeon are included. Every pulsatile perforator was dissected to document its location on the thigh, emerging location (septum/muscle), size, course, and origin.

Results:

Thirty-seven patients with 115 perforators were identified. Ten percent of perforators were septocutaneous, 37 percent were musculoseptocutaneous, and 52 percent were musculocutaneous. Forty-seven percent of perforators emerged on the septum between the rectus femoris and the vastus lateralis. Eighty-one percent of patients had one or more perforators in the “hot zone.” Medium and large perforators were more frequently located in the proximal and hot zones. All perforators originated from the vascular tree of the lateral circumflex femoral artery, with 10 percent originating from the transverse branch, 28 percent originating from the oblique branch, and 62 percent originating from the descending branch.

Conclusions:

A high proportion of musculoseptocutaneous perforators were identified. The clinical relevance of this is to be very cautious on the skin paddle design while harvesting the flap.
Hyperbaric Oxygen Therapy in Management of Diabetic Foot Ulcers: Indocyanine Green Angiography May Be Used as a Biomarker to Analyze Perfusion and Predict Response to Treatment
Authors: Hajhosseini Babak , Chiou Grace J. , Virk Sarah S. , Chandra Venita , Moshrefi Shawn , Meyer Shannon , Kamperman Kathryn J. , Gurtner Geoffrey C.
Published: December 2020

The authors present indocyanine green angiography to assess the effects of hyperbaric oxygen therapy and as a potential biomarker to predict healing of chronic wounds. They hypothesize that favorable initial response to hyperbaric oxygen therapy (improved perfusion) would be an early indicator of eventual response to the treatment (wound healing). Two groups were recruited: patients with chronic wounds and unwounded healthy controls. Inclusion criteria included adults with only one active wound of Wagner grade III diabetic foot ulcer or caused by soft-tissue radionecrosis. Patients with chronic wounds underwent 30 to 40 consecutive hyperbaric oxygen therapy sessions, once per day, 5 days per week; controls underwent two consecutive sessions. Indocyanine green angiography was performed before and after the sessions, and perfusion patterns were analyzed. Healing was determined clinically and defined as full skin epithelialization with no clinical evidence of wound drainage. Fourteen chronic-wound patients and 10 controls were enrolled. Unlike unwounded healthy volunteers, a significant increase in indocyanine green angiography perfusion was found in chronic-wound patients immediately after therapy (p < 0.03). Moreover, the authors found that 100 percent of the wounds that demonstrated improved perfusion from session 1 to session 2 went on to heal within 30 days of hyperbaric oxygen therapy completion, compared with none in the subgroup that did not demonstrate improved perfusion (p < 0.01). This study demonstrates a beneficial impact of hyperbaric oxygen therapy on perfusion in chronic wounds by ameliorating hypoxia and improving angiogenesis, and also proposes a potential role for indocyanine green angiography in early identification of those who would benefit the most from hyperbaric oxygen therapy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Pushing the Envelope: Skin-Only Mastopexy in Single-Stage Nipple-Sparing Mastectomy with Direct-to-Implant Breast Reconstruction
Authors: Aliotta Rachel E. , Scomacao Isis , Duraes Eliana F. R. , Kwiecien Grzegorz J. , Durand Paul D. , Fanning Alicia , Moreira Andrea
Published: December 2020

Background:

Despite advances in skin envelope reduction techniques and experienced nipple-sparing mastectomy flap procedures, the rate of nipple malposition and secondary revision in these patients remains high and eligible candidates are limited. In this article, the authors present a novel technique combining skin reduction nipple-sparing mastectomy surgery with single-stage skin-only mastopexy and direct-to-implant reconstruction.

Methods:

A retrospective review was performed at a single institution from 2015 to 2018. All patients were operated on using this technique consecutively, by a breast and plastic surgeon team (A.F. and A.M.). Surgical technique and outcomes were compared with the currently accepted literature.

Results:

Twenty-six patients (40 breasts) underwent this technique; all were single-stage direct-to-implant reconstructions. The average body mass index was 31 kg/m2. A Wise pattern was used in 35 breasts (87.5 percent) and prepectoral placement was used in 25 breasts (62.5 percent). Overall complications included seroma [n = 6 (15 percent)], vertical/T-junction dehiscence [n = 4 (10 percent)], skin necrosis [n = 4 (10 percent)], superficial or partial nipple necrosis [n = 4 (10 percent)], with no total nipple-areola complex lost and no reconstructive failures at 18.7 months’ average follow-up.

Conclusions:

In this article, the authors share a novel reconstructive technique in which the skin envelope is reduced, the nipple-areola complex is repositioned, and a direct-to-implant reconstruction is performed in a single stage at the time of mastectomy. Consideration of pearls and pitfalls accompanies a review of the authors’ experienced complication profile, and is discussed in the context of current literature.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Truth-in-Advertising Laws: Are They Working? A Cross-Sectional Analysis of a “Plastic Surgeon” Patient Search Simulation
Authors: Chattha Anmol , Muste Justin , Chen Austin D. , Lee Bernard T. , Lin Samuel J. , Roth Malcolm Z.
Published: December 2020

Background:

Non–board-certified plastic surgeons performing cosmetic procedures and advertising as plastic surgeons may have an adverse effect on a patient’s understanding of their practitioner’s medical training and patient safety. The authors aim to assess (1) the impact of city size and locations and (2) the impact of health care transparency acts on the ratio of board-certified and non–American Board of Plastic Surgeons physicians.

Methods:

The authors performed a systematic Google search for the term “plastic surgeon [city name]” to simulate a patient search of online providers. Comparisons of board certification status between the top hits for each city were made. Data gathered included city population, regional location, practice setting, and states with the passage of truth-in-advertising laws.

Results:

One thousand six hundred seventy-seven unique practitioners were extracted. Of these, 1289 practitioners (76.9 percent) were American Board of Plastic Surgery–certified plastic surgeons. When comparing states with truth-in-advertising laws and states without such laws, the authors found no significant differences in board-certification rates among “plastic surgery” practitioners (88.9 percent versus 92.0 percent; p = 0.170). There was a significant difference between board-certified “plastic surgeons” versus out-of-scope practitioners on Google search between large, medium, and small cities (100 percent versus 92.9 percent versus 86.5; p < 0.001).

Conclusions:

Non–board-certified providers tend to localize to smaller cities. Truth-in-advertising laws have not yet had an impact on the way a number of non–American Board of Plastic Surgery–certified practitioners market themselves. There may be room to expand the scope of truth-in-advertising laws to the online world and to smaller cities.
Plastic Surgery and the Malpractice Industry
Authors: Boyd J. Brian , Moon Harry K. , Martin Susan , Mastrogiovanni Dena B.
Published: December 2020

The current status of the plastic surgeon in the medical liability spectrum and ways to avoid litigation are explored by using pooled national data from the Medical Professional Liability Association, private information from Applied Medico-Legal Solutions RRG, and a detailed literature search. The medical liability system in the United States costs $55.6 billion, or 2.4 percent of total health care spending. Plastic surgery accounts for 3.31 percent of reported claims and 3.16 percent of paid claims. Total payments for plastic surgeons represent 1.75 percent of the total paid for all specialties. Malpractice awards are relatively light for plastic surgeons. Nevertheless, they still have a 15 percent chance per year of being sued. However, 93 percent of cases will close with a dismissal or a settlement, and only 7 percent will go to trial. Of these, the plastic surgeon will prevail in 79 percent. Most importantly, 75 percent of all cases will result in no payment. To minimize the chances of a lawsuit, plastic surgeons should maintain excellent communication with their patients and participate in shared decision-making. They should take a leadership role and buy in to the performance of perioperative checklists, embrace patient education, and actively participate in Maintenance of Certification. They should be transparent in their dealings with patients by preoperatively declaring their policies on revisions, refunds, complications, and payments. Plastic surgeons must maintain complete and accurate medical records and participate in hospital-based programs of prophylaxis. They should be aware that postoperative infection is the single costliest adverse outcome and proactively deal with it.
The Emergence of Wernicke's Encephalopathy After Gastric Sleeve
Authors: Brown Terry , Parker Anna
Published: December 2020

Sleeve gastrectomy has emerged as one of the most common surgical interventions for individuals with obesity. There is evidence about the benefits of bariatric surgery including rapid weight loss and improvements in comorbidities; however, not much is known about its negative health consequences. This article investigates the prevalence of micronutrient deficiencies pre- and postoperatively in adults who have undergone a sleeve gastrectomy. The accompanying case report describes a patient with morbid obesity who developed Wernicke's encephalopathy due to complications after bariatric surgery. Also, it highlights the patient's care as well as missed opportunities to diagnose a micronutrient deficiency.
Increased Frequency of Nutritional Counseling Improves Weight Status and Lipids in Renal Transplant Recipients
Authors: Bunde Kelly , Gjesvold Donna , Kattelmann Kendra K. , McCormack Lacey A. , Vukovich Matthew D.
Published: December 2020

Patients commonly experience excessive weight gain (>10%) within 6 months to 1 year after renal transplant. The aim of this retrospective study of electronic medical records was to examine the association between number of nutritional counseling sessions with a registered dietitian nutritionist (RDN) with weight gain and lipids post-transplant. An analysis of covariance controlling for age and time between pre- and postmeasurements for weight, body mass index (BMI), and lipids was used to compare tertiles. Patients in tertile 1 (1–2 visits with RDN) experienced weight gain while patients in tertile 2 (3 visits) and tertile 3 (4–9 visits) did not gain weight. The change in weight was correlated with the changes in cholesterol (r = 0.23, P = .003) and triglyceride (r = 0.3, P = .0004). There were no differences among tertiles for female patients. Males in tertile 3 lost weight and improved BMI compared with male patients in tertile 1. Four or more visits with an RDN following renal transplantation are beneficial in preventing excessive weight gain. The change in weight was positively associated with blood lipids.
A Systematic Review of the Role of Thiamine Supplementation in Treatment of Refeeding Syndrome
Authors: Steiner Lea , Hewlings Susan
Published: December 2020

The purpose of this systematic review is to identify studies where measurable thiamine supplementation was provided to patients at risk for or with refeeding syndrome to improve treatment guidelines. A systematic review of PubMed and CINAHL Plus databases was conducted using the terms refeeding syndrome, hypophosphatemia, thiamine, and vitamin B1. A total of 173 articles were retrieved and 11 case studies and 1 retrospective study met inclusion criteria. All studies identified symptoms of thiamine deficiency, and all studies indicated thiamine supplementation was associated with improved clinical symptoms and no harmful outcomes. Average dose provided was 173-mg thiamine/day.
Cellular Mechanisms of Rejection of Optic and Sciatic Nerve Transplants: An Observational Study
Authors: Yonar Merve , Uehara Mayuko , Banouni Naima , Kasinath Vivek , Li Xiaofei , Jiang Liwei , Zhao Jing , Bei Fengfeng , Shin Su Ryon , Cetrulo Curtis L. , Annabi Nasim , Abdi Reza
Published: December 2020

Background.

Organ transplantation is a standard therapeutic strategy for irreversible organ damage, but the utility of nerve transplantation remains generally unexplored, despite its potential benefit to a large patient population. Here, we aimed to establish a feasible preclinical mouse model for understanding the cellular mechanisms behind the rejection of peripheral and optic nerves.

Methods.

We performed syngenic and allogenic transplantation of optic and sciatic nerves in mice by inserting the nerve grafts inside the kidney capsule, and we assessed the allografts for signs of rejection through 14 d following transplantation. Then, we assessed the efficacy of CTLA4 Ig, Rapamycin, and anti-CD3 antibody in suppressing immune cell infiltration of the nerve allografts.

Results.

By 3 d posttransplantation, both sciatic and optic nerves transplanted from BALB/c mice into C57BL/6J recipients contained immune cell infiltrates, which included more CD11b+ macrophages than CD3+ T cells or B220+ B cells. Ex vivo immunogenicity assays demonstrated that sciatic nerves demonstrated higher alloreactivity in comparison with optic nerves. Interestingly, optic nerves contained higher populations of anti-inflammatory PD-L1+ cells than sciatic nerves. Treatment with anti-CD3 antibody reduced immune cell infiltrates in the optic nerve allograft, but exerted no significant effect in the sciatic nerve allograft.

Conclusions.

These findings establish the feasibility of a preclinical allogenic nerve transplantation model and provide the basis for future testing of directed, high-intensity immunosuppression in these mice.
Isolation of a Highly Purified HSC-enriched CD34+CD90+CD45RA− Cell Subset for Allogeneic Transplantation in the Nonhuman Primate Large-animal Model
Authors: Radtke Stefan , Colonna Lucrezia , Perez Anai M. , Hoffman Michelle , Kean Leslie S. , Kiem Hans-Peter
Published: December 2020

Background.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common treatment for patients suffering from different hematological disorders. Allo-HCT in combination with hematopoietic stem cell (HSC) gene therapy is considered a promising treatment option for millions of patients with HIV+ and acute myeloid leukemia. Most currently available HSC gene therapy approaches target CD34-enriched cell fractions, a heterogeneous mix of mostly progenitor cells and only very few HSCs with long-term multilineage engraftment potential. As a consequence, gene therapy approaches are currently limited in their HSC targeting efficiency, very expensive consuming huge quantities of modifying reagents, and can lead to unwanted side effects in nontarget cells. We have previously shown that purified CD34+CD90+CD45RA− cells are enriched for multipotent HSCs with long-term multilineage engraftment potential, which can reconstitute the entire hematopoietic system in an autologous nonhuman primate transplant model. Here, we tested the feasibility of transplantation with purified CD34+CD90+CD45RA− cells in the allogeneic setting in a nonhuman primate model.

Methods.

To evaluate the feasibility of this approach, CD34+CD90+CD45RA− cells from 2 fully major histocompatibility complex-matched, full sibling rhesus macaques were sort-purified, quality controlled, and transplanted. Engraftment and donor chimerism were evaluated in the peripheral blood and bone marrow of both animals.

Results.

Despite limited survival due to infectious complications, we show that the large-scale sort-purification and transplantation of CD34+CD90+CD45RA− cells is technically feasible and leads to rapid engraftment of cells in bone marrow in the allogeneic setting and absence of cotransferred T cells.

Conclusions.

We show that purification of an HSC-enriched CD34+ subset can serve as a potential stem cell source for allo-HCTs. Most importantly, the combination of allo-HCT and HSC gene therapy has the potential to treat a wide array of hematologic and nonhematologic disorders.
Postoperative Ultrasound in Kidney Transplant Recipients: Association Between Intrarenal Resistance Index and Cardiovascular Events
Authors: van de Kuit Anouk , Benjamens Stan , Sotomayor Camilo G. , Rijkse Elsaline , Berger Stefan P. , Moers Cyril , Bakker Stephan J.L. , Minnee Robert C. , Yakar Derya , Pol Robert A.
Published: December 2020

Background.

Doppler ultrasound, including intrarenal resistance index (RI) measurement, is a widely used modality to assess kidney transplantation (KTx) vascularization. The aim of this study is to gain insight in the associations between early postoperative RI measurements and cardiovascular events (CVEs), all-cause mortality, and death-censored graft survival.

Methods.

From 2015 to 2017, a prospective cohort study was conducted in patients in which RI measurement was performed immediately after KTx. The RI was calculated as (peak systolic velocity—end-diastolic velocity)/peak systolic velocity. End points were CVEs, all-cause mortality, and graft failure. Kaplan-Meier analyses (logrank test) were used for differences in end points. Univariate and multivariate associations were investigated by means of Cox regression analyses.

Results.

RI cutoff of 0.70 was used. We included 339 recipients, of which 271 (80%) had an RI ≤ 0.70 and 68 (20%) had an RI > 0.70. CVEs were observed in 27 (8%) patients, 27 (8%) patients died, and 17 (5%) patients had graft failure during a median follow-up of 37 months (interquartile range, 33–43). Kaplan-Meier analyses and univariate Cox regression indicated a significant association with overall CVE-free survival (hazard ratios [HR], 2.79; P = 0.011; logrank test, P = 0.008) and all-cause mortality (HR, 2.59; P = 0.017; logrank test, P = 0.013) for patients with an RI above and below 0.70. An independent association was shown between an RI > 0.70 and CVE-free survival (HR, 2.48; P = 0.042) when deceased donation was not included in the model.

Conclusions.

In the early postoperative period, a high RI showed to be associated with CVEs after adjustment for cardiovascular risk factors, whereas no independent association was found with overall survival and graft failure. For the interpretation of RI measurements after KTx surgery, patients’ cardiovascular state should be taken into consideration.
Assessing model mismatch and model selection in a Bayesian uncertainty quantification analysis of a fluid-dynamics model of pulmonary blood circulation
Authors: Paun L. Mihaela , Colebank Mitchel J. , Olufsen Mette S. , Hill Nicholas A. , Husmeier Dirk
Published: December 2020

This study uses Bayesian inference to quantify the uncertainty of model parameters and haemodynamic predictions in a one-dimensional pulmonary circulation model based on an integration of mouse haemodynamic and micro-computed tomography imaging data. We emphasize an often neglected, though important source of uncertainty: in the mathematical model form due to the discrepancy between the model and the reality, and in the measurements due to the wrong noise model (jointly called ‘model mismatch’). We demonstrate that minimizing the mean squared error between the measured and the predicted data (the conventional method) in the presence of model mismatch leads to biased and overly confident parameter estimates and haemodynamic predictions. We show that our proposed method allowing for model mismatch, which we represent with Gaussian processes, corrects the bias. Additionally, we compare a linear and a nonlinear wall model, as well as models with different vessel stiffness relations. We use formal model selection analysis based on the Watanabe Akaike information criterion to select the model that best predicts the pulmonary haemodynamics. Results show that the nonlinear pressure–area relationship with stiffness dependent on the unstressed radius predicts best the data measured in a control mouse.
Mechanism and regulation of P element transposition
Authors: Ghanim George E. , Rio Donald C. , Teixeira Felipe Karam
Published: December 2020

P elements were first discovered in the fruit fly
Drosophila melanogaster
as the causative agents of a syndrome of aberrant genetic traits called hybrid dysgenesis. This occurs when P element-carrying males mate with females that lack P elements and results in progeny displaying sterility, mutations and chromosomal rearrangements. Since then numerous genetic, developmental, biochemical and structural studies have culminated in a deep understanding of P element transposition: from the cellular regulation and repression of transposition to the mechanistic details of the transposase nucleoprotein complex. Recent studies have revealed how piwi-interacting small RNA pathways can act to control splicing of the P element pre-mRNA to modulate transposase production in the germline. A recent cryo-electron microscopy structure of the P element transpososome reveals an unusual DNA architecture at the transposon termini and shows that the bound GTP cofactor functions to position the transposon ends within the transposase active site. Genome sequencing efforts have shown that there are P element transposase-homologous genes (called THAP9) in other animal genomes, including humans. This review highlights recent and previous studies, which together have led to new insights, and surveys our current understanding of the biology, biochemistry, mechanism and regulation of P element transposition.
Novel perspectives of target-binding by the evolutionarily conserved PP4 phosphatase
Authors: Karman Zoltan , Rethi-Nagy Zsuzsanna , Abraham Edit , Fabri-Ordogh Lilla , Csonka Akos , Vilmos Peter , Debski Janusz , Dadlez Michal , Glover David M. , Lipinszki Zoltan
Published: December 2020

Protein phosphatase 4 (PP4) is an evolutionarily conserved and essential Ser/Thr phosphatase that regulates cell division, development and DNA repair in eukaryotes. The major form of PP4, present from yeast to human, is the PP4c-R2-R3 heterotrimeric complex. The R3 subunit is responsible for substrate-recognition via its EVH1 domain. In typical EVH1 domains, conserved phenylalanine, tyrosine and tryptophan residues form the specific recognition site for their target's proline-rich sequences. Here, we identify novel binding partners of the EVH1 domain of the
Drosophila
R3 subunit, Falafel, and demonstrate that instead of binding to proline-rich sequences this EVH1 variant specifically recognizes atypical ligands, namely the FxxP and MxPP short linear consensus motifs. This interaction is dependent on an exclusively conserved leucine that replaces the phenylalanine invariant of all canonical EVH1 domains. We propose that the EVH1 domain of PP4 represents a new class of the EVH1 family that can accommodate low proline content sequences, such as the FxxP motif. Finally, our data implicate the conserved Smk-1 domain of Falafel in target-binding. These findings greatly enhance our understanding of the substrate-recognition mechanisms and function of PP4.
Detection and tracking of cracks based on thermoelastic stress analysis
Authors: Middleton C. A. , Weihrauch M. , Christian W. J. R. , Greene R. J. , Patterson E. A.
Published: December 2020

Thermoelastic stress analysis using arrays of small, low-cost detectors has the potential to be used in structural health monitoring. However, evaluation of the collected data is challenging using traditional methods, due to the lower resolution of these sensors, and the complex loading conditions experienced. An alternative method has been developed, using image decomposition to generate feature vectors which characterize the uncalibrated map of the magnitude of the thermoelastic effect. Thermal data have been collected using a state-of-the-art photovoltaic effect detector and lower cost, lower thermal resolution microbolometer detectors, during crack propagation induced by both constant amplitude and frequency loading, and by idealized flight cycles. The Euclidean distance calculated between the feature vectors of the initial and current state can be used to indicate the presence of damage. Cracks of the order of 1 mm in length can be detected and tracked, with an increase in the rate of change of the Euclidean distance indicating the onset of critical crack propagation. The differential feature vector method therefore represents a substantial advance in technology for monitoring the initiation and propagation of cracks in structures, both in structural testing and in-service using low-cost sensors.
Phantom of the forest or successful citizen? Analysing how Northern Goshawks (Accipiter gentilis) cope with the urban environment
Authors: Merling de Chapa Manuela , Courtiol Alexandre , Engler Marc , Giese Lisa , Rutz Christian , Lakermann Michael , Müskens Gerard , van der Horst Youri , Zollinger Ronald , Wirth Hans , Kenntner Norbert , Krüger Oliver , Chakarov Nayden , Müller Anna-Katharina , Looft Volkher , Grünkorn Thomas , Hallau André , Altenkamp Rainer , Krone Oliver
Published: December 2020

By 2040, roughly two-thirds of humanity are expected to live in urban areas. As cities expand, humans irreversibly transform natural ecosystems, creating both opportunities and challenges for wildlife. Here, we investigate how the Northern Goshawk (Accipiter gentilis) is adjusting to urban environments. We measured a variety of behavioural and ecological parameters in three urban and four rural study sites. City life appeared related to all parameters we measured. Urban female goshawks were overall 21.7 (CI95%5.13–130) times more likely to defend their nestlings from humans than rural females. Urban goshawks were 3.64 (CI95%2.05–6.66) times more likely to feed on pigeons and had diets exhibiting lower overall species richness and diversity. Urban females laid eggs 12.5 (CI95%7.12–17.4) days earlier than rural individuals and were 2.22 (CI95%0.984–4.73) times more likely to produce a brood of more than three nestlings. Nonetheless, urban goshawks suffered more from infections with the parasiteTrichomonas gallinae, which was the second most common cause of mortality (14.6%), after collisions with windows (33.1%). In conclusion, although city life is associated with significant risks, goshawks appear to thrive in some urban environments, most likely as a result of high local availability of profitable pigeon prey. We conclude that the Northern Goshawk can be classified as an urban exploiter in parts of its distribution.
Seasonal shifts in the competitive ability of macroalgae influence the outcomes of coral–algal competition
Authors: Brown Kristen T. , Bender-Champ Dorothea , Hoegh-Guldberg Ove , Dove Sophie
Published: December 2020

Understanding the effects of natural processes on coral–algal competition is an important step in identifying the role of macroalgae in perturbed coral reef ecosystems. However, studies investigating coral–algal interactions are often conducted in response to a disturbance, and rarely incorporate seasonal variability. Here, naturally occurring coral–algal interactions were assessedin situfour times a year over 2 years across eight sites spanning diverse benthic communities. In over 6500 recorded coral–algal interactions, cyanobacteria and turf algae were found to be the most damaging regardless of season, resulting in visible damage to coral in greater than 95% of interactions. Macroalgae that primarily compete using chemical mechanisms were found to be more damaging than those that compete using physical mechanisms (e.g. abrasion), with both groups demonstrating decreased competitive ability in summer. While crustose coralline algae were the least damaging to competing coral, during summer, it became three times more competitive. Our results demonstrate that the competitive ability of macroalgae and the outcomes of coral–algal competition can fluctuate in seasonal cycles that may be related to biomass, production of chemical defences and/or physical toughness. The results of this study have important implications for understanding the trajectory and resilience of coral reef ecosystems into the future.
GARD is a pan-cancer predictor of radiation therapy benefit
Authors: Scott Jacob G. , Sedor Geoffrey , Ellsworth Patrick , Scarborough Jessica A. , Ahmed Kamran , Oliver Daniel E. , Eschrich Steven A. , Torres-Roca Javier F. , Kattan Michael W.
Published: December 2020

Background

Despite advances in cancer genomics, radiation therapy (RT) is still prescribed based on an empiric one-size-fits-all paradigm. Previously, we proposed a novel algorithm using the genomic adjusted radiation dose (GARD) to personalize RT prescription dose based on the biological effect of a given physical RT dose, calculated using individual tumor genomics. We hypothesize that GARD will reveal interpatient heterogeneity associated with opportunities to improve outcomes compared to physical RT dose alone. To test this hypothesis, and the GARD-based RT dosing paradigm, we performed a pooled pan-cancer analysis in 11 separate clinical cohorts of 1,615 unique patients with 7 different cancer types that represent all available cohorts with the data required to calculate GARD, together with clinical outcome.

Methods

Using 11 previously-published datasets of cancers including breast, head and neck, non-small cell lung, pancreas, endometrium, melanoma and glioma, we defined two clinical endpoints: (i) time to first recurrence and (ii) overall survival, comprising 1,298 (982 +RT, 316 -RT) and 677 patients (424 +RT, 253 -RT), respectively. We used Cox regression stratified by cohort to test association between GARD and outcome with separate models using RT dose and sham-GARD for comparison. Interaction tests between GARD and treatment (+/- RT) were performed using the Wald statistic.

Results

Pooled analysis of all available data reveal that GARD as a continuous variable is associated with recurrence (HR = 0.982, CI [0.970, 0.994], p = 0.002) and survival (HR = 0.970, CI [0.953, 0.988], p = 0.001). The interaction test revealed the effect of GARD on survival depends on whether or not that patient received RT (Wald statistic: p=0.011). Physical RT dose and sham-GARD were not significantly associated with either outcome.

Conclusions

The biologic effect of radiation therapy, as quantified by GARD, is significantly associated with recurrence and survival for those patients treated with radiation: it is predictive of RT benefit; and physical RT dose is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalizing RT prescription dose.
Development and Evaluation of Two Rapid Indigenous IgG-ELISA immobilized with ACE-2 Binding Peptides for Detection Neutralizing Antibodies Against SARS-CoV-2
Authors: Sil Bijon Kumar , Adnan Nihad , Oishee Mumtarin Jannat , Ali Tamanna , Jahan Nowshin , Khandker Shahad Saif , Kobatake Eiry , Mie Masayasu , Khondoker Mohib Ullah , Haq Md. Ahsanul , Jamiruddin Mohd. Raeed
Published: December 2020

COVID-19 pandemic situation demands effective serological tests with a view to adopting and developing policy for disease management, determining protective immunity as well as for sero-epidemiological study. Our study aims to develop and evaluate two rapid in-house ELISA assays targeting neutralizing antibodies (IgG) against S1 subunit of spike in SARS-CoV-2 and Receptor Binding Domain (RBD), as well as comparative analysis with nucleocapsid (NCP) ELISA. The assays were conducted with 184 samples in three panels collected from 134 patients. Panel 1 and 2 consist of RT-PCR positive samples collected within two weeks and after two weeks of symptom onset, respectively. Negative samples are included in panel 3 from healthy donors and pre-pandemic dengue patients. The total assay time has been set 30 minutes for both of the ELISA assays. Results show that S1 and RBD ELISA demonstrates 73.68% and 84.21% sensitivities, respectively for samples collected within two weeks, whereas 100% sensitivities were achieved by both for samples that were collected after two weeks of the onset of symptoms. S1-ELISA shows 0% positivity to panel 3 while for RBD-ELISA the figure is 1%. A strong correlation (rs=0.804, p<0.0001)) has been observed between these two assays. When compared with NCP-ELISA, S1 slightly better correlation (rs=0.800, p<0.0001) than RBD (rs=0.740, p<0.0001). Our study suggests S1-ELISA as more sensitive one than the RBD or nucleocapsid ELISA during the later phase of infection, while for overall sero-monitoring RBD specific IgG ELISA is recommended. Moreover, non-reactivity to dengue emphasize the use of these assays for serosurveillance of COVID-19 in the dengue endemic regions.

Highlights

The total assay time of these assays are 30 minutes.

Sensitivity of S1 specific IgG ELISA for samples tested within 14 days of disease presentation is 73.68% while RBD specific ELISA demonstrates a sensitivity of 84.21%,

Both of the assays under investigation can successfully detect all the cases (100% sensitivity) if the samples are tested after 14 days of onset of diseases.

Specificity of S1-ELISA assay is 100%, whereas RBD specific IgG ELISA is 99% specific.

The assays can be employed in dengue-endemic countries

Among the three in-house IgG ELISA, assay system specific to S1 is found to be more sensitive and specific for retrospective serosurveillance.

For acute to late phase, as well as retrospective serosurveillance of COVID-19, RBD-ELISA can be a method of choice for SARS-CoV-2 prevalent areas.
Knowledge, attitudes, and perceptions of the Greek population regarding the COVID-19 pandemic during the national lockdown (March 23 - May 03, 2020): A web-based cross-sectional study
Authors: Anestis Andreas , Lomvardeas Odysseas , Papadakis Nikolaos
Published: December 2020

Objective

The study assessed the knowledge, attitudes, and perceptions toward the COVID-19 pandemic during the total lockdown of spring 2020 in Greece.

Methods

A web-based cross-sectional study was conducted from April 13 to May 5, 2020. Adult residents of Greece anonymously completed an online survey that was distributed through email and social media. A total of 1396 fully complete questionnaires were collected. Demographic questions, questions regarding the knowledge about the disease etiology, diagnosis and prevention, and questions related to the respondents’ attitude and perception toward the restriction measures and the confidence in different kinds of institutions providing information were included in the survey items. The appropriate statistical analyses were conducted according to the type of variable and the research question.

Results

The highest knowledge scores were found in females (74.8%, p = 0.015), individuals over 60 years old (77.3%, p < 0.001) and individuals having completed post-secondary or tertiary education (76.5%, p < 0.001). Five attitude patterns toward the pandemic were identified: “trust in institutions”, “trust in the restriction measures”, “trust in media and the internet”, “trust in traditional institutions”, and “measures deniers”. Age, education, and knowledge score were the factors defining the attitudinal patterns revealed.

Conclusions

Education and public awareness of scientifically accurate information are the means for eliminating individually and socially irresponsible and dangerous behaviors and protecting public health in periods of health crises.
Immunogenicity and crossreactivity of antibodies to SARS-CoV-2 nucleocapsid protein
Authors: Dobaño Carlota , Santano Rebeca , Jiménez Alfons , Vidal Marta , Chi Jordi , Melero Natalia Rodrigo , Popovic Matija , López-Aladid Rubén , Fernández-Barat Laia , Tortajada Marta , Carmona-Torre Francisco , Reina Gabriel , Torres Antoni , Mayor Alfredo , Carolis Carlo , García-Basteiro Alberto L. , Aguilar Ruth , Moncunill Gemma , Izquierdo Luis
Published: December 2020

COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We indentified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognised N229E N, and IgGs to HKU1 N recognised SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha-rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.