bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrathecal IgM Synthesis Is Associated with Spinal Cord Manifestation and Neuronal Injury in Early MS
Authors: Oechtering Johanna , Lincke Therese , Schaedelin Sabine , Décard Bernhard F. , Maceski Aleksandra , Orleth Annette , Meier Stephanie , Willemse Eline , Buchmann Arabella , Khalil Michael , Derfuss Tobias , Benkert Pascal , Heijnen Ingmar , Regeniter Axel , Müller Stefanie , Achtnichts Lutz , Lalive Patrice , Salmen Anke , Pot Caroline , Gobbi Claudio , Kappos Ludwig , Granziera Cristina , Leppert David , Schlaeger Regina , Lieb Johanna M. , Kuhle Jens ,   and for the Swiss MS Cohort Study
Published: March 2022

Objective

Intrathecal Immunoglobulin M synthesis (IgMIntrathecal Fraction (IF)+) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgMIF+ is associated with spinal cord manifestation and higher neuroaxonal damage in early MS.

Methods

In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non‐spinal clinical syndrome (2) spinal vs cerebral T2‐weighted (T2w) and (3) contrast‐enhancing (CE) lesion counts with IgGIF+ (vs IgGIF−) or IgMIF+ (vs IgMIF−) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgGIF and IgMIF (>0% vs 0%, respectively): (1) OCGB−/IgGIF−/IgMIF−; (2) OCGB+/IgGIF−/IgMIF−; (3) OCGB+/IgGIF+/IgMIF−; and (4) OCGB+/IgGIF+/IgMIF+. Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters.

Results

Patients with a spinal syndrome had a 8.36‐fold higher odds of IgMIF+ (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgMIF+ (but not of IgGIF+); this was not the case for cerebral lesions. OCGB+/IgGIF+/IgMIF+ category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01).

Interpretation

Intrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022;91:814–820
Nickel‐Catalyzed Thermal Redox Functionalization of C(sp3)−H Bonds with Carbon Electrophiles**
Authors: Gong Yuxin , Su Lei , Zhu Zhaodong , Ye Yang , Gong Hegui
Published: March 2022

C(sp3)−H bond coupling with carbon electrophiles remains rarely explored under thermo‐driven hydrogen atom transfer (HAT) conditions due to the challenge of integrating oxidation and reduction in a single operation. We report here a Ni‐catalyzed arylation and alkylation of C(sp3)−H bonds with organohalides to forge C(sp3)−C bonds by merging economical Zn and tBuOOtBu (DTBP) as the external reductant and oxidant. The mild and easy‐to‐operate protocol enables facile carbofunctionalization of N‐/O‐α‐ and cyclohexane C−H bonds, and preparation of a few intermediates of bioactive compounds and drug derivatives. Preliminary mechanistic studies implied addition of an alkyl radical to a NiII salt.
Print path‐dependent contact temperature dependency for 3D printing using fused filament fabrication
Authors: Xu Yao , Huang Miaozi , Schlarb Alois K.
Published: March 2022

This paper focuses on the effects of different time spans and thus different contact temperatures when a molten strand contacts an adjacent already solidified strand in a plane during 3D printing with fused filament fabrication. For this purpose, both the manufacturing parameters and the geometry of the component are systematically varied and the effect on morphology and mechanical properties is investigated. The results clearly show that even with identical printing parameters, the transitions between the individual layers are much more visible with long time spans until fusion and lead to low mechanical properties. In contrast, short spans lead to hardly visible welds and high mechanical properties. Transferring the findings to different component sizes ultimately verifies that the average temperature at the time of contact between the already solidified and the currently deposited strand is decisive for component quality. In order to generate high component qualities, this finding must therefore be taken into account in the future in the path generation strategy, i.e., in so‐called slicing.
UVA Light‐promoted Catalyst‐free Cyclization of Vinyl Selenides: Green and Efficient Synthesis of C3‐Unsubstituted 2‐Selanyl Benzochalcogenophenes
Authors: Perin Gelson , Peglow Thiago J. , Penteado Filipe , Nobre Patrick C. , Silva Krigor B. , Stach Guilherme , Barcellos Thiago , Lenardão Eder J. , Roehrs Juliano A.
Published: March 2022

A metal‐ and catalyst‐free photo‐promoted cyclization of properly substituted vinyl selenides was developed using UVA irradiation. A total of eighteen new C3‐unsubstituted 2‐selanyl benzochalcogenophenes (benzofurans, benzothiophenes and benzoselenophenes) were prepared in 30–86% yield after irradiation with UVA at room temperature. The usefulness of the title compounds was demonstrated in the easy functionalization of the remaining free C−H bond of the benzochalcogenophenes to form new C−Se and C−Br bonds by simple procedures. Furthermore, the reaction can be performed under natural sunlight irradiation and the solvent is easily reused further in several subsequent runs.
Amorphous CoV Phosphate Nanosheets as Efficient Oxygen Evolution Electrocatalyst
Authors: Dong Yuming , Zhao Tao , Zhong Dazhong , Liu Guang , Hao Genyan , Li Jinping , Zhao Qiang
Published: March 2022

The oxygen evolution reaction (OER) is crucial for hydrogen production. However, OER with four‐electron transfer requires electrocatalysts to speed up its sluggish kinetics in alkaline solutions. Herein, amorphous CoV phosphate (denoted as CoV−Pi) nanosheets synthesized by a straightforward one‐step hydrothermal approach is reported, which provide a low overpotential of 320 mV at 10 mA cm−2, a small Tafel slope down to 48.8 mV dec−1 and long‐term durability over 80 h. The efficient activity is ascribed to the amorphous nanosheets structure, high electrochemically active surface area, enhanced surface wettability and the synergistic effect of the active metal atoms. This study significantly indicates that CoV−Pi is a promising alternative to replace expensive noble metal‐based catalysts for electrochemical water splitting.
Wait, did I do that? Effects of previous decisions on moral decision‐making
Authors: Frechen Niklas , Brouwer Susanne
Published: March 2022

Previous studies have investigated moral decision‐making by using moral dilemmas that involve a single decision. This article extends this paradigm, introducing two‐stage scenarios to examine how moral decision‐making is influenced by previous decisions in the same narrative—especially whether people tend to stay consistent or to reconsider within a morally challenging situation. It further compares decision‐making between two‐stage and one‐stage scenarios. In Study 1 (N = 239), participants read scenarios requiring two successive decisions of harming one person to spare multiple people (utilitarian action), or vice versa (deontological action), within the same narrative. Second decisions were mostly found to be consistent with first decisions. Remarkably, inconsistent responding (switching) was robustly observed in about 29% of cases. Study 2 (N = 63), using one‐stage scenarios, showed that having made a previous decision in the same narrative generally decreased utilitarian responding. Potential explanations for these phenomena are discussed. The present article concludes that prior choices within the same setting significantly influence decision‐making. It also reveals the potential of gaining new insights using multiple‐stage scenarios in moral decision‐making research.
Favipiravir (SARS‐CoV‐2) degradation impurities: Identification and route of degradation mechanism in the finished solid dosage form using LC/LC–MS method
Authors: Vemuri Divya Kumar , Gundla Rambabu , Konduru Naresh , Mallavarapu Ravindra , Katari Naresh Kumar
Published: March 2022

Favipiravir finished dosage was approved for emergency use in many countries to treat SARS‐CoV‐2 patients. A specific, accurate, linear, robust, simple, and stability‐indicating HPLC method was developed and validated for the determination of degradation impurities present in favipiravir film‐coated tablets. The separation of all impurities was achieved from the stationary phase (Inert sustain AQ‐C18, 250 × 4.6 mm, 5‐μm particle) and mobile phase. Mobile phase A contained KH2PO4 buffer (pH 2.5 ± 0.05) and acetonitrile in the ratio of 98:2 (v/v), and mobile phase B contained water and acetonitrile in the ratio of 50:50 (v/v). The chromatographic conditions were optimized as follows: flow rate, 0.7 mL/min; UV detection, 210 nm; injection volume, 20 μL; and column temperature, 33°C. The proposed method was validated per the current International Conference on Harmonization Q2 (R1) guidelines. The recovery study and linearity ranges were established from the limit of quantification to 150% optimal concentrations. The method validation results were found to be between 98.6 and 106.2% for recovery and r2 = 0.9995–0.9999 for linearity of all identified impurities. The method precision results were achieved below 5% of relative standard deviation. Forced degradation studies were performed in chemical and physical stress conditions. The compound was sensitive to chemical stress conditions. During the study, the analyte degraded and converted to unknown degradation impurities, and its molecular mass was found using the LC–MS technique and established degradation pathways supported by reaction of mechanism. The developed method was found to be suitable for routine analysis of research and development and quality control.
Aligning digitalisation and sustainable development? Evidence from the analysis of worldviews in sustainability reports
Authors: Niehoff Silke
Published: March 2022

The digitalisation of industrial production and the actual positive and negative consequences for sustainable development are not yet sufficiently understood. This study describes and evaluates the linkages between corporate digitalisation and sustainability management based on qualitative data analysis of sustainability reports of DAX 30 companies and applying the concept of sustainability worldviews. The results show a predominate worldview of weak or business‐centred sustainability on digitalisation, which could potentially pose a threat to sustainable development. In particular, the focus on customer demands without stakeholder involvement and the worldview of digitalisation as a way of doing ‘business as‐usual’ but in a more effective way reproduces unsustainable economic patterns. A holistic sustainable approach on digitalisation should also include possible negative impacts like increased resource consumption which is not the case yet in the studied companies. Different types of ‘sustainability worldviews on digitalisation’ can be distinguished. While ‘Pioneer’ companies can inform policy‐making, the other types of ‘Intermediates’, ‘Indecisive’ and ‘Laggards’ could be addressed by information exchange, support and regulation to promote a more sustainable worldview on corporate digitalisation. The ‘Unsustainable’ digitalisation type would be the most difficult to address with soft policy instruments and requires a more regulated approach.
Hypoxia and reperfusion injury are not associated with subdural haemorrhages in young children: A retrospective study of drowning victims, with and without return of spontaneous circulation
Authors: Lopez Nicholas , Quan Linda , Feldman Kenneth
Published: March 2022

Despite lack of an evidence basis, the hypothesis that hypoxia causes subdural haemorrhage (SDH) continues to be raised. Recently, the hypothesis included reperfusion after cardiac arrest as a cause of SDH. To determine the incidence of SDH in children under four years old following severe hypoxia and subsequent reperfusion, fatal drownings in children under four years old who were autopsied between 1974 through 1995 in the Western Washington Drowning Database were reviewed. A total of 88 drowning deaths were identified. Their median age was 2.0 years; 11 per cent (10/88) were under one year old. Fifty‐three per cent (47/88) died in the field and 47 per cent (41/88) had temporary return of spontaneous circulation. SDH was identified in none of the children. Intracranial haemorrhage was identified in two children: subarachnoid haemorrhage was found in a neonate who drowned right after birth; the second was an epidural bleed directly below a surgical burr hole. This study provides additional evidence that SDH is not caused by severe hypoxia and reperfusion events.
One‐Pot Synthesis and in Silico Molecular Docking Studies of Arylselanyl Hydrazides as Potential Antituberculosis Agents
Authors: Borges Elton L. , Goulart Helen A. , Perin Gelson , Schneider Paulo H. , Rieder Guilherme S. , Nogara Pablo A. , da Rocha João B. T.
Published: March 2022

The present study reports a simple two‐step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H3PO2/PEG‐400) as an alternative reducing system and hydrazine hydrate (NH2NH2⋅xH2O/50–60 %). This single‐vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3‐(arylselanyl)propane‐hydrazides 4a–e and 2‐(arylselanyl)acetohydrazides 5a–e with good yields by accelerating the reduction of −Se−Se− bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH). Therefore, we perform in silico molecular docking studies, using the lactoperoxidase enzyme, in order to verify whether the INH Se derivatives could interact in a similar way to INH at the active site of the mammalian enzyme. The in silico results indicated a similar type of interaction of the arylselanyl hydrazide derivatives with that of INH. In view of the similar in silico interaction of the selenium derivatives of INH, the arylselanyl hydrazide derivatives reported here should be tested against Mycobacterium tuberculosis in vitro.
In Vivo Efficacy, Mechanistic Study and Synergistic Interaction of Precocene II with Norfloxacin against Methicillin‐Resistant Staphylococcus aureus
Authors: Agarwal Karishma , Sinha Sneha , Parmanand  , Rani Mina Pooja , Verma Surendra Chandra , Swaroop Verma Ram , Tandon Sudeep , Pal Anirban , Pandurang Darokar Mahendra , Gupta Atul
Published: March 2022

Ageratum conyzoides L. (Asteraceae) possesses wound healing, antimicrobial, and anti‐inflammatory activities. Traditionally, this plant is used in skincare. The essential oil (EO) of A. conyzoides aerial parts contains the chromenes precocene I (1) and precocene II (2) as major constituents. This study evaluated precocene II (2) for its in vivo efficacy, mechanistic analysis, and synergistic interaction with norfloxacin against methicillin‐resistant Staphylococcus aureus (MRSA). The study showed that 2 interacted synergistically (Fractional Inhibitory Concentration Index, FICI≤0.5) with norfloxacin and oxacillin and reduced their MIC values significantly. These observations were further validated using the mice model and showed a significant reduction in bacterial load at much lower doses of 2 and norfloxacin without toxicity at 200 mg/kg body weight. Mechanistic studies revealed that 2 regulates bacterial resistance against clinical isolates of S. aureus through membrane disturbance in a dose‐ and time‐dependent manner. Further, precocene II (2) damaged the membrane of the bacteria, as observed from the increased membrane depolarization and uptake of propidium iodide. It also displayed high selectivity towards S. aureus over mammalian cell lines. The in vitro results highlighted the synergistic activity of 2 through the cell membrane damage without any detrimental effect on mammalian cells. In vivo results showed that 2 in combination with norfloxacin significantly reduced bacterial load at much lower concentrations through synergistic interaction without apparent toxicity.
Anti‐Tyrosinase Compounds from the Deep‐Sea‐Derived ActinomyceteGeorgeniasp. 40DY180
Authors: Chen Jianwei , Wang Siqi , Xu Yiming , Zhang Huawei , Wang Hong
Published: March 2022

With the aim of finding new marine‐derived skincare promoters, an assay‐guided approach was employed to discover tyrosinase‐modulating compounds from marine actinomycete. Here we describe a new 2,5‐piperazinedione, named georgenione A (1), together with two previously described compounds, 5‐(4’‐hydroxybenzyl)hydantoin (2) and cyclo(Trp‐Gly) (3), produced by actinomyceteGeorgeniasp. 40DY180, isolated from deep‐sea sediments collected in the Pacific Ocean. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR and high‐resolution mass spectrometric data. 5‐(4’‐hydroxybenzyl)hydantoin (2) displayedin vitropotent anti‐tyrosinase activity with IC50value of 36 μM, comparable to the commercially used positive control kojic acid (IC50=46 μM) and arbutin (IC50=100 μM). Compounds1–3were firstly reported from marine actinomyceteGeorgeniasp.
Artemisinin and l‐carnitine combination therapy alters the erythrocytes redox status
Authors: Basaki Mehdi , Hashemvand Akbar , Tayefi‐Nasrabadi Hossein , Panahi Yousef , Dolatyarieslami Mahdi
Published: March 2022

Hematopoiesis is a sensitive target of artemisinin (ART) and its derivatives, and hemolysis is one of their commonly reported side effects. l‐carnitine (LC), an amino acid derivative involved in lipid metabolism, is beneficial for hematological parameters. Sixty adult laboratory mice were randomly divided into six groups. Group I (control) received saline and corn oil; groups II and III received therapeutic (50 mg/kg) and toxic (250 mg/kg) doses of ART, respectively; groups IV and V received 370 mg/kg LC along with the 50 and 250 mg/kg ART, respectively; and group VI received 370 mg/kg LC. Drugs were administered orally for 7 consecutive days. The erythrocyte glucose 6‐phosphate dehydrogenase (G6PD), catalase (CAT), and peroxidase (POX) activity, and the reduced glutathione (GSH) level were assessed by colorimetric methods. ART reduced the G6PD activity both at therapeutic and toxic doses. The therapeutic dose of ART reduced the CAT activity and the GSH level, nonsignificantly. The toxic dose of ART reduced the CAT activity and increased the POX activity. LC reduced the G6PD, CAT, and POX activities and increased GSH level. The therapeutic dose of ART and LC showed synergy in reducing the G6PD activity. LC and ART combination reduced POX activity and increased GSH level without any significant effect on the CAT activity. Inhibition of G6PD may be a potentially new mechanism of ART action. Coadministration of LC with ART or following treatment with ART may have protective effects on erythrocytes.
Sporadic adult‐onset brainstem hyperkalemic periodic paralysis masquerading as recurrent transient ischemic attacks
Authors: Liang Kathryn M.A. , Liang Bertrand C.
Published: March 2022

We report a case of adult‐onset, sporadic, hyperkalemic periodic paralysis with primary brainstem musculature symptoms masquerading as recurrent transient ischemic attacks. Unilateral brainstem weakness could be induced with rapid eye blinking, which was followed by lower extremity weakness and cramping. Treatment with acetazolamide and albuterol ameliorated the patient's attacks.
Fadenzug von Heißklebstoffen beim Raupenauftrag
Authors: Todorovic Mira , Fürtauer Siegfried , Hoffmann Udo , Burth Dirk , Sängerlaub Sven
Published: March 2022

Fadenzug ist ein immer wieder vorkommendes, unerwünschtes Phänomen bei Schmelzklebstoffen, die durch Raupenauftrag appliziert werden. Der Fadenzug acht verschiedener Heißklebstoffe für verpackungsrelevante Anwendungen wurde bei verschiedenen Temperaturen und Abständen von Düsenkopf und Trägermaterial sowie mit unterschiedlichen Düsenarten analysiert. Größere Abstände führten in den meisten Fällen zu längeren Fäden. Für den Einfluss der Temperatur und der Viskosität wurden keine eindeutigen Korrelationen gefunden. Die Verwendung von Nadelsitzventilen führte zu weniger Fadenzug im Vergleich zu Kugelsitzventilen. Die Düsengröße hatte keinen Einfluss. Es konnte für alle Klebstoffe eine Kombination von Messbedingungen gefunden werden, bei der kein bzw. kaum Fadenzug auftrat. Erfahrungsgemäß sind diese oft nicht optimal für die Applikation und die Eigenschaften des Klebstoffs.
Mastocytosis presenting with mast cell‐mediator release‐associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features
Authors: Rama Tiago Azenha , Morgado José Mário , Henriques Ana , Escribano Luis , Alvarez‐Twose Iván , Sanchez‐Muñoz Laura , Moreira André , Romão José , Órfão Alberto , Matito Almudena
Published: March 2022

Background

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo‐oxygenase (COX), subsequent depletion of prostaglandin E2 and release of leukotrienes.

Objectives

Here, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease.

Methods

Medical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings.

Results

Overall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR.

Conclusions

Our results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX‐2 inhibitor, while the remaining may be challenged with ibuprofen.
A new metric for feature selection on short text datasets
Authors: Cekik Rasim , Uysal Alper Kursat
Published: March 2022

In recent years, short texts are everywhere, especially in social media networks. Short text classification is an essential task for various applications related to the operations on short text documents. In many cases, using the entire feature set causes the high dimensionality problem in short text data. This problem reason of time‐consuming and negatively impacts the performance of classifiers. This study presents an effective feature selection algorithm called XY method, which represents the features on XY line and calculates the distance of a feature to the XY line. Also, a value named λ is calculated. According to this value, the terms are divided into different regions such as negative, positive, and third to determine their discrimination capability. The novel XY method aims to select as few terms as possible in the negative region. The proposed method is evaluated using four different short text datasets with Macro‐F1 success measure. In comparisons with other existing feature selection algorithms such as chi‐square, information gain, deviation from Poisson distribution, recently proposed max‐min ratio, and distinguishing feature selector demonstrate that the XY method achieves either better or competitive performance in significantly reduced various feature sizes.
Heterogeneous reconfigurable architectures for machine learning dataflows
Authors: Oliveira Westerley C. , Canesche Michael , Reis Lucas , Nacif José Augusto M. , Ferreira Ricardo S.
Published: March 2022

This work explores the placement and routing of machine learning applications' dataflow graphs on different heterogeneous coarse‐grained reconfigurable architectures (CGRA). We analyze three different types of processing element (PE) heterogeneity, the first concerning the interconnection pattern, the second being on the kind of operations a single PE can execute, and the last concerning the PE buffer resources. This analysis aim to propose a fair reduction to the overall cost in comparison to the homogeneous CGRA architecture. We compare our results with the homogeneous case and one of the state‐of‐the‐art tools for placement and routing (P&R). Our algorithm executed, on average, 52% faster than VPR 8.1 (Versatile Place and Route), which is an open‐source academic tool designed for the FPGA placement and routing phases, reaching better mapping in 66% of cases and achieving the same results in 26% of cases. Furthermore, a heterogeneous architecture reduces the cost without losing performance in 76% of the cases considering multiplier heterogeneity. We propose a novel heterogeneous buffer architecture that minimizes the buffer resources by 56.3% for K‐means dataflow patterns. We also show that a heterogeneous border chess architecture outperforms a homogeneous one. In addition, our mapping reaches optimal instances of single tree dataflows compared to classical Lee/Choi and H‐trees.
Effect of Electron Donating/Withdrawing Groups on Molecular Photoswitching of Functionalized Hemithioindigo Derivatives: a Computational Multireference Study
Authors: Lea Martin R. , Stavros Vasilios G. , Maurer Reinhard J.
Published: March 2022

Hemithioindigos are a versatile group of molecules with the ability to undergo double bond isomerisation upon light excitation. Using electronic structure theory, a detailed description of the photoisomerisation of hemithioindigo and five of its functionalized derivatives is reported. We use a combination of Density Functional Theory (DFT), approximate second order Coupled Cluster (CC2), and multireference methods such as the complete active space self‐consistent field (CASSCF) method to probe how isomerisation capabilities of functionalized hemithioindigo derivatives are affected by functionalisation with both electron donating and withdrawing groups. We demonstrate that important properties such as the thermal barrier, electronic absorption spectra and, to an extent, the mechanism can all show pronounced differences compared to the parent hemithioindigo molecule. Our results demonstrate how the inclusion of functional groups can have important effects on its photoisomerisation capabilities, which in turn, can influence the fate of these molecules upon light excitation and their utility as molecular switches.
How to Build an Image‐Processing Pipeline for Automating Multiparameter Histocytometry Analysis
Authors: Munoz‐Erazo Luis , Schmidt Alfonso J. , Shinko Diana , Price Kylie M.
Published: March 2022

Until relatively recently, analysis of imaging data has been primarily quantitative and limited to 3‐4 markers. The advancement of various technologies overcoming this marker limitation provided the capability of analyzing multiparameter imaging data down to the single cell level, termed histocytometry. Currently, most published end‐to‐end histocytometric analysis of imaging data is performed using expensive commercial programs or freely available analysis packages that require significant knowledge of programming languages for execution. Here we present a protocol that performs cell segmentation, phenotyping and spatial analysis, using software with easy‐to‐use GUIs (graphical user interfaces). These protocols allow the user to derive spatial and phenotypical data for the analysis of multiparameter microscopic images from most imaging platforms in a low‐cost manner. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Cell Segmentation and generation of histocytometric .csv file

Basic Protocol 2: Phenotyping of cell populations

Basic Protocol 3: Spatial relationship analyses of phenotyped populations

Support Protocol 1: Nuclei Segmentation Accuracy Test

Support Protocol 2: Correcting y‐axis Inversion of Histocytometry Data Relative to Original Image File
Fund managers acting as impact investors: Strategies, practices, and tensions
Authors: Bandini Federica , Chiappini Helen , Pallara Francesca
Published: March 2022

Using a multi case‐study analysis, we shed light on the strategies, practices, and tensions of fund managers acting as impact investors. Results show that while some fund managers experience tension between the social and financial aspects of specific, although relevant, components of the business model, other fund managers experience challenges throughout the business model. The governance component emerges as the most relevant issue and this may help explain why impact washing is a key topic in the impact investing discussion. Relevant implications for practitioners and policy makers are also discussed.
Butterflies teach beautiful lessons about leadership
Authors: Hodges Dawn Z.
Published: March 2022

I have lived an hour away from Callaway Gardens in Georgia for over 20 years now. I've driven past the gates numerous times, but never stopped. Recently I coaxed my husband into taking me to the Cecil B. Day Butterfly Center in the Gardens. The center is 7,300 square feet with over 1,000 panes of glass and state‐of‐the‐art mechanical systems. According to the Center's website, it is home to more than 2,000 tropical butterflies of 50 different species, which fluctuate in diversity and density.
Program death ligand‐1 immunocytochemistry in lung cancer cytological samples: A systematic review
Authors: Satturwar Swati , Girolami Ilaria , Munari Enrico , Ciompi Francesco , Eccher Albino , Pantanowitz Liron
Published: March 2022

In this era of personalized medicine, targeted immunotherapies like immune checkpoint inhibitors (ICI) blocking the programmed death‐1 (PD‐1)/program death ligand‐1 (PD‐L1) axis have become an integral part of treating advanced stage non‐small cell lung carcinoma (NSCLC) and many other cancer types. Multiple monoclonal antibodies are available commercially to detect PD‐L1 expression in tumor cells by immunohistochemistry (IHC). As most clinical trials initially required tumor biopsy for PD‐L1 detection by IHC, many of the currently available PD‐1/PD‐L1 assays have been developed and validated on formalin fixed tissue specimens. The majority (>50%) of lung cancer cases do not have a surgical biopsy or resection specimen available for ancillary testing and instead must rely primarily on fine needle aspiration biopsy specimens for diagnosis, staging and ancillary tests. Review of the literature shows multiple studies exploring the feasibility of PD‐L1 IHC on cytological samples. In addition, there are studies addressing various aspects of IHC validation on cytology preparations including pre‐analytical (e.g., different fixatives), analytical (e.g., antibody clone, staining platforms, inter and intra‐observer agreement, cytology‐histology concordance) and post‐analytical (e.g., clinical outcome) issues. Although promising results in this field have emerged utilizing cytology samples, many important questions still need to be addressed. This review summarizes the literature of PD‐L1 IHC in lung cytology specimens and provides practical tips for optimizing analysis.
Influence of catheter ablation for atrial fibrillation on atrial and ventricular functional mitral regurgitation
Authors: Masuda Masaharu , Sekiya Kimiko , Asai Mitsutoshi , Iida Osamu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Kanda Takashi , Tsujimura Takuya , Matsuda Yasuhiro , Hata Yosuke , Uematsu Hiroyuki , Toyoshima Taku , Higashino Naoko , Mano Toshiaki
Published: March 2022

Aims

The purpose of this study was to compare the impact of catheter ablation on cardiac structural reverse remodelling and atrial (AFMR) and ventricular (VFMR) functional mitral regurgitation (MR), and the long‐term prognosis of patients with AFMR and VFMR.

Methods and results

The retrospective study included persistent AF patients who had AFMR (n = 136, left atrial (LA) volume index >30 mL/m2 and left ventricular (LV) ejection fraction ≥40%) or VFMR (n = 31, LV ejection fraction <40% or LV regional asynergy) and had undergone the initial AF ablation from April 2015 to December 2019. Baseline and 6 month follow‐up echocardiography were performed to assess MR, LA, and LV sizes. MR improvement after ablation was comparable in the AFMR (64%) and VFMR groups (52%, P = 0.20). Patients with AFMR improvement showed a greater decrease in left atrial volume after ablation than those without (amount of change: −11.4 ± 15.1 vs. −2.3 ± 21.1 mL/m2, P = 0.01). Patients with VFMR improvement showed a greater increase in LV ejection fraction than those without (amount of change: 28.5 ± 13.6% vs. 9.0 ± 14.8%, P = 0.001). The composite endpoint of all‐cause death and heart failure hospitalization during the 2 year follow‐up period was more frequently observed in the VFMR than in the AFMR group (22.6% vs. 3.7%, P < 0.0001). Patients with MR improvement after catheter ablation less frequently demonstrated the composite endpoint than those without (1.9% vs. 15.6%, P < 0.0001).

Conclusions

Atrial functional mitral regurgitation and VFMR improvement after ablation were associated with atrial and ventricular reverse remodelling, respectively. It is possible that long‐term prognosis is better in patients with AFMR than with VFMR, and in those with MR improvement than in those without.
The association of improvement in left ventricular ejection fraction with outcomes in patients with heart failure with reduced ejection fraction: data from CHAMP‐HF
Authors: DeVore Adam D. , Hellkamp Anne S. , Thomas Laine , Albert Nancy M. , Butler Javed , Patterson J. Herbert , Spertus John A. , Williams Fredonia B. , Shen Xian , Hernandez Adrian F. , Fonarow Gregg C.
Published: March 2022

Aims

We assessed for an association between improvements in left ventricular ejection fraction (LVEF) and future outcomes, including health status, in routine clinical practice.

Methods and results

CHAMP‐HF was a registry of outpatients with heart failure (HF) and LVEF ≤40%. Enrolled participants completed the Kansas City Cardiomyopathy Questionnaire‐12 (KCCQ‐12) at regular intervals and were followed as part of routine care. We assessed for associations between improvements in LVEF (≥10%) over time and concurrent changes in KCCQ‐12, as well as the subsequent risk of poor outcomes. We included 2092 participants in the study. They had the following characteristics: median age 67 years (25th–75th percentile 58–75), 29% female, median duration of HF 2.7 years (0.6–6.8), and median baseline LVEF 30% (23–35). Of the study participants, 689 (33%) had a ≥10% absolute improvement in LVEF. Participants with an LVEF improvement also had an improvement in KCCQ‐12 overall summary score compared with participants without an LVEF improvement (+7.6 vs. +3.5, adjusted effect estimate +4.01 [95% confidence interval CI 2.3–5.7]). Similarly, subsequent all‐cause death or HF hospitalization occurred in 12% in the LVEF improvement group versus 25% in the group without an LVEF improvement (adjusted hazard ratio 0.50, 95% confidence interval 0.41–0.61).

Conclusion

In a large cohort of outpatients with chronic HF, improvements in LVEF were associated with improved health status and a reduced risk for future clinical events. These data underscore the importance of improvement in LVEF as a treatment target for medical interventions for patients with chronic HF.
Palladium(II)‐Catalyzed Direct Arylations of Quinoxalin‐2(1H)‐ones with Arylsulfonyl Chlorides
Authors: Nale Sagar D. , Datta Khanal Hari , Rok Lee Yong
Published: March 2022

A palladium‐catalyzed desulfitative coupling of quinoxalin‐2(1H)‐ones with arylsulfonyl chlorides is described. C3‐Arylquinoxalin‐2(1H)‐ones are readily accessible by reacting various arylsulfonyl chloride derivatives with quinoxalin‐2(1H)‐ones. The arylsulfonyl chloride undergoes palladium‐catalyzed C−S and S−Cl bond cleavage, which leads to direct desulfitative cross‐coupling with the quinoxalin‐2(H)‐one. Chloro‐ and fluoro‐aryl sulfonyl chlorides are successfully coupled with quinoxalin‐2(1H)‐ones without carbon–halogen bond cleavage.
Efficacy and safety of botulinum A toxin for the treatment of chronic peripheral neuropathic pain: A systematic review of randomized controlled trials and meta‐analysis
Authors: Hary Vincent , Schitter Sebastien , Martinez Valeria
Published: March 2022

Background and Objective

Botulinum toxin type A (BTX‐A) is a recently developed treatment for the management of peripheral neuropathic pain. The objective of this study was to provide a synthesis of the evidence concerning the efficacy and safety of subcutaneous botulinum toxin type A injections.

Databases and Data Treatment

We searched the MEDLINE, EMBASE, LILACS, Cochrane, and Clinical Trial Register databases for randomized controlled trials comparing subcutaneous BTX‐A to placebo injections for treating chronic peripheral neuropathic pain. The primary endpoint was the assessment of pain 1 month after the injection. The secondary outcomes were the assessment of pain at 3 months, neuropathic pain intensity and quality of life at 1 and 3 months, and adverse effects. A random‐effect meta‐analysis was performed on the combined data. Evidence quality was rated by the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method.

Results

Ten randomized controlled trials including 505 patients were included in this review (registration number CRD42021239108). At 1 and 3 months after injection, the BTX‐A groups had a lower mean difference (MD) in pain score (MD −1.87 (confidence intervals [CIs] −2.91; −0.83) and −1.38 (CI −1.95; −0.81), respectively). Subgroup analysis showed greater efficacy for diabetic polyneuropathy (MD −2.48, [−3.22; −1.74]). We found no impact of BTX‐A on quality of life and no difference in adverse effect between BTX‐A and placebo. The evidence was considered of moderate quality.

Conclusion

The pooled data suggest that subcutaneous BTX‐A injections have a clinically significant effect, decreasing pain for three months after the injection, but no benefit in terms of quality of life has yet been demonstrated.

Significance

We found that botulinum toxin is efficient and safe for the treatment of neuropathic pain, especially for diabetic polyneuropathy. Botulinum toxin type A, used for years in neurology, rehabilitation and physical medicine, has proved innocuous and effective, and should be considered as a serious alternative for pain treatment.
Electrochemiluminescence DNA Biosensor for HBV Based on Coralloid Poly(Aniline‐Luminol)‐MWCNTs and Catalysis of Ferrocene
Authors: Dong Ruirui , Zhang Yanhui , Huang Jiali , Habibul Marhaba , Li Guixin
Published: March 2022

A novel electrochemiluminescence biosensor was presented for the assay of hepatitis B virus (HBV) DNA. Coralloid poly(aniline‐luminol)‐MWCNTs was prepared on an electrode surface, which was followed by the attachment of capture DNA via amide bond formation. The HBV‐DNA and ferrocene labelled DNA hybridized with capture DNA to form a sandwich structure on electrode surface. Ferrocene can effectively increase the signal output of the ECL sensor due to the catalysis of ferrocene on electrochemiluminescence of luminol. The biosensor rendered a linear dependence over the range from 1.0×10−16 to 1.0×10−7 M with a low detection limit of 2.4×10−17 M.
Electrochemical hydrogen generation technology: Challenges in electrodes materials for a sustainable energy
Authors: Inocêncio Carlos V. M. , Holade Yaovi , Morais Claudia , Kokoh K. Boniface , Napporn Teko W.
Published: March 2022

Foresee advanced and innovative strategies is a key approach and constitutes a cornerstone for accessing clean, affordable, and reliable energy to satisfy the world's increasing prosperity and economic growth. To this end, hydrogen energy technologies parade as promising sustainable solutions to the looming energy crisis at either the small or large industrial scale, which will enable to reduce significantly our dependence on conventional energy sources based on fossil fuels without increasing atmospheric CO2 levels. Water electrolysis with renewable energy is one of the best solutions to produce hydrogen without COx (CO and CO2) emissions. However, the practical realization of this elegant opportunity of paramount importance is facing several challenges, among which are: (i) the efficient design of cathode and anode catalytic materials exhibiting improved intrinsic and durable activity; (ii) the scale‐up of the system for the large‐scale hydrogen production through the electrochemical water splitting. This review puts these opportunities and challenges into a broad context, discusses the recent research and technological advances, and finally provides several pathways and guidelines that could inspire the development of groundbreaking electrochemical devices for hydrogen production. It also points out the materials design and preparation for the efficient electrochemical production of the molecular hydrogen in acidic and alkaline environments, from a simple electrolytic solution to the water splitting reaction, which is also considered in the process. Furthermore, the main technology keys for designing a reliable electrochemical system will be noticed.
Create engaging ‘digital swag’ to connect with and yield prospective students
Authors: Taylor Zachary , Childs Joshua
Published: March 2022

In no uncertain terms, the COVID‐19 pandemic has changed how enrollment management offices recruit prospective students. Given the effect COVID‐19 had on travel, many enrollment management offices and admissions teams were grounded, meaning that admissions counselors needed to connect with prospective students and their families through digital technologies, including on streaming video platforms and social media.
Refertilization of depleted mantle peridotite in the Nagaland–Manipur ophiolite, north‐east India: Constraints from PGE, mineral, and whole‐rock geochemistry
Authors: Chaubey Monika , Singh Athokpam Krishnakanta , Singh Birendra P. , Imtisunep Sashimeren , Dutt Amrita , Satyanarayanan Manavalan , Premi Kshetrimayum , Abhirami Sethuraman G.
Published: March 2022

This paper discusses whole‐rock geochemistry, mineral chemistry, and platinum group element (PGE) systematics of depleted mantle rocks (harzburgite and dunite) from the northern part of Nagaland–Manipur Ophiolite (NMO), north‐east India, to comprehend their source features, fractionation behaviour of PGE during magmatic evolution, and its tectonic origin. The studied ultramafic rocks are characterized by a low concentration of CaO (0.57–0.71 wt%), Al2O3 (0.18–0.92 wt%) with ∑REE of 1.135–2.702 ppm and high concentrations of MgO (38.70–44.21 wt%), Cr (1,843–4,572 ppm), and Ni (894–4,138 ppm). They show U‐shaped REE patterns [LREE and HREE enrichment (La/Sm)N = 1.85–4.11, (Dy/Yb)N = 0.51–0.85]. Olivine ranges Fo 88.18 to Fo92.23, whereas Cpx and Opx range En44.84 to En47.89 and En86.37 to En93.37 respectively. The chrome spinel Cr# [Cr/(Cr + Al)] and Mg# [Mg/(Mg + Fe2+)] are 0.47–0.83 and 0.31–0.60, respectively, which indicates recrystallization from a boninitic magma in a Supra‐Subduction Zone setting. Conventional thermometry indicates the equilibration temperatures of the dunite sample yielded high temperatures of ~850°C, suggesting their formation due to later interaction with high‐temperature percolating melts. The PGE contents in harzburgite are low (125.6–142.8 ppb) as compared to the dunite (248–360 ppb). They have high PPGE/IPGE and negative Pt* (Pt/Pt* = 0.73) anomaly, which is characteristic of re‐entry of PPGE into the system via reaction with percolating basaltic melt in the mantle wedge. Significantly higher concentration of PPGEs than IPGEs in the samples, indicating recrystallization of PPGEs with early sulphide fractionation. The presence of significant Rh and Pd enhancements relative to Pt in all samples suggests that Pt was removed during PGE fractionation. This could be one of the reasons for both harzburgite and dunite's sulphide undersaturation. PGE distribution in NMO ultramafic rocks was therefore validated as being governed by sulphide saturation in parental magma and altered not only by partial melting but also by fractionation during their production in the Supra‐Subduction Zone environment.
Early‐life famine exposure, hunger recall, and later‐life health
Authors: Deng Zichen , Lindeboom Maarten
Published: March 2022

We use newly collected individual‐level hunger recall information from the China Family Panel Survey to estimate the causal effect of undernourishment on later‐life health. We develop a two‐sample instrumental variable (TSIV) estimator that can deal with heterogeneous samples. We find a nonlinear relationship between mortality rates, a commonly used famine indicator, and the individual hunger experience. The nonlinearity in famine exposure may explain the variation in the famine's effect on later‐life health found in previous studies. We also find that exposure to hunger early in life leads to worse health among females 50 years later. This effect is much larger than the reduced‐form effect found in previous studies. For males, we find no impact.
miRNA‐34c Suppresses Osteosarcoma Progression In Vivo by Targeting Notch and E2F
Authors: Bae Yangjin , Zeng Huan‐Chang , Chen Yi‐Ting , Ketkar Shamika , Munivez Elda , Yu Zhiyin , Gannon Francis H. , Lee Brendan H.
Published: March 2022

The expression of microRNAs (miRNAs) is dysregulated in many types of cancers including osteosarcoma (OS) due to genetic and epigenetic alterations. Among these, miR‐34c, an effector of tumor suppressor P53 and an upstream negative regulator of Notch signaling in osteoblast differentiation, is dysregulated in OS. Here, we demonstrated a tumor suppressive role of miR‐34c in OS progression using in vitro assays and in vivo genetic mouse models. We found that miR‐34c inhibits the proliferation and the invasion of metastatic OS cells, which resulted in reduction of the tumor burden and increased overall survival in an orthotopic xenograft model. Moreover, the osteoblast‐specific overexpression of miR‐34c increased survival in the osteoblast specific p53 mutant OS mouse model. We found that miR‐34c regulates the transcription of several genes in Notch signaling (NOTCH1, JAG1, and HEY2) and in p53‐mediated cell cycle and apoptosis (CCNE2, E2F5, E2F2, and HDAC1). More interestingly, we found that the metastatic‐free survival probability was increased among a patient cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) OS, which has lower expression of direct targets of miR‐34c that was identified in our transcriptome analysis, such as E2F5 and NOTCH1. In conclusion, we demonstrate that miR‐34c is a tumor suppressive miRNA in OS progression in vivo. In addition, we highlight the therapeutic potential of targeting miR‐34c in OS. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.