bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell cycle dynamics in the reprogramming of cellular identity
Authors: Hu Xiao , Eastman Anna E. , Guo Shangqin
Published: September 2019

Reprogramming of cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multidimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of the genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated replication. With this mindset, we summarize multiple scenarios where rapid cell cycle could interfere with cell fate copying and promote cell fate reprogramming. Prominent examples of cell fate regulation by specific cell cycle phases are also discussed. Overall, there is much to be learned regarding the relationship between cell fate reprogramming and cell cycle control. Harnessing cell cycle dynamics could greatly facilitate the derivation of desired cell types.
Ligand‐dependent intra‐ and interdomain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
Authors: Kovács Bertalan , Zajácz‐Epresi Nóra , Gáspári Zoltán
Published: September 2019

The postsynaptic density protein‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide‐binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic details of the effect of ligand binding, we generated conformational ensembles using available experimentally determined nuclear Overhauser effect interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomain structural changes induced by ligand binding modulate the probability of the occurrence of specific domain–domain orientations. Our results suggest that the β2‐β3 loop in the PDZ domains is a key regulatory region, which influences both intradomain motions and supramodular rearrangement.
Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets
Authors: Li Hongtu , Neelankal John Abraham , Nagatake Takahiro , Hamazaki Yoko , Jiang Fang‐Xu
Published: September 2019

The functional state (FS) of adult pancreatic islets is regulated by a large array of regulatory molecules including numerous transcription factors. Whether any islet structural molecules play such a role has not been well understood. Here, multiple technologies including bioinformatics analyses were used to explore such molecules. The tight junction family molecule claudin 4 (Cldn4) was the highest enriched amongst over 140 structural genes analysed. Cldn4 expression was ~75‐fold higher in adult islets than in exocrine tissues and was mostly up‐regulated during functional maturation of developing islet cells. Cldn4 was progressively down‐regulated in functionally compromised, dedifferentiating insulin‐secreting β cells and in db/db type 2 diabetic islets. Furthermore, the genetic deletion of Cldn4 impaired significantly the FS without apparently affecting pancreas morphology, islet architectural structure and cellular distribution, and secretion of enteroendocrine hormones. Thus, we suggest a previously unidentified role for Cldn4 in regulating the FS of islets, with implications in translational research for better diabetes therapies.
Some providers may proceed cautiously on latest legal challenge to insurer
Authors: Enos Gary
Published: September 2019

To those who might assume a federal lawsuit seeking class status for treatment providers wronged by insurance company actions would be receiving immediate and universal acclaim in the provider community, a little caution may be in order. While the latest lawsuit against United Behavioral Health (UBH) certainly will be interpreted by some addiction treatment providers as an opportunity to recover payments that were inappropriately denied (see ADAW, Sept. 23), the case also could launch a broader discussion of how best to guarantee that insured patients receive the care to which they are entitled.
AMA and ASAM have different views on SAMHSA NPRM
Authors: Knopf Alison
Published: September 2019

The comment period for the notice of proposed rulemaking (NPRM) that would allow law enforcement to have access to all patient records if it is investigating an alleged serious crime by a patient (see ADAW, Sept. 9) closed Sept. 25. There was no extension, as some (including the American Medical Association [AMA]) had requested (see ADAW, Sept. 23). This proposal, by the Substance Abuse and Mental Health Services Administration (SAMHSA), would alter 42 CFR Part 2 by allowing this access, also changing the definition of serious crime to include anything related to drug trafficking.
Treatment center sues Tennessee town over zoning ordinance
Authors: Knopf Alison
Published: September 2019

Last week, ReVIDA Recovery Centers, which provides medication‐assisted treatment for opioid use disorder, announced that it would sue to keep its treatment program in Morristown, Tennessee, where the city has denied the company based on zoning. “Our patients are our first priority,” said CEO Lee Dilworth on September 25.
Nanomedicine‐Enabled Modulation of Tumor Hypoxic Microenvironment for Enhanced Cancer Therapy
Authors: Wang Jinping , Zhang Beilu , Sun Jingyu , Wang Yuhao , Wang Hongjun
Published: October 2019

Hypoxia is a common condition of solid tumors that is mainly caused by enhanced tumor proliferative activity and dysfunctional vasculature. In the treatment of hypoxic human solid tumors, many conventional therapeutic approaches (e.g., oxygen‐dependent photodynamic therapy, anticancer drug‐based chemotherapy or X‐ray induced radiotherapy) become considerably less effective or ineffective. In recent years, various strategies have been explored to deliver or generate oxygen inside solid tumors to overcome tumorous hypoxia and show promising evidence to improve the antitumor efficiency. In this review, the extrinsic regulation of tumor hypoxia via nanomaterial delivery is discussed followed by a summary of the mechanisms through which the modulated tumor hypoxic microenvironment improves therapeutic efficacy. The review concludes with future perspectives, to specifically address the translation of nanomaterial‐based therapeutic strategies for clinical applications.
Understanding the Superior Stability of Single‐Molecule Magnets on an Oxide Film
Authors: Studniarek Michał , Wäckerlin Christian , Singha Aparajita , Baltic Romana , Diller Katharina , Donati Fabio , Rusponi Stefano , Brune Harald , Lan Yanhua , Klyatskaya Svetlana , Ruben Mario , Seitsonen Ari Paavo , Dreiser Jan
Published: October 2019

The stability of magnetic information stored in surface adsorbed single‐molecule magnets is of critical interest for applications in nanoscale data storage or quantum computing. The present study combines X‐ray magnetic circular dichroism, density functional theory and magnetization dynamics calculations to gain deep insight into the substrate dependent relevant magnetization relaxation mechanisms. X‐ray magnetic circular dichroism reveals the opening of a butterfly‐shaped magnetic hysteresis of DyPc2 molecules on magnesium oxide and a closed loop on the bare silver substrate, while density functional theory shows that the molecules are only weakly adsorbed in both cases of magnesium oxide and silver. The enhanced magnetic stability of DyPc2 on the oxide film, in conjunction with previous experiments on the TbPc2 analogue, points to a general validity of the magnesium oxide induced stabilization effect. Magnetization dynamics calculations reveal that the enhanced magnetic stability of DyPc2 and TbPc2 on the oxide film is due to the suppression of two‐phonon Raman relaxation processes. The results suggest that substrates with low phonon density of states are beneficial for the design of spintronics devices based on single‐molecule magnets.
Engineered pH‐inducible intein Mtu ΔI‐CM variants with markedly reduced premature cleavage activity
Authors: Lin Zhanglin , Zhao Qing , Wang Xu , Zhou Bihong , Xing Lei , Wang Jiangyun , Pistolozzi Marco , Zhao Lei , Wang Tingting
Published: October 2019

Inteins have been widely exploited for the purification of tagless proteins. Among them, pH‐inducible C‐terminal‐cleavage inteins enable the preparation of proteins and peptides with an authentic N‐terminus. However, a severe premature cleavage around neutral pH has limited the application of these inteins, especially when used in recombinant hosts such as Escherichia coli. By targeting the microenvironment of the two key histidine residues H429 and H439, we engineered Mtu ΔI‐CM intein to markedly reduce its premature cleavage. Kinetic analyses suggested that although the variants retained the pH dependence, they indeed cleaved slower, especially at pH 7.6. These variants resulted in higher yields for two model polypeptides than the original Mtu ΔI‐CM intein, when used in conjunction with a cleavable self‐assembling tag. This work suggests that more controllable pH‐inducible inteins can be obtained by manipulating the residues in the self‐cleavage sites and provide better performance for tag‐based protein preparation strategies.
A new liquefaction method for natural gas by utilizing cold energy and separating power of swirl nozzle
Authors: Bian Jiang , Cao Xuewen , Yang Wen , Gao Song , Xiang Chengcheng
Published: October 2019

A swirl nozzle with a central body was newly designed to make full use of the cold energy and separating power, and the coupling of swirling flow and condensation was realized based on a condensation model, a droplet surface tension model and a Reynolds stress model turbulence model. The flow and condensation characteristics of methane gas under supersonic swirling flow conditions were studied. The results show that the flow and condensation parameter distribution in the swirl nozzle are similar under varying swirling intensities, but the swirling performance improves with the increase in swirling intensity, and a tangential velocity is beneficial before the gas enters the nozzle. As the inlet temperature decreases or the inlet pressure increases, the liquefaction efficiency increases, and the gas condensation process can be promoted. With the advancement of the initial nucleation position and the increase in the droplet radius, the separation efficiency of the swirl nozzle increases.
Microwave‐Assisted Metal‐Free Decarboxylative Iodination/Bromination of Isoxazole‐4‐carboxylic Acids
Authors: Barak Dinesh S. , Dahatonde Dipak J. , Batra Sanjay
Published: September 2019

A microwave‐assisted metal‐free route to substituted 4‐haloisoxazoles via decarboxylative halogenation of substituted isoxazole‐4‐carboxylic acids using N‐iodosuccinimide (NIS) and N‐bromosuccinimide (NBS) in the presence of K3PO4 is described. It was discovered that the substitutions present at the 3‐position of differently 3,5‐disubstituted isoxazoles influenced the outcome of the protocol. The methodology is compatible for performing decarboxylative halogenation followed by decarboxylative Suzuki‐Miyaura and Sonogashira couplings as one‐pot process.
Effects of modifying visual inhaler spacer usage instructions on correct usage rate of untrained users
Authors: Topal Erdem , Arga Mustafa , Özmen Hakan , Doğru Mahmut , Alataş Cem , Muştu Elif Büşra , Çeliksoy Mehmet Halil
Published: October 2019

Background

Pressurized metered‐dose inhalers (pMDIs) used with spacers are considered the method of choice for delivery of inhaled drugs in preschool‐age children. The aim of this study was to determine the effects of modifying the visual inhaler spacer usage guidelines on the correct usage rate.

Methods

The parents and caregivers of patients <6 years old who were prescribed inhalers with spacers for the first time were included in our study. The participants were randomly divided into a modified visual inhaler spacer usage guidelines group and an unmodified visual inhaler spacer usage guidelines group. All study participants underwent face‐to‐face interviews and completed questionnaires.

Results

A total of 510 participants with a median age of 31 (range, 20‐46) years were included in this study. The modified visual guidelines group included 254 (49.6%) participants, and the unmodified visual guidelines group included 256 (50.4%) participants. One hundred sixty‐five (65.2%) of the 254 participants in the modified visual guidelines group correctly demonstrated the inhaler spacer technique. In contrast, only 21 (8.2%) of the 256 participants in the unmodified visual guidelines group correctly demonstrated the inhaler spacer technique (p< 0.001). When comparing the inhaler spacer usage steps between the 2 groups, the modified visual guidelines group demonstrated the steps more correctly and more quickly (p< 0.001).

Conclusion

The current visual inhaler spacer usage guidelines are insufficient. We believe that improving the visual inhaler spacer usage guidelines, in particular, will increase the correct usage rate and decrease the number of usage errors.
Advances in Disease Mechanisms and Translational Technologies: Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases
Authors: Kahlenberg J. Michelle , Kang Insoo
Published: September 2019

Autoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen‐ or damage‐associated molecular patterns via pattern‐recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions, including infectious, metabolic, autoinflammatory, and autoimmune diseases. The inflammasome generally comprises a PRR, procaspase 1, and an adaptor molecule connecting the PRR and procaspase 1. Upon inflammasome activation, procaspase 1 becomes active caspase 1 that converts pro–interleukin‐1β (proIL‐1β) and proIL‐18 into mature and active IL‐1β and IL‐18, respectively. The cytokines IL‐1β and IL‐18 have multipotent effects on immune and nonimmune cells and induce and promote systemic and local inflammatory responses. Human studies have shown increased levels of these cytokines, altered activation of inflammasome‐related molecules, and/or the presence of inflammasome activators in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, crystal‐induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs, such as the kidneys, joints, and salivary glands, as well as in the cardiovascular system. In animal models of rheumatic diseases, inflammation and tissue damage improve upon genetic or pharmacologic targeting of the inflammasome, supporting its pathogenic role. Herein, we review the clinicopathologic significance and therapeutic targeting of inflammasome activation in rheumatic diseases and related conditions based on recent findings.
The Hiyama Cross‐Coupling Reaction at Parts Per Million Levels of Pd: In Situ Formation of Highly Active Spirosilicates in Glycol Solvents
Authors: Ichii Shun , Hamasaka Go , Uozumi Yasuhiro
Published: September 2019

A palladium NNC‐pincer complex at a 5 mol ppm loading efficiently catalyzed the Hiyama coupling reaction of aryl bromides with aryl(trialkoxy)silanes in propylene glycol to give the corresponding biaryls in excellent yields. This method was applied to the syntheses of adapalene and a biaryl‐type liquid‐crystalline compound, as well as to the derivatization of dextromethorphan and norfloxacin. ESI‐MS and NMR analyses of the reaction mixture suggested the formation of pentacoordinate spirosilicate intermediates in situ. Preliminary theoretical studies revealed that the glycol‐derived silicate intermediates formed in situ are quite reactive silicon reagents in the transmetalation step.
Catalog of equatorial coordinates and B‐magnitudes of the Kitab's part of the FON project
Authors: Yuldoshev Q. , Protsyuk Y. , Relke H. , Ehgamberdiev S. , Muminov M. , Andruk V.
Published: October 2019

We present a catalog of stars with equatorial coordinates α and δ and B‐magnitudes of stars for the Kitab's section of the FON project (FON‐Kitab). The photographic plates of the FON project were exposed on the double telescope Double Zeiss Astrograph (DAZ, D/F = 40/300, 69″/mm) at the Kitab observatory of the Republic of Uzbekistan. A total of 1963 plates, with size of 5.5 × 5.5 degrees (30 × 30 cm or 13,000 × 13,000 pixels) were digitized by Epson Expression 10000XL scanner with 1,200 dpi resolution. The reduction of plates was processed in the four astronomical organizations: Ulugh Beg Astronomical Institute (UBAI) of the Uzbek Academy of Sciences; the Mykolaiv Astronomical Observatory of the Ministry of Education and Science of Ukraine; the Walter Hohmann Observatory of Essen, Germany; and the Main Astronomical Observatory of the National Academy of Sciences of Ukraine. The catalogue contains nearly 13.4 million stars and galaxies from 0° to −20° according to declination down to B = 17. m5 in the middle epoch of observation 1985.0. The coordinates of the stars and galaxies were obtained from the Tycho‐2 catalogue, while B‐magnitudes were determined in the system of photoelectric standards. The mean internal errors of the new catalogue for all objects were σαδ = 0. ′′23 and σB = 0. m15 (for the stars in the range of B = 5m − 14m, the errors are σαδ = 0. ′′085 and σB = 0. m054 for the equatorial coordinates and the B‐magnitudes, respectively). The convergence between the calculated and reference positions was σαδ = 0. ′′042. The convergence with the photoelectric B‐magnitudes is σB = 0. m16. External comparison with UCAC‐4 based on 9,892,697 or 73.8% cross‐identified objects yield σαδ = 0. ′′26.
Single Cell Omics: From Assay Design to Biomedical Application
Authors: Chen Wenyi , Li Shumin , Kulkarni Anuja Shreeram , Huang Lin , Cao Jing , Qian Kun , Wan Jingjing
Published: September 2019

Given the existence of cell heterogeneity, single cell analysis is undergoing a rapid expansion for life science and precision medicine. Recent numerous innovations in analytical platforms and instruments have re‐energized the field and led to the emergence of single cell omics with high sensitivity, throughput and multiplexity. The omics knowledge builds the bridge between underlying molecular changes and cell behavior, and facilitates a deeper understanding of disease development processes. Here, the authors highlight important achievements of single cell omics mainly including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, and discuss the biomedical applications of single cell omics in stem cells differentiation, immune cells function, nerve cells development and activity, and circulating tumor cells based cancer research.
Network meta-analysis of urinary retention and mortality after Lichtenstein repair of inguinal hernia under local, regional or general anaesthesia
Authors: Olsen J H H , Öberg S , Andresen K , Klausen T W , Rosenberg J
Published: October 2019

Background

Urinary retention and mortality after open repair of inguinal hernia may depend on the type of anaesthesia. The aim of this study was to investigate possible differences in urinary retention and mortality in adults after Lichtenstein repair under different types of anaesthesia.

Methods

Systematic searches were conducted in the Cochrane, PubMed and Embase databases, with the last search on 1 August 2018. Eligible studies included adult patients having elective unilateral inguinal hernia repair by the Lichtenstein technique under local, regional or general anaesthesia. Outcomes were urinary retention and mortality, which were compared between the three types of anaesthesia using meta-analyses and a network meta-analysis.

Results

In total, 53 studies covering 11 683 patients were included. Crude rates of urinary retention were 0·1 (95 per cent c.i. 0 to 0·2) per cent for local anaesthesia, 8·6 (6·6 to 10·5) per cent for regional anaesthesia and 1·4 (0·6 to 2·2) per cent for general anaesthesia. No death related to the type of anaesthesia was reported. The network meta-analysis showed a higher risk of urinary retention after both regional (odds ratio (OR) 15·73, 95 per cent c.i. 5·85 to 42·32; P < 0·001) and general (OR 4·07, 1·07 to 15·48; P = 0·040) anaesthesia compared with local anaesthesia, and a higher risk after regional compared with general anaesthesia (OR 3·87, 1·10 to 13·60; P = 0·035). Meta-analyses showed a higher risk of urinary retention after regional compared with local anaesthesia (P < 0·001), but no difference between general and local anaesthesia (P = 0·08).

Conclusion

Local or general anaesthesia had significantly lower risks of urinary retention than regional anaesthesia. Differences in mortality could not be assessed as there were no deaths after elective Lichtenstein repair. Registration number: CRD42018087115 (https://www.crd.york.ac.uk/prospero).
Effects of irisin on the dysfunction of blood–brain barrier in rats after focal cerebral ischemia/reperfusion
Authors: Guo Peipei , Jin Zhao , Wu Huisheng , Li Xinyi , Ke Jianjuan , Zhang Zongze , Zhao Qiu
Published: October 2019

Objective

To investigate whether irisin could protect against blood–brain barrier (BBB) dysfunction following focal cerebral ischemia/reperfusion in rats.

Methods and Materials

Seventy‐two adult male Sprague Dawley rats weighing 280–320 g were randomly divided into three groups: sham operation group (S), focal cerebral ischemia/reperfusion group (FC), and irisin group (IR). Focal cerebral ischemia was induced by improved thread occlusion of right middle cerebral artery (MCAO) for 2 hr followed by reperfusion for 24 hr in rats. After 24 hr of reperfusion, the neurological evaluation was performed by the method of Longa's score. The histopathological changes were observed by HE staining. The brain water content was determined by detecting the wet weight and dry weight. The BBB permeability was assessed by fluorescence spectrophotometer and fluorescence microscopy for Evans blue (EB) extravasation. The activity and expression of matrix metalloproteinase‐9 (MMP‐9) in different groups were detected by immunohistochemical staining, Western blot, and gel gelatin zymography.

Results

After MCAO, the neurological deficit scores, the infarct volume, the brain water content, and the EB content were higher in the FC group than those in the S group (p < .05). While after irisin treatment, these indicators mentioned above were lower than those in the IR group (p < .05). Moreover, the protein expression of MMP‐9 in the cortex increased significantly after MCAO, while irisin treatment could decrease the protein expression of MMP‐9 in the cortex (p < .05).

Conclusion

Our data suggest that irisin can attenuate brain damage both morphologically and functionally and protect BBB from disruption after focal cerebral ischemia/reperfusion, which is highly associated with the inhibition of the expression and activity of MMP‐9 in the brain tissue.
Virtual instrumentation based learning methodology for teaching power system measurement and protection
Authors: Betancourt Ramón J. , González‐López Juan M. , Espejo Emilio B. , Pérez‐González Marco A. , Laureano Efraín V. , Ledesma Jaime A.
Published: September 2019

In this work, virtual instrumentation based learning methodology is presented for teaching measurement and protection in power systems courses at the Faculty of Electromechanical Engineering of the University of Colima, Mexico. The proposed methodology uses the project‐based learning method for developing experience learning. The students develop the hardware which can be used with the conventional machinery laboratory equipment and it considers the necessary security aspects to provide students with safe studying conditions by avoiding the risk of hazards. Through the use of low‐cost voltage and current sensors, the variables of interest of the equipment under measurement and protection are reduced to suitable values for the data acquisition system (DAQ). The voltage and current signals are processed using the LabVIEW® environment and the algorithms for power metering and the most common relays are developed. Acting signals coming from the DAQ are interfaced with the electrical machines by appropriate contactors and which simulates the power switchgear. The implemented hardware and the algorithms developed, allow students to measure the power consumption of conventional loads and to reproduce the most used relays by the electrical industry. This proposal represents an alternative to the high costs of didactic equipment. Finally, a survey provides a good insight of how the application of virtual instrumentation in the teaching process impacts the development of professional skills in the ambit of measurement and protection of power systems.
SIRT4 enhances the sensitivity of ER‐positive breast cancer to tamoxifen by inhibiting the IL‐6/STAT3 signal pathway
Authors: Xing Jilin , Li Ji , Fu Lin , Gai Junda , Guan Jingqian , Li Qingchang
Published: October 2019

Recent advances in endocrine therapy have improved the prospects for estrogen receptor‐positive breast cancer. Tamoxifen is an effective drug for patients with estrogen receptor‐positive breast cancer, but the development of resistance is common. Therefore, discovering ways to enhance the sensitivity of cancer cells to tamoxifen may help improve breast cancer treatment. We studied the biological role of sirtuin 4 (SIRT4) in tamoxifen‐treated MCF7 and T47D cells. The levels of the MYC proto‐oncogene (MYC) and cyclin D1 (CCND1) were detected by western blotting and quantitative reverse transcription‐polymerase chain reaction in breast cancer cells with SIRT4 overexpression or depletion. Immunofluorescence and western blotting were used to assess the phosphorylation status of signal transducer and activator of transcription 3 (STAT3). SIRT4 overexpression decreased the half maximal inhibitory concentration of tamoxifen in MCF7 and T47D cells, while its depletion increased it. Thus, SIRT4 enhances the sensitivity of breast cancer cells to tamoxifen. Moreover, western blotting revealed decreased STAT3 phosphorylation after SIRT4 transfection. The transcription and translation of MYC and CCND1, target genes of the STAT3 pathway, were also blocked. Immunofluorescence revealed that pathway activation and nuclear STAT4 translocation were suppressed when SIRT4 was overexpressed. Furthermore, the effects of SIRT4 overexpression or depletion on proliferation could be offset by STAT3 activation or inhibition. Taken together, these results demonstrate that SIRT4 enhances the tamoxifen sensitivity of breast cancer cells by inhibiting the STAT3 signaling pathway. With this knowledge, therapeutic strategies with reduced drug resistance risk may be developed.
Successful Multidisciplinary Management of an Endodontic‐Periodontal Lesion Associated With a Palato‐Radicular Groove: A Case Report
Authors: Katwal Diksha , Fiorica Jennifer K. , Bleuel Jane , Clark Stephen J.
Published: September 2019

Introduction

This case report describes the collaborative management of an extensive combined endodontic‐periodontal lesion related to a long palato‐radicular groove (PRG) on a maxillary lateral incisor. Cases with similar severity have been reported minimally in the endodontic journals but even less in the periodontal journals. This case report illustrates the result of multidisciplinary treatment of the combined lesions associated with PRG.

Case Presentation

A 63‐year‐old patient presented with a periapical radiolucency on tooth #10. After evaluation, the patient was diagnosed with an endodontic‐periodontal lesion associated with PRG. After being informed of a guarded prognosis, the patient consented to a surgical procedure in an effort to retain the tooth. Management of the case involved a combination of endodontic therapy, odontoplasty under dental operating microscopy to attempt to eliminate the root anomaly, and periodontal regenerative procedures with allografts and a resorbable barrier membrane. Clinical examination and the cone‐beam computed tomography scan at a 2‐year postoperative visit revealed a substantial reduction in probing depth and significant bone fill of the defect.

Conclusions

In the past, a long PRG in combination with a periapical lesion often resulted in extraction of the tooth. With accurate assessment of the etiology of the defect, patient education, and a multidisciplinary approach, teeth with a PRG may be retained with a stable outcome for years.
Exploratory examination of clinician perspectives on positive memories and post‐traumatic stress disorder interventions
Authors: Contractor Ateka A. , Caldas Stephanie V. , Dolan Megan , Banducci Anne N. , Jin Ling
Published: October 2019

Despite the role of positive memories in the aetiology and maintenance of post‐traumatic stress disorder (PTSD), most PTSD interventions primarily focus on traumatic memories. To aid the development of a PTSD‐specific technique focused on processing positive memories, we gathered formative input from practicing clinicians on the content, format, feasibility and acceptability of this proposed intervention technique. We recruited licensed clinicians (n = 46) through professional networks and psychology organisation Listservs, provided a description of a positive memory processing technique, and administered a questionnaire querying perspectives on the proposed technique. Most clinicians reported using positive memories in PTSD therapy (67.39%) and interest in addressing them in depth/frequently (71.74%). They reported that (a) positive memory processing could increase positive thoughts (82.50%), feelings (80%) and memory specificity (75%); (b) optimal intervention components included defining a positive memory as a peak experience (characterised by strong positive affect, a positive and impactful change on one's life, and overwhelming joy/happiness; 57.50%), identifying 1–3 memories (25.64%–33.33%), discussing them in session to elicit positive elements (68.57%–82.86%), tracking affect intensity/valence (57.14%), and using this technique to augment trauma‐focused interventions (57.14%); and (c) feasibility indicators included perceived acceptability to clients (80.65%) and clinicians (66.67%), practicality (51.61%), successful implementation considering resources/time (63.33%), ease of learning (51.61%) and positive impact on therapy satisfaction/tolerability (54.84%–58.06%). Taken together, our study provides parameters for the development and investigation of a PTSD‐specific positive memory processing technique.
Stabilization of Hydroxynitrile Lyases from Two Variants of Passion Fruit, Passiflora edulis Sims and Passiflora edulis Forma flavicarpa, by C‐Terminal Truncation
Authors: Nuylert Aem , Motojima Fumihiro , Khanongnuch Chartchai , Hongpattarakere Tipparat , Asano Yasuhisa
Published: September 2019

Because the synthesis of chiral compounds generally requires a broad range of substrate specificity and stable enzymes, screening for better enzymes and/or improvement of enzyme properties through molecular approaches is necessary for sustainable industrial development. Herein, the discovery of unique hydroxynitrile lyases (HNLs) from two species of passion fruits, Passiflora edulis forma flavicarpa (yellow passion fruit, PeHNL‐Ny) and Passiflora edulis Sims (purple passion fruit, PeHNL‐Np), isolated and purified from passion fruit leaves is reported. These are the smallest HNLs (comprising 121 amino acids). Amino acid sequences of both enzymes are 99 % identical; there is a difference of one amino acid in a consensus sequence. PeHNL‐Np has an Ala residue at position 107 and is nonglycosylated at Asn105. Because it was confirmed that natural and glycosylated PeHNL‐Ny showed superior thermostability, pH stability, and organic tolerance to that of PeHNL‐Np, it has been speculated that protein engineering around the only glycosylation site, Asn105, located at the C‐terminal region of PeHNL‐Ny, might contribute to the stabilization of PeHNL. Therefore, the focus is on improved stability of the nonglycosylated PeHNL by truncating its C‐terminal region. The C‐terminal‐truncated PeHNLΔ107 was obtained by truncating 15 amino acids from the C terminus followed by expression in Escherichia coli. PeHNLΔ107 expressed in E. coli was not glycosylated, and showed improved thermostability, solvent stability, and reusability similar to that of the wild‐type glycosylated form of PeHNL expressed in Pichia pastoris. These data reveal that the lack of the high‐flexibility region at the C terminus of PeHNL might be a possible reason for improving the stability of PeHNL.
Multiple myeloma with clivus involvement, neurological symptoms, and 45 g/L proteinorachia
Authors: Chantran Yannick , Lavillegrand Jean‐Rémi , Lefrere Bertrand , Gaillet Antoine , Aucouturier Pierre , Garderet Laurent
Published: October 2019

The mechanical obstruction of cerebrospinal fluid (CSF) flow can lead to very high hyperproteinorachia. In myeloma, tumoral clivus obstruction can cause such high proteinorachia, associated with paraprotein detection in the CSF in absence of intrathecal synthesis.
Preoperative endoscopic tattooing for colonic polyp localization: From blue to black
Authors: Blouhos Konstantinos , Boulas Konstantinos A. , Paraskeva Aikaterini , Gravalidou Ioanna , Chatzipourganis Konstantinos , Triantafyllidis Alexandros , Hatzigeorgiadis Anestis
Published: September 2019

When surgical polypectomy and not segmental resection is planned, preoperative endoscopic tattooing with high‐volume undiluted methylene blue should be avoided as it can result in colon perforation.
The sublingual use of atropine in the treatment of clozapine‐induced sialorrhea: A systematic review
Authors: Van der Poorten Thomas , De Hert Marc
Published: September 2019

Clozapine is considered the golden standard in the treatment of therapy‐resistant schizophrenia; however, it associated with bothersome side effects such as sialorrhea. Current evidence suggests that the sublingual use of atropine seems to be safe and effective and could be considered as a first‐line treatment of clozapine‐induced sialorrhea.
Prenatal diagnosis of vasa previa and the course of the cord vessels contribute to the safety of cesarean sections: A case report
Authors: Aoki Mihoko , Obata Soichiro , Odagami Mizuha , Miyagi Etsuko , Aoki Shigeru
Published: September 2019

Vasa previa can occur even in cases without placental malposition and the precise diagnosis of vasa previa, and the course of the cord vessels contributes to a safe delivery. The color Doppler is a useful and easy‐to‐use device to confirm the presence of vasa previa.
A case of effective oral rehabilitation after mandibular resection
Authors: Kataoka Toshiyuki , Akagi Yuichi , Kagawa Chie , Sasaki Ryo , Okamoto Toshihiro , Ando Tomohiro
Published: September 2019

Radical mandible resection causes significant functional and cosmetic impairment. Nonvascularized bone reconstruction and oral rehabilitation using fixed prosthesis with dental implants enabled recovery of appearance and mastication function.
Bimetal Networked Nanosheets CoxNi3−xS2 as An Efficient Electrocatalyst for Hydrogen Evolution
Authors: Yao Jing , Bai Lina , Ma Xinzhi , Zhang Mingyi , Li Lu , Zhou Gang , Gao Hong
Published: September 2019

For the first time, 3D networked CoxNi3−xS2 nanosheets were facilely grown on Ni foam via two‐step hydrothermal method forming a composite electrode (CoxNi3−xS2/NF) for electrocatalytic hydrogen evolution reaction (HER) under alkaline condition. With x value being 1.4, the as‐prepared Co1.4Ni1.6S2/NF shows superior performance as a HER electrode with low overpotentials of 68 mV, 160 mV and 226 mV at current densities of 10, 50 and 100 mA cm−2 respectively and exhibits remarkable electrochemical durability for 50 h in 1.0 M KOH solution. We propose that the synergistic and electron‐coupling effect between Co and Ni atoms in the CoxNi3−xS2/NF networked nanosheets lead to abundant active sites on surface and optimizes electronic structure. Density functional theory calculations indicate the introduction of Co atom can reduce the adsorption of H* thus optimize the hydrogen adsorption free energy. The CoxNi3−xS2 nanosheets not only break through the limitations of traditional Ni−Co−S materials at the ratio of Ni and Co : S as 3 : 4 but also improve the activity of hydrogen evolution. The 3D CoxNi3−xS2/NF nanomaterials become a promising alternative to the Pt‐based electrocatalysts for hydrogen evolution.
Model‐Informed Dose Selection for Xentuzumab, a Dual Insulin‐Like Growth Factor‐I/II—Neutralizing Antibody
Authors: Parra‐Guillen Zinnia P. , Schmid Ulrike , Janda Alvaro , Freiwald Matthias , Troconiz Iñaki F.
Published: September 2019

Over the past decade, the insulin‐like growth factor (IGF)‐signaling pathway has gained substantial interest as potential therapeutic target in oncology. Xentuzumab, a humanized IgG1 monoclonal antibody, binds to IGF‐I and IGF‐II thereby inhibiting the downstream signaling essential for survival and tumor growth. This pathway is further regulated by circulating IGF binding proteins (IGFBPs). In this work, a mechanistic model characterizing the dynamics and interactions of IGFs, IGFBPs, and Xentuzumab has been developed to guide dose selection. Therefore, in vitro and in vivo literature information was combined with temporal IGF‐I, IGF‐II, and IGFBP‐3 total plasma concentrations from two phase I studies. Based on the established quantitative framework, the time‐course of free IGFs as ultimate drug targets not measured in clinics was predicted. Finally, a dose of 1000 mg/week—predicted to reduce free IGF‐I and free IGF‐II at steady‐state by at least 90% and 64%, respectively—was suggested for phase II.
Examining the Use of Real‐World Evidence in the Regulatory Process
Authors: Beaulieu‐Jones Brett K. , Finlayson Samuel G. , Yuan William , Altman Russ B. , Kohane Isaac S. , Prasad Vinay , Yu Kun‐Hsing
Published: September 2019

The 21st Century Cures Act passed by the United States Congress mandates the US Food and Drug Administration to develop guidance to evaluate the use of real‐world evidence (RWE) to support the regulatory process. RWE has generated important medical discoveries, especially in areas where traditional clinical trials would be unethical or infeasible. However, RWE suffers from several issues that hinder its ability to provide proof of treatment efficacy at a level comparable to randomized controlled trials. In this review article, we summarized the advantages and limitations of RWE, identified the key opportunities for RWE, and pointed the way forward to maximize the potential of RWE for regulatory purposes.
Melamine‐Based Microporous Organic Framework Thin Films on an Alumina Membrane for High‐Flux Organic Solvent Nanofiltration
Authors: Amirilargani Mohammad , Yokota Giovana N. , Vermeij Gijs H. , Merlet Renaud B. , Delen Guusje , Mandemaker Laurens D. B. , Weckhuysen Bert M. , Winnubst Louis , Nijmeijer Arian , de Smet Louis C. P. M. , Sudhölter Ernst J. R.
Published: September 2019

Microporous polymer frameworks have attracted considerable attention to make novel separation layers owing to their highly porous structure, high permeability, and excellent molecular separation. This study concerns the fabrication and properties of thin melamine‐based microporous polymer networks with a layer thickness of around 400 nm, supported on an α‐alumina support and their potential use in organic solvent nanofiltration. The modified membranes show excellent solvent purification performances, such as n‐heptane permeability as high as 9.2 L m−2 h−1 bar −1 in combination with a very high rejection of approximately 99 % for organic dyes with molecular weight of ≥457 Da. These values are higher than for the majority of the state‐of‐the‐art membranes. The membranes further exhibit outstanding long‐term operation stability. This work significantly expands the possibilities of using ceramic membranes in organic solvent nanofiltration.
Genetic diversity and demographic history of introduced sika deer on the Delmarva Peninsula
Authors: Kalb David M. , Delaney Deborah A. , DeYoung Randy W. , Bowman Jacob L.
Published: September 2019

The introduction of non‐native species can have long‐term effects on native plant and animal communities. Introduced populations are occasionally not well understood and offer opportunities to evaluate changes in genetic structure through time and major population changes such as bottleneck and or founder events. Invasive species can often evolve rapidly in new and novel environments, which could be essential to their long‐term success. Sika deer are native to East Asia, and their introduction and establishment to the Delmarva Peninsula, USA, is poorly documented, but probably involved ≥1 founder and/or bottleneck events. We quantified neutral genetic diversity in the introduced population and compared genetic differentiation and diversity to the presumed source population from Yakushima Island, Japan, and a captive population of sika deer in Harrington, Delaware, USA. Based on the data from 10 microsatellite DNA loci, we observed reduced genetic variation attributable to founder events, support for historic hybridization events, and evidence that the population did originate from Yakushima Island stocks. Estimates of population structure through Bayesian clustering and demographic history derived from approximate Bayesian computation (ABC), were consistent with the hypothesized founder history of the introduced population in both timing and effective population size (approximately five effective breeding individuals, an estimated 36 generations ago). Our ABC results further supported a single introduction into the wild happening before sika deer spread throughout the Delmarva. We conclude that free‐ranging sika deer on Delmarva are descended from ca. five individuals introduced about 100 years ago from captive stocks of deer maintained in the United Kingdom. Free‐ranging sika deer on Delmarva have lost neutral diversity due to founder and bottleneck events, yet populations have expanded in recent decades and show no evidence of abnormalities associated with inbreeding. We suggest management practices including increasing harvest areas and specifically managing sika deer outside of Maryland.
Evolutionary relationship of fat body endoreduplication and queen fecundity in termites
Authors: Nozaki Tomonari , Matsuura Kenji
Published: September 2019

Endoreduplication or nuclear genome replication without cell division is widely observed in the metabolically active tissues of plants and animals. The fat body cells of adult female insects produce abundant yolk proteins and become polyploid, which is assumed to accelerate egg production. Recently, it was reported that in termites, endopolyploidy in the fat body occurs only in queens but not in the other females; however, the relationship between the fecundity and ploidy level in the fat body remains unclear. Termite queens exhibit a huge variation in their egg‐producing capacity among different species; queens in the species with a foraging lifestyle, in which workers leave the nest to forage outside, are much more fecund than those in the species living in a single piece of wood. In this study, we conducted ploidy analyses on three foragings and three wood‐dwelling termites via flow cytometry. In all the species, the fat body of queens contained significantly more polyploid cells than that of other nonreproductive females, considering their body size effect. However, the male fat body, which is not involved in yolk production, did not show consistency in polyploid cell numbers among the species studied. Moreover, highly fecund queens in foraging termites exhibit higher levels of endopolyploidy in their fat body than those with less fecundity in wood‐dwelling termites. These results suggest that endopolyploidy in the fat body of termite queens can boost their egg production, and the level of endopolyploidy in their fat body is linked to their fecundity. Our study provides a novel insight into the evolutionary relationship between endoreduplication and caste specialization in social insects.
Predicting resilience of ecosystem functioning from co‐varying species' responses to environmental change
Authors: Greenwell Matthew P. , Brereton Tom , Day John C. , Roy David B. , Oliver Tom H.
Published: September 2019

Understanding how environmental change affects ecosystem function delivery is of primary importance for fundamental and applied ecology. Current approaches focus on single environmental driver effects on communities, mediated by individual response traits. Data limitations present constraints in scaling up this approach to predict the impacts of multivariate environmental change on ecosystem functioning.

We present a more holistic approach to determine ecosystem function resilience, using long‐term monitoring data to analyze the aggregate impact of multiple historic environmental drivers on species' population dynamics. By assessing covariation in population dynamics between pairs of species, we identify which species respond most synchronously to environmental change and allocate species into “response guilds.” We then use “production functions” combining trait data to estimate the relative roles of species to ecosystem functions. We quantify the correlation between response guilds and production functions, assessing the resilience of ecosystem functioning to environmental change, with asynchronous dynamics of species in the same functional guild expected to lead to more stable ecosystem functioning.

Testing this method using data for butterflies collected over four decades in the United Kingdom, we find three ecosystem functions (resource provisioning, wildflower pollination, and aesthetic cultural value) appear relatively robust, with functionally important species dispersed across response guilds, suggesting more stable ecosystem functioning. Additionally, by relating genetic distances to response guilds we assess the heritability of responses to environmental change. Our results suggest it may be feasible to infer population responses of butterflies to environmental change based on phylogeny—a useful insight for conservation management of rare species with limited population monitoring data.

Our approach holds promise for overcoming the impasse in predicting the responses of ecosystem functions to environmental change. Quantifying co‐varying species' responses to multivariate environmental change should enable us to significantly advance our predictions of ecosystem function resilience and enable proactive ecosystem management.
Hypervalent Iodine(III) Reagent Mediated Regioselective Cycloaddition of Aldoximes with Enaminones
Authors: Yoshimura Akira , Jarvi Melissa E. , Shea Michael T. , Makitalo Cody L. , Rohde Gregory T. , Yusubov Mekhman S. , Saito Akio , Zhdankin Viktor V.
Published: September 2019

An efficient oxidative cycloaddition of enaminones with nitrile oxides generated in situ from respective aldoximes using hypervalent iodine reagents has been developed. Reactions of various aldoximes with enaminones in the presence of [hydroxy(tosyloxy)iodo]benzene involved the regioselective cycloaddition reaction resulting in the formation of the 3,4‐disubstituted isoxazoles in moderate to good yields. Structures of several isoxazole products were confirmed by a single X‐ray crystallography.