bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune‐related adverse events of a PD‐L1 inhibitor plus chemotherapy versus a PD‐L1 inhibitor alone in first‐line treatment for advanced non–small cell lung cancer: A meta‐analysis of randomized control trials
Authors: Wang Manting , Liang Hengrui , Wang Wei , Zhao Shen , Cai Xiuyu , Zhao Yi , Li Caichen , Cheng Bo , Xiong Shan , Li Jianfu , He Jianxing , Liang Wenhua 
Published: October 2020

BackgroundThe addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD‐L1) inhibitor is a more effective option as a first‐line treatment for advanced non–small cell lung cancer (NSCLC). It might also inhibit an overactive immune response and thereby reduce immune‐related adverse events (irAEs). This meta‐analysis assessed the rate of irAEs with a PD‐(L)1 inhibitor plus chemotherapy (I+C) versus a PD‐(L)1 inhibitor alone (I) and evaluated the indirect relative risk (RR) of I+C versus I.MethodsThe protocol of this study was registered with PROSPERO (CRD42020139923). The pooled rates of irAEs at different grades were calculated by a single‐arm meta‐analysis weighted by sample size, and RRs were determined by direct meta‐analysis and indirect treatment comparison.ResultsOverall, I+C had a lower rate of grade 3 or higher irAEs than I (7.1% vs 10.6%; indirect RR, 0.516; 95% confidence interval [CI], 0.291‐0.916), although irAEs of any grade were similar. The rate of pneumonitis with I+C was lower than the rate with I for any grade (5.9% vs 7.1%; indirect RR, 0.217; 95% CI, 0.080‐0.588) and for grade 3 or higher. In the endocrine system, I+C was associated with a lower overall ratein comparison with I (16.1% vs 20.1%; indirect RR, 0.260; 95% CI, 0.120‐0.564), whereas irAEs of the digestive system were similar with I+C and I. In other systems, I+C decreased the rate of skin reactions, including rash, in comparison with I (10.4% vs 12.9%; indirect RR, 0.474; 95% CI, 0.299‐0.751). The rate of grade 3 or higher skin reactions (excluding rash) also decreased with I+C versus I (1.1% vs 2.0%) with an indirect RR of 0.158 (95% CI, 0.032‐0.765), whereas other included irAEs were similar.ConclusionsIn comparison with a PD‐(L)1 inhibitor alone, a combination with chemotherapy for the first‐line treatment of NSCLC decreased the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.Lay Summary

In the first‐line treatment of advanced non–small cell lung cancer (NSCLC), the addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD‐(L)1) inhibitor is a more effective option.

Adding chemotherapy might reduce immune‐related adverse events (irAEs). Thus, this article assesses the rate of irAEs with a PD‐(L)1 inhibitor plus chemotherapy (I+C) in comparison with a PD‐(L)1 inhibitor alone (I) and evaluates the indirect relative risk (RR) with I+C versus I.

The key finding is that in comparison with a PD‐(L)1 inhibitor alone, a combination with chemotherapy for the first‐line treatment of NSCLC decreases the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.
Using Cross‐Correlated Spin Relaxation to Characterize Backbone Dihedral Angle Distributions of Flexible Protein Segments
Authors: Kauffmann Clemens , Zawadzka‐Kazimierczuk Anna , Kontaxis Georg , Konrat Robert 
Published: October 2020

AbstractCrucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross‐correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR‐encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins.
Preface to Special Issue of ChemSusChem on Green Carbon Science: CO2 Capture and Conversion
Authors: Corma Avelino 
Published: October 2020

AbstractGreen carbon science concerns the efficient use of carbon resources and the minimization of CO2 emissions. In this preface to the Special Issue entitled Green Carbon Science: CO2 Capture and Conversion, Professor Avelino Corma offers his thoughts on how the capture and utilization of CO2 can aid the transition to more sustainable production of energy and chemicals.
Unusual cerebrospinal fluid finding of intracytoplasmic granules in metaplastic carcinoma of the breast with acinar differentiation
Authors: Sardana Ruhani , Parwani Anil V , Cui Xiaoyan , Balakrishna Jayalakshmi 
Published: October 2020

AbstractCerebrospinal fluid (CSF) evaluation for total and differential cell count is a common practice in pathology for evaluation of various disease conditions. Although rare, these CSF samples yield interesting and unusual morphological findings, which are not only of academic interest, but also may play key roles in diagnosis. For diagnosing metastatic carcinoma in brain and meninges, CSF examination is one of the important tools along with imaging studies. Metaplastic breast carcinoma (MBC) encompasses a rare (<1% of all breast cancers), aggressive and highly heterogeneous group of tumors. MBC is almost always estrogen receptor, progesterone receptor and Her2 negative (triple negative) and shows frequent early distant metastases as well as sub‐optimal response to systemic therapies. The involvement of leptomeninges is most commonly associated with these triple‐ negative subtypes. In this report, we present an unusual case of malignant cells with prominent intracytoplasmic granules in CSF smears of a 46‐year‐old female with metastatic MBC with acinar differentiation. An extensive review of literature in English language did not return any other reports of a similar finding.
Adult‐onset diabetes in Middle Eastern immigrants to Sweden: Novel subgroups and diabetic complications—The All New Diabetes in Scania cohort diabetic complications and ethnicity
Authors: Bennet Louise , Nilsson Christopher , Mansour‐Aly Dina , Christensson Anders , Groop Leif , Ahlqvist Emma 
Published: October 2020

AbstractBackgroundMiddle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro‐ and microvascular complications between diabetes patients of Middle Eastern and European origin.MethodsThis study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro‐ and microvascular complications were assessed using cox‐regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c.FindingsIn Iraqi immigrants versus native Swedes, severe insulin‐deficient diabetes was almost twice as common (27.9 vs. 16.2% p < 0.001) but severe insulin‐resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06–3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05–0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group.InterpretationPeople with diabetes, born in the Middle East present with a more insulin‐deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.
Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis
Authors: Gotvaldová Klára , Hájková Kateřina , Borovička Jan , Jurok Radek , Cihlářová Petra , Kuchař Martin 
Published: October 2020

AbstractPsilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to the neurotransmitter serotonin. Psilocybin and its pharmacologically active metabolite psilocin in particular are known for their psychoactive effects. These substances typically occur in most species of the genus Psilocybe (Fungi, Strophariaceae). Even the sclerotia of some of these fungi known as “magic truffles” are of growing interest in microdosing due to them improving cognitive function studies. In addition to microdosing studies, psilocybin has also been applied in clinical studies, but only its pure form has been administrated so far. Moreover, the determination of tryptamine alkaloids is used in forensic analysis.In this study, freshly cultivated fruit bodies of Psilocybe cubensis were used for monitoring stability (including storage and processing conditions of fruiting bodies). Furthermore, mycelium and the individual parts of the fruiting bodies (caps, stipes, and basidiospores) were also examined. The concentration of tryptamines in final extracts was analyzed using ultra‐high‐performance liquid chromatography coupled with mass spectrometry. No tryptamines were detected in the basidiospores, and only psilocin was present at 0.47 wt.% in the mycelium. The stipes contained approximately half the amount of tryptamine alkaloids (0.52 wt.%) than the caps (1.03 wt.%); however, these results were not statistically significant, as the concentration of tryptamines in individual fruiting bodies is highly variable. The storage conditions showed that the highest degradation of tryptamines was seen in fresh mushrooms stored at −80°C, and the lowest decay was seen in dried biomass stored in the dark at room temperature.
Kinetic profile of N,N‐dimethyltryptamine and β‐carbolines in saliva and serum after oral administration of ayahuasca in a religious context
Authors: Lanaro Rafael , Mello Sueli Moreira , da Cunha Kelly Francisco , Silveira Gabriela , Corrêa‐Neto Nelson Francisco , Hyslop Stephen , Cabrices Oscar G. , Costa Jose Luiz , Linardi Alessandra 
Published: October 2020

AbstractAyahuasca is a beverage obtained from Banisteriopsis caapi plus Psychotria viridis. B. caapi contains the β‐carbolines harmine, harmaline, and tetrahydroharmine that are monoamine oxidase inhibitors and P. viridis contains N,N‐dimethyltryptamine (DMT) that is responsible for the visionary effects of the beverage. Ayahuasca use is becoming a global phenomenon, and the recreational use of DMT and similar alkaloids has also increased in recent years; such uncontrolled use can lead to severe intoxications. In this investigation, liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to study the kinetics of alkaloids over a 24 h period in saliva and serum of 14 volunteers who consumed ayahuasca twice a month in a religious context. We compared the area under the curve (AUC), maximum concentration (Cmax), time to reach Cmax (Tmax), mean residence time (MRT), and half‐life (t1/2), as well as the serum/saliva ratios of these parameters. DMT and β‐carboline concentrations (Cmax) and AUC were higher in saliva than in serum and the MRT was 1.5–3.0 times higher in serum. A generalized estimation equations (GEEs) model suggested that serum concentrations could be predicted by saliva concentrations, despite large individual variability in the saliva and serum alkaloid concentrations. The possibility of using saliva as a biological matrix to detect DMT, β‐carbolines, and their derivatives is very interesting because it allows fast noninvasive sample collection and could be useful for detecting similar alkaloids used recreationally that have considerable potential for intoxication.
Thermal transgenerational effects remain after two generations
Authors: Lee Who‐Seung , Salinas Santiago , Lee Young‐Rog , Siskidis Jo Anne , Mangel Marc , Munch Stephan B. 
Published: October 2020

AbstractTransgenerational plasticity (TGP) is increasingly recognized as a mechanism by which organisms can respond to environments that change across generations. Although recent empirical and theoretical studies have explored conditions under which TGP is predicted to evolve, it is still unclear whether the effects of the parental environment will remain beyond the offspring generation. Using a small cyprinodontid fish, we explored multigenerational thermal TGP to address two related questions. First (experiment 1), does the strength of TGP decline or accumulate across multiple generations? Second (experiment 2), how does the experience of a temperature novel to both parents and offspring affect the strength of TGP? In the first experiment, we found a significant interaction between F1 and F2 temperatures and juvenile growth, but no effect of egg diameter. The strength of TGP between F0 and F1 generations was similar in both experiments but declined in subsequent generations. Further, experience of a novel temperature accelerated the decline. This pattern, although similar to that found in other species, is certainly not universally observed, suggesting that theoretical and empirical effort is needed to understand the multigenerational dynamics of TGP.
Biogeographic differences in plant–soil biota relationships contribute to the exotic range expansion of Verbascum thapsus
Authors: Dieskau Julia , Bruelheide Helge , Gutknecht Jessica , Erfmeier Alexandra 
Published: October 2020

Abstract

Exotic plant species can evolve adaptations to environmental conditions in the exotic range. Furthermore, soil biota can foster exotic spread in the absence of negative soil pathogen–plant interactions or because of increased positive soil biota–plant feedbacks in the exotic range. Little is known, however, about the evolutionary dimension of plant–soil biota interactions when comparing native and introduced ranges.

To assess the role of soil microbes for rapid evolution in plant invasion, we subjected Verbascum thapsus, a species native to Europe, to a reciprocal transplant experiment with soil and seed material originating from Germany (native) and New Zealand (exotic). Soil samples were treated with biocides to distinguish between effects of soil fungi and bacteria. Seedlings from each of five native and exotic populations were transplanted into soil biota communities originating from all populations and subjected to treatments of soil biota reduction: application of (a) fungicide, (b) biocide, (c) a combination of the two, and (d) control.

For most of the investigated traits, native populations showed higher performance than exotic populations; there was no effect of soil biota origin. However, plants developed longer leaves and larger rosettes when treated with their respective home soil communities, indicating that native and exotic plant populations differed in their interaction with soil biota origin. The absence of fungi and bacteria resulted in a higher specific root length, suggesting that V. thapsus may compensate the absence of mutualistic microbes by increasing its root–soil surface contact.

Synthesis. Introduced plants can evolve adaptations to soil biota in their new distribution range. This demonstrates the importance of biogeographic differences in plant–soil biota relationships and suggests that future studies addressing evolutionary divergence should account for differential effects of soil biota from the home and exotic range on native and exotic populations of successful plant invaders.
Vegetation growth and landscape genetics of Tillandsia lomas at their dry limits in the Atacama Desert show fine‐scale response to environmental parameters
Authors: Koch Marcus A. , Stock Clara , Kleinpeter Dorothea , del Río Camilo , Osses Pablo , Merklinger Felix F. , Quandt Dietmar , Siegmund Alexander 
Published: October 2020

Abstract

Ecosystem dry limits have been studied in the context of species biology, fitness, and interactions with biotic and abiotic parameters, but the interactive effects of these parameters remain underexplored. Therefore, information on the putative effects of global climate change on these ecosystems is often lacking.

We analyzed the interplay between fine‐scale landscape genetics and biotic and abiotic factors of terrestrial Tillandsia lomas in the hyperarid Atacama Desert, characterized by a fog‐dependent vegetation type almost entirely dominated by one single vascular plant species.

We showed that metapopulations of Tillandsia landbeckii are genetically connected over many hundreds of square kilometers, and despite having a large potential for clonal propagation, genetic diversity is regionally and locally structured. At the landscape level, genetic diversity correlates well with fitness parameters such as growth, flowering, and vegetation density. We also observed fine‐scale correlation with a 3‐D landscape model indicating a positive feedback with seasonal fog occurrence and availability. The various interactions of biotic and abiotic factors resulted in regular linear banding patterns of vegetation arranged orthogonally toward the landscape slope. Ex situ growth experiments indicated that T. landbeckii grows at optimal rates in this extreme hyperarid environment, and we can extrapolate mean biomass production for this ecosystem.

Synthesis. Our results suggest that the unique ecosystem of terrestrial Tillandsia lomas in the hyperarid Atacama Desert is an evolutionarily balanced and fine‐scaled system. The vegetation itself is composed of long‐lived and persistent modules. We developed a descriptive model of the various interacting factors, thereby also highlighting the severe threat caused by global climate change potentially associated with fog disturbance patterns along the Chilean Pacific coast.
Influence of soil warming and N‐addition on sap flux density and stem radius variation in boreal stands in Quebec, Canada
Authors: Balducci Lorena , Deslauriers Annie , De Barba Daniele , Rossi Sergio , Houle Daniel , Bergeron Yves , Morin Hubert 
Published: October 2020

AbstractClimate change is projected to intensify the global hydrological cycle and increase temperatures. Excess N deposition could limit plant productivity because of a lack of plant–soil system efficiency with reduced water availability. However, the effects of soil warming and N‐addition on tree water transport and water use remain poorly understood. This study aimed to quantify the effects of soil warming and N‐addition associated with meteorological variables on the sap flux density and stem radius variation in black spruce (Picea mariana [Mill.] B.S.P.). From 2008 to 2014, we conducted a long‐term experiment on mature trees growing in two stands (Bernatchez [BER] and Simoncouche [SIM]) at different latitudes to evaluate the effect of soil warming (H) and N‐addition. During 2014, we investigated soil and plant water status between May and August, sap flux density from July to August and stem radius variation over the whole year. At the colder, northern site (BER), we detected a significant increase in sap flux density with the H‐treatment, whereas no effect was observed at the warmer, southern site (SIM). At BER, diurnal sap flux density in H × N‐addition treatment showed a significant effect in the afternoon near the peak of day compared with the other treatments. We found no significant effects of independent single or combined factors on soil and plant water status and stem radius variation at either site. Under climate change, black spruce at more northern sites could have a better water use and storage for wood productivity than those at more southern sites.
Toxic Effects of Polychlorinated Biphenyl Congeners and Aroclors on Embryonic Growth and Development
Authors: Singleman Corinna , Zimmerman Alison , Harrison Elise , Roy Nirmal K. , Wirgin Isaac , Holtzman Nathalia G. 
Published: October 2020

Abstract
Polychlorinated biphenyls (PCBs) cause significant health and reproductive problems in many vertebrates. Exposure during embryogenesis likely leads to defects in organ development, compromising survival and growth through adulthood. The present study identifies the impact of PCBs on the embryonic development of key organs and resulting consequences on survival and growth. Zebrafish embryos were treated with individual PCB congeners (126 or 104) or one of 4 Aroclor mixtures (1016, 1242, 1254, or 1260) and analyzed for changes in gross embryonic morphology. Specific organs were assessed for defects during embryonic development, using a variety of transgenic zebrafish to improve organ visualization. Resulting larvae were grown to adulthood while survival and growth were assayed. Embryonic gross development on PCB treatment was abnormal, with defects presenting in a concentration-dependent manner in the liver, pancreas, heart, and blood vessel organization. Polychlorinated biphenyl 126 treatment resulted in the most consistently severe and fatal phenotypes, whereas treatments with PCB 104 and Aroclors resulted in a range of more subtle organ defects. Survival of fish was highly variable although the growth rates of surviving fish were relatively normal, suggesting that maturing PCB-treated fish that survive develop compensatory strategies needed to reach adulthood. Life span analyses of fish from embryogenesis through adulthood, as in the present study, are scarce but important for the field because they help identify foci for further studies. Environ Toxicol Chem 2021;40:187–201. © 2020 SETAC
Neuronal brain‐derived neurotrophic factor manipulates microglial dynamics
Authors: Onodera Junya , Nagata Hidetaka , Nakashima Ai , Ikegaya Yuji , Koyama Ryuta 
Published: October 2020

AbstractBrain‐derived neurotrophic factor (BDNF), a main member of the neurotrophin family that is active in the brain, supports neuronal survival and growth. Microglial BDNF affects both the structural and functional properties of neurons. In contrast, whether and how neuronal BDNF affects microglial dynamics remain largely undetermined. Here, we examined the effects of BDNF on the properties of microglia in the CA3 region of the hippocampus. We chose this site because the axonal boutons of hippocampal mossy fibers, which are mostly formed in the CA3 region, contain the highest levels of BDNF in the rodent brain. We transfected mouse dentate granule cells with an adeno‐associated virus that encodes both a BDNF short hairpin RNA (shRNA) and red fluorescent protein to examine the effects of mossy fiber‐derived BDNF on microglia. Based on immunohistochemistry, BDNF knockdown with an shRNA resulted in an increase in microglial density in the mossy fiber pathway and increased engulfment of mossy fiber axons by microglia. In addition, we performed time‐lapse imaging of microglial processes in hippocampal slice cultures to examine the effects of BDNF on microglial motility. Time‐lapse imaging revealed increases in the motility of microglial processes and the engulfment of mossy fiber synapses by microglia when BDNF signaling was pharmacologically blocked. Thus, neuronal BDNF prevents microglia from engulfing mossy fiber synapses in the hippocampus.