bluuebunny/crossref_metadata_2025_split huggingface dataset:
Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial
Authors: Spaner David E. , Luo Yuxuan , Wang Guizhei , Gallagher Jennifer , Tsui Hubert , Shi Yonghong 
Published: November 2021

AbstractPreclinical observations that killing of chronic lymphocytic leukemia (CLL) cells was dexamethasone (DEX) were enhanced by concomitant inhibition of Bruton’s tyrosine kinase and janus kinases (JAKs) motivated a phase II trial to determine if clinical responses to ibrutinib could be deepened by DEX and the JAK inhibitor ruxolitinib. Patients on ibrutinib at 420 mg daily for 2 months or with abnormal serum β2M levels after 6 months or with persistent lymphadenopathy or splenomegaly after 12 months were randomized to receive DEX 40 mg on days 1–4 of a 4‐week cycle for six cycles alone (three patients) or with ruxolitinib 15 mg BID on days 1–21 of each cycle (five patients). Ruxolitinib dosing was based on a previous phase I trial. Steroid withdrawal symptoms and significantly decreased serum IgG levels occurred in all patients regardless of their exposure to ruxolitinib. A fatal invasive fungal infection was seen in a patient taking DEX without ruxolitinib. Complete responses anticipated with addition of ruxolitinib were not seen. Gene expression studies suggested ruxolitinib had turned off interferon signaling in CLL cells and turned on genes associated with the activation of NFκB by TNF‐α. Ruxolitinib increased blood levels of TNF‐α by cycle 3 and decreased the inhibitory cytokine IL‐10. These results suggest ruxolitinib releases activating signals for CLL cells that persist in patients on ibrutinib. This inhibitory JAK signaling may contribute to the therapeutic activity of ibrutinib. Thus JAK inhibitors provide no added value with ibrutinib for disease control and should be used with caution in CLL patients. Combining glucocorticoids with ibrutinib may increase the risk of serious infects.
Machine Learning Enabled Screening of Single Atom Alloys: Predicting Reactivity Trend for Ethanol Dehydrogenation
Authors: Kumar Amrish , Iyer Jayendran , Jalid Fatima , Ramteke Manojkumar , Khan Tuhin S. , Haider M. Ali 
Published: November 2021

AbstractA machine learning (ML) approach implementing the gradient boosting regressor (GBR) algorithm is applied to predict the binding energies of oxygen (EO) and carbon (EC) atoms on single atom alloys (SAAs) of Cu, Ag and Au. Readily available periodic properties of the transition metals are utilized as input features in the model. Their relative contribution in adsorbate‐metal interaction is assessed to develop a comprehensive descriptor. In test runs, the ML model is observed to predict EO and EC with significantly reduced errors (∼0.2 eV). Further, ML approach is augmented with an ab initio microkinetic model (MKM) for non‐oxidative dehydrogenation (NODH) of ethanol. The ML‐MKM is calculated to yield higher turnover frequency for ethanol conversion on NiAu, NiAg, and PtAg SAAs as compared to their monometallic counterparts Au and Ag catalysts. Overall, the ML model provides a rationale for feature selection to synthesize catalytically active SAAs of group 11 elements using fast‐track in silico screening.
Efficient Site‐Selective Immobilization of Aldehyde‐Tagged Peptides and Proteins by Knoevenagel Ligation
Authors: Janson Nils , Heinks Tobias , Beuel Tobias , Alam Sarfaraz , Höhne Matthias , Bornscheuer Uwe T. , Fischer von Mollard Gabriele , Sewald Norbert 
Published: November 2021

AbstractThe aldehyde tag is appropriate to selectively label proteins, prepare antibody‐drug conjugates or to immobilize enzymes or antibodies for biotechnological and medical applications. The cysteine within the consensus sequence CxPxR of the aldehyde tag is specifically oxidized by the formylglycine‐generating enzyme (FGE) to the non‐canonical and electrophilic amino acid Cα‐formylglycine (FGly). Subsequent reductive amination is a common method for site‐directed immobilization, which usually results in poor immobilization efficiency due to the reaction conditions. Here, we introduce a new solid support like agarose modified with an aryl substituted pyrazolone (Knoevenagel reagent) that was obtained in a facile and efficient 2‐step synthesis. The modified agarose allowed the site‐selective and efficient immobilization of aldehyde‐containing small molecules, peptides and proteins – in particular enzymes – at physiological pH (6.2–8.2) without any additive or catalyst needed. In comparison to reductive amination, higher loadings and activities were achieved in various buffers at different concentrations and temperatures.
Steric Repulsion Induced Conformational Switch in Supramolecular Structures
Authors: Norvaiša Karolis , Maguire Sophie , Donohoe Claire , O'Brien John E. , Twamley Brendan , Gomes‐da‐Silva Ligia C. , Senge Mathias O. 
Published: November 2021

AbstractInspired by the rigidified architecture of ‘picket‐fence’ systems, we propose a strategy utilizing strain to impose intramolecular tension in already peripherally overcrowded structures leading to selective atropisomeric conversion. Employing this approach, tuneable shape‐persistent porphyrin conformations were acquired exhibiting distinctive supramolecular nanostructures based on the orientation of the peripheral groups. The intrinsic assemblies driven by non‐covalent bonding interactions form supramolecular polymers while encapsulating small molecules in parallel channels or solvent‐accessible voids. The developed molecular strain engineering methodologies combined with synthetic approaches have allowed the introduction of the pivalate units creating a highly strained molecular skeleton. Changes in the absorption spectrum indicated the presence of severe steric repulsions between the peripheral groups which were confirmed by single crystal X‐ray analysis. To release the steric strain introduced by the peripheral units, thermal equilibration strategies were used to selectively convert the most abundant atropisomer to the desirable minor one.
Tris(tetramethylguanidinyl)phosphine: The Simplest Non‐ionic Phosphorus Superbase and Strongly Donating Phosphine Ligand
Authors: Buß Florenz , Röthel Maike B. , Werra Janina A. , Rotering Philipp , Wilm Lukas F. B. , Daniliuc Constantin G. , Löwe Pawel , Dielmann Fabian 
Published: November 2021

AbstractWe report the synthesis and properties of the much sought‐after tris(1,1,3,3‐tetramethylguanidinyl) phosphine P(tmg)3, a crystalline, superbasic phosphine accessible through a short and scalable procedure from the cheap and commercially available bulk chemicals 1,1,3,3‐tetramethylguanidine, tris(dimethylamino)‐phosphine and phosphorus trichloride. The new phosphine exhibits exceptional electron donor properties and readily forms transition metal complexes with gold(I), palladium(II) and rhodium(I) precursors. The formation of zwitterionic Lewis base adducts with carbon dioxide and sulfur dioxide was explored. In addition, the complete series of phosphine chalcogenides was prepared from the reaction of P(tmg)3 with N2O and the elemental chalcogens.
Total Synthesis of Pulvomycin D
Authors: Fritz Lukas , Wienhold Sebastian , Hackl Sabrina , Bach Thorsten 
Published: November 2021

AbstractA synthetic route to the pulvomycin class of natural products is presented, which culminated in the first synthesis of a pulvomycin, pulvomycin D. Key elements of the strategy include a pivotal aldol reaction which led to bond formation between the C24‐C40 and the C8‐C23 fragment. The remaining C1‐C7 fragment was attached by a Yamaguchi esterification completing the assembly of the 40 carbon atoms within the main skeleton. Ring closure to the 22‐membered lactone ring was achieved in the final stages of the synthesis by a Heck reaction. The completion of the synthesis required the removal of six silyl protecting groups in combination with olefin formation at C26‐C27 by a Peterson elimination.
Papillary thyroid carcinoma tall cell variant shares accumulation of mitochondria, mitochondrial DNA mutations, and loss of oxidative phosphorylation complex I integrity with oncocytic tumors
Authors: Tsybrovskyy Oleksiy , De Luise Monica , de Biase Dario , Caporali Leonardo , Fiorini Claudio , Gasparre Giuseppe , Carelli Valerio , Hackl Dominik , Imamovic Larisa , Haim Silke , Sobrinho‐Simões Manuel , Tallini Giovanni 
Published: November 2021

AbstractPapillary thyroid carcinoma tall cell variant (PTC‐TCV), a form of PTC regarded as an aggressive subtype, shares several morphologic features with oncocytic tumors. Pathogenic homoplasmic/highly heteroplasmic somatic mitochondrial DNA (mtDNA) mutations, usually affecting oxidative phosphorylation (OXPHOS) complex I subunits, are hallmarks of oncocytic cells. To clarify the relationship between PTC‐TCV and oncocytic thyroid tumors, 17 PTC‐TCV and 16 PTC non‐TCV controls (cPTC) were subjected to: (1) transmission electron microscopy (TEM) to assess mitochondria accumulation, (2) next‐generation sequencing to analyze mtDNA and nuclear genes frequently mutated in thyroid carcinoma, and (3) immunohistochemistry (IHC) for prohibitin and complex I subunit NDUFS4 to evaluate OXPHOS integrity. TEM showed replacement of cytoplasm by mitochondria in PTC‐TCV but not in cPTC cells. All 17 PTC‐TCV had at least one mtDNA mutation, totaling 21 mutations; 3/16 cPTC (19%) had mtDNA mutations (p < 0.001). PTC‐TCV mtDNA mutations were homoplasmic/highly heteroplasmic, 16/21 (76%) mapping within mtDNA‐encoded complex I subunits. MtDNA mutations in cPTC were homoplasmic in 2 cases and at low heteroplasmy in the third case, 2/3 mapping to mtDNA‐encoded complex I subunits; 2/3 cPTC with mtDNA mutations had small tall cell subpopulations. PTC‐TCV showed strong prohibitin expression and cPTC low‐level expression, consistent with massive and limited mitochondrial content, respectively. All 17 PTC‐TCV showed NDUFS4 loss (partial or complete) and 3 of 16 cPTC (19%) had (partial) NDUFS4 loss, consistent with lack of complex I integrity in PTC‐TCV (p < 0.001). IHC loss of NDUFS4 was associated with mtDNA mutations (p < 0.001). Four BRAF V600E mutated PTCs had loss of NDUSF4 expression limited to neoplastic cell subpopulations with tall cell features, indicating that PTCs first acquire BRAF V600E and then mtDNA mutations. Similar to oncocytic thyroid tumors, PTC‐TCV is characterized by mtDNA mutations, massive accumulation of mitochondria, and loss of OXPHOS integrity. IHC loss of NDUFS‐4 can be used as a surrogate marker for OXPHOS disruption and to reliably diagnose PTC‐TCV.
Insulating Polymers as Additives to Bulk‐Heterojunction Organic Solar Cells: The Effect of Miscibility
Authors: Liu Chunhui , Xiao Chengyi , Xie Chengcheng , Zhu Qinglian , Chen Qiaomei , Ma Wei , Li Weiwei 
Published: November 2021

AbstractAdding insulating polymers to conjugated polymers is an efficient strategy to tailor their mechanical properties for flexible organic electronics. In this work, we selected two insulating polymers as additives for high‐performance photoactive layers and investigated the mechanical and photovoltaic properties in organic solar cells (OSCs). The insulating polymers were found to reduce the electron mobilities in the photoactive layers, and hence the power conversion efficiencies were significantly decreased. More importantly, we found that the insulating polymers exhibited negative effect on the mechanical properties of the photoactive layers, with reduced Young's modulus and low crack onset strains. Further studies revealed that the insulating polymers had poor miscibility with the photoactive layers, providing large domains and more cavities in blend thin films, which act as negative effect for the tensile test. The studies indicate that rational selection of insulating polymers, especially enhancing the non‐covalent interaction with the photoactive layers, will be critically important for the stretchable OSCs.
Oral function is associated with the body and muscle mass indices of middle‐aged dental patients
Authors: Nishi Tomotaka , Ohta Midori , Takano Tomofumi , Ogami Koichiro , Ueda Takayuki , Sakurai Kaoru 
Published: November 2021

AbstractObjectivesUndernutrition is associated with frailty, one of the common reasons for seeking long‐term care. In older adults, nutritional status is known to be associated with oral function; however, it is not yet known if there is a similar association in middle‐aged adults. The present study determined the association between nutritional status and oral function in middle‐aged adults.Material and methodsThis cross‐sectional study was conducted in 117 outpatients aged 40–64 years who underwent dental check‐up at a private dental clinic. Factors associated with oral function, including oral moisture, number of teeth present, oral diadochokinesis, tongue pressure, lip‐seal strength, and masticatory performance, were evaluated. Body mass index (BMI), fat‐free mass index (FFMI), and skeletal muscle mass index (SMI) were analyzed as nutritional statuses. Pearson's correlation analysis was conducted to determine the correlation between nutritional statuses and other variables. Multiple linear regression analysis was performed, with adjustment for age and sex, using BMI, FFMI, or SMI as response variables and oral moisture, maximum tongue pressure, lip‐seal strength, oral diadochokinetic rate, and masticatory performance as explanatory variables.ResultsAll nutritional statuses showed significant correlation with maximum tongue pressure and lip‐seal strength. Multiple linear regression analysis revealed that BMI was associated with maximum tongue pressure and lip‐seal strength, whereas FFMI and SMI showed significant association with sex, maximum tongue pressure, and lip‐seal strength.ConclusionsIn middle‐aged outpatients at a regional dental clinic, lip‐seal strength and tongue pressure were positively associated with BMI, FFMI, and SMI.
Discovery of c.577del in EPO: Investigations into endogenous EPO double‐band detected in blood with SAR‐PAGE
Authors: Zhou Xinmiao , He Sen , Zezhou Li , Jiayu Wang , Zhou Wen , Liu Xinchao , Zhao Meiping , Zhang Lisi 
Published: November 2021

AbstractRecently, some athletes were repetitively found to have rEPO positive results, including a characterized double‐band pattern in blood samples, in routine doping analysis. In contrast to previous findings from excretion studies, this double‐band pattern showed the same relative intensity even when the samples were collected weeks (/months) apart. We therefore suspected that these “positive” doping control samples were related with a novel pathway of endogenous EPO production. Thus, follow‐up investigations were warranted to characterize the origin of such analytical test results and to avoid the issuing of adverse analytical findings in the absence of rEPO by identifying the root cause of these “constantly positives.” In this study, we designed and conducted a series of causal studies, including population screening of EPO profiles, exploration of EPO de‐N‐glycosylation, single nucleotide polymorphism (SNP) browsing in EPO, sequencing of EPO exons, genealogical analysis of the c.577del EPO variant, and finally expression and investigation of mutant EPO. In summary, we found that these “constantly positives” were related to endogenous EPO production associated with the c.577del EPO variant. The frequency of this variant was 0.39% in our Chinese population pool. The mutant EPO encoded by this variant is 27 amino acids longer than the wild‐type. The molecular weight of this mutant EPO is approximately the same as that of rEPO, exhibiting a similar electrophoretic behavior. To prevent charges against carriers of the c.577del variant, a revised rEPO testing strategy has been implemented in the new version of TD EPO.
Double (W1/O/W2) and Simple (O/W2) Emulsions Prepared with Soybean Flour Dispersion and Vegetable Fat: Partial Coalescence Promotion by Polyglycerol Polyricinoleate and Calcium
Authors: Rando María S. , Palazolo Gonzalo G. , Márquez Andrés L. 
Published: November 2021

AbstractThe objective is to study the partial coalescence process in calcium‐fortified double (W1/O/W2) and simple (O/W2) emulsions prepared with soybean flour dispersion as continuous aqueous (W2) phase and vegetable fat plus polyglycerol polyricinoleate (PGPR) as lipophilic emulsifier (at varied concentration) in lipid phase. Calcium chloride is included in the dispersed aqueous (W1) phase and the W2 phase of W1/O/W2 and O/W2 emulsions, respectively. No partial coalescence is observed in the O/W2 emulsion without PGPR and calcium, while the inclusion of the emulsifier and/or divalent cation promotes the phenomenon. The presence of PGPR in lipid phase or calcium in W2 phase can enhance capture efficiency because of the decrease of electrostatic and steric repulsions between fat globules, the modification of fat crystals, and/or the increased size of individual globules. W1/O/W2 emulsions show a lower partial coalescence degree in comparison to O/W2 emulsions prepared with the same components, attributed to the isolation of a fraction of added calcium in the W1 phase of the former systems. PGPR produces microstructural and rheological changes over time in emulsions subjected to prolonged cold storage; but its effect is reduced in the presence of calcium, probably because of the formation of stronger globule aggregates.Practical applications: This article deals with two parallel phenomena occurring in W1/O/W2 and O/W2 emulsions prepared with soybean flour dispersion as W2 phase and vegetable fat in lipid phase: the promotion of partial coalescence by the lipophilic emulsifier, PGPR; and the aggregation of proteins and fat globules due to the presence of calcium in W2 phase. In this way, the effects of PGPR and/or calcium on partial coalescence are studied in these systems, analyzing their microstructure and rheology. The encapsulation of calcium within the W1 phase of W1/O/W2 emulsions and its impact on partial coalescence is also analyzed. The results obtained in this work can be relevant for the formulation of calcium‐fortified, vegetable food emulsions, showing a texture similar to whipped dairy cream, where PGPR concentration or calcium release can be controlled to adjust the rheological characteristics of the system.
Emerging on‐chip electrokinetic based technologies for purification of circulating cancer biomarkers towards liquid biopsy: A review
Authors: Shi Leilei , Esfandiari Leyla 
Published: November 2021

AbstractEarly detection of cancer can significantly reduce mortality and save lives. However, the current cancer diagnosis is highly dependent on costly, complex, and invasive procedures. Thus, a great deal of effort has been devoted to exploring new technologies based on liquid biopsy. Since liquid biopsy relies on detection of circulating biomarkers from biofluids, it is critical to isolate highly purified cancer‐related biomarkers, including circulating tumor cells (CTCs), cell‐free nucleic acids (cell‐free DNA and cell‐free RNA), small extracellular vesicles (exosomes), and proteins. The current clinical purification techniques are facing a number of drawbacks including low purity, long processing time, high cost, and difficulties in standardization. Here, we review a promising solution, on‐chip electrokinetic‐based methods, that have the advantage of small sample volume requirement, minimal damage to the biomarkers, rapid, and label‐free criteria. We have also discussed the existing challenges of current on‐chip electrokinetic technologies and suggested potential solutions that may be worthy of future studies.
3D printing of anisotropic Sm–Fe–N nylon bonded permanent magnets
Authors: Gandha Kinjal , Paranthaman M. P. , Sales Brian C. , Wang Haobo , Dalagan Adrian , Lamichhane Tej N. , Parker David S. , Nlebedim Ikenna C. 
Published: November 2021

AbstractFabricating a bonded magnet with a near‐net shape in suitable thermoplastic polymer binders is of paramount importance in the development of cost‐effective energy technologies. In this work, anisotropic Sm2Fe17N3 (Sm–Fe–N) bonded magnets are additively printed using SmFeN anisotropic magnetic particles in a polymeric binder polyamide‐12 (PA12). The anisotropic SmFeN bonded magnets are fabricated by Big Area Additive Manufacturing followed by post‐printing alignment in a magnetic field. Optimal post‐alignment results in an enhanced remanence of ∼0.68 T in PA12 reflected in a parallel‐oriented (aligned) measured direction. The maximum energy product achieved for the additively printed anisotropic bonded magnet of Sm–Fe–N in PA12 polymer is 78.8 KJ m−3. Our results show advanced processing flexibility with 3D printing of the development of SmFeN nylon bonded magnets designed for applications with no critical rare earth magnets.
Poly- and Perfluorinated Alkyl Substances in Air and Water from Dhaka, Bangladesh
Authors: Morales-McDevitt Maya E. , Dunn Matthew , Habib Ahsan , Vojta Simon , Becanova Jitka , Lohmann Rainer 
Published: November 2021

Abstract
Bangladesh hosts extensive textile manufacturing, for some of which per- and polyfluorinated alkyl substances (PFAS) have been used to impart water and dirt repellency, among other things. Textile waste emissions to the atmosphere and discharge into rivers and other bodies of water could present a significant concern for human and ecosystem health, but there is little information on PFAS in Bangladesh. To assess the presence of ionic PFAS and their precursors in air and water from Dhaka, Bangladesh, polyethylene sheets were deployed for 28 days as passive samplers for neutral PFAS in outdoor air and water, while ionic PFAS were measured from discrete water grabs. Fluorotelomer alcohols (FTOHs) were detected at almost all sites in air and water; the most frequently detected compound was 6:2 FTOH, ranging from below instrumental detection limits (&lt;IDL) to 70 ng m−3 in air and from &lt;IDL to −19 ng L−1 in water. Of the ionic PFAS, perfluorobutanoic acid (PFBA), perfluorohexanoic acid, perfluorooctanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid dominated in frequency of detection and magnitude, with concentrations ranging from 1.8 to 19.0 ng L−1 in surface waters. The prevalence of 6:2 FTOH and PFBA across sites probably reflects their use in textile manufacturing and could indicate the industry's switch to shorter-chain PFAS alternatives. Environ Toxicol Chem 2022;41:334–342. © 2021 SETAC
Abstract
Concentration of PFAS in air and water from Dhaka Bangladesh during winter (January–March) of 2020. Water concentrations were obtained from discrete water grabs, while air concentrations were derived from polyethylene (PE) passive sampling. FTS = fluorotelomer sulfonate; PFCA = perfluorocarboxylic acid; PFSA = perfluorosulfonic acid.