bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Birth of Naloxone: An Intellectual History of an Ambivalent Opioid
Authors: Kolbe Laura , Fins Joseph J. 
Published: October 2021

AbstractNaloxone, which reverses the effects of opioids, was synthesized in 1960, though the hunt for opioid antagonists began a half-century earlier. The history of this quest reveals how cultural and medical attitudes toward opioids have been marked by a polarization of discourse that belies a keen ambivalence. From 1915 to 1960, researchers were stymied in seeking a “pure” antidote to opioids, discovering instead numerous opioid molecules of mixed or paradoxical properties. At the same time, the quest for a dominant explanatory and therapeutic model for addiction was likewise unsettled. After naloxone’s discovery, new dichotomizing language arose in the “War on Drugs,” in increasingly divergent views between addiction medicine and palliative care, and in public debates about layperson naloxone access. Naloxone, one of the emblematic drugs of our time, highlights the ambivalence latent in public and biomedical discussions of opioids as agents of risk and relief.
Pacemaker use for the treatment of reflex-mediated syncope: 40-year experience at a single paediatric institution
Authors: Huang Thomas , O’Leary Edward , Alexander Mark E. , Bevilacqua Laura , Fynn-Thompson Francis , DeWitt Elizabeth S. , Bezzerides Vassilios J. , Mah Douglas Y. 
Published: October 2021

AbstractIntroduction:Reflex-mediated syncope occurs in 15% of children and young adults. In rare instances, pacemakers are required to treat syncopal episodes associated with transient sinus pauses or atrioventricular block. This study describes a single centre experience in the use of permanent pacemakers to treat syncope in children and young adults.Materials and methods:Patients with significant pre-syncope or syncope and pacemaker implantation from 1978 to 2018 were reviewed. Data collected included the age of presentation, method of diagnosis, underlying rhythm disturbance, age at implant, type of pacemaker implanted, procedural complications and subsequent symptoms.Results:Fifty patients were identified. Median age at time of the first syncopal episode was 10.2 (range 0.3–20.4) years, with a median implant age of 14.9 (0.9–34.3) years. Significant sinus bradycardia/pauses were the predominant reason for pacemaker implant (54%), followed by high-grade atrioventricular block (30%). Four (8%) patients had both sinus pauses and atrioventricular block documented. The majority of patients had dual-chamber pacemakers implanted (58%), followed by ventricular pacemakers (38%). Median follow-up was 6.7 (0.4–33.0) years. Post-implant, 4 (8%) patients continued to have syncope, 7 (14%) had complete resolution of their symptoms, and the remaining reported a decrease in their pre-syncopal episodes and no further syncope. Twelve (24%) patients had complications, including two infections and eight lead malfunctions.Conclusions:Paediatric patients with reflex-mediated syncope can be treated with pacing. Complication rates are high (24%); as such, permanent pacemakers should be reserved only for those in whom asystole from sinus pauses or atrioventricular block has been well documented.
The Illustration of Mīrkhwānd's Rauḍat al-ṣafā, RAS Ms. P. 38
Authors: MELVILLE CHARLES 
Published: October 2021

AbstractThe celebrated universal Islamic history, Mīrkhwānd's Tārīkh-i Rauḍat al-ṣafā, written in Herat in the late Timurid period, became a model for later Persian histories, but has not yet been the subject of any substantial critical analysis as a work of historical literature, or in terms of its manuscript transmission. Although numerous copies exist of different volumes of the text, only a handful have been illustrated, providing another dimension to the reception and ‘reading' of the chronicle. This paper focuses on the fourth volume of Mīrkhwānd's history, on the Persian dynasties up to the rise of Timur, four copies of which have been illustrated, among them the Royal Asiatic Society’s manuscript no. P. 38. After detailing the ten pictures in the manuscript, the article concludes with a discussion of their character and purpose.
Policy sequencing to reduce tropical deforestation
Authors: Furumo Paul R. , Lambin Eric F. 
Published: October 2021

Non-technical summaryTropical deforestation continues apace despite a proliferation of commitments made by companies and governments to control it. Halting and reversing deforestation requires multiple, complementary interventions by state and non-state actors at different scales. We argue that the order in which these instruments and actors are introduced into the policy mix matters. Sequences of interventions from case studies in Latin America show that government commitment is a critical first step, implemented through command-and-control measures and then incentives. Combined with REDD+, they create an enabling environment for supply chain initiatives. A more coordinated and deliberate polycentric governance is needed to achieve zero-deforestation.Technical summaryAvoided deforestation provides a natural climate solution for reducing emissions while generating co-benefits for people and nature. However, unleashing this potential requires improved governance. Diverse coalitions of actors are designing interventions to protect forests, each with different motivations and specialization of strategies. We introduce a policy sequencing framework to advance our understanding of how to improve polycentric zero-deforestation governance. Focusing on commodity production in Costa Rica, Brazil, and Colombia, we reconstructed the policy mix of zero-deforestation interventions across three domains – domestic public policies, REDD+, and supply chain initiatives. We classified interventions according to their instrument mechanism – disincentives, incentives, enabling measures – and when they were introduced into the policy mix. We found a sequence of interventions that reflects stages of forest cover dynamics, but also depends on local political will and institutional capacity. Government command-and-control measures are needed early in the policy sequence to slow deforestation, with incentives added to increase legal compliance. REDD+ helps governments build an enabling environment that supports supply chain initiatives seeking to increase forest cover at later stages of the sequence. Policy sequencing and policyscape concepts advance the design of more deliberate polycentric forest governance that enhances actor coordination and instrument synergies in the policy mix.Social media summaryHow do we stop deforestation? The policy options are well-known, but the order in which they are introduced matters.
Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer
Authors: Hou Ming-Feng , Ou-Yang Fu , Li Chung-Liang , Chen Fang-Ming , Chuang Chieh-Han , Kan Jung-Yu , Wu Cheng-Che , Shih Shen-Liang , Shiau Jun-Ping , Kao Li-Chun , Kao Chieh-Ni , Lee Yi-Chen , Moi Sin-Hua , Yeh Yao-Tsung , Cheng Chien-Ju , Chiang Chih-Po 
Published: October 2021

AbstractIn Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer.Bacteroides fragiliswas specifically found in young women of premenopausal statuses andKlebsiella pneumoniaein older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.
Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis
Authors: Edwards Lariah , McCray Nathan L. , VanNoy Brianna N. , Yau Alice , Geller Ruth J. , Adamkiewicz Gary , Zota Ami R. 
Published: October 2021

Abstract
Background
Fast food consumption is associated with biomarkers of ortho-phthalates exposures. However, the chemical content of fast food is unknown; certain ortho-phthalates (i.e., di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP)) have been phased out and replaced with other plasticizers (e.g., dioctyl terephthalate (DEHT)).

Objective
We conducted a preliminary study to examine ortho-phthalate and replacement plasticizer concentrations in foods and food handling gloves from U.S. fast food restaurants.

Methods
We obtained hamburgers, fries, chicken nuggets, chicken burritos, cheese pizza (n = 64 food samples) and gloves (n = 3) from restaurants and analyzed them for 11 chemicals using gas chromatography mass spectrometry.

Results
We found DEHT at the highest concentrations in both foods (n = 19; median = 2510 µg/kg; max = 12,400 µg/kg) and gloves (n = 3; range: 28–37% by weight). We detected DnBP and DEHP in 81% and 70% of food samples, respectively. Median DEHT concentrations were significantly higher in burritos than hamburgers (6000 µg/kg vs. 2200 µg/kg; p < 0.0001); DEHT was not detected in fries. Cheese pizza had the lowest levels of most chemicals.

Significance
To our knowledge, these are the first measurements of DEHT in food. Our preliminary findings suggest that ortho-phthalates remain ubiquitous and replacement plasticizers may be abundant in fast food meals.

Impact statement
A selection of popular fast food items sampled in this study contain detectable levels of replacement plasticizers and concerning ortho-phthalates. In addition, food handling gloves contain replacement plasticizers, which may be a source of food contamination. These results, if confirmed, may inform individual and regulatory exposure reduction strategies.
Human hepatocyte-derived extracellular vesicles attenuate the carbon tetrachloride-induced acute liver injury in mice
Authors: Kakizaki Masatoshi , Yamamoto Yuichiro , Nakayama Shunya , Kameda Kazuaki , Nagashima Etsuko , Ito Masatoshi , Suyama Takashi , Matsuzaki Yumi , Chiba Tetsuhiro , Sumiyoshi Hideaki , Inagaki Yutaka , Kotani Ai 
Published: October 2021

AbstractAcute liver injury (ALI) induced by chemicals or viruses can progress rapidly to acute liver failure (ALF), often resulting in death of patients without liver transplantation. Since liver transplantation is limited due to a paucity of donors, expensive surgical costs, and severe immune rejection, novel therapies are required to treat liver injury. Extracellular vesicles (EVs) are used for cellular communication, carrying RNAs, proteins, and lipids and delivering them intercellularly after being endocytosed by target cells. Recently, it was reported that EVs secreted from human hepatocytes have an ability to modulate the immune responses; however, these roles of EVs secreted from human hepatocytes were studied only with in vitro experiments. In the present study, we evidenced that EVs secreted from human hepatocytes attenuated the CCL4-induced ALI by inhibiting the recruitment of monocytes through downregulation of chemokine receptor in the bone marrow and recruitment of neutrophils through the reduction of C-X-C motif chemokine ligand 1 (CXCL1) and CXCL2 expression levels in the liver.
Loss of exosomal LncRNA HCG15 prevents acute myocardial ischemic injury through the NF-κB/p65 and p38 pathways
Authors: Lin Beiyou , Chen Xi , Lu Chuanghong , Xu Jianjun , Qiu Yumin , Liu Xin , Song Haoyu , Chen Ang , Xiong Jie , Wang Kun , Yuan Yuan , Shi Lile , Zhong Lintao , Jiang Xiaofei 
Published: October 2021

AbstractExosomes are nanosized bilayer membrane vesicles that may mediate intercellular communication by transporting bioactive molecules, including noncoding RNAs, mRNAs, and proteins. Research has shown that exosomes play an important role in acute myocardial infarction (AMI), but the function and regulation of exosomal long noncoding RNAs (lncRNAs) in AMI are unclear. Thus, RNA sequencing (RNA-Seq) was conducted to investigate the exosomal lncRNA transcriptome from MI patients and identified 65 differentially expressed lncRNAs between the MI and control groups. HCG15, one of the differentially expressed lncRNAs, was verified to have the highest correlation with cTnT by qRT-PCR, and it also contributed to the diagnosis of AMI by receiver operating characteristic (ROC) analysis. Upregulation of HCG15 expression facilitated cardiomyocyte apoptosis and inflammatory cytokine production and inhibited cell proliferation. We also confirmed that HCG15 was mainly wrapped in exosomes from AC16 cardiomyocytes under hypoxia, which contributed to cardiomyocyte apoptosis, the release of inflammatory factors, and inhibition of cell proliferation via the activation of the NF-κB/p65 and p38 pathways, whereas suppressing the expression of HCG15exerted opposite effects, In addition, Overexpression of HCG15 aggravated cardiac IR injury in C57BL/6J mice. This study not only helps elucidate exosomal lncRNA function in AMI pathogenesis but also contributes to the development of novel therapeutic strategies.
Structural basis of the P4B ATPase lipid flippase activity
Authors: Bai Lin , Jain Bhawik K. , You Qinglong , Duan H. Diessel , Takar Mehmet , Graham Todd R. , Li Huilin 
Published: October 2021

AbstractP4 ATPases are lipid flippases that are phylogenetically grouped into P4A, P4B and P4C clades. The P4A ATPases are heterodimers composed of a catalytic α-subunit and accessory β-subunit, and the structures of several heterodimeric flippases have been reported. The S. cerevisiae Neo1 and its orthologs represent the P4B ATPases, which function as monomeric flippases without a β-subunit. It has been unclear whether monomeric flippases retain the architecture and transport mechanism of the dimeric flippases. Here we report the structure of a P4B ATPase, Neo1, in its E1-ATP, E2P-transition, and E2P states. The structure reveals a conserved architecture as well as highly similar functional intermediate states relative to dimeric flippases. Consistently, structure-guided mutagenesis of residues in the proposed substrate translocation path disrupted Neo1’s ability to establish membrane asymmetry. These observations indicate that evolutionarily distant P4 ATPases use a structurally conserved mechanism for substrate transport.
Poleward migration of western North Pacific tropical cyclones related to changes in cyclone seasonality
Authors: Feng Xiangbo , Klingaman Nicholas P. , Hodges Kevin I. 
Published: October 2021

AbstractThe average location of observed western North Pacific (WNP) tropical cyclones (TCs) has shifted north over the last several decades, but the cause remains not fully understood. Here we show that, for the annual average, the observed northward migration of WNP TCs is related to changes in TC seasonality, not to a northward migration in all seasons. Normally, peak-season (July–September) TCs form and travel further north than late-season (October–December) TCs. In recent decades, related to less frequent late-season TCs, seasonally higher-latitude TCs contribute relatively more to the annual-average location and seasonally lower-latitude TCs contribute less. We show that the change in TC seasonality is related to the different responses of late-season and peak-season TC occurrence to a stronger Pacific Walker Circulation. Our findings provide a perspective on long-term trends in TC activity, by decomposing the annual-average statistics into seasonal components, which could respond differently to anthropogenic forcing.
Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition
Authors: Pomatto-Watson Laura C. D. , Bodogai Monica , Bosompra Oye , Kato Jonathan , Wong Sarah , Carpenter Melissa , Duregon Eleonora , Chowdhury Dolly , Krishna Priya , Ng Sandy , Ragonnaud Emeline , Salgado Roberto , Gonzalez Ericsson Paula , Diaz-Ruiz Alberto , Bernier Michel , Price Nathan L. , Biragyn Arya , Longo Valter D. , de Cabo Rafael 
Published: October 2021

AbstractCancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.
Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling
Authors: Wang Jiajia , Wang Jiaying , Hong Wenxiang , Zhang Lulu , Song Liqian , Shi Qi , Shao Yanfei , Hao Guifeng , Fang Chunyan , Qiu Yueping , Yang Lijun , Yang Zhaoxu , Wang Jincheng , Cao Ji , Yang Bo , He Qiaojun , Weng Qinjie 
Published: October 2021

AbstractOptineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders.
Potential value and chemical characterization of gut microbiota derived nitrogen containing metabolites in feces from Periplaneta americana (L.) at different growth stages
Authors: Lv Weiqi , Cui Ying , Xue Gen , Wang Ziyan , Niu Lu , Chai Xin , Wang Yuefei 
Published: October 2021

AbstractThe American cockroach, Periplaneta americana (L.), is able to highly survive in various complicated environments around the globe, and often considered as a pest. In contrast, billions of P. americana have been massively reared in China and extensively used as a medicinal insect, due to its function for preventing and treating ulceration and heart failure. Considering the possibility that microbiota-derived metabolites could be an effective source to identify promising candidate drugs, we attempted to establish a rapid method for simultaneous determination of gut microbiota metabolites from medicinal insects. In this study, network pharmacology approach and ultra-performance liquid chromatography (UPLC) technique were employed to reveal the potential pharmacological activity and dynamics variation of nitrogen-containing metabolites (NCMs) originated from the gut microbiota of breeding P. americana at different growth stages. A metabolites-targets-diseases network showed that NCMs are likely to treat diseases such as ulceration and cancer. The analysis of NCMs' content with the growth pattern of P. americana indicated that the content of NCMs declined with P. americana aging. Both principal component analysis and orthogonal partial least squares discriminant analysis suggested that 8-hydroxy-2-quinolinecarboxylic acid and 8-hydroxy-3,4-dihydro-2(1H)-quinolinone are the potential differential metabolic markers for discriminating between nymphs and adults of P. americana. Moreover, the developed UPLC method showed an excellent linearity (R2 > 0.999), repeatability (RSD < 2.6%), intra- and inter-day precisions (RSD < 2.2%), and recovery (95.5%–99.0%). Collectively, the study provides a valuable strategy for analyzing gut microbiota metabolites from insects and demonstrates the prospects for discovering novel drug candidates from the feces of P. americana.
Immediate application of negative pressure wound therapy following lower extremity flap reconstruction in sixteen patients
Authors: Chen Chun-Yu , Kuo Shyh-Ming , Tarng Yih-Wen , Lin Kai-Cheng 
Published: October 2021

AbstractNegative pressure wound therapy (NPWT) is usually applied in wound management and soft-tissue salvage after the development of complications. However, immediate postoperative application of NPWT over the flap coverage is seldom reported. We evaluate the effectiveness of immediate postoperative application of NPWT following fasciocutaneous or muscle flap coverage for lower leg reconstruction. A retrospective review of patients who underwent either fasciocutaneous or muscle flap coverage of lower leg soft-tissue defects applied with NPWT immediately after surgery was conducted in a level I trauma center. Sixteen patients, with an average age of 51.2 years, were included in the study. Nine patients had trauma-related soft-tissue loss, six had subsequent soft-tissue defects after debridement, and one had burn injury. Two patients had been treated with free anterolateral thigh flaps, 11 with pedicle flaps, and three with muscle flaps. All flaps survived except for those in two patients with venous congestion on postoperative day 1, which needed further debridement and skin grafting. Therefore, the use of immediate incisional NPWT is an alternative for wound care following flap coverage. The U-shaped design allows easy flap observation and temperature check. Furthermore, this method eliminates any concerns of vascular pedicle compression under negative pressure.