bluuebunny/crossref_metadata_2025_split huggingface dataset:
The measurement and health risk assessment of polychlorinated biphenyls in butter samples using the QuEChERS/GC‐MS method
Authors: Yaminifar Somaye , Aeenehvand Saeed , Ghelichkhani Gilda , Ahmadloo Mahsa , Arabameri Majid , Moazzen Mojtaba , Shariatifar Nabi 
Published: August 2021

The aim of this study was to evaluate non‐dioxin‐like polychlorinated biphenyls (NDL‐PCBs) and the health risk from butter samples using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) modified method and gas chromatography/mass spectrometry (GC‐MS). A total of 60 traditional and industrial butter samples were collected from the local markets of Tehran, Iran, and were subjected to GC‐MS. The results showed that the mean concentration of total NDL‐PCBs in samples was 21.701 ± 9.02 ng/g fat. The amounts of PCBs in traditional butter samples were higher than in the industrial samples. PCB concentrations in all samples were lower than the European Union standard (40 ng/g fat). The 95th percentile incremental lifetime cancer risk of total NDL‐PCBs for children (1.79E−5) and adults (3.80E−6) was less than the acceptable risk level (10−4).
Venous air embolism in CT coronary angiography
Authors: Davies Alexander , Mathur Namit , Lau Theodore , Crossett Marcus , Lau Kenneth K 
Published: August 2021

AbstractIntroductionVenous air embolization (VAE) from IV lines is a risk with IV contrast administration. The incidence of VAE ranges from 7% to 23%. While life‐threatening VAE is rare, there is the potential risk of serious cerebrovascular events from paradoxical systemic air embolization (SAE) in patients with congenital intracardiac shunts. CT coronary angiogram (CTCA) hypothetically carries a higher risk of VAE as it requires dual injections as compared to single bolus dose contrast used in CT chest (CTC). The aim of this study was to assess the risk of VAE using CTCA as compared to conventional CTC. The incidence of cardiac shunts and their association with paradoxical SAE were also investigated.MethodsA retrospective study was conducted at a tertiary hospital. Adult patients undergoing CTCA and CTC over a 6‐month period in 2017 were included. Images were reviewed on PACS for the presence of VAE. Electronic medical records were interrogated for evidence of neurological sequelae or requiring neurological imaging (CTB/MRIB) within 1 month of the initial imaging.Results508 patients were included, 408 underwent CTCA and 100 underwent CTC. The VAE incidence in CTCA was 24% (94 patients) and 10% in the CTC (10 patients). This was statistically significant. Among the CTCA group, 36% (108 patients) had an intracardiac shunt. No statistically significant difference in VAE incidence was identified in CTCA patients with shunts vs without shunts. There was no incidence of SAE in both groups.ConclusionVAE is more common with CTCA than conventional CTC. There were no cases of paradoxical SAE found.
Complete spontaneous remission of small cell lung cancer in the absence of specific treatment: A case report
Authors: Song Sung Heon , Ha Chang Won , Kim Changhwan , Seong Gil Myeong 
Published: August 2021

AbstractSmall cell lung cancer (SCLC) is a unique tumor that has a distinct clinical behavior and dismal prognosis. If untreated, it can become aggressively malignant, and life expectancy could be limited to weeks. Spontaneous regression of lung cancer has rarely been reported, and among them SCLC is even rarer. The underlying mechanisms of spontaneous regression are poorly understood. Here, we report a case of complete spontaneous SCLC remission in an elderly patient.
Endemic New Zealand aphids (Hemiptera: Aphididae) parasitised by native Aphidiinae (Hymenoptera: Braconidae), not biological control parasitoids
Authors: Bulman Simon , Drayton Gabrielle M , Cameron Peter J , Teulon David A J , Walker Graham P 
Published: August 2021

AbstractAlmost all known Aphidiinae (Hymenoptera: Braconidae) parasitoid species in New Zealand have been introduced as biological control agents (BCAs) for introduced aphids or have self‐introduced. The New Zealand endemic aphid (Hemiptera: Aphididae) fauna consists of a small number of species that are parasitised, on occasion, by Aphidiinae that remain unidentified. A persistent concern has been that introduced BCAs are among the parasitoids attacking the rare endemic aphids. After 14 years of collection, 66 cytochrome oxidase I (COI) gene sequences were obtained from emerged parasitoids, mummies or by specific PCR from parasitised New Zealand aphids. Parasitoid samples were from 13 aphid species (eight endemic, plus five introduced species feeding on native plants) at 20 locations. The Aphidiinae COI sequences comprised two new clades of native New Zealand parasitoids. One species‐rich clade appeared to represent a radiation after dispersal to New Zealand, whereas the second clade consisted only of parasitoids from a single endemic host. The patterns of aphid/parasitoid associations were strongly suggestive of host specificity towards the endemic aphids, while a subgroup of the newly discovered native Aphidiinae was found parasitising four introduced aphid species, despite the short time period these aphids are assumed to have been in New Zealand. We found no evidence for attack of endemic aphids by introduced BCAs or other introduced aphidiines. On the rare occasions that parasitism was detected in the most common endemic Aphidinae aphid, Aphis cottieri Carver, 1999, it was by a native Aphidiinae lineage, not by Aphidius ervi Haliday, 1834.
Drugs and bugs: Negative affect, psychostimulant use and withdrawal, and the microbiome
Authors: Forouzan Shadab , McGrew Keely , Kosten Therese A. 
Published: August 2021

AbstractBackground and ObjectivesA growing body of literature demonstrates that the human microbiota plays a crucial role in health and disease states, as well as in the body's response to stress. In addition, the microbiome plays a role in psychological well‐being and regulating negative affect. Regulation of negative affect is a factor in psychostimulant abuse disorders. We propose a risk chain in which stress leads to negative affect that places an individual at risk to develop or relapse to psychostimulant abuse disorder. Stress, negative affect, and psychostimulant use all alter the gut microbiome.MethodsThis review brings together the literature on affective disorders, stress, and psychostimulant abuse disorders to assess possible modulatory actions of the gut–brain axis to regulate these conditions.ResultsStudies reviewed across the various disciplines suggest that the dysbiosis resulting from drug use, drug withdrawal, or stress may cause an individual to be more susceptible to addiction and relapse. Probiotics and prebiotics reduce stress and negative affect.Scientific SignificanceTreatment during the withdrawal phase of psychostimulant abuse disorder, when the microbiome is altered, may ameliorate the symptoms of stress and negative affect leading to a reduced risk of relapse to psychostimulant use.
Examination of testicular lumicrine regulation of activins and immunoregulatory genes in the epididymal caput
Authors: Wijayarathna Rukmali , Genovese Rosemary , Meinhardt Andreas , Loveland Kate L , Groome Nigel P , Hinton Barry T , Hedger Mark P 
Published: August 2021

AbstractBackgroundImmunoregulatory genes encoding activin A (Inhba) and B (Inhbb), and indolamine 2,3‐dioxygenase‐1 (Ido1) are highly expressed in the murine caput epididymidis, which also has a network of intraepithelial mononuclear phagocytes. This environment is postulated to promote immunological tolerance to epididymal sperm. The factors regulating the immunoregulatory agents in the epididymal caput are poorly understood.ObjectivesThis study aimed to investigate the potential role of testicular lumicrine factors in regulating activin and other immune‐related genes in the caput epididymidis.Materials and methodsThe efferent ducts in adult C57/Bl6 mice were exposed and ligated bilaterally. Serum and tissues were collected seven days later. Animals with bilateral sham ligation and animals with no ligations (collectively referred to as the “intact” group) were used as controls.ResultsPressure‐induced seminiferous epithelial damage due to intratubular fluid accumulation was observed in all ligated testes. Testicular inhibin was significantly increased and testosterone was elevated in some animals following bilateral ligation, but serum testosterone, serum LH, and serum inhibin were normal. Ligation caused epithelial regression in the initial segment, with similar but less severe effects in other caput segments. Activin A staining by immunohistochemistry in the epithelium was reduced in bilateral ligation, particularly in the initial segment, with moderately reduced staining intensity in the rest of the caput. Inhba expression within the caput was not significantly affected by bilateral ligation, but Inhbb was reduced by more than 60%. Transcripts encoding the macrophage‐specific receptor Cx3cr1 were significantly reduced following bilateral ligation, but other immune cell markers, Ido1, and inflammatory genes were unaffected.ConclusionThese data indicate that testicular lumicrine secretion regulates several genes that are preferentially expressed in the initial segment, but has marginal effects on genes such as those encoding activin A and IDO1, which are expressed more widely in the caput.
To offer or request? Disclosing variants of uncertain significance in prenatal testing
Authors: Watts Gabriel , Newson Ainsley J. 
Published: August 2021

AbstractThe use of genomic testing in pregnancy is increasing, giving rise to questions over how the information that is generated should be offered and returned in clinical practice. While these tests provide important information for prenatal decision‐making, they can also generate information of uncertain significance. This paper critically examines three models for approaching the disclosure of variants of uncertain significance (VUS), which can arise from forms of genomic testing such as prenatal chromosomal microarray analysis (CMA). Contrary to prevailing arguments, we argue that respect for reproductive autonomy does not justify adopting a model on which an offer to disclose VUS is a routine part of genetic counselling. Instead, we contend that a commitment both to solidarity between healthcare providers and pregnant women and to the acceptance of a novel principle of caution under normative uncertainty means that we should instead adopt a model of VUS disclosure that imposes a strong presumption against offering to disclose VUS. The upshot of this is that it should be standard practice to only offer to disclose VUS when this is requested by the woman undergoing CMA. We defend our position against claims that arise from an alleged right to such information and that a presumption against an offer will lead to inequity.
Normative force of appeals to personhood in dementia care: A critical examination of Kitwood's account of personhood
Authors: Soofi Hojjat 
Published: August 2021

AbstractIn this paper, I critically examine Kitwood's account of personhood for people with dementia. His account has been influential in supporting appeals to personhood in both clinical and bioethical literature on dementia care. I demonstrate that Kitwood's account does not run into common objections against invoking personhood as a normative notion, namely, the objection of exclusionary implications and the objection of redundancy. I argue, however, that Kitwood's account suffers from two other major conceptual issues. These include (a) unreasonable social contingency, and thus, precariousness, of his notion of personhood for people with dementia; and (b) insufficient theoretical connection between his account of personhood and his proposed list of indicators of well‐being for people with dementia. Despite these issues, I do not agree with the following view: that, in the context of dementia care, scholars should refrain from appealing to personhood considerations. Instead, I defend the view that while Kitwood fails to offer a compelling theoretical account of personhood of people with dementia, his empirically driven list of indicators of well‐being and his notion of malignant social phycology seem to be sensitive to key ethical considerations relevant to dementia care. I propose that we pursue alternative ways of explaining what is morally (un) desirable about them without (explicit) appeal to personhood.
Public health, induced abortion, and spontaneous abortion
Authors: Simkulet William 
Published: August 2021

AbstractBruce P. Blackshaw and Daniel Rodger contend that if we assume fetuses are persons, then abortion is a public health crisis that justifies overriding a gestational mother's rights and compelling her to carry the fetus to term, but dawdle addressing greater public health crises like spontaneous abortion and hunger. They draw a distinction between deliberate and indeliberate harm to justify restricting rights in the former, but not the latter; but such distinction fails to justify restricting rights in most public health crises. Furthermore, it fails to justify curtailing abortion rights as unwilling gestational mothers might deliberately induce abortion in self‐defense, merely indeliberately harming the fetus.
Bayesian adaptive trial design for a continuous biomarker with possibly nonlinear or nonmonotone prognostic or predictive effects
Authors: Liu Yusha , Kairalla John A. , Renfro Lindsay A. 
Published: August 2021

AbstractAs diseases like cancer are increasingly understood on a molecular level, clinical trials are being designed to reveal or validate subpopulations in which an experimental therapy has enhanced benefit. Such biomarker‐driven designs, particularly “adaptive enrichment” designs that initially enroll an unselected population and then allow for later restriction of accrual to “marker‐positive” patients based on interim results, are increasingly popular. Many biomarkers of interest are naturally continuous, however, and most existing design approaches either require upfront dichotomization or force monotonicity through algorithmic searches for a single marker threshold, thereby excluding the possibility that the continuous biomarker has a nondisjoint and truly nonlinear or nonmonotone prognostic relationship with outcome or predictive relationship with treatment effect. To address this, we propose a novel trial design that leverages both the actual shapes of any continuous marker effects (both prognostic and predictive) and their corresponding posterior uncertainty in an adaptive decision‐making framework. At interim analyses, this marker knowledge is updated and overall or marker‐driven decisions are reached such as continuing enrollment to the next interim analysis or terminating early for efficacy or futility. Using simulations and patient‐level data from a multi‐center Children's Oncology Group trial in Acute Lymphoblastic Leukemia, we derive the operating characteristics of our design and compare its performance to a traditional approach that identifies and applies a dichotomizing marker threshold.
Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1‐dioxide derivatives as potent STAT3 inhibitors
Authors: Li Wen‐Zhen , Xi Hui‐Zhi , Wang Yi‐Jie , Ma Hong‐Bo , Cheng Zhi‐Qiang , Yang Yu , Wu Meng‐Ling , Liu Ting‐Mei , Yang Wen , Wang Qin , Liao Meng‐Ya , Xia Yong , Zhang Yi‐Wen 
Published: August 2021

AbstractAs a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1‐dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3‐dependent dual‐luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3‐mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
A microdosing framework for absolute bioavailability assessment of poorly soluble drugs: A case study on cold‐labeled venetoclax, from chemistry to the clinic
Authors: Alaarg Amr , Menon Rajeev , Rizzo David , Liu Yemin , Bien Jeffrey , Elkinton Tricia , Grieme Timothy , Asmus Lutz R. , Salem Ahmed Hamed 
Published: August 2021

AbstractThis work presents an end‐to‐end approach for assessing the absolute bioavailability of highly hydrophobic, poorly water‐soluble compounds that exhibit high nonspecific binding using venetoclax as a model drug. The approach utilizes a stable labeled i.v. microdose and requires fewer resources compared with traditional approaches that use radioactive 14C‐labeled compounds. The stable labeled venetoclax and internal standard were synthesized, then an i.v. formulation was developed. In the clinical study, female subjects received a single oral dose of venetoclax 100 mg followed by a 100‐µg i.v. dose of cold‐labeled 13C‐venetoclax at the oral time of maximum concentration (Tmax). The i.v. microdose was prepared as an extemporaneous, sterile compounded solution on the dosing day by pharmacists at the clinical site. Several measures were taken to ensure the sterility and safety of the i.v. preparation. A sensitive liquid chromatography‐tandem mass spectrometry method was developed to allow the detection of plasma levels from the i.v. microdose. Plasma samples were collected through 72 h, and pharmacokinetic parameters were estimated using noncompartmental methods. Postdosing sample analysis demonstrated the consistency of the preparations and allowed the precise calculation of the pharmacokinetic parameters based on the actual injected dose. The absolute bioavailability of venetoclax was estimated at 5.4% under fasting conditions. Venetoclax extraction ratio was estimated to be 0.06 suggesting that the fraction transferred from the enterocytes into the liver is limiting venetoclax bioavailability. The proposed framework can be applied to other highly hydrophobic, poorly water‐soluble compounds that exhibit high nonspecific binding to support the understanding of their absorption and disposition mechanisms and guide formulation development.
Aestivation as a response to climate change: the Great Banded Grayling Brintesia circe in Central Europe
Authors: Birch Robert J. , Markl Gregor , Gottschalk Thomas K. 
Published: August 2021

1. Climate change has forced species to shift distribution, alter migration behaviour, or change phenology. One of these adaptation strategies is aestivation to overcome hot, dry summers. For example, the abundance of the Great Banded Grayling Brintesia circe Fabricius (Lepidoptera, Nymphalidae) in Southern Germany used to show one flight peak between June and August, while now, a bimodal phenological record suggests 3–4 weeks of aestivation during the driest summer weeks.2. To study this new phenomenon, a capture‐mark‐recapture study was performed in two nature reserves in Southern Germany during 92 days in 2019 and 2020. Gender, wing condition, and exact location of individuals of B. circe were recorded. These data show that in June (first flight period), 76%, 481 of 635 captured individuals were males, while in late August and September (second flight period), ≥95%, 452 of 462 were females. No individual marked during the first flight period was recaptured during the second flight period.3. The results imply that mating takes place during the first flight period only, especially females aestivate, probably to avoid oviposition during the hottest and driest parts of the summer and that an unknown part of the population may disperse out or into the investigated habitats. This behaviour appears to have changed during the last decades probably as an adaptation to climate change. Females of B. circe are forced to oviposit later in summer as earlier eggs laid during hotter and drier times are less likely to develop successfully.
Diagnosis of upper respiratory tract disorders in horses using a cheap, smartphone‐connected, flexible and steerable borescope
Authors: Neuckermans Z. , Paulussen E. , Verhaeghe L.‐M. , van Loon G. 
Published: August 2021

SummaryBackgroundEndoscopy is essential for the diagnosis of upper respiratory tract (URT) disorders in horses but equipment is expensive. An industrial borescope might be used to visualise the URT when an endoscope is not available.ObjectivesTo investigate the applicability of a cheap, smartphone‐connected, flexible and steerable borescope to perform URT endoscopy in horses.Study designProspective descriptive study.MethodsIn horses with a clinical indication, endoscopy was first performed with a borescope and subsequently with a veterinary endoscope, which was used as gold standard. Typical URT structures of interest (depending on clinical signs) were digitally recorded. Recordings of both examinations were reviewed by a blinded observer.ResultsOne hundred horses underwent both endoscopic examinations via the right (n = 100) and left (n = 24) nasal passage. In 81/83 attempts, the ethmoidal labyrinth and sinus ostia were visualised on the right side and in 22/24 attempts on the left side. Pharyngeal and laryngeal structures could always be visualised except in 6 horses where the tip of the epiglottis could not be seen due to technical failure of the steering mechanism. In 66/72 attempts, the trachea could be visualised proximally, of which the carina was visualised in 59. Borescope and endoscope grading scores for pharyngeal lymphoid hyperplasia, recurrent laryngeal neuropathy and tracheal mucus were identical in 88/100, 93/100 and 48/59 horses, respectively. The remainder differed only one or two subgrades. The borescope was replaced halfway through the study as the steering mechanism started to fail after 45 to 50 examinations.Main limitationsLack of reliability and the absence of a working channel of this particular borescope model.ConclusionsA flexible, steerable borescope, connected to a smartphone, allows visualising specific parts of the URT in horses.
Skin microbiome alterations in seborrheic dermatitis and dandruff: A systematic review
Authors: Tao Rong , Li Ruoyu , Wang Ruojun 
Published: August 2021

AbstractSeborrheic dermatitis (SD) and dandruff (DF) are common chronic inflammatory skin diseases characterized by recurrent greasy scales, sometimes with erythema and itchiness. Although the exact pathophysiology of the disease is still unclear, current theories highlight the role of microbes on the skin surface in the pathogenesis of SD. Here, we conducted a systematic review to investigate the skin microbiome alterations in patients with SD/DF. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between 1 January 2000 and 31 December 2020. A total of 12 studies with 706 SD/DF samples and 379 healthy samples were included in this study. The scalp and face were predominated by the fungi of Ascomycota and Basidiomycota and the bacteria of Actinobacteria and Firmicutes. In general, the included studies demonstrated an increased Malassezia restricta/Malassezia globosa ratio and a reduction in the Cutibaterium/Staphylococcus ratio in the setting of SD/DF. Staphylococcus was associated with epidermal barrier damage, including elevated levels of trans‐epidermal water loss and pH, while Cutibacterium had a positive correlation with water content. Malassezia was also found to be related to an increased itching score and disease severity. Further studies focusing on the interactions between various microbes and the host and microbes can help us to better understand the pathogenesis of SD/DF.