bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and treatment of hemophagocytic lymphohistiocytosis in hospitalized children with Ehrlichia infection
Authors: Cabler Stephanie S. , Hogan Patrick G. , Fritz Stephanie A. , Bednarski Jeffrey J. , Hunstad David A.
Published: July 2020

We report a large cohort of pediatric patients with human monocytic ehrlichiosis (HME), enabling an estimated incidence of secondary hemophagocytic lymphohistiocytosis (HLH) in hospitalized children with HME. Among 49 children with PCR‐confirmed Ehrlichia infection, 8 (16%) met current criteria for HLH. Those with HLH had more significant hematologic abnormalities and longer durations from symptom onset to admission and definitive anti‐infective therapy. Among these eight, three received chemotherapy plus doxycycline, one of whom died; the other five were treated with doxycycline without chemotherapy, and all survived without HLH recurrence. Our findings demonstrate that antimicrobial therapy alone can successfully resolve Ehrlichia‐associated HLH.
Interventional radiotherapy (brachytherapy) achieves very good long‐term quality of life in children and adolescents with soft‐tissue sarcoma
Authors: Sütterlin Anna Lotte , Demmert Martin , Kovács György , Claviez Alexander , Schulz Christian , Lauten Melchior
Published: July 2020

Background

Effective local therapy (surgery, radiation) and systemic multidrug chemotherapy are mandatory for curing childhood sarcoma. The standard radiation therapy for pediatric patients with soft‐tissue sarcoma (STS) is external beam radiotherapy (EBRT). Because EBRT may cause long‐term side effects with adverse effects on the patients’ health and quality of life (QoL), alternative strategies are required. Interventional radiotherapy (IRT; brachytherapy) is established as a standard treatment for several tumors in adulthood. Single‐center series have reported low levels of late effects and improved QoL in survivors treated with IRT in childhood. However, IRT is still applied infrequently in pediatric patients.

Methods

Thirty patients with STS were treated with IRT between 1992 and 2012 at the University Hospital Schleswig Holstein, Germany. Five patients were lost to follow‐up, and 25 patients (mean age at time of data collection 24.8 years [range, 10.7‐36.1]) could be analyzed focusing on overall survival and QoL (EORTC‐C30 questionnaire). For more detailed information regarding general and health‐specific questions, a separate questionnaire was developed.

Results

Nineteen of 25 patients were alive 13.4 [1.6‐25.2] years after first cancer disease, and the three‐year overall survival was 76% (SE, 0.09). The score of QoL/global health status (76.2 [16.6‐100]) in our patients outvalues the European (66.1) and equals the German (75.9) reference value.

Conclusion

IRT is an effective treatment option for pediatric patients with localized STS. Its role among other radiation dose‐sparing techniques such as proton beam therapy has to be defined in prospective studies.
Undifferentiated sarcoma of the liver: Multicenter international experience of the Cooperative Soft‐Tissue Sarcoma Group and Polish Paediatric Solid Tumor Group
Authors: Murawski Maciej , Scheer Monika , Leuschner Ivo , Stefanowicz Joanna , Bonar Jolanta , Dembowska‐Bagińska Bożenna , Kaliciński Piotr , Koscielniak Ewa , Czauderna Piotr , Fuchs Jörg
Published: July 2020

Background

Undifferentiated embryonal sarcomas of the liver (UESL) are extremely rare and continue to pose a diagnostic and therapeutic challenge. The aim of the study was to present a multicenter experience of the German CWS and Polish PPSTG groups in the treatment of UESL in children.

Procedure

Twenty‐five patients were treated according to the CWS‐96, CWS‐2002, and CYVADIC protocols. Distant metastases were observed in four cases (16%). In four cases, an initial disease presentation mimicked other entities. A pure cystic appearance of liver mass led to misdiagnosis of hydatid cyst in three cases. In one case, laparotomy was performed due to the signs of appendicitis, and bleeding from ruptured liver tumor was found. All these patients were finally diagnosed as UESL.

Results

Thirteen patients received preoperative chemotherapy. Partial response was observed in 10 cases. Tumor resection was performed in 20 patients (primary resections, 12; delayed resections–, 8). In five patients, the primary tumor never became operable. The macroscopically complete resection rate was 95% (19/20). Postoperative chemotherapy was given to 20 children. Local radiotherapy was used in three children. After a median follow‐up time of 136 months, 17 patients (68%) were alive with no evidence of disease. All children with unresectable tumor and three out of four patients with distant metastases died. The five‐year overall survival (OS) rate was 72%.

Conclusions

In summary, a complete tumor excision plays the central role in the treatment of UESL. A cystic presentation of the liver lesion on imaging does not exclude the diagnosis of malignant tumor.
The state of the science for communication training in pediatric oncology: A systematic review
Authors: Kaye Erica C. , Cannone Daniel , Snaman Jennifer M. , Baker Justin N. , Spraker‐Perlman Holly
Published: July 2020

Within the field of pediatric oncology, communication skills training (CST) has been recognized as a high priority by professional and accrediting organizations. However, the effectiveness of formalized CST interventions for pediatric oncology providers remains poorly understood. We systematically searched PubMed, Web of Science, Scopus, and PsycInfo for original research articles assessing the effectiveness and quality of CST interventions targeting pediatric oncology clinicians. From 971 deduplicated references, eight articles representing six communication interventions were eligible for inclusion. This review summarizes the existing literature with respect to CST content, intervention methodology, targeted outcome metrics, measurement tools, short‐term and sustained benefits, design biases, and availability of materials to allow for reproduction of interventions. Ultimately, studies on CST in pediatric oncology are few, heterogeneous, and lacking in standardized outcome metrics; however, synthesis of the available literature suggests feasibility and effectiveness. Increased scientific rigor is needed, and specific recommendations to advance the field are described.
Analysis of plant secondary metabolism using stable isotope‐labelled precursors
Authors: Arroo Randolph R.J. , Bhambra Avninder S. , Hano Christophe , Renda Gülin , Ruparelia Ketan C. , Wang Meng F.
Published: July 2020

Introduction

Analysis of biochemical pathways typically involves feeding a labelled precursor to an organism, and then monitoring the metabolic fate of the label. Initial studies used radioisotopes as a label and then monitored radioactivity in the metabolic products. As analytical equipment improved and became more widely available, preference shifted the use stable ‘heavy’ isotopes like deuterium (2H)‐, carbon‐13 (13C)‐ and nitrogen‐15 (15N)‐atoms as labels. Incorporation of the labels could be monitored by mass spectrometry (MS), as part of a hyphenated tool kits, e.g. Liquid chromatography (LC)–MS, gas chromatography (GC)–MS, LC–MS/MS. MS offers great sensitivity but the exact location of an isotope label in a given metabolite cannot always be unambiguously established. Nuclear magnetic resonance (NMR) can also be used to pick up signals of stable isotopes, and can give information on the precise location of incorporated label in the metabolites. However, the detection limit for NMR is quite a bit higher than that for MS.

Objectives

A number of experiments involving feeding stable isotope‐labelled precursors followed by NMR analysis of the metabolites is presented. The aim is to highlight the use of NMR analysis in identifying the precise fate of isotope labels after precursor feeding experiments. As more powerful NMR equipment becomes available, applications as described in this review may become more commonplace in pathway analysis.

Conclusion and Prospects

NMR is a widely accepted tool for chemical structure elucidation and is now increasingly used in metabolomic studies. In addition, NMR, combined with stable isotope feeding, should be considered as a tool for metabolic flux analyses.
Effects of Co‐administration of Sulfonylureas and Antimicrobial Drugs on Hypoglycemia in Patients with Type 2 Diabetes Using a Case‐Crossover Design
Authors: Lee Sera , Ock Miyoung , Kim Hun‐Sung , Kim Hyunah
Published: July 2020

Objectives

The purpose of this study was to investigate the effect of sulfonylureas (SUs) and antimicrobial co‐administration on hypoglycemia in patients with type 2 diabetes mellitus (T2DM).

Methods

We conducted a case‐crossover study using the Korean Health Insurance Review and Assessment Service‐National Inpatient Sample database, using data from 2014 to 2016. Hospitalized adult patients with T2DM who were diagnosed with hypoglycemia and prescribed SUs for at least 120 days were included. Different risk ratings of severity of drug–drug interactions were considered, including “level X, D, or C” in Lexi‐Interact online and “contraindicated, major, or moderate” in Micromedex. Exposure to antimicrobials in the 30‐day period before the first hypoglycemia diagnosis was assessed. Two control periods (61–90 and 91–120 days) were matched before the diagnosis date. Conditional logistic regression analysis was conducted to compare the odds of antimicrobial exposure.

Results

A total of 9339 patients were included. The mean age of the patients was 71.3 ± 10.6 years, and 4818 (51.6%) were women. An increased risk of hypoglycemia was associated with co‐administration of SUs and certain antimicrobials (adjusted odds ratio [aOR] 2.56, 95% confidence interval [CI] 2.34–2.80). The antimicrobial agents that were associated with an increased risk of hypoglycemia, when co‐administered with SUs, were sulfonamides (aOR 2.99, 95% CI 1.99–4.52), fluoroquinolones (aOR 2.62, 95% CI 2.38–2.89), macrolides (aOR 2.48, 95% CI 1.88–3.27), and tetracyclines (aOR 1.56, 95% CI 1.05–2.33).

Conclusions

Co‐administration with SUs and certain antimicrobials increased the risk of hypoglycemia. Thus, clinically relevant interactions in patients concurrently using SUs and antimicrobials should be monitored, especially within 30 days after co‐administration.
Element content and distribution has limited, tolerance metric dependent, impact on salinity tolerance in cultivated sunflower (Helianthus annuus)
Authors: Temme Andries A. , Burns Victoria A. , Donovan Lisa A.
Published: July 2020

Disruption of ion homeostasis is a major component of salinity stress's effect on crop yield. In cultivated sunflower prior work revealed a negative relationship between vigor and salinity tolerance. Here, we determined the association of elemental content/distribution traits with salinity tolerance, both with and without taking vigor (biomass in control treatment) into account. We grew seedlings of 12Helianthus annuusgenotypes in two treatments (0, 100 mM NaCl). Plants were measured for biomass (+allocation), and element content (Na, P, K, Ca, Mg, S, Fe, B, Mn, Cu, Zn) in leaves (young and mature), stem, and roots. Genotype tolerance was assessed as both proportional decline of biomass and as expectation deviation (deviation from the observed relationship between vigor and proportional decline in biomass). Genotype rankings on these metrics were not the same. Elemental content and allocation/distribution were highly correlated both at the plant and organ level. Suggestive associations between tolerance and elemental traits were fewer and weaker than expected and differed by tolerance metric. Given the highly correlated nature of elemental content, it remains difficult to pinpoint specific traits underpinning tolerance. Results do show that taking vigor into account is important when seeking to determining traits that can be targeted to increase tolerance independent of vigor, and that the multivariate nature of associated traits should additionally be considered.
Promoting emotional wellness in children with CF, part II: Mental health assessment and intervention
Authors: Georgiopoulos Anna M. , Christon Lillian M. , Filigno Stephanie S. , Mueller Amy , Prieur Mary G. , Boat Thomas F. , Smith Beth A.
Published: July 2020

This is the second of two companion papers that examine the emotional wellness of children with cystic fibrosis (CF) during the early years of life, defined here as the period between birth and age 12. Both papers promote optimal mental health and well‐being, with an emphasis on early identification and intervention. The first paper explores child and family resilience. Here, we discuss strategies for pediatric CF teams to provide routine, systematic mental health assessment, anticipatory guidance, brief intervention, and triage to evidence‐based treatment when needed, while addressing barriers to accessing care. Many mental health conditions emerge before the age of 12, with the potential for lifelong effects on individuals, their families, and society. Living with a chronic illness such as CF can further increase the risk of mental health concerns and, in a bidirectional manner, their consequences for the quality of life, sustaining daily care, and health outcomes. There has been a significant focus in recent years on the mental health and wellness of adolescents and adults with CF, but less attention to specifics of depression and anxiety in younger children, or to other common pediatric comorbidities including trauma, developmental disorders such as attention‐deficit/hyperactivity disorder or autism spectrum disorder, and oppositional behavior. Given the availability of psychometrically sound screening instruments and effective interventions, routinely addressing the mental health of children with CF and their families is feasible to integrate within multidisciplinary CF care, allowing for a personalized approach respecting individual needs, values, and goals.
Multigrid preconditioners for the mixed finite element dynamical core of the LFRic atmospheric model
Authors: Maynard Christopher , Melvin Thomas , Müller Eike Hermann
Published: July 2020

Due to the wide separation of time‐scales in geophysical fluid dynamics, semi‐implicit time integrators are commonly used in operational atmospheric forecast models. They guarantee the stable treatment of fast (acoustic and gravity) waves, while not suffering from severe restrictions on the time‐step size. To propagate the state of the atmosphere forward in time, a nonlinear equation for the prognostic variables has to be solved at every time step. Since the nonlinearity is typically weak, this is done with a small number of Newton or Picard iterations, which in turn require the efficient solution of a large system of linear equations with unknowns. This linear solve is often the computationally most costly part of the model. In this article an efficient linear solver for the LFRic next‐generation model currently being developed by the Met Office is described. The model uses an advanced mimetic finite element discretisation which makes the construction of efficient solvers challenging as compared to models using standard finite‐difference and finite‐volume methods. The linear solver hinges on a bespoke multigrid preconditioner of the Schur‐complement system for the pressure correction. By comparing it to Krylov subspace methods, the superior performance and robustness of the multigrid algorithm is demonstrated for standard test cases and realistic model set‐ups. In production mode, the model will have to run in parallel on hundreds of thousands of processing elements. As confirmed by numerical experiments, one particular advantage of the multigrid solver is its excellent parallel scalability due to its avoidance of expensive global reduction operations.
A multireference configuration interaction study with singles and doubles of some mesoionic rings: reaction and activation free energies for the ring‐opening reaction
Authors: da Silva Filho Antônio João , de Santana Otávio Luís , do Monte Elizete Ventura , do Monte Silmar Andrade
Published: July 2020

For the first time, multireference configuration interaction with singles and doubles (MR‐CISD) calculations (including extensivity corrections, MR‐CISD+Q) have been performed to study the ring‐opening reactions of the following mesoionic rings and their 2, 3, and 4 methyl‐substituted derivatives: (a) 1,3‐oxazol‐5‐one, (c) 1,3‐oxazol‐5‐thiolate, and (d) 1,3‐thiazol‐5‐thiolate. The ring‐opening reaction of the parent 1,3‐thiazol‐5‐one mesoionic ring (b) has also been studied. The effect of methyl and S replacement on the reaction and activation free energies (ΔG and ΔG†, respectively) is studied. For a, the effect of methyl replacement on C2 is almost negligible, while on N3 and C4, it is significantly larger, especially in the latter position. The open structure (ketene form) of a is considerably more stable, and the replacement of the exocyclic O by S stabilizes the ketene tautomer even more and increases ΔG† considerably. On the other hand, replacement of the endocyclic O by S (yielding b) completely prevents the formation of the open structure, while replacement of both endo and exo atoms strongly stabilizes the cyclic structure and leads to a remarkably high value of ΔG†. In some cases, the relative polarity of the stationary points is used to estimate how ΔG and ΔG† are expected to change as one goes from the gas phase to aprotic polar solvents. A linear correlation between the multiconfigurational character of the mesoionic rings and ΔG† has been observed, and such correlation is used to estimate the ΔG† values for the methyl‐substituted c and d. The largest barrier (13.78 kcal/mol) has been obtained for the 4‐methyl‐1,3‐thiazol‐5‐thiolate (4‐m‐d).
Hierarchical Porous Nitrogen‐Doped Carbon Modified with Nickel Nanoparticles for Selective Ultradeep Desulfurization
Authors: Ganiyu Saheed A. , Tanimu Abdulkadir , Azeez Musa O. , Alhooshani Khalid
Published: July 2020

We report herewith, a biomass derived carbon from groundnut shell (GN‐AC) treated with melamine to achieve nitrogen‐doped carbon (CN), followed by modification with nickel‐precursor by solid‐state impregnation to achieve reticulated nickel nanoparticles‐modified nitrogen‐doped carbon (Ni‐CN) adsorbent. Incorporation of heteroatoms and the subsequent loading of nickel nanoparticles on the porous carbon exhibits fast and remarkable adsorption capacity for dibenzothiophene. The sulfur removal efficiencies of CN and Ni‐CN are 40.49 and 44.77 mg‐S/g‐adsorbent, respectively, compared to 29.63 mg‐S/g achieved for bare carbon in 500 ppmw‐S. This excellent performance is attributed to synergy effect of nitrogen heteroatoms and nickel nanoparticles with improved surface chemistry and textural properties. The physical‐chemical properties of the adsorbents were characterized by Boehm titration, N2‐physisorption, FTIR, XRD, XPS, Raman, SEM and TEM. The kinetics and isotherms investigation of the adsorbents data fitted pseudo‐first order and Langmuir models, respectively. The Ni‐CN adsorbent also displays an excellent selectivity and regeneration potential for commercial viability.
Chemical Assembling of Heterometallic {Cd–M} (M=Li, Mg, Eu, Tb) Molecules with 3,5‐Di‐tert‐butylbenzoate Bridges and N‐Donor Ligands
Authors: Shmelev Maxim A. , Gogoleva Natalia V. , Sidorov Alexey A. , Nelyubina Yulia A. , Dolgushin Fyodor M. , Voronina Yulia K. , Kiskin Mikhail A. , Aleksandrov Grigory G. , Varaksina Evgenia A. , Taydakov Ilya V. , Eremenko Igor L.
Published: July 2020

It was shown that the reaction of potassium 3,5‐di‐tert‐butylbenzoate (Kbzo) and Cd(NO3)2 in EtOH gave the [Cd3(H2O)(EtOH)3(bzo)6]⋅EtOH complex (I). The use of Li(bzo) or Mg(bzo)2 salts in this reaction in the presence of excess 2,4‐lutidine or a stoichiometric amount of 1,10‐phenanthroline initiated the crystallization of the polymer [CdLi2(H2O)(EtOH)2(bzo)4]n (II) containing no N‐donor ligands or trinuclear complexes [Cd2Mg(bzo)6(L)2]⋅Solv (L, Solv=lut, 2EtOH (III); phen, 6CH2Cl2 (IV)) that included coordinated N‐donors. The use of Eu(bzo)3 as the source of Ln ions in the presence of a stoichiometric amount of lut gave trinuclear carboxylates [EuCd2(H2O)2(EtOH)2(bzo)7]⋅3EtOH (V) and [TbCd2(H2O)(EtOH)3(bzo)7]⋅2EtOH⋅2.7H2O (VI) containing no lut molecules. It was found that the incorporation of coordinated N‐donors was observed only if a 10‐fold excess of pyridine or a stoichiometric amount of 2,2’‐dipyridyl was added to the reaction medium in the presence of Ln(NO3)3⋅6H2O (Ln=Eu, Tb) or Ln(bzo)3, respectively. In these cases, trinuclear {Cd−Ln} complexes were formed, which contained a terminal N‐donor ligand, [LnCd2(bzo)6(NO3)(py)4]⋅1.5MeCN (Ln=Eu (VII), Tb (VIII)), [EuCd2(H2O)(bzo)7(bpy)2]⋅2THF⋅3H2O⋅MeCN (IX) and [TbCd2(H2O)(bzo)7(bpy)2] (X)). The structures of the new compounds were determined by single‐crystal X‐ray diffraction analysis. The complexes were characterized by luminescence spectroscopy, IR spectra, CHN‐analysis and fluorescence analysis.
Novel Nicotinonitriles and Thieno[2,3‐b]pyridines as Potent Biofilm and COX‐2 Inhibitors: Synthesis, In Vitro and In Silico Studies
Authors: Sanad Sherif M. H. , Mekky Ahmed E. M.
Published: July 2020

Pyridine‐2(1H)‐thiones were used to prepare two novel series of nicotinonitriles and thieno[2,3‐b]pyridines using piperazine as an eco‐friendly catalyst and under ultrasonic irradiation. The in vitro antibacterial activities of both series were estimated against different Gram‐positive and negative bacterial strains. 2‐((4‐(Benzo[d][1,3]dioxol‐5‐yl)‐3‐cyano‐6‐(thiophen‐2‐yl)pyridin‐2‐yl)thio)acetamide (13 b) gave the least MIC/MBC values of 4.8/9.6, 4.8/9.6 and 9.6/19.7 μM against each of Staphylococcus aureus, Escherichia coli and Streptococcus mutans, respectively, when compared with Ciprofloxacin. Compound 13 b showed also the best biofilm inhibition activities with IC50 values in the range of 5.2‐7.3 μM against S. aureus, S. mutans and E. coli bacterial strains when compared with Ciprofloxacin. Moreover, the most potent antibacterial derivatives were subjected to further evaluation of their cytotoxic activity against HEPG2 and MCF‐7 cell lines as well as their capability to inhibit COX‐2 enzyme. 13 b exhibited the best cytotoxic activity against HEPG2 and MCF‐7 cell lines with IC50 of 23.9 and 29.8 μM, respectively, when compared with Doxorubicin. Also, 13 b revealed nearly inhibition activity equipotent to Celecoxib with IC50 of 0.12 μM. The in silico study was performed to predict the capability of the novel nicotinonitriles and thienopyridines as potent inhibitors of COX‐2 enzyme.
Synthesis, Characterization, and Antiproliferative Activity Studies of Novel Benzimidazole‐Imidazopyridine Hybrids as DNA Groove Binders
Authors: Caymaz Bahar , Yıldız Ufuk , Akkoç Senem , Gerçek Zuhal , Şengül Abdurrahman , Coban Burak
Published: July 2020

A novel benzimidazole‐imidazo[1,2‐a]pyridine hybrid; 2‐(imidazo[1,2‐a]pyridine‐8‐yl)benzimidazole and its symmetrical bis‐ derivative 2,2′‐bis‐(imidazo[1,2‐a]pyridine‐8‐yl)‐1H,1H′‐[5,5′]‐bisbenzimidazole were synthesized and characterized. It was found that these two compounds have a strong DNA groove binding and peroxide mediated DNA‐cleavage properties. Furthermore, these molecules were screened against three different human cell lines namely HepG2, DLD‐1 and MDA‐MB‐231, and these compounds were found to have high cytotoxic activities.
Screening of α‐Glucosidase Inhibitors from Houttuynia cordata and Evaluation of the Binding Mechanisms
Authors: Zhang Xueli , Cheng Bingjie , Liu Xixia , Li Yani , Hou Jianjun , Chen Sirui , Chen Jiamin , Li Shuyue
Published: July 2020

α‐glucosidase inhibitors have been used to treat diabetes for many years. Recently, natural products have attracted much attention, because they are kinds of safety source to screen α‐glucosidase inhibitor. In this study, we separated two monomers (quercitrin and afzelin) from Houttuynia cordata with notable inhibitory activity against α‐glucosidase, and evaluated inhibitory kinetics and the binding mechanisms. The 50% inhibitory concentration (IC50) of the quercitrin and afzelin were 0.231±0.033 mg/mL and 0.215±0.004 mg/mL, which were lower than the IC50 of acarbose. The inhibitory type between α‐glucosidase and the two monomers was a competitive inhibition, which is similar to acarbose and could compete binding sites. The fluorescence spectroscopy showed that quercitrin and afzelin statically quenched the fluorescence of α‐glucosidase. Circular dichroism and molecular docking analyses indicated that quercitrin and afzelin changed the alpha‐helix structure of α‐glucosidase and bound with the key amino acids through hydrophobic interactions, hydrogen bonds and salt bridge interaction. This study is the first time to clarify the inhibitory kinetics and binding mechanisms of quercitrin and afzelin on α‐glucosidase.
Computationally‐Guided Investigation of Dual Amine/pi Lewis Acid Catalysts for Direct Additions of Aldehydes and Ketones to Unactivated Alkenes and Alkynes
Authors: Greve Eric , Porter Jacob D. , Dockendorff Chris
Published: July 2020

Dual amine/pi Lewis acid catalyst systems have been reported for intramolecular direct additions of aldehydes/ketones to unactivated alkynes and occasionally alkenes, but related intermolecular reactions are rare and not presently of significant synthetic utility, likely due to undesired coordination of enamine intermediates to the metal catalyst. We reasoned that bulky metal ligands and bulky amine catalysts could minimize catalyst poisoning and could facilitate certain examples of direct intermolecular additions of aldehydes/ketones to alkenes/alkynes. Density Functional Theory (DFT) calculations were performed that suggested that pyridine‐2,6‐bis(oxazoline) (PyBOX)‐Pt(II) catalysts for alkene/alkyne activation could be combined with MacMillan's imidazolidinone organocatalyst for aldehyde/ketone activation to facilitate desirable C−C bond formations, and certain reactions were calculated to be more exergonic than catalyst poisoning pathways. Consistent with the calculations, preformed enamines generated from the MacMillan imidazolidinone did not displace ethylene from a biscationic (t‐Bu)PyBOX‐Pt2+ complex. The desired intermolecular C−C bond formation was not observed under several different conditions, but this novel catalytic system facilitated an intramolecular C−C bond formation (Conia‐ene type reaction) with a formyl alkyne substrate.
Recent Development in Applications of Synthetic Phenoxazines and Their Related Congeners: A Mini‐Review
Authors: Onoabedje Efeturi A. , Ayogu Jude I. , Odoh Amaechi S.
Published: July 2020

Phenoxazines have gained enormous interest because of their diverse applications in both material science and chemotherapy. They exhibit numerous biological activities, ranging from anti‐malarial, anticancer, antiviral, antidiabetic, anti‐Alzheimer, antioxidant, anti‐inflammatory, to antibiotic and many more. Actinomycin D, for instance, which embodies a phenoxazine scaffold, displays both antibiotic and anticancer property. Phenoxaxines have also found usefulness in organic light‐emitting diodes, fluorescent probes and dye‐sensitized solar cells. Over the years, various research groups have strived for several structural modifications targeting new derivatives of phenoxazines with improved properties. This present review highlights the progress, challenges and prospects in medicinal and material applications of phenoxazine moiety to provide greater insight into the development of future derivatives with improved properties.
An AIE‐Active Tetraphenylethylene‐Based Cyclic Urea as a Selective and Efficient Optical and Colorimetric Chemosensor for Fluoride Ions
Authors: Nadimetla Dinesh N. , Zalmi Geeta A. , Bhosale Sheshanath V.
Published: July 2020

Anion sensing is a very challenging and important issue in many diverse fields, including biological, medical and environmental sciences. In this paper, we report the serendipitous synthesis of a tetraphenylethylene (TPE) bearing a cyclic urea (coded as: 1). This easy‐to‐make, simple chemosensor shows high selectivity towards fluoride (F−) ions. Importantly, this work demonstrates two important factors: firstly, the use of cyclic urea for ion sensing and secondly, the use of aggregation induced emission (AIE)‐ TPE signalling units. This selective fluoride sensing can be observed by the naked eye, UV‐vis absorption, fluorescence spectroscopy, and 1H‐NMR spectroscopy. Solutions of sensor 1 are fluorescent in DMSO with fluorescence quantum yield Φ=1.3 and upon addition of fluoride ions the emission is quenched with ΦF=0.07. Notably, other anions, such as CN−, AcO−, NO3−, H2PO4−, HSO4−, I−, OH−, ClO4−, SCN− and Cl−, do not show any quenching effect. The binding constant (K) between sensor 1 and fluoride was found to be 4.90×108 M−2 with a detection limit of 30 μM. We also studied AIE‐activity of 1 in THF/water mixture. As such the fluorescence quantum yield (ΦF) of 1 in pure THF solution shown to be 0.05 % which was enhanced 22‐fold to 1.98 and 6.65 % at fw=90 and 99 %, respectively. This is clear confirmation that compound 1 is AIE active due to decreased solubility and increased molecular self‐assembly as the water fraction is increased.
Production of Benzenecarboxylic Acids from Geting Bituminous Coal through Oxidation with NaOCl Enhanced by Pretreatment with H2O2
Authors: Liu Fang‐Jing , Bie Lei‐Lei , Guang‐Hui  , Guo Jia‐Pei , Huang Zai‐Xing , Zong Zhi‐Min , Wei Xian‐Yong
Published: July 2020

Benzenecarboxylic acids (BCAs) are valuable chemicals with a wide range of applications, which can be produced from coals via mild oxidation. Herein, an effective approach for producing BCAs from Geting bituminous coal (GBC) is reported through oxidation with NaOCl aqueous solution enhanced by pretreatment with H2O2 aqueous solution. Both GBC and pretreated GBC (PTGBC) undergo oxidation with NaOCl at 30 °C for 24 h. The results show that pretreatment with H2O2 enhance the yields of non‐chlorine BCAs and meanwhile suppress producing chloro‐substituted BCAs from GBC. BCAs produced from oxidation of PTGBC have a high total yield of 21.0 wt %, among which benzenedicarboxylic acids, benzenetricarboxylic acids, and benzenetetracarboxylic acids are predominant. The distributions of BCAs reveal that GBC has more cata‐condensed aromatics and peri‐condensed aromatics than polyaryls moieties. The possible mechanisms for enhancing BCAs production by pretreatment with H2O2 are discussed.
Chemoselective Detection of 2,4,6‐trinitrophenol by Ground State Adduct Formation via Protonation of Quinoline Moiety of Non‐heme Ligands with Structural Evidence
Authors: Harmalkar Sarvesh S. , Naik Ankita V. , Nilajakar Madhuri K. , Dhuri Sunder N.
Published: July 2020

Four quinoline based non‐heme tetradendate ligands viz. N,N′‐di(quinolin‐8‐yl)ethane‐1,2‐diamine (BQENH2) 1, N,N′‐di(quinolin‐8‐yl)propane‐1,3‐diamine 2 (BQPNH2), N,N′‐di(quinolin‐8‐yl)butane‐1,4‐diamine (BQEBNH2) 3 and N,N′‐di(quinolin‐8‐yl)hexane‐1,6‐diamine (BQEHNH2) 4 are structurally characterized and used in selective detection of 2,4,6‐trinitrophenol (TNP) with high quenching constants. The plausible reaction mechanism involves ground state protonation of quinoline nitrogen atoms in compounds 1–4 by TNP with formation of picrate adducts (1 a‐4 a). The protonation of 1–4 is confirmed by infrared, 1H‐NMR spectroscopies, powder XRD and the single crystal structure analysis of 1 a and 4 a. Crystal structures further infer that after protonation, 1 a and 4 a are stabilized by intramolecular hydrogen bonding.
Telechelic Carboxyl‐Terminated Polynorbornenes and Copolym‐ers via Chain‐Transfer Ring‐Opening Metathesis Polymerization
Authors: Wang Xixi , Dai Lu , Jie Suyun , Bu Zhiyang , Li Bo‐Geng
Published: July 2020

Carboxyl‐terminated polynorbornenes (CTPNB) have been prepared via ring‐opening metathesis polymerization (ROMP) catalyzed by Grubbs II catalyst (G2) in the presence of maleic acid (MA) as a chain transfer agent (CTA). The influences of reaction conditions on the molecular weight of products, including molar ratios of C=C/G2, C=C/CTA and amount of solvent were investigated. The results indicated that the molecular weight of CTPNBs could be controlled by varying the molar ratio of C=C/G2 or C=C/CTA. In addition, norbornene (NB) was copolymerized with cyclooctene (COE) in order to obtain carboxyl‐terminated copolymers via chain‐transfer ROMP. The unsaturated carboxyl‐terminated (co)polymers were further hydrogenated by using p‐toluenesulfonyl hydrazide/tri‐n‐propylamine reagents. The structures of polymers were characterized by FT‐IR, NMR and MALDI‐TOF mass spectroscopy, and their thermal properties were determined by DSC and TGA.
Substratum‐associated microbiota
Authors: Furey Paula C. , Lee Sylvia S. , Clemans Daniel L.
Published: July 2020

Highlights of new, interesting, and emerging research findings on substratum‐associated microbiota covered from a survey of 2019 literature from primarily freshwaters provide insight into research trends of interest to the Water Environment Federation and others interested in benthic, aquatic environments. Coverage of topics on bottom‐associated or attached algae and cyanobacteria, though not comprehensive, includes new methods, taxa new‐to‐science, nutrient dynamics, auto‐ and heterotrophic interactions, grazers, bioassessment, herbicides and other pollutants, metal contaminants, and nuisance, and bloom‐forming and harmful algae. Coverage of bacteria, also not comprehensive, focuses on the ecology of benthic biofilms and microbial communities, along with the ecology of microbes like Caulobacter crescentus, Rhodobacter, and other freshwater microbial species. Bacterial topics covered also include metagenomics and metatranscriptomics, toxins and pollutants, bacterial pathogens and bacteriophages, and bacterial physiology. Readers may use this literature review to learn about or renew their interest in the recent advances and discoveries regarding substratum‐associated microbiota.

Practitioner points

This review of literature from 2019 on substratum‐associated microbiota presents highlights of findings on algae, cyanobacteria, and bacteria from primarily freshwaters.

Coverage of algae and cyanobacteria includes findings on new methods, taxa new to science, nutrient dynamics, auto‐ and heterotrophic interactions, grazers, bioassessment, herbicides and other pollutants, metal contaminants, and nuisance, bloom‐forming and harmful algae.

Coverage of bacteria includes findings on ecology of benthic biofilms and microbial communities, the ecology of microbes, metagenomics and metatranscriptomics, toxins and pollutants, bacterial pathogens and bacteriophages, and bacterial physiology.

Highlights of new, noteworthy and emerging topics build on those from 2018 and will be of relevance to the Water Environment Federation and others interested in benthic, aquatic environments
Implementation of long solids retention time activated sludge process for rural residential community
Authors: Campbell Ken , Wang Jianmin , Tucker Robert , Struemph Chris
Published: July 2020

Most rural communities in the United States are facing increasingly rigorous effluent criteria, especially ammonia, for their wastewater treatment facilities. A new baffled bioreactor (BBR) technology, which employs a preanoxic activated sludge process operated with a long solids retention time (SRT), was installed in a small community in Missouri to address the more stringent effluent limits. In a recent full‐year normal operation cycle (2018), the average effluent concentrations of BOD5, TSS, and ammonia‐nitrogen were 3.2, 2.2, and 0.5 mg/L, respectively, with removal efficiencies of 96%, 85%, and 98%, respectively. All these parameters were significantly better than their respective permit limits. The long SRT afforded an enhanced factor of safety for the process, conferring the ability to nitrify at sustained ambient temperatures as low as −22°C. Long SRT also resulted in significant reductions in waste sludge production, resulting in dramatically reduced operational costs for sludge handling. Ultimately, the long SRT activated sludge process afforded the ability to meet stringent effluent quality standards including ammonia and the numerous unique challenges that are inherent to small flows.

Practitioner points

Small community hydraulic and mass loadings are highly variable and difficult to quantify during facility design.

A long SRT activated sludge process warrants superior performance and enhanced factor of safety.

The long SRT process with preanoxic zones generated no excess sludge during the extended operation period, significantly simplifying plant operation.

Long SRT process is well suited to accommodate wastewater variability associated with small communities while maintaining superior treatment quality.
Personal Narrative: Out of the Mikvah, into the World
Authors: Mirvis Tova
Published: July 2020

In this personal essay, Tova Mirvis describes her religious evolution concerning the Jewish ritual of mikvah, or women’s immersion into a bath to attain a state of ritual purity. Her initiation begins before her wedding night, when she is accompanied by her mother to the mikvah to be purified before having sex for the first time. The practice continues each month, at the conclusion of her menstrual period. As the years go by, Mirvis begins to experience doubt about her religious observance in general and adherence to the practice of mikvah in particular, chafing at the requirement to ‘cleanse’ herself monthly. Mirvis writes that her discomfort over time leads her to experiment with other forms of ritual immersion and, eventually, she leaves the religious world that had been so central to her.
(In)Visible Bleeding: The Menstrual Concealment Imperative
Authors: Wood Jill M.
Published: July 2020

Wood offers a new conceptual framework, “the menstrual concealment imperative”, to explain how women’s internalization of menstrual discourse contributes to their disembodiment and self-objectification through menstrual “management”. This chapter critiques the medical system and menstrual hygiene industry for the (bio)medicalization of menstruation that establishes women as diseased and as unable to know their bodies. Wood suggests that women’s vigilance about menstrual concealment is not freely chosen, but a required self-disciplinary practice rooted in menstrual discourse that characterizes menstruation as stigmatized, taboo, and therefore shrouded in secrecy. The concealment imperative is a form of social control and a body project that keeps women disembodied and objectified. As a conceptual tool it has implications to understand the various ways that women’s bodies are regulated both at individual and social levels.
“You Will Find Out When the Time Is Right”: Boys, Men, and Menstruation
Authors: Erchull Mindy J.
Published: July 2020

This chapter reviews the scant amount of research that exists about the relationship that boys and men—who are not menstruators—have with menstruation. In looking at this relationship, Erchull sheds light on how boys and men learn about menstruation, what they actually know about it, and what beliefs and attitudes they hold about both menstruation and menstruators. The author pays special attention to fathers and the role they can play in educating their children about menstruation. Erchull concludes that, while there are still many questions and much to be learned, the knowledge, beliefs, and attitudes that boys and men hold about menstruation influence them in their interactions with menstruators.
Policy and Practice Pathways to Addressing Menstrual Stigma and Discrimination
Authors: Patkar Archana
Published: July 2020

Patkar traces the efforts in various countries to break the silence and stigma surrounding menstruation and to develop national policies on menstrual hygiene. She argues that changes in social norms, institutions, and behaviors linked to taboo topics are best facilitated by simple, evidence-based policies anchored in voice and participation. She asserts that men are willing and essential agents of change for gender equality when presented with pragmatic problems and implementable solutions. Basic noncontroversial and essential services and infrastructure, such as taps and toilets, serve as powerful entry points to articulating, exploring, and addressing wider gender and exclusion issues. Drawing on her experiences working with governments in Africa and Asia and reflecting on her journey over the past decades, Patkar outlines a methodology and pathway to transform the silence around menstruation into policy and action.
Bleeding in Jail: Objectification, Self-Objectification, and Menstrual Injustice
Authors: Roberts Tomi-Ann
Published: July 2020

In this first-person recollection, Roberts describes in frank detail an expert witness in a civil rights case on behalf of former inmates subjected to a strip and body cavity search in a women's jail. As Roberts relates, the procedure was monitored by female deputies and conducteden masse, and those who were menstruating had to remove their soiled tampons or pads in front of the group and, in some cases, bleed down their legs and onto the floor. Deputies are alleged to have verbally abused the inmates during the procedure. This case, Roberts says, has opened her eyes to the ways the shame and disgust that menstruation engenders gets deployed to debase disenfranchised women. Roberts asserts that this is a uniquely misogynist form of punishment, meted out by and against bodies and minds that have been colonized by objectification and self-objectification, becoming a grotesque platform to dehumanize women who land on the wrong side of the law and who live in bodies that menstruate.
The Messy Politics of Menstrual Activism
Authors: Bobel Chris , Fahs Breanne
Published: July 2020

In this chapter, Bobel and Fahs first describe a brief history of menstrual activism alongside its more recent iterations in both policy and radical social activism. They review the collective call to reduce stigma and shame around menstruation as part of the enduring project of loosening the social control of women’s bodies. The authors then turn to an analysis of menstrual humor, menstrual art, and menstrual activism today, respectively. This is followed by an examination of the hazards and possibilities of doing menstrual activist work, including politics of menstrual language and the trivializations and hostilities that can plague this work. Finally, Bobel and Fahs offer a politically charged outline for the future of menstrual activism.
Transnational Engagements: Women’s Experiences of Menopause
Authors: Perianes Milena Bacalja , Kissling Elizabeth Arveda
Published: July 2020

In this chapter, Perianes and Kissling examine informal interviews about menopause experiences and discourse conducted among participants in four nations: British-Iranian Shardi Nahavandi interviewed her Persian mother; Swetha Sridhar interviewed her mother and grandmother, all currently from different regions of India; Ursula Maschette Santos spoke with three women from her community in São Paulo, Brazil; and Jennifer Poole conducted a focus group discussion with 17 participants of the NGO Medical Services Pacific in Fiji, which included six men. Noting that each nation and community has its own norms and traditions, the authors find common themes of ambivalence around aging, community silence about menopause, and insufficient education or preparation for the menopause transition.
Superorganisms of the Protist Kingdom: A New Level of Biological Organization
Authors: Lamża Łukasz
Published: July 2020

The concept of superorganism has a mixed reputation in biology—for some it is a convenient way of discussing supra-organismal levels of organization, and for others, little more than a poetic metaphor. Here, I show that a considerable step forward in the understanding of superorganisms results from a thorough review of the supra-organismal levels of organization now known to exist among the “unicellular” protists. Limiting the discussion to protists has enormous advantages: their bodies are very well studied and relatively simple (as compared to humans or termites, two standard examples in most discussions about superorganisms), and they exhibit an enormous diversity of anatomies and lifestyles. This allows for unprecedented resolution in describing forms of supra-organismal organization. Here, four criteria are used to differentiate loose, incidental associations of hosts with their microbiota from “actual” superorganisms: (1) obligatory character, (2) specific spatial localization of microbiota, (3) presence of attachment structures and (4) signs of co-evolution in phylogenetic analyses. Three groups—that have never before been described in the philosophical literature—merit special attention: Symbiontida (also called Postgaardea), Oxymonadida and Parabasalia. Specifically, it is argued that in certain cases—forBihospites bacatiandCalkinsia aureus(symbiontids),Streblomastix strix(an oxymonad),Joenia annectensandMixotricha paradoxa(parabasalids) andKentrophoros(a ciliate)—it is fully appropriate to describe the whole protist-microbiota assocation as a single organism (“superorganism”) and its elements as “tissues” or, arguably, even “organs”. To account for this level of biological complexity, I propose the term “structured superorganism”.
Finite Element Error Estimates on Geometrically Perturbed Domains
Authors: Minakowski Piotr , Richter Thomas
Published: July 2020

We develop error estimates for the finite element approximation of elliptic partial differential equations on perturbed domains, i.e. when the computational domain does not match the real geometry. The result shows that the error related to the domain can be a dominating factor in the finite element discretization error. The main result consists of $$H^1$$

H
1

- and $$L^2$$

L
2

-error estimates for the Laplace problem. Theoretical considerations are validated by a computational example.
Use of translational modeling and simulation for quantitative comparison of PF-06804103, a new generation HER2 ADC, with Trastuzumab-DM1
Authors: Betts Alison , Clark Tracey , Jasper Paul , Tolsma John , van der Graaf Piet H. , Graziani Edmund I. , Rosfjord Edward , Sung Matthew , Ma Dangshe , Barletta Frank
Published: July 2020

A modeling and simulation approach was used for quantitative comparison of a new generation HER2 antibody drug conjugate (ADC, PF-06804103) with trastuzumab-DM1 (T-DM1). To compare preclinical efficacy, the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of PF-06804103 and T-DM1 was determined across a range of mouse tumor xenograft models, using a tumor growth inhibition model. The tumor static concentration was assigned as the minimal efficacious concentration. PF-06804103 was concluded to be more potent than T-DM1 across cell lines studied. TSCs ranged from 1.0 to 9.8 µg/mL (n = 7) for PF-06804103 and from 4.7 to 29 µg/mL (n = 5) for T-DM1. Two experimental models which were resistant to T-DM1, responded to PF-06804103 treatment. A mechanism-based target mediated drug disposition (TMDD) model was used to predict the human PK of PF-06804103. This model was constructed and validated based on T-DM1 which has non-linear PK at doses administered in the clinic, driven by binding to shed HER2. Non-linear PK is predicted for PF-06804103 in the clinic and is dependent upon circulating HER2 extracellular domain (ECD) concentrations. The models were translated to human and suggested greater efficacy for PF-06804103 compared to T-DM1. In conclusion, a fit-for-purpose translational PK/PD strategy for ADCs is presented and used to compare a new generation HER2 ADC with T-DM1.