bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neuroeconomic signature of opioid craving: How fluctuations in craving bias drug-related and nondrug-related value
Authors: Biernacki Kathryn , Lopez-Guzman Silvia , Messinger John C. , Banavar Nidhi V. , Rotrosen John , Glimcher Paul W. , Konova Anna B. 
Published: December 2021

AbstractHow does craving bias decisions to pursue drugs over other valuable, and healthier, alternatives in addiction? To address this question, we measured the in-the-moment economic decisions of people with opioid use disorder as they experienced craving, shortly after receiving their scheduled opioid maintenance medication and ~24 h later. We found that higher cravers had higher drug-related valuation, and that moments of higher craving within-person also led to higher drug-related valuation. When experiencing increased opioid craving, participants were willing to pay more for personalized consumer items and foods more closely related to their drug use, but not for alternative “nondrug-related” but equally desirable options. This selective increase in value with craving was greater when the drug-related options were offered in higher quantities and was separable from the effects of other fluctuating psychological states like negative mood. These findings suggest that craving narrows and focuses economic motivation toward the object of craving by selectively and multiplicatively amplifying perceived value along a “drug relatedness” dimension.
Genomic landscape of a relict fir-associated fungus reveals rapid convergent adaptation towards endophytism
Authors: Yuan Zhilin , Wu Qi , Xu Liangxiong , Druzhinina Irina S , Stukenbrock Eva H , Nieuwenhuis Bart P S , Zhong Zhenhui , Liu Zhong-Jian , Wang Xinyu , Cai Feng , Kubicek Christian P , Shan Xiaoliang , Wang Jieyu , Shi Guohui , Peng Long , Martin Francis M 
Published: December 2021

Abstract
Comparative and pan-genomic analyses of the endophytic fungus Pezicula neosporulosa (Helotiales, Ascomycota) from needles of the relict fir, Abies beshanzuensis, showed expansions of carbohydrate metabolism and secondary metabolite biosynthetic genes characteristic for unrelated plant-beneficial helotialean, such as dark septate endophytes and ericoid mycorrhizal fungi. The current species within the relatively young Pliocene genus Pezicula are predominantly saprotrophic, while P. neosporulosa lacks such features. To understand the genomic background of this putatively convergent evolution, we performed population analyses of 77 P. neosporulosa isolates. This revealed a mosaic structure of a dozen non-recombining and highly genetically polymorphic subpopulations with a unique mating system structure. We found that one idiomorph of a probably duplicated mat1-2 gene was found in putatively heterothallic isolates, while the other co-occurred with mat1-1 locus suggesting homothallic reproduction for these strains. Moreover, 24 and 81 genes implicated in plant cell-wall degradation and secondary metabolite biosynthesis, respectively, showed signatures of the balancing selection. These findings highlight the evolutionary pattern of the two gene families for allowing the fungus a rapid adaptation towards endophytism and facilitating diverse symbiotic interactions.
GPR120 induces regulatory dendritic cells by inhibiting HK2-dependent glycolysis to alleviate fulminant hepatic failure
Authors: Yu Hongshuang , Yang Wanlin , Huang Jiefang , Miao Xiang , Wang Bei , Ren Xiaohui , Gu Yuting , Wang Qiwei , Ding Xinyuan , Guo Xin , Qian Fengtao , Zhang Yanyun , Xu Huanbai , Zheng Leizhen , Jin Min 
Published: December 2021

AbstractFulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. UsingPropionibacterium acnes(P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn’t directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86lowregulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.
Trend towards virtual and hybrid conferences may be an effective climate change mitigation strategy
Authors: Tao Yanqiu , Steckel Debbie , Klemeš Jiří Jaromír , You Fengqi 
Published: December 2021

AbstractSince 2020, the COVID-19 pandemic has urged event holders to shift conferences online. Virtual and hybrid conferences are greener alternatives to in-person conferences, yet their environmental sustainability has not been fully assessed. Considering food, accommodation, preparation, execution, information and communication technology, and transportation, here we report comparative life cycle assessment results of in-person, virtual, and hybrid conferences and consider carbon footprint trade-offs between in-person participation and hybrid conferences. We find that transitioning from in-person to virtual conferencing can substantially reduce the carbon footprint by 94% and energy use by 90%. For the sake of maintaining more than 50% of in-person participation, carefully selected hubs for hybrid conferences have the potential to slash carbon footprint and energy use by two-thirds. Furthermore, switching the dietary type of future conferences to plant-based diets and improving energy efficiencies of the information and communication technology sector can further reduce the carbon footprint of virtual conferences.
Charge-transfer regulated visible light driven photocatalytic H2 production and CO2 reduction in tetrathiafulvalene based coordination polymer gel
Authors: Verma Parul , Singh Ashish , Rahimi Faruk Ahamed , Sarkar Pallavi , Nath Sukhendu , Pati Swapan Kumar , Maji Tapas Kumar 
Published: December 2021

AbstractThe much-needed renewable alternatives to fossil fuel can be achieved efficiently and sustainably by converting solar energy to fuels via hydrogen generation from water or CO2 reduction. Herein, a soft processable metal-organic hybrid material is developed and studied for photocatalytic activity towards H2 production and CO2 reduction to CO and CH4 under visible light as well as direct sunlight irradiation. A tetrapodal low molecular weight gelator (LMWG) is synthesized by integrating tetrathiafulvalene (TTF) and terpyridine (TPY) derivatives through amide linkages and results in TPY-TTF LMWG. The TPY-TTF LMWG acts as a linker, and self-assembly of this gelator molecules with ZnII ions results in a coordination polymer gel (CPG); Zn-TPY-TTF. The Zn-TPY-TTF CPG shows high photocatalytic activity towards H2 production (530 μmol g−1h−1) and CO2 reduction to CO (438 μmol g−1h−1, selectivity > 99%) regulated by charge-transfer interactions. Furthermore, in situ stabilization of Pt nanoparticles on CPG (Pt@Zn-TPY-TTF) enhances H2 evolution (14727 μmol g−1h−1). Importantly, Pt@Zn-TPY-TTF CPG produces CH4 (292 μmol g−1h−1, selectivity > 97%) as CO2 reduction product instead of CO. The real-time CO2 reduction reaction is monitored by in situ DRIFT study, and the plausible mechanism is derived computationally.
R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability
Authors: Mosler Thorsten , Conte Francesca , Longo Gabriel M. C. , Mikicic Ivan , Kreim Nastasja , Möckel Martin M. , Petrosino Giuseppe , Flach Johanna , Barau Joan , Luke Brian , Roukos Vassilis , Beli Petra 
Published: December 2021

AbstractTranscription poses a threat to genomic stability through the formation of R-loops that can obstruct progression of replication forks. R-loops are three-stranded nucleic acid structures formed by an RNA–DNA hybrid with a displaced non-template DNA strand. We developed RNA–DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DDX41 in opposing R-loop and double strand DNA break accumulation in promoters. DDX41 is enriched in promoter regions in vivo, and can unwind RNA–DNA hybrids in vitro. R-loop accumulation upon loss of DDX41 is accompanied with replication stress, an increase in the formation of double strand DNA breaks and transcriptome changes associated with the inflammatory response. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia in adulthood. We propose that R-loop accumulation and genomic instability-associated inflammatory response may contribute to the development of familial AML with mutated DDX41.
Reinforcing the supply chain of umifenovir and other antiviral drugs with retrosynthetic software
Authors: Lin Yingfu , Zhang Zirong , Mahjour Babak , Wang Di , Zhang Rui , Shim Eunjae , McGrath Andrew , Shen Yuning , Brugger Nadia , Turnbull Rachel , Trice Sarah , Jasty Shashi , Cernak Tim 
Published: December 2021

AbstractThe global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C–H bonds into C–C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains.
Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma
Authors: Lu Xiuxiu , Sabbasani Venkata R. , Osei-Amponsa Vasty , Evans Christine N. , King Julianna C. , Tarasov Sergey G. , Dyba Marzena , Das Sudipto , Chan King C. , Schwieters Charles D. , Choudhari Sulbha , Fromont Caroline , Zhao Yongmei , Tran Bao , Chen Xiang , Matsuo Hiroshi , Andresson Thorkell , Chari Raj , Swenson Rolf E. , Tarasova Nadya I. , Walters Kylie J. 
Published: December 2021

AbstractProteasome substrate receptor hRpn13 is a promising anti-cancer target. By integrated in silico and biophysical screening, we identified a chemical scaffold that binds hRpn13 with non-covalent interactions that mimic the proteasome and a weak electrophile for Michael addition. hRpn13 Pru domain binds proteasomes and ubiquitin whereas its DEUBAD domain binds deubiquitinating enzyme UCHL5. NMR revealed lead compound XL5 to interdigitate into a hydrophobic pocket created by lateral movement of a Pru β-hairpin with an exposed end for Proteolysis Targeting Chimeras (PROTACs). Implementing XL5-PROTACs as chemical probes identified a DEUBAD-lacking hRpn13 species (hRpn13Pru) present naturally with cell type-dependent abundance. XL5-PROTACs preferentially target hRpn13Pru, causing its ubiquitination. Gene-editing and rescue experiments established hRpn13 requirement for XL5-PROTAC-triggered apoptosis. These data establish hRpn13 as an anti-cancer target for multiple myeloma and introduce an hRpn13-targeting scaffold that can be optimized for preclinical trials against hRpn13Pru-producing cancer types.
Ontogenetic shifts from social to experiential learning drive avian migration timing
Authors: Abrahms Briana , Teitelbaum Claire S. , Mueller Thomas , Converse Sarah J. 
Published: December 2021

AbstractMigrating animals may benefit from social or experiential learning, yet whether and how these learning processes interact or change over time to produce observed migration patterns remains unexplored. Using 16 years of satellite-tracking data from 105 reintroduced whooping cranes, we reveal an interplay between social and experiential learning in migration timing. Both processes dramatically improved individuals’ abilities to dynamically adjust their timing to track environmental conditions along the migration path. However, results revealed an ontogenetic shift in the dominant learning process, whereby subadult birds relied on social information, while mature birds primarily relied on experiential information. These results indicate that the adjustment of migration phenology in response to the environment is a learned skill that depends on both social context and individual age. Assessing how animals successfully learn to time migrations as environmental conditions change is critical for understanding intraspecific differences in migration patterns and for anticipating responses to global change.
Superspreading quantified from bursty epidemic trajectories
Authors: Kirkegaard Julius B. , Sneppen Kim 
Published: December 2021

AbstractThe quantification of spreading heterogeneity in the COVID-19 epidemic is crucial as it affects the choice of efficient mitigating strategies irrespective of whether its origin is biological or social. We present a method to deduce temporal and individual variations in the basic reproduction number directly from epidemic trajectories at a community level. Using epidemic data from the 98 districts in Denmark we estimate an overdispersion factor k for COVID-19 to be about 0.11 (95% confidence interval 0.08–0.18), implying that 10 % of the infected cause between 70 % and 87 % of all infections.
Efficacy of a multidisciplinary care protocol for the treatment of operated hip fracture patients
Authors: Salvador-Marín Jorge , Ferrández-Martínez Francisco Javier , Lawton Cort D. , Orozco-Beltrán Domingo , Martínez-López Jose Fernando , Kelly Bryan T. , Marzo-Campos Juan Carlos 
Published: December 2021

AbstractTo assess the effects of a multidisciplinary care protocol on cost, length of hospital stay (LOS), and mortality in hip-fracture-operated patients over 65 years. Prospective cohort study between 2011 and 2017. The unexposed group comprised patients who did not receive care according to the multidisciplinary protocol, while the exposed group did. Variables analyzed were demographics, medical comorbidities, treatment, blood parameters, surgical delay, LOS, re-admissions, mortality, and a composite outcome considering in-hospital mortality and/or LOS > 10 days. We performed a Poisson regression and cost analysis. The cohort included 681 patients: 310 unexposed and 371, exposed. The exposed group showed a shorter surgical delay (3.0 vs. 3.6 days; p < 0.001), and a higher proportion received surgery within 48 h (46.1% vs. 34.2%, p = 0.002). They also showed lower rates of 30-day readmission (9.4% vs. 15.8%, p = 0.012), 30-day mortality (4.9% vs. 9.4%, p = 0.021), in-hospital mortality (3.5% vs. 7.7%; p = 0.015), and LOS (8.4 vs. 9.1 days, p < 0.001). Multivariable analysis showed a protective effect of the protocol on the composite outcome (risk ratio 0.62, 95% CI 0.48–0.80, p < 0.001). Hospital costs were reduced by EUR 112,153.3. A multidisciplinary shared care protocol was associated with a reduction in the LOS, surgical delay, 30-day readmissions, and in-hospital and 30-day mortality, in hip-fracture-operated patients.
A retrospective analysis of fibrinolytic and adjunctive antithrombotic treatment during cardiopulmonary resuscitation
Authors: Weiss Armin , Frisch Christoph , Hornung Rouven , Baubin Michael , Lederer Wolfgang 
Published: December 2021

AbstractSynergistic effects of fibrinolytic and additional antithrombotic treatment during cardiopulmonary resuscitation in out-of-hospital cardiac arrest of assumed cardiac origin were evaluated retrospectively. Data were drawn from electronic files of the physician-staffed Emergency Medical Services Tyrol. During a 22-month observation period 53 adult patients were treated with tenecteplase (mean 7641 IU), 19 (32.1%) of whom received additional antithrombotic treatment with heparin (4000–5000 IU) and acetylsalicylic acid (250–500 mg). Lasting return of spontaneous circulation occurred in four of 34 patients who received fibrinolytic treatment only and in seven of 19 patients with additional antithrombotic treatment (p = 0.037). Four of five patients who were discharged from hospital had received additional antithrombotic treatment during CPR and were in appropriate neurological status (CPC 1). Considering the small sample size in this retrospective study, the argument may be still be made that fibrinolytic and adjunctive antithrombotic treatment during cardiopulmonary resuscitation in out-of-hospital cardiac arrest of assumed cardiac origin may increase the chances for survival.
Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane
Authors: Kim Dong Ju , Jung Mi-Young , Park Joo-Hee , Pak Ha-Jin , Kim Martha , Chuck Roy S. , Park Choul Yong 
Published: December 2021

AbstractIntraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye. In this study, an intraocular implant, MXF-HA, that combines hyaluronic acid (HA) and moxifloxacin (MXF) was developed to increase the efficiency of intraocular drug delivery after surgery. MXF-HA is manufactured as a thin, transparent, yellow-tinted membrane. When inserted into the eye in a dry state, MXF-HA is naturally hydrated and settles in the eye, and the MXF contained therein is delivered by hydrolysis of the polymer over time. It was confirmed through in vivo experiments that MXF delivery was maintained in the anterior chamber of the eye at a concentration sufficient to inhibit Pseudomonas aeruginosa and Staphylococcus aureus for more than 5 days after implantation. These results suggest that MXF-HA can be utilized as a potential drug delivery method for the prevention and treatment of bacterial infections after ophthalmic surgery.
Altered cardiac mitochondrial dynamics and biogenesis in rat after short-term cocaine administration
Authors: Wen Shuheng , Unuma Kana , Funakoshi Takeshi , Aki Toshihiko , Uemura Koichi 
Published: December 2021

AbstractAbuse of the potent psychostimulant cocaine is widely established to have cardiovascular consequences. The cardiotoxicity of cocaine is mainly associated with oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics and biogenesis, as well as the mitochondrial unfolded protein response (UPRmt), guarantee cardiac mitochondrial homeostasis. Collectively, these mechanisms act to protect against stress, injury, and the detrimental effects of chemicals on mitochondria. In this study, we examined the effects of cocaine on cardiac mitochondrial dynamics, biogenesis, and UPRmt in vivo. Rats administered cocaine via the tail vein at a dose of 20 mg/kg/day for 7 days showed no structural changes in the myocardium, but electron microscopy revealed a significant increase in the number of cardiac mitochondria. Correspondingly, the expressions of the mitochondrial fission gene and mitochondrial biogenesis were increased after cocaine administration. Significant increase in the expression and nuclear translocation of activating transcription factor 5, the major active regulator of UPRmt, were observed after cocaine administration. Accordingly, our findings show that before any structural changes are observable in the myocardium, cocaine alters mitochondrial dynamics, elevates mitochondrial biogenesis, and induces the activation of UPRmt. These alterations might reflect cardiac mitochondrial compensation to protect against the cardiotoxicity of cocaine.
Reverse heat flow with Peltier-induced thermoinductive effect
Authors: Okawa Kenjiro , Amagai Yasutaka , Fujiki Hiroyuki , Kaneko Nobu-Hisa 
Published: December 2021

AbstractThe concept of “thermal inductance” expands the options of thermal circuits design. However, the inductive component is the only missing components in thermal circuits unlike their electromagnetic counterparts. Herein, we report an electrically controllable reverse heat flow, in which heat flows from a low-temperature side to a high-temperature side locally and temporarily in a single material by imposing thermal inertia and ac current. This effect can be regarded as an equivalent of the “thermoinductive” effect induced by the Peltier effect. We derive the exact solution indicating that this reverse heat flow occurs universally in solid-state systems, and that it is considerably enhanced by thermoelectric properties. A local cooling of 25 mK is demonstrated in (Bi,Sb)2Te3, which is explained by our exact solution. This effect can be directly applicable to the potential fabrication of “thermoinductor” in thermal circuits.
Critical assessment of genome-scale metabolic models of Arabidopsis thaliana
Authors: Zamani Amirzakaria Javad , Marashi Sayed-Amir , Malboobi Mohammad Ali , Lohrasebi Tahmineh , Forouzan Esmail 
Published: December 2021

The quality of a ale metabolic model is important for obtaining accurate predictions. In this study, we have evaluated the quality of available GSMMs for Arabidopsis thaliana. by inspecting some important properties.