bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE‐826
Authors: Nishio Shin , Yonemori Kan , Usami Tomoka , Minobe Shinichiro , Yunokawa Mayu , Iwata Takashi , Okamoto Aikou , Aoki Yoichi , Itamochi Hiroaki , Takekuma Munetaka , Harano Kenichi , Yamamoto Keiko , Maruko Takeshi , Ugai Hiroyuki , Tekin Cumhur , Colombo Nicoletta , Fujiwara Keiichi , Hasegawa Kosei , Ushijima Kimio
Published: July 2022

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression‐free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double‐blind, placebo‐controlled KEYNOTE‐826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD‐L1 combined positive score (CPS) ≥1, all‐comers, and PD‐L1 CPS ≥10. Fifty‐seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD‐L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16–0.77]), all‐comers (n = 57; 0.45 [0.22–0.90]), and patients with PD‐L1 CPS ≥10 (n = 25; 0.36 [0.12–1.07]). HRs (95% CI) for OS were 0.38 (0.14–1.01), 0.41 (0.17–1.00), and 0.37 (0.10–1.30), respectively. Incidence of grade 3–5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE‐826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer.
Supplementation with omega‐3 or omega‐6 fatty acids attenuates platelet reactivity in postmenopausal women
Authors: Yamaguchi Adriana , Stanger Livia , Freedman John Cody , Prieur Amanda , Thav Rachel , Tena Jennyfer , Holman Theodore R. , Holinstat Michael
Published: July 2022

Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. There is evidence suggesting that ω‐3 polyunsaturated fatty acids (PUFAs) and ω‐6 PUFAs have cardioprotective effects in these women. However, a mechanistic understanding of how these fatty acids regulate platelet function is unknown. In this study, we supplemented postmenopausal women with fish oil (ω‐3 fatty acids) or evening primrose oil (ω‐6 fatty acids) and investigated the effects on their platelet activity. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion, and activation of integrin αIIbβ3 at basal levels and in response to agonist were tested in postmenopausal women following a supplementation and washout period. Supplementation with fish oil or primrose oil attenuated the thrombin receptor PAR4‐induced platelet aggregation. Supplementation with ω‐3 or ω‐6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin αIIbβ3 activation. Interestingly, after the washout period following supplementation with primrose oil, platelet aggregation was similarly attenuated. Additionally, for either treatment, the observed protective effects post‐supplementation on platelet dense granule secretion and basal levels of integrin activation were sustained after the washout period, suggesting a long‐term shift in platelet reactivity due to fatty acid supplementation. These findings begin to elucidate the underlying mechanistic effects of ω‐3 and ω‐6 fatty acids on platelet reactivity in postmenopausal women. Hence, this study supports the beneficial effects of fish oil or primrose oil supplementation as a therapeutic intervention to reduce the risk of thrombotic events in postmenopausal women. https://clinicaltrials.gov/ct2/show/NCT02629497.
Catalog competition: Theory and experimental evidence
Authors: Xefteris Dimitrios , Barreda‐Tarrazona Iván , García‐Gallego Aurora , Georgantzís Nikolaos
Published: July 2022

This paper compares the standard location‐then‐pricing Hotelling duopoly with a catalog competition game in which firms simultaneously decide locations and prices. We consider a three‐location space and continuous pricing and fully characterize the unique symmetric equilibrium. In both games, firms employ mixed strategies, producing a mainstream product more often than a specialized one. In the catalog game, prices are always above the marginal cost of production, whereas in the sequential model, prices converge to the marginal cost when firms produce the same variety. We experimentally test our theoretical predictions in the laboratory, finding strong evidence in favor of most of them.
Hyperperfusion Tmax mapping for nonconvulsive status epilepticus in the acute setting: A pilot case–control study
Authors: Romoli Michele , Merli Elena , Galluzzo Simone , Muccioli Lorenzo , Testoni Stefania , Zaniboni Anna , Contardi Sara , Simonetti Luigi , Tinuper Paolo , Zini Andrea
Published: July 2022

Objective

Nonconvulsive status epilepticus (NCSE) is misdiagnosed in >50% of cases in the emergency department. Computed tomographic perfusion (CTP) has been implemented in the hyperacute setting to detect seizure‐induced hyperperfusion. However, the diagnostic value of CTP is limited by the lack of thresholds for hyperperfusion and high interrater variability. This pilot case–control study aims at identifying the diagnostic value of reverse Tmax (rTmax) in differentiating NCSE from acute ischemic stroke in the hyperacute setting.

Methods

We enrolled patients with NCSE (Salzburg criteria‐based diagnosis) and stroke cases 1:1 matched for clinical features and time of presentation. CTP standard maps (mean transit time [MTT]–cerebral blood volume–cerebral blood flow [CBF]) and rTmax maps were elaborated and rated by two experts in CTP blinded to the final diagnosis. Hyperperfusion was adjudicated for standard CTP maps as an increase in CBF and a decrease in MTT, and for rTmax as the presence of a black area on 3‐, 2‐, and 1‐s threshold maps. Cronbach alpha was used for interrater agreement; receiver operating curve analysis was run to measure accuracy with area under the curve.

Results

Overall, 34 patients were included (17 NCSE, 17 stroke; time from onset to imaging = 2 h for both groups). People with NCSE were older and more frequently had a history of epilepsy. NCSE patients had hyperperfusion on rTmax maps in 11 of 17 cases versus zero of 17 in stroke. Intra‐ and interrater reliability was higher for rTmax than for standard CTP maps (κ = 1 vs. κ = .6). rTmax was 82% (95%CI = 67–97%) accurate in predicting NCSE versus stroke in the hyperacute setting. Agreement between neuroimaging and electroencephalography (EEG) was limited at a hemispheric level for standard CTP maps, whereas rTMax had agreement with EEG largely reaching the sublobar level.

Significance

rTmax mapping might represent a reliable tool to spot NCSE‐induced hyperperfusion with a threshold‐based reproducible approach. Further studies are needed for validation and implementation in the differential diagnosis of focal neurological deficit in the hyperacute setting.
Towards a model for determining patent revenue odds: An empirical study of technology transfer offices
Authors: Leite Rafael Angelo Santos , Walter Cicero Eduardo , Reis Igor Bezerra , de Sousa Pedro Elias Figueredo , de Aragão Iracema Machado , Au‐Yong‐Oliveira Manuel
Published: July 2022

Technology transfer offices (TTO) were created with the mission of executing innovation policy and its technology transfer to industry. Most studies regarding TTO focus on the context of developed countries, so there is a lack of research on the subject in emerging economies, such as Brazil. In addition, the issue of how diverse the skills of the team of a given TTO should be for their best revenue performance is still little addressed. In this sense, the present study aims to identify which characteristics of the TTO, related to their human resources, influence obtaining revenue from the patents that constitute their portfolios. To achieve this objective, 272 TTO in Brazil were analysed with the help of the Logistic Regression technique, based on Maximum Likelihood Estimation. A remarkable conclusion that emerges from our results is that the universities to increase their revenue must invest in full‐time employees (e.g., rather than in scholarship students, as tends to be the norm) and foster the inventions' communications, as well as to attract and retain employees with skills directly related to knowledge fields such as Law, Engineering, and Communication (quite surprisingly, Management and Economics graduates are not included). The combination of these factors can increase the probabilities or odds of a given TTO obtaining revenue. Thus, our results contribute to TTO human resource practices, especially those in structuring stages, such as those in Brazil and Latin American countries.
A Framework for Inserting Visually Supported Inferences into Geographical Analysis Workflow: Application to Road Safety Research
Authors: Beecham Roger , Lovelace Robin
Published: July 2022

Road safety research is a data‐rich field with large social impacts. Like in medical research, the ambition is to build knowledge around risk factors that can save lives. Unlike medical research, road safety research generates empirical findings from messy observational datasets. Records of road crashes contain numerous intersecting categorical variables, dominating patterns that are complicated by confounding and, when conditioning on data to make inferences net of this, observed effects that are subject to uncertainty due to diminishing sample sizes. We demonstrate how visual data analysis approaches can inject rigor into exploratory analysis of such datasets. A framework is presented whereby graphics are used to expose, model and evaluate spatial patterns in observational data, as well as protect against false discovery. Evidence for the framework is presented through an applied data analysis of national crash patterns recorded in STATS19, the main source of road crash information in Great Britain. Our framework moves beyond typical depictions of exploratory data analysis and transfers to complex data analysis decision spaces characteristic of modern geographical analysis.
Comparison of Radiocarbon‐ and Background Location‐Corrections on Soil‐Gas CO2 Flux‐Based NSZD Rate Measurements at Petroleum Impacted Sites
Authors: Zimbron Julio A.
Published: July 2022

The measurement of contaminant natural source zone depletion (NSZD) rates has become an important tool to manage petroleum contaminated sites. Most NSZD rate measurement methods rely on a balance on the biodegradation by‐products (either carbon or heat). Carbon balance‐based methods stoichiometrically convert measured soil‐gas CO2 flux related to contaminant degradation to equivalent contaminant mass loses. CO2 flux‐based methods require separating the fraction of the total CO2 flux produced by NSZD from the fraction of CO2 flux produced by natural soil processes (due to modern carbon turnover). Two method corrections are available to distinguish the nature of the measured CO2 flux: (1) The background location correction subtracts a measurement from an unimpacted location from measurements collected at impacted locations, and (2) a location‐specific radiocarbon (14C) analysis that differentiates the modern and old carbon fractions of each total CO2 measurement. This work evaluates both correction approaches using 36 measurements at impacted locations from five sites. The 14C‐corrected data shows that the magnitude and variability of the modern carbon‐related fraction (noise) and the NSZD related fossil fuel signal are similar, suggesting a location‐specific correction is more valid. Only one sparsely vegetated arid site showed close agreement between both corrections (14C‐ and background location). These results highlight the strong effect of the correction method used on NSZD rate measurements, and the importance of considering data quality on the subsequent data management process.
Chondroblastoma‐like osteosarcoma: a clinicopathological and molecular study of a rare osteosarcoma variant
Authors: Gaeta Raffaele , Righi Alberto , Gambarotti Marco , Aretini Paolo , Lessi Francesca , Mazzanti Chiara Maria , Mancini Irene , Pinzani Pamela , Belgio Beatrice , Sbaraglia Marta , Dei Tos Angelo Paolo , Franchi Alessandro
Published: July 2022

Objective

Chondroblastoma‐like osteosarcoma (CBLOS) is a rare and poorly understood variant of OS. We examined the clinicopathological, immunohistochemical and molecular features of six CBLOSs to highlight the differences with conventional high‐grade OS (CHGOS) and CB, including CB with aggressive features.

Methods

We performed histone 3.3 mutation analysis by gene sequencing and/or immunohistochemistry in all cases, while whole exome sequencing (WES) was performed on two CB‐like osteosarcomas and 11 conventional high‐grade OS.

Results

CBLOSs were predominantly localised at acral sites and involved mainly male subjects with a mean age of 29 years. One patient who had metastases at presentation died of disease, while another patient who developed multiple local recurrences and lung metastases was alive with no evidence of disease (ANED) at 294 months. The remaining patients were ANED after a mean interval of 70.8 months. Histologically, all CBLOS presented aggressive features, including nuclear atypia and infiltrative growth. Immunohistochemistry with H3F3 K36M mutant antibody was negative in all CBLOSs, and none of the five tumours tested by gene sequencing had H3F3B mutations. Conversely, all CBs presented the H3F3B K36M variant and were positive for immunostaining with the H3F3 K36M antibody. Two CBLOSs analysed by WES differed in amount and type of mutation from 11 cases of CHGOS. Moreover, CBLOSs showed lower copy number alteration (CNA) score values than CHGOSs.

Conclusions

CBLOS presents a different genetic background and a less aggressive clinical behaviour in comparison with CHGOS. Search of the H3F3B K36M mutation is useful in the differential diagnosis with CB.
Kindergarten teachers promote the participation experience of African Asylum‐Seeker families
Authors: Eliyahu‐Levi Dolly
Published: July 2022

African asylum seekers live in Israel in the realities of poverty, racism, and personal insecurity. From a sociological point of view, Participation is taking part in social processes, interacting with people, texts and technologies and it may affect all areas of life. This is a qualitative‐interpretive study that examines through interviews the participation experience from the perspective of eight African couples and six Israeli kindergarten teachers. The findings indicate: (1) Increasing the parents' sense of belonging, (2) Increasing the cultural participation, (3) Increasing community cohesion. Findings reveal a tension between the parents' desire to be involved and my reality of poverty and working around the clock that prevents their presence in educational activities. Under such complex conditions, kindergarten teachers worked to establish a positive personal relationship, strengthen the parents' sense of ability, overcome language barriers, and cultivate a sense of belonging from a perception that increasing participation would help them deal with integration challenges and livelihoods social rejection. The study has a theoretical and practical contribution, and its findings may be used by educators and policymakers regarding principles for action to promote the experience of participation and involvement of parents in educational settings.
On the Injustice of Dysfunctional Upbringing
Authors: Theofilopoulou Areti
Published: July 2022

Empirical evidence shows that certain parental behaviours cause pervasive harms for children. These behaviours are not limited to abuse and neglect but include other non‐abusive, non‐neglectful behaviour such as invalidation. In this article, I argue that such cases of dysfunctional upbringing are unjust on three broad grounds. First, they seriously interfere with the ideal of equality of opportunity. Second, they entail violations of children's basic rights and interests, including their interest in developing the capacity for autonomy and their interest in enjoying the intrinsic goods of childhood. And third, they are criminogenic and raise a host of problems for criminal justice. For these reasons, justice requires preventing unjust parental behaviours, rather than attempting to redress them once they have already occurred. To identify the appropriate forward‐looking interventions, I distinguish the epistemic from the psychological causes of dysfunctional parental behaviours and argue that different interventions are required to tackle each cause. The former should include mandatory education on the potential harms of certain parental behaviours, while the latter should focus on therapeutic measures that address the unconscious and emotional mechanisms of our behaviour.
The association between common serum adipokines levels and postmenopausal osteoporosis: A meta‐analysis
Authors: Shu Linyuan , Fu Yimu , Sun Hui
Published: July 2022

The clinical relevance of blood levels of adipokines in individuals with postmenopausal osteoporosis (PMOP) has not been previously clarified. We performed this meta‐analysis to clarify the association between three common adipokines levels and the occurrence of PMOP. PubMed, Embase, Cochrane library, and China National Knowledgement Infrastructure (CNKI) were searched for collecting articles published before 31 October 2021, without language and status restrictions. Fourteen studies met the selection criteria. Meta‐analysis revealed that blood leptin level was remarkably lower (mean difference [MD], −1.94; 95% confidence interval [CI], −3.83 to −0.06; I2 = 96%) and adiponectin level was remarkably higher (MD, 3.48; 95% CI, 2.36 to 4.60; I2 = 90%) in individuals with PMOP than healthy individuals with normal bone mineral density (BMD). However, the statistical difference in leptin level was changed after eliminating the confounding influence of leptin sources and assay approaches. Furthermore, a positive association (r = 0.28) between leptin level and body mass index (BMI) as well as a negative association (r = −0.33) between adiponectin level and BMD was found. Moreover, adiponectin had the highest probability of predicting PMOP (84%). Current evidence suggests that leptin positively affects BMI and adiponectin negatively affects BMD, and adiponectin is the most relevant adipokine negatively associated with PMOP.
The impact of body mass index on clinicopathological features of nonalcoholic fatty liver disease in Taiwan
Authors: Lin Chih‐Lin , Tai Chi‐Ming , Huang Jee‐Fu , Liu Chun‐Jen , Chen Hui‐Fen , Cheng Pin‐Nan , Chen Chi‐Yi , Peng Cheng‐Yuan , Wang Chia‐Chi , Weng Shih‐Han , Tseng Tai‐Chung , Kao Jia‐Horng
Published: July 2022

Background and Aim

The aim of this study was to assess the impact of body mass index (BMI) on the clinical and histological characteristics of patients with nonalcoholic fatty liver disease (NAFLD).

Methods

Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled from 2007 to 2019. For comparison, all of the patients were divided into lean body mass (< 23 kg/m2), overweight (23–24.9 kg/m2), and obesity (BMI ≧ 25 kg/m2).

Results

A total of 572 patients with histologically confirmed NAFLD, including 40 (6.99%) lean body mass, 54 (9.44%) overweight, and 478 (83.57%) obese patients, were recruited. Obese NAFLD patients had significantly higher grade of steatosis (grade 3: 29.92% vs 22.22% vs 12.5%, P < 0.0001) and hepatocyte ballooning (grade 2: 14.85% vs 12.96% vs 12.5%, P < 0.0001) than overweight and lean NAFLD patients. The prevalence of nonalcoholic steatohepatitis (NASH) was 22.5%, 25.93%, and 36.19% in lean, overweight, and obese NAFLD patients, respectively. Obesity was significantly associated with fibrosis severity (P = 0.03). The fibrosis index based on four factors (FIB‐4) score can identify NAFLD patients without significant fibrosis or with cirrhosis. The areas under the receiver‐operating characteristic curve of FIB‐4 score to identify patients without significant fibrosis or with cirrhosis were 0.82 (95% confidence interval [CI]: 0.69–0.96) and 0.87 (95% CI: 0.76–0.99) in lean patients; 0.77 (95% CI: 0.61–0.93) and 0.81 (95% CI: 0.59–1.0) in overweight patients; and 0.77 (95% CI: 0.72–0.82) and 0.89 (95% CI: 0.85–0.92) in obese patients.

Conclusions

The majority of NAFLD patients are obese, as defined by BMI. Obesity was significantly associated with NASH and hepatic fibrosis severity in patients with NAFLD.
Mesenchymal stem cell‐exosome‐mediated matrix metalloproteinase 1 participates in oral leukoplakia and carcinogenesis by inducing angiogenesis
Authors: Li Shufang , Han Ying , Lu Mingxing , Liu Zijian , Jin Jianqiu , Guo Qianyun , Wang Yixiang , Liu Hongwei
Published: July 2022

Background

In the malignant progression of oral leukoplakia (OLK) to oral squamous cell carcinoma (OSCC), the density of microvessels and expression of angiogenesis‐related molecules increases. Emerging evidence indicates that mesenchymal stem cells (MSCs) play an indispensable role in the tumor microenvironment. However, the role and mechanism of action of oral MSCs in inducing angiogenesis remain unclear. Therefore, it is necessary to explore the molecules and mechanisms that play a role in the tissue microenvironment.

Methods

Exosomes were collected from normal oral mucosa (N‐Exo), OLK (OLK‐Exo), and OSCC (Ca‐Exo) MSCs, and their pro‐angiogenic capacity was evaluated in human umbilical vein endothelial cells (HUVECs) and a subcutaneously implanted tumor model in nude mice. Quantitative proteomics analysis was used to compare the exosome‐derived proteins between N‐Exo, OLK‐Exo, and Ca‐Exo.

Results

Compared with that of the N‐Exo and control, OLK‐Exo and Ca‐Exo treatment significantly promoted HUVEC migration, invasion, and tube‐formation capability. In the nude mice model, immunofluorescence of CD31 showed that OLK‐Exo and Ca‐Exo substantially improved neovascularization around the grafts. Quantitative proteomics analysis revealed that matrix metalloproteinase 1 (MMP1) levels were significantly higher in the OLK‐Exo and Ca‐Exo groups than in the N‐Exo groups. Silencing MMP1 expression reversed the functional promoting effect of OLK‐Exo and Ca‐Exo on HUVECs.

Conclusion

Exosomes from OLK‐MSCs and Ca‐MSCs have a stronger pro‐angiogenic ability through high MMP1 content. This new finding provides insight into the intervention with the secretion of MSC‐derived exosomes, which may be an innovative strategy for carcinogenesis.
Association between forage mycotoxins and liver disease in horses
Authors: Durham Andy E.
Published: July 2022

Background

Outbreaks of liver disease in horses are common but the etiology of most remains unknown. Forage mycotoxins have been suspected to be a cause.

Objectives

To examine the association between outbreaks of liver disease and the presence of mycotoxins in forage stored on the same premises.

Animals

Premises were identified where ≥4 horses were contemporaneously affected by liver disease, and a control group was formed from premises where ≥4 horses had been examined and found to have no evidence of liver disease.

Methods

Forage was collected from 29 case and 12 control premises. The forage was analyzed for mycotoxin content using a liquid chromatography/mass spectrometry method, targeting 54 mycotoxins. The presence and distribution of mycotoxins between case and control samples was compared.

Results

Mycotoxins were found in 23/29 (79%) case samples and 10/12 (83%) control samples (P > .99; relative risk, 0.93; 95% confidence interval [CI], 0.64‐1.75). Median (interquartile range [IQR]) total mycotoxin concentration was similar in case and control samples (85.8 μg/kg [1.6‐268] vs. 315 μg/kg [6.3‐860]; P = .16). Ten mycotoxins were found exclusively in case premises comprising fumonisin B1, 15‐acetyldeoxynivalenol, deoxynivalenol, zearalenone, aflatoxins B1 and G1, methylergonovine, nivalenol, verruculogen, and wortmannin. The median (IQR) concentration of fumonisin B1 was significantly higher in case versus control samples (0 μg/kg [0‐81.7] vs. 0 μg/kg [0‐0]; P = .04).

Conclusions and Clinical Importance

Several mycotoxins with known hepatotoxic potential were found, alone or in combination, exclusively at case premises, consistent with the hypothesis that forage‐associated mycotoxicosis may be a cause of outbreaks of liver disease in horses in the United Kingdom.
Microbial mediation of salinity stress response varies by plant genotype and provenance over time
Authors: Lumibao Candice Y. , Torres Martínez Lorena , Megonigal J. Patrick , Van Bael Sunshine A. , Blum Michael J.
Published: July 2022

Although it is becoming widely appreciated that microbes can enhance plant tolerance to environmental stress, the nature of microbial mediation of exposure responses is not well understood. We addressed this deficit by examining whether microbial mediation of plant responses to elevated salinity is contingent on the environment and factors intrinsic to the host. We evaluated the influence of contrasting environmental conditions relative to host genotype, provenance and evolution by conducting a common‐garden experiment utilizing ancestral and descendant cohorts of Schoenoplectus americanus genotypes recovered from two 100+ year coastal marsh seed banks. We compared S. americanus productivity and trait variation as well as associated endophytic microbial communities according to plant genotype, provenance, and age cohort under high and low salinity stress with and without native soil inoculation. The magnitude and direction of microbial mediation of S. americanus responses to elevated salinity varied according to individual genotype, provenance, as well as temporal shifts in genotypic variation and G × E (gene by environment) interactions. Relationships differed between plant traits and the structure of endosphere communities. Our findings indicate that plant‐microbe associations and microbial mediation of plant stress are not only context‐dependent but also dynamic. Our results additionally suggest that evolution can shape the fate of marsh ecosystems by altering how microbes confer plant tolerance to pressures linked to global change.
L’inférence dans les romans judiciaires d’Émile Gaboriau
Authors: Ventura Daniela
Published: July 2022

L’injection de l’heuristique dans le romanesque est loin d’être un recours littéraire nouveau. Un certain nombre de romanciers (tels Voltaire, Balzac, Bernanos, Robbe‐Grillet ou Butor) ne se sont pas privés d’y toucher. Ceci dit, ce sont notamment les écrivains attitrés du genre policier qui s’y sont spécialisés. En effet, l’expression la plus pure de l’heuristique se trouve dans le genre policier et, notamment, dans sa forme matricielle. Cette étude pluridisciplinaire se centre sur la trajectoire logico‐argumentative du texte littéraire. Nous nous proposons d’analyser les inférences amenant, dans le texte, à la découverte. Nous nous intéresserons, en définitive, à l’art detrouveret partant, de connaître. Pour illustrer le processus heuristique, nous examinerons l’œuvre romanesque policière d’un écrivain du XIXesiècle, Émile Gaboriau, en nous focalisant sur lemodus operandietcogitandide l’un de ses héros : M. Lecoq.
A nuclear reckoning
Authors: Cortright David
Published: July 2022

Russia's nuclear saber rattling in the war against Ukraine has increased the risk of nuclear weapons use and the danger of nuclear war. It also undermines global nonproliferation norms. Seeking a negotiated end to the war in Ukraine is an urgent priority for reducing the nuclear danger. Global security depends on renewing the diplomatic agenda for reducing and eliminating nuclear weapons.
Works council ‘disaffection’ and establishment survivability
Authors: Addison John T. , Teixeira Paulino , Grunau Philipp , Bellmann Lutz
Published: July 2022

This article investigates the association between a measure of works council heterogeneity and plant closings in Germany, 2006–2015. Two datasets are used to identify failed establishments, while institutional heterogeneity is captured by management perceptions of the role of the works council in managerial decision making and also by allowing for works council learning. The potential moderating role of sectoral collective bargaining is also examined. We report that works councils per se are not associated with plant closure. Rather, it is establishments with disaffected councils that display higher rates of closure. The latter result does not obtain where such establishments are covered by sectoral agreements; an outcome that is consistent with the literature on the mitigation of rent‐seeking behaviour, and one that also receives support from our finding that plants with dissonant councils are more likely than their consensual counterparts to transition into sectoral bargaining coverage. On the other hand, there is only limited evidence of works council learning.
Co‐expression of transcription factors ZmC1 and ZmR2 establishes an efficient and accurate haploid embryo identification system in maize
Authors: Chen Chen , Liu Xiaoqing , Li Suzhen , Liu Chenxu , Zhang Yuling , Luo Lili , Miao Liqing , Yang Wenzhu , Xiao Zijian , Zhong Yu , Li Jiansheng , Chen Rumei , Chen Shaojiang
Published: July 2022

Because of their high efficiency during chromosome doubling, immature haploid maize (Zea mays L.) embryos are useful for doubled haploid production. The R1‐nj marker is commonly used in doubled haploid breeding and has improved the efficiency of haploid identification. However, its effectiveness is limited by genetic background and environmental factors. We addressed this technical challenge by developing an efficient and accurate haploid embryo identification marker through co‐expression of two transcription factor genes (ZmC1 and ZmR2) driven by the embryo–aleurone‐specific bidirectional promoter PZmBD1; these factors can activate anthocyanin biosynthesis in the embryo and aleurone layer during early seed development. We developed a new haploid inducer, Maize Anthocyanin Gene InduCer 1 (MAGIC1), by introducing the transgenes into the haploid inducer line CAU6. MAGIC1 could identify haploids at 12 days after pollination, which is nine days earlier than CAU6. Importantly, MAGIC1 increased haploid identification accuracy to 99.1%, compared with 88.3% for CAU6. In addition, MAGIC1 could effectively overcome the inhibition of anthocyanin synthesis in some germplasms. Furthermore, an upgraded anthocyanin marker was developed from ZmC1 and ZmR2 to generate MAGIC2, which could identify haploids from diploids due to differential anthocyanin accumulation in immature embryos, coleoptiles, sheaths, roots, leaves, and dry seeds. This haploid identification system is more efficient and accurate than the conventional R1‐nj‐based method, and it simplifies the haploid identification process. Therefore, this system provides technical support for large‐scale doubled haploid line production.
A Golgi‐localized glycosyltransferase, OsGT14;1, is required for growth of both roots and shoots in rice
Authors: Wang Peitong , Yamaji Naoki , Ma Jian Feng
Published: July 2022

Glycosyltransferases (GTs) form a large family in plants and are important enzymes for the synthesis of various polysaccharides, but only a few members have been functionally characterized. Here, through mutant screening with gene mapping, we found that an Oryza sativa (rice) mutant with a short‐root phenotype was caused by a frame‐shift mutation of a gene (OsGT14;1) belonging to the glycosyltransferase gene family 14. Further analysis indicated that the mutant also had a brittle culm and produced lower grain yield compared with wild‐type rice, but the roots showed similar root structure and function in terms of the uptake of mineral nutrients. OsGT14;1 was broadly expressed in all organs throughout the entire growth period, with a relatively high expression in the roots, stems, node I and husk. Furthermore, OsGT14;1 was expressed in all tissues of these organs. Subcellular observation revealed that OsGT14;1 encoded a Golgi‐localized protein. Mutation of OsGT14;1 resulted in decreased cellulose content and increased hemicellulose, but did not alter pectin in the cell wall of roots and shoots. The knockout of OsGT14;1 did not affect the tolerance to toxic mineral elements, including Al, As, Cd and salt stress, but did increase the sensitivity to low pH. Taken together, OsGT14;1 located at the Golgi is required for growth of both roots and shoots in rice through affecting cellulose synthesis.
ABO, secretor, and Lewis carbohydrate histo‐blood groups are associated with autoimmune neutropenia of early childhood in Danish patients
Authors: Kløve‐Mogensen Kirstine , Steffensen Rudi , Masmas Tania Nicole , Glenthøj Andreas , Haunstrup Thure Mors , Ratcliffe Paul , Höglund Petter , Hasle Henrik , Nielsen Kaspar René
Published: July 2022

Background

Autoimmune neutropenia of early childhood (AIN) is caused by autoantibodies directed against antigens on the neutrophil membrane. The ABO, secretor, and Lewis histo‐blood group systems control the expression of carbohydrate antigens and have previously been linked to autoimmune diseases. We aimed to investigate the association between genotypes and the risk of AIN in Danish patients.

Study Design and Methods

One hundred fifty‐four antibody‐positive AIN patients were included. Controls (n = 400) were healthy unrelated Danish blood donors. Molecular determination of ABO, secretor (FUT2), and Lewis (FUT3) genotypes were determined using real‐time polymerase chain reaction (qPCR) or Sanger sequencing to infer the prevalence of Lewis antigens (Lea and Leb) and secretor (SeSe or Sese) or nonsecretor (sese) phenotypes.

Results

Blood type O was more common in controls (46.8%) than in AIN patients (36.4%) (OR = 0.65; p = 0.028). Secretors of H Leb antigens were less frequent among AIN patients (25.2%) than controls (35.0%) (OR = 0.62; p = 0.037).

Discussion

ABO blood group antigens and the secretion of these antigens are associated with a diagnosis of AIN. The mechanism underlying the association between autoimmunity and interaction among ABO, secretor, and Lewis genotypes has not yet been elucidated, but several studies indicate a connection to the gut microbiota.
Microstructural, mechanical, and in vitro corrosion properties of biodegradable Mg-Ag alloys
Authors: Elen Levent , Turen Yunus , Ahlatci Hayrettin , Unal Mehmet , Ergin Deniz
Published: July 2022

In this study, casting, extrusion, biocorrosion, and corrosive wear properties of 0.5 wt. % (Zn, Ca, and Nd) element added Mg—3 wt. % Ag alloys were investigated. According to the test results, it was observed that the grain refinement occurred with the effect of Zn and Ca element additions in the as-cast alloys and thus some mechanical properties of the alloys improved. Similarly, the extrusion process provided grain refinement and improved mechanical properties. As a result of in vitro corrosion tests, similar results were also obtained in the as-cast alloys, while this situation became more apparent in the extruded alloys and exhibited more homogeneous corrosion properties. In the corrosive wear tests, the wear rate of the extruded alloys generally showed a decreasing trend. However, both the as-cast and extruded Mg—3 wt. %Ag—0.5 wt. % Ca alloys exhibited the lowest wear rate.
Systematic simulation of the interactions of pleckstrin homology domains with membranes
Authors: Le Huray Kyle I. P. , Wang He , Sobott Frank , Kalli Antreas C.
Published: July 2022

Pleckstrin homology (PH) domains can recruit proteins to membranes by recognition of phosphatidylinositol phosphate (PIP) lipids. Several family members are linked to diseases including cancer. We report the systematic simulation of the interactions of 100 mammalian PH domains with PIP-containing membranes. The observed PIP interaction hotspots recapitulate crystallographic binding sites and reveal a number of insights: (i) The β1 and β2 strands and their connecting loop constitute the primary PIP interaction site but are typically supplemented by interactions at the β3-β4 and β5-β6 loops; (ii) we reveal exceptional cases such as the Exoc8 PH domain; (iii) PH domains adopt different membrane-bound orientations and induce clustering of anionic lipids; and (iv) beyond family-level insights, our dataset sheds new light on individual PH domains, e.g., by providing molecular detail of secondary PIP binding sites. This work provides a global view of PH domain/membrane association involving multivalent association with anionic lipids.
Early knapping techniques do not necessitate cultural transmission
Authors: Snyder William D. , Reeves Jonathan S. , Tennie Claudio
Published: July 2022

Early stone tool production, or knapping, techniques are claimed to be the earliest evidence for cultural transmission in the human lineage. Previous experimental studies have trained human participants to knap in conditions involving opportunities for cultural transmission. Subsequent knapping was then interpreted as evidence for a necessity of the provided cultural transmission opportunities for these techniques. However, a valid necessity claim requires showing that individual learning alone cannot lead to early knapping techniques. Here, we tested human participants (
N
= 28) in cultural isolation for the individual learning of early knapping techniques by providing them with relevant raw materials and a puzzle task as motivation. Twenty-five participants were technique naïve according to posttest questionnaires, yet they individually learned early knapping techniques, therewith producing and using core and flake tools. Early knapping techniques thus do not necessitate cultural transmission of know-how and could likewise have been individually derived among premodern hominins.
The “teapot in a city”: A paradigm shift in urban climate modeling
Authors: Villefranque Najda , Hourdin Frédéric , d’Alençon Louis , Blanco Stéphane , Boucher Olivier , Caliot Cyril , Coustet Christophe , Dauchet Jérémi , El Hafi Mouna , Eymet Vincent , Farges Olivier , Forest Vincent , Fournier Richard , Gautrais Jacques , Masson Valéry , Piaud Benjamin , Schoetter Robert
Published: July 2022

Urban areas are a high-stake target of climate change mitigation and adaptation measures. To understand, predict, and improve the energy performance of cities, the scientific community develops numerical models that describe how they interact with the atmosphere through heat and moisture exchanges at all scales. In this review, we present recent advances that are at the origin of last decade’s revolution in computer graphics, and recent breakthroughs in statistical physics that extend well-established path-integral formulations to nonlinear coupled models. We argue that this rare conjunction of scientific advances in mathematics, physics, computer, and engineering sciences opens promising avenues for urban climate modeling and illustrate this with coupled heat transfer simulations in complex urban geometries under complex atmospheric conditions. We highlight the potential of these approaches beyond urban climate modeling for the necessary appropriation of the issues at the heart of the energy transition by societies.
Instability mediated self-templating of drop crystals
Authors: Cai Lingzhi , Marthelot Joel , Brun P.-T.
Published: July 2022

The breakup of liquid threads into droplets is prevalent in engineering and natural settings. While drop formation in these systems has a long-standing history, existing studies typically consider axisymmetric systems. Conversely, the physics at play when multiple threads are involved and the interaction of a thread with a symmetry breaking boundary remain unexplored. Here, we show that the breakup of closely spaced liquid threads sequentially printed in an immiscible bath locks into crystal-like lattices of droplets. We rationalize the hydrodynamics at the origin of this previously unknown phenomenon. We leverage this knowledge to tune the lattice pattern via the control of injection flow rate and nozzle translation speed, thereby overcoming the limitations in structural versatility typically seen in existing fluid manipulations paradigms. We further demonstrate that these drop crystals have the ability to self-correct and propose a simple mechanism to describe the convergence toward a uniform pattern of drops.
Early Events in Reovirus Infection Influence Induction of Innate Immune Response
Authors: Abad Andrew T. , Danthi Pranav
Published: July 2022

Viruses must infect host cells to replicate, often killing the host cell in the process. However, hosts can activate defenses to limit viral replication and protect the organism.
Aminotransferase SsAro8 Regulates Tryptophan Metabolism Essential for Filamentous Growth of Sugarcane Smut Fungus
Sporisorium scitamineum
Authors: Cui Guobing , Huang Chengwei , Bi Xinping , Wang Yixu , Yin Kai , Zhu Luyuan , Jiang Zide , Chen Baoshan , Deng Yi Zhen
Published: July 2022

Sugarcane smut caused by the basidiomycete fungus
S. scitamineum
leads to massive economic losses in sugarcane plantation globally. Dikaryotic hyphae formation (filamentous growth) and biofilm formation are two important aspects in
S. scitamineum
pathogenesis, yet the molecular regulation of these two processes was not as extensively investigated as that in the model pathogenic fungi, e.g.,
Candida albicans
,
Ustilago maydis
, or
Cryptococcus neoformans
.
Asymmetric propagation mechanism of hydraulic fracture networks in continental reservoirs
Authors: Liu Jingshou , Mei Lianfu , Ding Wenlong , Xu Ke , Yang Haimeng , Liu Yang
Published: July 2022

Hydraulic fracturing technology is relatively mature in North America, but under complex geological conditions, such as those in China, the application of this technology still faces great challenges. At present, techniques for the numerical simulation of hydraulic fracture networks are mainly based on the prediction of the fracture half-height and half-length, which cannot capture the heterogeneity of continental low-permeability sandstone reservoirs in China and the distribution of the asymmetric hydraulic fracture network present in them. Therefore, determining the asymmetric propagation mechanism of hydraulic fracture networks is very important for improving the recovery rates of continental reservoirs. In this paper, taking the Ordos Basin in China as an example, the spatial distribution of the stress field of a heterogeneous continental reservoir is precisely predicted by reservoir mechanical heterogeneity modeling. By using a microseismic monitoring method, the 3-D morphology of the hydraulic fracture network is determined. Through the coupling of multisource data, the frequency distributions of the determined in situ stress magnitudes in different hydraulic fracturing stages are obtained. The propagation direction of the hydraulic fracture network changes under the control of the horizontal stress difference (Δσ) and the presence of natural fractures. The smaller Δσ is, the greater the deflection of the hydraulic fracture propagation direction. The asymmetric propagation of these fractures is related to the frequency distribution of Δσ. As the frequency of Δσ approaches a normal distribution, the two wings of the hydraulic fracture network become basically equal in length, and as Δσ deviates more from a normal distribution, the difference between the two wings of the hydraulic fracture network increases. These research results will provide new insight for modeling, exploring, and developing continental reservoirs.
Traumatic pseudocyst of the lung following blunt trauma to the chest
Authors: Desale Akshay Nanaji , Badhe Padma Vikram , Nair Megha Gireesan , Rane Chaitanya Dilip
Published: July 2022

Traumatic pseudocysts of the lung are a rare complication following blunt trauma to the chest. Differentiating them from other cystic lesions of the lung is important. Traumatic pseudocysts usually occur in children and young adults who present with haemoptysis and persistent pain. History of trauma and radiological evaluation with a chest radiograph and a CT scan help in making the diagnosis. Follow-up chest radiographs showing resolution of the pseudocyst can confirm thediagnostic confirmation. This is a report of one such patient, a young man who improved after conservative treatment, with spontaneous radiological resolution of the pseudocyst.
Thrombus calcification after removing peripherally inserted central catheters in extremely preterm infants
Authors: Shima Takashi , Kusuda Takeshi , Kan Nobuhiko , Kinjo Tadamune
Published: July 2022

Pericatheter thrombus calcification is a complication that arises due to central venous catheter insertion and is particularly rare in peripherally inserted central catheters (PICCs). In this case report, we reviewed the clinical course of two neonates experiencing thrombus calcification. The first case involved a male neonate weighing 445 g. His PICC dwelt in the superior vena cava for over 49 days. Although a radiograph after removal did not show any silhouette, subsequent radiographs and CT depicted a catheter-like outline. Percutaneous intravascular retrieval was performed to salvage the object. Pathological examination revealed it to be a calcified cast. The calcified thrombosis was successfully dissolved with 6 months of warfarin therapy. The second case involved a male neonate weighing 534 g. After PICC removal, a catheter-like structure was shown on ultrasonograms. It was determined that invasive procedures were unnecessary for diagnosing the calcified thrombosis based on experience with the first case.