bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evolutionary algorithm based feature selection and fuzzy rule reduction technique for the prediction of skin cancer
Authors: Jha Saurabh , Mehta Ashok Kumar 
Published: November 2021

SummaryIn current years, the death rate from skin cancers (SCs) tends to develop pretty. Various research verified that SC rank third as a deadliest disease, after breast and lung cancer. It will become vital to diagnose this malignancy at an early stage. The objective of this research is to mix machine learning and soft computing techniques to gain higher accuracy within the prediction of SC. To play out the exploration work, we utilized two data sets, one from “Save Life Hospital,” India, and the other is the UCI repository skin cancer data set. In this article, three meta‐heuristic algorithms, the FS_GA, the FS_PSO, and the FS_ACO, were used to select the best features from the data set provided to it. The AFRG_algorithm generates a set of fuzzy rules automatically and the RR_algorithm reduces certain fuzzy rules from the fuzzy system. For the SCC_dataset, the end accuracy obtained was 97.67%, 98.45%, and 99.22%. For the UCI_dataset, the end accuracy obtained was 98.81%, 99.72%, and 99.67%. Experimental results on the used datasets show that the proposed method strikingly improves the forecast exactitude of skin malignancy.
Structure and Photophysical Properties of 1,1,2,2‐Tetra(1‐anthryl)ethane: A C(sp3)−C(sp3) Bond Substituted with Four Anthracene Units
Authors: Aoki Shu , Tsurumaki Eiji , Yamashina Masahiro , Wakamatsu Kan , Toyota Shinji 
Published: November 2021

AbstractThe title aromatic compound comprising four anthracene units was synthesized by the McMurry coupling of di(1‐anthryl) ketone as a hydrogenated product in 65 % yield. The molecule forms a C2 symmetric structure with the ap conformation about the C(sp3)−C(sp3) single bond, as revealed by X‐ray analysis and DFT calculations. The UV/vis and fluorescence spectra of this compound were compared with those of anthracene, di(1‐anthryl)methane, and 1,2‐di(1‐anthryl)ethane. The fluorescence spectrum showed a broad emission band at 450 nm having a long lifetime at 21 ns, which was assignable to an excimer‐type emission, in contrast to the other reference compounds. The characteristic photophysical property is discussed in terms of the molecular structure with the aid of the noncovalent interaction plots and the conformational analysis.
Lipid raft‐disrupting miltefosine preferentially induces the death of colorectal cancer stem‐like cells
Authors: Park So‐Yeon , Kim Jee‐Heun , Choi Jang‐Hyun , Lee Choong‐Jae , Lee Won‐Jae , Park Sehoon , Park Zee‐Yong , Baek Jeong‐Heum , Nam Jeong‐Seok 
Published: November 2021

AbstractBackgroundLipid rafts (LRs), cholesterol‐enriched microdomains on cell membranes, are increasingly viewed as signalling platforms governing critical facets of cancer progression. The phenotype of cancer stem‐like cells (CSCs) presents significant hurdles for successful cancer treatment, and the expression of several CSC markers is associated with LR integrity. However, LR implications in CSCs remain unclear.MethodsThis study evaluated the biological and molecular functions of LRs in colorectal cancer (CRC) by using an LR‐disrupting alkylphospholipid (APL) drug, miltefosine. The mechanistic role of miltefosine in CSC inhibition was examined through normal or tumour intestinal mouse organoid, human CRC cell, CRC xenograft and miltefosine treatment gene expression profile analyses.ResultsMiltefosine suppresses CSC populations and their self‐renewal activities in CRC cells, a CSC‐targeting effect leading to irreversible disruption of tumour‐initiating potential in vivo. Mechanistically, miltefosine reduced the expression of a set of genes, leading to stem cell death. Among them, miltefosine transcriptionally inhibited checkpoint kinase 1 (CHEK1), indicating that LR integrity is essential for CHEK1 expression regulation. In isolated CD44high CSCs, we found that CSCs exhibited stronger therapy resistance than non‐CSC counterparts by preventing cell death through CHEK1‐mediated cell cycle checkpoints. However, inhibition of the LR/CHEK1 axis by miltefosine released cell cycle checkpoints, forcing CSCs to enter inappropriate mitosis with accumulated DNA damage and resulting in catastrophic cell death.ConclusionOur findings underscore the therapeutic potential of LR‐targeting APLs for CRC treatment that overcomes the therapy‐resistant phenotype of CSCs, highlighting the importance of the LR/CHEK1 axis as a novel mechanism of APLs.
Large‐scale genomic sequencing reveals adaptive opportunity of targeting mutated‐PI3Kα in early and advanced HER2‐positive breast cancer
Authors: Guo Lin‐Wei , Li Xiao‐Guang , Yang Yun‐Song , Lu Xun‐Xi , Han Xiang‐Chen , Lang Guan‐Tian , Chen Li , Shao Zhi‐Ming , Hu Xin 
Published: November 2021

AbstractBackgroundFew studies have discussed the contradictory roles of mutated‐PI3Kα in HER2‐positive (HER2+) breast cancer. Thus, we characterised the adaptive roles of PI3Kα mutations among HER2+ tumour progression.MethodsWe conducted prospective clinical sequencing of 1923 Chinese breast cancer patients and illustrated the clinical significance of PIK3CA mutations in locally advanced and advanced HER2+ cohort. A high‐throughput PIK3CA mutations‐barcoding screen was performed to reveal impactful mutation sites in tumour growth and drug responses.ResultsPIK3CA mutations acted as a protective factor in treatment‐naïve patients; however, advanced/locally advanced patients harbouring mutated‐PI3Kα exhibited a higher progressive disease rate (100% vs. 15%, p = .000053) and a lower objective response rate (81.7% vs. 95.4%, p = .0008) in response to trastuzumab‐based therapy. Meanwhile, patients exhibiting anti‐HER2 resistance had a relatively high variant allele fraction (VAF) of PIK3CA mutations; we defined the VAF > 12.23% as a predictor of poor anti‐HER2 neoadjuvant treatment efficacy. Pooled mutations screen revealed that specific PI3Kα mutation alleles mediated own biological effects. PIK3CA functional mutations suppressed the growth of HER2+ cells, but conferred anti‐HER2 resistance, which can be reversed by the PI3Kα‐specific inhibitor BYL719.ConclusionsWe proposed adaptive treatment strategies that the mutated PIK3CA and amplified ERBB2 should be concomitantly inhibited when exposing to continuous anti‐HER2 therapy, while the combination of anti‐HER2 and anti‐PI3Kα treatment was not essential for anti‐HER2 treatment‐naïve patients. These findings improve the understanding of genomics‐guided treatment in the different progressions of HER2+ breast cancer.
Analytical and medico‐legal problems linked to the presence of delta‐8‐tetrahydrocannabinol (delta‐8‐THC): Results from urine drug testing in Sweden
Authors: Helander Anders , Johansson Malin , Andersson Annika , Villén Tomas 
Published: November 2021

AbstractDuring routine urine drug testing for cannabis use targeting delta‐9‐tetrahydrocannabinol carboxylic acid (delta‐9‐THC‐COOH) at the Karolinska University Laboratory in Sweden, an unknown interfering peak was observed in the liquid‐chromatographic–tandem mass‐spectrometric (LC–MS/MS) confirmative analysis. The peak showed the same exact mass and most abundant fragments as delta‐9‐THC‐COOH but a slightly shorter retention time, thereby not fulfilling all requirements for a positive identification. The analytical results suggested that it was a similar compound, and with access to reference material, it could be identified as the double bond isomer delta‐8‐THC‐COOH. Delta‐8‐THC has recently become popular as a recreational drug, although its legality varies and is sometimes unclear. In Sweden, all THC isomers are classified substances. The slight difference in retention times was sufficient to distinguish the THC‐COOH isomers in the routine LC–MS/MS method, but another LC method allowed better peak separation and individual quantification. At the Karolinska University Laboratory, delta‐8‐THC‐COOH was first observed in April 2020, and the highest incidence was noted in June 2020 when it was present in 5.3% of all THC‐COOH‐positive samples. The incidence later decreased to today only occasional findings. Large differences in the relative presence of the isomers in the urine samples indicated different origin, for example, synthetically produced pure delta‐8‐THC, or mixtures of both THC isomers formed during combustion of cannabidiol (CBD). In conclusion, the appearance of delta‐8‐THC and other isomers on the recreational drug market risks causing analytical and medico‐legal problems, due to confusion with delta‐9‐THC.
Variation in male‐built nest volume with nesting‐support quality, colony, and egg production in whiskered terns
Authors: Paillisson Jean‐Marc , Chambon Rémi 
Published: November 2021

AbstractNest building can represent an energetically costly activity for a variety of animal taxa. Besides, the determinants of within‐species variation in the design of nests, notably with respect to natural and sexual selection, are still insufficiently documented. Based on an observational study, we examined the influence of nesting conditions (nesting‐support quality, colony, laying date, and year) on male‐built nest volume and also its potential role as a postmating sexually selected display in the whiskered ternChlidonias hybrida. This tern species is a monogamous colonial bird with obligate biparental care breeding on aquatic vegetation. Hence, large nesting platforms are expected to be a selective advantage because they would better withstand adverse environmental conditions and provide a secure structure for eggs. Nest size may also serve as a postmating sexual trait, and variation in egg production would be positively associated with nest size. We found that nest volume was adjusted to different environmental cues. A positive relationship was found between nest volume and nesting‐support quality, indicating that the leaf density of white waterlily is essential for nest stability. Variation in nest volume was not correlated to colony size but varied among colonies and years. Male‐built nest volume was also positively associated with mean egg volume per clutch but not with clutch size. The fitness consequences of building a large nest are yet to be studied, and additional investigations are recommended to better understand whether the activity of males early during breeding season (e.g., nest building and courtship feeding performance) really serves as postmating sexually selected signals.
Comparing whole‐genome shotgun sequencing and DNA metabarcoding approaches for species identification and quantification of pollen species mixtures
Authors: Bell Karen L. , Petit Robert A. , Cutler Anya , Dobbs Emily K. , Macpherson J. Michael , Read Timothy D. , Burgess Kevin S. , Brosi Berry J. 
Published: November 2021

AbstractMolecular identification of mixed‐species pollen samples has a range of applications in various fields of research. To date, such molecular identification has primarily been carried out via amplicon sequencing, but whole‐genome shotgun (WGS) sequencing of pollen DNA has potential advantages, including (1) more genetic information per sample and (2) the potential for better quantitative matching. In this study, we tested the performance of WGS sequencing methodology and publicly available reference sequences in identifying species and quantifying their relative abundance in pollen mock communities. Using mock communities previously analyzed with DNA metabarcoding, we sequenced approximately 200Mbp for each sample using Illumina HiSeq and MiSeq. Taxonomic identifications were based on the Kraken k‐mer identification method with reference libraries constructed from full‐genome and short read archive data from the NCBI database. We found WGS to be a reliable method for taxonomic identification of pollen with near 100% identification of species in mixtures but generating higher rates of false positives (reads not identified to the correct taxon at the required taxonomic level) relative to rbcL and ITS2 amplicon sequencing. For quantification of relative species abundance, WGS data provided a stronger correlation between pollen grain proportion and sequence read proportion, but diverged more from a 1:1 relationship, likely due to the higher rate of false positives. Currently, a limitation of WGS‐based pollen identification is the lack of representation of plant diversity in publicly available genome databases. As databases improve and costs drop, we expect that eventually genomics methods will become the methods of choice for species identification and quantification of mixed‐species pollen samples.
1,3‐Diethynyl‐5‐(X)‐benzene‐Bridged [Cp*(dppe)Fe]n+ Units: Effect of Substituents on the Metal‐Metal Interactions
Authors: Lepont Joseph , Roisnel Thierry , Hamon Jean‐René , Lapinte Claude 
Published: November 2021

AbstractThe new complexes [1,3‐{Cp*(dppe)Fe−C≡C‐}2‐5‐(X)‐(C6H3)] (X=CH3, [m‐1 b]; X=C(O)OCH3, [m‐1 c]; X=C≡C−4−C6H4−C(O)OCH3, [m‐1 d]; X=C≡C−4−C6H4‐NO2, [m‐1 e]) were prepared by reaction of the iron chloride Cp*(dppe)FeCl (4) and the proligands 3 b–e obtained by a cross coupling reaction between the suitable aryl dibromides and trimethylsylilacethylene. After purification the complexes [m‐1 b–e] were isolated in yields ranging from 14 to 37 % and characterized by elemental analysis, high‐resolution, ESI‐mass spectra, multinuclear NMR, cyclic voltammetry, and IR spectroscopy. The complexes [m‐1 b], [m‐1 d], and [m‐1 e] were also characterized by XRD analyses on single crystals. The doubly oxidized complexes [m‐1 b–e](PF6)2 were prepared (in ca. 64–87 % yields) by treatment of a CH2Cl2 solution of the corresponding neutral complexes [m‐1 b–e] with two equiv. of [(C5H5)2Fe](PF6). The mixed‐valence complexes (MV) [m‐1 b–e](PF6) were obtained by comproportionation between one equiv. of [m‐1 b–e] and one equiv. of [m‐1 b–e](PF6)2. CV, IR and NIR data led to the conclusion that the MV [m‐1 b–e](PF6) complexes are weakly coupled Class II MV derivatives and the distribution of the charge between the alkynyl iron centers and the phenyl ring might be tuned by the X‐substituents in a limited extend.
Trapping Experiments during Reductive Debrominations of Aminotribromosilanes with Alkenes
Authors: Keuter Jan , Hepp Alexander , Lips Felicitas 
Published: November 2021

AbstractIn‐situ generated amido‐substituted disilynes (SiMe3)2N−Si≡Si−N(SiMe3)2 1 and (SiMe3)DippN−Si≡Si−N(SiMe3)Dipp 2 were observed examined upon the reductive dehalogenation of the tribromosilanes {N(SiMe3)2}SiBr3 3 and {N(SiMe3)Dipp}SiBr3 4 with Rieke magnesium (Mg*). Both disilynes were trapped with ethylene to yield the double [2+1] and [2+2] cycloaddition products 5 and 6, respectively. The transient disilynes 1 and 2 were investigated with DFT calculations that revealed 1 to feature more triple bond character than 2. The in‐situ generated disilyne 2 was further quenched with 1,5‐cyclooctadiene to yield the double [2+2] cycloaddition product 7. In the presence of cyclooctatetraene, the reductive debromination of 4 with Mg* generates the bromo‐substituted silacyclopentene 8. This species was also isolated with 2,3‐dimethyl‐1,3‐butadiene used as trapping reagent as the major product 9, besides the side product 10, that comprises two cyclotrisilene rings linked via a butene unit. The formation of 10 shows that a cyclotrisilene can occur as a side product during the reductive debromination of 4 in the presence of the alkene.
Dysregulated anterior insula reactivity as robust functional biomarker for chronic pain—Meta‐analytic evidence from neuroimaging studies
Authors: Ferraro Stefania , Klugah‐Brown Benjamin , Tench Christopher R , Yao Shuxia , Nigri Anna , Demichelis Greta , Pinardi Chiara , Bruzzone Maria Grazia , Becker Benjamin 
Published: November 2021

AbstractNeurobiological pain models propose that chronic pain is accompanied by neurofunctional changes that mediate pain processing dysfunctions. In contrast, meta‐analyses of neuroimaging studies in chronic pain conditions have not revealed convergent evidence for robust alterations during experimental pain induction. Against this background, the present neuroimaging meta‐analysis combined three different meta‐analytic approaches with stringent study selection criteria for case–control functional magnetic resonance imaging experiments during acute pain processing with a focus on chronic pain disorders. Convergent neurofunctional dysregulations in chronic pain patients were observed in the left anterior insula cortex. Seed‐based resting‐state functional connectivity based on a large publicly available dataset combined with a meta‐analytic task‐based approach identified the anterior insular region as a key node of an extended bilateral insula‐fronto‐cingular network, resembling the salience network. Moreover, the meta‐analytic decoding showed that this region presents a high probability to be specifically activated during pain‐related processes, although we cannot exclude an involvement in autonomic processes. Together, the present findings indicate that dysregulated left anterior insular activity represents a robust neurofunctional maladaptation and potential treatment target in chronic pain disorders.
E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination
Authors: Ding Ming‐Jie , Fang Hao‐Ran , Zhang Jia‐Kai , Shi Ji‐Hua , Yu Xiao , Wen Pei‐Hao , Wang Zhi‐Hui , Cao Sheng‐Li , Zhang Yi , Shi Xiao‐Yi , Zhang Hua‐Peng , He Yu‐Ting , Yan Bing , Tang Hong‐Wei , Guo Dan‐Feng , Gao Jie , Liu Zhen , Zhang Li , Zhang Shui‐Jun , Zhang Xiao‐Jing , Guo Wen‐Zhi 
Published: November 2021

Abstract

Background and Aims
Hepatic ischemia‐reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear.

Approach and Results
RNF5 expression was significantly down‐regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia‐reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte‐specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48‐linked ubiquitination, thereby inhibiting the activation of apoptosis‐regulating kinase 1 (ASK1) and its downstream c‐Jun N‐terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR.

Conclusions
We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5‐PGAM5 axis may be a promising therapeutic target for HIR.
Even a little sleepiness influences neural activation and clinical reasoning in novices
Authors: Cleland Jennifer , Gates Laura J. , Waiter Gordon D. , Ho Vincent B. , Schuwirth Lambert , Durning Steven 
Published: November 2021

AbstractBackground and aimsSleepiness influences alertness and cognitive functioning and impacts many aspects of medical care, including clinical reasoning. However, dual processing theory suggests that sleepiness will impact clinical reasoning differently in different individual, depending on their level of experience with the given condition. Our aim, therefore, was to examine the association between clinical reasoning, neuroanatomical activation, and sleepiness in senior medical students.MethodsOur methodology replicated an earlier study but with novices rather than board‐certified physicians. Eighteen final‐year medical students answered validated multiple‐choice questions (MCQs) during an fMRI scan. Each MCQ was projected in three phases: reading, answering, and reflection (modified think aloud). Echo‐planar imaging (EPI) scans gave a time series that reflected blood oxygenation level dependent (BOLD) signal in each location (voxel) within the brain. Sleep data were collected via self‐report (Epworth Sleepiness Scale) and actigraphy. These data were correlated with answer accuracy using Pearson correlation.ResultsAnalysis revealed an increased BOLD signal in the right dorsomedial prefrontal cortex (P < .05) during reflection (Phase 3) associated with increased self‐reported sleepiness (ESS) immediately before scanning. Covariate analysis also revealed that increased BOLD signal in the right supramarginal gyrus (P < .05) when reflecting (Phase 3) was associated with increased correct answer response time. Both patterns indicate effortful analytic (System 2) reasoning.ConclusionOur findings that novices use System 2 thinking for clinical reasoning and even a little (perceived) sleepiness influences their clinical reasoning ability to suggest that the parameters for safe working may be different for novices (eg, junior doctors) and experienced physicians.
Heavy uterine bleeding in adolescent caused by uterine vascular lesion: A case report
Authors: Le Dao Thi Anh , Nguyen Anh Duy , Phan Giang Hoang , Pham Nha Ba , Vuong Thang Toan , Nguyen Tuan Quang 
Published: November 2021

AbstractObjectiveTo analyze a case of heavy uterine bleeding in adolescence caused by an arteriovenous malformation (AVM) in Hanoi Obstetrics and Gynecology Hospital, Vietnam.MethodsWe observed a case of a 14‐year‐old girl, without vaginal sexual intercourse experience, having heavy uterine bleeding caused by AVM. She underwent a laparoscopic operation at the hospital for vascular lesions in the uterine anterior wall, which caused an internal hemorrhage of 1500 ml blood loss into the peritoneal cavity. Three years later, this patient was hospitalized twice for massive vaginal bleeding.ResultsResults of ultrasound and magnetic resonance imaging indicated a uterine intramural mass with enlarged vessels connecting to the endometrial cavity. A pelvic digital subtraction angiography was performed and showed profuse bleeding from a ruptured branch of the left uterine artery. This artery was embolized at Bach Mai hospital and the bleeding was stopped. The patient had stable health and normal menstrual periods after 4 months of follow up.ConclusionAbnormal mass with dilated vessels in the myometrium in a patient experiencing heavy uterine bleeding is an exclusive sign of uterine vascular malformation and can be treated by angioembolization.