bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPRESSION OF CONCERN: The effect of Spirulina sauce, as a functional food, on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease patients: A randomized double‐blinded clinical trial
Authors: Mazloomi Seyed Mohammad , Samadi Mohammad , Davarpanah Hajar , Babajafari Siavash , Clark Cain C. T. , Ghaemfar Zohreh , Rezaiyan Mojtaba , Mosallanezhad Abdolhamid , Shafiee Maryam , Rostami Hosein
Published: June 2021

Objective

This study sought to investigate the effect of Spirulina on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease (NAFLD) patients.

Methods

This randomized, double‐blind clinical trial was performed on 46 NAFLD patients. Subjects were allocated to consume either Spirulina sauce or placebo, each 20 g/day for 8 weeks. Fatty liver grade, liver enzymes, anthropometric parameters, blood pressure, and serum lipids, glucose, insulin, malondialdehyde, and antioxidant capacity were assessed pre‐ and postintervention.

Results

Fatty liver grade was significantly different between the two groups. A significant change for ALT (alanine aminotransferase) and AST (aspartate aminotransferase) was seen between the two groups (p = .03 and .02, respectively), while ALP (alkaline phosphatase) serum levels were not significantly different within or between groups. Pertaining to glycemic profile, all variables, except HOMA‐IR, were not significantly different within or between groups. Finally, statistically significant changes were seen in both MDA (malondialdehyde) and TAC (total antioxidant capacity) among the groups (p = .04 and <.001, respectively).

Conclusions

Spirulina may improve fatty liver grade by modifying liver enzymes, oxidative stress, and some lipid profiles; however, there was effect of Spirulina on anthropometric characteristics and blood pressure.
The association between dietary approaches to stop hypertension diet and mediterranean diet with metabolic syndrome in a large sample of Iranian adults: YaHS and TAMYZ Studies
Authors: Hassani Zadeh Shirin , Salehi‐Abargouei Amin , Mirzaei Masoud , Nadjarzadeh Azadeh , Hosseinzadeh Mahdieh
Published: June 2021

Dietary patterns are considered as a modifiable risk factor for metabolic syndrome (MetS). Therefore, the present study aimed to evaluate the association between the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean (MED) dietary patterns and MetS. This cross‐sectional study was conducted on the data from recruitment phase of prospective studies on Iranian adults known as Yazd Health Study (YaHS) and Yazd Nutrition Study (TAMYZ). MetS was diagnosed among 2,221 adults based on the Adult Treatment Panel III criteria. The participants' dietary intake was assessed by a validated food frequency questionnaire. According to the predefined methods, DASH and MED scores were calculated. Multivariate logistic regression was used to evaluate the relationship of DASH and MED dietary patterns with MetS. The prevalence of MetS was 28.8% in the present study. Women who were in the highest quintile of DASH in comparison with those who were in the first quintile tended to decrease the odds of MetS after adjusting for the potential confounders (OR: 0.50, CI: 0.27–0.95). There was a significant decreasing trend in the odds of MetS across increasing quintiles of the DASH in women (p‐trend = .006). Also, the highest adherence to DASH reduced the odds of abdominal obesity (OR: 0.34, CI: 0.15–0.77) in women. Although adherence to MED dietary pattern had no significant relationship with MetS, moderate adherence to this dietary pattern could decrease the odds of fasting blood glucose levels (OR: 0.57, CI: 0.33–0.97) and abdominal obesity (OR: 0.42, CI: 0.20–0.87) in women. We found evidence indicating a significant protective association between DASH and METs and its component in women. Hence, more prospective studies are needed to confirm our findings in other populations.
Inverse molecular docking reveals a novel function of thymol: Inhibition of fat deposition induced by high‐dose glucose in Caenorhabditis elegans
Authors: Ban Fangfang , Hu Liangbin , Zhou Xiao‐Hui , Zhao Yanyan , Mo Haizhen , Li Hongbo , Zhou Wei
Published: June 2021

As a natural product isolated from thyme oil in thyme, thymol (2‐isopropyl‐5‐methylphenol) harbors antiviral, antioxidant, and other properties, and thus could be potentially used for the treatment of various diseases. However, the function of thymol has not been comprehensively studied. Here, we applied an inverse molecular docking approach to identify unappreciated functions of thymol. Potential targets of thymol in humans were identified by the server of DRAR‐CPI, and targets of interest were then assessed by GO and KEGG pathway analysis. Subsequently, homologous proteins of these targets in Caenorhabditis elegans were identified by Blast tool, and their three‐dimensional structures were achieved using Swiss‐Model workspace. Interaction between thymol and the targeted proteins in worms was verified using AutoDock 4.0. Analyses of the targets revealed that thymol could be potentially involved in the glycolysis/gluconeogenesis and fatty acid degradation pathways. To verify the activity of thymol on lipid deposition in vivo, the C. elegans model was established. The lipid content of nematodes induced by high‐dose glucose was determined by Oil Red O and Nile Red staining, and gene expression was assessed by qRT‐PCR. The results showed that thymol might lead to the acceleration of β‐oxidation by upregulating cpt‐1, aco, fabp, and tph‐1, causing the descent of lipid content in nematodes. Our findings indicated that thymol could be potentially used for the treatment of chronic metabolic diseases associated with increased fatty acid deposition.
Features of hippocampal astrocytic domains and their spatial relation to excitatory and inhibitory neurons
Authors: Refaeli Ron , Doron Adi , Benmelech‐Chovav Aviya , Groysman Maya , Kreisel Tirzah , Loewenstein Yonatan , Goshen Inbal
Published: June 2021

The mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in hippocampi made transparent by CLARITY, and determined the elaborate structure, distribution, and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the morphology of thousands of reconstructed domains. We then determined the excitatory somatic content of CA1 astrocytes, and measured the distance between inhibitory neuronal somata to the nearest astrocyte soma. We find that on average, there are almost 14 pyramidal neurons per domain in the CA1, increasing toward the pyramidal layer midline, compared to only five excitatory neurons per domain in the amygdala. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This work provides a comprehensive large‐scale quantitative foundation for studying neuron‐astrocyte interactions.
Bleeding complications in patients with squamous cell carcinoma of the head and neck
Authors: Bergamini Cristiana , Ferris Robert L. , Xie Jing , Mariani Gabriella , Ali Muzammil , Holmes William C. , Harrington Kevin , Psyrri Amanda , Cavalieri Stefano , Licitra Lisa
Published: June 2021

Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti‐EGFR agents or immune checkpoint inhibitors. In contrast, anti‐VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications.
Sinonasal adenocarcinoma: Population‐based analysis of demographic and socioeconomic disparities
Authors: Low Christopher M. , Balakrishnan Karthik , Smith Byron M. , Stokken Janalee K. , O'Brien Erin K. , Van Gompel Jamie J. , Rowan Nicholas R. , Choby Garret
Published: June 2021

Background

Sinonasal adenocarcinoma (SNAC) is a rare tumor. The impact of health disparities on survival, stage at presentation, and utilization of surgery is not well understood in patients with SNAC.

Methods

The Surveillance, Epidemiology, and End Results database was queried for cases of SNAC from 1973 to 2015. Cases were analyzed to assess for disparities in presentation, treatment, and survival.

Results

SNAC was identified in 630 patients. In a multivariate model of overall survival, an age increase of 10 years (Hazard Ratio (HR) = 1.37, p < 0.001), male sex (HR = 1.26, p = 0.045), and more recent decade of diagnosis (HR = 0.74, p < 0.001) were significantly related to time‐to‐death. There is a higher rate of SNAC‐related death in counties with more rural populations (p = 0.027).

Conclusion

Future interventions targeting rural and less well‐educated populations may improve care with the goal of increasing the span of healthy life and reducing survival disparities related to SNAC.
Sex‐Specific Regulation of Interferon‐γ Cytotoxicity in Mouse Liver by Autophagy
Authors: Shen Yang , Cingolani Francesca , Malik Shoaib Ahmad , Wen Jing , Liu Yunshan , Czaja Mark J.
Published: June 2021

Background and Aims

Interferon‐γ (IFNγ) is a central activator of immune responses in the liver and other organs. IFNγ triggers tissue injury and inflammation in immune diseases, which occur predominantly in females for unknown reasons. Recent findings that autophagy regulates hepatotoxicity from proinflammatory cytokines led to an examination of whether defective hepatocyte autophagy underlies sex‐specific liver injury and inflammation induced by IFNγ.

Approach and Results

A lentiviral autophagy‐related 5 (Atg5) knockdown was performed to decrease autophagy‐sensitized alpha mouse liver (AML 12) hepatocytes to death from IFNγ in combination with IL‐1β or TNF. Death was necrosis attributable to impaired energy homeostasis and adenosine triphosphate depletion. Male mice with decreased autophagy from a tamoxifen‐inducible, hepatocyte‐specific Atg5 knockout were resistant to IFNγ hepatotoxicity whereas female knockout mice developed liver injury and inflammation. Female mice had increased IFNγ‐induced signal transducer and activator of transcription 1 (STAT1) levels compared to males. Blocking STAT1, but not interferon regulatory factor 1, signaling prevented IFNγ‐induced hepatocyte death in autophagy‐deficient AML12 cells and female mice. The mechanism of death is STAT1‐induced overexpression of nitric oxide synthase 2 (NOS2) as in vitro hepatocyte death and in vivo liver injury were blocked by NOS2 inhibition.

Conclusions

Decreased hepatocyte autophagy sensitizes mice to IFNγ‐induced liver injury and inflammation through overactivation of STAT1 signaling that causes NOS2 overexpression. Hepatotoxicity is restricted to female mice, suggesting that sex‐specific effects of defective autophagy may underlie the increased susceptibility of females to IFNγ‐mediated immune diseases.
Subsequent attempt tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia; a single institute experience
Authors: Ureshino Hiroshi , Kamachi Kazuharu , Nishioka Atsujiro , Okamoto Sho , Katsuya Hiroo , Yoshimura Mariko , Kubota Yasushi , Ando Toshihiko , Kimura Shinya
Published: June 2021

Discontinuation of tyrosine kinase inhibitors (TKIs) is now a feasible therapeutic goal for patients with chronic phase chronic myeloid leukemia (CML‐CP). Whereas approximately half of patients experience molecular relapse, after resuming with any TKI; the majority re‐achieve a deep molecular response (DMR). It is unclear whether such patients who re‐achieve a durable DMR can discontinue TKI safely again. Here, we retrospectively assessed first, second, and third attempts to stop TKIs in patients with CML‐CP. At the first attempt, 28 out of a total of 53 patients achieved sustained treatment‐free remission (TFR; 53.4%; 95% confidence interval [CI], 39.0%–65.9%). Subsequently, 10 of 25 patients attempted a second TKI discontinuation, and in all cases, this was after receiving second‐generation TKIs. Four of 10 patients successfully achieved TFR (37.5%; 95% CI, 9.9%–65.9%). All patients who relapsed at the second TKI discontinuation attempt were re‐administered TKIs, and soon achieved at least a major molecular remission. All six second relapse patients had a loss of MR4.5 at 3 months after TKI discontinuation. These findings suggest that second and third attempts to successfully stop TKI treatment are feasible in patients with CML‐CP.
Perinatal outcome in monochorionic twin pregnancies after selective fetal reduction using radiofrequency ablation
Authors: Dadhwal Vatsla , Sharma K. Aparna , Rana Anubhuti , Sharma Akash , Singh Lakhwinder
Published: June 2021

Objective

To study the perinatal outcomes in women with complicated monochorionic twin pregnancies undergoing selective fetal reduction using radiofrequency ablation (RFA).

Methods

This retrospective study included 44 patients with monochorionic twin pregnancies, between 14 and 28 weeks of pregnancy, who underwent RFA for selective fetal reduction. Perinatal and maternal outcomes and procedure‐related complications were analyzed.

Results

The procedure was technically successful in all 44 cases. Indications for selective fetal reduction included twin‐to‐twin transfusion syndrome (52.3%), twin reversed arterial perfusion (20.5%), twins discordant for anomaly (15.9%), and selective fetal growth restriction (11.4%). Median gestational age at procedure was 222/7 weeks (range 14–266/7). Live birth rate was 77.3% with three neonatal deaths; so overall survival was 70.5%. Median procedure‐to‐delivery interval was 123/7 weeks (range 24/7–23). There were eight losses before 24 weeks of pregnancy, which included two co‐twin deaths. Median gestational age at delivery was 35 weeks (interquartile range 321/7–37 weeks). The preterm delivery rate was 66.7% (24/36) and preterm prelabor rupture of membranes (PPROM) occurred in 22.7% (10/44) of patients.

Conclusion

Selective fetal reduction using RFA is safe and effective in complicated monochorionic pregnancies. However, the rates of PPROM and preterm delivery remain high.
Safety and efficiency of modified sacrospinous ligament fixation for apical prolapse: Long‐term studies and outcomes
Authors: Hu Pan , Zhong ChunYan , Lu Shentao , Lei Li , Wang Ying , Liu LuBin
Published: June 2021

Objective

To explore the safety and efficiency of modified sacrospinous ligament fixation (MSSF) for apical prolapse.

Methods

A retrospective cohort study. Patients diagnosed with apical prolapse from 2014 to 2019 were recruited and divided into three groups: sacrospinous ligament fixation (SSF), MSSF, and laparoscopic sacral hysteropexy (LSH). All surgical characteristics were obtained and information concerning complications was collected and compared among these three groups.

Results

A total of 710 patients were included: 108 in the SSF group, 260 in the LSH group, and 342 in the MSSF group. The MSSF and SSF groups took less surgical time (P < 0.001) and had shorter hospital stays (P < 0.001). All three methods can significantly change prolapses to point C on the POP quantification score (P < 0.001). Prevalence of vaginal and pelvic pain after surgery was higher in the SSF group (8/108; 7.41%) (P = 0.028), and urinary incontinence was higher in the LSH group (22/260; 8.46%) (P = 0.010). In the LSH group more patients experienced constipation and dyschezia after surgery (prevalence 18/260; 6.92%; P = 0.048). Recurrence of pelvic organ prolapse in the MSSF group (15/324; 4.39%) and LSH group (12/260; 4.62%) was much lower than in the SSF group (16/108; 14.81%) (P < 0.001).

Conclusion

The efficacy of MSSF is commendable with low recurrence of POP and few complications in long‐term follow up.
The impact of prolonged second stage in twins on perinatal outcomes
Authors: Zidan Ragda , Saad Niveen , Siegler Yoav , Justman Naphtali , Mick Ido , Ben‐Asher Hila , Beloosesky Ron , Ginsberg Yuval , Weiner Zeev , Zipori Yaniv
Published: June 2021

Objective

To assess the duration of the second stage of labor in twin pregnancies in relation to maternal and neonatal outcomes.

Methods

A retrospective study between 2014 and 2020. Eligible cases were twin pregnancies that reached the second stage. The pre‐defined groups were based on the total time spent in the second stage of labor; Group 1 (<1 h), group 2 (1–2 h), and group 3 (>2 h), which was considered the prolonged second stage group.

Results

Among the 439 planned vaginal births, successful vaginal delivery of both twins was achieved in 63.8%. Prolonged second stage was observed in 25.8% (89/345). Nulliparity (odds ratio [OR] 7.72, 95% confidence interval [CI] 4.5–13.4) and use of epidural analgesia (OR 5.45, 95% CI 1.2–24.7), were the only independent variables significantly associated with prolonged second stage. Prolonged second stage was associated with a greater risk of intrapartum cesarean delivery (32.6%, P < 0.001), combined delivery (10.1%, P < 0.001), chorioamnionitis (8.3%, P = 0.006) and a admission to neonatal intensive care unit of at least one of the twins (30.3%, P = 0.02).

Conclusion

Prolonged second stage of labor affects maternal and fetal outcome in twin pregnancies.
A forecast of maternal deaths with and without vaccination of pregnant women against COVID‐19 in Mexico
Authors: Lumbreras‐Marquez Mario I. , Fields Kara G. , Campos‐Zamora Melissa , Rodriguez‐Bosch Mario R. , Rodriguez‐Sibaja Maria J. , Copado‐Mendoza Diana Y. , Acevedo‐Gallegos Sandra , Farber Michaela K.
Published: June 2021

Synopsis

With 100% COVID‐19 vaccination among pregnant women during May and June of 2021, the overall predicted number of maternal deaths for 2021 in Mexico would significantly decrease.
Aerial and ground‐based assessments of preemergence herbicide effects on St. Augustinegrass grow‐in
Authors: Wilber Amy L. , McCurdy James D. , Czarnecki Joby M. P. , Stewart Barry R. , Dong Hongxu
Published: June 2021

Preemergence herbicides reduce weed competition during turfgrass establishment, yet little is known regarding preemergence herbicide safety on plugged St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze]. Field research was conducted in 2019 to evaluate the effects of prodiamine, pendimethalin, liquid‐ and granular‐applied oxadiazon, S‐metolachlor, atrazine, atrazine + S‐metolachlor, dithiopyr, and indaziflam on St. Augustinegrass grow‐in. St. Augustinegrass was established vegetatively. Herbicides were applied one day after planting. Visual cover and multispectral reflectance (handheld and aerial) were collected weekly. Chlorophyll Index‐Red Edge (CI‐RE), Ratio Vegetation Index (RVI), and Normalized Difference Vegetation Index (NDVI) were calculated. Indaziflam, which is not labeled for St. Augustinegrass grow‐in or sod production, was included as a treated check and increased days to reach 50% cover and maximum index values from handheld and aerial methods. Prodiamine increased days to reach 50% cover for all response variables except aerial‐derived CI‐RE and RVI. Atrazine as well as granular‐ and liquid‐applied oxadiazon did not increase time to reach 50% visual cover and maximum vegetation index responses relative to the nontreated.
HOXA5 induces M2 macrophage polarization to attenuate carotid atherosclerosis by activating MED1
Authors: Jing Yuchen , Gao Bai , Han Zhiyang , Xin Shijie
Published: June 2021

Macrophage polarization is of great importance in the formation of atherosclerotic plaque. Homeobox A5 (HOXA5), one of the homeobox transcription factors, has been revealed to be closely associated with macrophage phenotype switching. This study aims to investigate the role of HOXA5 in carotid atherosclerosis (CAS). Herein, the role of HOXA5 was explored in polarized RAW264.7 macrophages in vitro and ApoE−/− mice in vivo. Interestingly, compared with that in M0 macrophages, both the mRNA and protein expression levels of HOXA5 were decreased in lipopolysaccharide (LPS)/interferon (IFN)‐γ‐induced M1 macrophages, while increased in IL‐4‐induced M2 macrophages. In addition, in the presence of IL‐4, HOXA5‐overexpressing RAW264.7 cells preferred to polarizing toward M2 phenotypes. Furthermore, we found that HOXA5 bound to the promoter region and activated the expression of mediator subunit 1 (MED1), a gene known to regulate macrophage differentiation. Knocking MED1 down inhibited HOXA5‐enhanced M2 macrophage polarization. In vivo, the CAS model was induced in ApoE−/− mouse fed with a Western‐type diet and placed a perivascular carotid collar. Decreased mRNA and protein expressions of HOXA5 were observed in carotid arteries of CAS mice. Forced overexpression of HOXA5 reduced intimal hyperplasia and lipid accumulation in carotid vessels, and it also promoted the polarization of macrophages to M2 subtypes. The expression of MED1 was decreased in atherosclerotic carotid vessels, while HOXA5 overexpression restored its change. Collectively, HOXA5 in carotid arteries is involved in the macrophage M1/M2 switching in atherosclerotic plaque, which may be associated with its transcriptional regulation of MED1.
The lethal internal face of the coronaviruses: Kidney tropism of the SARS, MERS, and COVID19 viruses
Authors: Motavalli Roza , Abdelbasset Walid Kamal , Rahman Heshu Sulaiman , Achmad Muhammad Harun , Sergeevna Nataliya Klunko , Zekiy Angelina Olegovna , Adili Ali , Khiavi Farhad Motavalli , Marofi Faroogh , Yousefi Mehdi , Ghoreishizadeh Shadi , Shomali Navid , Etemadi Jalal , Jarahian Mostafa
Published: June 2021

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS‐CoV‐2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS‐CoV and the SARS‐CoV. According to several investigations, SARS‐CoV causes proteinuria and renal impairment or failure. The SARS‐CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS‐CoV infection. And recently, during the 2019‐nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.
Parameterizing elastic network models to capture the dynamics of proteins
Authors: Koehl Patrice , Orland Henri , Delarue Marc
Published: June 2021

Coarse‐grained normal mode analyses of protein dynamics rely on the idea that the geometry of a protein structure contains enough information for computing its fluctuations around its equilibrium conformation. This geometry is captured in the form of an elastic network (EN), namely a network of edges between its residues. The normal modes of a protein are then identified with the normal modes of its EN. Different approaches have been proposed to construct ENs, focusing on the choice of the edges that they are comprised of, and on their parameterizations by the force constants associated with those edges. Here we propose new tools to guide choices on these two facets of EN. We study first different geometric models for ENs. We compare cutoff‐based ENs, whose edges have lengths that are smaller than a cutoff distance, with Delaunay‐based ENs and find that the latter provide better representations of the geometry of protein structures. We then derive an analytical method for the parameterization of the EN such that its dynamics leads to atomic fluctuations that agree with experimental B‐factors. To limit overfitting, we attach a parameter referred to as flexibility constant to each atom instead of to each edge in the EN. The parameterization is expressed as a non‐linear optimization problem whose parameters describe both rigid‐body and internal motions. We show that this parameterization leads to improved ENs, whose dynamics mimic MD simulations better than ENs with uniform force constants, and reduces the number of normal modes needed to reproduce functional conformational changes.
Performance evaluation of leukocyte differential on the hematology analyzer Celltac G compared with two hematology analyzers, reference flow cytometry method, and two manual methods
Authors: Yamade Kenji , Yamaguchi Toshihiro , Nagai Yutaka , Kamisako Toshinori
Published: June 2021

Background

The automated hematology analyzer Celltac G (Nihon Kohden) was designed to improve leukocyte differential performance. Comparison with analyzers using different leukocyte detection principles and differential leukocyte count on wedge film (Wedge‐Diff) shows its clinical utility, and comparison with immunophenotypic leukocyte differential reference method (FCM‐Ref) shows its accuracy performance.

Methods

For method comparison, 598 clinical samples and 46 healthy volunteer samples were selected. The two comparative hematology analyzers (CAAs) used were XN‐9000 (Sysmex) and CELL‐DYN Sapphire (Abbott). The FCM‐Ref provided by the Japanese Society for Laboratory Hematology was selected, and a flow cytometer Navios (Beckman‐Coulter) was used. In manual differential, two kinds of automated slide makers were used: SP‐10 (Sysmex) for wedge technique and SPINNER‐2000 (Lion‐Power) for spinner technique. The spinner technique avoids the issue of Wedge‐Diff smudge cells by removing the risk of breaking cells and non‐uniformity of blood cell distribution on films (Spinner‐Diff).

Results

The Celltac G showed sufficient comparability (r = 0.67–1.00) with the CAAs for each leukocyte differential counting value at 0.00–40.87(109/L), and sufficient comparability (r = 0.73–0.97) with FCM‐Ref for each leukocyte differential percentage at 0.4–78.5. The identification ratio of the FCM‐Ref in CD45‐positive cells was 99.7% (99.4% to 99.8%). Differences were found between FCM‐Ref/Celltac G/XN‐9000/Spinner‐Diff and Wedge‐Diff for monocytes and neutrophils. The appearance ratio of smudge cells on wedge and spinner film was 12.5% and 0.5%.

Conclusion

The Celltac G hematology analyzer's leukocyte differential showed adequate accuracy compared with the CAAs, FCM‐Ref, and two manual methods and was considered suitable for clinical use.
Prediction of Fluoxetine and Norfluoxetine Pharmacokinetic Profiles Using Physiologically Based Pharmacokinetic Modeling
Authors: Jeong Hyeon‐Cheol , Chae Yoon‐Jee , Lee Sooyeun , Kang Wonku , Yun Hwi‐yeol , Shin Kwang‐Hee
Published: June 2021

Fluoxetine is a selective serotonin reuptake inhibitor that is metabolized to norfluoxetine by cytochrome P450 (CYP) 2D6, CYP2C19, and CYP3A4. A physiologically based pharmacokinetic model for fluoxetine and norfluoxetine metabolism was developed to predict and investigate changes in concentration‐time profiles according to fluoxetine dosage in the Korean population. The model was developed based on the Certara repository model and information gleaned from the literature. Digitally extracted clinical study data were used to develop and verify the model. Simulations for plasma concentrations of fluoxetine and norfluoxetine after a single dose of 60 or 80 mg fluoxetine were made based on 1000 virtual healthy Korean individuals using the SimCYP version 19 simulator. The mean ratios (simulated/observed) after a single administration of 80 mg fluoxetine for maximum plasma concentration, area under the plasma concentration–time curve, and apparent clearance were 1.12, 1.08, and 0.93 for fluoxetine; the ratios of maximum plasma concentration and area under the plasma concentration–time curve were 1.08 and 1.08, respectively, for norfluoxetine, indicating that the simulated concentration‐time profiles of fluoxetine and norfluoxetine fitted the observed profiles well. The developed model was used to predict plasma fluoxetine and norfluoxetine concentration‐time profiles after repeated administrations of fluoxetine in Korean volunteers. This physiologically based pharmacokinetic model could provide basic understanding of the pharmacokinetic profiles of fluoxetine and its metabolite under various situations.
Predoctoral substance use disorders curricula: A survey analysis and experiential pedagogy
Authors: Odusola Folarin , Kaufman Joshua , Turrigiano Eva , Aydinoglo Nicole , Shulman Matisyahu , Kidd Jeremy , Hu Mei‐Chen , Levin Frances R.
Published: June 2021

Substance Use Disorders (SUD) are chronic health conditions with heritability characteristics, environmental influences, long‐term management considerations and they cooccur. The US opioid epidemic is a crisis of both prescription and nonprescription opioid use. Clinicians now have access to evidence‐based practices but the evolving trends require continuous attention including curriculum initiatives for dental schools. The purpose of this study was to obtain information about the content and educational strategies of current SUD curricula, beneficial educational products for a standardized curriculum and perceived barriers toward standardization. Invitations were sent to 64 US dental schools describing the purpose of this study and a link to complete the survey was provided. Fully completed responses were received from 32 (50.0%) of the schools. Descriptive statistics was used to analyze the data. Most dental schools surveyed (81.3%) have a curriculum for SUD with classroom lectures being the most commonly used teaching method (96.2%), followed by online modules (42.3%). About 30% of the responding schools provided additional educational experiences. Instruction occurred mostly in second (73.1%) and third (77.0%) academic years. Opioids, alcohol, nicotine, and marijuana were the most frequently taught substance classes. Curriculum standardization with online modules (81.3%), case‐based exercises (59.4%), and simulation with standardized patients (43.8%) was considered desirable to improve student competency in the management of patients with SUD. Lack of time (62.5%), space (56.3%), and faculty (50.0%) were cited as the most common barriers to curriculum initiatives. Experiential and achievable options for improving SUD curriculum were highlighted.
Initial experience of endoscopic ultrasound‐guided antegrade covered stent placement with long duodenal extension for malignant distal biliary obstruction (with video)
Authors: So Hoonsub , Oh Dongwook , Takenaka Mamoru , Minaga Kosuke , Uemura Shinya , Iwashita Takuji , Saito Tomotaka , Nakai Yousuke , Kim Seon Ok , Park Do Hyun
Published: June 2021

Background/Purpose

This study aimed to evaluate the feasibility of endoscopic ultrasound (EUS)‐guided antegrade covered stent placement with long duodenal extension (EASL) for malignant distal biliary obstruction (MDBO) with duodenal obstruction (DO) or surgically altered anatomy (SAA) after failed endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Outcomes were technical and clinical success, reintervention rate, adverse events, stent patency, and overall survival. Inverse probability of treatment weighting (IPTW) and competing‐risk analysis were performed to compare with conventional EUS‐BD.

Results

Twenty‐five patients (DO, n = 18; SAA, n = 7) were included. The technical and clinical success rates were 96% and 84%, respectively. Reintervention occurred in two patients (8.3%). Adverse events occurred in six patients (24%; two cholangitis, 16%; four mild postprocedural pancreatitis [24% (n = 4/17) in patients with non‐pancreatic cancers]). The median patency was 9.4 months, and the overall survival was 2.73 months. After IPTW adjustment, the median patency in the EASL (n = 25) and conventional EUS‐BD (n = 29) were 10.1 and 6.5 months, respectively (P = .018).

Conclusions

EASL has acceptable clinical outcomes with a low reintervention rate but higher rate of postprocedural pancreatitis in patients with non‐pancreatic cancers. Randomized trials comparing EASL and conventional EUS‐BD for MDBO with pancreatic cancers and DO/SAA after failed ERCP are needed to validate our findings.
Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes
Authors: Zeng Zhaolong , Ma Xiangzheng , Guo Yifan , Ye Baodong , Xu Maosheng , Wang Wei
Published: June 2021

Background

Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL‐IQ (iterative decomposition of water and fat with echo asymmetry and least‐squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues.

Purpose

To determine if IDEAL‐IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS.

Study Type

Retrospective.

Population

Fifty‐seven patients with AA, 21 patients with MDS, and 24 healthy controls.

Field Strength/Sequence

3.0 T, IDEAL‐IQ sequence.

Assessment

Three independent observers evaluated the IDEAL‐IQ images and measured FF and R2* in the left posterior superior iliac spine.

Statistical Tests

Kruskal–Wallis test, linear correlations, and Bland–Altman analysis were used. A P‐value of <0.05 was considered statistically significant.

Results

The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553).

Data Conclusion

Quantitative IDEAL‐IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS.

Level of Evidence

3

Technical Efficacy Stage

2
Nutrition competencies for undergraduate medical education: Results of an international interdisciplinary consensus
Authors: Cardenas Diana , Díaz Gustavo , Fuchs‐Tarlovsky Vanessa , Cristina Gonzalez Maria , Carrasco Fernando , Cano Angélica María Pérez , Bermúdez Charles , Maza Claudia , Ferraresi Eduardo , Lipovestky Fernando , Villafana Haydee , Arenas‐Márquez Humberto , Calvo Isabel , Cordova Ludwig Roberto Alvarez , Canicoba Marisa , Sánchez Paola , Santana Sergio , Tihista Serrana , Adrianza de Baptista Gertrudis M. , Garcia Yawelida , Correia Maria Isabel Toulson Davisson
Published: June 2021

Background

The gap between the nutrition education provided to medical students and the nutrition competencies and attitudes needed for physicians to provide adequate nutrition care is a global concern. There is no universally accepted benchmark on nutrition competencies for doctors. The objective of this study was to establish, by expert consensus, the objectives of undergraduate nutrition medial education, the nutrition core competencies, and strategies for curriculum development in medical nutrition education.

Methods

We administered a Delphi survey to systematically gather the opinion of a panel of Latin American experts in nutrition. The survey questionnaire was constructed considering scientific literature by using a 5‐point Likert scale. Consensus was defined as >70% agreement on the importance of an item (Likert scale 4 and 5).

Results

A four‐round Delphi survey was conducted for this research. In the second, third, and fourth rounds, we validated a total of 130 competencies by consensus, which were distributed into four different thematic areas: (1) basic nutrition concepts, (2) public nutrition and nutrition prevention throughout the life cycle, (3) nutrition status and disease, and (4) nutrition care process.

Conclusion

The curricula for general physician education in medical school must include health promotion, prevention, and treatment of diseases related to nutrition. This goal can be reached by integrating ≤130 competencies into four different fundamental areas.
Clinico‐pathological significance of suspicious peritoneal cytology in endometrial cancer
Authors: Matsuo Koji , Matsuzaki Shinya , Miller Heather , Nusbaum David J. , Walia Saloni , Matsuzaki Satoko , Shimada Muneaki , Klar Maximilian , Roman Lynda D.
Published: June 2021

Background and Objectives

Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer.

Methods

A population‐based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I–III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine‐Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology.

Results

Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution‐hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29–2.20, p < 0.001) and all‐cause mortality (adjusted‐HR: 1.55, 95% CI: 1.27–1.90, p < 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72–0.99, p = 0.049).

Conclusion

Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.
Recent advances of the ionic chiral selectors for chiral resolution by chromatography, spectroscopy and electrochemistry
Authors: Wu Datong , Ma Cong , Fan Gao‐Chao , Pan Fei , Tao Yongxin , Kong Yong
Published: June 2021

Ionic chiral selectors have been received much attention in the field of asymmetric catalysis, chiral recognition, and preparative separation. It has been shown that the addition of ionic chiral selectors can enhance the recognition efficiency dramatically due to the presence of multiple intermolecular interactions, including hydrogen bond, π–π interaction, van der Waals force, electrostatic ion‐pairing interaction, and ionic‐hydrogen bond. In the initial research stage of the ionic chiral selectors, most of work center on the application in chromatographic separation (capillary electrophoresis, high‐performance liquid chromatography, and gas chromatography). Differently, more and more attention has been paid on the spectroscopy (nuclear magnetic resonance, fluorescence, ultraviolet and visible absorption spectrum, and circular dichroism spectrum) and electrochemistry in recent years. In this tutorial review as regards the ionic chiral selectors, we discuss in detail the structural features, properties, and their application in chromatography, spectroscopy, and electrochemistry.
Predictors of Respiratory Dysfunction at Diagnosis of Robin Sequence
Authors: Duarte Daniele W. , Schweiger Claudia , Manica Denise , Fagondes Simone , Fleith Iran J. , Rojas Juan J. C. , Zanin Eduardo M. , Portinho Ciro P. , Collares Marcus V. M.
Published: June 2021

Objectives/Hypothesis

Robin sequence (RS) consists of associated micrognathia, glossoptosis, and respiratory dysfunction, with or without cleft palate. Studies on how different patient characteristics impact the severity of respiratory dysfunction are scarce and contradictory; this study investigates how different features affect respiratory obstruction severity at diagnosis of RS in controlled analysis.

Study Design

Retrospective cohort study that enrolled 71 RS patients under 90 days old who received care in our institution from 2009 to 2020.

Methods

The primary outcome, respiratory dysfunction, was categorized into four severity groups and analyzed using a multinomial logistic regression model that considered age, sex, mandible length, cleft palate, syndromic diagnosis, other airway anomalies, and degree of glossoptosis.

Results

Mandible length, syndromic diagnosis, and Yellon grade 3 glossoptosis were related to poorer respiratory outcomes (need for respiratory support). In univariate analysis, for each additional 1 mm of mandible length at diagnosis, a mean reduction of 28% in the risk of needing respiratory support was observed (OR = 0.72; 0.58–0.89); syndromic diagnosis and grade 3 glossoptosis also raised the risk (OR = 6.50; 1.59–26.51 and OR = 12.75; 1.03–157.14, respectively). In multivariate analysis, only mandible length significantly maintained its effects (OR = 0.73; 0.56–0.96), a 27% reduction.

Conclusions

Mandible length was an independent predictor for more severe respiratory dysfunction in RS patients, with larger mandibles showing protective effects. Syndromic diagnosis and Yellon grade 3 glossoptosis are also likely to be associated with poorer respiratory outcomes, although this was not demonstrated in multivariate analysis.

Level of Evidence

4 Laryngoscope, 131:2811–2816, 2021
Fundamental Limitations of Huygens’ Metasurfaces for Optical Beam Shaping
Authors: Gigli Carlo , Li Qitong , Chavel Pierre , Leo Giuseppe , Brongersma Mark L. , Lalanne Philippe
Published: June 2021

Optical dielectric metasurfaces composed of arrayed nanostructures are expected to enable arbitrary spatial control of incident wavefronts with subwavelength spatial resolution. For phase modulation, one often resorts to two physical effects to implement a 2π‐phase excursion. The first effect relies on guidance by tall nanoscale pillars and the second one exploits resonant confinement by nanoresonators with two degenerate Mie resonances. The first approach requires high aspect ratios, while the second one, known as Huygens’ metasurfaces, is much flatter, and thus easier to manufacture. The two approaches are compared, more focusing on conceptual rather than technological issues, and fundamental limitations with the latter are identified. The origin of the limitations based on general arguments are explained, such as reciprocity, multimode/monomode operation, and symmetry breaking.
Utility of Preoperative Computed Tomography–Based Body Metrics in Relation to Postoperative Complications in Pediatric Liver Transplantation Recipients
Authors: Verhagen Martijn V. , Levolger Stef , Hulshoff Jan Binne , Werner Maureen J. M. , van der Doef Hubert P. J. , Viddeleer Alain R. , de Kleine Ruben H. , de Haas Robbert J.
Published: June 2021

Computed tomography (CT)‐derived body metrics such as skeletal muscle index (SMI), psoas muscle index (PMI), and subcutaneous fat area index (ScFI) are measurable components of sarcopenia, frailty, and nutrition. While these body metrics are advocated in adults for predicting postoperative outcomes after liver transplantation (LT), little is known about their value in pediatric populations. This study assessed the relation between preoperative CT‐based body metrics and postoperative short‐term outcomes in pediatric LT recipients. Patients aged 0‐18 years who underwent a primary LT were retrospectively included (n = 101; median age 0.5 years; range 0.2‐17.1). SMI, PMI, and ScFI were derived from preoperative axial CT slices. Postoperative outcomes and complications within 90 days were correlated with the CT‐based body metrics. To classify postoperative infections, the Clavien‐Dindo (CD) classification was used. Subgroup analyses were performed for age groups (<1, 1‐10, and >10 years old). An optimal threshold for test performance was defined using Youden’s J‐statistic and receiver operating characteristic curve as appropriate. ScFI was significantly (P = 0.001) correlated with moderate to severe postoperative infections (CD grade 3‐5) in children aged <1 year, with the optimal ScFI threshold being ≤27.1 cm2/m2 (sensitivity 80.4% and specificity 77.8%). A weak negative correlation between SMI and the total duration of hospital stay (R = −0.3; P = 0.01) and intensive care unit (ICU) stay (R = −0.3; P = 0.01) was observed in children aged <1 year. No other associations between CT‐based body metrics and postoperative outcomes were shown. In children aged <1 year with cirrhotic liver disease undergoing LT, preoperative CT‐based body metrics were correlated with moderate to severe postoperative infections (ScFI) and with longer duration of hospital and ICU stay (SMI), and thus can be considered important tools for pre‐LT risk assessment.
Medicaid Expansion Association With End‐Stage Liver Disease Mortality Depends on Leniency of Medicaid Hepatitis C Virus Coverage
Authors: Wahid Nabeel A. , Lee Jihui , Kaplan Alyson , Fortune Brett E. , Safford Monika M. , Brown Robert S. , Rosenblatt Russell
Published: June 2021

The Affordable Care Act expanded Medicaid around the same time that direct‐acting antivirals became widely available for the treatment of hepatitis C virus (HCV). However, there is significant variation in Medicaid HCV treatment eligibility criteria between states. We explored the combined effects of Medicaid expansion and leniency of HCV coverage under Medicaid on liver outcomes. We assessed state‐level end‐stage liver disease (ESLD) mortality rates, listings for liver transplantation (LT), and listing‐to‐death ratios (LDRs) for adults aged 25 to 64 years using data from United Network for Organ Sharing and Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research. States were divided into 4 nonoverlapping groups based on expansion status on January 1, 2014 (expansion versus nonexpansion) and leniency of Medicaid HCV coverage (lenient versus restrictive coverage). Joinpoint regression analysis evaluated the significant changes in slope over time (joinpoints) during the pre‐expansion (2009‐2013) and postexpansion (2014‐2018) time periods. We found significant changes in the annual percent change for population‐adjusted ESLD deaths between 2014 and 2015 in all cohorts except for the nonexpansion/restrictive cohort, in which deaths increased at the same annual percent change from 2009 to 2018 (annual percent change of +2.5%; 95% confidence interval [CI], 1.8‐3.3]). In the expansion/lenient coverage cohort, deaths increased at an annual percent change of +2.6% (95% CI, 1.8‐3.5) until 2014 and then tended to decrease at an annual percent change of −0.4% (95% CI, −1.5 to 0.8). LT listings tended to decrease over time for all cohorts. For LDRs, only the expansion/lenient and expansion/restrictive cohorts had statistically significant joinpoints. Improvements in ESLD mortality and LDRs were associated with both Medicaid expansion and leniency of HCV coverage under Medicaid. These findings suggest the importance of implementing more lenient and widespread public health insurance to improve liver disease outcomes, including mortality.