bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depth filter material process interaction in the harvest of mammalian cells
Authors: Parau Maria , Pullen James , Bracewell Daniel G. 
Published: February 2023

AbstractUpstream advances have led to increased mAb titers above 5 g/L in 14‐day fed‐batch cultures. This is accompanied by higher cell densities and process‐related impurities such as DNA and Host Cell Protein (HCP), which have caused challenges for downstream operations. Depth filtration remains a popular choice for harvesting CHO cell culture, and there is interest in utilizing these to remove process‐related impurities at the harvest stage. Operation of the harvest stage has also been shown to affect the performance of the Protein A chromatography step. In addition, manufacturers are looking to move away from natural materials such as cellulose and Diatomaceous Earth (DE) for better filter consistency and security of supply. Therefore, there is an increased need for further understanding and knowledge of depth filtration. This study investigates the effect of depth filter material and loading on the Protein A resin lifetime with an industrially relevant high cell density feed material (40 million cells/ml). It focuses on the retention of process‐related impurities such as DNA and HCP through breakthrough studies and a novel confocal microscopy method for imaging foulant in‐situ. An increase in loading of the primary‐synthetic filter by a third, led to earlier DNA breakthrough in the secondary filter, with DNA concentration at a throughput of 50 L/m2 being more than double. Confocal imaging of the depth filters showed that the foulant was pushed forward into the filter structure with higher loading. The additional two layers in the primary‐synthetic filter led to better pressure profiles in both primary and secondary filters but did not help to retain HCP or DNA. Reduced filtrate clarity, as measured by OD600, was 1.6 fold lower in the final filtrate where a synthetic filter train was used. This was also associated with precipitation in the Protein A column feed. Confocal imaging of resin after 100 cycles showed that DNA build‐up around the outside of the bead was associated with synthetic filter trains, leading to potential mass transfer problems.
Hypoxia‐induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase‐1 in multiple myeloma
Authors: Abe Ko , Ikeda Sho , Nara Miho , Kitadate Akihiro , Tagawa Hiroyuki , Takahashi Naoto 
Published: February 2023

AbstractBackgroundMultiple myeloma (MM) is a hematopoietic malignancy for which proteasome inhibitors have become available in recent years. However, many patients develop resistance to these drugs during treatment. Therefore, it is important to elucidate the mechanisms underlying resistance acquisition by proteasome inhibitors. Side population (SP) cells, which have a high drug efflux capacity and hypoxic responses in the microenvironment have both provided important insights into drug resistance in MM; however, little is known about the characteristics of SP cells in hypoxic microenvironments.MethodsWe performed cDNA microarray analysis for SP and non‐SP obtained from RPMI‐8226 and KMS‐11 cell lines cultured for 48 h in normoxic and hypoxic conditions (1% O2). Genes specifically upregulated in hypoxic SP were examined.ResultsOur comprehensive gene expression analysis identified HMOX1, BACH2, and DUX4 as protein‐coding genes that are specifically highly expressed in SP cells under hypoxic conditions. We have shown that HMOX1/heme oxygenase‐1 (HMOX1/HO‐1) is induced by hypoxia‐inducible reactive oxygen species (ROS) and reduces ROS levels. Furthermore, we found that HMOX1 contributes to hypoxia‐induced resistance to proteasome inhibitors in vitro and in vivo. Excessive ROS levels synergistically enhance bortezomib sensitivity. In clinical datasets, HMOX1 had a strong and significantly positive correlation with MAFB but not MAF. Interestingly, hypoxic stimulation increased MAFB/MafB expression in myeloma cells; in addition, the knockdown of MAFB under hypoxic conditions suppressed HMOX1 expression.ConclusionThese results suggest that the hypoxia‐ROS‐HMOX1 axis and hypoxia‐induced MafB may be important mechanisms of proteasome inhibitor resistance in hypoxic microenvironments.
No association of malignant B‐cell non‐Hodgkin lymphomas with ipsilateral SARS‐CoV‐2 vaccination
Authors: Claaß Luise Victoria , Mayr Patrick , Paschold Lisa , Weber Thomas , Terziev Denis , Jehs Bertram , Brill Richard , Dober Johannes , Märkl Bruno , Wickenhauser Claudia , Czapiewski Piotr , Trepel Martin , Claus Rainer , Binder Mascha 
Published: February 2023

AbstractPurposeSARS‐CoV‐2 vaccines cause acute ipsilateral lymph node swelling in an important proportion of vaccines. Thus far, no malignant lymphadenopathies have been reported in temporal context to vaccination in the ipsilateral draining lymph node areas.Experimental designPrompted by two cases with unilateral axillary lymphomas that occurred ipsilaterally to prior SARS‐CoV‐2 vaccination, we systematically retrieved all B‐cell non‐Hodgkin lymphomas at two German University Medical Centers diagnosed before and after introduction of SARS‐CoV‐2 vaccines in Germany. Available lymphoma tissue (n=19) was subjected to next‐generation immunosequencing of the IGH locus. Malignant clonotypes were mined in the CoVabDab database and published data sets from 342 uninfected individuals, 55 individuals 28 days after anti‐SARS‐CoV‐2 vaccination and 139 individuals with acute COVID‐19 together encompassing over 1 million CDR3 sequences in total.ResultsOf 313 newly diagnosed cases in the two centers and observation periods, 27 unilateral manifestations in the defined deltoid draining regions were identified. The majority thereof were diffuse large B‐cell lymphomas (18 of 27 cases). Eleven unilateral cases were diagnosed in the era of SARS‐CoV‐2 vaccination and 16 in the control period before introduction of such vaccines. Of the 11 unilateral lymphomas that occurred during the vaccination period, ten had received a SARS‐CoV‐2 vaccine prior to lymphoma diagnosis. These cases were further evaluated. While left‐sided were more frequent than right‐sided lymphomas (19 vs 8 cases), no statistically significant association of vaccination site and laterality of the lymphoma manifestation was found. The unilateral lymphomas showed a normal range of B‐cell receptors typically found in these lymphoma subtypes with no evidence for anti‐SARS‐CoV‐2 sequences in the malignant clonotype.ConclusionsTogether, we found no evidence that the current SARS‐CoV‐2 vaccines could serve as a trigger for lymphomagenesis in the draining lymph node areas of the deltoid region used for vaccination.
Deacetylation of Arabinofuranosylated Xylopyranosyl Residues Related to Plant Xylan: Significant Differences Between Xylan Deacetylases Classified into Various Carbohydrate Esterase Families
Authors: Bella Maroš , Poláková Monika , Puchart Vladimír 
Published: February 2023

AbstractA chemical synthesis of two novel phenyl glycosides of trisaccharides related to acetylarabinoxylan is described. The trisaccharides bear acetyl and arabinofuranosyl moieties at the non‐reducing‐end xylopyranosyl residue, which is substituted at positions 2 and 3. Both compounds were treated with various xylan deacetylases classified in different carbohydrate esterase (CE) families and significant differences between the families were found. While the arabinosylation hampers deacetylation by CE2‐CE5 and CE12 family members, both epitopes are deesterified by CE1 and in particular CE6 enzymes. The 3‐O‐acetylated 2‐O‐arabinosylated compound is also processed by CE7 and majority of CE16 esterases, but not by a hitherto non‐classified Flavobacterium johnsoniae acetylxylan esterase. The data suggests that a slow deesterification of the 2‐O‐acetylated 3‐O‐arabinosylated compound may be due to the acetyl group migration followed by deacetylation of this migration product.
Severe length‐dependent peripheral polyneuropathy in a patient with subacute combined spinal cord degeneration secondary to recreational nitrous oxide abuse: A case report and literature review
Authors: Bonev Ventzislav , Wyatt Mark , Barton Matthew J. , Leitch Michael A. 
Published: February 2023

AbstractNitrous oxide abuse can have detrimental effects on the central and peripheral nervous systems. This case study report aims to demonstrate a combination of severe generalized sensorimotor polyneuropathy and cervical myelopathy related to vitamin B12 deficiency following nitrous oxide abuse. We present a clinical case study and literature review examining primary research—published between 2012 and 2022—reporting nitrous oxide abuse affecting the spinal cord (myelopathy) and peripheral nerves (polyneuropathy); 35 articles were included in the review with a total of 96 patients, where the mean “patients” age was 23.9 years and were in a 2:1 male/female ratio. Of the 96 cases, within the review, 56% of patients were diagnosed with polyneuropathy, most commonly impacting the nerves of the lower limb (62%), while 70% of patients were diagnosed with myelopathy, most commonly impacting the cervical region (78%) on the spinal cord. In our clinical case study, a 28‐year‐old male underwent a multitude of diagnostic investigations for bilateral “foot drop” and sense of lower limb stiffness as ongoing complications of a vitamin B12 deficiency secondary to recreational nitrous oxide abuse. Both the literature review and our case report emphasize the dangers of recreational nitrous oxide inhalation, colloquially termed “nanging” and the risks it presents to both the central and peripheral nervous systems, which is erroneously considered by many recreational drug users to be less harmful than other illicit substances.
Superficial temporal artery access for carotid artery stenting: A case report
Authors: Csavajda Ádám , Nardai Sándor , Bertrand Olivier F. , Ruzsa Zoltán 
Published: February 2023

AbstractPercutaneous intervention of patients who suffer from generalized vascular disease is often a great challenge due to the limited accessibility of the access gates. We discuss the case of a 66‐year‐old man who presented with critical right internal carotid artery (ICA) stenosis after previous hospitalization due to stroke. In addition to arteria lusoria, the patient had known bilateral femoral amputation, occlusion of the left ICA and significant three‐vessel coronary artery disease. After unsuccessful common carotid artery (CCA) cannulation from the right distal radial artery access, we successfully performed the diagnostic angiography and the planned right ICA‐CCA intervention using superficial temporal artery (STA) puncture. We showed that STA access can be used as an alternative and additional access site for diagnostic carotid artery angiography and intervention when standard access sites alone are insufficient.
Pt : Ge Ratio as a Lever of Activity and Selectivity Control of Supported PtGe Clusters in Thermal Dehydrogenation**
Authors: Poths Patricia , Zandkarimi Borna , Alexandrova Anastassia N. , Jimenez‐Izal Elisa 
Published: February 2023

AbstractEthylene is a key molecule in the chemical industry and it can be obtained through the catalytic dehydrogenation of ethane. Pt‐based catalysts show high performance toward alkane dehydrogenation, but suffer from coke formation and sintering that deactivate the catalyst. Ge was recently discovered to be a promising alloying element that suppresses deactivation of Pt while preserving its catalytic activity toward alkane dehydrogenation. This work explores the effect of the Ge content in supported PtGe cluster alloys, on the activity toward ethane dehydrogenation, selectivity against deeper dehydrogenation and coking, and sintering resistance. The model proposed herein is a tetrameric Pt cluster supported on magnesia, with varying amounts of added Ge. The phase diagram for these clusters was computed using global optimization at the density functional theory level, and under the paradigm of a statistical ensemble of many states populated by clusters at catalytic temperatures. The phase diagram shows that various Ge contents should be synthetically accessible, with Pt4Ge/MgO and Pt4Ge4/MgO being the most likely phases. The subsequent adsorption and mechanistic studies show that the clusters with the 1 : 4 Ge to Pt ratio (Pt4Ge/MgO) feature the largest resistance to sintering and best selectivity in the ethane dehydrogenation toward ethylene. Clusters without Ge are too active and easily coke, whereas clusters with higher Ge content start losing the catalytic activity toward ethane dehydrogenation. Thus, Ge concentration is a lever of control of Pt cluster stability and selectivity, and of cluster catalyst design. The effect of the Ge concentration on the cluster properties is explained on the basis of the electronic structure.
Drop Size Distributions as a Function of Dispersed Phase Viscosity: Experiments and Modeling
Authors: Hohl Lena , Röhl Susanne , Kraume Matthias 
Published: February 2023

AbstractDetailed measurements of dynamic and steady‐state drop size distributions were performed in liquid‐liquid systems with water and different silicone oils using an in situ endoscope technique in a discontinuously operated stirred tank. The oils used as the dispersed phase vary in dynamic viscosity, while density and interfacial tension are nearly constant. The performance of a population balance model for partially mobile interfaces and its ability to predict steady‐state and dynamic Sauter mean diameters and the complete drop size distributions as a function of dispersed phase viscosity and different process parameters are evaluated. Furthermore, the impact of different daughter drop size distribution shapes on simulation results is quantified.
Fluorescence Detection of the Persistent Organic Pollutant Chlordecone in Water at Environmental Concentrations
Authors: Della‐Negra Oriane , Kouassi Aya Esther , Dutasta Jean‐Pierre , Saaidi Pierre‐Loïc , Martinez Alexandre 
Published: February 2023

AbstractChlordecone (CLD), a Persistent Organic Pollutant, is still present in water and food chain of the French West Indies (FWI), leading to dramatical public health problems. One of the major issues is the lack of an easy, non‐expensive, sensitive and robust method for the detection of chlordecone to ensure chlordecone‐free water and foods for the residents of the FWI. This study reports on the development of a fluorescent molecular cage that allows a simple and convenient detection of chlordecone in water at environmental concentration. The specific structural features of chlordecone prompted the choice of hemicryptophanes as receptor. First, the size, shape of the cavity, as well as the recognition units, were optimized to identify the most efficient non fluorescent host for CLD complexation. Then, this selected compound was equipped with fluorophores at different positions in order to find the most efficient system for CLD detection by fluorescence. Among the two most promising fluorescent cages, the newly synthesized hemicryptophane with biphenyl moieties allowed the development of a fast, easy, reproducible and cheap procedure to detect CLD in water. Based on its sensitivity and scalability, with modulation of hemicryptophane, concentration, CLD concentrations were estimated over five orders of magnitude (10−2–103 μg/L) including the environmental levels of contamination and the permissible limit for drinking water in the FWI.
Double Addition vs. Ring Closure: Systematic Reactivity Study of CO(NCO)2 and CO(NCS)2 towards Hydrogen Halides
Authors: Pfeiffer Jonathan , Günther Hennes , Völlinger Lena , Botros Demian , Scheibe Benjamin , Möbs Martin , Kraus Florian , Weigend Florian , Tambornino Frank 
Published: February 2023

AbstractThe reactivity of carbonyl diisocyanate, CO(NCO)2, and carbonyl diisothiocyanate, CO(NCS)2 with nucleophiles shows different patterns: Whereas carbonyl diisocyanate adds two equivalents of nucleophile forming carbonyl bis(carbamoylhalides), carbonyl diisothiocyanate only adds one equivalent and undergoes intramolecular ring closure, resulting in the formation of substituted thiadiazines. In this study we have reacted both carbonyl diisocyanate and carbonyl diisothiocyanate with the full series of hydrogen halides HF to HI, isolating carbonyl bis(carbamoylfluoride) (1), ‐chloride (2), ‐bromide (3), and ‐iodide (4) as well as (6‐chloro‐2,3‐dihydro‐2‐thioxo‐4H‐1,3,5‐thiadiazin‐4‐one (5), and 6‐bromo‐2,3‐dihydro‐2‐thioxo‐4H‐1,3,5‐thiadiazin‐4‐one (6). The compounds were analysed by single‐crystal X‐ray diffraction, NMR spectroscopy, IR and Raman spectroscopy, and elemental analysis. Quantum mechanical calculations show thermodynamic reasons for the differences in reactivity.
The Boekelheide Rearrangement of Pyrimidine N‐oxides as a Case Study of Closed or Open Shell Reactions ‐ Experimental and Computational Evidence for the Participation of Radical Intermediates
Authors: Kurzawa Timon , Zimmer Reinhold , Würthwein Ernst‐Ulrich , Reissig Hans‐Ulrich 
Published: February 2023

AbstractIn a case study, the acetic anhydride‐promoted reaction of a model pyrimidine N‐oxide to the corresponding 4‐acetoxymethyl‐substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin‐4‐yl)methyl radical is one of the key species of the rearrangement. This interpretation was supported by the fact that rearrangements performed in solvents which can easily lose hydrogen atoms, afford considerable quantities of products incorporating the solvent. With TEMPO the key radical could be trapped. Other carboxylic acid anhydrides confirm the conclusion that the Boekelheide rearrangement of the model pyrimidine N‐oxide proceeds, at least in part, via radical intermediates. The high level closed and open shell quantum chemical calculations show that concerted [3,3]‐sigmatropic rearrangements or stepwise processes, either via ion pairs or via radicals, are energetically feasible.
White Light‐Emitting Electrochemical Cells Employing Phosphor‐Sensitized Thermally Activated Delayed Fluorescence to Approach All‐Phosphorescent Device Efficiencies
Authors: Chen Xuan‐Jun , Huang Yu‐Ting , Luo Dian , Chang Chih‐Hao , Lu Chin‐Wei , Su Hai‐Ching 
Published: February 2023

AbstractSolid‐state light‐emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low‐cost display and lighting applications. In this work, novel white LECs based on phosphor‐sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue‐green phosphorescent host doped with a deep‐red TADF guest. Efficient singlet‐to‐triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self‐quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor‐sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all‐phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor‐sensitized TADF white LECs are potential candidates for efficient white light‐emitting devices.
Ruthenium‐Catalyzed Cycloaddition for Introducing Chemical Diversity in Second‐Generation β‐Lactamase Inhibitors
Authors: Bouchet Flavie , Barnier Jean‐Philippe , Sayah Ines , Bagdad Youcef , Miteva Maria A. , Arthur Michel , Ethève‐Quelquejeu Mélanie , Iannazzo Laura 
Published: February 2023

AbstractRuthenium(II) alkyne azide cycloaddition (RuAAC) is an attractive reaction to access 1,5‐triazole derivatives and is applicable to internal alkynes. Here, we explore RuAAC to introduce molecular diversity on the diazabicyclooctane (DBO) scaffold of β‐lactamase inhibitors. The methodology presented is fully regioselective and enabled synthesis of a series of 1,5‐triazole DBOs and trisubstituted analogues. Molecular modelling and biological evaluation revealed that the DBO substituents provided putative stabilizing interactions in the active site of broad‐spectrum β‐lactamase KPC‐2 and promising activity against a hyperpermeable strain of Escherichia coli producing KPC‐2.
A Computational Workflow for Analysis of 3′ Tag‐Seq Data
Authors: Paropkari Akshay D. , Bapat Priyanka S. , Sindi Suzanne S. , Nobile Clarissa J. 
Published: February 2023

AbstractRNA‐sequencing (RNA‐seq) is a gold‐standard method to profile genome‐wide changes in gene expression. RNA‐seq uses high‐throughput sequencing technology to quantify the amount of RNA in a biological sample. With the increasing popularity of RNA‐seq, many variations on the protocol have been proposed to extract unique and relevant information from biological samples. 3′ Tag‐Seq (also called TagSeq, 3′ Tag‐RNA‐Seq, and Quant‐Seq 3′ mRNA‐Seq) is one RNA‐seq variation where the 3′ end of the transcript is selected and amplified to yield one copy of cDNA from each transcript in the biological sample. We present a simple, easy‐to‐use, and publicly available computational workflow to analyze 3′ Tag‐Seq data. The workflow begins by trimming sequence adapters from raw FASTQ files. The trimmed sequence reads are checked for quality using FastQC and aligned to the reference genome, and then read counts are obtained using STAR. Differential gene expression analysis is performed using DESeq2, based on differential analysis of gene count data. The outputs of this workflow are MA plots, tables of differentially expressed genes, and UpSet plots. This protocol is intended for users specifically interested in analyzing 3′ Tag‐Seq data, and thus normalizations based on transcript length are not performed within the workflow. Future updates to this workflow could include custom analyses based on the gene counts table as well as data visualization enhancements. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Running the 3′ Tag‐Seq workflowSupport Protocol: Generating genome indices