bluuebunny/crossref_metadata_2025_split huggingface dataset:
2‐Methoxypropylacetate‐1 [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) for 2‐methoxypropylacetate‐1 [
70657‐70‐4
]. Available publications and unpublished study reports are described in detail.

Critical effects of 2‐methoxypropylacetate‐1 are its irritancy and teratogenicity. A MAK value of 5 ml/m
3
had been set. This value is now reaffirmed based on the findings on the irritancy of the substance in a 28‐day inhalation study with rats.

Since a local effect is critical, Peak Limitation Category I with excursion factor of 2 has been set. 2‐Methoxypropylacetate‐1 remains assigned to Pregnancy Risk Group B and it also remains designated with an “H” (for substances that can be absorbed through the skin in toxicologically relevant amounts).
Monochloressigsäure, Natriummonochloracetat [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated monochloroacetic acid [
79‐11‐8
] together with sodium monochloroacetate [
3926‐62‐3
] considering all toxicological endpoints. Monochloroacetic acid is a strong acid and dissociates in biological media. Therefore, also data for sodium monochloroacetate are used to evaluate the systemic toxicity.

Monochloroacetic acid is corrosive to the eyes but there are no inhalation studies from which a NOAEC for local effects can be derived. Therefore, a maximum concentration at the workplace (MAK value) of 2 mg/m
3
(0.5 ml/m
3
), which has been set for the better investigated phosphoric acid, is also established for monochloroacetic acid. As irritation is the critical effect, monochloroacetic acid is classified in Peak Limitation Category I. By analogy with phosphoric acid, an excursion factor of 2 is set.

In chronic studies in rats, a NOAEL for sodium monochloroacetate of 3.5 mg/kg body weight and day for males was found for depressed body weight gain and diminished liver and kidney weights. After toxicokinetic scaling, extrapolation to humans and application of the preferred value approach, a MAK value of 2 mg/m
3
for the inhalable fraction is set. Since systemic effects of sodium monochloroacetate are critical, it is assigned to Peak Limitation Category II. From the half‐life of 3 hours in rat plasma, an excursion factor of 2 is derived.

In a study with monochloroacetic acid in rats, the NOAEL for developmental toxicity was 70 mg/kg body weight. This dose corresponds to a concentration of 121 mg/m
3
at the workplace, which is about 60 times as high as the MAK value of 2 mg/m
3
. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and monochloroacetic acid and its sodium salt are classified in Pregnancy Risk Group C. Monochloroacetic acid is DNA‐damaging in vitro at concentrations which are also cytotoxic, but it is not an alkylating agent. Overall, the acid and its sodium salt are not regarded as genotoxic and they are not carcinogenic in rats and mice. Monochloroacetic acid in concentrations which are not irritating to the skin is not taken up via the skin in toxicologically relevant amounts. The sodium salt, however, is expected to penetrate the skin in amounts contributing to toxicity and is therefore designated with “H”. Both compounds are not expected to be sensitizers.
Dichloressigsäure und ihre Salze [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dichloroacetic acid [
79‐43‐6
] to derive a maximum concentration at the workplace (MAK value) and to review its carcinogenicity classification.

The critical effects are irritation, carcinogenicity in the liver of rats and mice as well as neurotoxicity. After oral application, dichloroacetic acid or its sodium salt have tumour‐promoting effects and are carcinogenic in the liver of rats and mice. The NOAEL for carcinogenic effects in rats is 3.6 mg/kg body weight. In mice, a NOAEL cannot be derived. Dichloroacetic acid is not mutagenic in most tests in vitro and in vivo. The mechanisms involved in the tumour development in the liver are most likely interference with energy metabolism, oxidative stress and inhibition of apoptosis. As the primary mode of action is non‐genotoxic, dichloroacetic acid and its salts are classified in Carcinogen Category 4.

Dichloroacetic acid is corrosive to the eye and the skin of rabbits. As no inhalation studies are available to evaluate possible irritating effects on the respiratory tract, the structurally similar trichloroacetic acid is used as a read‐across. Therefore, a MAK value of 0.2 ml/m
3
corresponding to 1.1 mg/m
3
, is derived for dichloroacetic acid. Accordingly, a MAK value of 1.1 mg/m
3
for the inhalable fraction, measured as the acid, is set for the salts. As the local effect is critical, the acid and its salts are assigned to Peak Limitation Category I with an excursion factor of 1.

As skin contact to dichloroacetate may contribute significantly to systemic toxicity, the salts are designated with “H”. Skin contact is not expected to contribute significantly to the systemic toxicity of dichloroacetic acid. Sensitization is not expected from the available data.
Azinphos‐methyl [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated azinphos‐methyl [
86‐50‐0
] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.

In human studies, the critical effect of acetylcholinesterase (AChE) inhibition was not observed up to 0.25 or 0.29 mg/kg body weight and day in men after oral application up to 28 days. The NOAELs (no observed adverse effect levels) from studies with rodents or dogs are in the same range. Based on these valid data, the MAK value is increased to 1 mg/m
3
for the inhalable fraction. Since a systemic effect is critical, Peak Limitation Category II is retained. As AChE inhibition is almost irreversible with a half‐life of 30 hours and a steady‐state is reached after 2 weeks, the excursion factor of 8 is confirmed.

There is no adequate margin between the NOAELs for developmental and perinatal toxicity in rats and mice and the MAK value. Therefore, azinphos‐methyl is assigned to Pregnancy Risk Group B. Starting from the lowest calculated air concentration of 1.18 mg/m
3
as the NAEC for perinatal toxicity and taking into account the absence of teratogenic effects in all studies, damage to the embryo or foetus is unlikely at concentrations of 0.1 mg/m
3
and below. Exposure to this or lower concentrations would be the prerequisite for an assignment to Pregnancy Risk Group C.

Azinphos‐methyl is neither genotoxic nor carcinogenic.
Skin contact is expected to contribute significantly to systemic toxicity and azinphos‐methyl remains designated with “H”. Azinphos‐methyl has been shown to be skin sensitizing in the guinea pig. The substance is therefore labelled with “Sh”.
Biomonitoring is recommended in addition to personal protective measures. A reduction of the erythrocytic AChE activity to 70% of the reference value (biological tolerance value for AChE inhibitors) must not be exceeded.
Methyl acrylate [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of 5 ml/m3for methyl acrylate [96‐33‐3] considering the endpoints local and developmental toxicity as well as genotoxicity. Available publications and unpublished study reports are described in detail. The critical effect in a two‐year inhalation study with rats was reserve cell hyperplasia with loss of ciliated and olfactory cells in the transitional nasal epithelium at the lowest concentration of 15 ml/m3. In a two‐generation reproduction toxicity study with a NOAEC of 5 ml/m3, degeneration with regeneration of the olfactory epithelium, hyperplasia of the transitional epithelium as well as hyperplasia and hypertrophy of the goblet cells were observed. A lower confidence limit of the benchmark dose for an extra risk of 5% increase of the critical effect incidence (BMDL05) of 6.8 ml/m3as a substitute for a NOAEC was calculated from the data of the two‐year inhalation study. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the MAK value for methyl acrylate has been lowered to 2 ml/m3. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are confirmed, in analogy to ethyl acrylate. The NOAECs for developmental toxicity in rats and rabbits are sufficiently high so that damage to the embryo or foetus is unlikely when the MAK value is not exceeded. Thus, methyl acrylate is classified in Pregnancy Risk Group C. The substance is clastogenic in vitro but not in vivo and was not carcinogenic in a 2‐year inhalation study in rats. There are only a few cases of contact sensitization in humans but there is a positive result in a local lymph node assay. Data on airway sensitization are still not available. Methyl acrylate remains designated with “Sh”. Skin absorption was calculated to contribute significantly to the systemic toxicity and methyl acrylate is designated with an “H”.
2‐(2‐Hydroxyphenyl)‐5‐aminothiazoles: Synthesis and Properties Involving Dual Emissions
Authors: Murai Toshiaki , Yoshihara Mari , Yamaguchi Kirara , Minoura Mao 
Published: April 2019

Abstract2‐(2‐Hydroxyphenyl)‐5‐aminothiazoles were prepared by two different methods to elucidate their photophysical properties. The first synthetic method involved the addition of thioamide dianions derived from secondary thioamides and nBuLi to thioforamides. Alternatively, Pd‐catalyzed sequential addition of aromatic groups and diarylamines to commercially available thiazoles led to the precursors of the desired thiazoles. The molecular structures of the resulting thiazoles were determined by X‐ray analyses. The thiazoles showed dual‐emission in cyclohexane and in the solid state.
In Vitro Selection of Circular DNA Aptamers for Biosensing Applications
Authors: Liu Meng , Yin Qingxin , Chang Yangyang , Zhang Qiang , Brennan John D. , Li Yingfu 
Published: April 2019

AbstractWe report on the first effort to select DNA aptamers from a circular DNA library, which resulted in the discovery of two high‐affinity circular DNA aptamers that recognize the glutamate dehydrogenase (GDH) from Clostridium difficile, an established antigen for diagnosing Clostridium difficile infection (CDI). One aptamer binds effectively in both the circular and linear forms, the other is functional only in the circular configuration. Interestingly, these two aptamers recognize different epitopes on GDH, demonstrating the advantage of selecting aptamers from circular DNA libraries. A sensitive diagnostic test was developed to take advantage of the high stability of circular DNA aptamers in biological samples and their compatibility with rolling circle amplification. This test is capable of identifying patients with active CDI using stool samples. This work represents a significant step forward towards demonstrating the practical utility of DNA aptamers in clinical diagnosis.
Functionality‐Independent DNA Encoding of Complex Natural Products
Authors: Ma Peixiang , Xu Hongtao , Li Jie , Lu Fengping , Ma Fei , Wang Shuyue , Xiong Huan , Wang Wei , Buratto Damiano , Zonta Francesco , Wang Nan , Liu Kaiwen , Hua Tian , Liu Zhi‐Jie , Yang Guang , Lerner Richard A. 
Published: April 2019

AbstractDNA encoded chemical libraries (DELs) link the powers of genetics and chemical synthesis via combinatorial optimization. Through combinatorial chemistry, DELs can grow to the unprecedented size of billions to trillions. To take full advantage of the DEL approach, linking the power of genetics directly to chemical structures would offer even greater diversity in a finite chemical world. Natural products have evolved an incredible structural diversity along with their biological evolution. Herein, we used traditional Chinese medicines (TCMs) as examples in a late‐stage modification toolbox approach to annotate these complex organic compounds with amplifiable DNA barcodes, which could be easily incorporated into a DEL. The method of end‐products labeling also generates a cluster of isomers with a single DNA tag at different sites. These isomers provide an additional spatial diversity for multiple accessible pockets of targeted proteins. Notably, a novel PARP1 inhibitor from TCM has been identified from the natural products enriched DEL (nDEL).
Von Peptiden lernen: eine Strategie für das Design funktionaler Präzisionspolymer‐Sequenzen
Authors: Maron Eva , Swisher Jordan H. , Haven Joris J. , Meyer Tara Y. , Junkers Tanja , Börner Hans G. 
Published: April 2019

AbstractDer Zugang zu Sequenzen für funktionale Präzisionspolymere kann aufgrund der Reihenfolge von Seitengruppenfunktionen eines bekannten Peptids ermöglicht werden. Die direkte Übersetzung einer Peptidsequenz, die zuvor als Solubilisator für den Photosensibilisator meta‐Tetra(hydroxyphenyl)chlorin selektiert wurde, in zwei verschiedene Präzisionspolymere wird gezeigt. Die resultierenden peptidmimetischen Formulierungsadditive auf Basis monodisperser Oligo(N‐substituierter‐acrylamide) und Oligo(2‐substituierter‐α‐hydroxycarbonsäuren) weisen scharf definierte Sequenz‐Eigenschafts‐Beziehungen auf und übertreffen in einigen Fällen die Wirkstoffkapazität und Freisetzungskinetiken des peptidischen Vorbilds, wobei Solubilisatoren mit bis zu 40 % höherer Beladbarkeit und 27‐fach schnellerer Freisetzung erreicht werden.
Nanopore Sequencing Accurately Identifies the Mutagenic DNA Lesion O6‐Carboxymethyl Guanine and Reveals Its Behavior in Replication
Authors: Wang Yu , Patil Kiran M. , Yan Shuanghong , Zhang Panke , Guo Weiming , Wang Yuqin , Chen Hong‐Yuan , Gillingham Dennis , Huang Shuo 
Published: April 2019

AbstractO6‐carboxymethylguanine (O6‐CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O6‐CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O6‐CMG. A unique O6‐CMG signal was observed during NPS and a single‐event call accuracy of >95 % was achieved. Moreover, O6‐CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.
Probing the Formation of a Seleninic Acid in Living Cells by the Fluorescence Switching of a Glutathione Peroxidase Mimetic
Authors: Ungati Harinarayana , Govindaraj Vijayakumar , Narayanan Megha , Mugesh Govindasamy 
Published: April 2019

AbstractGlutathione peroxidase (GPx) is a selenoenzyme that protects cells against oxidative damage. Although the formation of a seleninic acid (‐SeO2H) by this enzyme during oxidative stress has been proposed, a selenic acid has not been identified in cells. Herein, we report that the formation of a seleninic acid can be monitored in living cells by using a redox‐active ebselen analogue with a naphthalimide fluorophore. The probe reacts with H2O2 to generate the highly fluorescent seleninic acid. The electron withdrawing nature of the ‐SeO2H moiety and strong Se⋅⋅⋅O interactions, which prevent the photoinduced electron transfer, are responsible for the fluorescence.
Essential and Ubiquitous: The Emergence of Lanthanide Metallobiochemistry
Authors: Daumann Lena J. 
Published: April 2019

AbstractLanthanide biochemistry—A surprise around every corner: lanthanides as biologically essential metals. This statement was until recently, unthinkable. This minireview presents the recent developments in the emerging field of rare‐earth element biochemistry from a coordination chemist's point of view and discusses why nature might have chosen these elements to have a catalytic role in alcohol dehydrogenase enzymes as they are found in methanotrophic and methylotrophic bacteria.
Quinolone derivatives and their antifungal activities: An overview
Authors: Zhang Bo 
Published: April 2019

AbstractMore than 300 million people suffer from the incidence of life‐threatening invasive fungal infections, resulting in over 1.35 million deaths annually. Currently, the antifungal agents available in clinics are rather limited, and the rapid development of resistance to the existing antifungal drugs has further aggravated mortality. Quinolones possess a broad spectrum of chemotherapeutic properties and demonstrate considerable antifungal activities as well. Various quinolone derivatives have been screened for their antifungal activities, and some of them exhibit excellent potency against both drug‐susceptible and drug‐resistant fungi. This review aims to outline the recent advances in quinolone derivatives as potential antifungal agents and summarize the structure–activity relationship, to provide insights for the rational design of more active candidates.
2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis
Authors: Angeles‐Han Sheila T. , Ringold Sarah , Beukelman Timothy , Lovell Daniel , Cuello Carlos A. , Becker Mara L. , Colbert Robert A. , Feldman Brian M. , Holland Gary N. , Ferguson Polly J. , Gewanter Harry , Guzman Jaime , Horonjeff Jennifer , Nigrovic Peter A. , Ombrello Michael J. , Passo Murray H. , Stoll Matthew L. , Rabinovich C. Egla , Sen H. Nida , Schneider Rayfel , Halyabar Olha , Hays Kimberly , Shah Amit Aakash , Sullivan Nancy , Szymanski Ann Marie , Turgunbaev Marat , Turner Amy , Reston James 
Published: April 2019

ObjectiveTo develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).MethodsPediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong.ResultsDue to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision‐threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss.ConclusionThis guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.
Perceptions and Attitudes toward Brain Donation among the Chinese People
Authors: Zhang Qi , Deng Jing , Li Ya‐Nan , Gou Yue , Yan Xiao‐Xin , Li Fang , Pan Ai‐Hua 
Published: April 2019

Postmortem human brain donation is crucial to both anatomy education and research. The China Human Brain Banking Consortium was established recently to foster brain donation in China. The purpose of this study was to gain information about the public perception of and attitudes toward brain donation and to identify factors that may impact the willingness to participate in brain donation among the Chinese people. A specifically designed questionnaire was delivered to community residents in Changsha (the capital city of Hunan province) with a total of 1,249 completed forms returned and statistically analyzed. The majority of the participants considered that brain donation would help medical research and education, and 32.0% of respondents agreed that the brain donation would help change the traditional Chinese funeral belief in keeping the body intact after death. However, participants aged over 60 years old were less supportive of this concept. Among all participants, 63.7% stated that they were not knowledgeable about brain donation, while 26.4% explicitly expressed a willingness to participate in brain donation. Age, gender, monthly household income, and knowledge about brain donation significantly affected the willingness. Compared with other age groups, a higher proportion of participants aged over 60 years old preferred to be informed by a medical college. To promote brain donation in China, especially among the elderly, better communication of its medical benefits and a reinterpretation of the Confucius view of the human body should be provided. Efforts are also needed to provide appropriate forums and sources of brain donation information to targeted communities and society in general.