bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Hypothesis Testing in Conjoint Analysis
Authors: Liu Guoer , Shiraito Yuki 
Published: January 2023

AbstractConjoint analysis is widely used for estimating the effects of a large number of treatments on multidimensional decision-making. However, it is this substantive advantage that leads to a statistically undesirable property, multiple hypothesis testing. Existing applications of conjoint analysis except for a few do not correct for the number of hypotheses to be tested, and empirical guidance on the choice of multiple testing correction methods has not been provided. This paper first shows that even when none of the treatments has any effect, the standard analysis pipeline produces at least one statistically significant estimate of average marginal component effects in more than 90% of experimental trials. Then, we conduct a simulation study to compare three well-known methods for multiple testing correction, the Bonferroni correction, the Benjamini–Hochberg procedure, and the adaptive shrinkage (Ash). All three methods are more accurate in recovering the truth than the conventional analysis without correction. Moreover, the Ash method outperforms in avoiding false negatives, while reducing false positives similarly to the other methods. Finally, we show how conclusions drawn from empirical analysis may differ with and without correction by reanalyzing applications on public attitudes toward immigration and partner countries of trade agreements.
Detecting and Correcting for Separation in Strategic Choice Models
Authors: Crisman-Cox Casey , Gasparyan Olga , Signorino Curtis S. 
Published: January 2023

AbstractSeparation or “perfect prediction” is a common problem in discrete choice models that, in practice, leads to inflated point estimates and standard errors. Standard statistical packages do not provide clear advice on how to correct these problems. Furthermore, separation can go completely undiagnosed in fitting advanced models that optimize a user-supplied log-likelihood rather than relying on pre-programmed estimation procedures. In this paper, we both describe the problems that separation can cause and address the issue of detecting it in empirical models of strategic interaction. We then consider several solutions based on penalized maximum likelihood estimation. Using Monte Carlo experiments and a replication study, we demonstrate that when separation is detected in the data, the penalized methods we consider are superior to ordinary maximum likelihood estimators.
Reducing milking frequency from 3 to 2 times daily in early lactation: effects on milk production, health and body condition
Authors: Lehmann Jesper Overgård , Kristensen Troels , Mogensen Lisbeth 
Published: January 2023

AbstractThe objective of this experiment was to investigate the effect of reducing early lactation milking frequency on milk yield and persistency through lactation and early lactation fat mobilization, measured by body condition score (BCS) and BHB in milk. We hypothesized that milking cows twice per day in early lactation before milking them 3 times per day for the remaining lactation would cause less fat mobilization in early lactation, a lower peak milk yield but improved persistency throughout lactation compared with milking cows 3 times per day for the entire lactation. The experiment took place on 2 commercial dairy farms in Denmark. All cows calving in a period of nine months (n = 239) in their current first and later parities were randomly allocated at dry-off to 1 of 3 treatments based on expected calving date. The treatments were (1) cows milked 2 times per day for 1 week after calving, (2) cows milked 2 times per day for 4 weeks after calving and (3) cows milked 2 times per day for 7 weeks after calving. All cows were then milked 3 times per day for the remaining lactation. Milk yield peaked 3.3 and 3.6 d later and milk yield persistency improved with 18 and 19 g per day when cows were milked 2 times per day for 4 and 7 weeks, respectively, compared with milking 2 times per day for 1 week after calving. We found a significant highest milk BHB in treatment 2, but the underlying effect of milking cows 2 times per day for 4 weeks compared with 1 or 7 weeks was unclear. In conclusion, we did not confirm our hypothesis that milking cows 2 times per day compared to 3 times in early lactation would reduce fat mobilization and reduce peak yield. We did, however, find an improved milk yield persistency, which partially offset a numerical reduction in peak yield, and hence there was no significant effect of reducing early lactation milking frequency on total lactation (305 DIM) milk yield.
Socio-economic factors correlating with illegal use of giraffe body parts
Authors: Muneza Arthur B. , Amakobe Bernard , Kasaine Simon , Kramer Daniel B. , Githiru Mwangi , Roloff Gary J. , Hayward Matt W. , Montgomery Robert A. 
Published: January 2023

AbstractUnsustainable hunting, both illegal and legal, has led to the extirpation of many species. In the last 35 years giraffeGiraffaspp. populations have declined precipitously, with extinctions documented in seven African countries. Amongst the various reasons for these population declines, poaching is believed to play an important role in some areas. Giraffes are primarily hunted for consumption and for the use of their body parts as trophies and in traditional medicine. However, the socio-economic factors that correlate with the use of giraffe body parts are not well understood. We conducted our study in Tsavo Conservation Area, Kenya, which experiences high levels of poaching. We used semi-structured surveys amongst 331 households to document how giraffe body parts are typically acquired and their intended use (i.e. trophy, medicinal or consumptive). We then used logistic regression models to assess the correlations between nine socio-economic factors and the use of giraffe body parts. We found that giraffe body parts had mostly consumptive and trophy uses. One-time suppliers, opportunistic access and widely known markets were the most common means of acquiring giraffe body parts. Results from our models showed that three variables (gender: men, occupation: tourism worker, and land ownership) were correlated significantly and positively with the use of giraffe body parts. We describe the complex links between socio-economic factors and the use of giraffe body parts and highlight the importance of implementing mitigation measures adapted to local contexts to combat a challenge that many species of conservation concern are facing.
Theoretical error analysis of spotlight-based instrument localization for retinal surgery
Authors: Zhou Mingchuan , Hennerkes Felix , Liu Jingsong , Jiang Zhongliang , Wendler Thomas , Nasseri M. Ali , Iordachita Iulian , Navab Nassir 
Published: January 2023

AbstractRetinal surgery is widely considered to be a complicated and challenging task even for specialists. Image-guided robot-assisted intervention is among the novel and promising solutions that may enhance human capabilities therein. In this paper, we demonstrate the possibility of using spotlights for 5D guidance of a microsurgical instrument. The theoretical basis of the localization for the instrument based on the projection of a single spotlight is analyzed to deduce the position and orientation of the spotlight source. The usage of multiple spotlights is also proposed to check the possibility of further improvements for the performance boundaries. The proposed method is verified within a high-fidelity simulation environment using the 3D creation suite Blender. Experimental results show that the average positioning error is 0.029 mm using a single spotlight and 0.025 mm with three spotlights, respectively, while the rotational errors are 0.124 and 0.101, which shows the application to be promising in instrument localization for retinal surgery.
Multiple-drawing dynamic Friedman urns with opposite-reinforcement
Authors: Gao Shuyang , Aguech Rafik 
Published: January 2023

AbstractIn this study, we consider a class of multiple-drawing opposite-reinforcing urns with time-dependent replacement rules. The class has the symmetric property of a Friedman-type urn. We divide the class into a small-increment regime and a large-increment regime. For small-increment schemes, we prove almost-sure convergence and a central limit theorem for the proportion of white balls by stochastic approximation. For large-increment schemes, by assuming the affinity condition, we show almost-sure convergence of the proportion of white balls by martingale theory and present a way to identify the limit distribution of the proportion of white balls.
Variable grammars are variable across registers: future temporal reference in English
Authors: Engel Alexandra , Szmrecsanyi Benedikt 
Published: January 2023

AbstractIt is widely accepted that internal constraints on variation are not modulated by social and stylistic factors (e.g., Labov, 2010:265). Is this also true for register differences as a special type of sociostylistic factor? To address this question, we investigate future temporal reference (FTR) variation in English (It'll be funversusIt's gonna be fun) via a variationist corpus study (n= 2,600 tokens) and a supplementary rating experiment (n= 114 participants) across four broad registers: conversations, parliamentary debates, blogs, and newspaper prose. Multivariate analysis of the corpus dataset indicates that register modulates the effect of five out of nine internal constraints, suggesting that variable grammars vary considerably across registers. The experiment confirms that language users are indeed sensitive to, and aware of, the register-specificity of how variation is conditioned. We conclude by discussing the implications of our findings for variationist sociolinguistics and for variational linguistics in general.
Longitudinal associations between early childhood irritability and adolescent depression symptoms in autistic children are mediated by peer relationships but not educational engagement
Authors: Carter Leno Virginia , Wright Nicola , Pickles Andrew , Bedford Rachael , Zaidman-Zait Anat , Kerns Connor , Zwaigenbaum Lonnie , Duku Eric , Bennett Teresa , Georgiades Stelios , Smith Isabel M. , Richards Annie , Vaillancourt Tracy , Szatmari Peter , Elsabbagh Mayada ,   The Pathways in ASD Study Team
Published: January 2023

AbstractIn the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3–5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.
The Geodynamic Implications of Passive Margin Subduction in Northwest Turkey
Authors: Campbell C. F. , Mueller M. A. , Taylor M. H. , Ocakoğlu F. , Möller A. , Métais G. , Coster P. M. C. , Beard K. C. , Licht A. 
Published: January 2023

AbstractThe number of subduction zones that facilitated the northward translation of the Anatolide‐Tauride continental terrane derived from Gondwana to the southern margin of Eurasia at the longitude of western Turkey is debated. We hypothesized that if two north dipping subduction zones facilitated incipient collision in western Turkey, a late Cretaceous arc would have formed within the Neotethys and along the southern margin of Eurasia. To determine if an island arc formed within the Neotethys we investigated the sedimentary record of the Central Sakarya basin, which was deposited along the southern margin of Eurasia from 85 to 45 million years ago. Detrital zircon deposited within the lower levels of the Central Sakarya basin (the Değirmenözü Formation) are associated with south to north‐directed paleocurrents and exhibit a unimodal late Cretaceous age peak sourced from isotopically juvenile mantle melts. Zircon maximum depositional ages from the Değirmenözü Formation cluster between 95 and 90 Ma and are 5–10 Myr older than biostratigraphic depositional ages. Between 95 and 80 Ma, a 12‐unit shift from mantle to crustal derived εHf values occurs in the overlying Yenipazar Formation. We explain the absence of Paleozoic, Eurasian‐sourced detrital zircon, the rapid shift from mantle to crustal derived εHf values, and lag time in terms of passive margin subduction within an isolated intra‐oceanic subduction zone, whose island arc was reworked from south to north into the Central Sakarya basin during incipient collision. Thus, widely outcropping late Cretaceous plutonic rocks within Eurasia must have belonged to an additional convergent margin.
Mixed Layer Temperature Budget in the Arabian Sea During Winter 2019 and Spring 2019: The Role of Diapycnal Heat Flux
Authors: Jofia J. , Girishkumar M. S. , Ashin K. , Sureshkumar N. , Shivaprasad S. , Pattabhi Ram Rao E. 
Published: January 2023

AbstractSea surface temperatures (SSTs) simulated by almost all models in Coupled Model Inter‐comparison Project phase five are consistently colder (∼−1°C to −4°C) than the observation in the northern Arabian Sea (AS) during winter and spring. These biases significantly weaken the seasonal and extended summer monsoon prediction skills and climate change projection's reliability in this region. To understand the relative contribution of diapycnal heat flux (Jh) compared to other terms in the mixed layer (ML) temperature (MLT) budget during these two seasons, we use time series of vertical profiles of microstructure shear measurements collected in the northeastern AS (NEAS) at 18.4°N and 67.4°E during January 10–17, 2019 (W19) and May 7–21, 2019 (S19). It is found that the vertical processes term and net surface heat flux together determine the bulk of MLT tendency during S19 and W19, and the contribution of the horizontal advection and Jh is relatively smaller. The mean value of Jh (∼−2 W m−2) at the base of the ML shows a comparable magnitude during W19 and S19, and the median values of diapycnal diffusivity (Kρ) at the ML base are not significantly different between W19 (∼3.1 × 10−6 m2 s−1) and S19 (∼5.2 × 10−6 m2 s−1). Besides, Kρ and Jh values were estimated using different Kρ‐Richardson number (Ri) based interior ocean parameterization schemes at the ML base in the NEAS overestimated with respect to observation. The alleged role of overestimation of Kρ and Jh in parameterization schemes on model simulation of cold SST bias in the AS is also discussed.
The genetic basis of major depressive disorder
Authors: Flint Jonathan 
Published: January 2023

AbstractThe genetic dissection of major depressive disorder (MDD) ranks as one of the success stories of psychiatric genetics, with genome-wide association studies (GWAS) identifying 178 genetic risk loci and proposing more than 200 candidate genes. However, the GWAS results derive from the analysis of cohorts in which most cases are diagnosed by minimal phenotyping, a method that has low specificity. I review data indicating that there is a large genetic component unique to MDD that remains inaccessible to minimal phenotyping strategies and that the majority of genetic risk loci identified with minimal phenotyping approaches are unlikely to be MDD risk loci. I show that inventive uses of biobank data, novel imputation methods, combined with more interviewer diagnosed cases, can identify loci that contribute to the episodic severe shifts of mood, and neurovegetative and cognitive changes that are central to MDD. Furthermore, new theories about the nature and causes of MDD, drawing upon advances in neuroscience and psychology, can provide handles on how best to interpret and exploit genetic mapping results.
MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer
Authors: Yang Qian , Kong Shan , Yu Jiajia , Xu Yanhua , Tao Mei , Ma Shuo , Tang Chenxue , Shen Xianjuan , Tang Zhiyuan , Ju Shaoqing 
Published: January 2023

AbstractGlycerophospholipid signal and fatty acid metabolism are closely related to the occurrence and progression of tumours, and metabolic reprogramming caused by hydrolytic enzymes plays an important role in gastric cancer (GC). Here, we performed whole transcriptome sequencing and combined qRT-PCR to screen out the significantly high expression of fatty acid amide hydrolase (FAAH) in GC tissues, which was further verified in both TCGA and Oncomine databases. Functional tests confirmed that FAAH played an oncogene role in GC, and silencing FAAH could delay tumour growth, inhibit tumour metastasis, and promote cell apoptosis both in vitro and in vivo. FAAH-mediated lipid metabolism reprogramming through coordinated regulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signalling and activated the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis to promote GC progression. Luciferase reporter assay and immunofluorescence-fluorescence in situ hybridization (IF-FISH) were applied to validate the interactions of miR-1275/FAAH. Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development.
Inhibition of autophagy and MEK promotes ferroptosis in Lkb1-deficient Kras-driven lung tumors
Authors: Bhatt Vrushank , Lan Taijin , Wang Wenping , Kong Jerry , Lopes Eduardo Cararo , Wang Jianming , Khayati Khoosheh , Raju Akash , Rangel Michael , Lopez Enrique , Hu Zhixian Sherrie , Luo Xuefei , Su Xiaoyang , Malhotra Jyoti , Hu Wenwei , Pine Sharon R. , White Eileen , Guo Jessie Yanxiang 
Published: January 2023

AbstractLKB1 and KRAS are the third most frequent co-mutations detected in non-small cell lung cancer (NSCLC) and cause aggressive tumor growth. Unfortunately, treatment with RAS-RAF-MEK-ERK pathway inhibitors has minimal therapeutic efficacy in LKB1-mutant KRAS-driven NSCLC. Autophagy, an intracellular nutrient scavenging pathway, compensates for Lkb1 loss to support Kras-driven lung tumor growth. Here we preclinically evaluate the possibility of autophagy inhibition together with MEK inhibition as a treatment for Kras-driven lung tumors. We found that the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and the MEK inhibitor Trametinib displays synergistic anti-proliferative activity in KrasG12D/+;Lkb1-/- (KL) lung cancer cells, but not in KrasG12D/+;p53-/- (KP) lung cancer cells. In vivo studies using tumor allografts, genetically engineered mouse models (GEMMs) and patient-derived xenografts (PDXs) showed anti-tumor activity of the combination of HCQ and Trametinib on KL but not KP tumors. We further found that the combination treatment significantly reduced mitochondrial membrane potential, basal respiration, and ATP production, while also increasing lipid peroxidation, indicative of ferroptosis, in KL tumor-derived cell lines (TDCLs) and KL tumors compared to treatment with single agents. Moreover, the reduced tumor growth by the combination treatment was rescued by ferroptosis inhibitor. Taken together, we demonstrate that autophagy upregulation in KL tumors causes resistance to Trametinib by inhibiting ferroptosis. Therefore, a combination of autophagy and MEK inhibition could be a novel therapeutic strategy to specifically treat NSCLC bearing co-mutations of LKB1 and KRAS.
USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy
Authors: Campos-Iglesias Diana , Fraile Julia M. , Bretones Gabriel , Montero Alejandro A. , Bonzon-Kulichenko Elena , Vázquez Jesús , López-Otín Carlos , Freije José M. P. 
Published: January 2023

AbstractThe spindle assembly checkpoint (SAC) is an essential mechanism that ensures the accurate chromosome segregation during mitosis, thus preventing genomic instability. Deubiquitinases have emerged as key regulators of the SAC, mainly by determining the fate of proteins during cell cycle progression. Here, we identify USP49 deubiquitinase as a novel regulator of the spindle checkpoint. We show that loss of USP49 in different cancer cell lines impairs proliferation and increases aneuploidy. In addition, USP49-depleted cells overcome the arrest induced by the SAC in the presence of nocodazole. Finally, we report new binding partners of USP49, including ribophorin 1, USP44, and different centrins.
Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons
Authors: Garone Maria Giovanna , Salerno Debora , Rosa Alessandro 
Published: January 2023

AbstractMutations in RNA binding proteins (RBPs) have been linked to the motor neuron disease amyotrophic lateral sclerosis (ALS). Extensive auto-regulation, cross-regulation, cooperation and competition mechanisms among RBPs are in place to ensure proper expression levels of common targets, often including other RBPs and their own transcripts. Moreover, several RBPs play a crucial role in the nervous system by localizing target RNAs in specific neuronal compartments. These include the RBPs FUS, FMRP, and HuD. ALS mutations in a given RBP are predicted to produce a broad impact on such delicate equilibrium. Here we studied the effects of the severe FUS-P525L mutation on common FUS and FMRP targets. Expression profiling by digital color-coded molecular barcoding in cell bodies and neurites of human iPSC-derived motor neurons revealed altered levels of transcripts involved in the cytoskeleton, neural projection and synapses. One of the common targets is HuD, which is upregulated because of the loss of FMRP binding to its 3′UTR due to mutant FUS competition. Notably, many genes are commonly altered upon FUS mutation or HuD overexpression, suggesting that a substantial part of the effects of mutant FUS on the motor neuron transcriptome could be due to HuD gain-of-function. Among altered transcripts, we also identified other common FUS and FMRP targets, namely MAP1B, PTEN, and AP2B1, that are upregulated upon loss of FMRP binding on their 3’UTR in FUS-P525L motor neurons. This work demonstrates that the impairment of FMRP function by mutant FUS might alter the expression of several genes, including new possible biomarkers and therapeutic targets for ALS.