bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial transcription factor A plays opposite roles in the initiation and progression of colitis‐associated cancer
Authors: Yang Shirong , He Xianli , Zhao Jing , Wang Dalin , Guo Shanshan , Gao Tian , Wang Gang , Jin Chao , Yan Zeyu , Wang Nan , Wang Yongxing , Zhao Yilin , Xing Jinliang , Huang Qichao 
Published: June 2021

AbstractBackgroundMitochondria are key regulators in cell proliferation and apoptosis. Alterations in mitochondrial function are closely associated with inflammation and tumorigenesis. This study aimed to investigate whether mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA transcription and replication, is involved in the initiation and progression of colitis‐associated cancer (CAC).MethodsTFAM expression was examined in tissue samples of inflammatory bowel diseases (IBD) and CAC by immunohistochemistry. Intestinal epithelial cell (IEC)‐specific TFAM‐knockout mice (TFAM△IEC) and colorectal cancer (CRC) cells with TFAM knockdown or overexpression were used to evaluate the role of TFAM in colitis and the initiation and progression of CAC. The underlying mechanisms of TFAM were also explored by analyzing mitochondrial respiration function and biogenesis.ResultsThe expression of TFAM was downregulated in active IBD and negatively associated with the disease activity. The downregulation of TFAM in IECs was induced by interleukin‐6 in a signal transducer and activator of transcription 3 (STAT3)/miR‐23b‐dependent manner. In addition, TFAM knockout impaired IEC turnover to promote dextran sulfate sodium (DSS)‐induced colitis in mice. Of note, TFAM knockout increased the susceptibility of mice to azoxymethane/DSS‐induced CAC and TFAM overexpression protected mice from intestinal inflammation and colitis‐associated tumorigenesis. By contrast, TFAM expression was upregulated in CAC tissues and contributed to cell growth. Furthermore, it was demonstrated that β‐catenin induced the upregulation of TFAM through c‐Myc in CRC cells. Mechanistically, TFAM promoted the proliferation of both IECs and CRC cells by increasing mitochondrial biogenesis and activity.ConclusionsTFAM plays a dual role in the initiation and progression of CAC, providing a novel understanding of CAC pathogenesis.
Preliminary Structural Data Revealed That the SARS‐CoV‐2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity
Authors: Khan. Abbas , Wei Dong‐Qing , Kousar Kafila , Abubaker Jehad , Ahmad Sajjad , Ali Javaid , Al‐Mulla Fahd , Ali Syed Shujait , Nizam‐Uddin N. , Mohammad Sayaf Abrar , Mohammad Anwar 
Published: June 2021

AbstractThe evolution of new SARS‐CoV‐2 variants around the globe has made the COVID‐19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor‐binding motif (RBM) of the receptor‐binding domain (RBD) spike glycoprotein, i. e. L452R‐E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R‐E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic‐stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural‐dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS‐CoV‐2 variants.
Direct Visualization of Substitutional Li Doping in Supported Pt Nanoparticles and Their Ultra‐selective Catalytic Hydrogenation Performance
Authors: Chen Tianyi , Foo Christopher , Zheng Jianwei J. W. , Fang Huihuang , Nellist Peter , Tsang Shik Chi Edman 
Published: June 2021

AbstractIt has only recently been established that doping light elements (lithium, boron, and carbon) into supported transition metals can fill interstitial sites, which can be observed by the expanded unit cell. As an example, interstitial lithium (intLi) can block H filling octahedral interstices of palladium metal lattice, which improves partial hydrogenation of alkynes to alkenes under hydrogen. In contrast, herein, we report intLi is not found in the case of Pt/C. Instead, we observe for the first time a direct ‘substitution’ of Pt with substitutional lithium (subLi) in alternating atomic columns using scanning transmission electron microscopy‐annular dark field (STEM‐ADF). This ordered substitutional doping results in a contraction of the unit cell as shown by high‐quality synchrotron X‐ray diffraction (SXRD). The electron donation of d‐band of Pt without higher orbital hybridizations by subLi offers an alternative way for ultra‐selectivity in catalytic hydrogenation of carbonyl compounds by suppressing the facile CO bond breakage that would form alcohols.
Effect of a “Zn Bridge” on the Consecutively Tunable Retention Characteristics of Volatile Random Access Memory Materials
Authors: Guo Jiacong , Zhang Yankun , Tian Guofeng , Ji Deyang , Qi Shengli , Wu Dezhen 
Published: June 2021

AbstractPolyimide memory materials with a donor–acceptor structure based on a charge‐transfer mechanism exhibit great potential for next‐generation information storage technology due to their outstanding high‐temperature resistance and good dimensional and chemical stability. Precisely controlling memory performance by limited chemical decoration is one of core challenges in this field. Most reported work mainly focuses on designing novel and elaborate electron donors or acceptors for the expected memory behavior of polyimides; this takes a lot of time and is not always efficacious. Herein, we report a series of porphyrinated copolyimides coPI−Znx (x=5, 10, 20, 50, 80), where x represents the mole percentage of Zn ion in the central core of the porphyrin. Experimental and theoretical analysis indicate that the Zn ion could play a vital bridge role in promoting the formation and stabilization of a charge‐transfer complex by enhancing the hybridization of local and charge transfer (HLCT) excitations of porphyrinated polyimides, endowing coPI−Znx with volatile random access memory performance and continuously tunable retention time. This work could provide one simple strategy to precisely regulate memory performance merely by altering the metal content in porphyrinated polyimides.
Driving the Emission Towards Blue by Controlling the HOMO‐LUMO Energy Gap in BF2‐Functionalized 2‐(Imidazo[1,5‐a]pyridin‐3‐yl)phenols
Authors: Colombo Gioele , Attilio Ardizzoia G. , Furrer Julien , Therrien Bruno , Brenna Stefano 
Published: June 2021

AbstractSeveral boron compounds with 2‐(imidazo[1,5‐a]pyridin‐3‐yl)phenols, differentiated by the nature of the substituent (R) in the para position of the hydroxy group, have been synthesized and thoroughly characterized both in solution (1H, 13C, 11B, 19F NMR) and in the solid state (X‐ray). All derivatives displayed attractive photophysical properties like very high Stokes shift, high fluorescence quantum yields and a good photostability in solution. Time‐Dependent Density Functional Theory (TD‐DFT) calculations allowed to define the main electronic transitions as intra ligand transitions (1ILT), which was corroborated by the Natural Transition Orbitals (NTOs) shapes. The HOMO‐LUMO energy gap was correlated to the electronic properties of the substituent R on the phenolic ring, as quantified by its σp Hammett constant.
Glycol Chitosan Functionalized with a Gd(III) Chelate as a Redox‐responsive Magnetic Resonance Imaging Probe to Label Cell Embedding Alginate Capsules
Authors: Padovan Sergio , Carrera Carla , Catanzaro Valeria , Grange Cristina , Koni Malvina , Digilio Giuseppe 
Published: June 2021

AbstractOne possibility for the non‐invasive imaging of encapsulated cell grafts is to label the lumen of cell embedding capsules with a redox‐responsive probe, as an increased extracellular reducing potential can be considered as a marker of hypoxia‐induced necrosis. A Gd(III)‐HPDO3A‐like chelate has been conjugated to glycol‐chitosan through a redox‐responsive disulphide bond to obtain a contrast agent for Magnetic Resonance Imaging (MRI). Such a compound can be interspersed with fibroblasts within the lumen of alginate‐chitosan capsules. Increasing reducing conditions within the extracellular microenvironment lead to the reductive cleavage of the disulphide bond and to the release of gadolinium in the form of a low molecular weight, non‐ionic chelate. The efflux of such chelate from capsules is readily detected by a decrease of contrast enhancement in T1‐weighted MR images.
N‐Heterocyclic Iod(az)olium Salts – Potent Halogen‐Bond Donors in Organocatalysis
Authors: Boelke Andreas , Kuczmera Thomas J. , Lork Enno , Nachtsheim Boris J. 
Published: June 2021

AbstractThis article describes the application of N‐heterocyclic iod(az)olium salts (NHISs) as highly reactive organocatalysts. A variety of mono‐ and dicationic NHISs are described and utilized as potent XB‐donors in halogen‐bond catalysis. They were benchmarked in seven diverse test reactions in which the activation of carbon‐ and metal‐chloride bonds as well as carbonyl and nitro groups was achieved.N‐methylated dicationic NHISs rendered the highest reactivity in all investigated catalytic applications with reactivities even higher than all previously described monodentate XB‐donors based on iodine(I) and (III) and the strong Lewis acid BF3.
Mechanosynthesis of Eutectics of Anti‐Inflammatory Drug Ethenzamide – A Comparison with Analogous Cocrystals
Authors: Rajbongshi Trishna , Kumar Sarmah Kashyap , Ganduri Ramesh , Cherukuvada Suryanarayan , Arhangelskis Mihails , Thakuria Ranjit 
Published: June 2021

AbstractMechanochemical milling of ethenzamide (ETZ), a nonsteroidal anti‐inflammatory drug, with substituted aromatic carboxylic acids as well as anti‐tuberculosis drug pyrazinamide (PZA) resulted in the formation of eutectics. Although a large number of cocrystals as well as polymorphic cocrystals are reported for ETZ, for the first time we have synthesized six eutectics including an instance of a drug‐drug eutectic system. Supramolecular synthon energy calculations validate the formation of eutectic mixtures over cocrystals with coformers considered in our study.
Assessment of gender representation in clinical trials leading to FDA approval for oncology therapeutics between 2014 and 2019: A systematic review‐based cohort study
Authors: Dymanus Kyle A. , Butaney Mohit , Magee Diana E. , Hird Amanda E. , Luckenbaugh Amy N. , Ma Merry W. , Hall Mary E. , Huelster Heather L. , Laviana Aaron A. , Davis Nancy B. , Terris Martha K. , Klaassen Zachary , Wallis Christopher J. D. 
Published: June 2021

BackgroundEnsuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals.MethodsAn observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation.ResultsThere were 149 clinical trials with 59,988 participants—60.3% and 39.7% were male and female, respectively—leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, –26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials).ConclusionsFor many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated.Lay Summary

This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively.

Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented.

Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.
The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival
Authors: Greer Anna C. , Lanes Andrea , Poorvu Philip D. , Kennedy Patricia , Thomas Ann M. , Partridge Ann H. , Ginsburg Elizabeth S. 
Published: June 2021

BackgroundMany young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes.MethodsThe authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation–positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation–negative [FP–]).ResultsThe characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP–, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP–, 15.5% BRCA+; P = .021). The median follow‐up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP–, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56‐0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP–, 26 days; aHR, 0.41; CI, 0.24‐0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP–, 33 days; aHR, 0.58; CI, 0.38‐0.90). Adjusted 3‐ and 5‐year invasive disease–free survival (IDFS) rates were comparable between the 2 groups (3‐year IDFS: FP+, 85.4%; FP–, 79.4%; P = .411; 5‐year IDFS: FP+, 73.7%; FP–, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3‐year OS: FP+, 95.5%; FP–, 93.5%; P = .854; 5‐year OS: FP+, 84.2%; FP–, 81.4%; P = .700).ConclusionsFP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.
Reassessing the measurement and presence of therapeutic misconception in a phase 1 setting
Authors: Abernethy Eli R. , Campbell Gavin P. , Hianik Rachel S. , Thomson Mary Catherine , Blee Shannon M. , Sibold Hannah C. , Dixon Margie D. , Switchenko Jeffrey M. , Pentz Rebecca D. 
Published: June 2021

BackgroundTherapeutic misconception (TM) refers to research subjects' failure to distinguish the goals of clinical research from standard personal care. TM has traditionally been determined by questioning the patient about the research study's purpose. Recent research, however, has questioned whether TM is as prevalent as reported due to discrepancies between patient/researcher interpretations of TM questions. The authors have created an interview tool receptive to these advancements to more accurately determine the prevalence of TM.MethodsPatients were questioned about the trial's purpose as follows: 1) “Is the trial mostly intending to help research and gain knowledge?,” 2) “Is it mostly intending to help you as a person?,” or 3) “Don't know.” Participants were then asked what they thought this question was asking: A) “What my own intentions are for participating,” B) “What the official purpose of the research study is,” or C) “Not sure.” A patient exhibited TM by answering that the official trial purpose was to help him or her.ResultsPatients (n = 98) had a mean age of 60 years, were mostly White (64%), had a combined family annual income ≥$60,000 (61%), and 49% had a college degree. Twelve of 98 patients (12%) definitely exhibited TM. This was much lower than the author's original finding of 68% in a similar cohort. Twenty‐four of 98 patients (24.5%) were unclear about what one or both questions were asking and could not be categorized.ConclusionsPreviously, a patient was thought to have TM if they answered that the purpose of the trial was to benefit to him or her. An additional query about how patients interpreted that question revealed only 12% definitely had TM.Lay Summary

Therapeutic misconception (TM) refers to research subjects' failure to distinguish the goals of clinical research from standard personal care.

TM signals a basic misunderstanding of the purpose of clinical research, threatening valid informed consent to participate in clinical trials.

TM has traditionally been determined by questioning patients about their research study's purpose. Recent research, however, has questioned whether TM is as prevalent due to discrepancies between patient/researcher interpretations of TM questions.

By developing an interview‐tool receptive to these advancements, we report a lower TM estimate in the phase 1 setting (12%) than we found previously in a similar cohort (68%).
Fractal motor activity regulation and sex differences in preclinical Alzheimer's disease pathology
Authors: Gao Lei , Li Peng , Gaba Arlen , Musiek Erik , Ju Yo‐El S. , Hu Kun 
Published: June 2021

AbstractIntroductionDegradation in fractal motor activity regulation (FMAR), a measure of multiscale self‐similarity of motor control, occurs in aging and accelerates with clinical progression to Alzheimer's disease (AD). Whether FMAR changes occur during the pre‐symptomatic phase of the disease in women and men remains unknown.MethodsFMAR was assessed in cognitively normal participants (n = 178) who underwent 7 to 14 days of home actigraphy. Preclinical AD pathology was determined by amyloid imaging‐Pittsburgh compound B (PiB) and cerebrospinal fluid (CSF) phosphorylated‐tau181 (p‐tau) to amyloid beta 42 (Aβ42) ratio.ResultsDegradation in daytime FMAR was overall significantly associated with preclinical amyloid plaque pathology via PiB+ imaging (beta coefficient β = 0.217, standard error [SE] = 0.101, P = .034) and increasing CSF tau181‐Aβ42 ratio (β = 0.220, SE = 0.084, P = .009). In subset analysis by sex, the effect sizes were significant in women for PiB+ (β = 0.279, SE = 0.112, P = .015) and CSF (β = 0.245, SE = 0.094, P = .011) but not in men (both Ps > .05). These associations remained after inclusion of daily activity level, apolipoprotein E ε4 carrier status, and rest/activity patterns.DiscussionChanges in daytime FMAR from actigraphy appear to be present in women early in preclinical AD. This may be a combination of earlier pathology changes in females reflected in daytime FMAR, and a relatively underpowered male group. Further studies are warranted to test FMAR as an early noncognitive physiological biomarker that precedes the onset of cognitive symptoms.
Directional movement of consumer fronts associated with creek heads in salt marshes
Authors: Vu Huy D. , Pennings Steven C. 
Published: June 2021

AbstractConsumers often deplete local resources and aggregate along edges of remaining resources, forming “consumer fronts.” We examined the factors that promoteSesarma reticulatumcrab aggregations at saltmarsh creek heads to explain the directional but slow movement of these fronts. We also created artificial creek heads to test the hypothesis that hydrological conditions at creek heads create superior habitat for crabs. Soil temperatures were ˜11–12% cooler, hydrogen sulfide concentrations lower (0.0 vs. ˜0.58 mg/L), and dissolved oxygen concentrations twofold higher at the creek head versus the marsh platform. In the artificial creek‐head experiment, altering hydrological conditions led to lower dissolved sulfide levels, higher dissolved oxygen levels, and increased densities of crab burrows andSesarmacrabs. Moreover, the elevation of the soil surface declined rapidly at artificial creek heads versus controls, suggesting that crabs were increasing erosion. Our results suggest that abiotic conditions for crabs are better at the leading edge of the creek head than the trailing edge, explaining the directional movement of the front. Moreover, the speed at which the front propagates appears to be limited by the rate at which the creekhead erodes, rather than by crab mobility. The directional and slow movement ofSesarmafronts compared to consumer fronts of other invertebrates appears to result from the inextricable link betweenSesarmaand marsh geomorphology, whereas other consumer fronts are associated mostly with food resources.
Electronic Properties of Rhenium(I) Carbonyl Complexes Bearing Strongly Donating Hexahydro‐Pyrimidopyrimidine Based Ligands
Authors: Auvray Thomas , Pal Amlan K. , Hanan Garry S. 
Published: June 2021

AbstractRe(I) tricarbonyl complexes have been synthesized using bi‐ and tridentate ligands equipped with one or two hexahydro‐pyrimidopyrimidine (hpp) units attached to either a pyridine or a pyrazine ring. These complexes have been characterized by NMR, ESI‐MS, vibrational and optical spectroscopies as well as electrochemistry. Their structures were determined via single‐crystal X‐ray crystallography and modelled using both DFT and TD‐DFT methods. The complexes are non‐emissive in solution at room temperature but display emission with mixed intra ligand (major) and metal‐ligand (minor) charge transfer characters at 77 K. Additionally, both pyrazine‐based complexes appear to be emissive in the solid state, presumably due to the presence of intermolecular interactions, as observed in the crystal structure.
Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis
Authors: Hazelard Damien , Compain Philippe 
Published: June 2021

Abstract1,6‐Anhydrosugars provide a valuable source of building blocks for the synthesis of a wide range of compounds of interest, from natural products to medicines. The unique reactivity of these functionalized, homochiral synthons is controlled by the 1,6‐anhydro bridge which locks the conformation of the pyranose ring, provides a dual protection of two hydroxyl groups, and either protects or activates the anomeric position. The concomitant release of the primary hydroxyl group at C‐6 during the ring‐opening step limits protecting group manipulations and enables the design of highly convergent synthetic strategies. In recent years, many examples of stereocontrolled ring‐opening of 1,6‐anhydrosugars by a diversity of nucleophiles, including hetero‐ and C‐nucleophiles, have been reported. The purpose of this review is to present an overview of the recent advances, applications and challenges associated with this process.
Intramolecular Electrochemical Oxybromination of Olefins for the Synthesis of Isoxazolines in Batch and Continuous Flow
Authors: Prabhakar Kale Ajit , Nikolaienko Pavlo , Smirnova Kristina , Rueping Magnus 
Published: June 2021

AbstractA highly regioselective protocol for the synthesis of isoxazolines through cascade C−O and C−Br bond formation has been developed. The electrochemical approach uses traceless electrons as a sole source of oxidant, thus avoiding the use of stoichiometric organic or inorganic oxidants and provides a mild and environmentally benign alternative pathway for the synthesis of a wide range of valuable substituted isoxazolines from alkenyl oximes in good yields.