bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward role of westerly‐monsoon interplay in linking interannual variations of late spring precipitation over the southeastern Tibetan Plateau
Authors: Song Chengyu , Wang Jing , Liu Yanju , Zhang Ling , Ding Yihui , Li Qiaoping , Shen Xinyong , Song Yanling , Yan Yuping
Published: November 2021

A recent study reported a notable westerly‐monsoon interplay (WMI) to the northeast of the Tibetan Plateau in boreal summer. However, this study introduces another striking and unique WMI over the southeastern TP (SETP) in late spring (May), emphasizing the critical roles of the upstream mid‐latitude westerly and the downstream Bay of Bengal (BOB) summer monsoon (BOBSM) in linking interannual variations of precipitation over SETP. In this study, the research SETP domain (22.5°–27.5°N, 87.5°–97.5°E) as well as a westerly index (WI) over the pivotal upstream westerly domain (22.5°–30°N, 65°–80°E) and a monsoon index (MI) over the pivotal downstream BOBSM domain (12.5°–22.5°N, 87.5°–100°E) are defined to investigate connections between the westerly and BOBSM and their combined effects on precipitation over SETP. The results indicate that the mid‐latitude westerly and BOBSM show opposite effects on precipitation over SETP. The weaker westerly and the stronger BOBSM correspond to enhanced SETP precipitation, and vice versa. The enhanced BOBSM acts as a predominant role on the strengthening of precipitation, while the decelerated westerly plays a secondary dynamical amplification role. To quantify their synergistic roles in linking SETP precipitation, a WMI index is defined. Statistical analysis suggests that this newly defined WMI index has a higher positive correlation with the precipitation over SETP. The correlation has a prominent increase compared to individual correlations between WI/MI and SETP precipitation, and dynamic conditions in high WMI index years are more favorable for the formation of SETP precipitation. The possible mechanism is that the BOBSM southerly strengthens and the southern branch of the upstream mid‐latitude westerly weakens in high WMI index years, resulting in an anomalous cyclone over the northwestern BOB and an anomalous anticyclone over the western TP. The anomalous cyclone resembles a Rossby wave response to the increased precipitation over SETP, and the precipitation in turn contributes to maintaining the BOB cyclonic anomaly and the above anticyclonic anomaly via the latent heating release. This positive feedback effect is conducive to enhanced SETP precipitation.
More autosomal dominant SPG18 cases than recessive? The first AD‐SPG18 pedigree in Chinese and literature review
Authors: Chen Shuai , Zou Jin‐Long , He Shuang , Li Wei , Zhang Jie‐Wen , Li Shu‐Jian
Published: November 2021

Objective

Hereditary spastic paraplegia (HSP) due to ERLIN2 gene mutations was designated as spastic paraplegia 18 (SPG18). To date, SPG18 families/cases are still rarely reported. All early reported cases shared the autosomal recessive (AR) inheritance pattern. Over the past 3 years, autosomal dominant (AD) or sporadic SPG18 cases had been continuously reported. Here, we reported the clinical and genetic features of the first autosomal dominant SPG18 pedigree in Chinese.

Methods

We conducted detailed medical history inquiry, neurological examinations of the proband and his family members, and charted the family tree. The proband underwent brain and cervical magnetic resonance imaging (MRI), electromyography (EMG), and whole exome sequencing. Sanger sequencing was performed to verify the genetic variation in the proband and some family members. A literature review of all reported SPG18 families/cases was carried out to summarize the clinical‐genetic characteristics of SPG18 under different inheritance patterns.

Results

Four patients were clinically diagnosed as chronic spastic paraplegia in three consecutive generations with the autosomal dominant inheritance model. All the patients presented juvenile‐adolescent onset and gradually worsening pure HSP phenotype. Clinical phenotypes were consistent within the family. Whole exome sequencing in the proband identified a previously reported heterozygous c.502G > A (p.V168M) mutation in exon 8 of ERLIN2 gene. This mutation was cosegregated with the phenotype in the family and was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. To date, eight AR‐SPG18 families, five AD‐SPG18 families, and three sporadic cases had been reported. Clinical phenotype of AD‐SPG18 was juvenile‐adolescent onset pure HSP, while the phenotype of AR‐SPG18 was mostly complicated HSP with earlier onset and more severe conditions. In rare cases, the initial spastic paraplegia could evolve to rapidly progressive amyotrophic lateral sclerosis (ALS).

Conclusions

We reported the first autosomal dominant SPG18 pedigree in Chinese Han population, which added more pathogenic evidence for V168M mutation. As more SPG18 cases reported, the essentials of SPG18 need to be updated in clinical practice. Special attentions should be given in gene test for upper motor neuron disorders in case of missing heterozygous mutations in ERLIN2.
Reinforcing or counterproductive behaviors for sustainable entrepreneurship? The influence of causation and effectuation on sustainability orientation
Authors: Johnson Matthew P. , Hörisch Jacob
Published: November 2021

Effectuation, as an emerging theoretical approach in entrepreneurship, is receiving increasing attention in research and practice. Still, the integration of effectuation in sustainable entrepreneurship literature is sparse, and its influence on the sustainability orientation of ventures has so far not been examined in the academic literature. This article, therefore, investigates the influence that causal and effectual behaviors have on the sustainability orientation of established entrepreneurial ventures. This is important to consider, especially if entrepreneurial behaviors were to influence sustainability orientation negatively, this could potentially thwart the venture's ability to create lasting sustainability value. Based on a quantitative survey among 140 sustainable ventures, we find support for the hypothesis that causal behaviors reinforce sustainability orientation. We demonstrate that effectual behaviors exert a positive influence on sustainability orientation as well. Thus, the experimentation and flexibility of goals that ventures possess reflect that effectual behaviors are not at the expense of sustainability orientation. These results can inform sustainable entrepreneurs and educators to use both behaviors purposefully and highlight causal and effectual behaviors are equally important elements for sustainable entrepreneurship education.
Sustainability risk and portfolio management—A strategic scenario method for sustainable product development
Authors: Villamil Carolina , Schulte Jesko , Hallstedt Sophie
Published: November 2021

Companies need to strategically develop their portfolio and find the balance between being proactive and passive in relation to sustainability. In this study, a strategic perspective based on backcasting from overarching socio‐ecological sustainability principles was used as a lens to understand how companies might adapt their product portfolios to avoid threats and exploit opportunities on increasingly sustainability‐driven markets. The study shows that sustainability performance, market success, and time are key areas to be considered in the product portfolio process to ensure short‐term profitability and long‐term competitiveness. A novel method was developed and tested in one academic group and two companies to explore how such a strategic sustainability perspective can support the product portfolio process in practice. The results indicate that the strategic layered double‐flow scenario method, including different time horizons, was supportive in identifying opportunities and avoid risks in the sustainable development process at the company.
Age‐specific prevalence of human papillomavirus and abnormal cytology at baseline in a diverse statewide prospective cohort of individuals undergoing cervical cancer screening in Mississippi
Authors: Clarke Megan A. , Risley Carolann , Stewart Mary W. , Geisinger Kim R. , Hiser Laree M. , Morgan Jody C. , Owens Kenyata J. , Ayyalasomayajula Krishna , Rives Rhonda M. , Jannela Ashish , Grunes Dianne E. , Zhang Lei , Schiffman Mark , Wagner Sarah , Boland Joseph , Bass Sara , Wentzensen Nicolas
Published: November 2021

Background

Mississippi (MS) has among the highest rates of cervical cancer incidence and mortality in the United States, with disproportionately higher rates among Blacks compared to Whites. Here, we evaluate the prevalence of high‐risk human papillomavirus (HPV) and abnormal cytology in a representative baseline sample from a diverse statewide cohort of individuals attending cervical screening in MS from the STRIDES Study (STudying Risk to Improve DisparitiES in cervical cancer).

Methods

We included individuals aged 21–65 years undergoing screening at the University of Mississippi Medical Center (UMMC) and the Mississippi State Department of Health (MSDH) from May to November 2018. We calculated age‐specific HPV prevalence, overall and by partial HPV16/18 genotyping, and abnormal cytology by race.

Results

A total of 6871 individuals (mean age 35.7 years) were included. HPV prevalence was 25.6% and higher in Blacks (28.0%) compared to Whites (22.4%). HPV prevalence was significantly higher in Blacks aged 21–24 years (50.2%) and 30–34 years (30.2%) compared to Whites in the same age groups (32.1% and 20.7%; p < 0.0001, respectively). The prevalence of high‐grade cytologic abnormalities, a cytologic sign of cervical precancer, peaked earlier in Blacks (ages 25–29) compared to Whites (35–39). For comparison, we also analyzed HPV prevalence data from the National Health and Nutrition Examination Survey (NHANES, 2013–2016) and observed similar racial differences in HPV prevalence among women aged 21–24 years.

Conclusions

Our findings suggest that Blacks undergoing cervical cancer screening in MS have higher prevalence of other high‐risk 12 HPV types at younger ages and experience an earlier peak of high‐grade cytologic abnormalities compared to Whites.
Management recommendations for pancreatic manifestations of von Hippel–Lindau disease
Authors: Laks Shachar , van Leeuwaarde Rachel , Patel Dhaval , Keutgen Xavier M. , Hammel Pascal , Nilubol Naris , Links Thera P. , Halfdanarson Thorvardur R. , Daniels Anthony B. , Tirosh Amit ,   for the Pancreatic Manifestations Recommendations Development Subcommittee of the VHL Alliance
Published: November 2021

Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018‐2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL‐related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL‐related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL‐related pancreatic manifestations.
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

In 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

The 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

Background

Lipid 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.

Methods

This 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.

Results

Miltefosine 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.

Conclusion

Our 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

Background

Few 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.

Methods

We 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.

Results

PIK3CA 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.

Conclusions

We 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

During 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

Nest 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

Molecular 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

The 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

In‐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

Neurobiological 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

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

Background and aims

Sleepiness 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.

Methods

Our 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.

Results

Analysis 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.

Conclusion

Our 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

Objective

To analyze a case of heavy uterine bleeding in adolescence caused by an arteriovenous malformation (AVM) in Hanoi Obstetrics and Gynecology Hospital, Vietnam.

Methods

We 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.

Results

Results 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.

Conclusion

Abnormal 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.
COVID‐19 in pregnant women and children: Insights on clinical manifestations, complexities, and pathogenesis
Authors: Meyyazhagan Arun , Pushparaj Karthika , Balasubramanian Balamuralikrishnan , Kuchi Bhotla Haripriya , Pappusamy Manikantan , Arumugam Vijaya Anand , Easwaran Murugesh , Pottail Lalitha , Mani Poonkothai , Tsibizova Valentina , Di Renzo Gian Carlo
Published: November 2021

Pregnancy changes the body's immune system to counteract the spectrum of infections, including COVID‐19, which can pose complications. Pregnant women are less likely to contract COVID‐19 infections than the general public. However, pregnant women are at slightly increased risk of becoming severely unwell if they do catch COVID‐19, and congenital conditions in pregnant women may worsen the state of infection and lead to critical stages and even mortality. The possibility of vertical transmission has been reported in only a few cases of COVID‐19; however, it was not noted in cases of SARS and MERS. Vaccination coverage in pregnant women remains a challenge. Children are the next suspected and vulnerable population to acquire infection after the first and second waves. Children are disproportionately infected compared with older populations, but the severity of infection is less compared to adults. This review highlights the complexities of COVID‐19 in pregnant women and the underlying reasons why children tend to be comparatively less severely affected. Ethnicity, nutrition, lifestyle, and therapeutics influence the severity of infection in children. Low expression of angiotensin‐converting enzyme 2 receptors, indigenous virus competence, and maternal immunity is the first‐line defense for children against COVID‐19. Habituating herbal medicines from childhood may help support a robust and defensive immune system to counteract novel antigens and encourage healthy generations.
Systematic review of the safety, immunogenicity, and effectiveness of COVID‐19 vaccines in pregnant and lactating individuals and their infants
Authors: Fu Winnie , Sivajohan Brintha , McClymont Elisabeth , Albert Arianne , Elwood Chelsea , Ogilvie Gina , Money Deborah
Published: November 2021

Background

There is significant risk of complications and vulnerability to severe COVID‐19 disease in pregnancy, yet hesitancy exists around COVID‐19 vaccination during pregnancy and lactation.

Objective

To summarize the safety, immunogenicity, and effectiveness of COVID‐19 vaccines in pregnancy and lactation.

Search strategy

A systematic search of MEDLINE, Embase, PubMed, medRxiv, and bioRxiv.

Selection criteria

Identified original studies published on pregnant and/or lactating individuals who received one or more doses of a COVID‐19 vaccine.

Data collection and analysis

A descriptive summary organized by safety, immunogenicity, and effectiveness outcomes of COVID‐19 vaccination in pregnancy and lactation.

Main results

In total, 23 studies were identified. Humoral response and functional immunity were interrogated and found. Increasing placental transfer ratios in cord blood were associated with increasing time from the first vaccine dose to delivery. Safety data indicated that pregnant and lactating populations experienced vaccine‐related reactions at similar rates to the general population. No increased risk of adverse obstetrical or neonatal outcomes were reported. One study demonstrated that pregnant individuals were less likely to experience COVID‐19 when vaccinated.

Conclusion

COVID‐19 vaccination in pregnant and lactating individuals is immunogenic, does not cause significant vaccine‐related adverse events or obstetrical and neonatal outcomes, and is effective in preventing COVID‐19 disease.
Lessening of the pervasiveness of interpersonal patterns in borderline personality disorder explains symptom decrease after treatment: A process analysis
Authors: Kramer Ueli , Beuchat Hélène , Grandjean Loris , Seragnoli Federico , Djillali Slimane , Choffat Chloe , George Elisa , Despland Jean‐Nicolas , Kolly Stéphane , de Roten Yves
Published: November 2021

Background

Problematic interpersonal patterns, as defined by the core conflictual relationship theme (CCRT) method, are part of the clinical presentation of clients with borderline personality disorder (BPD). So far, we do not know whether the pervasiveness of interpersonal patterns changes and if this change explains therapy outcome.

Methods

In a secondary analysis of a randomized controlled trial on a brief version of psychiatric treatment for BPD, a treatment with a psychodynamic focus, the present study included N = 39 clients. One early session and one late session of the treatment were transcribed and analyzed using the CCRT method.

Results

It appeared that pervasiveness of the predominant CCRT decreased over the course of the brief treatment; this effect was robust across treatment conditions. Change in pervasiveness in any CCRT component explained a small portion of variance of the decrease in borderline symptoms observed at the end of treatment.

Discussion

Lessening of pervasiveness of problematic in‐session interpersonal patterns may be hypothesized as potential mechanism of effective treatment for BPD which should be tested in controlled designs.
Clinicopathologic models predicting non‐sentinel lymph node metastasis in cutaneous melanoma patients: Are they useful for patients with a single positive sentinel node?
Authors: Rentroia‐Pacheco Barbara , Tjien‐Fooh Félicia J. , Quattrocchi Enrica , Kobic Ajdin , Wever Renske , Bellomo Domenico , Meves Alexander , Hieken Tina J.
Published: November 2021

Background and Objectives

Of clinically node‐negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non‐sentinel lymph nodes (NSLNs). Approximately 80% of SLN‐positive patients have a single positive SLN.

Methods

To assess whether state‐of‐the‐art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single‐institution cohort of 143 patients with cN0 SLN‐positive primary melanoma who underwent subsequent completion lymph node dissection. We used sensitivity (SE) and positive predictive value (PPV) to characterize the ability of the models to identify patients at high risk for NSLN disease.

Results

Across Stage III patients, all clinicopathologic models tested had comparable performances. The best performing model identified 52% of NSLN‐positive patients (SE = 52%, PPV = 37%). However, for the single SLN‐positive subgroup (78% of cohort), none of the models identified high‐risk patients (SE > 20%, PPV > 20%) irrespective of the chosen probability threshold used to define the binary risk labels. Thus, we designed a new model to identify high‐risk patients with a single positive SLN, which achieved a sensitivity of 49% (PPV = 26%).

Conclusion

For the largest SLN‐positive subgroup, those with a single positive SLN, current model performance is inadequate. New approaches are needed to better estimate nodal disease burden of these patients.
Hsa‐miR‐335 enhances cell migration and invasion in lung adenocarcinoma through targeting Copine‐1
Authors: Wang Yang , Zhang Jing , Zhong Li‐Ye , Huang Shang‐Jia , Yu Nan‐Nan , Ouyang Lan , Niu Yu‐Long , Chen Jun‐Xiong , Lu Chun‐Hua , He Qing‐Yu
Published: November 2021

Lung adenocarcinoma (LAC) is one of the most common pulmonary adenocarcinomas with a high peak of mortality, and metastasis is the main culprit of LAC deaths. microRNAs play important role in cancer metastasis, and thus are regarded as potential diagnostic and prognostic markers for human cancers. However, many miRNAs exhibit dual roles in diverse cellular contexts. Here, we revealed that hsa‐miR‐335, a previously reported tumor suppressor, exhibited an oncogenic role in LAC. Overexpression of miR‐335 enhanced the abilities of A549 and H1299 cells to invade and migrate by regulating epithelial‐mesenchymal transition, while inhibition of miR‐335 exhibited an opposite effect in vitro and in vivo. Mechanically, miR‐335 inhibited the expression of Copine‐1 (CPNE1), an NF‐κB suppressor, through interacting with its mRNA 3′UTR, while mutating the binding sites abolished this inhibitory effect. This finding not only highlights the suppressive effect of CPNE1 on cell motility, but also provides new insight into miR‐335 in promoting LAC metastasis.
Longitudinal associations between facets of sleep and adiposity in youth
Authors: LeMay‐Russell Sarah , Schvey Natasha A. , Kelly Nichole R. , Parker Megan N. , Ramirez Eliana , Shank Lisa M. , Byrne Meghan E. , Swanson Taylor N. , Kwarteng Esther A. , Faulkner Loie M. , Djan Kweku G. , Zenno Anna , Brady Sheila M. , Yang Shanna B. , Yanovski Susan Z. , Tanofsky‐Kraff Marian , Yanovski Jack A.
Published: November 2021

Objective

Beyond sleep duration, other facets of sleep such as variability and timing may be associated with obesity risk in youth. However, data are limited. Using a longitudinal design, this study tested whether multiple facets of sleep were associated with fat mass gain over 1 year.

Methods

A convenience sample of non‐treatment‐seeking youth (age 8‐17 years) wore actigraphy monitors for 14 days. Average weekly sleep duration, within‐person sleep duration variability, weekend catch‐up sleep, bedtime and wake time shift, social jet lag, bedtime, wake time, and sleep midpoint were calculated. The association of each facet of baseline sleep with 1‐year fat mass, adjusting for baseline fat mass and height, was examined.

Results

A total of 137 youths (54.0% female; mean [SD], age 12.5 [2.6] years; 28.4% non‐Hispanic Black or African American; baseline fat mass = 15.3 [8.9] kg; 1‐year fat mass = 17.0 [10.0] kg; 28.5% with baseline overweight or obesity) were studied. Wake time (p = 0.03) and sleep midpoint (p = 0.02) were inversely associated with 1‐year fat mass, such that earlier wake time and midpoint were associated with higher 1‐year fat mass. No other facet of sleep was significantly associated with 1‐year fat mass (p > 0.09).

Conclusions

Using objective measures, youth with earlier wake times and sleep midpoints had greater gains in fat mass. Additional research is needed to determine whether sleep timing may be a modifiable target to prevent pediatric obesity.
Development of new and validated HPTLC methods for the qualitative and quantitative analysis of hyperforin, hypericin and hyperoside contents in Hypericum species
Authors: Saçıcı Esra , Yesilada Erdem
Published: November 2021

Purpose

Hypericum perforatum L. (St. John's wort) is a medicinally important member of Hypericaceae. Many pharmacological activities have been mostly attributed to its hyperforin, hypericin and/or hyperoside contents. Therefore, qualitative and quantitative determinations of these ingredients are essential to justify the beneficial effects of St. John's wort on health. In the European Pharmacopoeia, the TLC and HPLC methods were given for this purpose. High performance thin layer chromatography (HPTLC) has recently become increasingly used as a suitable technique for analysing herbal drugs. This study aims to develop new and validated HPTLC methods to analyse these active components in different Hypericum spp. to find other suitable species to replace the official plant.

Methods

Three different mobile phases were developed: n‐hexane‐ethyl acetate (8:2) for hyperforin analysis, toluene‐chloroform‐ethyl acetate‐formic acid (8:5:3.5:0.6) for hypericin analysis and ethyl acetate‐formic acid‐acetic acid‐water (15:2:2:1) for hyperoside analysis. These newly developed and validated HPTLC systems were further applied to determine their concentrations in different Hypericum species.

Results

Hyperforin concentration was found between 6.40 to 26.40 mg/g only in H. triquetrifolium, H. scabrum and two H. perforatum samples; hypericin was detected between 0.81 and 1.41 mg/g only in H. bithynicum, H. perfoliatum, H. triquetrifolium and two H. perforatum samples; and hyperoside was identified in all tested specimens ranging from 1.01 to 9.73 mg/g. The new HPTLC methods developed and validated in the present study may ensure reliable results for the qualification and quantification of hyperforin, hypericin and hyperoside contents in Hypericum species.