bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractHemorrhage 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

AbstractBackgroundSinonasal 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.MethodsThe 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.ResultsSNAC 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).ConclusionFuture 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

AbstractDiscontinuation 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

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

AbstractObjectiveTo explore the safety and efficiency of modified sacrospinous ligament fixation (MSSF) for apical prolapse.MethodsA 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.ResultsA 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).ConclusionThe 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

AbstractObjectiveTo assess the duration of the second stage of labor in twin pregnancies in relation to maternal and neonatal outcomes.MethodsA 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.ResultsAmong 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).ConclusionProlonged 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

SynopsisWith 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

AbstractPreemergence 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

AbstractMacrophage 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

AbstractThe 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

AbstractCoarse‐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

AbstractBackgroundThe 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.MethodsFor 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).ResultsThe 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%.ConclusionThe 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

AbstractFluoxetine 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.