bluuebunny/crossref_metadata_2025_split huggingface dataset:
First reliable chronology for the Early Khvalynian Caspian Sea transgression in the Lower Volga River valley
Authors: Kurbanov Redzhep , Murray Andrew , Thompson Warren , Svistunov Mikhail , Taratunina Natalia , Yanina Tamara 
Published: October 2020

During the late Quaternary, dramatic changes in relative sea level (~170 m) are known to have occurred in the Caspian Sea. However, all previous attempts at resolving the uncertainty associated with the timing of these transgressive/regressive events, primarily using radiocarbon, have produced inconclusive or controversial results. Here we present the first reliable chronology for the largest known transgression (Early Khvalynian). This was derived using optically stimulated luminescence (OSL) analysis of sand‐sized quartz, with support from infrared stimulated luminescence (IRSL) from K‐rich feldspar grains, all extracted from 16 sediment samples collected along the Lower Volga River. These samples were taken from loessic sediments, marine clays (known as Chocolate Clays) and the overlying modern soils exposed at three sections (Srednyaya Akhtuba, Raygorod, Leninsk) ~200 km upstream of the present‐day estuary. The differential bleaching rates of the quartz OSL and feldspar IRSL signals were used to evaluate the degree of resetting of quartz (and feldspar) signals; it was possible to conclude that all signals, and particularly quartz OSL, were sufficiently reset at deposition to allow accurate age estimation. Our results show unambiguously that the Early Khvalynian marine Chocolate Clays present at all three sections were deposited post‐LGM, between ~17 and ~13.1 ka ago. These age estimates are further constrained by those from the overlying Kastanozem soils (9.6–0.7 ka) and underlying loess‐soil series (32–19 ka), confirming a young (17–13 ka) age of the transgressive stage of the Early Khvalynian. Relative sea level during this period must have been well above the sampling altitudes of 11.7 m a.s.l. (Srednyaya Akhtuba), 11.3 m a.s.l. (Raygorod) and 4.7 m a.s.l. (Leninsk) to explain the absence of significant alluvial sand and to allow the deposition of the fine Chocolate Clays marker horizon.
Proposing synchronous oligometastatic non–small‐cell lung cancer based on progression after first‐line systemic therapy
Authors: Miyawaki Taichi , Wakuda Kazushige , Kenmotsu Hirotsugu , Miyawaki Eriko , Mamesaya Nobuaki , Kobayashi Haruki , Omori Shota , Ono Akira , Naito Tateaki , Murakami Haruyasu , Notsu Akifumi , Mori Keita , Harada Hideyuki , Endo Masahiro , Ohde Yasuhisa , Takahashi Kazuhisa , Takahashi Toshiaki 
Published: October 2020

AbstractDespite the importance of accurate disease definitions for effective management and treatment decisions, there is currently no consensus on what constitutes oligometastatic non–small‐cell lung cancer (NSCLC). Predominant patterns of initial progressive disease (PD) after first‐line systemic therapy have been shown to be a substantial basis for local ablative therapy (LAT) for all disease sites in patients with oligometastatic NSCLC, suggesting that these patterns could be helpful in defining synchronous oligometastatic NSCLC. Therefore, this retrospective study aimed to propose a threshold number of metastases for synchronous oligometastatic NSCLC, based on the pattern of initial PD after first‐line systemic therapy. The cut‐off threshold number of metastases compatible with synchronous oligometastatic NSCLC was determined using receiver operating characteristic (ROC) curve analyses of PD at the initially involved sites alone. ROC analysis of 175 patients revealed that the presence of 1‐3 metastases before first‐line treatment (sensitivity, 85.9%; specificity, 97.3%; area under the curve, 0.91) was compatible with oligometastatic NSCLC, therefore we divided patients into oligometastatic NSCLC and non‐oligometastatic NSCLC groups. Multivariate logistic regression analyses revealed oligometastatic NSCLC to be the only independent predictor of PD at initially involved sites alone (odds ratio 165.7; P < .001). The median survival times in patients with oligometastatic or non‐oligometastatic NSCLC were 23.0 and 10.9 mo (hazard ratio, 0.51; P = .002), respectively. Based on these findings, we propose synchronous oligometastatic NSCLC as 1‐3 metastases in accordance with patterns of initial progression. The result of our study might be contributory to provide a common definition of synchronous oligometastatic NSCLC.
The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
Authors: Nagaoka Satoshi , Yamada Daisaku , Eguchi Hidetoshi , Yokota Yuki , Iwagami Yoshifumi , Asaoka Tadafumi , Noda Takehiro , Kawamoto Koichi , Gotoh Kunihito , Kobayashi Shogo , Miyoshi Eiji , Doki Yuichiro , Mori Masaki 
Published: October 2020

AbstractInterleukin‐33 (IL‐33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL‐33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL‐33 is released during hepatectomy for CCA, subsequently facilitating the development of subclinical CCA and eventually leading to recurrent disease. IL‐33 expression was assessed in various samples from both humans and mice including resected liver and paired plasma samples collected at hepatectomy and after surgery, and its influences on recurrent disease and patient prognosis were determined. Homogenized human liver samples with high or low IL‐33 expression were added to the culture medium of human CCA cells, and the changes in proliferation and migration were evaluated. To examine the effects of inhibiting the IL‐33 release induced by hepatectomy, syngraft transplantation of murine CCA cells was performed in C57BL/6J mice with or without IL‐33 blockade. The amount of IL‐33 released into the plasma during hepatectomy correlated with the background liver expression. High expression of IL‐33 in the liver was an independent risk factor for recurrence. Homogenized liver tissue strongly expressing IL‐33 increased both the proliferation and migration of tumor cells. Mice who underwent hepatectomy exhibited CCA progression in the remnant liver, whereas blockade of IL‐33 during hepatectomy inhibited tumor progression. Thus, we concluded that surgery for CCA with curative intent paradoxically induced IL‐33 release, which facilitated CCA recurrence, and anti–IL‐33 therapy during hepatectomy might reduce the risk of CCA recurrence.
Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort
Authors: Jullien Nicolas , Saveanu Alexandru , Vergier Julia , Marquant Emeline , Quentien Marie Helene , Castinetti Frederic , Galon‐Faure Noémie , Brauner Raja , Marrakchi Turki Zinet , Tauber Maité , El Kholy Mohamed , Linglart Agnès , Rodien Patrice , Fedala Nora Soumeya , Bergada Ignacio , Cortet‐Rudelli Christine , Polak Michel , Nicolino Marc , Stuckens Chantal , Barlier Anne , Brue Thierry , Reynaud Rachel ,   the Genhypopit Network
Published: October 2020

AbstractContextThe international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism.AimsTo describe main phenotype patterns and their evolution through life.DesignPatients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2.ResultsAmong 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations.ConclusionThis large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.
Differential incorporation of scientific advances affects coastal habitat restoration practice
Authors: Hughes A. Randall , Edwards Peter , Grabowski Jonathan H. , Scyphers Steven , Williams Susan L. 
Published: October 2020

AbstractUnderstanding the diffusion of innovative ideas, behaviors, and technologies could reduce disconnects between conservation science and management, such as the science‐practice gap between biodiversity research and restoration practice. To assess knowledge uptake as an indicator of diffusion of innovation in restoration practice, we conducted an online survey of two organizations focused on coastal habitat restoration: Coastal and Estuarine Research Federation (CERF) and International Coral Reef Society (ICRS). We evaluated experience restoring particular habitats, along with perceptions of the purpose of restoration, the metrics used to evaluate restoration success, and the challenges to successful restoration. We then examined the perceived importance of genetic diversity for restoration success as an indicator of knowledge‐practice transfer in conservation strategy. The practice of coastal habitat restoration diverged by organization and habitat: a higher percentage of CERF members had restored oysters, marshes, and seagrasses compared to ICRS, whereas the reverse was true for corals. Views of the purpose of restoration, the site selection process, and the challenges to successful restoration were similar. Despite similarities in perceptions of the restoration process, the two organizations had variable indications of knowledge‐practice transfer: ICRS respondents ranked the importance of genetic diversity as a restoration strategy higher than did CERF respondents. The perceived importance of genetic diversity also differed by habitat, with both CERF and ICRS respondents ranking diversity as more important for corals. The more successful transfer of knowledge to practice in the coral community indicates that the disconnect between genetic diversity research and restoration practice is surmountable. In addition, it serves as a potential strategy for promoting the spread of innovative restoration practices to achieve long‐term recovery of ecosystems.
Pediatric lung transplantation as standard of care
Authors: Werner Raphael , Benden Christian 
Published: October 2020

AbstractFor infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long‐term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra‐corporal life support as “bridge to transplantation”. In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post‐transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence‐based data on immunosuppression are scarce. Drug‐related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long‐term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re‐transplant; however, numbers of pediatric patients undergoing lung re‐transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate.
Defusing Land Disputes? The Politics of Land Certification and Dispute Resolution in Burundi
Authors: Tchatchoua‐Djomo Rosine , van Leeuwen Mathijs , van der Haar Gemma 
Published: October 2020

ABSTRACTThere is a growing interest in localized land registration, in which user rights are acknowledged and recorded through a community‐based procedure, as an alternative to centralized titling to promote secure tenure in sub‐Saharan Africa. Localized land registration is expected to reduce land disputes, yet it remains unclear how it impacts disputes in practice. This is an urgent question for war‐affected settings that experience sensitive land disputes. This article discusses findings from ethnographic fieldwork in Burundi on pilot projects for land certification. It identifies three ways in which certification feeds into land conflicts rather than preventing or resolving them. First, land certification represents a chance for local people to enter a new round of claim making, as those ignored or disenfranchised in earlier rounds see new opportunities. Second, it offers an avenue for institutional competition between different land‐governing institutions. Third, certification provides politicians with openings to interfere in tenure relations and to expand their support base. The authors conclude that these problems are not simply a matter of inadequate policy design. Rather, there are crucial political dimensions to land conflicts and land tenure in Burundi, which means that land registration programmes run the risk of inflaming conflictive property relations in rural communities.
Computational modelling of attentional bias towards threat in paediatric anxiety
Authors: Thompson Abigail , Steinbeis Nikolaus 
Published: October 2020

AbstractComputational modelling can be used to precisely characterize the cognitive processes involved in attentional biases towards threat, yet so far has only been applied in the context of adult anxiety. Furthermore, studies investigating attentional biases in childhood anxiety have largely used tasks that conflate automatic and controlled attentional processes. By using a perceptual load paradigm, we separately investigate contributions from automatic and controlled processes to attentional biases towards negative stimuli and their association with paediatric anxiety. We also use computational modelling to investigate these mechanisms in children for the first time. In a sample of 60 children (aged 5‐11 years) we used a perceptual load task specifically adapted for children, in order to investigate attentional biases towards fearful (compared with happy and neutral) faces. Outcome measures were reaction time and percentage accuracy. We applied a drift diffusion model to investigate the precise cognitive mechanisms involved. The load effect was associated with significant differences in response time, accuracy and the diffusion modelling parameters drift rate and extra‐decisional time. Greater anxiety was associated with greater accuracy and the diffusion modelling parameter ‘drift rate’ on the fearful face trials. This was specific to the high load condition. These findings suggest that attentional biases towards fearful faces in childhood anxiety are driven by increased perceptual sensitivity towards fear in automatic attentional systems. Our findings from computational modelling suggest that current attention bias modification treatments should target perceptual encoding directly rather than processes occurring afterwards.
RLTPR Q575E: A novel recurrent gain‐of‐function mutation in patients with adult T‐cell leukemia/lymphoma
Authors: Uchida Yuichiro , Yoshimitsu Makoto , Hachiman Miho , Kusano Shuichi , Arima Naosuke , Shima Kodai , Hayashida Maiko , Kamada Yuhei , Nakamura Daisuke , Arai Akihiko , Tanaka Yuetsu , Hara Hiromitsu , Ishitsuka Kenji 
Published: October 2020

AbstractObjectivesAdult T‐cell leukemia/lymphoma (ATL) is an intractable T‐cell malignancy caused by long‐term infection with human T‐cell leukemia virus type‐1 (HTLV‐1). While ATL pathogenesis has been associated with HTLV‐1‐derived oncogenic proteins, including Tax and HBZ, the contribution of genomic aberrations remains poorly defined.MethodsTo elucidate the genomic basis of ATL, whole exome sequencing was performed on cells from 47 patients with aggressive ATL.ResultsWe discovered the novel mutation RLTPR Q575E in four patients (8.5%) with a median variant allele frequency of 0.52 (range 0.11‐0.68). Despite being reported in cutaneous T‐cell lymphoma, three ATL patients carrying RLTPR Q575E lacked skin involvement. Patients carrying RLTPR Q575E also harbored CARD11 (75%), PLCG1 (25%), PRKCB (25%), or IKBKB (25%) mutations related to TCR/NF‐κB signaling. Jurkat cells transfected with RLTPR Q575E cDNA displayed increased NF‐κB activity and significantly increased IL‐2 mRNA levels under stimulation. RLTPR Q575E increased the interaction between RLTPR and CARD11, while RLTPR directly interacted with Tax.ConclusionsWe identified, and functionally validated, a novel gain‐of‐function mutation in patients with aggressive ATL. During TCR activation by Tax or gain‐of‐function mutations, RLTPR Q575E selectively upregulates NF‐κB signaling and may exert oncogenic effects on ATL pathogenesis.
Regulation of indoleamine 2, 3‐dioxygenase in hippocampal microglia by NLRP3 inflammasome in lipopolysaccharide‐induced depressive‐like behaviors
Authors: Zhang Shanshan , Zong Ying , Ren Zhonggan , Hu Juntao , Wu Xinyuan , Xiao Honglei , Qin Song , Zhou Guomin , Ma Yuanyuan , Zhang Yaodong , Yu Jin , Wang Kaidi , Lu Guocai , Liu Qiong 
Published: October 2020

AbstractIn the brain, NLRP3 (Nucleotide‐binding oligomerization domain, leucine‐rich repeat, and pyrin‐domain‐containing 3) inflammasome is mainly expressed in microglia located in the hippocampus and other mood‐regulated regions, which are particularly susceptible to stress. The activation of NLRP3 inflammasome and production of the activation products may contribute to the development of depressive disorder and memory deficits. Indoleamine 2, 3‐dioxygenase (IDO) is a key factor mediating inflammation and major depressive disorder (MDD). We here generated NLRP3 and apoptosis‐associated speck‐like protein containing caspase recruitment domain (ASC)‐knockout mice, respectively, to verify the effects of NLRP3 or ASC deficiency on lipopolysaccharide (LPS)‐induced depressive‐like behaviors, neuroinflammation, and regulation of IDO expression. Furthermore, we treated these mice with the antidepressant clomipramine (CLO) to observe its effect on depressive‐like behaviors and the expression of the NLRP3 inflammasome and LPS‐induced IDO. We found that intraperitoneal LPS administration led to marked depressive‐like behavior and neuroinflammation. NLRP3 or ASC deficiency attenuated LPS‐induced depressive‐like symptoms and increased IDO gene expression, which was accompanied by inhibition of LPS‐induced microglial activation, suggesting that IDO may be a downstream mediator of the NLRP3 inflammasome in inflammation‐mediated depressive‐like behaviors. Clomipramine administration ameliorated depressive‐like behavior in LPS‐treated mice by regulating the expression of ASC and IDO. In conclusion, NLRP3 inflammasome is involved in LPS‐induced depressive‐like behaviors, and that NLRP3 and ASC may play roles in regulating IDO expression in microglia. This may be a potential mechanism for its involvement in MDD. The antidepressant effect of clomipramine may be exerted through the regulation of ASC‐mediated expression of IDO.
Testing the effect of tACS over parietal cortex in modulating endogenous alpha rhythm and temporal integration windows in visual perception
Authors: Ronconi Luca , Melcher David , Junghöfer Markus , Wolters Carsten H. , Busch Niko A. 
Published: October 2020

AbstractNeural oscillations in the alpha band (8–12 Hz) have been proposed as a key mechanism for the temporal resolution of visual perception. Higher alpha frequencies have been related to improved segregation of visual events over time, whereas lower alpha frequencies have been related to improved temporal integration. Similarly, also the phase of ongoing alpha has been shown to correlate with temporal integration/segregation. To test a causal relationship between alpha oscillations and perception, we here employed multi‐channel transcranial alternating current stimulation (mc‐tACS) over the right parietal cortex, whereas participants performed a visual temporal integration/segregation task that used identical stimuli with different instructions. Before and after mc‐tACS we recorded the resting‐state electroencephalogram (EEG) to extract the individual alpha frequency (IAF) and delivered electrical stimulation at slightly slower and faster frequencies (IAF±2 Hz). We hypothesized that this would not only drive endogenous alpha rhythms, but also affect temporal integration and segregation in an opposite way. However, the mc‐tACS protocol used here did not consistently increase or decrease the IAF after the stimulation and did not affect temporal integration/segregation accuracy as expected. Although we found some preliminary evidence for an influence of tACS phase on temporal integration accuracy, the ongoing phase of mc‐tACS oscillations did not reliably modulate temporal integration/segregation accuracy in a sinusoidal way as would have been predicted by an effective entrainment of brain oscillations. These findings may guide future studies using different stimulation montages for investigating the role of cortical alpha oscillations for human vision.
Is the “end‐of‐study guess” a valid measure of sham blinding during transcranial direct current stimulation?
Authors: Turner Christopher , Jackson Catherine , Learmonth Gemma 
Published: October 2020

AbstractStudies using transcranial direct current stimulation (tDCS) typically incorporate a fade‐in, short‐stimulation, fade‐out sham (placebo) protocol, which is assumed to be indistinct from a 10–30 min active protocol on the scalp. However, many studies report that participants can dissociate active stimulation from sham, even during low‐intensity 1 mA currents. We recently identified differences in the perception of an active (10 min of 1 mA) and a sham (20 s of 1 mA) protocol that lasted for 5 min after the cessation of sham. In the present study we assessed whether delivery of a higher‐intensity 2 mA current would exacerbate these differences. Two protocols were delivered to 32 adults in a double‐blinded, within‐subjects design (active: 10 min of 2 mA, and sham: 20 s of 2 mA), with the anode over the left primary motor cortex and the cathode on the right forehead. Participants were asked “Is the stimulation on?” and “How sure are you?” at 30 s intervals during and after stimulation. The differences between active and sham were more consistent and sustained during 2 mA than during 1 mA. We then quantified how well participants were able to track the presence and absence of stimulation (i.e. their sensitivity) during the experiment using cross‐correlations. Current strength was a good classifier of sensitivity during active tDCS, but exhibited only moderate specificity during sham. The accuracy of the end‐of‐study guess was no better than chance at predicting sensitivity. Our results indicate that the traditional end‐of‐study guess poorly reflects the sensitivity of participants to stimulation, and may not be a valid method of assessing sham blinding.