bluuebunny/crossref_metadata_2025 huggingface dataset:
When individual rights collide: Know how to prepare, respond
Authors: Porter Michael
Published: June 2021

The Sixth Circuit Court of Appeals (covering Michigan, Ohio, Kentucky, and Tennessee) recently allowed a faculty member's First Amendment lawsuit to move forward after the university disciplined him for violating Title IX by failing to follow the institution's gender pronoun policy. Meriwether v. Hartop et al., 992 F.3d 492 (6th Cir. 2021).
Clinicopathological features and lymph node and distant metastasis patterns in patients with gastroenteropancreatic mixed neuroendocrine‐non‐neuroendocrine neoplasm
Authors: Zhang Panpan , Li Zhongwu , Li Jie , Li Jian , Zhang Xiaotian , Lu Zhihao , Sun Yu , Li Yan , Zhou Jun , Wang Xicheng , Peng Zhi , Shen Lin , Lu Ming
Published: June 2021

Objective

Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine‐non‐neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN.

Methods

Continuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed.

Results

This study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non‐)neuroendocrine component was observed in 40 patients (23.7%; <30% of the tumor). Among the enrolled patients, 80 underwent surgical removal of the primary tumor and lymph nodes (LNs), and 34 with distant metastasis underwent biopsy of both primary tumor and metastatic lesions. In patients with LN metastasis, 68.8% (55/80) exhibited a pure component of either neuroendocrine (NE) or adenocarcinoma/squamous carcinoma (AS) in metastatic LNs, while 20% (16/80) showed different components in different LNs, and only 11.2% (9/80) exhibited both NE and AS components in the same LN. In patients with distant metastases, 26.5% (9/34) possessed coexisting NE and AS components in the distant metastases, 70.6% (24/34) were regarded as a pure NE component, and 2.9% (1/34) were comprised of a pure AS component.

Conclusion

Lymph node and distant metastases exhibited distinct metastatic patterns in patients with MiNEN. The major pathological component in regional LNs may have influenced the proportion of the two components within the primary tumor, but distant metastases were dominated by the NE component.
Open‐wedge high tibial osteotomy for the treatment of osteoarthritis of both knee and ankle in the same leg: A report of two cases
Authors: Baek Ji‐Hoon , Lee Su Chan , Jin Hosun , Ahn Hye Sun , Nam Chang Hyun
Published: June 2021

We report two cases of patients with concurrent osteoarthritis of the knee and ipsilateral ankle. The patients were treated with high tibial osteotomy (HTO). In well‐planned and selected cases, HTO may be effective in treating not only the knee, but also the ankle in patients with ipsilateral double‐joint osteoarthritis.
Inappropriate prescription of corticosteroid therapy during inflammatory ileo‐colitis revealing disseminated tuberculosis with digestive involvement: Two case reports
Authors: Razafindrazoto Chantelli Iamblaudiot , Randriamifidy Nitah Harivony , Rakotomalala Jolivet Auguste , Ralaizanaka Behoavy Mahafaly , Rakotomaharo Mialitiana , Hasina Laingonirina Domoina Harivonjy , Maherison Sonny , Rasolonjatovo Anjaramalala Sitraka , Rakotozafindrabe Andry Lalaina Rinà , Rabenjanahary Tovo Harimanana , Razafimahefa Soloniaina Hélio , Ramanampamonjy Rado Manitrala
Published: June 2021

It is essential to differentiate intestinal tuberculosis from Crohn's disease because of the therapeutic implications of Crohn's disease, which can exacerbate the symptoms of tuberculosis.
Response to pegylated interferon in a COVID‐19 positive male with metastatic jejunal neuroendocrine tumor treated with everolimus
Authors: Frankel Arthur E. , Yip Wai C. , Naik Eknath , Hasselbalch Hans C.
Published: June 2021

A 61‐year‐old male on everolimus had chronic SARS‐CoV‐2 infection. Addition of pegylated interferon cleared viral RNA and supports combination therapy with everolimus plus interferon for COVID‐19.
A rare case of Levofloxacin‐related Iliopsoas and Achilles tendon rupture
Authors: Bedi Prabhjot Singh , Kuriakose Kiran , Kim Jay , Lewis Paul B , Singh Vikas K
Published: June 2021

Achilles tendon rupture is a well‐documented adverse effect of Fluoroquinolones; however, herein we present a case of complete iliopsoas and Achilles, and partial semimembranosus tendon rupture secondary to Levofloxacin.
Chest imaging of hypersensitivity pneumonitis induced by heroin abuse
Authors: Bond Michael C. , Butler Kenneth H. , Richardson Adam C. , Blosser Kelly M.
Published: June 2021

Long‐term abuse of nasally inhaled substances such as heroin can result in life‐threatening hypersensitivity pneumonitis and respiratory distress. In the setting of hypoxia, a chest CTA is often necessary to see the extent of the lung involvement and to rule out pulmonary emboli.
Electrochemical and Plasmon‐induced Grafting of n‐Dopable π‐Conjugated Oligomers
Authors: Bastide Mathieu , Frath Denis , Gam‐Derouich Sarra , Lacroix Jean‐Christophe
Published: June 2021

The functionalization of electrodes by the reduction of diazonium cations generated in situ from 4‐(2,3‐diethylthieno[3,4‐b]pyrazine‐5‐yl)aniline has been investigated. The thienopyrazine unit of this molecule is a precursor of n‐dopable π‐conjugated oligomers. Electrochemical reduction of diazonium cation coats the electrode with organic layers. Raman, IR, and XPS analyses show that their composition corresponds to that of the starting monomer, while AFM scratching measurements indicate thicknesses below 10 nm. The electrochemical responses of various reversible redox couples on the modified electrodes show that the attached layer is insulating in the positive potential range but can be n‐doped at negative potential and switches to a conductive state. Moreover, oligo(4‐(2,3‐diethylthieno[3,4‐b]pyrazine‐5‐yl)phenyl) can be selectively grafted onto gold nanoparticles (AuNPs) by plasmon‐induced diazonium reduction. A 10–20 nm‐thick organic layer is easily grafted onto each gold nanoparticle by visible‐light illumination in a few minutes without any reducing agent or molecular photocatalyst. This result is attributed to the transfer of hot electrons from the excited plasmonic NPs to the diazonium, confirms that localized surface plasmon resonance can induce nanolocalized electrochemical reactions, and contributes to the emerging field of “plasmonic electrochemistry”.
Host‐Guest Interaction in Ethylene and Ethane Separation on Zeolitic Imidazolate Frameworks as Revealed by Solid‐State NMR Spectroscopy
Authors: Xiao Yuqing , Chu Yueying , Li Shenhui , Chen Fang , Gao Wei , Xu Jun , Deng Feng
Published: June 2021

The separation of ethane/ethylene mixture by using metal‐organic frameworks (MOFs) as adsorbents is strongly associated with the pore size‐sieving effect and the adsorbent‐adsorbate interaction. Herein, solid‐state NMR spectroscopy is utilized to explore the host‐guest interaction and ethane/ethylene separation mechanism on zeolitic imidazolate frameworks (ZIFs). Preferential access to the ZIF‐8 and ZIF‐8‐90 frameworks by ethane compared to ethylene is directly visualized from two‐dimensional 1H‐1H spin diffusion MAS NMR spectroscopy and further verified by computational density distributions. The 1H MAS NMR spectroscopy provides an alternative for straightforwardly extracting the adsorption selectivity of ethane/ethylene mixture at 1.1∼9.6 bar in ZIFs, which is consistent with the IAST predictions.
A Facile Construction of Bisheterocyclic Methane Scaffolds through Palladium‐Catalyzed Domino Cyclization
Authors: Qi Hongbo , Han Kaiming , Chen Shufeng
Published: June 2021

Main observation and conclusion

A convenient palladium‐catalyzed domino cyclization reaction for the construction of bis(benzofuranyl)methane scaffolds bearing an all‐carbon quaternary center has been described. In the cascade process, one C(sp2)—O bond, two C(sp2)—C(sp3) bonds as well as two benzofuran rings are formed in a single synthetic sequence. The approach shows wide scope of substrates and good functional‐group tolerance. Moreover, this methodology is successfully extended to the synthesis of benzofuranyl methyl chromane derivatives.
Autophagy‐Dependent Ferroptosis as a Therapeutic Target in Cancer
Authors: Liu Li , Li Liqi , Li Menghuan , Luo Zhong
Published: June 2021

Ferroptosis is an iron‐dependent form of cell death associated with the accumulation of labile iron and cytotoxic lipid peroxides. Increasing evidence reveals that ferroptosis is not a self‐standing phenomenon and has close connections with other cellular events. Remarkably, recent insights show that ferroptosis is dependent on autophagy, which is a lysosomal degradation pathway responsible for the recycling of damaged cellular components under survival stress. Autophagy is capable of contributing to ferroptosis through degradation of the ferritin, an iron‐storage protein, accompanied with the accumulation of iron levels and lipid ROS. The interplay between autophagy and ferroptosis also reveals emerging opportunities for novel tumor therapies, which has inspired the development of many treatment strategies capable of inducing ferroptosis in tumor cells via autophagic pathways based on molecular and nanoparticulate agents. In this review, we summarize the specific molecular and regulatory networks of autophagy‐dependent ferroptosis and highlight their pathophysiological impact on various aspects of tumor cells. A perspective was also provided regarding the preliminary therapeutic exploitation of ferroptosis/autophagy crosstalk for tumor treatment.
A variant of teaching‐learning‐based optimization and its application for minimizing the cost of Workflow Execution in the Cloud Computing
Authors: Ram Satya Deo K. , Srivastava Shashank , Kumar Mishra Krishn
Published: June 2021

Teaching learning‐based optimization (TLBO) was proposed by Rao to solve optimization problems. It is based on the theory of teaching‐learning mechanism. Although it performs well in unimodal problems yet its performance is not good in multimodal problems. To further improve this algorithm's performance and make it suitable for both unimodal problems and multimodal problems, we made some major changes in the theory and the algorithm's operators. The proposed algorithm is able to capture diverse optimal solutions in less number of iterations and is very good for solving multimodal problems. This newly created variant of TLBO is named generalized TLBO (GTLBO). The performance of GTLBO is tested on CEC−06, 2019 benchmark functions and other 15 classical benchmark functions, and it is found that the proposed algorithm is performing better comparatively. Then it is simulated for solving the workflow scheduling problem in CloudSim. Standard scientific workflow applications as Montage, Epigenomics, Sipht, and a sample workflow are used as dataset to test algorithms' performance in cloud environments. Our proposed approach, GTLBO, provides the proper distribution of workloads and offers minimal execution‐cost for the workflow applications. Results reflect the supremacy of the proposed algorithm GTLBO comparatively.
General mentalizing, emotional theory of mind and interpersonal mistrust in anorexia nervosa: The validation of the Hebrew version of the Cambridge mindreading face‐task
Authors: Rothschild‐Yakar Lily , Goshen Dor , Enoch‐Levy Adi , Raanan Hadas , Gur Eitan , Stein Daniel , Golan Ofer
Published: June 2021

Objective

This study had two goals. The first was to validate and examine the potential of the Hebrew version of the Cambridge Mindreading face task (CAMHeb)—an ecological measure of emotional theory of mind (eToM)—to assess eToM in individuals with anorexia nervosa (AN). The second goal was to examine whether interpersonal mistrust would mediate the relation between mentalizing and eToM and the severity of AN.

Method

The validity of the CAMHeb was examined using well‐established measures of mentalizing ability and eToM in 45 young female patients with AN and 53 control participants. Next, the mediation model was assessed using a subsample of 33 AN patients and 34 controls, in which interpersonal mistrust was additionally assessed.

Results

The CAMHeb correlated with the measures of mentalizing ability and eToM. The CAMHeb, along with the measure of general mentalizing, significantly differentiated between the AN and control groups. The associations of general mentalizing and CAMHeb with eating disorder (ED) symptoms were mediated by interpersonal mistrust.

Conclusion

The CAMHeb is a valid measure of deficient eToM in AN. In therapy, an increase in mentalizing ability and accurate eToM may enhance interpersonal trust, which may further contribute to attenuation of AN symptoms.
PharmVar GeneFocus: CYP2C9
Authors: Sangkuhl Katrin , Claudio‐Campos Karla , Cavallari Larisa H. , Agundez Jose A.G. , Whirl‐Carrillo Michelle , Duconge Jorge , Del Tredici Andria L. , Wadelius Mia , Rodrigues Botton Mariana , Woodahl Erica L. , Scott Stuart A. , Klein Teri E. , Pratt Victoria M. , Daly Ann K. , Gaedigk Andrea
Published: June 2021

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs, including nonsteroidal anti‐inflammatory drugs, phenytoin, antidiabetic agents, and angiotensin receptor blockers. Variable CYP2C9 activity is of particular importance regarding efficacy and safety of warfarin and siponimod as indicated in their package inserts. This GeneFocus provides a comprehensive overview and summary of CYP2C9 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium.
Development of ripple reduced solar photovoltaic regulators using boomerang sliding mode control strategy
Authors: MS Kamalesh , Nattuthurai Senthilnathan , Chokkalingam Bharatiraja , Muthusamy Sabarimuthu , Cherukupalli Kumar
Published: June 2021

DC–DC boost converters are extensively used in wide range of solar photovoltaic (PV) applications. A common problem in PV regulator is the presence of ripples in output voltage and output current, due to the oscillations in PV power, inaccurate switching, and inadmissible inductor peak currents. In general, conventional boost converters are widely used in PV regulator; however, conventional PWM‐controlled boost converters are upgraded to sliding mode controller (SMC)‐based PWM controllers, which has been elaborated in the literature. However, SMC‐based boost converter experiences the following problems: (i) presence of ripples in the output current and (ii) dynamic instability during sudden change in load current. This paper addresses the aforementioned problems and proposes a boomerang trajectory‐based SMC (BT‐SMC) control strategy for ripple mitigation in conventional DC–DC boost converters specifically used in PV regulator. BT‐SMC tracker tracks the reference wave shape and controls the duty cycle, with respect to the switching frequency to have a ripple mitigated output. This self‐adapting system provides an adequate reduction in ripples and rapid convergence of error nearest to zero. A detailed analysis on switching frequency transition, load variation, trajectory control, and its stability existence is conducted, and the proposed system is implemented using dSPACE‐MicroLabBox‐DS1202.
Designing a reliable and energy‐efficient cross‐layer protocol for wireless sensor networks
Authors: Alabady Salah Abdulghani , Alhajji Sukaina Shukur
Published: June 2021

Due to the energy scarcity that the wireless sensor networks currently face, many energy‐efficient protocols have been developed and proposed in different layers, especially in the data link and network layers, as a large amount of energy consumed by the transceiver, idle‐listening, collision, selecting the correct nodes to act as routers, long‐distance transmission, etc., which are the responsibility of data link and network layers. Since these protocols address the reasons for energy loss in one layer and neglect the treatment of energy loss in other layers, as each layer of the TCP/IP module has its own features and has no control over the other layers. Therefore, there was a need for a cross‐layer design. In this paper, an energy‐efficient cross‐layer between MAC layer and network layer has been proposed using slotted ALOHA based p‐persistent CSMA MAC protocol and Enhance Energy Conservation based on Residual Energy and Distance (EECRED) in order to reduce energy consumption and increase the network lifetime. The performance of the proposed cross‐layer protocol is evaluated by simulating the protocol using the MATLAB simulation. The simulation results are compared with the Fuzzy and Ant Colony Optimization (ACO) based MAC/Routing cross‐layer protocol (FAMACRO), FAMACRO for wireless sensor networks (FAMACROW), fuzzy cross‐layer LEACH, routing‐MAC, and Energy‐efficient Cross‐layer‐sensing Clustering Method (ECCM) protocols to ensure the efficiency of the proposed cross‐layer. The simulation results show that the proposed cross‐layer protocol is very energy efficient, provides stable networks, consumes little energy, and significantly increases the life of the network compared to the single‐layer protocols where the improvement rate was 45%, 53%, 37%, 91%, and 28.72% compared to FAMACRO, FAMAROW, fuzzy cross‐layer LEACH, routing‐MAC, and ECCM protocols respectively in terms of the number of alive nodes or residual energy.
Canadian Indigenous Cognitive Assessment (CICA): Inter‐rater reliability and criterion validity in Anishinaabe communities on Manitoulin Island, Canada
Authors: Walker Jennifer D. , O'Connell Megan E. , Pitawanakwat Karen , Blind Melissa , Warry Wayne , Lemieux Andrine , Patterson Christopher , Allaby Cheryl , Valvasori Meghan , Zhao Yantao , Jacklin Kristen
Published: June 2021

Introduction

Despite increasing dementia rates, few culturally informed cognitive assessment tools exist for Indigenous populations. The Canadian Indigenous Cognitive Assessment (CICA) was adapted with First Nations on Manitoulin Island, Canada, and provides a brief, multi‐domain cognitive assessment in English and Anishinaabemowin.

Methods

Using community‐based participatory research (CBPR) methods, we assessed the CICA for inter‐rater and test–retest reliability in 15 individuals. We subsequently evaluated validity and established meaningful CICA cut‐off scores in 55 individuals assessed by a geriatrician.

Results

The CICA demonstrated strong reliability (intra‐class coefficient = 0.95 [0.85,0.98]). The area under the curve (AUC) was 0.98 (0.94, 1.00), and the ideal cut‐point to identify likely cases of dementia was a score of less than or equal to 34 with sensitivity of 100% and specificity of 85%.

Discussion

When used with older First Nations men and women living in First Nations communities, the CICA offers a culturally safe, reliable, and valid assessment to support dementia case‐finding.
Potential use of serum‐derived bovine immunoglobulin/protein isolate for the management of COVID‐19
Authors: Utay Netanya S. , Asmuth David M. , Gharakhanian Shahin , Contreras Moises , Warner Christopher D. , Detzel Christopher J.
Published: June 2021

COVID‐19 manifests as a mild disease in most people but can progress to severe disease in nearly 20% of individuals. Disease progression is likely driven by a cytokine storm, either directly stimulated by SARS‐CoV‐2 or by increased systemic inflammation in which the gut might play an integral role. SARS‐CoV‐2 replication in the gut may cause increased intestinal permeability, alterations to the fecal microbiome, and increased inflammatory cytokines. Each effect may lead to increased systemic inflammation and the transport of cytokines and inflammatory antigens from the gut to the lung. Few interventions are being studied to treat people with mild disease and prevent the cytokine storm. Serumderived bovine immunoglobulin/protein isolate (SBI) may prevent progression by (1) binding and neutralizing inflammatory antigens, (2) decreasing gut permeability, (3) interfering with ACE2 binding by viral proteins, and (4) improving the fecal microbiome. SBI is therefore a promising intervention to prevent disease progression in COVID‐19 patients.
New image‐processing technology for endoscopic ultrasound‐guided fine‐needle aspiration biopsy specimen evaluation in patients with pancreatic cancer
Authors: Okuwaki Kosuke , Imaizumi Hiroshi , Kida Mitsuhiro , Masutani Hironori , Watanabe Masafumi , Adachi Kai , Tadehara Masayoshi , Tamaki Akihiro , Iwai Tomohisa , Yamauchi Hiroshi , Hasegawa Rikiya , Kaneko Toru , Kurosu Takahiro , Koizumi Wasaburo
Published: June 2021

Objectives

We evaluated the usefulness of a newly developed system with which the total amount of whitish cores in endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNAB) samples is automatically calculated (automated multiband imaging system [AMUS]).

Methods

From 30 prospectively enrolled patients suspected of having pancreatic cancer, four EUS‐FNAB specimens per patient were obtained. Following AMUS calculations, two specimens were prepared after stereomicroscopy‐guided manual division into whitish and reddish sections (isolation group), and the other two were prepared without such division (no‐isolation group). The relation of the AMUS results pertaining to the length of the manually measured whitish cores (stereo‐microscopically visible white core [SVWC]) and the sample suitability for pathologic evaluation were analyzed.

Results

Histological diagnostic accuracy was 90%; median SVWC length, 14 mm; and median area of whitish core calculated using the AMUS, 13 mm2. The SVWC length correlated with whitish core amount (ρ = 0.83, p < 0.01) and adequacy score (ρ = 0.50, p < 0.01). The whitish core amount correlated with the adequacy score (ρ = 0.40, p < 0.01). The area under the receiver‐operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.84 (p < 0.01; cutoff ≥ 8 mm2, sensitivity 92.5%). Subgroup analysis (isolation vs. no‐isolation group) revealed no significant between‐group differences in the median histological adequacy (p = 0.27) or tumor cell content ratio (p = 0.28). The median scores for degree of blood contamination were significantly lower in the isolation group than in the no‐isolation group (p < 0.01).

Conclusion

AMUS is a simple on‐site verification procedure for determining the appropriate sampling tissue quantity for high diagnostic accuracy.
The effect of fire on ant assemblages does not depend on habitat openness but does select for large, gracile predators
Authors: Bishop Tom R. , Tomlinson Andy , McNeice Travers , Sfenthourakis Spyros , Parr Catherine L.
Published: June 2021

Ecosystems can respond in a variety of ways to the same agent of disturbance. In some contexts, fire causes large and long‐lasting changes to ecological communities. In others, fire has a limited or short‐lived impact on assemblages of animals and plants. Understanding why this occurs is critical if we are to manage these kinds of disturbances across the globe. A recent synthesis proposed that these seemingly idiosyncratic responses to fire can be understood in the context of habitat openness pre‐disturbance. Assemblages in open habitats should respond less to a single fire event that those in closed habitats. We provide a test of this hypothesis by examining the response of ant (Hymenoptera: Formicidae) communities to large‐scale fire events in three habitats of different natural canopy openness on the Peloponnese peninsula in Greece. We also test the hypothesis that assemblage responses to fire are trait dependent. Fire simplifies the physical structure of the environment, increases insolation, and limits opportunities for ants to exploit herbivorous feeding strategies. Consequently, we predict that ants will face a strong environmental filter between unburnt and recently burnt plots, which will be reflected in their functional morphology. Our analysis shows that burnt plots have more individual ants, more species and an almost complete compositional change relative to unburnt plots. These changes do not depend on initial canopy openness. Rather, we suggest that openness must be interpreted relative to the study taxon; for ants, openness should be measured closer to the ground level. In our study, ground‐level openness does not vary across the plots, which may explain the results. Furthermore, ants in burnt plots are significantly larger, have relatively longer legs, relatively longer mandibles, and more elongate heads. This morphotype fits with our prediction of ants that can move and feed successfully in the burnt micro‐landscape. Ultimately, more work is needed to fully explore the relationship between habitat openness and the response to fire. Our results showing a filtered set of ant morphologies in burnt environments suggest that ant traits may offer a further way forward to understand the faunal response to fire and disturbance in general.
Analyzing long‐term water quality of lakes in Rhode Island and the northeastern United States with an anomaly approach
Authors: Hollister J. W. , Kellogg D. Q. , Kreakie B. J. , Shivers S. D. , Milstead W. B. , Herron E. M. , Green L. T. , Gold A. J.
Published: June 2021

Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long‐term datasets. Recent analysis of the LAke multi‐scaled GeOSpatial and temporal database for the Northeast (LAGOS‐NE) United States found stable water quality in the northeastern and midwestern United States; however, sub‐regional trends may be obscured. We used the University of Rhode Island’s Watershed Watch Volunteer Monitoring Program (URIWW) dataset to determine if there were sub‐regional (i.e., 3000 km2) water quality trends. URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 yr. The LAGOS‐NE and URIWW datasets allowed for comparison of water quality trends at regional and sub‐regional scales, respectively. We assessed regional (LAGOS‐NE) and sub‐regional (URIWW) trends with yearly median anomalies calculated on a per‐station basis. Sub‐regionally, temperature and chlorophyllaincreased from 1993 to 2016. Total nitrogen, total phosphorus, and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOS‐NE dataset showed similar trends to prior studies of the LAGOS‐NE with chlorophylla, total nitrogen, and N:P all stable over time. Total phosphorus did show a very slight increase. In short, algal biomass, as measured by chlorophyllain Rhode Island lakes and reservoirs increased, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. Additionally, we demonstrated both the value of long‐term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site‐specific anomalies for analyzing for long‐term water quality trends.
Iron/2,6‐Di(pyrazol‐1‐yl)pyridine Complexes with a Discotic Pattern of Alkyl or Alkynyl Substituents
Authors: Galadzhun Iurii , Kulmaczewski Rafal , Cespedes Oscar , Halcrow Malcolm A.
Published: June 2021

2,6‐Di(4‐iodopyrazol‐1‐yl)pyridine is converted to 2,6‐di(4‐{alkyn‐1‐yl}pyrazol‐1‐yl)pyridine (L1R; R’=CnH2n−3, n=12, 14, 16) derivatives by Sonogashira reactions. Hydrogenation of these intermediates yields the corresponding 2,6‐di(4‐alkylpyrazol‐1‐yl)pyridine (L2R; R=CnH2n+1) derivatives. Homoleptic Fe[BF4]2 complexes of all these ligands were prepared, bearing four long chain substituents in a discotic‐type array. Crystallographic data from two L1R ligands imply the alkynyl substituents do not undergo intermolecular interdigitation in the solid state, which could explain the lower crystallinity and ill‐defined spin‐crossover in their iron complexes. Solid [Fe(L2R)2][BF4]2 (n=12 and 14) exhibit an irreversible, abrupt low→high‐spin event near 350 K, which is not associated with solvent loss and may involve disordering of their alkyl chain conformations. No mesophase behavior was observed from any of these compounds.
Organocatalytic Desymmetrization of Meso‐Aziridines Via Asymmetric Intramolecular Rearrangement
Authors: Costanzo Martina , Cortigiani Mauro , Gillick‐Healy Malachi W. , Kelly Brian G. , Monasterolo Claudio , Adamo Mauro F. A.
Published: June 2021

Herein we report the first organocatalytic method for the desymmetrization of meso‐aziridines that does not require the use of an external nucleophilic reagent. The process was designed upon a base promoted rearrangement of bicyclic meso‐cyclopentanone aziridines, that progresses in intramolecular fashion to provide densely functionalized cyclic ketones, key intermediates for the preparation of Active Pharmaceutical Ingredients. The key enantio‐determining step proceeded under the catalysis of a bifunctional thiourea organocatalyst. The process provides an entry to a class of highly functionalized chiral amines, 4‐aminocyclopentenones, not accessible with previous desymmetrization methods. The ambiphilic nature of the products makes them versatile synthetic intermediates in the preparation of natural products and popular antiviral nucleoside inhibitors, for example abacavir.
A Highly Congested Dioxapyrenophane from an Attempted Synthesis of the Highly‐Strained 1,1,6,6‐Tetramethyl[6](2,11)teropyrenophane
Authors: Ghods Ghasemabadi Parisa , Zhao Yuming , Bodwell Graham J.
Published: June 2021

Synthetic studies aimed at the synthesis of 1,1,6,6‐tetramethyl[6](2,11)teropyrenophane (3 a) led to the synthesis of the structurally unusual dioxa[6.3.3](7,1,3)pyrenophane 29. The strategic approach to access 3 a resembled the one that was successfully applied in the synthesis of the higher homologues 3 b‐e, but had a key difference: three‐atom bridges were utilized instead of two‐atom bridges in the construction of the intermediate pyrenophanes which were slated to serve as precursors to access 3 a. After stepwise approaches to construct the bridges failed, it was found that two ether bridges could be installed easily in the same reaction to afford dioxa[6.3.3](7,1,3)pyrenophane 29. Considerable steric congestion around the dioxa[3.3]metacyclophane substructure arises from the presence of a methyl group on each of the benzylic positions of the three‐atom bridges. Although the conversion of 29 into a [6](2,11)teropyrenophane was unsuccessful, the finding that ether bridges in this structurally uncommon dioxacyclophane could be formed easily offers new opportunities for the synthesis of related cyclophanes that may ultimately serve as viable precursors for the synthesis of [n](2,11)teropyrenophanes.
Di‐ and Trifluorinated 2‐Azidobenzimidazole Derivatives: Synthesis, Photooxygenation, and 19F NMR Prediction
Authors: Kanitz Nils E. , Fresia Marvin , Jones Peter G. , Lindel Thomas
Published: June 2021

The photoreactivity of a series of hitherto unknown, multiply fluorinated 2‐azidobenzimidazole derivatives was investigated. The synthesis of the starting material includes regioselective p‐defluorination of nitrobenzene derivatives employing Ogoshi's conditions. If the 6‐position was unsubstituted, irradiation in the presence of N‐protected amino acids at 300 nm (Rayonet) led to the formation of arylesters by oxygenation of the 6‐position in good to excellent yields and perfect regioselectivity. We did not observe any displacement of fluoride. If the 6‐position itself was fluorinated, alternative positions of the benzene portion were attacked. Mechanistically, the reaction proceeds through ring opening of the singlet nitrene to the cyanodiimine or via the iminobenzimidazolium ion. The availability of a set of fluorinated photo‐adducts prompted the quantum chemical calculation of their 19F NMR chemical shifts. Even with the most suitable method investigated (ωB97XD/TApr‐cc‐pVDZ), deviations of up to 5 ppm from the experimental values were observed, underlining the importance of experimental measurements.
Quinoline‐Based Silylium Ions: Synthesis, Structure and Lewis Acidity
Authors: Kumar Nivesh , Laye Claire , Robert Frédéric , Landais Yannick
Published: June 2021

Heteroarylsilyl cations elaborated from a quinoline skeleton have been prepared from the corresponding silanes, and their structures were studied by 1H, 29Si, and 15N NMR. DOSY experiments and DFT calculations were also carried out which showed that the silyl cation center is stabilized intramolecularly by the quinoline nitrogen atom (N1), forming a highly strained and quasi planar 4‐membered ring. Oxygenated and nitrogenated substituents at the C4 position on the quinoline ring were shown to reinforce the Si−N1 interaction through a p‐π conjugation. The Lewis acidity of this class of silylium was finally determined using Müller's nitrilium method.
Harvesting energy from high‐frequency impinging water droplets by a droplet‐based electricity generator
Authors: Wang Lili , Song Yuxin , Xu Wanghuai , Li Wanbo , Jin Yuankai , Gao Shouwei , Yang Siyan , Wu Chenyang , Wang Steven , Wang Zuankai
Published: June 2021

Harvesting energy from water, in the form of raindrops, river, and ocean waves, is of considerable importance and has potential applications in self‐powered electronic devices and large‐scale energy needs. Recently, the droplet‐based electricity generator has shown an increase by several orders of magnitude in electrical output, overcoming the drawback of traditional droplet‐based device limited by interfacial effects. Despite this exciting result, the output performance of this novel droplet‐based electricity generator is limited by relatively low frequency of impinging droplets owing to the formation of a continuous liquid film at high impact frequency, which might hinder its practical applications. To overcome this challenge, here, we report the design of a superhydrophobic surface based droplet electricity generator, referred to as SHS‐DEG, which can timely shed water droplets from the surface without the formation of liquid film at high impact frequency, and thereby generating enhanced average electrical output. Moreover, our SHS‐DEG exhibits many distinctive advantages over conventional design including robustness, long‐term durability, and power generation stability even in harsh environments. We envision that the ability to harvest electrical energy from water droplets at high impact frequency has promising applications in various energy‐harvesting systems.

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A liquid‐solid model to optimize the application of friction reducers for hydraulic fracturing/cutting in the underground coal mine
Authors: Xiong Wei , Shen Kai , Ba Quanbin , Liu Yanbao , Zhou Houquan
Published: June 2021

Friction reducers are widely applied to reduce friction losses in the natural oil and gas industry. The application of hydraulic fracturing in underground coal mines results in a new issue for friction reducers: The hydraulic fluid, mixed with a friction reducer, should reduce friction loss to maintain the hydraulic pressure while simultaneously discharging coal particles to clean the borehole. Most previous studies have focused on the former aspect, ignoring the discharge capacity of coal particles. To compensate for this shortcoming, a coupled flow model of coal particles and hydraulic fluid is proposed considering the interactions between the two phases and characteristics of the coal particles. The model was implemented and solved using the finite element method approach (COMSOL Multiphysics), and the impact of the injection velocity, hydraulic fluid viscosity, and stacking angle of coal particles was investigated. Before simulation, an experiment was conducted to determine the viscosity range and velocity dependency of the hydraulic fluid with a flow‐loop instrument. A field application was conducted based on simulation results. The viscosity of 2.5 mPa s is a critical value around which the maximum friction reduction efficiency can be achieved, and the discharge capacity of coal particles can be enhanced significantly above this value. The applications of hydraulic fracturing or hydraulic cutting should be coupled with the viscosity of the hydraulic fluid. The injection velocity should be sufficiently high, and the time interval of the water spray should be sufficiently large for the low‐viscosity hydraulic fluid. The stacking angle of the coal particles has little influence on the long‐term discharge process. An upward borehole is recommended for the consideration of coal particle discharge because of the gravity effect. This work provides constructive suggestions and guidance for underground hydraulic fracturing and hydraulic cutting.
Fmrp regulates oligodendrocyte lineage cell specification and differentiation
Authors: Doll Caleb A. , Scott Kayt , Appel Bruce
Published: June 2021

Neurodevelopment requires the precise integration of a wide variety of neuronal and glial cell types. During early embryonic development, motor neurons and then oligodendrocyte precursor cells (OPCs) are specified from neural progenitors residing in the periventricular pMN progenitor domain of the spinal cord. Following gliogenesis, OPCs can differentiate as oligodendrocytes (OLs)—the myelinating glial cells of the central nervous system—or remain as OPCs. To generate unique cell types capable of highly divergent functions, these specification and differentiation events require specialized gene expression programs. RNA binding proteins (RBPs) regulate mRNA localization and translation in the developing nervous system and are linked to many neurodevelopmental disorders. One example is Fragile X syndrome (FXS), caused by the loss of the RBP fragile X mental retardation protein (FMRP). Importantly, infants with FXS have reduced white matter and we previously showed that zebrafish Fmrp is autonomously required in OLs to promote myelin sheath growth. We now find that Fmrp regulates cell specification in pMN progenitor cells such that fmr1 mutant zebrafish generate fewer motor neurons and excess OPCs. Fmrp subsequently promotes differentiation of OPCs, leading to fewer differentiating OLs in the developing spinal cord of fmr1 larvae. Although the early patterning of spinal progenitor domains appears largely normal in fmr1 mutants during early embryogenesis, Shh signaling is greatly diminished. Taken together, these results suggest cell stage‐specific requirements for Fmrp in the specification and differentiation of oligodendrocyte lineage cells.
Function–structure coupling: White matter functional magnetic resonance imaging hyper‐activation associates with structural integrity reductions in schizophrenia
Authors: Jiang Yuchao , Duan Mingjun , Li Xiangkui , Huang Huan , Zhao Guocheng , Li Xuan , Li Shicai , Song Xufeng , He Hui , Yao Dezhong , Luo Cheng
Published: June 2021

White matter (WM) microstructure deficit may be an underlying factor in the brain dysconnectivity hypothesis of schizophrenia using diffusion tensor imaging (DTI). However, WM dysfunction is unclear in schizophrenia. This study aimed to investigate the association between structural deficits and functional disturbances in major WM tracts in schizophrenia. Using functional magnetic resonance imaging (fMRI) and DTI, we developed the skeleton‐based WM functional analysis, which could achieve voxel‐wise function–structure coupling by projecting the fMRI signals onto a skeleton in WM. We measured the fractional anisotropy (FA) and WM low‐frequency oscillation (LFO) and their couplings in 93 schizophrenia patients and 122 healthy controls (HCs). An independent open database (62 schizophrenia patients and 71 HCs) was used to test the reproducibility. Finally, associations between WM LFO and five behaviour assessment categories (cognition, emotion, motor, personality and sensory) were examined. This study revealed a reversed pattern of structure and function in frontotemporal tracts, as follows. (a) WM hyper‐LFO was associated with reduced FA in schizophrenia. (b) The function–structure association was positive in HCs but negative in schizophrenia patients. Furthermore, function–structure dissociation was exacerbated by long illness duration and severe negative symptoms. (c) WM activations were significantly related to cognition and emotion. This study indicated function–structure dys‐coupling, with higher LFO and reduced structural integration in frontotemporal WM, which may reflect a potential mechanism in WM neuropathologic processing of schizophrenia.
Placenta‐specific protein 1 promotes cell proliferation via the AKT/GSK‐3β/cyclin D1 signaling pathway in gastric cancer
Authors: Liu Dongyang , Shi Ke , Fu Mingshi , Chen Feng
Published: June 2021

Gastric cancer is a malignant tumor with a poor prognosis. Therefore, it is important to search for molecules that play a vital role in the development, diagnosis, and treatment of this disease. Placenta‐specific 1 (PLAC1) is one of the cancer‐testis antigens; it plays an important role in both placental development and tumorigenesis. However, the role of PLAC1 in gastric cancer has not been fully investigated, and its underlying mechanism needs further study. We first explored the expression and clinical relevance of PLAC1 in gastric cancer and performed gene set enrichment analysis of PLAC1‐related genes using online databases. Subsequently, we studied the function and mechanism of PLAC1 in gastric cancer cells through in vitro experiments. Our results showed that PLAC1 is highly expressed in gastric cancer, is associated with poor prognosis, and can promote gastric cancer cell proliferation through the AKT/GSK‐3β/cyclin D1 signaling pathway. Moreover, we discovered that AKTi attenuates the effect of PLAC1. Our study further revealed the role and mechanism of PLAC1 in gastric cancer and suggested that this antigen might be a useful molecular marker for gastric cancer diagnosis, prognosis, and treatment.
Exploring the molecular basis of UG‐rich RNA recognition by the human splicing factor TDP‐43 using molecular dynamics simulation and free energy calculation
Authors: Sun Han , Chen Wei , Chen Lin , Zheng Wenqing
Published: June 2021

Transactivation response element RNA/DNA‐binding protein 43 (TDP‐43) is involved in the regulation of alternative splicing of human neurodegenerative disease‐related genes through binding to long UG‐rich RNA sequences. Mutations in TDP‐43, most in the homeodomain, cause neurological disorders such as amyotrophic lateral sclerosis and fronto temporal lobar degeneration. Several mutants destabilize the structure and disrupt RNA‐binding activity. The biological functions of these mutants have been characterized, but the structural basis behind the loss of RNA‐binding activity is unclear. Focused on the specific TDP‐43‐ssRNA complex (PDB code 4BS2), we applied molecular dynamics simulations and the molecular mechanics Poisson‐Boltzmann surface area free energy calculation to characterize and explore the structural and dynamic effects between ssRNA and TDP‐43. The energetic analysis indicated that the intermolecular van der Waals interaction and nonpolar solvation energy play an important role in the binding process of TDP‐43 and ssRNA. Compared with the wild‐type TDP‐43, the reduction of the polar or non‐polar interaction between all the mutants F149A, D105A/S254A, R171A/D174A, F147L/F149L/F229L/F231L and ssRNA is the main reason for the reduction of its binding free energy. Decomposing energies suggested that the extensive interactions between TDP‐43 and the nitrogenous bases of ssRNA are responsible for the specific ssRNA recognition by TDP‐43. These results elucidated the TDP‐43‐ssRNA interaction comprehensively and further extended our understanding of the previous experimental data. The uncovering of TDP‐43‐ssRNA recognition mechanism will provide us useful insights and new chances for the development of anti‐neurodegenerative drugs.
Development of a voltammetric method for the determination of rapamycin in pharmaceutical samples at pretreated pencil graphite electrode
Authors: Karaboduk Kuddusi
Published: June 2021

This paper describes an electroanalytical method for the determination of rapamycin using a pretreated pencil graphite electrode (P‐PGE) by differential pulse voltammetry. The electrodes were successfully characterized by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, and Fourier transform infrared. The influences of instrumental and chemical parameters were investigated and optimized for the determination of rapamycin. Oxidation peak current obtained for rapamycin at P‐PGE was 10.5 times higher than that obtained for PGE. In pH = 3.0 H3PO4, a well‐defined irreversible anodic peak occurred at 1.07 V, which was attributed to the electro‐oxidation of rapamycin at P‐PGE. Under optimized conditions, the oxidation peak current of rapamycin was linear with its concentration in the range of 0.01–250 μmol/L, and the detection limit was 0.0075 μmol/L (S/N = 3). Also, the P‐PGE exhibited good reproducibility (relative SD [RSD] = 2.17% for 10 electrodes at different times using the same procedure), repeatability (RSD = 2.09% for 10 measurements with same electrode), and stability (95.80% for 10 days). The P‐PGE was simple to prepare and the method was successfully applied for the determination of rapamycin in spiked and real samples. In addition, for comparison, high‐performance liquid chromatographic method with ultraviolet (UV) detector was used for the determination of rapamycin.
A Target‐Mediated Drug Disposition Model to Explain Nonlinear Pharmacokinetics of the 11β‐Hydroxysteroid Dehydrogenase Type 1 Inhibitor SPI‐62 in Healthy Adults
Authors: Wu Nan , Katz David A. , An Guohua
Published: June 2021

SPI‐62 is a selective and potent small‐molecule inhibitor of 11β‐hydroxysteroid dehydrogenase type 1 (HSD‐1). SPI‐62 has demonstrated substantial and complex nonlinear pharmacokinetics (PK) in humans that is characterized by unusually low plasma exposure at low doses, dose‐dependent volume of distribution, nonlinear PK following the first dose, and dose‐proportional PK at steady state, as well as unusually high accumulation ratios at low doses. The most likely explanation for the observed nonlinearity of SPI‐62 is the saturable binding of SPI‐62 to its pharmacological target HSD‐1, a phenomenon known as target‐mediated drug disposition (TMDD). Because of the nonlinear and complex PK of SPI‐62, the relationship among SPI‐62 dose, exposure, and response is no longer intuitive and consequently dose selection can be challenging. To facilitate dose selection and clinical trial design, in the current study population PK analysis was performed to characterize SPI‐62 dose‐exposure relationship in humans quantitatively. SPI‐62 PK was best characterized by a 2‐compartment TMDD model with 3 transit absorption compartments. The model was successfully established to explain the substantial and unusual nonlinear PK of SPI‐62 in humans, and it provided adequate fitting for both single‐ and multiple‐dose data. Our modeling work has provided a strong foundation for dose selection in future SPI‐62 clinical trials.