bluuebunny/crossref_metadata_2025 huggingface dataset:
Erlangian Approximations for Finite-Horizon Ruin Probabilities
Authors: Asmussen Soren , Avram Florin , Usabel Miguel
Published: February 2005

For the Cramér-Lundberg risk model with phase-type claims, it is shown that the probability of ruin before an independent phase-type time H coincides with the ruin probability in a certain Markovian fluid model and therefore has an matrix-exponential form. When H is exponential, this yields in particular a probabilistic interpretation of a recent result of Avram & Usabel. When H is Erlang, the matrix algebra takes a simple recursive form, and fixing the mean of H at T and letting the number of stages go to infinity yields a quick approximation procedure for the probability of ruin before time T. Numerical examples are given, including a combination with extrapolation.
Bonus-Malus Systems: “Lack of Transparency” and Adequacy Measure
Authors: Verico Paola
Published: February 2005

Based on a recent contribution by Baione and others in this Journal, some consequences of the decrease of the mean merit coefficient for portfolios of Bonus-Malus policies, and some alternative ways to measure the “quality” of a Bonus-Malus system are discussed.
Transition Intensities for a model for Permanent Health Insurance
Authors: Cordeiro Isabel Maria Ferraz
Published: February 2005

The purpose of this paper is to obtain approximations to the transition intensities defined for a multiple state model for Permanent Health Insurance (PHI) which enables us to analyse PHI claims by cause of disability.

The approximations to the transition intensities are obtained using a set of PHI data classified by 18 sickness categories and the graduations of the transition intensities defined for a simpler model proposed in Continuous Mortality Investigation Reports, 12 (1991).

In order to derive the approximations to the recovery and mortality of the sick intensities for our model, we carry out tests of hypotheses based on the distributions of average sickness durations. The approximations to the sickness intensities are obtained by estimating a statistical model for the number of claim inceptions, which can be formulated as a generalized linear model.
Scale Mixtures Distributions in Insurance Applications
Authors: Choy S.T. Boris , Chan C.M.
Published: February 2005

In this paper non-normal distributions via scale mixtures are introduced into insurance applications. The symmetric distributions of interest are the Student-tand exponential power (EP) distributions. A Bayesian approach is adopted with the aid of simulation to obtain posterior summaries. We shall show that the computational burden for the Bayesian calculations is alleviated via the scale mixtures representations. Illustrative examples are given.
The Valuation and Hedging of Variable Rate Savings Accounts
Authors: de Jong Frank , Wielhouwer Jacco
Published: February 2005

Variable rate savings accounts have two main features. The interest rate paid on the account is variable and deposits can be invested and withdrawn at any time. However, customer behaviour is not fully rational and withdrawals of balances are often performed with a delay. This paper focuses on measuring the interest rate risk of variable rate savings accounts on a value basis (duration) and analyzes the problem how to hedge these accounts. In order to model the embedded options and the customer behaviour we implement a partial adjustment specification. The interest rate policy of the bank is described in an error-correction model.
Setting a Bonus-Malus Scale in the Presence of Other Rating Factors: Taylor's Work Revisited
Authors: Pitrebois Sandra , Denuit Michel , Walhin Jean-François
Published: February 2005

In this paper, we propose an analytic analogue to the simulation procedure described in Taylor (1997). We apply the formulas to a Belgian data set and discuss the interaction between a priori and a posteriori ratemakings.
Robust Bayesian Experience Rating
Authors: Schnieper René
Published: February 2005

Different rating methods which allow for exceptional large claims are discussed. A robust Bayesian statistical model is proposed which can cope with non negative, skewed data. An example from fire insurance is analyzed. The performance of the posterior mean is compared to the performance of a robust credibility estimator.
Optimal Premium Plans for Reinsurance with Reinstatements
Authors: Hess Klaus TH. , Schmidt Klaus D.
Published: February 2005

The present paper is concerned with optimal premium plans for a reinsurance contract with reinstatements. In the reinsurance contract considered here, constant reinstatement premiums are due when the reinsurer’s loss exceeds certain bounds. For this reinsurance contract we examine the existence of a premium plan which minimizes the expected squared difference between the loss and the total premium income of the reinsurer. We show that an optimal premium plan exists, that it is unique, and that it satisfies the net premium principle.
Opportunities for Pharmacogenetic Testing to Guide Dosing of Medications in Youths With Medicaid
Authors: Tang Girdwood Sonya , Hall Matthew , Antoon James W. , Kyler Kathryn E. , Williams Derek J. , Shah Samir S. , Orth Lucas E. , Goldman Jennifer , Feinstein James A. , Ramsey Laura B.
Published: February 2024

Importance

There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement.

Objectives

To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug.

Design, Setting, and Participants

This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022.

Main Outcomes and Measures

PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs.

Results

The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019.

Conclusions and Relevance

In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.
Recall of Autobiographical Memories Following Odor vs Verbal Cues Among Adults With Major Depressive Disorder
Authors: Leiker Emily K. , Riley Emma , Barb Scott , Lazzaro Sair K. , Compère Laurie , Webb Carolyn , Canovali Gia , Young Kymberly D.
Published: February 2024

Importance

Major depressive disorder (MDD) is associated with deficits in autobiographical memory (AM) recall, which is thought to stem from disruptions in effortful recall. Understanding whether these deficits are mitigated when recall is stimulated more directly, such as by odor cues, could inform therapeutic interventions for MDD.

Objective

To evaluate whether deficits in specific AM recall in MDD are mitigated when odor cues vs word cues are used to prompt memory.

Design, Setting, and Participants

This cross-sectional study assessed recall of specific AMs in response to both odor cues and word cues (in a randomized, counterbalanced order) in a repeated measures design. Data were collected between September 2021 and November 2022. The study took place at the University of Pittsburgh School of Medicine in Pennsylvania and included adults with a primary diagnosis of MDD, according to the Mini International Neuropsychiatric Interview. Data were analyzed from January to June 2023.

Main Outcomes and Measures

The primary outcome measure was the percentage of specific AMs recalled in response to odor-cued memories vs word-cued memories. Additional outcome measures included ratings of arousal, vividness, repetition, and recall response time for odor-cued memories vs word-cued memories.

Results

Thirty-two adults (mean [SD] age, 30.0 [10.1] years; 26 [81.3%] female; 6 [18.8%] male) with a primary diagnosis of MDD completed the study. Participants recalled more specific AMs for odor cues than word cues (mean [SD], 68.4% [20.4%] vs 52.1% [23.3%]; Cohen d, 0.78; P < .001). Additionally, odor-cued recall was rated more arousing (mean [SD], 3.0 [0.8] vs 2.6 [0.7]; Cohen d, 1.28; P < .001) and vivid (mean [SD], 3.3 [0.7] vs 3.0 [0.7]; Cohen d, 0.67; P < .001), and was slower than word-cued recall (mean [SD], 14.5 [3.6] vs 8.9 [3.4] seconds; Cohen d, 1.18; P < .001). When compared with the population mean for word cues in healthy controls (80%), participants recalled fewer specific memories in response to words (Cohen d, 1.18; P < .001), supporting the presence of overgenerality. Notably, the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean (Cohen d, 0.26; P = .15).

Conclusions and Relevance

In this cross-sectional study, adults with MDD recalled more specific AMs in response to odor cues compared with word cues. This study suggests that AM deficits may only be observed when verbal cues are used and provides a potential new method for increasing specific AM recall in patients with MDD.
Preclinical efficacy of carfilzomib in BRAF‐mutant colorectal cancer models
Authors: Maione Federica , Oddo Daniele , Galvagno Federica , Falcomatà Chiara , Pandini Marta , Macagno Marco , Pessei Valeria , Barault Ludovic , Gigliotti Chiara , Mira Alessia , Corti Giorgio , Lamba Simona , Riganti Chiara , Castella Barbara , Massaia Massimo , Rad Roland , Saur Dieter , Bardelli Alberto , Di Nicolantonio Federica
Published: February 2024

Serine/threonine‐protein kinase B‐raf (BRAF) mutations are found in 8–15% of colorectal cancer patients and identify a subset of tumors with poor outcome in the metastatic setting. We have previously reported that BRAF‐mutant human cells display a high rate of protein production, causing proteotoxic stress, and are selectively sensitive to the proteasome inhibitors bortezomib and carfilzomib. In this work, we tested whether carfilzomib could restrain the growth of BRAF‐mutant colorectal tumors not only by targeting cancer cells directly, but also by promoting an immune‐mediated antitumor response. In human and mouse colorectal cancer cells, carfilzomib triggered robust endoplasmic reticulum stress and autophagy, followed by the emission of immunogenic‐damage‐associated molecules. Intravenous administration of carfilzomib delayed the growth of BRAF‐mutant murine tumors and mobilized the danger‐signal proteins calreticulin and high mobility group box 1 (HMGB1). Analyses of drug‐treated samples revealed increased intratumor recruitment of activated cytotoxic T cells and natural killers, concomitant with the downregulation of forkhead box protein P3 (Foxp3)+ T‐cell surface glycoprotein CD4 (CD4)+ T cells, indicating that carfilzomib promotes reshaping of the immune microenvironment of BRAF‐mutant murine colorectal tumors. These results will inform the design of clinical trials in BRAF‐mutant colorectal cancer patients.
The National Artificial Intelligence Research Institutes program and its significance to a prosperous future
Authors: Donlon James J.
Published: February 2024

The U.S. National Artificial Intelligence (AI) Research Institutes program is introduced, and its significance is discussed relative to the guiding national AI research and development strategy. The future of the program is also discussed, including, the strategic priorities guiding the potential for new AI Institutes of the future, initiatives for building a broader ecosystem to connect Institutes into a strongly interconnected network, and the building of new AI capacity and fostering partnerships in minority‐serving institutions.
Increased Confidence and Deeper Understanding of Fatigue Following Participation in Fatigue Education and Management Education in Systemic Sclerosis: A Mixed Methods Evaluation of a Virtual Intervention
Authors: Poole Janet L. , Carandang Kristine , Connolly Deirdre
Published: February 2024

Objective

No fatigue‐specific programs exist for people with systemic sclerosis (SSc) despite the burden of fatigue and negative impact on daily activities. This study used a convergent parallel mixed methods design to evaluate the impact of an adapted virtual intervention, Fatigue and Activity Management Education in Systemic Sclerosis (FAME‐iSS), in the United States.

Methods

Eighteen people with SSc participated in three separate six‐week FAME‐iSS programs. Participants completed the modified Fatigue Impact Scale (m‐FIS), the Self‐Efficacy for Performing Energy Conservation Strategies Assessment (SEPESCA), the Patient‐Reported Outcomes Measurement Information System (PROMIS) Self‐Efficacy for Managing Symptoms, and the Hospital Anxiety and Depression Scale (HADS) before, immediately after, and three months post intervention. Data were analyzed using descriptive and nonparametric inferential statistics. Participants’ perceptions of the program and their use of fatigue management strategies were qualitatively analyzed using content analysis.

Results

Eighty‐nine percent of participants were women with a mean ± SD age of 52.0 ± 11.6 years and a mean ± SD disease duration of 13.7 ± 14.5 years, and more than 70% had a college degree. Significant improvements were observed for self‐efficacy on the PROMIS Self‐Efficacy for Managing Symptoms (P = 0.002) and SEPESCA (P = 0.016) immediately post intervention, which continued to significantly improve up to the three‐month follow‐up (P = 0.006 and 0.035, respectively). Significant improvements were also observed for the m‐FIS between baseline and the three‐month follow‐up (P = 0.029). Participants reported a deeper understanding of fatigue and that they liked sharing strategies and experiences with each other along with the facilitator, citing that “there was a power in our group because we had a common condition.”

Conclusion

FAME‐iSS resulted in improvements in the impact of fatigue and self‐efficacy for managing symptoms and performing energy conservation strategies. Feedback was positive, and the virtual format allowed for greater accessibility and sharing of strategies.
Synergistic Corrosion Engineering on Metallic Manganese Toward High‐Performance Electrochemical Energy Storage
Authors: Sun Xiaobo , Wang Tuan , Lyv Wei , Xu Enhao , Chen Jinxuan , Wu Hao , Cai Wenlong , Zhang Yun , Wu Kaipeng
Published: February 2024

MnO/rGO with enhanced electrochemical kinetic properties is widely investigated as electrode for high‐performance electrochemical energy storage (EES) devices. However, the synthesis of MnO/rGO via traditional methods suffers from low atomic utilization and complex techniques that are undesirable for practical implementation. Different from existing fabrication strategies, here using metallic manganese as Mn source, a novel, eco‐friendly, and corrosion engineering‐based approach to address the above issues is demonstrated. It is thermodynamically feasible as supported by the E‐pH analysis and for the first time, a significant synergetic effect is observed between NH4+ and GO in strengthening the metallic Mn corrosion reaction. Particularly, in the “ammonia circulation” process, the NH3 molecule, derived from NH4+, acts as a “carrier” for Mn2+ to facilitate its transfer by forming [Mn(NH3)2]2+, which effectively prevents “in situ corrosion”. The phase and structure evolution during the reaction are clarified, and the synergistic corrosion mechanism is also proposed. Benefiting from the efficient lithium‐ion evolution kinetics, Mn─O─C bond formed between MnO and rGO and outstanding structural integrity, the resultant MnO/rGO demonstrates exceptional EES performances in both lithium‐ion batteries and lithium‐ion capacitors. This finding will offer potential for mild, cost‐effective, and environmentally friendly fabrication of other graphene‐based metal oxide electrodes using corrosion engineering.
Engineering Biomaterials to Model Immune‐Tumor Interactions In Vitro
Authors: Skirzynska Arianna , Xue Chang , Shoichet Molly S.
Published: February 2024

Engineered biomaterial scaffolds are becoming more prominent in research laboratories to study drug efficacy for oncological applications in vitro, but do they have a place in pharmaceutical drug screening pipelines? The low efficacy of cancer drugs in phase II/III clinical trials suggests that there are critical mechanisms not properly accounted for in the pre‐clinical evaluation of drug candidates. Immune cells associated with the tumor may account for some of these failures given recent successes with cancer immunotherapies; however, there are few representative platforms to study immune cells in the context of cancer as traditional 2D culture is typically monocultures and humanized animal models have a weakened immune composition. Biomaterials that replicate tumor microenvironmental cues may provide a more relevant model with greater in vitro complexity. In this review, the authors explore the pertinent microenvironmental cues that drive tumor progression in the context of the immune system, discuss how these cues can be incorporated into hydrogel design to culture immune cells, and describe progress toward precision oncological drug screening with engineered tissues.
Fully Printable and Reconfigurable Hufu‐type Electroluminescent Devices for Visualized Encryption
Authors: Luo Ziqing , Chen Wenfu , Lai Mengnan , Shi Shiyang , Chen Pengyu , Yang Xiaolong , Chen Zhan , Wang Ben , Zhang Yaokang , Zhou Xuechang
Published: February 2024

Hufu, serving as evidence of imperial authorization in ancient China, comprises two parts in the form of tiger‐shaped tallies that only become effective when matched. Drawing inspiration from the concept of Hufu, a reconfigurable electroluminescent (EL) device is designed by separating conventional integral devices into two parts that contain the EL layer (part A) and the transparent electrode (part B), respectively. The key to realizing such strategy is employing an adhesive and stretchable polymer gel composite as the transparent electrodes for the EL devices. The polymer gel composite facilitates robust yet reversible contact between the EL layer and transparent electrode, enabling high‐performance and stretchable EL devices that can be readily disassembled and reassembled: the EL devices can maintain ≈81% of their initial luminance after 1000 times of repeated disassembly and reassembly. Moreover, the precursor ink of the polymer gel composite is compatible with a wide variety of coating and printing technologies, such as spin‐coating, inkjet printing, dispensing, and brush painting. Importantly, the reconfigurable feature of the devices opens up a new path to encryption display systems, and as a proof‐of‐concept, EL encrypted password, and content‐changeable digital clock are demonstrated.
Gradient Pores Enhance Charge Storage Density of Carbonaceous Cathodes for Zn‐Ion Capacitor
Authors: Li Xinyuan , Cai Congcong , Hu Ping , Zhang Bao , Wu Peijie , Fan Hao , Chen Zhuo , Zhou Liang , Mai Liqiang , Fan Hong Jin
Published: February 2024

Engineering carbonaceous cathode materials with adequately accessible active sites is crucial for unleashing their charge storage potential. Herein, activated meso‐microporous shell carbon (MMSC‐A) nanofibers are constructed to enhance the zinc ion storage density by forming a gradient‐pore structure. A dominating pore size of 0.86 nm is tailored to cater for the solvated [Zn(H2O)6]2+. Moreover, these gradient porous nanofibers feature rapid ion/electron dual conduction pathways and offer abundant active surfaces with high affinity to electrolyte. When employed in Zn‐ion capacitors (ZICs), the electrode delivers significantly enhanced capacity (257 mAh g−1), energy density (200 Wh kg−1 at 78 W kg−1), and cyclic stability (95% retention after 10 000 cycles) compared to nonactivated carbon nanofibers electrode. A series of in situ characterization techniques unveil that the improved Zn2+ storage capability stems from size compatibility between the pores and [Zn(H2O)6]2+, the co‐adsorption of Zn2+, H+, and SO42−, as well as reversible surface chemical interaction. This work presents an effective method to engineering meso‐microporous carbon materials toward high energy‐density storage, and also offers insights into the Zn2+ storage mechanism in such gradient‐pore structures.
Amorphous Gallium Oxide Nanosheets with Broad Absorption and Spin Polarization for Si‐Based UV‒Vis‒NIR Photodetectors
Authors: Yu Junling , Wu Geng , Han Xiao , Liu Peigen , You Su , Yang Qing , Hong Xun
Published: February 2024

Achieving broad light absorption and high carrier separation efficiency is crucial for wide‐bandgap semiconductors to enable broadband photodetection applications. Here, amorphous gallium oxide nanosheets feature with broad absorption and spin polarization Wis synthesized, and assembled with graphene and p‐Si, realizing UV‒vis‒NIR photodetection. Extended X‐ray absorption fine structure reveals that a‐GaOx NSs possess lower tetrahedral Ga occupation (10%) compared to crystalline β‐Ga2O3 (50%). UV‒vis‒NIR diffuse reflectance spectra and magnetic hysteresis loops demonstrate broad absorption and weak ferromagnetism of a‐GaOx NSs, respectively. Density functional theory calculation further reveals sub‐gap states and spin polarization in a‐GaOx NSs. Moreover, combined with Mott–Schottky curves, photoluminescence and time‐resolved photoluminescence spectra inferred the effective suppression of carrier recombination via spin polarization of a‐GaOx NSs. The graphene/a‐GaOx NSs/p‐Si photodetector incorporates a back‐to‐back rectifying junction, acquiring a dark current as low as 63 pA. All photogenerated carriers are in the depletion region of the photodetector favouring efficient charge separation. This photodetector exhibits a response time of τrise<60 ms and τfall<120 ms, and high specific detectivity 1013 Jones over 254–1064 nm light.
High‐Efficiency Near‐Infrared OLED Enabled by Exciplex‐Forming Hosts and a New Organic Fluorescent Emitter
Authors: Chen Yi‐Yun , Kung Yu‐Cheng , Wang Miaosheng , Lo Yuan‐Chih , Chia Yao‐Te , Wang Chun‐Kai , Chen Deng‐Gao , Cheng Ju‐Ting , Chou Pi‐Tai , Wu Chichi , Li Elise Y. , Hu Bin , Hung Wen‐Yi , Wong Ken‐Tsung
Published: February 2024

Two blends comprising new dicyanopyrazine‐based acceptors (m‐CN and p‐CN) and a carbazole‐based donor CPTBF are explored for exciplex formation. The CPTBF:m‐CN and CPTBF:p‐CN blends show the signature red‐shifted emission together with the delayed fluorescence observed in time‐resolved measurement, manifesting the characteristics of thermally activated delayed fluorescence (TADF). The electroluminescence (EL) device employing CPTBF:m‐CN (CPTBF:p‐CN) blend as the emitting layer (EML) achieved an EQE of 5.22% (2.05%) with the EL λmax centered at 607 nm (625 nm). The exciplex excitons can be efficiently extracted by a new benzobisthiadiazole‐based near‐infrared (NIR) emitter DCzPBBT, where a device is configured with CPTBF:m‐CN: (5 wt.%) DCzPBBT as the EML to achieve a high EQE of 5.32% and an EL λmax 758 nm. Further increase of the doping concentration to 10 wt.% of DCzPBBT exhibits a bathochromic shifted EL λmax to 772 nm with 94% spectral coverage in the NIR (>700 nm) region, while the device EQE retains at 4.06%. The superior device performance stems from the highly efficient energy transfer between the exciplex‐forming host and NIR dopant together.
A Single Amino Acid Able to Promote High‐Temperature Ring‐Opening Polymerization by Dual Activation
Authors: Gabirondo Elena , Świderek Katarzyna , Marin Edurne , Maiz‐Iginitz Ainhoa , Larranaga Aitor , Moliner Vicent , Etxeberria Agustin , Sardon Haritz
Published: February 2024

Amino acids are indispensable compounds in the body, performing several biological processes that enable proper functioning. In this work, it is demonstrated that a single amino acid, taurine, is also able to promote the ring‐opening polymerization (ROP) of several cyclic monomers under industrially relevant conditions. It is shown that the unique zwitterionic structure of taurine, where the negatively charged sulfonic acid group and the protonated amine group are separated by two methylene groups, not only provides high thermal stability but also leads to a dual activation mechanism, which is corroborated by quantum mechanical calculations. This unique mechanism allows for the synthesis of polylactide of up to 50 kDa in bulk at 180 °C with good end‐group fidelity using a highly abundant catalyst. Furthermore, cytotoxicity tests confirm that PLLA synthesized with taurine is non‐toxic. Moreover, it is demonstrated that the presence of taurine does not have any detrimental effect on the thermal stability of polylactide, and therefore polymers can be used directly without any post‐polymerization purification. It is believed that the demonstration that a simple structure composed of a single amino acid can promote polymerization can bring a paradigm shift in the preparation of polymers.
Early‐season biomass and weather enable robust cereal rye cover crop biomass predictions
Authors: Huddell Alexandra , Needelman Brian , Law Eugene P. , Ackroyd Victoria J. , Bagavathiannan Muthukumar V. , Bradley Kevin , Davis Adam S. , Evans Jeffery A. , Everman Wesley Jay , Flessner Michael , Jordan Nicholas , Schwartz‐Lazaro Lauren M. , Leon Ramon G. , Lindquist John , Norsworthy Jason K. , Shergill Lovreet S. , VanGessel Mark , Mirsky Steven B.
Published: February 2024

Farmers need accurate estimates of winter cover crop biomass to make informed decisions on termination timing or to estimate potential release of nitrogen from cover crop residues to subsequent cash crops. Utilizing data from an extensive experiment across 11 states from 2016 to 2020, this study explores the most reliable predictors for determining cereal rye cover crop biomass at the time of termination. Our findings demonstrate a strong relationship between early‐season and late‐season cover crop biomass. Employing a random forest model, we predicted late‐season cereal rye biomass with a margin of error of approximately 1,000 kg ha−1 based on early‐season biomass, growing degree days, cereal rye planting and termination dates, photosynthetically active radiation, precipitation, and site coordinates as predictors. Our results suggest that similar modeling approaches could be combined with remotely sensed early‐season biomass estimations to improve the accuracy of predicting winter cover crop biomass at termination for decision support tools.

Core Ideas

Cereal rye winter cover crop biomass modeled on data from 35 site‐years.

We found a strong relationship between early and late‐season biomass.

Random forest model with early‐season biomass and weather data performed well.

Similar approach could improve decision support tools for cover crop management.
Foldaxane‐Based Switchable [c2]Daisy Chains
Authors: Liao Sibei , Tang Jie , Ma Chunmiao , Yu Lu , Tan Ying , Li Xuanzhu , Gan Quan
Published: February 2024

Artificial molecular muscles are highly attractive in the field of molecular machinery due to their unique properties of contraction and stretching motion. However, the synthesis of molecular muscles poses formidable challenges as it is hindered by undesirable yields and poor selectivity. Herein, we present a procedure for the dynamic assembly of foldaxane‐based [c2]daisy chains, wherein the hermaphroditic sequences consisting of aromatic helices and peptide rods are interlocked through inter‐strand hydrogen‐bonding interactions. The binding complementarity facilitates a selective and efficient assembly of [c2]daisy chain structures, inhibiting the creation of by‐products. Introducing multiple recognition sites confers the system with contraction and stretching motion actuated by chemical stimuli. The rate of this muscle‐like motion is calculated to be 0.8 s−1, which is 107 times faster than that of complex dissociation.
Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury
Authors: Chase Davis H. , Bebenek Adrian M. , Nie Pengju , Jaime‐Figueroa Saul , Butrin Arseniy , Castro Danielle A. , Hines John , Linhares Brian M. , Crews Craig M.
Published: February 2024

Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed “undruggable”. Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA‐approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure‐based drug design approach, aided by mass‐spectrometry and X‐ray crystallography, to develop DHC‐156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase‐inhibition from this novel scaffold while demonstrating that DHC‐156 induces the post‐translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies.
Tertiary Amides as Directing Groups for Enantioselective C−H Amination using Ion‐Paired Rhodium Complexes
Authors: Paterson Kieran J. , Dahiya Amit , Williams Benjamin D. , Phipps Robert J.
Published: February 2024

Enantioselective C−H amination at a benzylic methylene is a vital disconnection towards chiral benzylamines. Here we disclose that butyric and valeric acid‐derived tertiary amides can undergo highly enantioselective benzylic amination using an achiral anionic Rh complex that is ion‐paired with a Cinchona alkaloid‐derived chiral cation. A broad scope of compounds can be aminated encompassing numerous arene substitutions, amides, and two different chain lengths. Excellent tolerance of ortho substituents was observed, which has not been achieved before in asymmetric intermolecular C−H amination with Rh. We speculate that the tertiary amide group of the substrate engages in hydrogen bonding interactions directly with the chiral cation, enabling a high level of organisation at the transition state for C−H amination. This is in contrast with our previous work where a substrate bearing a hydrogen bond donor was required. Control experiments led to the discovery that methyl ethers also function as proficient directing groups under the optimised conditions, potentially also acting as hydrogen bond acceptors. This finding has the promise to dramatically expand the applicability of our ion‐paired chiral catalysts.
A Ferroptosis‐Inducing Arsenene‐Iridium Nanoplatform for Synergistic Immunotherapy in Pancreatic Cancer
Authors: Zhao Xinyang , Wang Xingyun , Zhang Wei , Tian Tian , Zhang Jingyi , Wang Jing , Wei Wei , Guo Zijian , Zhao Jing , Wang Xiuxiu
Published: February 2024

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two‐dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis‐inducing effects with high drug loading capacity and, importantly, excellent anti‐cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin‐loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis‐induced chemotherapy with immunotherapy via an all‐in‐one strategy, providing new insights for future pancreatic cancer therapy.
Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T‐cell expansion
Authors: Xie Yangzhi , Chen Liang , Chen Jiacheng , Chen Yongjun
Published: February 2024

Objective

Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg.

Methods

Hemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo.

Results

We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion.

Conclusion

These findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
Causal association between systemic lupus erythematosus and the risk of migraine: A Mendelian randomization study
Authors: Ren Meixuan , Yu Hangtian , Xiao Bing , Zhao Yan , Yan Jiewei , Liu Jianghong
Published: February 2024

Background

Numerous studies have found that patients with systemic lupus erythematosus (SLE) often have comorbid headache, especially migraine. However, the causal relationship between genetically determined SLE and migraine risk remains unclear. Therefore, we conducted a Mendelian randomization (MR) study to explore this causal association.

Methods

Genome‐wide association studies (GWAS) provided the instrumental variables. We selected summary data from GWAS of SLE as exposure (5201 SLE patients and 9066 controls). Both outcome GWAS data were from the Finnish Gene GWAS, including migraine with aura, migraine with aura and triptan purchases, and migraine without aura. The main MR approach was inverse‐variance weighted. Pleiotropy and heterogeneity were detected using the MR pleiotropy residual sum and outlier, MR‐Egger intercept test, leave‐one‐out analysis, and Cochran's Q test.

Results

There was a significant association between genetically predicted SLE susceptibility and increased risk of migraine with aura [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.02–1.08, p = .001]. The result was consistent when the outcome was migraine with aura and triptan purchases [OR = 1.05, 95% CI = 1.02–1.08, p = .001]. However, we found no association between SLE and migraine without aura. Our MR study showed no pleiotropy or heterogeneity.

Conclusions

Our study indicates that genetic susceptibility to SLE increases the incidence of migraine with aura but not migraine without aura. It is necessary for the routine evaluation and early recognition of migraine in patients with SLE in clinical settings.
Quality Evaluation of Asparagus officinalis by Profile of Amino Acids and Mineral Elements in Different Parts Combined with Chemometrics Methods
Authors: Liu Wei , Sun Mengyu , He Yinglong , Guo Qi , Zhang Lixia , Wang Zhihao , Zhang Guofeng
Published: February 2024

Asparagus officinalis has a homologous value in medicine and vegetables. Its immature stem, commonly called asparagus, is a central edible part. Asparagus skin and leaf also contain rich nutrients. However, these parts are often discarded. This study investigated amino acid and mineral elements in immature stem, skinless asparagus, asparagus skin, and leaf. Their quality was further evaluated by chemometrics methods such as principal component analysis and neural network analysis. The results showed amino acid content was high in immature stem and skinless asparagus and low in leaf, whereas the mineral elements were in four parts. Quality evaluation results showed four parts were divided into three grades. Immature stem and skinless asparagus were grouped into cluster 1 with the best quality as high‐quality raw materials in food and health‐care products. Meanwhile, three AA (Cys, His, Arg) and two mineral elements (Na, Cr) were identified as quality evaluation iconic substances.
Chemical Constituents of a Marine‐derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity
Authors: Zhao ZhiYuan , Cen FuLing , Mo TuXiang , Li WanShan , Ying Chen Guang
Published: February 2024

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H−K (1–4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine‐derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR‐ESI‐MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti‐inflammatory activities of compounds 1–12 were tested. Unfortunately, all of isolated compounds were inactivity.
Biophysical and Biochemical Characterization of Structurally Diverse Small Molecule Hits for KRAS Inhibition
Authors: Pagba Cynthia V. , Gupta Amit K. , Dilsha Kasuni , Sadrpour Parisa , Jakubec Jacob , Prakash Priyanka , van der Hoeven Dharini , Cho Kwang‐Jin , Gilbertson Scott , Gorfe Alemayehu A.
Published: February 2024

We describe six compounds as early hits for the development of direct inhibitors of KRAS, an important anticancer drug target. We show that these compounds bind to KRAS with affinities in the low micromolar range and exert different effects on its interactions with binding partners. Some of the compounds exhibit selective binding to the activated form of KRAS and inhibit signal transduction through both the MAPK or the phosphatidylinositide 3‐kinase PI3K‐protein kinase B (AKT) pathway in cells expressing mutant KRAS. Most inhibit intrinsic and/or SOS‐mediated KRAS activation while others inhibit RAS‐effector interaction. We propose these compounds as starting points for the development of non‐covalent allosteric KRAS inhibitors.
Aldehyde Reductase Activity of Carboxylic Acid Reductases
Authors: Winkler Margit , Breuer Hannah G. , Schober Lukas
Published: February 2024

Carboxylic acid reductase enzymes (CARs) are well known for the reduction of a wide range of carboxylic acids to the respective aldehydes. One of the essential CAR domains ‐ the reductase domain (R‐domain) ‐ was recently shown to catalyze the standalone reduction of carbonyls, including aldehydes, which are typically considered to be the final product of carboxylic acid reduction by CAR. We discovered that the respective full‐length CARs were equally able to reduce aldehydes. Herein we aimed to shed light on the impact of this activity on aldehyde production and acid reduction in general. Our data explains previously inexplicable results and a new CAR from Mycolicibacterium wolinskyi is presented.
Recurrent peri‐myocarditis: A rarer but unfortunate redundant presentation of thyroid storm
Authors: Nabin K. C. , Bhattarai Pratik , Zahid Erum , Pasha Muhammad Nabeel
Published: February 2024

Key Clinical Message

Thyroid storm represents a critical and life‐threatening complication from hyperthyroidism, with a notable mortality risk. Limited literature reports have explored the correlation between thyroid storm and peri‐myocarditis, although the precise pathophysiological underpinnings remain unclear. The pathophysiology of how thyroid storm and peri‐myocarditis are associated is not clearly understood; however, unfavorable prognostic factors include atrial fibrillation and recurrent thyrotoxicosis. Here, we present a case concerning recurrent peri‐myocarditis concomitant with a thyroid storm.
CO2 Photoreduction Product Selectivity with TiO2−Cu Nanocatalysts under Different Reaction Media
Authors: Nascimento Victor R. S. , Torres Juliana A. , Iga Gustavo D. , dos Santos Allef Leite , Egues Silvia M. , Filho José B. G. , Ferreira Luiz F. R. , Ribeiro Caue
Published: February 2024

This study explores photocatalytic conversion of CO2 using TiO2−Cu heterojunctions with different Cu contents and investigates influence of different reaction media on the process efficiency. The use of KOH favored liquid products, especially ethanol. An analysis of H2 production as the main competitive reaction was done. Sodium oxalate led to an increase in H2 evolution by approximately 600 μmol g‐1 compared to pure water, in the presence of CO2 in the reaction medium, but the blank test (without CO2) indicates a lower H2 yield (~136 μmol g−1), which suggests that the competitive reaction with CO2 also plays a role in H2 production. This role was related to the decrease of the initial pH from approximately 8.5 to 5.2, stabilizing at 5.5 at the end of the 6 h reaction. In an environment saturated with N2, the pH increases to 9 and stabilizes at 7.8 at the end of the process. In the presence of acetic acid, both CO and H2 production were suppressed, with a significant increase in the selectivity for methane via cleavage of the acid‘s carbon bond. The findings underscore the importance of optimizing reaction conditions to achieve higher yields of desired products in the photocatalytic conversion of CO2.
Hypervalent Iodine Compounds in Carbohydrate Chemistry: Glycosylation, Functionalization and Oxidation
Authors: Mahanti Mukul , Bhaskar Pal Kumar , Wallentin Carl Johan , Galan M. Carmen
Published: February 2024

This mini review article provides an overview on the use of hypervalent iodine compounds (HICs) in carbohydrate synthesis, focusing on their chemistry and recent applications. HICs are similar to transition metals in their reactivity but have the added benefit of being environmentally benign, and are therefore commonly used as selective oxidants and eco‐friendly reagents in organic synthesis. Herein, we summarize various synthetic uses of hypervalent iodine reagents in reactions such as glycosylation, oxidations, functionalization, and C−C bond‐forming reactions. The goal of this review is to illustrate the advantages and versatility of using HICs as an environmentally sustainable alternative to heavy metals in carbohydrate chemistry.
Chlorajaponins A—Q, Lindenane‐Related Sesquiterpenoid Dimers from Chloranthus japonicus and Their Biological Activities
Authors: Feng Wei‐Jiao , Gu Yue , Huang Pei‐Zhi , Yang Hong‐Ying , Zhang Rui , He Yi‐Lin , Lv Ting‐Hong , Li Ya , Gao Kun
Published: February 2024

Comprehensive Summary

Seventeen undescribed lindenane‐related sesquiterpenoid dimers, chlorajaponins A—Q (1—17), and 13 reported analogs (18—30) were isolated from Chloranthus japonicus Sieb. Compound 1 possesses an unprecedented 3/5/7/5/5/6/5/3 fused octacyclic scaffold, featuring a 6(5→4)‐abeo‐lindenane monomer, while 2 exhibits a 3/5/6/6/5/6/5/3 fused octacyclic scaffold. Their structures were determined through a combination of spectroscopic analyses and X‐ray crystallography. Compounds 1, 2, and 18 demonstrated significant inhibitory effects on lipid accumulation and effectively reduced the levels of triglycerides and total cholesterol, as well as the levels of aspartate aminotransferase and alanine aminotransferase in a HepG2 cell model. In addition, compounds 1, 2, and 18 significantly suppressed the protein expression of the fatty acid synthase (FASN) and the sterol regulatory element‐binding protein 1 (SREBP1). Moreover, the anti‐inflammatory assay showed that compounds 19—22 and 25 inhibited the NO production induced by lipopolysaccharide in RAW 264.7 macrophages with IC50 values of 7.89 ± 0.44, 6.25 ± 0.46, 2.98 ± 0.29, 10.77 ± 0.60, and 3.60 ± 0.28 μmol/L.
Induction of Paraquat‐Mediated Parkinsonian Phenotype in Zebrafish
Authors: Harini V. S. , Marimuthu Raghunath , Tantry M. S. Ananthakrishna , Santhakumar Kirankumar
Published: February 2024

Paraquat (PQ) is a well‐known neurotoxin closely associated with neurodegenerative Parkinson's disease (PD). Zebrafish are utilized as a model for PD research because of their well‐defined neuropathology and locomotor behavior. Here, we highlight protocols for inducing PD using PQ and analyzing locomotor activity in adult zebrafish. Basic Protocol 1 details the treatment of adult male zebrafish with 60 mg/kg PQ via intraperitoneal injection to induce a PD‐like phenotype, followed by the steps to perform a locomotor assay. Basic Protocol 2 provides step‐by‐step guidance for processing the acquired videos in ToxTrac software to understand the locomotor parameters of 0.9% saline– and 60 mg/kg PQ–injected adult zebrafish. The simplicity of the treatment strategy, low‐cost video acquisition setup, and free video processing make these protocols accessible without prior experience. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Development of Parkinson's disease features in adult zebrafish

Basic Protocol 2: ToxTrac analysis for locomotor assay