bluuebunny/crossref_metadata_2025 huggingface dataset:
Chondrocyte‐to‐osteoblast transformation in mandibular fracture repair
Authors: Wong Sarah A. , Hu Diane P. , Slocum Joshua , Lam Charles , Nguyen Michael , Miclau Theodore , Marcucio Ralph S. , Bahney Chelsea S.
Published: November 2020

The majority of fracture research has been conducted using long bone fracture models, with significantly less research into the mechanisms driving craniofacial repair. However, craniofacial bones differ from long bones in both their developmental mechanism and embryonic origin. Thus, it is possible that their healing mechanisms could differ. In this study we utilize stabilized and unstabilized mandible fracture models to investigate the pathways regulating repair. Whereas fully stable trephine defects in the ramus form bone directly, mechanical motion within a transverse fracture across the same anatomical location promoted robust cartilage formation before boney remodeling. Literature investigating long bone fractures show chondrocytes are a direct precursor of osteoblasts during endochondral repair. Lineage tracing with Aggrecan‐CreERT2::Ai9 tdTomato mice demonstrated that mandibular callus chondrocytes also directly contribute to the formation of new bone. Furthermore, immunohistochemistry revealed that chondrocytes located at the chondro‐osseous junction expressed Sox2, suggesting that plasticity of these chondrocytes may facilitate this chondrocyte‐to‐osteoblast transformation. Based on the direct role chondrocytes play in bone repair, we tested the efficacy of cartilage grafts in healing critical‐sized mandibular defects. Whereas empty defects remained unbridged and filled with fibrous tissue, cartilage engraftment produced bony‐bridging and robust marrow cavity formation, indicating healthy vascularization of the newly formed bone. Engrafted cartilage directly contributed to new bone formation since a significant portion of the newly formed bone was graft/donor‐derived. Taken together these data demonstrate the important role of chondrocyte‐to‐osteoblast transformation during mandibular endochondral repair and the therapeutic promise of using cartilage as a tissue graft to heal craniofacial defects.
Subgingival microbiome is associated with alveolar bone loss measured 5 years later in postmenopausal women
Authors: LaMonte Michael J. , Andrews Christopher A. , Hovey Kathleen M. , Buck Michael J. , Li Lu , McSkimming Daniel I. , Banack Hailey R. , Rotterman Jane , Sun Yijun , Kirkwood Keith L. , Wactawski‐Wende Jean
Published: November 2020

Background

The aim of this study was to quantify the association between subgingival microbiota and periodontal disease progression in older women, for which limited published data exist.

Methods

A total of 1016 postmenopausal women, aged 53 to 81 years, completed baseline (1997 to 2001) and 5‐year (2002 to 2006) dental exams that included probing depth, clinical attachment level, gingival bleeding, and radiographic alveolar crestal height (ACH). Baseline microbiota were measured in subgingival plaque using 16S rRNA sequencing. Associations between 52 microbiota we previously found statistically significantly associated with clinical periodontal disease at baseline, were examined with disease progression. The traditional Socransky microbiota complexes also were evaluated. Side‐by‐side radiograph comparisons were used to define progression as ≥2 teeth with ≥1 mm ACH loss or ≥1 new tooth loss to periodontitis. The association between baseline centered log(2) ratio transformed microbial relative abundances and 5‐year periodontal disease progression was measured with generalized linear models.

Results

Of 36 microbiota we previously showed were elevated in moderate/severe disease at baseline, 24 had statistically significantly higher baseline mean relative abundance in progressing compared with non‐progressing women (P < .05, all); which included all Socransky red bacteria (P. gingivalis, T. forsythia, T. denticola). Of 16 microbiota elevated in none/mild disease at baseline, five had statistically significantly lower baseline abundance in non‐progressing compared with progressing women (P < 0.05, all), including one Socransky yellow bacteria (S. oralis). When adjusted for baseline age, socioeconomic status, and self‐rated general health status, odds ratios for 5‐year progression ranged from 1.18 to 1.51 (per 1‐standard deviation increment in relative abundance) for microbiota statistically significantly (P < 0.05) positively associated with progression, and from 0.77 to 0.82 for those statistically significantly (P < 0.05) inversely associated with progression. These associations were similar when stratified on baseline levels of pocket depth, gingival bleeding, ACH, and smoking status.

Conclusions

These prospective results affirm clearly that subgingival microbiota are measurably elevated several years prior to progression of alveolar bone loss, and include antecedent elevations in previously undocumented taxa additional to known Socransky pathogenic complexes.
Detection of the historical Askja ad 1875 and modern Icelandic cryptotephras in varved lake sediments – results from a first systematic search in northern Poland
Authors: Kinder MaŁgorzata , Wulf Sabine , Appelt Oona
Published: November 2020

Volcanic ash can disperse thousands of kilometres from the source volcano and provide valuable chronostratigraphic markers for palaeoclimate studies. We present new cryptotephra findings of historical and modern Icelandic eruptions in annually laminated lacustrine sediment records from several sites within a 570 km SW–NE transect across northern Poland. Sediments from the two lakes Wąsoskie and Szurpiły contain glass shards originating from the Plinian Askja ad 1875 eruption and showing bimodal, rhyolitic and dacitic affinities. A further cryptotephra finding in Lake Lubińskie suggests a potential origin from the Hekla ad 1845 eruption. These new findings extend the tephra dispersal map towards the south‐east and provide valuable isochrons for the synchronisation of palaeoclimate proxy data at the termination of the Little Ice Age in central eastern Europe. Very low glass concentrations of modern cryptotephra in Lake Wąsoskie were potentially correlated with the Eyjafjallajökull ad 2010 eruption. Further findings in the uppermost sediments of lakes Szurpiły and Żabińskie in north‐eastern Poland tentatively suggest other sources from either the Hekla and/or Kamchatkan volcanoes.
Sandwich‐based surface‐enhanced Raman scattering probes for detection and quantification of malaria
Authors: Mhlanga Nikiwe , Domfe Thulaganyo , Skepu Amanda , Ntho Thabang A.
Published: November 2020

Malaria continues to be endemic in the middle‐ to low‐resourced regions of the world. One of the World Health Organization (WHO) global technical strategy goals towards 2030 is to lower the malaria infection by 90%. Attaining this ambitious goal entails early and accurate diagnosis of the parasite that will inform treatment measures to be taken. Herein, we report on the application of the surface‐enhanced Raman spectroscopy (SERS) platform to fabricate malaria bio‐sensing probes: lactate dehydrogenase (LDH) malaria antibodies (mAb) were immobilized on a SERS substrate and used to capture Plasmodium falciparum (pf) malaria antigen. A detection hybrid, Ag plasmonic metals labelled with a Raman reporter (SERS tag) and conjugated to a second LDH mAb, was hybridized on the captured antigen. The detection hybrid binds the antigen on a specific epitope, and the sandwich is interpreted using vibrational Raman spectroscopy that indirectly confirms the pfLDH malaria antigen via the Raman reporter label. The SERS probes showed specificity, sensitivity and rapidity in the detection of pfLDH. They are proposed for secondary confirmation of field‐based lateral flows and offer improved sensitivity and quantification capabilities.
Black tonal level reproduction in pulse‐width‐modulated high dynamic range displays
Authors: Boitard Ronan , Ploumis Stelios , Kumaran Raveen , Damberg Gerwin , Ballestad Anders
Published: November 2020

High dynamic range (HDR) workflows provide increased peak luminance and lower black levels leading to a significantly enhanced quality of experience. HDR pixels also represent more tonal values across the dynamic range by using a higher bit‐depth along with different perceptual transfer functions. However, many light‐emitting display devices modulate light using a limited bit‐depth in the linear domain. It is thus challenging for such display systems to achieve simultaneously high peak luminance and high amount of information in the shadows. In this paper, we summarize pulse‐width modulation (PWM) principles and its impact on low black level reproduction. We then assess the required bit‐depth to accurately reproduce shadow information of an HDR signal for different display capabilities. Finally, we describe several technology improvements that could improve the tonal level reproduction of PWM‐driven displays.
Predictors of Long‐Term Nasal Obstruction Symptom Evaluation Score Stability Following Septoplasty With Inferior Turbinate Reduction
Authors: Law Richard H. , Bazzi Talal D. , Van Harn Meredith , Craig John R. , Deeb Robert H.
Published: November 2020

Objectives/Hypothesis

Determine the postoperative Nasal Obstruction Symptom Evaluation (NOSE) score stability between 1 and ≥6 months after septoplasty with inferior turbinate reduction (ITR). Education level and occupation were evaluated to determine their effects on NOSE score stability during the postoperative period.

Study Design

Retrospective case series.

Methods

This was a retrospective case series. Patients were included if they underwent septoplasty with ITR for nasal obstruction due to septal deviation and inferior turbinate hypertrophy. NOSE scores were collected preoperatively, and at 1 and ≥6 months postoperatively. Education level and occupation were collected postoperatively via telephone survey. Changes in NOSE scores were compared between the different time points. Education level and occupation were analyzed to determine if they affected NOSE scores.

Results

There were 98 patients included, and 56 were male (57.1%). Mean NOSE scores preoperatively and at 1 and ≥6 months postoperatively were 72.1, 17.1, and 12.0, respectively. Patients demonstrated a statistically and clinically significant reduction in NOSE score at 1 month (−54.9, P < .001) and at ≥6 months postoperatively (−60.0, P < .001). The mean 6.2‐point decrease in NOSE score from 1 to ≥6 months was statistically, but not clinically significant. There were no significant differences in NOSE score changes based on educational level and occupation.

Conclusions

Patients achieved statistically and clinically significant reductions in NOSE scores at 1 months, with no clinically significant differences in NOSE scores at ≥6 months, suggesting NOSE score stability between these postoperative time points. Neither education level nor occupation influenced NOSE scores.

Level of Evidence

4 Laryngoscope, 131:E2105–E2110, 2021
Anterior Pedicled Lateral Nasal Wall Flap for Endonasal Lining: A Radiologic and Anatomical Study
Authors: Langdon Cristóbal , Yuen‐Ato Kathy , Pereira‐Perez Carla , Arancibia Claudio , Alobid Isam
Published: November 2020

Objectives/Hypothesis

The objective of this radiological/anatomical study was to evaluate the feasibility of a new endoscopic technique that uses the anterior pedicled lateral nasal flap (APLNW) for the endonasal lining in complex nasal reconstructions.

Study Design

An anatomical study was performed on 20 nasal fossae of cadaverous specimens to measure the area and lengths of the anterior pedicled nasal lateral wall flap. In addition, a radiological analysis with computed tomography was performed in 150 nostrils to determine the potential donor of the simple and extended flap in the nasal fossa floor. Complex nasal reconstruction with nasofrontal flap and internal lining using the lateral wall pedicled flap was performed in 3 patients.

Results

Complete reconstruction for the inner lining of the nasal tip and lateral nasal wall was achieved in the cadaveric study (10 specimens). The surface areas of the simple and extended APLNW flaps were 7.53 (standard deviation [SD] 1.25) cm2 and 24.6 (SD 3.14) cm2, respectively. Using computed tomography scans, we determined that to reconstruct defects secondary to full‐thickness nasal defects, the APLNW flap surface for the simple and extended versions was 7.90 (SD 1.68) cm2 and 23.64 (SD 4.7) cm2. We present one case were the APLNW flap was used.

Conclusions

The simple or expanded APLNW flap represents a feasible option to reconstruct the internal lining in complex nasal reconstruction.

Level of Evidence

NA Laryngoscope, 131:E1462–E1467, 2021
Needlestick Injury in Otolaryngology–Head and Neck Surgery Resident Programs
Authors: Ahadizadeh Emily N. , Quintanilla‐Dieck Lourdes , Pfeifer Hailey , Wax Mark K.
Published: November 2020

Objectives/Hypothesis

Up to 800,000 percutaneous injuries involving healthcare workers occur each year. The morbidity of needlestick injuries (NSIs) ranges from nothing to death. The incidence of NSI in otolaryngology residency is deemed to be high based on prior studies. This study aimed at defining the trends in otolaryngology residents regarding sharps exposure.

Study Design

Cross‐sectional study using survey/questionnaire.

Methods

Otolaryngology accredited residency programs in North America were surveyed in 2013 and 2017 regarding their experience with NSI and perceived risk of acquiring a blood‐borne infection.

Results

Surveys were received from 314 residents (31 programs). There was a total of 509 needlesticks, primarily occurring during junior years (post‐graduate year 1–3, 81%). Sixty‐eight percent of residents had experienced an NSI. Of the residents that had an injury, the mean number of sticks was 2.37 sticks/resident. Junior residents were less likely to report their injury compared to senior residents (50% vs. 30%). The primary reason for not reporting was the time commitment. Residents underestimated their risk of acquiring human immunodeficiency virus (51% of residents) and overestimated their risk of acquiring hepatitis C virus (90% of residents).

Conclusions

Occupational exposure is high in healthcare and particularly high in surgical trainees. The majority of otolaryngology trainees undergo a needlestick injury in their junior years. There continues to be underreporting of these injuries by residents, who report that the process is too time‐consuming. Most residents do not have an accurate understanding of their actual risk of acquiring a blood‐borne disease. These findings emphasize the need for education regarding risks and development of strategies to encourage reporting of injuries.

Level of Evidence

VI Laryngoscope, 131:E1076–E1080, 2021
Radiotherapy in Metastatic Oropharyngeal Cancer
Authors: Nguy Susanna , Oh Cheongeun , Karp Jerome M. , Wu Shengyang Peter , Li Zujun , Persky Michael J. , Hu Kenneth S. , Givi Babak , Tam Moses M.
Published: November 2020

Objectives

The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy.

Methods

We queried the NCDB from 2004–2015 for metastatic OPSCC patients at diagnosis with known HPV‐status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan–Meier method, Cox proportional hazards model, and propensity score‐matched analysis adjusting for demographic and disease‐specific prognostic factors.

Results

Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV‐status. Among these 556 patients, 49% were HPV‐positive and 56% received head and neck radiotherapy. With a median follow‐up of 17.5 months (IQR 6.0–163.4 months), radiotherapy was associated with significantly improved 1‐year OS (67% vs 58%, log‐rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62–0.97 P = .029). In HPV‐status subgroup analysis, a survival benefit was identified in HPV‐positive patients (1‐year OS 77% vs 67%, log‐rank P < .001) but not in HPV‐negative patients. Results were consistent on a propensity score‐matched analysis of 212 HPV‐positive matched patients (HR 0.66, 95% CI 0.49–0.83, P < .001).

Conclusion

The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV‐status, head and neck radiotherapy was associated with longer survival in those with HPV‐associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners.

Level of Evidence

3 Laryngoscope, 131:E1847–E1853, 2021
On pointwise decay rates of time‐periodic solutions to the Navier–Stokes equation
Authors: Nakatsuka Tomoyuki
Published: November 2020

We study the existence of a time‐periodic solution with pointwise decay properties to the Navier–Stokes equation in the whole space. We show that if the time‐periodic external force is sufficiently small in an appropriate sense, then there exists a time‐periodic solution of the Navier–Stokes equation such that and uniformly in as . Our solution decays faster than the time‐periodic Stokes fundamental solution and the faster decay of its spatial derivatives of higher order is also described.
Intravascular BOLD signal characterization of balanced SSFP experiments in human blood at high to ultrahigh fields
Authors: Pérez‐Rodas Marlon , Pohmann Rolf , Scheffler Klaus , Heule Rahel
Published: November 2020

Purpose

To investigate the intravascular contribution to the overall balanced SSFP (bSSFP) BOLD effect in human blood at high to ultrahigh field strengths (3 T, 9.4 T, and 14.1 T).

Methods

Venous blood prepared at two different oxygenation levels (deoxygenated: Y ≈ 71%, oxygenated: Y ≈ 94%) was measured with phase‐cycled bSSFP for varying TRs/flip angles at 3 T, 9.4 T, and 14.1 T. The oxygen sensitivity was analyzed by intrinsic MIRACLE (motion‐insensitive rapid configuration relaxometry)‐R2 estimation and passband signal differences. The intravascular BOLD‐related signal change was extracted from the measured data for microvasculature and macrovasculature, and compared with the extravascular contribution obtained by Monte Carlo simulations.

Results

The MIRACLE‐R2 values showed a characteristic increase with longer TRs in deoxygenated blood, corroborating that SE‐R2 data cannot be used to assess the intravascular bSSFP BOLD effect. Passband bSSFP signal differences measured at optimal flip angles of 30° at 3 T and 20° at 9.4 T/14.1 T revealed considerable relative intravascular contributions of 95%/70% at 3 T, 74%/43% at 9.4 T, 66%/46% at 14.1 T for TR = 5 ms, and 90%/65% at 3 T, 36%/27% at 9.4 T, 13%/15% at 14.1 T for TR = 10 ms in macrovascular/microvascular regimes.

Conclusion

The results indicate that intravascular effects have to be considered to better understand the origin of bSSFP BOLD contrast in functional MRI experiments, especially at short TRs. The MIRACLE‐R2 method demonstrated the ability to quantify the apparent decrease in R2 due to rapid RF refocusing.
Optimal segments for forwarding table size minimization in segment‐routed SDNs
Authors: Anbiah Anix , Sivalingam Krishna M.
Published: November 2020

Segment routing (SR) is a source routing paradigm where packet forwarding is based on a sequence of instructions known as segments identified using segment IDs (SIDs). An ordered list of SIDs identifies the source route and is carried in the packet headers. Switches in such networks use the SIDs to look up their forwarding tables and forward packets along the segments. Since various flows can share the segments, SR is a mechanism to avoid per‐flow state thereby minimizing the forwarding table size (FTS) of the switches. Software‐defined networks (SDNs) are suitable for SR since the source routing can be accomplished by a centralized controller. Typically, the segment list is limited to a maximum segment list depth (SLD). It can be shown that FTS varies inversely as the SLD. This paper studies the problem of minimizing the FTS given the set of flows and the SLD limitation, which is shown to be NP‐complete. An ILP formulation of the problem is used to solve the problem in relatively small networks. Two different heuristic solutions, BFH and CCH, are presented to solve this problem in large‐scale networks with up to 30,000 nodes and 250,000 flows and for three different network topologies (ring‐of‐rings, fat‐tree, and mesh). The heuristics are shown to perform up to 50% better than an existing FTS minimization technique. Further, CCH is shown to perform better in networks with a high prevalence of equal cost multipaths (ECMPs), while BFH performs better when ECMPs are few in number.
Degenerative joint disease in the Chalcolithic population of El Mirador cave (Sierra de Atapuerca, Spain): The vertebral column
Authors: Yustos Marta , Lozano Marina , Morales Juan I. , Iglesias‐Bexiga Javier , Vergès Josep M.
Published: November 2020

Degenerative joint disease (DJD) is one of the most common pathological conditions identified in the archaeological record and remains a health problem in modern populations. This study aimed to evaluate DJD of the vertebral column in a sample from a Chalcolithic collective burial at El Mirador cave (Sierra de Atapuerca, Spain) dated to 4,880–4,390 years cal. BP. Most of the human remains recovered were commingled and are in a good state of preservation. Traditionally, far too little attention has been paid to skeletal remains from secondary contexts. Bearing in mind the limitations inherent to this type of study, in this work, we applied an adapted methodology to examine the degree of vertebral degeneration considering the skeletal changes associated with DJD (i.e., osteophyte formation, porosity, lipping and/or eburnation). All data were evaluated at the 0.05 level using the chi‐squared statistic, and comparisons were made between age groups and between the spine regions. Our results showed a higher prevalence of DJD in the lumbar region, although eburnation was the least observed marker in the sample. Additionally, significant differences were found between age groups, with a greater manifestation of DJD in vertebral elements associated with the adult group. These results are consistent with those of other studies and are based on the hypothesis that DJD is highly correlated with age. Overall, the degree of vertebral degeneration is low, but taken together, these results suggest that some individuals from El Mirador cave may have suffered from DJD. Furthermore, the methodology proposed has demonstrated that valuable information can be obtained from commingled skeletal assemblages.
Osteocyte lacuno‐canalicular microstructure across the mid‐shaft femur in adult males from medieval England
Authors: Drew Elizabeth R. , Mahoney Patrick , Miszkiewicz Justyna J.
Published: November 2020

Archaeological human bone histology can reveal well‐preserved osteocyte lacunae, which are indicators of bone remodelling activity. Analyses of these lacunae can be useful when reconstructing past human mechanical loading histories or metabolic fluctuations from bone microstructure. However, the relationship between osteocyte lacunae density and morphology, and bone anatomical variation within archaeological samples is largely unknown. We examined osteocyte lacuno‐canalicular network morphology in medieval human femora to test if osteocyte lacunae change with anatomical site location. Osteocyte lacunae density (Ot.Dn) data were analysed statistically in 10 middle‐aged (35–50 years old) males dated to the 11th–16th century AD (Canterbury, England). A subsequent case study (n = 2) was conducted using two well‐preserved samples from which canaliculi number per lacuna (Ci.N) and canaliculi‐rich lacunae density (Ci.Dn) were preliminarily examined descriptively. The data were collected from cortical bone regions encompassing intracortical to subperiosteal mid‐shaft femoral bone, comparing anterior, posterior, medial and lateral locations interindividually and intraindividually. Results show that Ot.Dn varied significantly between the four anatomical regions (p = 0.001), with the medial and lateral femoral regions showing the highest median Ot.Dn. The median of Ci.N was also the highest on the medial aspect, but Ci.Dn did not change greatly across the four apects of the bone. The combination of these results suggests that mid‐shaft femoral anatomical location, which undergoes morphological change with biomechanical load, affects the expression of bone microstructure at the osteocyte lacuna level. This knowledge will benefit future osteoarchaeological methods that infer past behaviour from the human femur.
On an environmental sustainability problem
Authors: Viscolani Bruno
Published: November 2020

Beltratti et al proposed an environmental sustainability problem and stressed the importance of two related control problems, namely, the discounted utilitarian problem and the long‐run utility problem. From the analysis of the latter, they obtained the definition of the Green Golden Rule (GGR). We discuss the optimal steady‐state solutions of the first problem and provide new results, completing the known information on it. Then we tackle the second problem and its equivalent NLP problem of maximizing the steady‐state utility. We obtain that the solutions to the NLP problem depend on the capital accumulation features, like those of the first problem. This corrects and completes the original analysis of the GGR.
A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low‐grade glioma
Authors: Wright Karen D. , Yao Xiaopan , London Wendy B. , Kao Pei‐Chi , Gore Lia , Hunger Stephen , Geyer Russ , Cohen Kenneth J. , Allen Jeffrey C. , Katzenstein Howard M. , Smith Amy , Boklan Jessica , Nazemi Kellie , Trippett Tanya , Karajannis Matthias , Herzog Cynthia , Destefano Joseph , Direnzo Jennifer , Pietrantonio Jay , Greenspan Lianne , Cassidy Danielle , Schissel Debra , Perentesis John , Basu Mitali , Mizuno Tomoyuki , Vinks Alexander A. , Prabhu Sanjay P. , Chi Susan N. , Kieran Mark W.
Published: November 2020

Background

To evaluate efficacy, pharmacokinetics (PK) and pharmacodynamics of single‐agent everolimus in pediatric patients with radiographically progressive low‐grade glioma (LGG).

Methods

Everolimus was administered at 5 mg/m2 once daily as a tablet or liquid for a planned 48‐week duration or until unacceptable toxicity or disease progression. Patients with neurofibromatosis type 1 were excluded. PK and pharmacodynamic endpoints were assessed in consenting patients.

Results

Twenty‐three eligible patients (median age 9.2 years) were enrolled. All patients received prior chemotherapy (median number of prior regimens two) and/or radiotherapy (two patients). By week 48, two patients had a partial response, 10 stable disease, and 11 clinical or radiographic progression; two discontinued study prior to 1 year (toxicity: 1, physician determination: 1). With a median follow up of 1.8 years (range 0.2‐6.7 years), the 2‐, 3‐, and 5‐year progression‐free survivals (PFS) were 39 ± 11%, 26 ± 11%, and 26 ± 11%, respectively; two patients died of disease. The 2‐, 3‐, and 5‐year overall survival (OS) were all 93 ± 6%. Grade 1 and 2 toxicities predominated; two definitively related grade 3 toxicities (mucositis and neutropenia) occurred. Grade 4 elevation of liver enzymes was possibly related in one patient. Predose blood levels showed substantial variability between patients with 45.5% below and 18.2% above the target range of 5‐15 ng/mL. Pharmacodynamic analysis demonstrated significant inhibition in phospho‐S6, 4E‐BP1, and modulation of c‐Myc expression.

Conclusion

Daily oral everolimus provides a well‐tolerated, alternative treatment for multiple recurrent, radiographically progressive pediatric LGG. Based on these results, everolimus is being investigated further for this patient population.
Graphitic nanoparticles functionalized with epoxy moiety for enhancing the mechanical performance of hybrid carbon fiber reinforced polymer laminated composites
Authors: Khan Nazrul Islam , Halder Sudipta , Das Subhankar , Goyat Manjeet S.
Published: November 2020

Exceptional properties and unique structural features of graphene make it a successful secondary reinforcing agent for the enhancement of mechanical performance of hybrid carbon fiber reinforced polymer (CFRP) composites. In this study, graphitic nanoparticles (GrNPs) were functionalized with the epoxy moieties through the traditional silanization method and an innovative approach of grafting with epichlorohydrin and then reinforced in epoxy system to prepare nanocomposites and hybrid CFRP laminated composites. The morphological, structural, and thermal investigation revealed the successful functionalization of GrNPs. The tensile strengths of the nanocomposites were found significantly enhanced by ~36% due to incorporation of silanized GrNPs and ~30% due to incorporation of epichlorohydrin grafted GrNPs compared to the neat epoxy. The tensile strengths of the resulting CFRP composites reinforced with silanized and epichlorohydrin grafted GrNPs showed ~37% and ~36% improvements, respectively, as compared to the control sample. Comparing the results of silanized and epichlorohydrin grafted GrNPs nanocomposites, it has been found that silanization has better potential to improve the mechanical performance of the hybrid CFRP composites as compared to epichlorohydrin grafting.
Fetal mitochondrial DNA in maternal plasma in surrogate pregnancies: Detection and topology
Authors: Ma Mary‐Jane L. , Yakovenko Sergey , Zhang Haiqiang , Cheng Suk Hang , Apryshko Valentina , Zhavoronkov Alex , Jiang Peiyong , Chan K. C. Allen , Chiu Rossa W. K. , Lo Y. M. Dennis
Published: November 2020

Objectives

Due to the maternally‐inherited nature of mitochondrial DNA (mtDNA), there is a lack of information regarding fetal mtDNA in the plasma of pregnant women. We aim to explore the presence and topologic forms of circulating fetal and maternal mtDNA molecules in surrogate pregnancies.

Methods

Genotypic differences between fetal and surrogate maternal mtDNA were used to identify the fetal and maternal mtDNA molecules in plasma. Plasma samples were obtained from the surrogate pregnant mothers. Using cleavage‐end signatures of BfaI restriction enzyme, linear and circular mtDNA molecules in maternal plasma could be differentiated.

Results

Fetal‐derived mtDNA molecules were mainly linear (median: 88%; range: 80%–96%), whereas approximately half of the maternal‐derived mtDNA molecules were circular (median: 51%; range: 42%–60%). The fetal DNA fraction of linear mtDNA was lower (median absolute difference: 9.8%; range: 1.1%–27%) than that of nuclear DNA (median: 20%; range: 9.7%–35%). The fetal‐derived linear mtDNA molecules were shorter than the maternal‐derived ones.

Conclusion

Fetal mtDNA is present in maternal plasma, and consists mainly of linear molecules. Surrogate pregnancies represent a valuable clinical scenario for exploring the biology and potential clinical applications of circulating mtDNA, for example, for pregnancies conceived following mitochondrial replacement therapy.
High strength and bioactivity polyvinyl alcohol/collagen composite hydrogel with tannic acid as cross‐linker
Authors: Bai Zhongxiang , Wang Tianyou , Zheng Xin , Huang Yanping , Chen Yining , Dan Weihua
Published: November 2020

Hydrogels have great potential applications in biomedical materials, but their applications in complex physiological environments are severely limited by their weak strength and biotoxicity. Generally, synthetic polymer hydrogels and natural polymer hydrogels have complementary advantages in terms of mechanical strength and biological activity. Herein, tannic acid (TA), a natural material, was introduced into the polyvinyl alcohol/collagen (PVA‐COL) double network to prepare a hydrogel (PVA‐COL‐TA) with good bioactivity and mechanical properties. The tensile strength of the composite hydrogel can reach up to 20 times that of the pure PVA hydrogel. And the hydrogel after swelling under physiological conditions also exhibits stable mechanical properties. The introduction of TA can reduce the degradation rate of COL, enabling it to continue to exert biological activity. in vitro cytocompatibility experiments showed that PVA‐COL‐TA hydrogel has good sustained biological activity and the potential for biomedical materials.
Effect of molecular weight on molecular orientation and morphology of polypropylene sheets containing a β‐nucleating agent
Authors: Phulkerd Panitha , Yamazaki Atsuro , Iwasaki Shohei , Yamaguchi Masayuki
Published: November 2020

In this study, polypropylene (PP) films containing the β nucleating agent,N,N′‐dicyclohexyl‐2,6‐naphthalenedicarboxamide, were prepared using PP with three different molecular weights (low, medium, and high) by extrusion process with T‐shaped die. The structure and morphology of the films were studied after stretching. It was found that a unique molecular orientation, in which both thec‐axis and crystalline lamellae were oriented perpendicular to the flow direction, was formed in all undrawn film samples, irrespective of the molecular weights of the PP. In the PP sheets stretched in the machine direction, the low‐molecular‐weight sample containing the nucleating agent exhibited brittle properties owing to a lack of tie chains in the stretching direction. In contrast, cavitation was prominent in the medium (M‐PP)‐ and high (H‐PP)‐molecular‐weight samples. Notably, M‐PP containing the nucleating agent, with a high degree of molecular orientation, promoted the formation of a large number of voids. In H‐PP containing the nucleating agent, the presence of numerous tie chains inhibited cavitation, resulting in fewer voids. The experimental results demonstrated the influence of the molecular weight on the void structure, which will be useful in the field of microporous membranes.
In‐depth interrogation of protein thermal unfolding data with MoltenProt
Authors: Kotov Vadim , Mlynek Georg , Vesper Oliver , Pletzer Marina , Wald Jiri , Teixeira‐Duarte Celso M. , Celia Herve , Garcia‐Alai Maria , Nussberger Stephan , Buchanan Susan K. , Morais‐Cabral João H. , Loew Christian , Djinovic‐Carugo Kristina , Marlovits Thomas C.
Published: November 2020

Protein stability is a key factor in successful structural and biochemical research. However, the approaches for systematic comparison of protein stability are limited by sample consumption or compatibility with sample buffer components. Here we describe how miniaturized measurement of intrinsic tryptophan fluorescence (NanoDSF assay) in combination with a simplified description of protein unfolding can be used to interrogate the stability of a protein sample. We demonstrate that improved protein stability measures, such as apparent Gibbs free energy of unfolding, rather than melting temperature Tm, should be used to rank the results of thermostability screens. The assay is compatible with protein samples of any composition, including protein complexes and membrane proteins. Our data analysis software, MoltenProt, provides an easy and robust way to perform characterization of multiple samples. Potential applications of MoltenProt and NanoDSF include buffer and construct optimization for X‐ray crystallography and cryo‐electron microscopy, screening for small‐molecule binding partners and comparison of effects of point mutations.
Historical record of ammonium nitrate disasters
Authors: Prugh Richard W.
Published: November 2020

The recent incident in Beirut, Lebanon, on August 4, 2020, has raised the awareness of the explosion hazards of ammonium nitrate [AN]. Although AN has been used for many years as an ingredient in explosives and also as a fertilizer, recognition of AN as a self‐reactive material with the potential for detonation is not well‐known to regulatory authorities. As a consequence, inadequate control of storage has led to massive and disastrous explosions, typically following fire in the storage structures or in nearby storage of combustible materials. The purpose of this historical summary of AN incidents is to highlight the explosion hazards and to provide some insight into the measures that are needed to prevent such incidents.
Puerarin sensitized K562/ADR cells by inhibiting NF‐κB pathway and inducing autophagy
Authors: Liu Qi , Wang Changyuan , Meng Qiang , Wu Jingjing , Sun Huijun , Sun Pengyuan , Ma Xiaodong , Huo Xiaokui , Liu Kexin
Published: November 2020

Puerarin is an isoflavone isolated from Pueraria lobata (Willd.) Ohwi. In the present study, reversal effect and underlying mechanisms of puerarin on multidrug resistance (MDR) were investigated in K562/ADR cells. K562/ADR cells exhibited adriamycin (ADR) resistance and higher levels of MDR1 expression compared with K562 cells. Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells. The expression levels of MDR1 were down‐regulated by puerarin in K562/ADR cells. Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF‐α‐induced NF‐κB activation. The phosphorylation of IκB‐α was significantly suppressed by puerarin. In silico docking analyses suggested that puerarin well matched with the active sites of IκB‐α. Moreover, a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment. The significant increase in LC3‐II and beclin‐1 was also observed, indicating autophagy induction by puerarin in K562/ADR cells. Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells. Finally, puerarin inhibited phosphorylation of Akt and JNK. In conclusion, puerarin‐sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of NF‐κB pathway and autophagy induction via Akt inhibition.
Techniques for measuring carbon and oxygen isotope compositions of atmospheric CO2 via isotope ratio mass spectrometry
Authors: Manaj Savio , Kim Sang‐Tae
Published: November 2020

Measuring the stable isotope compositions of atmospheric CO2 is common in earth and atmospheric sciences, and various analytical methods have been developed utilizing continuous‐flow (CF) or dual‐inlet (DI) isotope ratio mass spectrometry (IRMS). Air is typically collected via passive, manual, or automated collection methods and the volume of the air sample ranges from 10 to 300 mL for CF‐IRMS to >1 L for DI‐IRMS to yield a measurable amount of atmospheric CO2 gas. It has been determined that the integrity of vials and flasks for air sample storage can be compromised after 3 days of air collection for δ13C values and within 10 hours for δ18O values. Air samples must be purified after collection to remove constituents of air, such as Ar, O2, N2, N2O, and water vapor, to avoid isobaric interferences during mass spectrometric measurement. Purification is generally undertaken by utilizing commercial or custom‐made preconcentration devices, the blanking method for CF‐IRMS, or an offline/online cryogenic separation using a vacuum line for DI‐IRMS. Ambient N2O is a component of air that may affect analytical results and thus must either be corrected for or be removed using a gas chromatographic column. In some cases, water is removed during air collection by using a common chemical desiccant, magnesium perchlorate (Mg(ClO4)2), or by a dry ice/alcohol mixture (−78°C). Lastly, a linearity issue for IRMS due to the low amount of purified CO2 from a typical ambient air sample must be considered. In general, analytical precisions of 0.02–0.21‰ and 0.04–0.34‰ for CF‐IRMS and 0.01–0.02‰ and 0.01–0.02‰ for DI‐IRMS are expected for δ13C and δ18O measurements, respectively.
Metal‐Free Multi‐Heteroatom‐Doped Carbon Bifunctional Electrocatalysts Derived from a Covalent Triazine Polymer
Authors: Zheng Yong , Song Hui , Chen Shan , Yu Xiaohui , Zhu Jixin , Xu Jingsan , Zhang Kai A. I. , Zhang Chao , Liu Tianxi
Published: November 2020

The construction of multi‐heteroatom‐doped metal‐free carbon with a reversibly oxygen‐involving electrocatalytic performance is highly desirable for rechargeable metal‐air batteries. However, the conventional approach for doping heteroatoms into the carbon matrix remains a huge challenge owing to multistep postdoping procedures. Here, a self‐templated carbonization strategy to prepare a nitrogen, phosphorus, and fluorine tri‐doped carbon nanosphere (NPF‐CNS) is developed, during which a heteroatom‐enriched covalent triazine polymer serves as a “self‐doping” precursor with C, N, P, and F elements simultaneously, avoiding the tedious and inefficient postdoping procedures. Introducing F enhances the electronic structure and surface wettability of the as‐obtained catalyst, beneficial to improve the electrocatalytic performance. The optimized NPF‐CNS catalyst exhibits a superb electrocatalytic oxygen reduction reaction (ORR) activity, long‐term durability in pH‐universal conditions as well as outstanding oxygen evolution reaction (OER) performance in an alkaline electrolyte. These superior ORR/OER bifunctional electrocatalytic activities are attributed to the predesigned heteroatom catalytic active sites and high specific surface areas of NPF‐CNS. As a demonstration, a zinc‐air battery using the NPF‐CNS cathode displays a high peak power density of 144 mW cm−2 and great stability during 385 discharging/charging cycles, surpassing that of the commercial Pt/C catalyst.
Amyloid beta is an early responder cytokine and immunopeptide of the innate immune system
Authors: Weaver Donald F.
Published: November 2020

A molecular level conceptualization of the pathogenesis of Alzheimer's disease (AD) remains elusive with many competing hypotheses, particularly via proteopathic and immunopathic mechanisms. However, these need not be competitive. If amyloid beta (Aβ) is regarded as an “early responder cytokine,” then proteopathic considerations become encompassed within an overarching hybrid proteopathic‐immunopathic mechanism. As argued in this commentary, Aβ is in fact a molecular constituent of the innate immune system. Aβ is an antimicrobial peptide (AMP) functioning not only as a killer peptide, but also as a modulatory immunopeptide. Aβ satisfies the definition of a cytokine, exhibiting interdependency with other cytokines. Aβ also satisfies the functional definition of a chemokine, existing within the AMP‐chemokine spectrum. Aβ, like conventional cytokines, both binds to and is released by microglial cells. Finally, Aβ interacts with the complement and Toll‐like receptor systems analogously to established cytokines. Aβ may thus be regarded as an effector molecule of innate immunity.
Imaging in gynecological disease (22): clinical and ultrasound characteristics of ovarian embryonal carcinomas, non‐gestational choriocarcinomas and malignant mixed germ cell tumors
Authors: Moro F. , Castellano L. M. , Franchi D. , Epstein E. , Fischerova D. , Froyman W. , Timmerman D. , Zannoni G. F. , Scambia G. , Valentin L. , Testa A. C. , Mascilini F.
Published: November 2020

Objective

To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non‐gestational choriocarcinoma and malignant mixed germ cell tumor.

Methods

This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non‐gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition.

Results

One patient with embryonal carcinoma, five patients with non‐gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14–77) years. Beta‐human chorionic gonadotropin levels were highest in non‐gestational choriocarcinomas and alpha‐fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38–216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular‐solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours.

Conclusions

A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology
Yoga: The Antidote for These Times
Authors: Ovissi Maryam
Published: November 2020

Yoga is a therapeutic tool that can address secondary trauma, such as that brought on by our collective experience with COVID‐19. There are things that we can do now to help mitigate the current spate of dysregulation associated with the pandemic. Supporting mental health well‐being is essential during this time. As we are now in the midst of collective trauma, it seems appropriate to bring yoga back to help us deal with what is called secondary traumatic stress. Yoga‐inspired tools can support you in your journey through COVID‐19 and also help you to navigate re‐entry into your life as we begin to emerge from the pandemic.
Introduction: Cultural Convergence at Dublin’s Gate Theatre
Authors: Pilný Ondřej , van den Beuken Ruud , Walsh Ian R.
Published: November 2020

The pioneering efforts of the Dublin Gate Theatre (est. 1928) stimulated the influx of experimental plays from the European Continent and North America to Ireland and inspired Irish theatre-makers to revolutionize their dramaturgy. This book examines the Gate’s poetics over the first three decades of its existence, discussing some of its remarkable productions in the comparative contexts of avant-garde theatre and of Hollywood cinema and popular culture. It also investigates cultural exchanges pertaining to the development of Irish-language theatre and the politics of the Gate. The introduction summarizes existing research about the Gate, outlines the book’s concept of cultural convergence and its overall approach – which is intent on the exploration of wider global contexts of the work of the Gate – and outlines the argument of the authors in the subsequent chapters.
The Internationalist Dramaturgy of Hilton Edwards and Micheál mac Liammóir
Authors: Dean Joan FitzPatrick , Markus Radvan
Published: November 2020

In part because the Gate explored an experimental dramaturgy, its artistic directors Micheál mac Liammóir and Hilton Edwards often wrote, spoke and advocated for a drama that could move beyond realism. The analysis of Hilton Edwards’s dramatic commentary reaches from his early articles on dramaturgy right up to his encounter with the Berliner Ensemble in 1956 that influenced Edwards’s most elaborate statement on drama, The Mantle of Harlequin (1958). An important part of Edwards’s vision was his cosmopolitanism, his refusal to view drama within a restricted national framework. Nationality, on the other hand, was more important for the self-styled Irishman Micheál mac Liammóir. On close inspection, however, we find that his outlook did not differ much from Edwards’s. Mac Liammóir’s main concern was for Irish(-language) drama to absorb elements from abroad, to escape the straitjacket of Abbey realism and to become distinctive in a global context.