bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis
Authors: Chauhan Amar Nath Singh , Mali Ghanshyam , Erande Rohan D. 
Published: February 2022

AbstractThe Diels‐Alder (DA) reaction is one of the fascinating synthetic strategies known for its pericyclic action and concerted mechanism that leads to various targets. Numerous synthetic pursuits have been rewarded with conceptually distinct and efficient ways. To date, extensive and spectacular accomplishments have been made in the field of Diels‐Alder chemistry to overcome the complexities of organic synthesis that inspired organic chemists to focus on expanding and establishing the postulates. In principle, DA reactions are governed by their straightforward reactivity pattern with a high degree of certainty, primarily attributed to the HOMO‐LUMO separation of reacting partners. Furthermore, general forecasts rely on account of background studies, conveniently hypothesizing the stereochemical outcomes and reaction dynamic pathways. DA has recently emerged as a technique for establishing a variety of products from the same reacting species under varying reaction conditions rather than a general reactivity profile. Such exceptional results are of significant interest in organic synthesis to pursue the challenges of unanticipated product establishment. Herein, we summarize the impressive finding of the remarkable switch in the regioselectivity and diastereoselectivity of DA reactions under a diverse set of reaction protocols in light of Diels‐Alder's unending importance in chemical science. This review aims to establish a beneficial account of Diels‐Alder towards the astonishing switches extended to study varying synthetic versions in organic synthesis protocols attributed to natural and biologically active scaffolds. This review also provides insight into distinct reaction dynamics in DA reactions that are subjected to access molecular frameworks ranging from simple to complicated ones to foster high levels of innovation in chemical sciences.
Mineral content analysis in the rib cross‐sections of Homo sapiens and Pan troglodytes and its implications for the study of Sts 14 costal remains
Authors: López‐Rey José María , Cambra‐Moo Óscar , González Martín Armando , Candelas González Nieves , Sánchez‐Andrés Ángeles , Tawane Mirriam , Cazenave Marine , Williams Scott A. , Bastir Markus , García‐Martínez Daniel 
Published: February 2022

AbstractIntroductionFrom an evolutionary perspective, the ribcage has changed substantially in the subfamily Homininae. Among many other features, the amount of mineralized tissues of the rib cross‐section at the midshaft could be informative about potential biomechanical changes during Homininae evolution. These changes would be related to the different loading stresses that each costal level has to deal with. Nevertheless, this knowledge remains hypothetical and has never been properly addressed.Materials and MethodsThis issue was assessed by analysing via micro‐CT the internal rib anatomy of the complete sets of ribs belonging to ten Homo sapiens and ten Pan troglodytes adult individuals. Additionally, five fossil ribs of Australopithecus africanus Sts 14 (costal levels 5–9) were also included to evaluate similarities with the two tested extant species.ResultsThe mineralized area of P. troglodytes rib cross‐sections was higher than that of H. sapiens. However, its serial change along the rib sequence (1–12/13) was similar in both species. The mineralized area of the Sts 14 rib cross‐sections was closer to H. sapiens than to P. troglodytes for costal levels 7–9 (Sts 14w) but not for levels 5 and 6, where it was distinct from both comparative samples.DiscussionThe variation in the amount of mineralized tissues along the rib sequence in H. sapiens and P. troglodytes might indicate a common upper‐lower thorax division probably linked to the insertions of the diaphragm. This variation is similar between ribs Sts 14w and the corresponding modern human costal levels, which could be potentially related to closer breathing kinematics in the lower thorax of Sts 14 and H. sapiens.
Electrocatalytic Allylic C−H Alkylation Enabled by a Dual‐Function Cobalt Catalyst**
Authors: Chen Ming , Wu Zheng‐Jian , Song Jinshuai , Xu Hai‐Chao 
Published: February 2022

AbstractThe direct functionalization of allylic C−H bonds with nucleophiles minimizes pre‐functionalization and converts inexpensive, abundantly available materials to value‐added alkenyl‐substituted products but remains challenging. Here we report an electrocatalytic allylic C−H alkylation reaction with carbon nucleophiles employing an easily available cobalt–salen complex as the molecular catalyst. These C(sp3)−H/C(sp3)−H cross‐coupling reactions proceed through H2 evolution and require no external chemical oxidants. Importantly, the mild conditions and unique electrocatalytic radical process ensure excellent functional group tolerance and substrate compatibility with both linear and branched terminal alkenes. The synthetic utility of the electrochemical method is highlighted by its scalability (up to 200 mmol scale) under low loading of electrolyte (down to 0.05 equiv) and its successful application in the late‐stage functionalization of complex structures.
Thionolactone as a Resin Additive to Prepare (Bio)degradable 3D Objects via VAT Photopolymerization**
Authors: Gil Noémie , Thomas Constance , Mhanna Rana , Mauriello Jessica , Maury Romain , Leuschel Benjamin , Malval Jean‐Pierre , Clément Jean‐Louis , Gigmes Didier , Lefay Catherine , Soppera Olivier , Guillaneuf Yohann 
Published: February 2022

AbstractThree‐dimensional (3D) printing and especially VAT photopolymerization leads to cross‐linked materials with high thermal, chemical, and mechanical stability. Nevertheless, these properties are incompatible with requirements of degradability and re/upcyclability. We show here that thionolactone and in particular dibenzo[c,e]‐oxepane‐5‐thione (DOT) can be used as an additive (2 wt %) to acrylate‐based resins to introduce weak bonds into the network via a radical ring‐opening polymerization process. The low amount of additive makes it possible to modify the printability of the resin only slightly, keep its resolution intact, and maintain the mechanical properties of the 3D object. The resin with additive was used in UV microfabrication and two‐photon stereolithography setups and commercial 3D printers. The fabricated objects were shown to degrade in basic solvent as well in a homemade compost. The rate of degradation is nonetheless dependent on the size of the object. This feature was used to prepare 3D objects with support structures that could be easily solubilized.
Overturned Loading of Inert CeO2to Active Co3O4for Unusually Improved Catalytic Activity in Fenton‐Like Reactions
Authors: Song Chunli , Zhan Qing , Liu Fei , Wang Chuan , Li Hongchao , Wang Xuan , Guo Xuefeng , Cheng Yingchun , Sun Wei , Wang Li , Qian Jieshu , Pan Bingcai 
Published: February 2022

AbstractIn the past decades, numerous efforts have been devoted to improving the catalytic activity of nanocomposites by either exposing more active sites or regulating the interaction between the support and nanoparticles while keeping the structure of the active sites unchanged. Here, we report the fabrication of a Co3O4−CeO2nanocomposite via overturning the loading direction, i.e., loading an inert CeO2support onto active Co3O4nanoparticles. The resultant catalyst exhibits unexpectedly higher activity and stability in peroxymonosulfate‐based Fenton‐like reactions than its analog prepared by the traditional impregnation method. Abundant oxygen vacancies (Ovwith a Co⋅⋅⋅Ov⋅⋅⋅Ce structure instead of Co⋅⋅⋅Ov) are generated as new active sites to facilitate the cleavage of the peroxide bond to produce SO4.−and accelerate the rate‐limiting step, i.e., the desorption of SO4.−, affording improved activity. This strategy is a new direction for boosting the catalytic activity of nanocomposite catalysts in various scenarios, including environmental remediation and energy applications.
Self‐Assembled Fluorescent Block Copolymer Micelles with Responsive Emission
Authors: Kurz Hannah , Hils Christian , Timm Jana , Hörner Gerald , Greiner Andreas , Marschall Roland , Schmalz Holger , Weber Birgit 
Published: February 2022

AbstractResponsive fluorescent materials offer a high potential for sensing and (bio‐)imaging applications. To investigate new concepts for such materials and to broaden their applicability, the previously reported non‐fluorescent zinc(II) complex [Zn(L)] that shows coordination‐induced turn‐on emission was encapsulated into a family of non‐fluorescent polystyrene‐block‐poly(4‐vinylpyridine) (PS‐b‐P4VP) diblock copolymer micelles leading to brightly emissive materials. Coordination‐induced turn‐on emission upon incorporation and ligation of the [Zn(L)] in the P4VP core outperform parent [Zn(L)] in pyridine solution with respect to lifetimes, quantum yields, and temperature resistance. The quantum yield can be easily tuned by tailoring the selectivity of the employed solvent or solvent mixture and, thus, the tendency of the PS‐b‐P4VP diblock copolymers to self‐assemble into micelles. A medium‐dependent off–on sensor upon micelle formation could be established by suppression of non‐micelle‐borne emission background pertinent to chloroform through controlled acidification indicating an additional pH‐dependent process.
Helicity Modulation in NIR‐Absorbing Porphyrin‐Ryleneimides
Authors: Balahoju Shivaprasad Achary , Maurya Yogesh Kumar , Chmielewski Piotr J. , Lis Tadeusz , Kondratowicz Mateusz , Cybińska Joanna , Stępień Marcin 
Published: February 2022

AbstractPeripheral substitution of a π‐extended porphyrin with bulky groups produces a curved chromophore with four helical stereogenic units. The curvature and stereochemistry of such porphyrins can be controlled by varying the substituents, coordinated metal ions, and apical ligands. In particular, when the achiral saddle‐shaped free bases are treated with large metal ions, i.e., CdIIor HgII, the resulting complexes convert to chiral propeller‐like configurations. X‐ray diffraction analyses show that apical coordination of a water molecule is sufficient to induce a notable bowl‐like distortion of the cadmium complex, which however retains its chiral structure. For phenyl‐ and tolyl‐substituted derivatives, the conversion is thermodynamically controlled, whereas complexes bearing bulky 4‐(tert‐butyl)phenyl groups transform into their chiral forms upon heating. In the latter case, the chiral Hg porphyrin was converted into the corresponding free base and other metal complexes without any loss of configurational purity, ultimately providing access to stable, enantiopure porphyrin propellers.
Design, synthesis, and characterization of PROTACs targeting the androgen receptor in prostate and lung cancer models
Authors: Gockel Lukas M. , Pfeifer Vladlena , Baltes Fabian , Bachmaier Rafael D. , Wagner Karl G. , Bendas Gerd , Gütschow Michael , Sosič Izidor , Steinebach Christian 
Published: February 2022

AbstractAlthough the androgen receptor (AR) is a validated target for the treatment of prostate cancer, resistance to antiandrogens necessitates the development of new therapeutic modalities. Exploiting the ubiquitin‐proteasome system with proteolysis‐targeting chimeras (PROTACs) has become a practical approach to degrade specific proteins and thus to extend the portfolio of small molecules used for the treatment of a broader spectrum of diseases. Herein, we present three subgroups of enzalutamide‐based PROTACs in which only the exit vector was modified. By recruiting cereblon, we were able to demonstrate the potent degradation of AR in lung cancer cells. Furthermore, the initial evaluation enabled the design of an optimized PROTAC with a rigid linker that degraded AR with a DC50 value in the nanomolar range. These results provide novel AR‐directed PROTACs and a clear rationale for further investigating AR involvement in lung cancer models.
Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus
Authors: Becker Yann L. C. , Gagné Jean‐Philippe , Julien Anne‐Sophie , Lévesque Tania , Allaeys Isabelle , Gougeard Nadine , Rubio Vicente , Boisvert François‐Michel , Jean Dominique , Wagner Eric , Poirier Guy G. , Fortin Paul R. , Boilard Éric 
Published: February 2022

ObjectiveMitochondria are organelles that exhibit several bacterial features, such as a double‐stranded genome with hypomethylated CpG islands, formylated proteins, and cardiolipin‐containing membranes. In systemic lupus erythematosus (SLE), mitochondria and their inner components are released into the extracellular space, potentially eliciting a proinflammatory response from the immune system. While cardiolipin and mitochondrial DNA and RNA are confirmed targets of autoantibodies, other antigenic mitochondrial proteins in SLE remain to be identified. The present study was undertaken to characterize the protein repertoire recognized by antimitochondrial antibodies (AMAs) in patients with SLE.MethodsUsing shotgun proteomic profiling, we identified 1,345 proteins, 431 of which were associated with the mitochondrial proteome. Immunoreactivities to several of these candidate proteins were assessed in serum samples from a local cohort (n = 30 healthy donors and 87 patients with SLE) using enzyme‐linked immunosorbent assay, and further analyzed for associations with demographic and disease characteristics.ResultsWe determined that IgG antibodies to the complement component C1q binding protein were significantly elevated in the patients with SLE (P = 0.049) and were also associated with lupus anticoagulant positivity (P = 0.049). Elevated levels of IgG antibodies against mitochondrial protein mitofusin 1 (MFN‐1) were promising predictors of SLE diagnosis in our cohort (adjusted odds ratio 2.99 [95% confidence interval 1.39–6.43], P = 0.0044). Moreover, increased levels of anti–MFN‐1 were associated with the presence of antiphospholipids (P = 0.011) and anti–double‐stranded DNA (P = 0.0005).ConclusionIn this study, we characterized the mitochondrial repertoire targeted by AMAs in the setting of SLE. Our results indicate that autoantibodies can recognize secreted and/or surface proteins of mitochondrial origin. Profiling of the AMA repertoire in large prospective cohorts may improve our knowledge of mitochondrial biomarkers and their usefulness for patient stratification.
Effects of berbamine against myocardial ischemia/reperfusion injury: Activation of the 5' adenosinemonophosphate‐activatedprotein kinase/nuclear factor erythroid2‐relatedfactor pathway and changes in the mitochondrial state
Authors: Xu Chennian , Liu Yang , Yang Jian , Zhai Mengen , Fan Zhenge , Qiao Rui , Jin Ping , Yang Lifang 
Published: February 2022

AbstractThis study was designed to investigate whether berbamine (BA)‐induced cardioprotective effects were related to 5′ adenosine monophosphate‐activated protein kinase (AMPK)/nuclear factor erythroid 2‐related factor (Nrf2) signaling and changes in the mitochondria in myocardial ischemia/reperfusion (I/R) injury. C57/BL6 mice were exposed to BA (10 mg/kg/d), with or without administration of the AMPK specific inhibitor compound C (5 mg/kg/d) or the Nrf2 specific inhibitor ML‐385 (30 mg/kg/d), and then subjected to a myocardial I/R operation. As expected, BA significantly improved post‐ischemic cardiac function, reduced infarct size and apoptotic cell death, decreased oxidative stress, and improved the mitochondrial state. Furthermore, BA markedly increased AMPK activation, Nrf2 nuclear translocation, and the levels of NAD(P)H quinone dehydrogenase and heme oxygenase‐1. Nevertheless, these BA‐induced changes were abrogated by compound C. In addition, ML‐385 also canceled the cardioprotective effects of BA but had little effect on AMPK activation. Our results demonstrate that BA alleviates myocardial I/R injury and the mitochondrial state by inhibiting apoptosis and oxidative stress via the AMPK/Nrf2 signaling pathway.
Impurity‐profiling UPLC methods for quantitative analysis of some antiemetics formulated with pyridoxine
Authors: Saad Ahmed S. , Draz Mohammed E. , Naguib Ibrahim A. , Zaazaa Hala E. , Lashien Adel S. , Abdallah Fatma F. 
Published: February 2022

AbstractCyclizine hydrochloride (CYC) and meclozine hydrochloride (MEC) are antihistaminic drugs generally co‐formulated with pyridoxine hydrochloride (PYR) to treat nausea and vomiting in pregnancy. Several analytical techniques have been applied for the determination of CYC or MEC with PYR, but determination of CYC impurity; benzhydrol (BEH) or MEC impurity; or 4‐chlorobenzophenone (BEP) has not been paid attention to. Therefore, micellar UPLC method is introduced for analysis of ternary mixtures containing PYR together with both CYC and BEH (mixture I) or MEC and BEP (mixture II). Chromatographic separation was achieved using a Hypersil gold C8 column (50 × 2.1 mm, 1.9 μm) using 0.01 M sodium dodecyl sulfate modified to pH 3.5 using phosphoric acid:acetonitrile (45:55 by volume) for mixture I and 0.1% sodium dodecyl sulfate, 0.1% sodium bicarbonate adjusted to pH 2.6 by phosphoric acid:acetonitrile (47:53 by volume) for mixture II as mobile phases. The separated peaks were detected at 230 and 245 nm for mixtures I and II, respectively. The adopted methods were validated in conformance with the International Conference on Harmonization (ICH) recommendations and were properly applied in commercial pharmaceutical formulation analysis. Comprehensive ecological comparison was achieved, confirming a higher ecological value of the presented methods compared to the earlier reported methods.
Clinical outcomes and Oncotype DX Breast Recurrence Score® in early‐stageBRCA‐associated hormone receptor‐positive breast cancer
Authors: Layman Rachel M. , Lin Heather , Gutierrez Barrera Angelica M. , Karuturi Meghan S. , Yam Clinton , Arun Banu K. 
Published: February 2022

AbstractBackgroundBRCA‐associated breast cancers tend to have distinctive features compared to sporadic breast cancers; further characterization can aid in optimizing treatment.MethodsThe study evaluated a patient cohort with early‐stage estrogen receptor positive, HER2 negative invasive breast cancer who had Oncotype DX Breast Recurrence Score®analysis and genetic testing for hereditary breast and ovarian cancer syndrome. Data on patients and their breast cancers with outcomes were collected and analyzed.Results745 patients were included, of whom 33 had pathogenic BRCA mutations (8BRCA1, 25BRCA2). Patients with BRCA mutations were younger and received more adjuvant chemotherapy, but less endocrine therapy and radiation therapy. BRCA‐associated breast cancers had less progesterone receptor expression, higher nuclear grade, and higher Oncotype DX Breast Recurrence Scores®with median Recurrence Score®29, compared to 16 in cancers without mutations (p < 0.0001). Breast cancer recurrence developed in 18% of patients with BRCA mutations and 9% of patient without mutations, although multivariate analysis of relapse‐free survival was not significant, HR 1.519 (95% confidence interval [CI] 0.64–3.58;p = 0.3401). After adjusting for Recurrence Score®, overall survival by BRCA status was improved HR 0.448 (95% CI 0.06–3.34;p = 0.4333).ConclusionsBRCA‐associated early‐stage hormone receptor‐positive breast cancers have higher Oncotype DX Breast Recurrence Score®compared to those without mutations. BRCA status did not significantly impact relapse‐free survival and overall survival. Larger clinical trials are needed to further assess the findings, and if confirmed, could impact clinical management of BRCA‐associated breast cancers.
Abusive head trauma follows witnessed infant shaking
Authors: Feldman Kenneth W. , Melville John D. , Johnson Katie L. , Valvano Thomas J. , Piper Anne C. , Lakin Karen L. , Petrak Channing S. 
Published: February 2022

AbstractAbuse is a frequent cause of infant subdural haemorrhages, retinal haemorrhages and neurological dysfunction. Confessed shaking, without impact, is one reported injury cause. However, this remains legally controversial. We evaluated whether witnessed shaking alone can cause typical abusive head trauma (AHT). Cases were collected by Helfer Society list‐serve solicitation for infants who developed signs and symptoms of AHT after independently witnessed shaking. We also reviewed a cross‐sectional observational, multi‐centre study (Examining Siblings to Recognize Abuse (ExSTRA)) of 2890 children evaluated for abuse between January 2010 and April 2011 who experienced independently witnessed shaking. Four children identified by the Helfer Society experienced witnessed shaking and developed clinical and radiological evidence of AHT, including subdural and retinal haemorrhages. Another two had neurological symptoms, but normal imaging. Nineteen (0.7%) ExSTRA subjects experienced witnessed shaking without impact injuries. Among them, one (5.9%) of the 17 subjects who were neuroimaged had AHT findings and additional abusive injuries. Three had neurologic symptoms but normal neuroimaging. Although shaking is rarely witnessed, these cases support that shaking alone can cause typical AHT injuries, including, but not limited to, acute neurological impairment, subdural haemorrhages and retinal haemorrhages. This information is important to the legal management of abused children.Key Practitioner Messages

Confessions document that infant shaking can cause abusive head trauma (AHT); however, this is disputed in courtrooms and by some physicians.
Ten infants developed clinical neurologic symptoms with or without radiologic findings of AHT after independently witnessed shaking. None had a history of cranial impacts, and all lacked physical findings suggesting impacts. They provide support for isolated shaking as a cause of AHT.
Diagnostic performance of intravascular ultrasound‐based fractional flow reserve versus angiography‐based quantitative flow ratio measurements for evaluating left main coronary artery stenosis
Authors: Sui Yonggang , Yang Min , Xu Yanlu , Wu Naqiong , Qian Jie 
Published: February 2022

AbstractObjectivesWe compared the diagnostic performance of the ultrasonic flow ratio (UFR) and quantitative flow ratio (QFR) for left main coronary artery (LMCA) stenosis.BackgroundEvaluation of LMCA stenosis remains challenging because of its complex pathogenesis and severity. Computing QFR allows rapid determination of fractional flow reserve (FFR) from coronary angiograms. A novel intravascular ultrasound (IVUS)‐based FFR (UFR) allows rapid FFR computation from IVUS images. Neither of the computational approaches required a pressure wire or hyperemia induction. Previous studies have validated the good diagnostic accuracy of QFR and UFR in identifying hemodynamically significant coronary stenosis using FFR as the reference standard.MethodsThis retrospective observational study enrolled consecutive patients with intermediate‐grade LMCA stenosis who underwent IVUS evaluation. UFR and QFR of all LMCA stenosis patients were assessed, their correlation and agreement were analyzed, and diagnostic performance of UFR in LMCA stenosis was evaluated.ResultsEighty‐three paired comparisons between UFR and QFR were obtained. UFR excellently correlated with QFR (r = 0.74, p < 0.01). The Bland‒Altman plot showed good agreement between UFR and QFR (mean differences: 0.01 ± 0.05, p = 0.34). The area under the curve of UFR for identifying physiological LMCA stenosis was 0.97 (95% confidence interval [CI]: 0.93–1.00, p < 0.01). The overall UFR diagnostic accuracy was 0.95 (95% CI: 0.88–0.99).ConclusionsUFR showed excellent correlation and good agreement with QFR in LMCA stenosis assessment, indicating that it is highly feasible to use UFR for functional evaluation of LMCA stenosis.