bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPLORATION PLAYS IN THE CAUCASUS REGION
Authors: Tari G. , Blackbourn G. , Boote D.R.D. , Sachsenhofer R.F. , Yukler A.
Published: June 2021

Exploration efforts around the Greater Caucasus region started towards the end of the 19th century and established a wide range of petroleum play types in various basin segments around the orogen. All these plays are associated with the flanks of the inverted thrust‐fold belt and the adjacent foreland basin systems, but display significant variation among the basin segments depending on the tectonostratigraphic units involved and the degree of exploration maturity. Whereas the same main source rocks have generated most of the hydrocarbons in all the basins (namely organic‐rich shales in the Oligocene – Lower Miocene Maykop Group and the Eocene Kuma Formation), it is primarily the trapping style, both proven and speculative, which is responsible for the broad spectrum of play types observed. Eleven play type diagrams across six main petroleum provinces of the Greater Caucasus region are presented in this paper and summarize the current exploration understanding of the existing discoveries and potential new play targets. These play cartoons offer a prospect‐scale summary of both mature producing and underexplored basin segments in a coherent visual manner, and are therefore intended to promote future exploration efforts in the Caucasus region. The testing of new play types requires the proper risking of the two most critical elements in the region: hydrocarbon kitchen effectiveness, and post‐charge trap modification. The de‐risking of these factors will require properly designed, fit‐for‐purpose acquisition of modern geological and geophysical data sets.
STRUCTURE AND EVOLUTION OF THE TEREK‐CASPIAN FOLD‐AND‐THRUST BELT: NEW INSIGHTS FROM REGIONAL SEISMIC DATA
Authors: Sobornov Konstantin
Published: June 2021

The Terek‐Caspian fold‐and‐thrust belt along the northern flank of the Greater Caucasus Mountain Range together with the adjacent foreland basin is one of the oldest oil‐producing regions in Russia. Despite the long history of exploration, recently acquired seismic data has provided new insights about the structural architecture and evolution of this area. Its structural development during the Neogene was constrained by a syn‐extensional tectonic fabric inherited from Jurassic rifting and extension of the Great Caucasus Basin. The structural framework of this basin controlled the distribution of syn‐extensional deposits, and the Cenozoic reactivation of lateral ramps resulted in along‐strike variations in structural style. Thus western, central and SE segments of the Terek‐Caspian foldbelt are recognised and are referred to here as the Terek‐Sunzha fold zone, the Dagestan Promontory, and the Maritime Zone in southern Dagestan.

Three principal episodes of Cenozoic compression in the Terek‐Caspian fold‐and‐thrust belt took place. The first episode in the Oligocene resulted in the inversion of pre‐existing normal faults with the coeval development of a foreland basin to the north of the thrust belt. The dominance of sediments of northerly provenance in the foreland basin suggests there was only moderate uplift of the Greater Caucasus at this time. However, significant uplift of the orogenic belt took place during later phases of Sarmatian (Late Miocene) and Akchagylian (Late Pliocene) compression. Erosion of the uplifting Greater Caucasus gave rise to the development of large‐scale, northerly prograding clinoforms which are clearly observed on seismic profiles in the foreland basin. Shortening was largely accommodated by wedge‐shaped thrusting facilitated by the presence of mechanically weak stratigraphic units.

Structural development of the Terek‐Sunzha fold zone in the west of the Terek‐Caspian fold‐and‐thrust belt was largely controlled by a Tithonian salt layer which provided an efficient basal detachment surface and which also supplied material to squeezed diapirs in front of the belt. To the east, the plan‐view shape and internal architecture of the Dagestan Promontory were influenced by the areal extent of the Lower‐Middle Jurassic depocentre of the palaeo‐Volga delta which is up to 10 km thick. In the Maritime Zone, the style of shortening was mostly controlled by the presence of a pre‐existing structural high composed of folded Palaeozoic‐Triassic strata in front of the fold‐thrust belt.
EOCENE VOLCANICLASTICS IN THE KARTLI BASIN, GEORGIA: A FRACTURED RESERVOIR SEQUENCE
Authors: Tari G. , Vrsic A. , Gumpenberger T. , Mekonnen E. , Hujer W. , Fallah M. , Tevzadze N. , Janiashvili A. , Pace P. , Ricciato A. , Alania V. , Enukidze O.
Published: June 2021

In the broader Caucasus region, multiple extrusive volcanic units are present within the Jurassic, Cretaceous, Eocene and Miocene sedimentary successions. Partial reworking of volcanic material from various provenance areas into Eocene, Oligocene and Miocene reservoir units is commonly observed in the Eastern Black Sea and in the Rioni, Kartli and Kura Basins of onshore Georgia. Reservoir quality has in general been negatively affected by volcanic rock fragments which may have undergone complex diagenetic alteration. However, despite concerns regarding reservoir quality, oil at the Samgori field, the largest field in Georgia (∼200 MM brl recovered), is hosted in altered Middle Eocene volcaniclastic sandstones interbedded with deep‐water turbidites. Previous studies of core material from numerous wells in this field showed that most of the oil is contained in altered, microfractured, laumontite‐rich tuffs which have fracture and cavernous net porosities averaging 12% and average permeability of 15 mD. The laumontite tuffs comprise only up to 20% of a tuffaceous sandstone section and occur as isolated lenses or pods on a sub‐seismic scale (i.e. 5‐10 m thick), causing highly variable oil productivity from one well to another.

The petrographic analysis of samples of Middle Eocene volcaniclastic sandstones from outcrops in the central part of the Kartli Basin around Tbilisi broadly confirms the main conclusions of studies completed some 30 years ago which were based on the analysis of subsurface samples. However, the surface samples analysed show that zeolitization events typically did not improve, but actually reduced, reservoir quality due to extensive zeolite cementation. The poor reservoir properties of the plug samples, which are age‐equivalent to the proven subsurface Middle Eocene reservoir interval, highlight fracturing as a key factor controlling the presence of exceptional producers (up to 9000 b/d) in the Samgori field complex. The study therefore underlines the critical role of fracturing of the Middle Eocene volcaniclastic reservoir sequence in the Kartli Basin.
GEOCHEMISTRY OF OILS IN THE TEREK‐CASPIAN FOREDEEP AND PRIKUMSK SWELL, NE GREATER CAUCASUS, SOUTHERN RUSSIA
Authors: Yandarbiev N. Sh. , Sachsenhofer R. F. , Ajuaba S. , Bechtel A. , Yandarbieva D. N.
Published: June 2021

Hydrocarbon reserves of the order of 1140 MM brl oe have been identified in the northern foreland of the eastern Greater Caucasus, principally in the Terek‐Caspian fold‐and‐thrust belt and the Prikumsk Swell in the north of the Terek‐Caspian foredeep. Despite the great economic significance of these areas and their long exploration history, the origin of the hydrocarbons is still poorly understood. In the present paper, geochemical data from 73 oil samples representing 28 fields are used to investigate the presence of oil families and to correlate the oils with potential source rocks.

Biomarker composition of oils in Cretaceous and Miocene reservoirs in the Terek‐Caspian fold‐and‐thrust belt is mainly controlled by reservoir depth (100‐5700 m) and maturity (0.70‐1.15 %Ro), and it is therefore difficult to separate maturity and facies effects. For example, a downward increase in diasterane/sterane ratios may indicate a change in source rock facies or may be attributed to increasing maturity. Some shallow oils are biodegraded. The presence of short‐chain n‐alkanes in biodegraded oils indicates recent hydrocarbon migration. Biomarker data (e.g. the presence of oleanane) and compound‐specific isotope data suggest that the Khadum Formation in the lower part of the Maikop Group is the main source rock. However data from Cretaceous and Paleogene organic‐rich rocks, which may also have contributed to the accumulated oils, are urgently needed in order to quantify their possible input.

In the Prikumsk Swell, at least two oil families, characterized by low and high C28/C29 sterane ratios respectively, can be distinguished in reservoir rocks of Triassic to Cretaceous age. Most oils are characterized by low C28/C29 sterane ratios and the absence of oleanane (“Group B oils”). These characteristics suggest a pre‐Upper Cretaceous source for the oils, which is also supported by the geological setting. Hierarchical cluster analysis suggests the presence of four sub‐groups (Sub‐Groups B1 to B4). Typically, biomarker ratios in oils in Cretaceous reservoirs are more uniform than those in Triassic and Jurassic reservoirs. Potential source rocks include Lower Triassic deep‐water clayey limestones and shales as well as Middle Jurassic and Aptian‐Albian marine shales. Three oil samples from Triassic and Cretaceous reservoirs form a separate oil family (“Group A”), which is genetically related to oils from the Terek‐Caspian fold‐and‐thrust belt. Group A oils have high C28/C29 sterane ratios and in general contain at least some oleanane. A contribution by Cenozoic source rocks to Group A oils is likely.
Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses
Authors: Knych Heather K. , Arthur Rick M. , Gretler Sophie R. , McKemie Daniel S. , Goldin Skyler , Kass Philip H.
Published: June 2021

Flunixin meglumine is a highly efficacious nonsteroidal anti‐inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post‐administration. Serum for determination of thromboxane concentrations and whole blood samples was collected at various time and challenged with lipopolysaccharide, calcium ionophore, or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flunixin, 5‐OH flunixin, and eicosanoids were measured using LC‐MS/MS and non‐compartmental pharmacokinetic analysis performed on concentration data. Serum concentrations of flunixin and 5‐OH flunixin were above the limit of quantitation at 96 h post‐administration in both serum and urine. The mean (range) for Cmax, Tmax and the terminal half‐life were 515.6 (369.7–714.0) ng/ml, 8.67 (8.0 12.0) h, and 22.4 (18.3–42.5) h, respectively. Following transdermal administration, based on effects on eicosanoid synthesis, flunixin meglumine inhibited cyclooxygenase 1 and 2 and 15‐lipooxygenase activity, with anti‐inflammatory effects lasting for 24–72 h.
Proprotein convertase subtilisin/kexin type 9 regulates the production of acute‐phase reactants from the liver
Authors: Jacome Sanz Dafne , Saralahti Anni K. , Pekkarinen Meeri , Kesseli Juha , Nykter Matti , Rämet Mika , Ojanen Markus J. T. , Pesu Marko
Published: June 2021

Background & Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) controls blood cholesterol levels by fostering the LDL receptor (LDLR) degradation in hepatocytes. Additionally, PCSK9 has been suggested to participate in immunoregulation by modulating cytokine production. We studied the immunological role of PCSK9 in Streptococcus pneumoniae bacteraemia in vivo and in a human hepatocyte cell line.

Methods

CRISPR/Cas9 mutagenesis was utilized to create pcsk9 knock‐out (KO) zebrafish, which were infected with S pneumoniae to assess the role of PCSK9 for the survival of the fish and in the transcriptomic response of the liver. The direct effects of PCSK9 on the expression of acute‐phase reaction (APR) genes were studied in HepG2 cells.

Results

The pcsk9 KO zebrafish lines (pcsk9tpu‐13 and pcsk9tpu‐2,+15) did not show developmental defects or gross phenotypical differences. In the S pneumoniae infected zebrafish, the mortality of pcsk9 KOs was similar to the controls. A liver‐specific gene expression analysis revealed that a pneumococcal challenge upregulated pcsk9, and that the pcsk9 deletion reduced the expression of APR genes, including hepcidin antimicrobial peptide (hamp) and complement component 7b (c7b). Accordingly, silencing PCSK9 in vitro in HepG2 cells using small interfering RNAs (siRNAs) decreased HAMP expression.

Conclusions

We demonstrate that PCSK9 is not critical for zebrafish survival in a systemic pneumococcal infection. However, PCSK9 deficiency was associated with the lower expression of APR genes in zebrafish and altered the expression of innate immunity genes in a human hepatocyte cell line. Overall, our data suggest an evolutionarily conserved function for PCSK9 in APR in the liver.
Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology
Authors: Galle Peter R. , Kudo Masatoshi , Llovet Josep M. , Finn Richard S. , Karwal Mark , Pezet Denis , Kim Tae‐You , Yang Tsai‐Sheng , Lonardi Sara , Tomasek Jiri , Phelip Jean‐Marc , Touchefeu Yann , Koh Su‐Jin , Stirnimann Guido , Liang Kun , Ogburn Kenyon D. , Wang Chunxiao , Abada Paolo , Widau Ryan C. , Zhu Andrew X.
Published: June 2021

Background & Aims

Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH‐2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load.

Methods

Meta‐analysis was conducted in patients with aHCC and alpha‐fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH‐2 trials. Individual patient‐level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre‐treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression‐free survival (PFS) were evaluated using the Kaplan‐Meier method and Cox proportional hazard model (stratified by study).

Results

Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P‐value = .23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55–0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55–1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40–0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver‐specific adverse events.

Conclusions

Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.
Ultra‐processed food is associated with features of metabolic syndrome and non‐alcoholic fatty liver disease
Authors: Ivancovsky‐Wajcman Dana , Fliss‐Isakov Naomi , Webb Muriel , Bentov Itay , Shibolet Oren , Kariv Revital , Zelber‐Sagi Shira
Published: June 2021

Background & aims

High consumption of ultra‐processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non‐alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related‐liver damage.

Methods

A cross‐sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non‐invasive assessment of NASH and significant fibrosis. A food‐frequency questionnaire was used to evaluate UPF consumption using the NOVA classification.

Results

A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31‐2.71,P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07‐2.19,P = .026; OR = 1.51, 1.08‐2.11,P = .017; OR = 1.55, 1.05‐2.29,P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07‐3.38,P = .030; OR = 2.26, 1.20‐4.26,P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03‐3.45,P = .039; OR = 2.85, 1.14‐7.14,P = .026 respectively).

Conclusions

High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever‐smoking may act synergistically with UPF to amplify the risk for fibrosis.
Autoimmune biomarkers in porto‐sinusoidal vascular disease: Potential role in its diagnosis and pathophysiology
Authors: Cerda Reyes Eira , González‐Navarro Europa Azucena , Magaz Marta , Muñoz‐Sánchez Guillermo , Diaz Alba , Silva‐Junior Gilberto , Triguero Ana , Lafoz Erica , Campreciós Genís , Orts Lara , Perez‐Campuzano Valeria , Seijo Susana , Rubio Laura , Turon Fanny , Baiges Anna , Hernández‐Gea Virginia , Álvarez‐Larran Alberto , Juan Manel , Garcia‐Pagan Juan Carlos
Published: June 2021

Background and aims

Porto‐sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD.

Methods

Thirty‐seven consecutive patients with PSVD and 39 with cirrhosis matched by gender, signs of portal hypertension and liver function were included (training set). By using Indirect Immunofluorescence, ELISA and slot‐blot methods data 22 autoantibodies were identified in patients with PSVD and cirrhosis. Presence of anti‐endothelial cells antibodies (AECA) was assayed by a cell‐based ELISA. Thirty‐one PSVD, 40 cirrhosis patients, 15 patients with splenomegaly associated with haematological disease and 14 healthy donors were included in a validation set.

Findings

The proportion of patients with at least one positive antibody was statistically significantly higher in patients with PSVD compared with cirrhosis (92% vs 56%; P < .01). Specifically, AECA were significantly more frequent in PSVD than in cirrhosis (38% vs 15%; P = .013). Results were confirmed in the validation set. In the overall population, presence of AECA had a 63% positive predictive value for diagnosing PSVD and a 71% negative predictive value, with a specificity of 94% when the 1/16 level is used as cut‐off. AECA positive serum samples react with a 68‐72 kDa protein of human liver endothelial sinusoidal cells.
A multi‐pronged, antiracist approach to optimize equity in medical school admissions
Authors: Robinett Kathryn , Kareem Raushanah , Reavis Kristin , Quezada Sandra
Published: June 2021

Background

Increasing the number of physicians who identify as an underrepresented minority (URM) has been a focus for decades. Despite the US Department of Health and Human Services establishing The Council on Graduate Medical Education focussing on the underrepresentation of minorities in medicine in 1990, US medical students in 1998‐1999 were15.2% URM and twenty years later, URM students comprise only 14.6% of matriculants. This reflected our experience at University of Maryland School of Medicine despite our diverse community where over 60% of the population identify as Black or African‐American. We share our strategies to mitigate bias in the admissions process and our resulting outcomes.

Methods

We implemented multiple interventions including interviewer training, recruitment strategies, holistic screening, changes in the interview process and increased racial, ethnic and gender diversity on our admissions committee. These changes were made over a two‐year period initially focussing on the committee, followed by focussed interventions for interviewers.

Results

With these interventions, we demonstrated an improvement in the number of URM applicants that matriculated. In 2019, we had the first class that was in which no one ethnicity or race comprised the majority of the class, with 54% of matriculants identifying as students of colour. In 2020, in addition to sustaining a majority of the class identifying as students of colour, the proportion of URM students increased from 10%‐13% for the preceding 3 years, to 24% of the entering class.

Conclusion

The number of physicians who identify as URM must be increased for the benefit of our patients and health care system. Unconscious bias training for interviewers, focused recruitment strategies, holistic screening deemphasising the MCAT, blinding interviewers to MCAT scores and GPA, and increasing admissions committee diversity are five concrete steps that yielded the desired outcome of increasing URM representation among our medical school matriculants.
Detection of Candidatus Bartonella odocoilei n. sp. in Lipoptena mazamae associated with white‐tailed deer in Campeche, Mexico
Authors: Lozano‐Sardaneta Y. N. , Blum‐Domínguez S. , Huerta H. , Tamay‐Segovia P. , Fernández‐Figueroa E. A. , Becker I. , Sánchez‐Montes S.
Published: June 2021

The deer ked Lipoptena mazamae (Diptera: Hippoboscidae) (Róndani), is a blood‐feeding obligate ectoparasite of several species of deer and brocket. However, at present little information is available about its role as a vector of hemoparasites. Nonetheless, it is considered a competent vector for the transmission of Bartonella species. The aim of this study was performing the morphological and molecular identification of ked flies and to carry out the detection of Bartonella. We collected specimens from Chiná, Campeche, Mexico associated with white‐tailed deer. Using polymerase chain reaction (PCR), of COI, gltA and rpoB genes, we were able to obtain the first barcode for L. mazamae from Mexico and identified a new species of Bartonella which was found with a prevalence of 73%. The data obtained in this study confirmed the presence of L. mazamae associated with white‐tailed deer and its possible role as vector of Candidatus Bartonella odocoilei n. sp. in Mexico and we considered that it may also be present in white‐tailed deer populations in the U.S.A. Additional investigations into Bartonella species associated with deer ked could provide further insight into their pathogenicity and its role as a zoonotic agent.
Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies
Authors: Gruber Victoria‐Elisabeth , Lang Judith , Endmayr Verena , Diehm Robert , Pimpel Birgit , Glatter Sarah , Anink Jasper J. , Bongaarts Anika , Luinenburg Mark J. , Reinten Roy J. , van der Wel Nicole , Larsen Per , Hainfellner Johannes A. , Rössler Karl , Aronica Eleonora , Scholl Theresa , Mühlebner Angelika , Feucht Martha
Published: June 2021

Aims

We aim to evaluate if the myelin pathology observed in epilepsy‐associated focal cortical dysplasia type 2B (FCD2B) and—histologically indistinguishable—cortical tubers of tuberous sclerosis complex (TSC) is primarily related to the underlying malformation or constitutes a secondary phenomenon due to the toxic microenvironment created by epileptic seizures. We also aim to investigate the possible beneficial effect of the mTOR pathway regulator everolimus on white matter pathology.

Methods

Primary mixed glial cell cultures derived from epilepsy surgery specimens of one TSC and seven FCD2B patients were grown on polycaprolactone fibre matrices and analysed using immunofluorescence and electron microscopy. Unaffected white matter from three age‐matched epilepsy patients with mild malformations of cortical development (mMCD) and one with FCD3D served as controls. Additionally, TSC2 knock‐out was performed using an oligodendroglial cell line. Myelination capacities of nanofibre grown cells in an inflammatory environment after mTOR‐inhibitor treatment with everolimus were further investigated.

Results

Reduced oligodendroglial turnover, directly related to a lower myelin content was found in the patients' primary cells. In our culture model of myelination dynamics, primary cells grown under ‘inflammatory condition’ showed decreased myelination, that was repaired by treatment with everolimus.

Conclusions

Results obtained in patient‐derived primary oligodendroglial and TSC2 knock‐out cells suggest that maturation of oligodendroglia and production of a proper myelin sheath seem to be impaired as a result of mTOR pathway disturbance. Hence, oligodendroglial pathology may reflect a more direct effect of the abnormal genetic programme rather than to be an inactive bystander of chronic epilepsy.
Economic impacts and risks of climate change under failure and success of the Paris Agreement
Authors: Estrada Francisco , Botzen W. J. Wouter
Published: June 2021

The Nationally Determined Contributions (NDCs) represent the world's first effort toward the Paris Agreement goal of keeping global temperature increase well below 2 °C and pursuing 1.5 °C. Little is known about how much the proposed mitigation efforts can reduce the risks and economic damages from unabated climate change and about the consequences if key emitters drop the Paris Agreement. Here, we use CLIMRISK, an integrated assessment model designed to support climate policy at the global, national, and subnational scales where mitigation and adaptation policy decisions are made. We characterize the consequences of unabated climate change and the benefits of current climate policy proposals by means of probabilistic estimates of the economic damages of climate change and uni‐ and multivariate dynamic climate risk indices at a detailed spatial resolution. The results presented reveal that the economic costs and risks are highly unequally distributed between and within countries and larger than previously estimated when warming in urban areas and temporal persistence of impacts are accounted for. Costs and risks can be significantly limited by strict implementation of NDCs, but increase noticeably under noncompliance by large emitters, like the United States.
New‐onset atrial fibrillation incidence and associated outcomes in the medical intensive care unit
Authors: Brunetti Ryan , Zitelny Edan , Newman Noah , Bundy Richa , Singleton Matthew J. , Dowell Jonathan , Dharod Ajay , Bhave Prashant D.
Published: June 2021

Background

In patients with critical medical illness, data regarding new‐onset atrial fibrillation (NOAF) is relatively sparse. This study examines the incidence, associated risk factors, and associated outcomes of NOAF in patients in the medical intensive care unit (MICU).

Methods

This single‐center retrospective observational cohort study included 2234 patients with MICU stays in 2018. An automated extraction process using ICD‐10 codes, validated by a 196‐patient manual chart review, was used for data collection. Demographics, medications, and risk factors were collected. Multiple risk scores were calculated for each patient, and AF recurrence was also manually extracted. Length of stay, mortality, and new stroke were primary recorded outcomes.

Results

Two hundred and forty one patients of the 2234 patient cohort (11.4%) developed NOAF during their MICU stay. NOAF was associated with greater length of stay in the MICU (5.84 vs. 3.52 days, p < .001) and in the hospital (15.7 vs. 10.9 days, p < .001). Patients with NOAF had greater odds of hospital mortality (odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.34–2.71, p < .001) and 1‐year mortality (OR = 1.37, 95% CI 1.02–1.82, p = .03). CHARGE‐AF scores performed best in predicting NOAF (area under the curve (AUC) 0.691, p < .001).

Conclusions

The incidence of NOAF in this MICU cohort was 11.4%, and NOAF was associated with a significant increase in hospital LOS and mortality. Furthermore, the CHARGE‐AF score performed best in predicting NOAF.
Single‐cell RNA‐seq describes the transcriptome landscape and identifies critical transcription factors in the leaf blade of the allotetraploid peanut (Arachis hypogaea L.)
Authors: Liu Hao , Hu Dongxiu , Du Puxuan , Wang Liping , Liang Xuanqiang , Li Haifen , Lu Qing , Li Shaoxiong , Liu Haiyan , Chen Xiaoping , Varshney Rajeev K , Hong Yanbin
Published: June 2021

Single‐cell RNA‐seq (scRNA‐seq) has been highlighted as a powerful tool for the description of human cell transcriptome, but the technology has not been broadly applied in plant cells. Herein, we describe the successful development of a robust protoplast cell isolation system in the peanut leaf. A total of 6,815 single cells were divided into eight cell clusters based on reported marker genes by applying scRNA‐seq. Further, a pseudo‐time analysis was used to describe the developmental trajectory and interaction network of transcription factors (TFs) of distinct cell types during leaf growth. The trajectory enabled re‐investigation of the primordium‐driven development processes of the mesophyll and epidermis. These results suggest that palisade cells likely differentiate into spongy cells, while the epidermal cells originated earlier than the primordium. Subsequently, the developed method integrated multiple technologies to efficiently validate the scRNA‐seq result in a homogenous cell population. The expression levels of several TFs were strongly correlated with epidermal ontogeny in accordance with obtained scRNA‐seq values. Additionally, peanut AHL23 (AT‐HOOK MOTIF NUCLEAR LOCALIZED PROTEIN 23), which is localized in nucleus, promoted leaf growth when ectopically expressed in Arabidopsis by modulating the phytohormone pathway. Together, our study displays that application of scRNA‐seq can provide new hypotheses regarding cell differentiation in the leaf blade of Arachis hypogaea. We believe that this approach will enable significant advances in the functional study of leaf blade cells in the allotetraploid peanut and other plant species.
Pragmatic Particularism
Authors: Buchanan Ray , Ian Schiller Henry
Published: June 2021

For theIntentionalist, utterance content is wholly determined by a speaker’s meaning‐intentions; the sentence uttered serves merely to facilitate the audience’s recovering these intentions. We argue that Intentionalists ought to beParticularists, holding that the only “principles” of meaning recovery needed are those governing inferences to the best explanation; “principles” that are both defeasible and, in a sense to be elaborated,variable. We discuss some ways in which some theorists have erred in trying to tame the “wild west” of pragmatics and context‐sensitivity – including recent work that makes essential appeal to the information structure of a discourse – and in so doing, offer a general recipe for defending the Particularist picture of utterance content and its recovery that we favor.
Extracellular vesicles of Echinococcus granulosus have therapeutic effects in allergic airway inflammation
Authors: Jeong Mi Jin , Kang Shin Ae , Choi Jun Ho , Lee Da In , Yu Hak Sun
Published: June 2021

Background

Previous studies have shown that Echinococcus granulosus cystic fluid can alleviate Th2 allergic airway inflammatory responses by increasing the number of CD4+CD25+ Foxp3+T (regulatory T; Treg) cells. Parasite‐derived extracellular vesicles (EV) are known to not only promote parasite infection by communicating between parasites but also regulate the inflammatory response by acting as an immunomodulatory agent in the host.

Methods

To evaluate the effect of EV extracted from the cystic fluid of E. granulosus on allergic airway inflammation, gene expression was investigated after administering EV to mouse lung epithelial cells (MLE‐12) following 2 h of pretreatment with Aspergillus proteins. An allergic airway inflammation animal model was used to investigate the regulation of the inflammatory response by EV and induced with ovalbumin.

Results

EV treatment significantly reduced airway resistance and the number of eosinophils and other immune cells in the bronchoalveolar lavage fluid and Th2‐ and Th17‐related cytokine levels. EV pretreatment decreased the number of IL‐4+CD4+T cells and increased the number of Treg cells in the lung‐draining lymph nodes and spleen.

Conclusions

Echinococcus granulosus cystic fluid derived EV ameliorated Th2 allergic airway inflammatory through Treg cells, similar to whole cystic fluid treatment. Thus, EV may be important immunomodulatory molecules in cystic fluid.
Enhanced insightfulness and neural activation induced by metaphorical solutions to appropriate mental distress problems
Authors: Yu Fei , Zhang Jianxin , Luo Jing , Zhang Wencai
Published: June 2021

Although the neural correlates of novelty and appropriateness of creative insight during cognitive tasks have been investigated in several studies, they have not been examined during mental distress in a psychotherapeutic setting. This study aimed to reveal the promoting effects of novelty and appropriateness processing on therapeutic insight in a micro‐psychotherapeutic setting. We examined the effects of appropriateness (between‐subject factor: appropriateness group, 20 participants; inappropriateness group, 21 participants) by manipulating the preceding negative scenarios that either fit or did not fit the subsequent solutions, and those of novelty (within‐subject factor) by varying the linguistic expressions for describing solutions (metaphorical, literal, or problem‐restatement). Event‐related functional magnetic resonance images were collected. We found the following effects: an interactive effect of the two factors on insightfulness and activation in the bilateral hippocampus and amygdala, right superior frontal gyrus, and left superior/middle temporal gyrus; a simple effect of novelty on activation in the bilateral inferior frontal gyrus, fusiform gyrus, and inferior/middle occipital gyrus; and a simple effect of appropriateness on activation in the left inferior parietal lobule. Our findings indicate that solutions with high novelty and appropriateness generate the highest levels of therapeutic insightfulness as well as the strongest activation in the hippocampus and amygdala, which may be involved in episodic memory encoding.
Vitrification of canine ovarian tissue using the Ovarian Tissue Cryosystem (OTC) device
Authors: Brandão Fabiana Aparecida Santilli , Alves Kele Amaral , de Brito Danielle Cristina Calado , Pereira Leda Maria Costa , de Morais Glayciane Bezerra , Ñaupas Lucy Vanessa Sulca , de Souza Samara Silva , Alves Benner Geraldo , Rodrigues Ana Paula Ribeiro , Teixeira Dárcio Ítalo Alves
Published: June 2021

The present study evaluated the effect of Ovarian Tissue Cryosystem (OTC) on follicular morphology and density, as well as on stromal cell density of vitrified canine ovarian tissue. Canine ovarian fragments collected from adult female dogs in stages of the random oestrous cycle were fixed (FC, fresh control) or vitrified (VIT) with an OTC device. After vitrification and warming, the fragments were fixed for histological analysis. Overall, the mean percentage of normal pre‐antral follicles decreased after vitrification procedure (FC: 74.5% ± 1.6% vs. VIT: 52.05% ± 1.5%). Although the rates of normal primordial (71.1% ± 1.8%) and secondary (0.7% ± 0.4%) follicles vitrified showed a reduction (p < .05), vitrification using OTC showed considerable preservation of follicles, when compared to the fresh control (81.1% ± 1.5% and 2.3% ± 0.6%, respectively). The mean follicular density was maintained after vitrification (FC: 199.65 ± 12.8 vs. VIT: 199.68 ± 10.8), whereas the stromal cell density decreased in the VIT group. Based on the results, we recommend the use of OTC for vitrification of canine ovarian tissue.
Macrophages in bovine term placenta: An ultrastructural and molecular study
Authors: Hooshmandabbasi Reyhaneh , Kazemian Ali , Zerbe Holm , Kowalewski Mariusz P. , Klisch Karl
Published: June 2021

Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the foetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi‐quantitative RT‐PCR to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. Semi‐quantitative RT‐PCR was used to define macrophage polarization in foetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1 polarization [interferon regulatory factor‐5 (IRF5), interleukin (IL)‐12A, IL12B] and in M2 polarization (IL10) were studied. Ultrastructurally, foetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry, macrophages were identified by a strong staining with the lysosomal marker Lysosome‐associated membrane glycoprotein 1 (LAMP‐1), while myofibroblast in the maternal stroma was positive for alpha‐smooth muscle actin. We used the LAMP‐1 marker to compare the density of foetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT‐PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1‐, compared to M2‐associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro‐inflammatory M1 polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than foetal macrophages.
Comparison of pregnancy per AI of heifers inseminated with sex‐sorted or conventional semen after oestrus detection or timed artificial insemination
Authors: Guner Baris , Selcuk Gulsum , Guclu Sevket , Sengul Sultan , Altun Ismail , Dikmen Serdal , Gumen Ahmet
Published: June 2021

The objective of the study was to compare the fertility after using sex‐sorted or conventional semen either with oestrus detection (EST) or timed artificial insemination (TAI) in Holstein heifers. Holstein heifers were randomly assigned to one of the following treatments in a 2 × 2 factorial design. Heifers in the EST group were inseminated with sex‐sorted (n = 114) or conventional semen (n = 100) after spontaneous or induced oestrus. Heifers in the TAI, subjected to the 5‐day Cosynch+Progesterone protocol (GnRH+P4 insertion‐5d‐PGF2α+P4 removal‐1d‐PGF2α‐2d‐GnRH+TAI), were inseminated with sex‐sorted (n = 113) or conventional semen (n = 88). Statistical analyses were performed using PROC GLIMMIX procedure of SAS 9.4 (SAS Institute Inc., Cary, NC). Overall P/AI was 60.7% for EST and 54.2% for TAI regardless of types of semen and 68.1% for conventional and 48.9% for sex‐sorted semen regardless of insemination strategies. Fertility of heifers inseminated with either sex‐sorted (53.5%; 44.2%) or conventional (69.0%; 67.0%) semen did not differ between EST and TAI respectively. Besides, the interaction between the semen type and the insemination strategy was not significant for P/AI. The embryonic loss was significantly greater with sex‐sorted semen (17.1%) compared to conventional semen (1.6%). There was no sire effect with sex‐sorted semen on P/AI (52.6% vs. 46.2%) and embryonic loss (16.4% vs. 18.0%). As expected, sex‐sorted semen resulted in more female calves (89.8% vs. 51.6%) than conventional semen. Thus, sex‐sorted semen can be used with 5‐day Cosynch+Progesterone protocol to eliminate the inadequate oestrus detection and to increase female calves born in dairy heifers.
Long-Term Spatial Modelling for Characteristics of Extreme Heat Events
Authors: Schliep Erin M. , Gelfand Alan E. , Abaurrea Jesús , Asín Jesús , Beamonte María A. , Cebrián Ana C.
Published: June 2021

There is increasing evidence that global warming manifests itself in more frequent warm days and that heat waves will become more frequent. Presently, a formal definition of a heat wave is not agreed upon in the literature. To avoid this debate, we consider extreme heat events, which, at a given location, are well-defined as a run of consecutive days above an associated local threshold. Characteristics of extreme heat events (EHEs) are of primary interest, such as incidence and duration, as well as the magnitude of the average exceedance and maximum exceedance above the threshold during the EHE. Using approximately 60-year time series of daily maximum temperature data collected at 18 locations in a given region, we propose a spatio-temporal model to study the characteristics of EHEs over time. The model enables prediction of the behaviour of EHE characteristics at unobserved locations within the region. Specifically, our approach employs a two-state space–time model for EHEs with local thresholds where one state defines above threshold daily maximum temperatures and the other below threshold temperatures. We show that our model is able to recover the EHE characteristics of interest and outperforms a corresponding autoregressive model that ignores thresholds based on out-of-sample prediction.
RNN-Based Counterfactual Prediction, With an Application to Homestead Policy and Public Schooling
Authors: Poulos Jason , Zeng Shuxi
Published: June 2021

This paper proposes a method for estimating the effect of a policy intervention on an outcome over time. We train recurrent neural networks (RNNs) on the history of control unit outcomes to learn a useful representation for predicting future outcomes. The learned representation of control units is then applied to the treated units for predicting counterfactual outcomes. RNNs are specifically structured to exploit temporal dependencies in panel data and are able to learn negative and non-linear interactions between control unit outcomes. We apply the method to the problem of estimating the long-run impact of US homestead policy on public school spending.
Inter‐County Migration and the Spatial Concentration of Poverty: Comparing Metro and Nonmetro Patterns*
Authors: Lichter Daniel T. , Parisi Domenico , Taquino Michael C.
Published: June 2021

We use panel data from the Panel Study of Income Dynamics (PSID) to document the changing volume and rate of intercounty migration among the poor. We evaluate whether the exchange of migrants between metro and nonmetro counties has exacerbated spatial disparities in poverty and whether some nonmetro counties have become “collecting grounds” for America's poor. The PSID highlights exceptionally high rates of intercounty migration among the nonmetro population, but especially among the poor. The results show that rural poor migrants circulate among nonmetro counties, often from one poor county to an even poorer one. This circulation of poor rural migrants has exacerbated the concentration of poverty in the most economically disadvantaged nonmetro counties. Concentrated poverty also is exacerbated by the migration of the “best and brightest” from nonmetro‐to‐metro counties, which also is associated with upward residential attainment (to counties with lower poverty rates). Significantly, metro‐to‐nonmetro migration is both selective of the poor and strongly associated with downward residential mobility to poorer nonmetro counties. Our findings are consistent with the hypothesis that poor nonmetro counties have become collecting grounds for America's poor.
The chromosome‐scale reference genome of Rubus chingii Hu provides insight into the biosynthetic pathway of hydrolyzable tannins
Authors: Wang Longji , Lei Ting , Han Guomin , Yue Junyang , Zhang Xueru , Yang Qi , Ruan Haixiang , Gu Chunyang , Zhang Qiang , Qian Tao , Zhang Niuniu , Qian Wei , Wang Qi , Pang Xiaojing , Shu Yue , Gao Liping , Wang Yunsheng
Published: June 2021

Rubus chingii Hu (Fu‐Pen‐Zi), a perennial woody plant in the Rosaceae family, is a characteristic traditional Chinese medicinal plant because of its unique pharmacological effects. There are abundant hydrolyzable tannin (HT) components in R. chingii that provide health benefits. Here, an R. chingii chromosome‐scale genome and related functional analysis provide insights into the biosynthetic pathway of HTs. In total, sequence data of 231.21 Mb (155 scaffolds with an N50 of 8.2 Mb) were assembled into seven chromosomes with an average length of 31.4 Mb, and 33 130 protein‐coding genes were predicted, 89.28% of which were functionally annotated. Evolutionary analysis showed that R. chingii was most closely related to Rubus occidentalis, from which it was predicted to have diverged 22.46 million years ago (Table S8). Comparative genomic analysis showed that there was a tandem gene cluster of UGT, carboxylesterase (CXE) and SCPL genes on chromosome 02 of R. chingii, including 11 CXE, eight UGT, and six SCPL genes, which may be critical for the synthesis of HTs. In vitro enzyme assays indicated that the proteins encoded by the CXE (LG02.4273) and UGT (LG02.4102) genes have tannin hydrolase and gallic acid glycosyltransferase functions, respectively. The genomic sequence of R. chingii will be a valuable resource for comparative genomic analysis within the Rosaceae family and will be useful for understanding the biosynthesis of HTs.
Intraoperative assessment of canine soft tissue sarcoma by deep learning enhanced optical coherence tomography
Authors: Ye Yu , Sun Weihong William , Xu Ronald X. , Selmic Laura E. , Sun Mingzhai
Published: June 2021

Soft tissue sarcoma (STS) is a locally aggressive and infiltrative tumour in dogs. Surgical resection is the treatment of choice for local tumour control. Currently, post‐operative pathology is performed for surgical margin assessment. Spectral‐domain optical coherence tomography (OCT) has recently been evaluated for its value for surgical margin assessment in some tumour types in dogs. The purpose of this study was to develop an automatic diagnosis system that can assist clinicians in real‐time for OCT image interpretation of tissues at surgical margins. We utilized a ResNet‐50 network to classify healthy and cancerous tissues. A patch‐based approach was adopted to achieve accurate classification with limited training data (80 cancer images, 80 normal images) and the validation set (20 cancer images, 20 normal images). The proposed method achieved an average accuracy of 97.1% with an excellent sensitivity of 94.3% on the validation set; the quadratic weighted κ was 0.94 for the STS diagnosis. In an independent test data set of 20 OCT images (10 cancer images, 10 normal images), the proposed method correctly differentiated all the STS images. Furthermore, we proposed a diagnostic curve, which could be evaluated in real‐time to assist clinicians in detecting the specific location of a lesion. In short, the proposed method is accurate, operates in real‐time and is non‐invasive, which could be helpful for future surgical guidance.