bluuebunny/crossref_metadata_2025 huggingface dataset:
There is no routine head and neck exam during the COVID‐19 pandemic
Authors: Chan Jason Y. K. , Tsang Raymond K. Y. , Yeung K. W. , Abdullah Victor , Ku Peter , Wong Eddy W. Y. , Mehta Nishchay , Orosco Ryan K. , Holsinger F. Christopher
Published: April 2020

Head and neck examinations are commonly performed by all physicians. In the era of the COVID‐19 pandemic caused by the SARS‐CoV‐2 virus, which has a high viral load in the upper airways, these examinations and procedures of the upper aerodigestive tract must be approached with caution. Based on experience and evidence from SARS‐CoV‐1 and early experience with SARS‐CoV‐2, we provide our perspective and guidance on mitigating transmission risk during head and neck examination, upper airway endoscopy, and head and neck mucosal surgery including tracheostomy.
Management of the difficult airway in the COVID‐19 pandemic: Illustrative complex head and neck cancer scenario
Authors: Rassekh Christopher H. , Jenks Carolyn M. , Ochroch E. Andrew , Douglas Jennifer E. , O'Malley Bert W. , Weinstein Gregory S.
Published: April 2020

Background

This case highlights challenges in the assessment and management of the “difficult airway” patient in the SARS‐CoV‐2 (COVID‐19) pandemic era.

Methods

A 60‐year‐old male with history of recent transoral robotic surgery resection, free flap reconstruction, and tracheostomy for p16+ squamous cell carcinoma presented with stridor and dyspnea 1 month after decannulation. Careful planning by a multidisciplinary team allowed for appropriate staffing and personal protective equipment, preparations for emergency airway management, evaluation via nasopharyngolaryngoscopy, and COVID testing. The patient was found to be COVID negative and underwent imaging which revealed new pulmonary nodules and a tracheal lesion.

Results

The patient was safely transorally intubated in the operating room. The tracheal lesion was removed endoscopically and tracheostomy was avoided.

Conclusions

This case highlights the importance of careful and collaborative decision making for the management of head and neck cancer and other “difficult airway” patients during the COVID‐19 epidemic.
Framework for prioritizing head and neck surgery during the COVID‐19 pandemic
Authors: Topf Michael C. , Shenson Jared A. , Holsinger F. Christopher , Wald Samuel H. , Cianfichi Lisa J. , Rosenthal Eben L. , Sunwoo John B.
Published: April 2020

The COVID‐19 pandemic has placed an extraordinary demand on the United States health care system. Many institutions have canceled elective and non‐urgent procedures to conserve resources and limit exposure. While operational definitions of elective and urgent categories exist, there is a degree of surgeon judgment in designation. In the present commentary, we provide a framework for prioritizing head and neck surgery during the pandemic. Unique considerations for the head and neck patient are examined including risk to the oncology patient, outcomes following delay in head and neck cancer therapy, and risk of transmission during otolaryngologic surgery. Our case prioritization criteria consist of four categories: urgent—proceed with surgery, less urgent—consider postpone > 30 days, less urgent—consider postpone 30 to 90 days, and case‐by‐case basis. Finally, we discuss our preoperative clinical pathway for transmission mitigation including defining low‐risk and high‐risk surgery for transmission and role of preoperative COVID‐19 testing.
Loss of c‐Jun N‐terminal Kinase 1 and 2 Function in Liver Epithelial Cells Triggers Biliary Hyperproliferation Resembling Cholangiocarcinoma
Authors: Cubero Francisco Javier , Mohamed Mohamed Ramadan , Woitok Marius M. , Zhao Gang , Hatting Maximilian , Nevzorova Yulia A. , Chen Chaobo , Haybaeck Johannes , de Bruin Alain , Avila Matias A. , Boekschoten Mark V. , Davis Roger J. , Trautwein Christian
Published: April 2020

Targeted inhibition of the c‐Jun N‐terminal kinases (JNKs) has shown therapeutic potential in intrahepatic cholangiocarcinoma (CCA)‐related tumorigenesis. However, the cell‐type‐specific role and mechanisms triggered by JNK in liver parenchymal cells during CCA remain largely unknown. Here, we aimed to investigate the relevance of JNK1 and JNK2 function in hepatocytes in two different models of experimental carcinogenesis, the dethylnitrosamine (DEN) model and in nuclear factor kappa B essential modulator (NEMO)hepatocyte‐specific knockout (Δhepa) mice, focusing on liver damage, cell death, compensatory proliferation, fibrogenesis, and tumor development. Moreover, regulation of essential genes was assessed by reverse transcription polymerase chain reaction, immunoblottings, and immunostainings. Additionally, specific Jnk2 inhibition in hepatocytes of NEMOΔhepa/JNK1Δhepa mice was performed using small interfering (si) RNA (siJnk2) nanodelivery. Finally, active signaling pathways were blocked using specific inhibitors. Compound deletion of Jnk1 and Jnk2 in hepatocytes diminished hepatocellular carcinoma (HCC) in both the DEN model and in NEMOΔhepa mice but in contrast caused massive proliferation of the biliary ducts. Indeed, Jnk1/2 deficiency in hepatocytes of NEMOΔhepa (NEMOΔhepa/JNKΔhepa) animals caused elevated fibrosis, increased apoptosis, increased compensatory proliferation, and elevated inflammatory cytokines expression but reduced HCC. Furthermore, siJnk2 treatment in NEMOΔhepa/JNK1Δhepa mice recapitulated the phenotype of NEMOΔhepa/JNKΔhepa mice. Next, we sought to investigate the impact of molecular pathways in response to compound JNK deficiency in NEMOΔhepa mice. We found that NEMOΔhepa/JNKΔhepa livers exhibited overexpression of the interleukin‐6/signal transducer and activator of transcription 3 pathway in addition to epidermal growth factor receptor (EGFR)‐rapidly accelerated fibrosarcoma (Raf)‐mitogen‐activated protein kinase kinase (MEK)‐extracellular signal‐regulated kinase (ERK) cascade. The functional relevance was tested by administering lapatinib, which is a dual tyrosine kinase inhibitor of erythroblastic oncogene B‐2 (ErbB2) and EGFR signaling, to NEMOΔhepa/JNKΔhepa mice. Lapatinib effectively inhibited cystogenesis, improved transaminases, and effectively blocked EGFR‐Raf‐MEK‐ERK signaling. Conclusion: We define a novel function of JNK1/2 in cholangiocyte hyperproliferation. This opens new therapeutic avenues devised to inhibit pathways of cholangiocarcinogenesis.
Molecular Dynamics Simulations of Antibiotic Ceftaroline at the Allosteric Site of Penicillin‐Binding Protein 2a (PBP2a)
Authors: Chiang Ying‐Chih , Wong Mabel T. Y. , Essex Jonathan W.
Published: April 2020

Methicillin‐resistant Staphylococcus aureus (MRSA) tolerates β‐lactam antibiotics by carrying out cell wall synthesis with the transpeptidase Penicillin‐binding protein 2a (PBP2a), which cannot be inhibited by β‐lactams. It has been proposed that PBP2a's active site is protected by two loops to reduce the probability of it binding with β‐lactams. Previous crystallographic studies suggested that this protected active site opens for reaction once a native substrate binds at an allosteric domain of PBP2a. This opening was proposed for the new β‐lactam ceftaroline's mechanism in successfully treating MRSA infections, i. e. by it binding to the allosteric site, thereby opening the active site to inhibition. In this work, we investigate the binding of ceftaroline at this proposed allosteric site using molecular dynamics simulations. Unstable binding was observed using the major force fields CHARMM36 and Amber ff14SB, and free energy calculations were unable to confirm a strong allosteric effect. Our study suggests that the allosteric effect induced by ceftaroline is weak at best.
Trends and Geographical Variability in Osteoporosis Treatment After Hip Fracture: A Multilevel Analysis of 30,965 Patients in the Region of Valencia, Spain
Authors: Hurtado Isabel , García-Sempere Aníbal , Peiró Salvador , Rodríguez-Bernal Clara , Sanfélix-Genovés José , Sanfélix-Gimeno Gabriel
Published: April 2020

Despite improvements in the therapeutic arsenal and the recommendations of guidelines, low rates of prescribing osteoporosis medications are being reported worldwide for patients surviving a hip fracture, and important geographical variation remain. We aimed to describe trends in the proportion of patients that receive osteoporosis medication after hip fracture and to analyze the geographical variation in the prescription of drug therapy and its associated factors in the region of Valencia, Spain. We studied a population-based retrospective cohort of 30,965 patients aged 65 years and older, discharged from hospital after a hip fracture from January 2008 to December 2015, who were followed up for 3 months after discharge to identify the presence of any prescription of osteoporosis medication. We conducted a multilevel multiple logistic regression analysis with two levels (individuals and health departments [HD]) to determine which individual covariates were associated with receiving a prescription of osteoporosis medication in the 3 months after discharge, as well as the importance of the HD of hospitalization. The percentage of patients treated in the region decreased from a maximum of 28.9% in 2009 to 16.4% in 2015. By sex, the proportion of women treated reached a maximum of 33.4% in 2009 and declined to 19% in 2015, while the proportion of men reached a maximum of 14% in 2011 and reduced to 8.1% in 2015. By health department, there was a noticeable variability in the rate of patients treated, ranging from 40.9% to 11.1% in the whole period (intraclass correlation coefficient [ICC] = 7.54%; median odds ratio [MOR] = 1.64). Proportion of treated patients decreased in 20 of the 24 HDs. Variability could be also observed with regard to choice of medication by HD. This situation pressingly demands action (both at the organizational and professional levels) focused on populations at a higher risk (such as hip fracture patients) that particularly address underutilization and unwarranted variation.
Severity of Topiramate‐Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity
Authors: Callisto Samuel P. , Illamola Sílvia M. , Birnbaum Angela K. , Barkley Christopher M. , Bathena Sai Praneeth R. , Leppik Ilo E. , Marino Susan E.
Published: April 2020

Drug side effects that impair cognition can lead to diminished quality of life and discontinuation of therapy. Topiramate is an antiepileptic drug that elicits cognitive deficits more frequently than other antiepileptic drugs, impairing multiple cognitive domains including language, attention, and memory. Although up to 40% of individuals taking topiramate may experience cognitive deficits, we are currently unable to predict which individuals will be most severely affected before administration. The objective of this study was to show the contributions of plasma concentration and working memory capacity in determining the severity of an individual's topiramate‐related cognitive impairment. Subjects were enrolled in a double‐blind, placebo‐controlled crossover study during which they received a single dose of either 100, 150, or 200 mg topiramate. Working memory function was assessed using a modified Sternberg working memory task with 3 memory loads administered 4 hours after dosing. After adjustment for differences in working memory capacity, each 1 μg/mL of topiramate plasma concentration was associated with a 3.6% decrease in accuracy for all memory loads. Placebo effects occurred as a function of working memory capacity, with individuals with high working memory capacity experiencing less severe placebo‐related impairment compared with those with low working memory capacity. Our results demonstrate that severity of topiramate‐related cognitive deficits occurs as a function of both drug exposure and baseline cognitive function. By identifying patient‐ and exposure‐related characteristics that modulate the severity of cognitive side effects, topiramate dosing strategies may be individually tailored in the future to prevent unwanted cognitive impairment.
Dynamic changes of histone acetylation and methylation in bovine oocytes, zygotes, and preimplantation embryos
Authors: Wu Xia , Hu Shuxiang , Wang Lingling , Li Yan , Yu Haiquan
Published: April 2020

Histone modifications play important roles in regulating chromatin dynamic changes. In this study, acetylated histone H3 lysine 9 and 18 (H3K9ac and H3K18ac), acetylated histone H4 lysine 5 and 8 (H4K5ac and H4K8ac), tri‐methylation histone H3 lysine 4 (H3K4me3), di‐methylation histone H3 lysine 9 (H3K9me2) are investigated in bovine oocytes, zygote, and preimplantation. During meiosis, H3K9ac and H3K18ac are erased after germinal vesicle breakdown, H4K8ac is erased after metaphase I (MI). Although H4K5ac is erased at MI, it is redetectable after this stage. However, histone methylations have no significant change during meiosis. During fertilization, intensive H4K5ac and H4K8ac are resumed on male and female chromatins at postfertilization 4 and 8 hr, respectively. H3K9ac and H3K18ac are resumed on both male and female chromatins at postfertilization 8 and 12 hr, respectively. H3K4me3 and H3K9me2 gradually increased on male chromatin after postfertilization 8 hr, while these two signals on female chromatin are detectable from postfertilization 2–18 hr. During embryo cleavage, H3K9ac, H3K18ac, and H3K4me3 are reduced at 8‐cell stage, and then start to increase. H4K5ac, H4K8ac, and H3K9me2 increase after the 4‐cell stage. At interphase, H4K5ac and H4K8ac are more intensive in nuclear periphery from 2‐ to 8‐cell stages. During mitosis, the signal of H4K8ac is intensive at chromosome periphery. In summary, during both oocyte meiosis and fertilization, the dynamic changes of both histone acetylations and methylations happen in a process of lysine residue‐specific and species‐specific. During preimplantation development, the dynamic patterns of both H3K9ac and H3K18ac are similar to that of H3K4me3, while the dynamic pattern of H4K5ac is similar to that of H4K8ac. These results will be helpful for understanding the effect of histone posttranslational modifications on bovine reproduction and development.
A qualitative study of Latinx parents' experiences of clinical exome sequencing
Authors: Luksic Daniel , Sukhu Radha , Koval Carrie , Cho Megan T. , Espinal Aileen , Rufino Katiana , Loarte Tania Vasquez , Chung Wendy K. , Wynn Julia
Published: April 2020

Clinical exome sequencing (CES) is an established method for genetic diagnosis and is used widely in clinical practice. Studies of the parental experience of CES, which inform guidelines for best practices for genetic counseling, have been predominately comprised of White, non‐Latinx participants. The aim of this study was to explore the parental experiences of CES in a Latinx community and to understand how their experiences are influenced by culture and language. We conducted semi‐structured interviews in English and Spanish with 38 Latinx parents of children who had CES. Some of the themes that emerged were common to those previously identified, including a sense of obligation to pursue testing and a mixed emotional response to their child's results. Parents who had lower education level and/or received care from a provider who did not share their language had more confusion about their child's CES results and greater dissatisfaction with care compared with parents who had higher education level and/or received care from a provider who spoke their language. We also found evidence of hampered shared decision making and/or disempowered patient decision making regarding CES testing. Our data suggest unique needs for Latinx families having CES, particularly those who are non‐English speaking when an interpreter is used. Our data support the value in continuing to take steps to improve culturally competent care by improving interpretation services and recruiting and training a genetic workforce that is ethnically, linguistically, and culturally diverse.
Risk factors for hepatocellular carcinoma in treated chronic hepatitis C patients–Relationship to smoking and alcohol
Authors: Matsuura Tomoka , Ohfuji Satoko , Enomoto Masaru , Tamori Akihiro , Kubo Shoji , Kioka Kiyohide , Kawada Norifumi , Fukushima Wakaba
Published: April 2020

Background and Aim

The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, in relation to the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virologic response (SVR).

Methods

This cross‐sectional study was conducted between 2014 and 2017 using self‐administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR without HCC following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the development of post‐SVR HCC for each factor.

Results

Of 202 participants, 18 patients were diagnosed with post‐SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95% CI, 1.08–83.90) and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95% CI, 1.37–12.46) were significantly associated with HCC. In addition, among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with never smokers, with marginal significance (OR, 5.61; 95% CI, 0.97–32.63).

Conclusions

In chronic hepatitis C patients with severe fibrosis, continuing smoking after achieving SVR could be a risk factor for post‐SVR HCC. The relationship between gastric or duodenal ulcer history and post‐SVR HCC should be investigated further.
Weight gain among treatment‐naïve persons with HIV starting integrase inhibitors compared to non‐nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada
Authors: Bourgi Kassem , Jenkins Cathy A , Rebeiro Peter F , Shepherd Bryan E. , Palella Frank , Moore Richard D , Althoff Keri N , Gill John , Rabkin Charles S , Gange Stephen J , Horberg Michael A , Margolick Joseph , Li Jun , Wong Cherise , Willig Amanda , Lima Viviane D , Crane Heidi , Thorne Jennifer , Silverberg Michael , Kirk Gregory , Mathews William C , Sterling Timothy R , Lake Jordan , Koethe John R ,   for the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD)
Published: April 2020

Introduction

Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD).

Methods

Adult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.

Results

Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).

Conclusions

PWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.
LV pacing as an alternative option to conventional RV pacing in a patient with tricuspid valve replacement
Authors: Iovev Svetoslav , Chilingirova Nezabravka
Published: April 2020

Tricuspid regurgitation (TR) is a relatively common anomaly. In patients with tricuspid valve repair/replacement (TVR)the control of atrioventricular conduction irregularity can be demanding, given the unavailability for implantation of the right ventricular (RV) endocardial lead, which is not recommended in such cases because of the risk of lead fracture at the valve site and valve damage or failure. Thus, epicardial lead may be an option; it requires a surgical procedure and it is not preferred in patients with prior thoracotomy. Lead implantation via coronary sinus (CS) can be an alternative to conventional right ventricular pacing in this patient population.
Cotton thread modified with ionic liquid copolymerized polymer for online in‐tube solid‐phase microextraction and HPLC analysis of nonsteroidal anti‐inflammatory drugs
Authors: Liu Zichun , Zhou Wei , Wang Chenlu , Hu Wei , Chen Zilin
Published: April 2020

Cotton fiber is a biodegradable material that possesses properties such as high specific area, adjustable shape, and hygroscopicity. In this work, organic polymer was directly in situ grown on the surface of cotton thread and packed into a poly(ether ether ketone) tube for online in‐tube solid‐phase microextraction. The novel strategy solves the problems like high backpressure and tedious optimization process of normal monolithic polymer‐based in‐tube solid‐phase microextraction capillary. The quaternary ammonium typed ionic liquid of 1‐allyl‐methylimidazolium chloride, 4‐vinylbiphenyl, and ethylene dimethacrylate were co‐polymerized and in situ grown on the surface of cotton thread as extraction phase. The solid‐phase microextraction tube showed excellent performance for the extraction of three nonsteroidal anti‐inflammatory drugs including ketoprofen, naproxen, and flurbiprofen due to the strong ion exchange and hydrophobic interactions. After online coupling with a high‐performance liquid chromatography system by six‐port valve, the method was applied for the quantitative analysis of nonsteroidal anti‐inflammatory drugs in human plasma samples showing good enrichment performance (enrichment factor between 263 and 279), high sensitivity, good linearity, and good reproducibility.
An Immunogenomic Investigation of Oral Cavity Squamous Cell Carcinoma in Patients Aged 45 Years and Younger
Authors: Maroun Christopher A. , Zhu Gangcai , Fakhry Carole , Gourin Christine G. , Seiwert Tanguy Y. , Vosler Peter S. , Tan Marietta , Koch Wayne , Eisele David W. , Pardoll Drew M. , Mandal Rajarsi
Published: April 2020

Objectives/Hypothesis

To investigate differences in the immunogenomic landscape among young patients presenting with oral cavity squamous cell carcinoma (OCSCC).

Study Design

Retrospective database review.

Methods

Normalized messenger mRNA expression data were downloaded from The Cancer Genome Atlas (TCGA) database. OCSCC patients were categorized into young and older age groups with a cutoff of 45 years. Human papillomavirus–positive tumors were excluded. Cell fractions, marker expression, and mutational load were compared between age groups using the Wilcoxon rank sum test. Adjustment for multiple comparisons was performed using the Benjamini‐Hochberg method, with a false discovery rate of 0.05.

Results

Two hundred forty‐five OCSCC tumors were included; 21 (8.6%) were young (37.1 ± 7.5 years) and 224 (91.4%) were older (64.5 ± 10.3 years). There was no significant difference between groups in the fraction of B and T lymphocytes, macrophages, monocytes, natural killers, and dendritic cells. Cytolytic activity score was decreased in young patients (8.33 vs. 18.9, P = .023). Additionally, young patients had significantly lower expression of immunomodulatory markers of immune activation, including PD‐1 (PDCD1, P = .003), CTLA4 (P = .025), TIGIT (P = .002), GITR (TNFRSF18, P = .005), OX40 (TNFRSF4, P = .009), LAG‐3 (P < .001), and TIM‐3 (HAVCR2, P = .002). Young patients had a significantly lower number of single nucleotide variant‐derived neoantigens (26.2 vs. 60.6, P < .001).

Conclusions

OCSCC patients aged 45 years and younger appear to have an attenuated immune response that may be related to a lower frequency of immunogenic mutations. This may contribute to the pathogenesis of these tumors, and ultimately help inform personalized immune‐based therapeutic strategies for young patients with OCSCC.

Level of Evidence

NA Laryngoscope, 131:304–311, 2021
Intravenous vs oral acetaminophen in sinus surgery: A randomized clinical trial
Authors: Bhoja Ravi , Ryan Matthew W. , Klein Kevin , Minhajuddin Abu , Melikman Emily , Hamza Mohamed , Marple Bradley F. , McDonagh David L.
Published: April 2020

Background

Multimodal perioperative analgesia including acetaminophen is recommended by current guidelines. The comparative efficacy of intravenous vs oral acetaminophen in sinus surgery is unknown. We aimed to determine whether intravenous or oral acetaminophen results in superior postoperative analgesia following sinus surgery.

Methods

This was a prospective randomized trial with blinded endpoint assessments conducted at a single large academic medical center. Subjects undergoing functional endoscopic sinus surgery were randomized to intravenous vs oral acetaminophen in addition to standard anesthetic and surgical care. The primary outcome was visual analogue scale pain score at 1 hour postoperatively.

Results

One hundred and ten adult patients were randomized; 9 were excluded from the data analysis. Fifty patients were assigned to intravenous acetaminophen and 51 to oral acetaminophen. Postoperative pain scores at 1 hour (primary endpoint) were not significantly different between the intravenous and oral acetaminophen groups. Similarly, there was no significant difference in pain scores at 24 hours postoperatively. Finally, there was no significant difference in postoperative opioid usage in the postanesthesia care unit or over the first 24 hours postoperatively.

Conclusions

This is the first comparative efficacy trial of oral vs intravenous acetaminophen in sinus surgery. There was no significant difference in pain scores at 1 or 24 hours postoperatively, and no difference in postoperative opioid use. Intravenous acetaminophen offers no apparent advantage over oral acetaminophen in patients undergoing sinus surgery.

Level of Evidence

1b
Combined climate change and nutrient load impacts on future habitats and eutrophication indicators in a eutrophic coastal sea
Authors: Wåhlström Iréne , Höglund Anders , Almroth‐Rosell Elin , MacKenzie Brian R. , Gröger Matthias , Eilola Kari , Plikshs Maris , Andersson Helén C.
Published: April 2020

Eutrophication and climate change will affect habitats of species and more generally, the structure and functioning of ecosystems. We used a three‐dimensional, coupled hydrodynamic‐biogeochemical model to investigate potential future changes in size and location of potential habitats of marine species during the 21st century in a large, eutrophicated brackish sea (the Baltic Sea, northern Europe). We conducted scenario projections under the combined impact of nutrient load and climate change. Possible future changes of the eutrophication state of this sea were also assessed through two policy‐relevant indicators. The results imply a physiologically more stressful environment for marine species by the end of the 21st century: volumes of higher salinity water become more hypoxic/anoxic and the volumes of low salinity, oxic water increase. For example, these results impact and reduce cod reproductive habitats. The decrease is mainly climate change induced in the Baltic basins less directly influenced by inflows of saline, oxic water to the Baltic Sea (E Gotland and Gdansk Basins). In basins more directly influenced by such inflows (Arkona and Bornholm Basins), the combined effect from climate change and nutrient loads is of importance. The results for the eutrophication state indicators clearly indicate a more eutrophic sea than at present without a rigorous nutrient reduction policy, that is, the necessity to implement the Baltic Sea Action Plan. The multidisciplinary, multiscenario assessment strategy presented here provides a useful concept for the evaluation of impacts from cumulative stresses of changing climate and socioeconomic pressures on future eutrophication indicators and habitats of marine species.
Evaluation of Fractional CO2 Versus Long Pulsed Nd:YAG Lasers in Treatment of Hypertrophic Scars and Keloids: A Randomized Clinical Trial
Authors: Tawfic Shereen O. , El‐Tawdy Amira , Shalaby Suzan , Foad Ahmed , Shaker Olfat , Sayed Safinaz S. , Metwally Dina
Published: April 2020

Background

Keloids and hypertrophic scars are challenging to both patients and physicians. They can be aesthetically disfiguring, functionally debilitating, and emotionally distressing. Lasers have introduced new mechanisms to improve scars both on aesthetic and symptomatic levels.

Aim of Work

Comparing the efficacy of fractional CO2 laser, long‐pulsed Nd:YAG laser and their combination in the treatment of hypertrophic scars and keloids on clinical, histopathological, and biochemical basis.

Patients and Methods

Thirty patients with hypertrophic scars and keloids were enrolled in the study. Three scars in each patient were randomly assigned to treatment modalities (i) Fractional CO2, (ii) Nd:YAG laser, (iii) Combined CO2 and Nd:YAG lasers. For each treatment area four sessions, 4–6 weeks apart were performed. Clinical evaluation was done before and 1 month following last session using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Routine hematoxylin and eosin, Masson's trichrome, and Orcein stains were used to evaluate the appearance and pattern of dermal collagen and elastic fibers. Image analysis was used to quantitatively assess the density of collagen and elastic fibers. Biochemical evaluation of tissue level of transforming growth factor‐β I (TGF‐β I) and TGF‐β III was performed using enzyme‐linked immunosorbent assay studies.

Results

Both VSS and POSAS showed significant improvement following treatment with the three used modalities. Collagen fibers showed significant improvement as regards appearance and pattern while it was insignificant as regards density. Elastic fibers density improvement was only significant in fractional CO2 (treatment area A). Hypertrophic scars showed more significant improvement with fractional CO2 laser, while in keloids there was no significant difference between the three modalities regarding improvement. Level of TGF‐β I showed significant reduction after treatment in all treatment modalities, while TGF‐β III levels showed insignificant elevation in all treatment modalities. Side effects were significantly higher in treatment area C (combined treatment).

Conclusion

Long pulsed Nd:YAG laser is effective and safe treatment of hypertrophic scars and keloids. Fractional CO2 laser yields better improvement in hypertrophic scars, while in keloids both fractional CO2 and Nd:YAG lasers achieve comparable improvement. Combination in the same session did not add significant additional benefit and the side effects profile was higher.

Limitations

small sample size and short follow‐up period. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Clinical and Histological Assessment of Combined Fractional CO2 Laser and Growth Factors Versus Fractional CO2 Laser Alone in the Treatment of Facial Mature Burn Scars: A Pilot Split‐Face Study
Authors: Weshahy Ragia H. , Aly Dalia G. , Shalaby Suzan , Mohammed Faisal N. , Sayed Khadiga S.
Published: April 2020

Background and Objectives

To investigate the therapeutic efficacy and safety of growth factors combined with fractional carbon dioxide (CO2) laser in comparison with fractional CO2 alone in a sample of patients with facial mature burn scars.

Study Design/Materials and Methods

Fifteen Egyptian patients with bilateral facial burn scars were treated with six sessions of fractional CO2 laser at 6‐week intervals. Following each laser session, a topical growth factors cocktail was applied to one side of the face in a split‐face manner. Clinical evaluation by Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (PSOS), and photography before and 2 months after the last laser session was done. Three millimeter punch biopsies were obtained from each side of the face pre‐ and 1‐month posttreatment to measure the mean area percent of collagen.

Results

Posttreatment, both VSS and PSOS scores decreased on both sides of the face being more significant on the growth factors treated side, showing more scar pliability and shorter downtime (P = 0.001). A significant difference in the mean area percent of collagen was also noted on both sides.

Conclusion

Adding topical growth factors to fractional CO2 laser treatments is effective and safe with better results as regards scar pliability and shorter downtime than fractional CO2 laser alone. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Comparative investigations into microstructural and mechanical properties of as‐cast and laser powder bed fusion (LPBF) fabricated duplex steel (1.4517)
Authors: Raffeis I. , Vroomen U. , Adjei‐Kyeremeh F. , Großmann D. , Hammelrath H. , Westhoff E. , Bremen S. , Boscolo Bozza D. , Bührig‐Polaczek A.
Published: April 2020

A methodology is presented that compares the microstructural and mechanical properties of as‐cast and additive‐made ferritic‐austenitic duplex steel 1.4517. Microstructure of approximately equal amounts of ferrite and austenite measured in as‐cast material could not be replicated in post heat‐treated laser powder bed fusion samples after 30 min and 60 min of post heat treatment. This is attributed to nitrogen loss during powder atomization which left fewer austenite formers. Post‐heat treated laser powder bed fusion samples of duplex structure had its austenite content repeatedly adjusted between 38 % and 40 %. As‐built laser powder bed fusion tensile specimens which had a ferritic microstructure recorded high tensile and yield strength but had very poor elongation. Post heat‐treated duplex laser powder bed fusion tensile specimen built in both horizontal and vertical orientations had good tensile and yield strength comparable to conventional casting processes; Tensile strength – 739 MPa (horizontal), 759 MPa (vertical); Yield strength (Rp0.2) – 489 MPa (horizontal), 525 MPa (vertical). The horizontally built duplex specimen had a very high elongation of 32 % than the vertical (11 %) or conventionally reported (22 %). This work establishes the 1.4517 duplex steel as a good candidate with good mechanical properties when processed by additive manufacturing.
Uniform regularity for the full compressible MHD system with zero heat conductivity
Authors: Fan Jishan , Wang Liangwei , Zhou Yong
Published: April 2020

In this work, we prove the uniform regularity of smooth solutions to the full compressible magnetohydrodynamics (MHD) system with zero heat conductivity.
Eicosapentaenoic and Docosahexaenoic Acids Differentially Alter Gut Microbiome and Reverse High‐Fat Diet–Induced Insulin Resistance
Authors: Zhuang Pan , Zhang Yu , Shou Qiyang , Li Haoyu , Zhu Ya'er , He Lilin , Chen Jingnan , Jiao Jingjing
Published: April 2020

Scope

To assess the individual effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin resistance (IR), gut microbiome, and gut metabolites in high‐fat‐diet‐induced obese (DIO) mice.

Methods and results

DIO mice are fed an either high‐fat diet (HFD), EPA (1% w/w) enriched HFD, or DHA (1% wt/wt) enriched HFD for 15 weeks. Both EPA and DHA supplements reverse hyperglycemia and IR but do not affect body weight in DIO mice while DHA exhibits a more pronounced ameliorative effect in male mice. Both EPA‐ and DHA‐enriched Lactobacillus and short‐chain fatty acids (SCFAs)‐producing species from Lachnospiraceae while reduced lipopolysaccharide (LPS)‐producing Bilophila and Escherichia/Shigella. Compared with EPA, DHA‐supplemented mice have more abundant propionic/butyric acid‐producing bacteria, including Coprococcus, Butyricimonas synergistica, Bacteroides acidifaciens, and Intestinimonas, and less‐abundant LPS‐correlated species Streptococcus and p‐75‐a5. The shifts in gut microbiome co‐occurred with the changes in levels of propionic/butyric acid, circulating LPS, and serotonin. Additionally, EPA/DHA supplementation attenuates adipose inflammation with upregulated glucose transporter 4 and Akt phosphorylation, indicating the improvement of insulin signaling.

Conclusion

EPA and DHA differentially reverse IR and relieve adipose inflammation while modulating gut microbiome and SCFAs/LPS production, underscoring the gut‐adipose axis as a primary target of EPA/DHA.
An approach to calculating large strain accumulation for discrete element simulations of granular media
Authors: Nguyen Nhu H.T. , Bui Ha H. , Nguyen Giang D.
Published: April 2020

For research on granular materials, establishing a method to calculate continuum strain from particle displacements is necessary for understanding the material behaviour at macro‐level and developing continuum constitutive models. Existing methods are generally based on constructing a mesh or background grid to calculate strain from particle motions. These methods offer rigorous ways to measure strain for granular materials; however, they suffer from several problems such as mesh distortion and lacking grid‐to‐particle strain mapping procedure, which hinders their capability of calculating strain accumulation during large deformation processes of granular media. To address this issue, this study proposes a new strain calculation method for discrete element simulations of granular materials. This method describes a particle assembly as an equivalent continuum system of material points, each of which corresponds to a particle centre and represents a continuous region with its initial volume/area presumably equal to the volume/area of Voronoi cells generated in accordance with the particle assembly configuration. Smooth Particle Hydrodynamics (SPH) interpolation functions are then employed to calculate strain for these material points. This SPH‐based method does not require any mesh or background grid for computation, leading to advantages in calculating strain accumulation under large deformation. Simulations of granular materials in both uniform and heterogeneous gradations were carried out, and strain results obtained by the proposed method indicate good agreements with analytical and numerical solutions. This demonstrates its potential for strain calculations in discrete element simulations of granular materials involving large deformations and/or large displacements.
Simultaneous topology and build orientation optimization for minimization of additive manufacturing cost and time
Authors: Fritz Kevin , Kim Il Yong
Published: April 2020

The ever‐present demand for increased performance in mechanical systems, and reduced cost and manufacturing time, has led to the adoption of computational design tools and innovative manufacturing methods. One such tool is topology optimization (TO), which often produces designs that are impracticable to manufacture. However, recent developments in additive manufacturing (AM) have made production of such complex designs feasible. Therefore, integration of these technologies has the potential to innovate the design and manufacture of mechanical components. This work presents a novel mathematical methodology for multiobjective minimization of structural compliance and AM cost and time, in simultaneous build orientation and density‐based TO. Component surface area and support volume were implemented in this method as the physical factors influencing AM cost and time. A new methodology was produced to approximate support volume throughout TO with variable build orientation, enabling direct minimization of support volume in the proposed optimization. The methodology allows derivation of sensitivity expressions, thereby permitting the use of efficient gradient‐based optimization solvers. Three numerical examples demonstrated that the proposed methodology can efficiently produce optimum build orientations and topologies, which significantly reduce structural compliance and AM cost and
time.
Neutrophils expressing lysyl oxidase‐like 4 protein are present in colorectal cancer liver metastases resistant to anti‐angiogenic therapy
Authors: Palmieri Vincent , Lazaris Anthoula , Mayer Thomas Z , Petrillo Stephanie K , Alamri Hussam , Rada Miran , Jarrouj George , Park Woong‐Yang , Gao Zu‐hua , McDonald Patrick P , Metrakos Peter
Published: April 2020

Colorectal cancer liver metastases (CRCLM) that present with a replacement histopathological growth pattern (HGP) are resistant to neoadjuvant anti‐angiogenic therapy. Surrogate biomarkers are not available to preoperatively identify patients with these tumors. Here we identify differentially expressed genes between CRCLM with a replacement HGP and those with a desmoplastic HGP using RNA sequencing. We demonstrate that LOXL4 is transcriptionally upregulated in replacement HGP CRCLM compared with desmoplastic HGP CRCLM and the adjacent normal liver. Interestingly, lysyl oxidase‐like 4 (LOXL4) protein was expressed by neutrophils present in the tumor microenvironment in replacement HGP CRCLM. We further demonstrate that LOXL4 expression is higher in circulating neutrophils of cancer patients compared with healthy control patients and its expression can be induced by stimulation with lipopolysaccharide and TNF‐α. Our study is the first to show the expression of LOXL4 in neutrophils and reveals the potential for LOXL4‐expressing neutrophils to support the replacement HGP phenotype and to serve as a surrogate biomarker for this subtype of CRCLM. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Moral Foundations Theory and the Psychology of Charitable Giving
Authors: Nilsson Artur , Erlandsson Arvid , Västfjäll Daniel
Published: April 2020

Moral foundations theory proposes that intuitions about what is morally right or wrong rest upon a set of universal foundations. Although this theory has generated a recent surge of research, few studies have investigated the real–world moral consequences of the postulated moral intuitions. We show that they are predictably associated with an important type of moral behaviour. Stronger individualizing intuitions (fairness and harm prevention) and weaker binding intuitions (loyalty, authority, and sanctity) were associated with the willingness to comply with a request to volunteer for charity and with the amount of self–reported donations to charity organizations. Among participants who complied with the request, individualizing intuitions predicted the allocation of donations to causes that benefit out–groups, whereas binding intuitions predicted the allocation of donations to causes that benefit the in–group. The associations between moral foundations and self–report measures of allocations in a hypothetical dilemma and concern with helping in–group and out–group victims were similar. Moral foundations predicted charitable giving over and above effects of political ideology, religiosity, and demographics, although variables within these categories also exhibited unique effects on charitable giving and accounted for a portion of the relationship between moral foundations and charitable giving. © 2020 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology
Effects of an intervention combining self‐care and self‐hypnosis on fatigue and associated symptoms in post‐treatment cancer patients: A randomized‐controlled trial
Authors: Grégoire Charlotte , Faymonville Marie‐Elisabeth , Vanhaudenhuyse Audrey , Charland‐Verville Vanessa , Jerusalem Guy , Willems Sylvie , Bragard Isabelle
Published: April 2020

Objective

Cancer has a lot of consequences such as fatigue, sleep disturbances, emotional distress, cognitive impairment and reduced physical activity. Some hypnosis‐based psychological interventions showed positive effects on fatigue, sleep and emotional distress, but generally focused on breast cancer patients. Our study aimed at assessing the effects of a group intervention combining self‐care and self‐hypnosis on quality of life of cancer patients.

Methods

Our longitudinal randomized‐controlled trial assessed the benefits of the intervention first on fatigue and secondly on associated symptoms (sleep, emotional distress, cognitive impairment and reduced physical activity) of post‐treatment cancer patients, and investigated predictors of the evolution of fatigue. All variables were measured with questionnaires and an actigraph (for sleep and physical activity).

Results

Ninety five women with different cancers were included in our study. Group‐by‐time effects were showed for fatigue, sleep, emotional distress and cognitive functioning: symptoms have improved in the intervention group compared to wait‐list control group. Three predictors of the evolution of fatigue were revealed: depression, anxiety and worry.

Conclusions

Our group intervention had benefits for post‐treatment cancer patients' quality of life. Impacting emotional distress could be important in order to decrease fatigue. Further studies are needed to replicate our results. This intervention could be easily implemented to improve quality of life of cancer patients.

Registration: ClinicalTrials.gov (NCT03144154). Retrospectively registered on the 1st of May, 2017.
Banishing the myths and dogmas surrounding the biotech Stradivarius
Authors: Schwarze Francis W. M. R. , Morris Hugh
Published: April 2020

Societal Impact Statement

The impact of global warming on wood formation means that it is becoming increasingly difficult to find superior‐quality resonance wood for the production of musical instruments. Using fungi, we can mimic the effects of a cold climate on wood, to produce biotech violins with a tone matching those of a Stradivarius. Our work has sparked worldwide interest from the media, music lovers, and violinmakers. Here we address concerns raised about the biotech violin and detail scientific advances made since the original publication of our work. We believe this mycowood technology will enable affordable and acoustically superior instruments to become available to talented young musicians who would otherwise be unable to afford their own Stradivarius.