bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex‐dependent alterations in hippocampal connectivity are linked to cerebrovascular and amyloid pathologies in normal aging
Authors: Schweitzer Noah , Li Jinghang , Thurston Rebecca C. , Lopresti Brian , Klunk William E. , Snitz Beth , Tudorascu Dana , Cohen Ann , Kamboh M. Ilyas , Halligan‐Eddy Edythe , Iordanova Bistra , Villemagne Victor L. , Aizenstein Howard , Wu Minjie
Published: October 2023

INTRODUCTION

Compared to males, females have an accelerated trajectory of cognitive decline in Alzheimer's disease (AD). The neurobiological factors underlying the more rapid cognitive decline in AD in females remain unclear. This study explored how sex‐dependent alterations in hippocampal connectivity over 2 years are associated with cerebrovascular and amyloid pathologies in normal aging.

METHODS

Thirty‐three females and 21 males 65 to 93 years of age with no cognitive impairment performed a face‐name associative memory functional magnetic resonance imaging (fMRI) task with a 2‐year follow‐up. We acquired baseline carbon 11‐labeled Pittsburgh compound B ([11C]PiB) positron emission tomography (PET) and T2‐weighted fluid‐attenuated inversion recovery (T2‐FLAIR) MRI to quantify amyloid β (Aβ) burden and white matter hyperintensity (WMH) volume, respectively.

RESULTS

Males had increased hippocampal‐prefrontal connectivity over 2 years, associated with greater Aβ burden. Females had increased bilateral hippocampal functional connectivity, associated with greater WMH volume.

DISCUSSION

These findings suggest sex‐dependent compensatory mechanisms in the memory network in the presence of cerebrovascular and AD pathologies and may explain the accelerated trajectory of cognitive decline in females.
Expanding the Range of Bioorthogonal Tags for Multiplex Stimulated Raman Scattering Microscopy
Authors: Murphy Neville , Tipping William J. , Braddick Henry J. , Wilson Liam T. , Tomkinson Nicholas C. O. , Faulds Karen , Graham Duncan , Farràs Pau
Published: October 2023

Multiplex optical detection in live cells is challenging due to overlapping signals and poor signal‐to‐noise associated with some chemical reporters. To address this, the application of spectral phasor analysis to stimulated Raman scattering (SRS) microscopy for unmixing three bioorthogonal Raman probes within cells is reported. Triplex detection of a metallacarborane using the B−H stretch at 2480–2650 cm−1, together with a bis‐alkyne and deuterated fatty acid can be achieved within the cell‐silent region of the Raman spectrum. When coupled to imaging in the high‐wavenumber region of the cellular Raman spectrum, nine discrete regions of interest can be spectrally unmixed from the hyperspectral SRS dataset, demonstrating a new capability in the toolkit of multiplexed Raman imaging of live cells.
Pushing Up the Size Limit of Boron‐doped peri‐Acenes: Modular Synthesis and Characterizations
Authors: Zhang Jin‐Jiang , Yang Lin , Liu Fupin , Serra Gianluca , Fu Yubin , Lucotti Andrea , Popov Alexey A. , Tommasini Matteo , Ma Ji , Feng Xinliang
Published: October 2023

Heteroatom‐doped peri‐acenes (PAs) have recently attracted considerable attention considering their fascinating physical properties and chemical stability. However, the precise sole addition of boron atoms along the zigzag edges of PAs remains challenging, primarily due to the limited synthetic approach. Herein, we present a novel one‐pot modular synthetic strategy toward unprecedented boron‐doped PAs (B‐PAs), including B‐[4,2]PA (1 a‐2), B‐[4,3]PA (1 b‐2) and B‐[7,2]PA (1 c‐3) derivatives, through efficient intramolecular electrophilic borylation. Their chemical structures are unequivocally confirmed with a combination of mass spectrometry, NMR, and single‐crystal X‐ray diffraction analysis. Notably, 1 b‐2 exhibits an almost planar geometry, whereas 1 a‐2 displays a distinctive bowl‐like distortion. Furthermore, the optoelectronic properties of this series of B‐PAs are thoroughly investigated by UV/Vis absorption and fluorescence spectroscopy combined with DFT calculation. Compared with their parent all‐carbon analogs, the obtained B‐PAs exhibit high stability, wide energy gaps, and high photoluminescence quantum yields of up to 84 %. This study reveals the exceptional ability of boron doping to finely tune the physicochemical properties of PAs, showcasing their potential applications in optoelectronics.
Switchable Organocatalysis from N‐heterocyclic Carbene‐Carbodiimide Adducts with Tunable Release Temperature**
Authors: Pham Le Dung , Smith‐Sweetser Red O. , Krupinsky Briana , Dewey Carolyn E. , Lamb Jessica R.
Published: October 2023

N‐Heterocyclic carbenes (NHCs) are powerful organocatalysts, but practical applications often require in situ generation from stable precursors that “mask” the NHC reactivity via reversible binding. Previously established “masks” are often simple small molecules, such that the NHC structure is used to control both catalytic activity and activation temperature, leading to undesirable tradeoffs. Herein, we show that NHC‐carbodiimide (CDI) adducts can be masked precursors for switchable organocatalysis and that the CDI substituents can control the reaction profile without changing the NHC structure. Large electronic variations on the CDI (e.g., alkyl versus aryl) drastically change the catalytically active temperature, whereas smaller perturbations (e.g., different para‐substituted phenyls) tune the catalyst release within a narrower window. This control was demonstrated for three classic NHC‐catalyzed reactions, each influencing the NHC‐CDI equilibrium in different ways. Our results introduce a new paradigm for controlling NHC organocatalysis as well as present practical considerations for designing appropriate masks for various reactions.
Preparation and characterization of high solid content cationic waterborne polyurethane with core‐shell structures
Authors: Mu Minghao , Liu Xinqiang , Bi Haisong , Wang Zheng , Qian Chengduo , Yao Baojian , Liu Yifan , Liu Xiufen , Li Xue
Published: October 2023

In this study, core‐shell structured cationic waterborne polyurethane (WPU) dispersions with high solid content were prepared. To this end, prepolymer A was synthesized from polytetramethylene ether glycol (PTMG), isophorone diisocyanate (IPDI), castor oil (CO) and 1,4‐butanediol (BDO) without integration of the hydrophilic groups. Prepolymer B with hydrophilic groups was prepared from PTMG, IPDI, CO, BDO and N‐methyldiethanol amine (MDEA). WPU dispersion with a core‐shell structure could be generated by mixing, neutralizing, and emulsifying of the prepolymer A and the prepolymer B. The results indicated that the generation of WPU dispersions through this technique exhibited a milky appearance while the pH values range from 5.30 to 5.60. The optimal combination of prepolymer A and prepolymer B (at a ratio of 5:5) resulted in a dispersion with the highest solid content (50.4%), lowest viscosity (69 mPa·s), and narrowest particle size distribution. As the proportion of prepolymer A to prepolymer B decreases, the tensile strength of WPU film reduces while the elongation at break and glass transition temperature increases. Moreover, initially the contact angle with water was decreased instead of increase. However, modifications in a ratio of prepolymer A and B was not showed any significant impact on the thermal stability performance of the WPU films.
Soybean polyenylphosphatidylcholine (PPC) is beneficial in liver and extrahepatic tissue injury: An update in experimental research
Authors: Mak Ki M. , Shekhar Aditya C.
Published: October 2023

Polyenylphosphatidylcholine (PPC) is a purified polyunsaturated phosphatidylcholine extract of soybeans. This article updates PPC's beneficial effects on various forms of liver cell injury and other tissues in experimental research. PPC downregulates hepatocyte CYP2E1 expression and associated hepatotoxicity, as well as attenuates oxidative stress, apoptosis, lipoprotein oxidation and steatosis in alcoholic and nonalcoholic liver injury. PPC inhibits pro‐inflammatory cytokine production, while stimulating anti‐inflammatory cytokine secretion in ethanol or lipopolysaccharide‐stimulated Kupffer cells/macrophages. It promotes M2‐type macrophage polarization and metabolic reprogramming of glucose and lipid metabolism. PPC mitigates steatosis in NAFLD through inhibiting polarization of pro‐inflammatory M1‐type Kupffer cells, alleviating metabolic inflammation, remodeling hepatic lipid metabolism, correcting imbalances between lipogenesis and lipolysis and enhancing lipoprotein secretion from hepatocytes. PPC is antifibrotic by preventing progression of alcoholic hepatic fibrosis in baboons and also prevents CCl4‐induced fibrosis in rats. PPC supplementation replenishes the phosphatidylcholine content of damaged cell membranes, resulting in increased membrane fluidity and functioning. Phosphatidylcholine repletion prevents increased membrane curvature of the endoplasmic reticulum and Golgi and decreases sterol regulatory element binding protein‐1‐mediated lipogenesis, reducing steatosis. PPC remodels gut microbiota and affects hepatic lipid metabolism via the gut‐hepatic‐axis and also alleviates brain inflammatory responses and cognitive impairment via the gut‐brain‐axis. Additionally, PPC protects extrahepatic tissues from injury caused by various toxic compounds by reducing oxidative stress, inflammation, and membrane damage. It also stimulates liver regeneration, enhances sensitivity of cancer cells to radiotherapy/chemotherapy, and inhibits experimental hepatocarcinogenesis. PPC's beneficial effects justify it as a supportive treatment of liver disease.
Triptorelin therapy for lower urinary tract symptoms (LUTS) in prostate cancer patients: A systematic meta‐analysis
Authors: Barrett Ravina , Birch Brian
Published: October 2023

Objective

This systematic meta‐analysis aimed to assess the effectiveness of triptorelin therapy in reducing lower urinary tract symptoms (LUTS) in men with prostate cancer (PCa).

Methods

The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. PubMed, Web of Science and EMBASE databases were searched for studies conducted between 2013 and 2023. Eligible studies included PCa patients undergoing androgen deprivation therapy (ADT) with triptorelin, with reported baseline and follow‐up International Prostate Symptom Scores (IPSS) and quality of life (QoL) data. The Newcastle–Ottawa Scale (NOS) was used to assess the risk of bias, and a random‐effects model was applied for the meta‐analysis.

Results

A total of 29 articles were identified, and three studies met the inclusion criteria. Triptorelin therapy showed a clinically significant reduction in IPSS over 48 weeks in PCa patients with moderate to severe LUTS. The meta‐analysis revealed a pooled effect size of 1.05 (95% CI: 0.65; 1.45), indicating a statistically significant improvement in LUTS. QoL also improved in patients receiving triptorelin therapy, although heterogeneity among the studies and a moderate to high risk of bias were noted.

Conclusion

Triptorelin therapy demonstrated a positive impact on LUTS in PCa patients. The meta‐analysis showed significant reductions in IPSS scores and improved QoL after 48 weeks of triptorelin treatment. However, the results should be interpreted cautiously due to study heterogeneity and potential biases. Further well‐designed studies are needed to confirm these findings and determine the optimal use of triptorelin for managing LUTS in men with PCa.

Implications for Practice

Triptorelin therapy may offer an effective treatment option for men with PCa experiencing moderate to severe LUTS. Its positive impact on QoL can lead to improved patient well‐being and treatment adherence. Clinicians should consider triptorelin as a potential treatment choice, especially in patients who may be reluctant to undergo surgical interventions for their LUTS. However, careful patient selection and close monitoring are essential due to the observed study heterogeneity and risk of bias. Future research should focus on evaluating triptorelin's cost‐effectiveness and comparing its efficacy with other LH‐RH agonists in managing LUTS in PCa patients.

Video Abstract: URL (Reviewers/Editors to select from) Link 1: https://brighton.cloud.panopto.eu/Panopto/Pages/Viewer.aspx?id=071419c8-1ad5-4502-a222-b04300c2ca5e

Link 2: https://brighton.cloud.panopto.eu/Panopto/Pages/Viewer.aspx?id=b6305a8a-b977-4fcd-a69e-b04300bed728
The role of language and emotional intelligence in judgments of real‐life social and moral transgressions among Greek, Hungarian, and British users of English
Authors: Dewaele Jean‐Marc , Mavrou Irini , Kyriakou Andreas , Lorette Pernelle
Published: October 2023

Previous research suggests that people are more prone to commit moral transgressions when they face moral dilemmas in a second language (LX) as opposed to their first language(s) (L1). This study investigated the influence of language, emotional intelligence, and the degree of severity of real moral transgressions on bilinguals' judgments of offense seriousness, the intensity of the emotions they experienced, and the punishments they proposed for the perpetrators. To this end, 256 British L1 users, 209 Greek–English bilinguals, and 187 Hungarian–English bilinguals watched four videos presenting moral transgressions of mild and extreme severity. Data were analyzed by means of robust linear mixed‐effects models and moderated mediation analyses. For the extreme severity videos, the results revealed strong correlations between offensiveness, emotionality ratings, and proposed punishments for the perpetrators. However, the Greek and the Hungarian participants who watched the videos in their LX English reported lower offensiveness and emotionality ratings and less harsh punishments for the perpetrators than they did in their L1 (Greek and Hungarian, respectively). Furthermore, the role of language in the proposed punishments for the perpetrators was mediated by emotional intensity, but only for the extreme severity stimuli. The results also suggest that higher levels of emotional intelligence are linked with tougher judgments of offense seriousness and stronger emotions when watching real moral transgressions. These findings highlight that the moral foreign language effect does not only exist in the hypothetical moral realm but affects perceptions of offensiveness and emotionality and decisions for the future of perpetrators in real‐life situations.
Life or death: A qualitative examination of mitigating and aggravating evidence presented in capital trials
Authors: Holleran Lisa Bell
Published: October 2023

The US Supreme Court has required that death penalty procedures narrow the class of persons eligible for a death sentence. Through the selection requirement, juries must use mitigating and aggravating evidence jointly to determine if a defendant is one of the worst of the worst, resulting in a sentence of life without parole or death. This study analyzed capital trial transcripts from the punishment phase to assess the type and amount of mitigating and aggravating evidence presented to jurors in cases resulting in life without parole and death. The main assumption of the research was that cases resulting in life without the possibility of parole (LWOP) would reveal patterns in the types of evidence presented and differing patterns in cases where the jury handed down a sentence of death. The study qualitatively examined the trial transcripts from the punishment phase of 18 capital murders (nine resulting in LWOP and nine in death). The extra‐legal factors from each LWOP case were matched to a death case to eliminate sentencing discrepancies based on jurisdiction, race of defendant or victim, aggravator, age etc. The results found no consistent patterns of evidence presented in cases resulting life without parole and some relevant patterns in sentences resulting in death.
Did court dismiss coach's Title VII claim?
Authors: Lyerly Eric
Published: October 2023

A Nigerian‐born Black man became the head coach of the Johnson County Community College men's soccer team. He was one of three Black head coaches at the college. The coach was extremely successful during his tenure and had the most soccer wins in school history.
Sustainability factors affecting caregivers' toy preferences: An evaluation of e‐commerce best sellers in Turkey
Authors: Halli Sinem , Kaya Cigdem , Arslanli Kerem Yavuz
Published: October 2023

Toys make a considerable clutter in homes over time unless managed responsibly. Given the ease of buying anything these days, especially toys, due to the rise of online shopping (Richards et al., 2020), toy piles can grow quickly. Current literature on the sustainability of toys is based on physical touch points, such as material, design, assembly, or transport, and suggested methods to enhance sustainability performance up to the “before‐use” phase. Our study focuses on how consumers address the issue of sustainability in toys, from the moment they intend to buy a toy to the time they terminate the toys' use, with a focus on green purchase behavior. We used data from a survey to depict 220 Turkish caregivers' perceptions of sustainability with snowball sampling to build an analytic hierarchy process system. The aim was to understand caregivers' approaches to toy sustainability factors in general and to interpret their motivations for green purchase activity. Among the eight sustainability criteria explicitly set for toys, child development‐related factors dominated durability, while price was found to be ineffective. This study of six best‐selling toys for 3–6‐year‐olds on a shopping site revealed that long‐term use is crucial for sustainability in toys. We observed that digital platforms are insufficient to convey the sustainability features of products, and thus propose a concept that evaluates the sustainability performance of toys and advises the consumer about the sustainability potential of the toys on the sales site.
Understanding institutionally supported free college programs
Authors: Carrier Jonathan W. , Scull W. Reed , Perkins Mark A. , Schaffer Joseph M.
Published: October 2023

This chapter examines institutionally funded free community college programs that address specific community workforce needs. Within the article, the authors showcase “Rediscover LCCC,” a foundation‐funded scholarship program at Laramie County Community College in Wyoming that pays students’ tuition and fees for up to three years in specific, high‐demand degree and certificate programs, such as information technology, healthcare, and the trades. Preliminary outcome data is shared. The article concludes by encouraging community college leaders to support such programs as a way for students to attain work‐ready degrees and certificates needed by the local community, without incurring student debt.
Meeting the promise and challenges of “Free College”: Research and practical insights from a community college scholarship program
Authors: Wang Yunwei , Wang Xueli , Wagner Brit , Romero‐Reyes Joseph
Published: October 2023

This chapter illustrates the potential promise and complexities of free college initiatives from the perspective of administrators, faculty, staff, and students who are involved in a scholarship program at a small Midwestern community college. Based on two waves of interviews conducted in 2019 and 2021 respectively, we found that, while largely supportive of the free college movement, the program participants shared clear reservations due to potential unintended burdens on the part of institutions, and compounding barriers for students that free tuition alone cannot solve. This chapter closes by presenting a series of implications to inform the implementation of “free college” to realize its full promise.
Community values: Exploring what undergraduate engineering students value in their community college experience
Authors: Maitra Debalina , Coley Brooke , Greene Clarreese
Published: October 2023

Previous research exploring the lived experiences of marginalized groups of students in STEM at community college settings is limited, despite the fact that community colleges have the potential to create pathways to 4‐year engineering degrees and diversify the STEM workforce. This study explored what underrepresented students in STEM valued most as they navigated community college. We conducted nineteen semi‐structured narrative interviews. Our findings suggested that the students found some of the values implicit compared to other explicit values mentioned by the participants. For example, they valued intimate class size, invested faculty, available tutors, and financial support as explicit values. They appreciated the low‐pressure environment, directional support, networking opportunities, and hands‐on learning as implicit values associated with their college experience. Our research has a direct implication on how such experiences influence students’ chosen pathways toward engineering careers, and institutions can learn directly to establish programs with an understanding of what they value.
The extremely rare case of aortic chordae tendineae strands: A case report with literature review
Authors: Khansari Nakisa , Salehi Amir Mohammad
Published: October 2023

Key Clinical Message

The aortic chordae tendineae strands (ACTS) is a rare complication that can induce aortic regurgitation. Reported cases of ACTS are very few, and this is the first case reported in Iran. Patients with unexplained aortic regurgitation should be carefully evaluated for ACTS, which can be easily observed by TEE; a decision regarding aortic valve surgery should be made based on the severity of AR. Herein we reported A 64‐year‐old male was admitted to our hospital for dyspnea on exertion. In transthoracic Echocardiography a fibrous band‐like chordae in the aortic root attached to the noncoronary cusp of the aorta was seen, which caused retraction of the noncoronary cusp, mal‐coaptation of the aortic valves, and severe eccentric jet posterior directed aortic regurgitation. As a result of the ACTS, the patient was diagnosed with severe aortic regurgitation (AR); due to the symptomatic severe AR, the patient underwent aortic valve surgical replacement.
New Insights into the Behaviour of Commercial Silicon Electrode MaterialsviaEmpirical Fitting of Galvanostatic Charge‐Discharge Curves
Authors: Huld Frederik T. , Eleri Obinna E. , Lou Fengliu , Yu Zhixin
Published: October 2023

Silicon (Si) materials for use in Lithium ion batteries (LIBs) are of continued interest to battery manufacturers. With an increasing number of commercially available Si materials, evaluating their performance becomes a challenge. Here, we use an empirical fitting function presented earlier to aid in the analysis of galvanostatic charge‐discharge data of commercial Si half‐cells with relatively high loading. We find that the fitting procedure is capable of detecting dynamic changes in the cell, such as reversible capacity fade of the Si electrode. This fading is found to be due to the highly lithiated Li2SiLi3.5Si phase and that the behaviour is strongly dependent on the potential of this phase. EIS reveals that the Si electrode is responsible for the reversible behaviour due to progressive loss of Li+leading to increasing resistance. SEM/EDX and XPS characterization are also employed to determine the origin of the irreversible resistance growth on the Si electrodes.
An Aminoisoxazole‐Based Proto‐RNA
Authors: Xu Felix , Wiedemann Stefan , Feldmann Jonas , Becker Sidney , Carell Thomas
Published: October 2023

The RNA world hypothesis predicts that life started with the development of replicating and catalytically active RNA, which evolved in a process of molecular evolution to increasingly complex chemical structures. RNA is, however, so complex that it has most likely formed from a precursor (proto‐RNA) that was more easily accessible in a prebiotic world. Recently, 3‐aminoisoxazoles (IO3) were identified as building blocks that can form under prebiotic conditions and can rearrange to give the nucleoside cytidine (C). The present study shows that the constitutional isomer 5‐aminoisoxazole (IO5) can undergo the same reaction to give uridine (U). Both compounds (IO3 and IO5), if embedded in RNA, react selectively to C and U, which are the main pyrimidine nucleosides of the genetic system. Importantly, the stereochemical outcome of the IO5 reaction in RNA depends on the neighboring bases. If they are β‐configured RNA nucleosides, the reaction proceeds with high selectivity to give exclusively the β‐configured U RNA base (anomeric control).
Optimization of 3D Synthetic Scaffolds for Neuronal Tissue Engineering Applications
Authors: Galindo Josué M. , San‐Millán Ms. Irene , Castillo‐Sarmiento Carlos A. , Ballesteros‐Yáñez Inmaculada , Vázquez Ester , Merino Sonia , Herrero M. Antonia
Published: October 2023

The increasing prevalence of neurodegenerative diseases has spurred researchers to develop advanced 3D models that accurately mimic neural tissues. Hydrogels stand out as ideal candidates as their properties closely resemble those of the extracellular matrix. A critical challenge in this regard is to comprehend the influence of the scaffold‘s mechanical properties on cell growth and differentiation, thus enabling targeted modifications. In light of this, a synthesis and comprehensive analysis of acrylamide‐based hydrogels incorporating a peptide has been conducted. Adequate cell adhesion and development is achieved due to their bioactive nature and specific interactions with cellular receptors. The integration of a precisely controlled physicochemical hydrogel matrix and inclusion of the arginine‐glycine‐aspartic acid peptide sequence has endowed this system with an optimal structure, thus providing a unique ability to interact effectively with biomolecules. The analysis fully examined essential properties governing cell behavior, including pore size, mechanical characteristics, and swelling ability. Cell‐viability experiments were performed to assess the hydrogel's biocompatibility, while the incorporation of grow factors aimed to promote the differentiation of neuroblastoma cells. The results underscore the hydrogel's ability to stimulate cell viability and differentiation in the presence of the peptide within the matrix.
New Protocol for the Synthesis of S‐Thioesters from Benzylic, Allylic and Tertiary Alcohols with Thioacetic Acid
Authors: Lachguar Abdelhak , Bandyopadhyay Uchchhal , Ech‐Chariy Mehdi , Vincendeau Sandrine , Audin Catherine , Daran Jean‐Claude , Manoury Eric , Poli Rinaldo , Deydier Eric
Published: October 2023

A new one‐pot solvent‐less reaction to convert benzylic, allylic, ferrocenyl or tertiary alcohols into S‐thioesters, bench‐stable and less odorous precursors of the corresponding thiols, which is based on reactions in neat thioacetic acid in the presence of tetrafluoroboric acid, is presented. Reaction monitoring by NMR and GC of the benzyl alcohol conversion indicated the intermediate formation of benzyl acetate and benzyl thionoacetate (PhCH2OC(S)CH3) prior to the slower conversion to the final S‐benzyl thioacetate product. Increasing the HBF4 concentration enhanced the reaction rate, giving good to excellent yield (up to 99 %) for a large scope of alcohols. Control experiments, with support of DFT calculations, have revealed a thermodynamically favorable, though requiring HBF4‐activation, disproportionation of CH3C(O)SH to CH3C(O)OH and CH3C(S)SH, the latter immediately decomposing to H2S and (MeC)4S6 but also generating the hitherto unreported [MeC(O)C(Me)S]2(μ‐S)2. Kinetic investigations demonstrated that the rate of benzyl alcohol conversion is second‐order in [PhCH2OH] and second order in [HBF4], while the rate of conversion of the benzyl acetate intermediate to S‐benzyl thioacetate is second order in [PhCOOMe] and fourth order in [HBF4]. The DFT calculations rationalize the need to two alcohol molecules and two protons to generate the reactive benzyl cation.
Stereoselective Synthesis of Allylic Alcohols via Substrate Control on Asymmetric Lithiation
Authors: Linne Yannick , Lücke Daniel , Gerdes Kjeld , Bajerke Kevin , Kalesse Markus
Published: October 2023

Allylic alcohols are a privileged motif in natural product synthesis and new methods that access them in a stereoselective fashion are highly sought after. Toward this goal, we found that chiral acetonide‐protected polyketide fragments performing the Hoppe–Matteson–Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities rendering this protocol a highly valuable alternative to the Nozaki–Hiyama–Takai–Kishi reaction. Various stereodyads and ‐triads were investigated to determine their substrate induction. The mostly strong inherent stereoinduction was attributed to a combination of steric and electronic effects.
Dynamic stationary subspace analysis based on Gaussian mixture models for ironmaking process monitoring
Authors: Zhang Hanwen , Fan Weiwei , Guo Houze , Yang Chunjie
Published: October 2023

Blast furnace ironmaking process monitoring is an important and challenging task. Due to the influence of hot blast stove switching and large fluctuations in the quality of raw materials, the measurements of ironmaking processes show obvious non‐stationary characteristics, and in addition, the observed data are also characterized by time‐series dynamic and non‐Gaussian characteristics. In this paper, a dynamic stationary subspace analysis method based on the Gaussian mixture model (DSSA–GMM) is proposed to address the difficulties in blast furnace ironmaking process monitoring. The time‐series dynamic relationship of the data is conducted by introducing a sliding time window. The Gaussian mixture model (GMM) is used to deal with the non‐Gaussian characteristics of the data, and the parameters of the GMMs are estimated using the expectation–maximization algorithm. The stationary projection matrix is obtained by optimizing the Kullback–Leibler (K–L) divergence between GMMs of different periods to realize the stationary subspace separation. Finally, the convex hull of the stationary subspace is established for fault detection, thus realizing the monitoring for non‐stationary and non‐Gaussian dynamic processes. The effectiveness of the DSSA–GMM method is verified by a numerical simulation and a dataset collected from an actual blast furnace ironmaking process.
Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients
Authors: Beatty Carol , Richardson Katherine P. , Tran Paul M. H. , Satter Khaled B. , Hopkins Diane , Gardiner Melissa , Sharma Ashok , Purohit Sharad
Published: October 2023

Background

Chronic uncontrolled hyperglycemia, a precursor to chronic low‐grade inflammation, is a leading cause of coronary artery disease (CAD) due to plaque buildup in type‐1 diabetes (T1D) patients. We evaluated levels of 22 inflammatory markers in cross‐sectional serum samples from 1222 subjects to evaluate their potential as risk factors for CAD in T1D patients.

Hypothesis

Circulating levels of markers of inflammation may be the risk factors for incident CAD.

Methods

The T1D subjects were divided into two groups: those without CAD (n = 1107) and with CAD (n = 115). Serum levels of proteins were assayed using multiplex immunoassays on a Luminex Platform. Differences between the two groups were made by univariate analysis. Multivariate logistic regression was used to ascertain the potential of proteins as risk factors for CAD. Influence of age, duration of diabetes, sex, hypertension, and dyslipidemia was determined in a stepwise manner. Serum levels of 22 proteins were combined into a composite score using Ridge regression for risk‐based stratification.

Results

Mean levels of CRP, IGFBP1, IGFBP2, insulin‐like growth factors binding protein‐6 (IGFBP6), MMP1, SAA, sTNFRI, and sTNFRII were elevated in CAD patients (n = 115) compared to T1D patients without CAD (nCAD, n = 1107). After adjusting for age, duration of diabetes, sex, hypertension, and dyslipidemia, higher levels of sTNFRI (odds ratio [OR] = 2.18, 1.1 × 10−3), sTNFRII (OR = 1.52, 1 × 10−2), and IGFBP6 (OR = 3.62, 1.8 × 10−3) were significantly associated with CAD. The composite score based on Ridge regression, was able to stratify CAD patients into low, medium, and high‐risk groups.

Conclusions

The results show activation of the TNF pathway in CAD patients. Evaluating these markers in serum can be a potential tool for identifying high‐risk T1D patients for intensive anti‐inflammatory therapeutic interventions.
Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives
Authors: Sun Xiaohuan , Ogbolu Victor C. , Baas Peter W. , Qiang Liang
Published: October 2023

Tau, one of the most abundant microtubule‐associated protein in neurons plays a role in regulating microtubule dynamics in axons, as well as shaping the overall morphology of the axon. Recent studies challenge the traditional view of tau as a microtubule stabilizer and shed new light on the complexity of its role in regulating various properties of the microtubule. While reducing tau levels shows therapeutic promise for early tauopathies, efficacy wanes in later stages due to resilient toxic tau aggregates and neurofibrillary tangles. Notably, tauopathies involve factors beyond toxic tau alone, necessitating a broader therapeutic approach. Overexpression of human tau in mouse models, although useful for answering some questions, may not accurately reflect disease mechanisms in patients with tauopathies. Furthermore, the interplay between tau and MAP6, another microtubule‐associated protein, adds complexity to tau's regulation of microtubule dynamics. Tau promotes the formation and elongation of labile microtubule domains, vital for cellular processes, while MAP6 stabilizes microtubules. A delicate balance between these proteins is important for neuronal function. Therefore, tau reduction therapies require a comprehensive understanding of disease progression, considering functional tau loss, toxic aggregates, and microtubule dynamics. Stage‐dependent application and potential unintended consequences must be carefully evaluated. Restoring microtubule dynamics in late‐stage tauopathies may necessitate alternative strategies. This knowledge is valuable for developing effective and safe treatments for tauopathies.
Sliding of antiparallel microtubules drives bipolarization of monoastral spindles
Authors: LaFountain Jr James R. , Seaman Catherine E. , Cohan Christopher S. , Oldenbourg Rudolf
Published: October 2023

Time‐lapse imaging with liquid crystal polarized light (LC‐PolScope) and fluorescent speckle microscopy (FSM) enabled this study of spindle microtubules in monoastral spindles that were produced in crane‐fly spermatocytes through flattening‐induced centrosome displacement. Monoastral spindles are found in several other contexts: after laser ablation of one of a cell's two centrosomes (in the work of Khodjakov et al.), in Drosophila “urchin” mutants (in the works of Heck et al. and of Wilson et al.), in Sciara males (in the works of Fuge and of Metz), and in RNAi variants of Drosophila S2 cells (in the work of Goshima et al.). In all cases, just one pole has a centrosome (the astral pole); the other lacks a centrosome (the anastral pole). Thus, the question: How is the anastral half‐spindle, lacking a centrosome, constructed? We learned that monoastral spindles are assembled in two phases: Phase I assembles the astral half‐spindle composed of centrosomal microtubules, and Phase II assembles microtubules of the anastral half through extension of new microtubule polymerization outward from the spindle's equatorial mid‐zone. That process uses plus ends of existing centrosomal microtubules as guiding templates to assemble anastral microtubules of opposite polarity. Anastral microtubules slide outward with their minus ends leading, thereby establishing proper bipolarity just like in normal biastral spindles that have two centrosomes.
Urinary IL‐6 and IL‐8 as predictive markers in bladder urothelial carcinoma: A pilot study
Authors: VandenBussche Christopher J. , Heaney Christopher D. , Kates Max , Hooks John J. , Baloga Kelly , Sokoll Lori , Rosenthal Dorothy , Detrick Barbara
Published: October 2023

Background

Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear.

Methods

Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL‐8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL‐6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations.

Results

Significantly elevated concentrations of IL‐6 and IL‐8 were detected in the urine from patients with urothelial carcinoma on follow‐up compared to patients with benign follow‐up. The presence of both IL‐6 and IL‐8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow‐up. The presence of the combination of both IL‐6 and IL‐8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL‐6 and IL‐8 concentrations in the urine from patients with HGUC vs. the hematuria cohort.

Conclusions

The presence of IL‐6 and IL‐8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.
The Patient's perspective on radiation therapy for anal cancer: Evaluation of expectations and stigma
Authors: Chaballout Basil H. , Chang Eric M. , Shaverdian Narek , Lee Percy P. , Beron Phillip J. , Steinberg Michael L. , Raldow Ann C.
Published: October 2023

Background

Little is known regarding anal cancer patients' perspectives on undergoing radiation therapy. Additionally, the stigma surrounding anal cancer diagnosis warrants a better understanding of the barriers to complete disclosure in patient‐healthcare team interactions.

Methods

Included patients had squamous cell carcinoma of the anus treated with definitive chemoradiation (CRT) from 2009 to 2018. Survey questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale.

Results

A total of 46 anal cancer patients who underwent CRT were surveyed, of which 72% responded. 73% of respondents indicated little to no pre‐treatment knowledge of CRT. 70% reported overall short‐term effects as worse than expected, most commonly with bowel habits (82%), energy (73%), and interest in sexual activity (64%). 39% reported overall long‐term effects to be worse than expected, most commonly with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%). However, 94% agreed they were better off after treatment. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, and 15% indicating they stopped having close relationships due to concerns over stigma.

Conclusions

Although patients' perceptions of the severity of short‐term CRT side effects were worse than expectations, the vast majority agreed they were better off after treatment. Targeted counseling on common concerns may improve the anal cancer treatment experience. A notable subset reported stigma associated with treatment, warranting further evaluation to understand the impact on the patient experience.
Genotype‐by‐environmental interaction effects on earliness, semi‐dwarfism, and yield of rice (Oryza sativa L.) mutants in Tamil Nadu, India
Authors: Pillai Madhavan Arumugam , R. Rajamadhan , E. Murugan , Michaelantonysamy Tamilarasi Andrew‐Peter‐Leon , Selvaraj Ramchander , Devadhasan Shoba , J. Ramalingham , Yasin Jeshima Khan , Jegadeesan Souframanien
Published: October 2023

Rice plant architecture improvement helps in the effective and efficient source–sink relationship to enhance yield. The most preferred plant architecture in rice is dwarf type. Improved White Ponni (IWP) is a tall, medium duration, released variety of Tamil Nadu, India, yielding 300 kg more than parental line White Ponni, which is suitable for second season transplanting. To induce variation in plant height to select semi‐dwarf mutants, IWP was subjected to mutagenesis in 2011 using different doses of gamma rays to develop semi‐dwarf and short‐duration mutants. The selection was carried out in segregating populations of M2, and an evaluation of selected better‐performing mutants was done up to 70 selected mutants in M5. Nineteen M5 homozygous, semi‐dwarf, and short‐duration mutants that outperformed the IWP were evaluated in 2015–2016 across five contrasting environments of Tamil Nadu in India. The genotypes were grown in a randomized complete block design with two replications with IWP as a control. In the additive main effects and multiplicative interaction (AMMI) biplot, the analysis revealed that PC1 and PC2 accounted for 49% and 18% of the variation, respectively. Interaction principal component analysis‐1 scores were observed for the mutants, viz., IWP‐15‐5, IWP‐22‐1, and IWP‐30‐5, indicating their superior performance. In the GGE biplot, E1 (Aduthurai), E4 (Coimbatore), and E5 (Thirupathisaram) were the ideal environments for selecting high‐yielding mutants. IWP‐6‐5 and IWP‐16‐2 were the stable mutants for yield (23.59 and 24.51 g, respectively) but with a lower mean than other mutants at favorable environments. Based on the two models, E2 (Killikulam) and E3 (Madurai) were the favorable locations for exploiting high yields; IWP‐30‐5, IWP‐22‐2, and IWP‐22‐3 were stable across environments. These stable, high‐yielding, and early maturing mutants show potential for further advancement and eventual release of new rice varieties.
Characteristics of positive horizontal margins in patients who underwent colorectal endoscopic submucosal dissection
Authors: Kawashima Kazumasa , Hikichi Takuto , Onizawa Michio , Gunji Naohiko , Watahiki Yu , Sakuma Chiharu , Mochimaru Tomoaki , Murakami Mai , Suzuki Osamu , Hashimoto Yuko , Kobayakawa Masao , Ohira Hiromasa
Published: October 2023

Objectives

Endoscopic submucosal dissection (ESD) enables en bloc resection of colorectal neoplasms, but occasionally results in positive horizontal margins (HMs). However, the site of the resected specimen that tends to be positive for HM has not been investigated. We aimed to clarify the characteristics associated with HMs in lesions resected en bloc with ESD.

Methods

Patients with colorectal neoplasms who underwent en bloc resection with ESD were included in this study. The patients were divided into negative HMs (HM0) and positive or indeterminate HMs (HM1) groups. The characteristics associated with HM1 resection were investigated. In addition, the local recurrence rate during endoscopic follow‐up for >6 months after ESD was observed.

Results

In total, 201 lesions were analyzed in 189 patients (HM0, 189 lesions; HM1, 12 lesions). The HM1 group had a significantly larger median lesion diameter (25 vs. 55 mm; p < 0.001) and more lesions with >50% circumference than did the HM0 group (p < 0.001). Furthermore, the prevalence of severe fibrosis was significantly higher in the HM1 group than in the HM0 group (p < 0.001). Positive horizontal sites of the resected specimens were more frequent at the oral and anal sites than at the lateral sites. No local recurrences were observed in either group.

Conclusions

The characteristics associated with HM1 depended on lesion size, particularly lesions with >50% circumference, and submucosal fibrosis.
The contribution of evolvability to the eco‐evolutionary dynamics of competing species
Authors: Bukkuri Anuraag , Pienta Kenneth J. , Amend Sarah R. , Austin Robert H. , Hammarlund Emma U. , Brown Joel S.
Published: October 2023

Evolvability is the capacity of a population to generate heritable variation that can be acted upon by natural selection. This ability influences the adaptations and fitness of individual organisms. By viewing this capacity as a trait, evolvability is subject to natural selection and thus plays a critical role in eco‐evolutionary dynamics. Understanding this role provides insight into how species respond to changes in their environment and how species coexistence can arise and be maintained. Here, we create a G‐function model of competing species, each with a different evolvability. We analyze population and strategy (= heritable phenotype) dynamics of the two populations under clade initiation (when species are introduced into a population), evolutionary tracking (constant, small changes in the environment), adaptive radiation (availability of multiple ecological niches), and evolutionary rescue (extreme environmental disturbances). We find that when species are far from an eco‐evolutionary equilibrium, faster‐evolving species reach higher population sizes, and when species are close to an equilibrium, slower‐evolving species are more successful. Frequent, minor environmental changes promote the extinction of species with small population sizes, regardless of their evolvability. When several niches are available for a species to occupy, coexistence is possible, though slower‐evolving species perform slightly better than faster‐evolving ones due to the well‐recognized inherent cost of evolvability. Finally, disrupting the environment at intermediate frequencies can result in coexistence with cyclical population dynamics of species with different rates of evolution.
“Show me how to use a microscope” – The development and evaluation of certification as direct assessment of practical lab skills
Authors: Eidesen Pernille Bronken , Bjune Anne E. , Lang Simone I.
Published: October 2023

Practical lab skills are rarely directly assessed. To improve constructive alignment between the described learning outcomes of practical skills and assessment, we developed and tested a certification procedure for microscopy skills. The procedure was embedded into the ordinary learning activity, so no additional time was needed. Three slightly different protocols were developed within the framework of sociocultural learning theory and built like a skill ladder, including direct peer assessment and elements of gamified learning. The protocols varied slightly in the way students were prepared for the certification, the number of steps/levels of achievement, and the consequences of failing. We tested the protocols at three different academic institutions and within 11 courses of varying sizes and academic levels in biology or geology. Feedbacks were collected through online surveys (n = 207) or orally after sessions. One protocol provided instruction videos as preparation material. Instruction videos provided increased understanding of the task, but tactile training was most important for learning. Regardless of institution, type of preparation, and level of former experience, the certification procedure made students clearly more engaged in the exercise. The majority reported that the certification procedure increased their motivation to learn, increased their perceived learning outcome, and was appropriate for assessing practical skills. Students with no or little experience in microscopy before the exercise were more positive about the certification procedure compared to skilled students, and the level of engagement and preparation was higher when there were some consequences of failing. Most students felt comfortable being certified by peers, but some students expressed concern about peers making mistakes. The presented certification procedure can easily be adapted to assess other practical skills and, with some adjustments, be an efficient method for assessment‐as‐learning, merging formative‐ and summative assessment.