bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene
Authors: Hagege Ermias , Grey Richard J. , Lopez Grisel , Roshan Lal Tamanna , Sidransky Ellen , Tayebi Nahid
Published: November 2017

Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p.Arg296Gln) from his father, while the second, Gly202Arg (c.721G>A; p.Gly241Arg) arose by either maternal germline mosaicism or as a de novo mutation. This is the first time mutation Gly202Arg has been reported to be inherited non‐traditionally. This report is part of a growing literature suggesting that GD can be inherited via germline or de novo mutations, and emphasizes that it is critical for clinicians to consider such inheritance when making diagnostic decisions or providing genetic counseling.
Brief communication: A re‐evaluation of the health index of southern Brazilian shellmound populations
Authors: Hubbe Mark , Green Madelyn K. , Cheverko Colleen M. , Neves Walter A.
Published: November 2017

Objectives

The southern Brazilian shellmounds provide archaeological evidence of prolonged human activity in the coast from approximately 6000 to 1000 BP. Shellmound building populations exploited the rich coastal estuarine zones, and the human remains recovered from them are important sources of information on health and overall lifestyle of these mid‐Holocene groups. Therefore, they were included in the Western Hemisphere Global History of Health project. The shellmounds contribute the highest Health Index in the Western Hemisphere, but these conclusions are based on collections that exclude postcranial remains. Here, we reconstruct the Health Index for one specific shellmound using both cranial and postcranial remains to determine whether the initial studies might misrepresent the relative health of the Brazilian shellmound builders.

Materials and methods

The Health Index was calculated for a sample of 18 complete skeletons recovered from the shellmound Porto do Rio Vermelho 02 (Santa Catarina Island, Brazil). The Heath Index was calculated with and without postcranial markers and the results are compared with the Western Hemisphere Global History of Health data.

Results

The Health Index for Porto do Rio Vermelho 02 is lower than the reported average for American series in the Western Hemisphere Global History of Health Project and considerably lower than the original index reported for Brazilian shellmounds. This discrepancy is due to an increased prevalence of infectious disease and low stature.

Conclusions

Although the Health Index remains a useful comparison statistic, re‐evaluation of fragmentary skeletal remains demonstrates the need for caution when applying it to incomplete skeletal series.
Severe pyoderma gangrenosum caused by myelodysplastic syndrome successfully treated with decitabine administered by a noncytotoxic regimen
Authors: Saleh Mostafa F. M. , Saunthararajah Yogen
Published: November 2017

Key Clinical Message

Pyoderma gangrenosum (PG) is a morbid necrotizing neutrophilic dermatoses for which current treatments are inadequate. Here, we describe the use of a novel noncytotoxic regimen of the deoxycytidine analog decitabine to treat underlying myeloid malignancy causing PG, to thereby produce safe and effective resolution of extensive PG.
Cobalt‐Catalyzed Annulation Reactions via C−H Bond Activation
Authors: Prakash Sekar , Kuppusamy Ramajayam , Cheng Chien‐Hong
Published: November 2017

Considerable research attention has been directed towards the use of first‐row transition metals in organic synthesis. The more abundant, and less expensive cobalt is considered to be an effective alternative for expensive second and third‐row noble metals, especially in C−H bond functionalization reactions. In this Minireview, we will summarize the features, and recent achievements of the Co‐catalyzed directing group assisted C−H activation/cyclization reactions and their mechanistic insights.
Mouse Eosinophils: Identification, Isolation, and Functional Analysis
Authors: Reichman Hadar , Rozenberg Perri , Munitz Ariel
Published: November 2017

Eosinophils are bone marrow–derived cells that differentiate in the bone marrow and migrate into the peripheral blood primarily under the regulation of interleukin (IL)–5. Eosinophil levels in the blood are relatively low. However, under steady‐state conditions and in settings of allergic inflammation, parasite infections, or even cancer, they migrate and mainly reside in mucosal tissues where they have key effector and immune‐modulating functions. Functional studies using eosinophils are not simple, since these cells are terminally differentiated and rapidly die in vitro. Thus, establishing simple methods to characterize, obtain, and functionally assess eosinophil activities is important. In this unit, we describe methodology for identifying tissue eosinophils by flow cytometry. In addition, we provide detailed methods for isolating eosinophils and for differentiating them from bone marrow cells for further functional studies. © 2017 by John Wiley & Sons, Inc.
Screening and Identifying Membrane Proteins Favorable for Crystallization
Authors: Kim Jared , Ng Ho Leung
Published: November 2017

This unit addresses several critical challenges associated with membrane protein crystallography by screening membrane proteins from Escherichia coli, Saccharomyces cerevisiae, and Sus scrofa cerebral tissue for biochemical properties favorable for crystallization. First, a tissue sample or cell pellet is obtained. The cells are isolated, washed, and then lysed either by sonication, bead beating, or manual homogenization. Membrane proteins are fractionated from the lysates by centrifugation and solubilized in a mild detergent suitable for crystallization, such as n‐dodecyl‐β‐maltoside (DDM). Detergent extracts are then centrifuged, heat precipitated, and filtered to remove insoluble, thermally unstable, and/or aggregated proteins. Samples are then prepared for analysis by mass spectrometry: proteins are precipitated by methanol/chloroform extraction and subjected to reduction, alkylation, and protease digestion. The resulting peptides are passed through a detergent removal column, desalted, rehydrated in 0.1% formic acid (v/v), and identified by LC‐MS/MS. © 2017 by John Wiley & Sons, Inc.
Highly Efficient and Robust Enantioselective Liquid–Liquid Extraction of 1,2‐Amino Alcohols utilizing VAPOL‐ and VANOL‐based Phosphoric Acid Hosts
Authors: Pinxterhuis Erik B. , Gualtierotti Jean‐Baptiste , Wezenberg Sander J. , de Vries Johannes G. , Feringa Ben L.
Published: November 2017

The large‐scale production of enantiopure compounds in a cost‐effective and environmentally friendly manner remains one of the major challenges of modern‐day chemistry. The resolution of racemates through enantioselective liquid–liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid–liquid extraction of 1,2‐amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now‐optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U‐tube experiments.
Developmental social isolation affects adult behavior, social interaction, and dopamine metabolite levels in zebrafish
Authors: Shams Soaleha , Amlani Shahid , Buske Christine , Chatterjee Diptendu , Gerlai Robert
Published: November 2017

The zebrafish is a social vertebrate and an excellent translational model for a variety of human disorders. Abnormal social behavior is a hallmark of several human brain disorders. Social behavioral problems can arise as a result of adverse early social environment. Little is known about the effects of early social isolation in adult zebrafish. We compared zebrafish that were isolated for either short (7 days) or long duration (180 days) to socially housed zebrafish, testing their behavior across ontogenesis (ages 10, 30, 60, 90, 120, 180 days), and shoal cohesion and whole‐brain monoamines and their metabolites in adulthood. Long social isolation increased locomotion and decreased shoal cohesion and anxiety in the open‐field in adult. Additionally, both short and long social isolation reduced dopamine metabolite levels in response to social stimuli. Thus, early social isolation has lasting effects in zebrafish, and may be employed to generate zebrafish models of human neuropsychiatric conditions.
New specific primers for amplification of the Internal Transcribed Spacer region in Clitellata (Annelida)
Authors: Liu Yingkui , Erséus Christer
Published: November 2017

Nuclear molecular evidence, for example, the rapidly evolving Internal Transcribed Spacer region (ITS), integrated with maternally inherited (mitochondrial) COI barcodes, has provided new insights into the diversity of clitellate annelids. PCR amplification and sequencing of ITS, however, are often hampered by poor specificity of primers used. Therefore, new clitellate‐specific primers for amplifying the whole ITS region (ITS: 29F/1084R) and a part of it (ITS2: 606F/1082R) were developed on the basis of a collection of previously published ITS sequences with flanking rDNA coding regions. The specificity of these and other ITS primers used for clitellates were then tested in silico by evaluating their mismatches with all assembled and annotated sequences (STD, version r127) from EMBL, and the new primers were also tested in vitro for a taxonomically broad sample of clitellate species (71 specimens representing 11 families). The in silico analyses showed that the newly designed primers have a better performance than the universal ones when amplifying clitellate ITS sequences. In vitro PCR and sequencing using the new primers were successful, in particular, for the 606F/1082R pair, which worked well for 65 of the 71 specimens. Thus, using this pair for amplifying the ITS2 will facilitate further molecular systematic investigation of various clitellates. The other pair (29F/1084R), will be a useful complement to existing ITS primers, when amplifying ITS as a whole.
Evidence of exceptional oyster‐reef resilience to fluctuations in sea level
Authors: Ridge Justin T. , Rodriguez Antonio B. , Fodrie F. Joel
Published: November 2017

Ecosystems at the land–sea interface are vulnerable to rising sea level. Intertidal habitats must maintain their surface elevations with respect to sea level to persist via vertical growth or landward retreat, but projected rates of sea‐level rise may exceed the accretion rates of many biogenic habitats. While considerable attention is focused on climate change over centennial timescales, relative sea level also fluctuates dramatically (10–30 cm) over month‐to‐year timescales due to interacting oceanic and atmospheric processes. To assess the response of oyster‐reef (Crassostrea virginica) growth to interannual variations in mean sea level (MSL) and improve long‐term forecasts of reef response to rising seas, we monitored the morphology of constructed and natural intertidal reefs over 5 years using terrestrial lidar. Timing of reef scans created distinct periods of high and low relative water level for decade‐old reefs (n = 3) constructed in 1997 and 2000, young reefs (n = 11) constructed in 2011 and one natural reef (approximately 100 years old). Changes in surface elevation were related to MSL trends. Decade‐old reefs achieved 2 cm/year growth, which occurred along higher elevations when MSL increased. Young reefs experienced peak growth (6.7 cm/year) at a lower elevation that coincided with a drop in MSL. The natural reef exhibited considerable loss during the low MSL of the first time step but grew substantially during higher MSL through the second time step, with growth peaking (4.3 cm/year) at MSL, reoccupying the elevations previously lost. Oyster reefs appear to be in dynamic equilibrium with short‐term (month‐to‐year) fluctuations in sea level, evidencing notable resilience to future changes to sea level that surpasses other coastal biogenic habitat types. These growth patterns support the presence of a previously defined optimal growth zone that shifts correspondingly with changes in MSL, which can help guide oyster‐reef conservation and restoration.
Squaramide‐Linked Chloramphenicol Base Hybrid Catalysts for the Asymmetric Michael Addition of 2,3‐Dihydrobenzofuran‐2‐carboxylates to Nitroolefins
Authors: Yan Linjie , Huang Guanxin , Wang Haifeng , Xiong Fangjun , Peng Haihui , Chen Fener
Published: November 2017

An array of hybrid catalysts incorporating a chloramphenicol base moiety linked to another chiral scaffold through a squaramide linker were developed and successfully used in the Michael addition of 2,3‐dihydrobenzofuran‐2‐carboxylates to nitroolefins. Control experiments suggested that the hybrid catalysts were more reactive than nonhybridized bifunctional catalysts, and matching of the chirality between the two scaffolds was crucial for high reactivity and stereoselectivity. These hybrid organocatalysts could be used with a variety of substrates. At a 0.5 mol‐% catalyst loading, a range of 2,3‐dihydrobenzofuran‐2‐carboxylates derivatives bearing quaternary and tertiary stereogenic centers were obtained in high yields (up to 98 %) with excellent enantioselectivities (up to 99 % ee) and moderate diastereoselectivities (up to 8:92 dr).
Experimental and simulation studies for reaction enhancement of catalytic CF4 hydrolysis by consecutive HF removal using a multi‐stage catalyst‐adsorbent reactor
Authors: Han Jae‐Yun , Kim Chang‐Hyun , Lee Boreum , Jeong Seonju , Lim Hankwon , Lee Kwan‐Young , Ryi Shin‐Kun
Published: November 2017

In this paper, a multi‐stage catalyst‐adsorbent reactor consisting of a series of catalyst and adsorbent beds is proposed for an effective tetrafluoromethane (CF4) abatement and conversion of corrosive hydrogen fluoride (HF) to CaF2, a useful chemical. Experimentally, enhanced CF4 conversions were observed in multi‐stage catalyst‐adsorbent reactors compared to a zero‐stage reactor (catalyst bed only) confirming sorption‐enhanced CF4 hydrolysis due to selective removal of HF during reaction. In addition, some useful design guidelines to select the number of stages and a proper time to replace adsorbents are presented. To develop a process simulation model to represent experimental data, Aspen HYSYS®, a commercial process simulator, was used providing a proper model to match experimental data quite reasonably. Based on experimental and simulative studies, a three‐ or four‐stage catalyst‐adsorbent reactor is recommended for CF4 abatement considering both reactor performance and capital/operating expenditures. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.
Sclerostin Antibody Augments the Anabolic Bone Formation Response in a Mouse Model of Mechanical Tibial Loading
Authors: Morse Alyson , Schindeler Aaron , McDonald Michelle M , Kneissel Michaela , Kramer Ina , Little David G
Published: November 2017

Decreased activity or expression of sclerostin, an endogenous inhibitor of Wnt/β-catenin signaling, results in increased bone formation and mass. Antibodies targeting and neutralizing sclerostin (Scl-Ab) have been shown to increase bone mass and reduce fracture risk. Sclerostin is also important in modulating the response of bone to changes in its biomechanical environment. However, the effects of Scl-Ab on mechanotransduction are unclear, and it was speculated that the loading response may be altered for individuals receiving Scl-Ab therapy. To address this, we carried out a 2-week study of tibial cyclic compressive loading on C57Bl/6 mice treated with vehicle or 100 mg/kg/wk Scl-Ab. Increases in bone volume, density, and dynamic bone formation were found with loading, and the anabolic response was further increased by the combination of load and Scl-Ab. To investigate the underlying mechanism, gene profiling by RNA sequencing (RNAseq) was performed on tibias isolated from mice from all four experimental groups. Major alterations in Wnt/β-catenin gene expression were found with tibial loading, however not with Scl-Ab treatment alone. Notably, the combination of load and Scl-Ab elicited a synergistic response from a number of specific Wnt-related and mechanotransduction factors. An unexpected finding was significant upregulation of factors in the Rho GTPase signaling pathway with combination treatment. In summary, combination therapy had a more profound anabolic response than either Scl-Ab or loading treatment alone. The Wnt/β-catenin and Rho GTPase pathways were implicated within bone mechanotransduction and support the concept that bone mechanotransduction is likely to encompass a number of interconnected signaling pathways. © 2017 American Society for Bone and Mineral Research.
Functional SNP in microRNA‐491‐5p binding site of MMP9 3′‐UTR affects cancer susceptibility
Authors: Pirooz Homeira Javadi , Jafari Niloofar , Rastegari Mozhdeh , Fathi‐Roudsari Mehrnoosh , Tasharrofi Nooshin , Shokri Gelareh , Tamadon Mona , Sazegar Hossein , Kouhkan Fatemeh
Published: November 2017

MicroRNAs (miRNA) are small RNA molecules that negatively regulate gene expression through base pairing interactions between 3′‐UTR of the target mRNAs and seed sequence of miRNA. Any changes in the recognition site could destroy binding sites or modify binding affinity, resulting in evasion from miRNA regulation. A putative binding site for miR‐491‐5p resides in 3′‐UTR of MMP9, and a genetic variant (rs1056628 A → C) is present in this region. The role of MMP9 over expression well marked in various cancers. However, whether rs1056628 SNP in miR‐491‐5p binding site of MMP9 3′‐UTR could abrogate its post‐transcriptional regulation and affect cancer susceptibility remains largely unknown. To test this, the rs1056628 SNP was genotyped in 300 cases of lung, gastric and breast cancers and 200 age‐ and sex‐matched healthy controls. The results showed that compared with the AA genotype, C was a risk genotype for all three cancers development and was also associated with gastric and breast cancers metastasis and invasion. Based on the base pairing analysis and secondary structure evaluation of MMP9 mRNA and miR‐491‐5p, we found that miR‐491‐5p had a higher binding affinity for A genotype than the C genotype. The Luciferase activity of MMP9 3′‐UTR indicates differential regulation of two genetic variations of MMP9. Overexpression of miR‐491‐5p decreased MMP9 mRNA level in cell lines of gastric, breast and lung cancers and thus leads to decreasing of the invasion ability. Therefore, for the first time we imply that the C variant of MMP9 contributes to the likelihood of gastric, breast and lung cancers susceptibility via a novel mechanism of subtle gene regulation through miRNA binding capacity.
Rn7SK small nuclear RNA is involved in neuronal differentiation
Authors: Bazi Zahra , Bertacchi Michele , Abasi Mozhgan , Mohammadi‐Yeganeh Samira , Soleimani Masoud , Wagner Nicole , Ghanbarian Hossein
Published: November 2017

Rn7SK‐mediated global transcriptional regulation, key function of this small nuclear RNA (snRNA), is mediated by inhibition of the positive transcription elongation factor b (P‐TEFb). Recently, we have identified a potential anti‐proliferative and tumor‐suppressive function of Rn7SK. However, its possible regulatory role in development and cell programming has not been investigated so far. Here, we examined transcriptional levels of Rn7SK in different mouse organs. Interestingly, an increased expression level of the RNA was observed in the brain. Furthermore, we could demonstrate that Rn7SK has a dynamic expression pattern during brain development from embryo to adult: 7SK snRNA expression was particularly high at embryonic day (E) 18.5 and adult stages, while a low level of this non‐coding RNA was detected at E11.5. Moreover, a decreased transcription level was identified in proliferating progenitors whereas a strong upregulation of Rn7SK was observed during neural differentiation in vivo. Similar to the in vivo situation, in vitro neuronal differentiation experiments employing embryonic stem cells (ESCs) demonstrated the same expression pattern of 7SK with high expression levels in differentiating neurons. Neuronal differentiation of ESCs was compromised when we knocked down Rn7SK, indicating an important role of 7SK in the acquisition of a neural fate.
Functional analysis of metallothionein MTT5 from Tetrahymena thermophila
Authors: Zhou Huanxin , Xu Jing , Wang Wei
Published: November 2017

Metallothioneins (MTs) constitute a superfamily of cysteine‐rich proteins that bind heavy‐metal ions by metal‐thiolate clusters. Five MT genes from Tetrahymena thermophila was subdivided into 7a (MTT1, MTT3, and MTT5) and 7b (MTT2 and MTT4) subfamilies. In the study, MTT5 was knocked out in Tetrahymena. The mutant cells were sensitive to Cd2+ and Pb2+ but poorly sensitive to Cu+. In the MTT5 knockout cells, the expression levels of MTT1 and MTT3 were significantly up‐regulated under Cd2+ and Pb2+ stresses, whereas the expression levels of MTT2 and MTT4 were significantly up‐regulated under Cu+ stress relative to those in the wild‐type cells. Furthermore, recombinant GST‐MTT5 was expressed in Escherichia coli/pGEX‐MTT5 and purified by affinity chromatography. Fluorescence quenching analysis showed that apoMTT5 can bind 8 Cd2+, 8 Pb2+, and 12 Cu+. The metal‐binding ability of the MTT5 complex followed the order of Pb2+ > Cd2+ > Cu+. Meanwhile, the half‐maximal inhibitory concentrations of the heavy‐metal ions for E. coli/pGEX‐MTT5 were as follows: Cu+ (483.9 µM) > Pb2+ (410.7 µM) > Cd2+ (130.8 µM). The accumulation of Cd2+, Pb2+, and Cu+ in the E. coli/pGEX‐MTT5 was enhanced relative to that of E. coli/pGEX‐4T. Results suggested that different MTs functionally compensated in Tetrahymena, and MTT5 was a potential candidate for cadmium and lead bioremediation.
A combination of Raspberry Pi and SoftEther VPN for controlling research devices via the Internet
Authors: Kuroda Toshikazu
Published: November 2017

Remote control over devices for experiments may increase the efficiency of operant research and expand the area where behavior can be studied. This article introduces a combination of Raspberry Pi® (Pi) and SoftEther VPN® that allows for such remote control via the Internet. The Pi is a small Linux computer with a great degree of flexibility for customization. Test results indicate that a Pi‐based interface meets the requirement for conducting operant research. SoftEther VPN® allows for establishing an extensive private network on the Internet using a single private Wi‐Fi router. Step‐by‐step instructions are provided in the present article for setting up the Pi along with SoftEther VPN®. Their potential for improving the way of conducting research is discussed.
Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis
Authors: Gomi Harumi , Solomkin Joseph S. , Schlossberg David , Okamoto Kohji , Takada Tadahiro , Strasberg Steven M. , Ukai Tomohiko , Endo Itaru , Iwashita Yukio , Hibi Taizo , Pitt Henry A. , Matsunaga Naohisa , Takamori Yoriyuki , Umezawa Akiko , Asai Koji , Suzuki Kenji , Han Ho‐Seong , Hwang Tsann‐Long , Mori Yasuhisa , Yoon Yoo‐Seok , Huang Wayne Shih‐Wei , Belli Giulio , Dervenis Christos , Yokoe Masamichi , Kiriyama Seiki , Itoi Takao , Jagannath Palepu , Garden O. James , Miura Fumihiko , de Santibañes Eduardo , Shikata Satoru , Noguchi Yoshinori , Wada Keita , Honda Goro , Supe Avinash Nivritti , Yoshida Masahiro , Mayumi Toshihiko , Gouma Dirk J. , Deziel Daniel J. , Liau Kui‐Hin , Chen Miin‐Fu , Liu Keng‐Hao , Su Cheng‐Hsi , Chan Angus C. W. , Yoon Dong‐Sup , Choi In‐Seok , Jonas Eduard , Chen Xiao‐Ping , Fan Sheung Tat , Ker Chen‐Guo , Giménez Mariano Eduardo , Kitano Seigo , Inomata Masafumi , Mukai Shuntaro , Higuchi Ryota , Hirata Koichi , Inui Kazuo , Sumiyama Yoshinobu , Yamamoto Masakazu
Published: November 2017

Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community‐acquired and healthcare‐associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class‐definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de‐escalation or termination of antimicrobial therapy are now important parts of decision‐making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
Tokyo Guidelines 2018: management bundles for acute cholangitis and cholecystitis
Authors: Mayumi Toshihiko , Okamoto Kohji , Takada Tadahiro , Strasberg Steven M. , Solomkin Joseph S. , Schlossberg David , Pitt Henry A. , Yoshida Masahiro , Gomi Harumi , Miura Fumihiko , Garden O. James , Kiriyama Seiki , Yokoe Masamichi , Endo Itaru , Asbun Horacio J. , Iwashita Yukio , Hibi Taizo , Umezawa Akiko , Suzuki Kenji , Itoi Takao , Hata Jiro , Han Ho‐Seong , Hwang Tsann‐Long , Dervenis Christos , Asai Koji , Mori Yasuhisa , Huang Wayne Shih‐Wei , Belli Giulio , Mukai Shuntaro , Jagannath Palepu , Cherqui Daniel , Kozaka Kazuto , Baron Todd H. , de Santibañes Eduardo , Higuchi Ryota , Wada Keita , Gouma Dirk J. , Deziel Daniel J. , Liau Kui‐Hin , Wakabayashi Go , Padbury Robert , Jonas Eduard , Supe Avinash Nivritti , Singh Harjit , Gabata Toshifumi , Chan Angus C. W. , Lau Wan Yee , Fan Sheung Tat , Chen Miin‐Fu , Ker Chen‐Guo , Yoon Yoo‐Seok , Choi In‐Seok , Kim Myung‐Hwan , Yoon Dong‐Sup , Kitano Seigo , Inomata Masafumi , Hirata Koichi , Inui Kazuo , Sumiyama Yoshinobu , Yamamoto Masakazu
Published: November 2017

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
HBV, HCV, and HBV/HCV co‐infection among HIV‐positive patients in Hunan province, China: Regimen selection, hepatotoxicity, and antiretroviral therapy outcome
Authors: Su Shu , Fairley Christopher K. , Sasadeusz Joe , He Jianmei , Wei Xiuqing , Zeng Huan , Jing Jun , Mao Limin , Chen Xi , Zhang Lei
Published: November 2017

Co‐infection with hepatitis B (HBV) and C (HCV) is common among people living with HIV (PLHIV). This study investigates the impacts of hepatitis co‐infection on antiretroviral therapy (ART) outcomes and hepatotoxicity in PLHIV. The cohort study included 1984 PLHIV. Hepatotoxicity was defined by elevated alanine aminotransferase (ALT) levels. ART outcomes were measured by CD4 cell counts, viral load, and mortality rate in patients. Among 1984 PLHIV, 184 (9.3%) were co‐infected with HBV and 198 (10.0%) with HCV and 54 (2.7%) were co‐infected with HBV and HCV. Of these patients, 156 (7.9%) had ALT elevation ≥ grade 1 at baseline. During the course of ART, the mortality rate and its adjusted hazard ratio (AHR) in PLHIV who were co‐infected with HCV (2.6/100 person‐years [py], AHR = 2.3, 95%CI 1.1‐4.7) was higher than for patients with mono‐infected HIV, as it was for those with an elevated ALT (4.4/100 py, AHR = 3.8, [1.7‐8.2]) at baseline compared to those with normal ALT. After 6‐12 months of ART, the incidence of hepatotoxicity among all the patients was 3.7/100 py. The risk of hepatotoxicity was higher in HCV co‐infected (18.6/100 py, adjusted odds ratio [AOR] = 12.4, [8.1‐18.2]) than HIV mono‐infected patients, and for all regimens (nevirapine: 30.0/100 py, 34.2, 7.3‐47.9; zidovudine/stavudine: 24.7/100 py, 22.1, 7.1‐25.5; efavirenz: 14.5/100 py, 9.4, 3.5‐19.2; lopinavir/ritonavir: 40.1/100 py, 52.2, 9.5‐88.2) except tenofovir (4.3/100 py, 4.9, 0.8‐9.5). Patients with HBV/HCV co‐infected had high hepatotoxicity (10.0/100 py, 6.3, 1.2‐23.3) over the same period. Patients with HCV co‐infection and HBV/HCV co‐infection demonstrated higher hepatotoxicity rate compared with HIV mono‐infected patients in China.
A novel biosensor with high signal‐to‐noise ratio for real‐time measurement of dopamine levels in vivo
Authors: Ishida Akimasa , Imamura Atsushi , Ueda Yoshitomo , Shimizu Takeshi , Marumoto Ryosuke , Jung Cha‐Gyun , Hida Hideki
Published: November 2017

Fast‐scan cyclic voltammetry (FSCV) is an established method for measuring dopamine (DA) levels in the brain in real time. However, it is difficult to discriminate DA from other monoamines such as serotonin (5‐hydroxytryptamine, 5‐HT) and norepinephrine (NE). We report a novel DA‐specific biosensor consisting of a carbon‐fiber electrode coated with an ion‐exchange membrane, a layer containing monoamine oxidase B, and a cellulose membrane. We performed FSCV using the probe to monitor the amount of DA in vitro and in vivo. First, we measured currents in vitro in phosphate‐buffered saline as we added one micromole each of DA, 5‐HT, and NE. The results confirmed that the biosensor selectively detected DA. Next, we implanted the probe in the striatum of male rats to investigate whether it could selectively detect changes in the DA content in vivo. The probe detected both the tonic change induced by methamphetamine administration and the phasic change induced by electrical stimulation of the medial forebrain bundle. In contrast, the electrode in the 6‐hydroxydopamine–lesioned striatum did not respond to systemic selective serotonin or serotonin/norepinephrine reuptake inhibitors, confirming its selectivity. Furthermore, the probe in the striatum could still detect changes in the DA level 1 week after electrode implantation. The results suggest that the novel biosensor can measure real‐time changes in DA levels in vivo with a relatively high signal‐to‐noise ratio.
Primary producers or consumers? Increasing phytoplankton bacterivory along a gradient of lake warming and browning
Authors: Wilken Susanne , Soares Margarida , Urrutia‐Cordero Pablo , Ratcovich Jens , Ekvall Mattias K. , Van Donk Ellen , Hansson Lars‐Anders
Published: November 2017

Eukaryotic phytoplankton form the basis of aquatic food webs and play a key role in the global carbon cycle. Many of these evolutionarily diverse microalgae are also capable of feeding on other microbes, and hence simultaneously act both as primary producers and consumers. The net ecosystem impact of such mixotrophs depends on their nutritional strategy which is likely to alter with environmental change. Many temperate lakes are currently warming at unprecedented rates and are simultaneously increasing in water color (browning) due to increased run‐off of humic substances. We hypothesized that the resulting reduction in light intensity and increased bacterial abundances would favor mixotrophic phytoplankton over obligate autotrophs, while higher temperatures might boost their rates of bacterivory. We tested these hypotheses in a mesocosm experiment simulating a gradient of increasing temperature and water color in temperate shallow lakes as expected to occur over the coming century. Mixotrophs showed a faster increase in abundance under the climate change scenario during spring, when they dominated the phytoplankton community. Furthermore, both bacterial abundances and rates of phytoplankton bacterivory increased under future climate conditions. Bacterivory contributed significantly to phytoplankton resource acquisition under future climate conditions, while remaining negligible throughout most of the season in treatments resembling today's conditions. Hence, to our knowledge, we here provide the first evidence for an increasing importance of bacterivory by phytoplankton in future temperate shallow lakes. Such a change in phytoplankton nutritional strategies will likely impact biogeochemical cycles and highlights the need to conceptually integrate mixotrophy into current ecosystem models.
Influence of parameter accuracy on pharmacokinetic analysis of hyperpolarized pyruvate
Authors: Sun Chang‐yu , Walker Christopher M. , Michel Keith A. , Venkatesan Aradhana M. , Lai Stephen Y. , Bankson James A.
Published: November 2017

Purpose

To explore the effects of noise and error on kinetic analyses of tumor metabolism using hyperpolarized [1‐13C] pyruvate.

Methods

Numerical simulations were performed to systematically investigate the effects of noise, the number of unknowns, and error in kinetic parameter estimates on kinetic analysis of the apparent rate of chemical conversion from hyperpolarized pyruvate to lactate (kPL). A pharmacokinetic model with two physical and two chemical pools of hyperpolarized spins was used to generate and analyze the synthetic data.

Results

The reproducibility of kPL estimates worsened quickly when peak signal‐to‐noise ratio for hyperpolarized pyruvate was below approximately 20. The accuracy of kPL estimates was most sensitive to errors in high excitation angles, the vascular blood volume fraction (vb), and the rate of pyruvate extravasation (kve), and was least sensitive to errors in the T1 of pyruvate. When vb and/or kve were fit as additional unknowns, the accuracy of kPL estimates suffered, and when the vascular input function of pyruvate was also fit, the reproducibility of kPL estimates worsened.

Conclusions

The accuracy and precision of kPL estimates improve substantially for peak signal‐to‐noise ratio above approximately 20. Accurate estimates of perfusion parameters (combinations of vb, kve, and the pyruvate vascular input function) and transmit calibration at high excitation angles have the greatest effect on the accuracy of kinetic analyses. Magn Reson Med 79:3239–3248, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Relationships between tissue microstructure and the diffusion tensor in simulated skeletal muscle
Authors: Berry David B. , Regner Benjamin , Galinsky Vitaly , Ward Samuel R. , Frank Lawrence R.
Published: November 2017

Purpose

To establish a series of relationships defining how muscle microstructure and diffusion tensor imaging (DTI) are related.

Methods

The relationship among key microstructural features of skeletal muscle (fiber size, fibrosis, edema, and permeability) and the diffusion tensor were systematically simulated over physiologically relevant dimensions individually, and in combination, using a numerical simulation application. Stepwise multiple regression was used to identify which microstructural features of muscle significantly predict the diffusion tensor using single‐echo and multi‐echo DTI pulse sequences. Simulations were also performed in models with histology‐informed geometry to investigate the relationship between fiber size and the diffusion tensor in models with real muscle geometry.

Results

Fiber size is the strongest predictor of λ2, λ3, mean diffusivity, and fractional anisotropy in skeletal muscle, accounting for approximately 40% of the variance in the diffusion model when calculated with single‐echo DTI. This increased to approximately 70% when diffusion measures were calculated from the short T2 component of the multi‐echo DTI sequence. This nonlinear relationship begins to plateau in fibers with greater than 60‐μm diameter.

Conclusions

As the normal fiber size of a human muscle fiber is 40 to 60 μm, this suggests that DTI is a sensitive tool to monitor muscle atrophy, but may be limited in measurements of muscle with larger fibers. Magn Reson Med 80:317–329, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Chemische Energiekonversion: aus Wasser und Wind
Authors: Boeltken Tim , Selinsek Manuel , Pfeifer Peter
Published: November 2017

Wind‐ und Sonnenenergie fallen zeitlich fluktuierend an, werden aber gerade dann oft nicht benötigt. Umgewandelt in synthetische und schadstoffarm verbrennende Kraftstoffe, lassen sich große Mengen solcher Energieformen speichern. Ein Karlsruher Unternehmen zeigt, wie es geht.
Wiederverwertung: alte Reifen fein mahlen
Authors: Kroll Lothar , Hoyer Stefan
Published: November 2017

Fahrzeugreifen sind hohen Kräften und einer intensiven Verschleißbeanspruchung ausgesetzt, weshalb sie besonders widerstandsfähige Werkstoffe enthalten. Die chemische Zusammensetzung etwa der Verstärkungsfüllstoffe wird am Ende der Nutzungsdauer allerdings zum Problem für das Recycling.
Objectively Measured Physical Activity and Sedentary Behavior in Successful Weight Loss Maintainers
Authors: Ostendorf Danielle M. , Lyden Kate , Pan Zhaoxing , Wyatt Holly R. , Hill James O. , Melanson Edward L. , Catenacci Victoria A.
Published: November 2017

Objective

The objective of this study was to compare patterns of objectively measured moderate‐to‐vigorous physical activity (MVPA, ≥ 3.00 metabolic equivalents [METs]), light‐intensity physical activity (LPA, 1.50‐2.99 METs), and sedentary behavior (SB, < 1.50 METs) in successful weight loss maintainers (WLMs), normal weight controls (NC), and controls with overweight/obesity (OC).

Methods

Participants (18‐65 y) were recruited in three groups: WLM (maintaining ≥ 13.6‐kg weight loss for ≥ 1 year, n = 30), NC (BMI matched to current BMI of WLM, n = 33), and OC (BMI matched to pre–weight loss BMI of WLM, n = 27). All participants wore the activPAL for 1 week.

Results

Compared with OC and NC, WLM spent more awake time in total MVPA (WLM: 9.6 ± 3.9%, NC: 7.1 ± 2.1%, OC: 5.9 ± 2.0%; P < 0.01) and more time in sustained (≥ 10 min) bouts of MVPA (WLM: 39 ± 33, NC: 17 ± 14, OC: 9 ± 11 min/d; P < 0.01). Compared with OC, WLM and NC spent more awake time in LPA (WLM: 29.6 ± 7.9%, NC: 29.1 ± 8.3%, OC: 24.8 ± 6.7%; P = 0.04) and less awake time sedentary (WLM: 60.8 ± 9.3%, NC: 63.8 ± 9.5%, OC: 69.3 ± 7.5%; P < 0.01).

Conclusions

Results provide additional data supporting the important role of MVPA in weight loss maintenance and suggest notable differences in LPA and SB between normal weight individuals and those with overweight/obesity. Increasing LPA and/or decreasing SB may be additional potential targets for weight management interventions.
Hematopoietic stem cell transplantation in Niemann–Pick disease type B monitored by chitotriosidase activity
Authors: Quarello Paola , Spada Marco , Porta Francesco , Vassallo Elena , Timeus Fabio , Fagioli Franca
Published: November 2017

Here, we report a patient with Niemann–Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness.
Single‐cell whole exome and targeted sequencing in NPM1/FLT3 positive pediatric acute myeloid leukemia
Authors: Walter Christiane , Pozzorini Christian , Reinhardt Katarina , Geffers Robert , Xu Zhenyu , Reinhardt Dirk , von Neuhoff Nils , Hanenberg Helmut
Published: November 2017

Background

The small portion of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) present in children and adolescents is often masked by the high background of AML blasts and normal hematopoietic cells. The aim of the current study was to establish a simple workflow for reliable genetic analysis of single LSC‐enriched blasts from pediatric patients.

Procedure

For three AMLs with mutations in nucleophosmin 1 and/or fms‐like tyrosine kinase 3, we performed whole genome amplification on sorted single‐cell DNA followed by whole exome sequencing (WES). The corresponding bulk bone marrow DNAs were also analyzed by WES and by targeted sequencing (TS) that included 54 genes associated with myeloid malignancies.

Results

Analysis revealed that read coverage statistics were comparable between single‐cell and bulk WES data, indicating high‐quality whole genome amplification. From 102 single‐cell variants, 72 single nucleotide variants and insertions or deletions (70%) were consistently found in the two bulk DNA analyses. Variants reliably detected in single cells were also present in TS. However, initial screening by WES with read counts between 50–72× failed to detect rare AML subclones in the bulk DNAs.

Conclusions

In summary, our study demonstrated that single‐cell WES combined with bulk DNA TS is a promising tool set for detecting AML subclones and possibly LSCs.
An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana‐Farber Cancer Institute ALL Consortium protocol 05‐001
Authors: Kahn Justine M. , Cole Peter D. , Blonquist Traci M. , Stevenson Kristen , Jin Zhezhen , Barrera Sergio , Davila Randy , Roberts Emily , Neuberg Donna S. , Athale Uma H. , Clavell Luis A. , Laverdiere Caroline , Leclerc Jean‐Marie , Michon Bruno , Schorin Marshall A. , Welch Jennifer J.G. , Sallan Stephen E. , Silverman Lewis B. , Kelly Kara M.
Published: November 2017

Purpose

This study compared the relative incidence of treatment‐related toxicities and the event‐free and overall survival between Hispanic and non‐Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana‐Farber Cancer Institute ALL Consortium protocol 05‐001.

Patients and methods

Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1–18 years with previously untreated ALL.

Results

Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05‐001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non‐Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5‐year event‐free survival (EFS) (79.4%; 95% CI: 71.6–85.2) and overall survival (OS) (89.2%; 95% CI: 82.7–93.4) than non‐Hispanic patients (EFS: 87.5%; 95% CI: 84.5–90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2–94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non‐Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome.

Conclusion

Hispanic children treated for ALL on DFCI 05‐001 had fewer bone‐related toxicities and inferior survival than non‐Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non‐biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.
Study on mechanical properties of unidirectional continuous carbon fiber‐reinforced PEEK composites fabricated by the wrapped yarn method
Authors: Xu Zhiping , Zhang Mei , Gao ShuoHui , Wang Guibin , Zhang Shuling , Luan Jiashuang
Published: November 2017

The purpose of this study was to investigate the mechanical properties of unidirectional continuous carbon fiber‐reinforced PEEK (CCF/PEEK) composites via the wrapped yarn method and to obtain optimum fabrication conditions. The composite plates were fabricated at different processing conditions and their mechanical properties (i.e., tensile, bending and short beam shear strength performance) were investigated in terms of thermal and fracture morphology characterizations. As the molding temperature and molding time increased, the mechanical properties of the composites enhanced due to the improved impregnation of the fibers, although there was potential matrix degradation. Moreover, slow cooling rate had little effect on the mechanical properties of the composites. Therefore, to obtain a combination of excellent mechanical properties and high production efficiency, a relatively high molding temperature, sufficient molding time and moderate cooling rate were optimal for the CCF/PEEK fabricated by the wrapped yarn method. POLYM. COMPOS., 40:56–69, 2019. © 2017 Society of Plastics Engineers
Synergistic effect of halloysite nanotubes on flame resistance of intumescent flame retardant poly(butylene succinate) composites
Authors: Wang Yuhai , Liu Cong , Shi Xiaohua , Liang Jiayuan , Jia Zhixin , Shi Guang
Published: November 2017

A novel intumescent flame retardant poly(butylene succinate) (IFR‐PBS) with antidripping property was prepared using halloysite nanotubes (HNTs) as the synergistic agent. Ammonium polyphosphate (APP), melamine (MA), pentaerythritol (PER), and halloysite nanotubes (HNTs) were added in PBS via melt blending. The effects of HNTs as the synergistic agent on the flame retardancy property, thermal property, and mechanical property of IFR‐PBS composites were investigated. Cone calorimetry revealed that partial substitution of IFR by HNTs (1.5 wt%) substantially improved the flame retardancy of IFR‐PBS with a reduction of heat release rate (HRR), total heat release (THR), and total smoke production (TSP). In addition, the limiting oxygen index value was increased from 42.1 to 58.2 with only 1.5 wt% addition of HNTs. The incorporation of HNTs also enhanced the thermal stability of the IFR‐PBS composites and reinforced the composites. Scanning electron microscopy (SEM) results showed that the composite containing HNTs had a tighter protective char layer after cone calorimeter test, which protected the underlying polymer from the external heating. Overall, the results indicated that suitable amounts of HNTs had a noticeable synergistic effect on the flame retardancy property of IFR‐PBS composites. POLYM. COMPOS., 40:202–209, 2019. © 2017 Society of Plastics Engineers