bluuebunny/crossref_metadata_2025_split huggingface dataset:
Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial
Authors: Atreya Raja , Kühbacher Tanja , Waldner Maximilian J , Hirschmann Simon , Drvarov Oliver , Abu Hashem Raed , Maaser Christian , Kucharzik Torsten , Dinter Johanna , Mertens Jessica , Schramm Christoph , Holler Babett , Mössner Joachim , Suzuki Kenji , Yokoyama Junji , Terai Shuji , Uter Wolfgang , Yoneyama Hiroyuki , Asakura Hitoshi , Hibi Toshifumi , Neurath Markus F 
Published: September 2023

Abstract

Background and Aims
Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC].

Methods
In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment.

Results
Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated.

Conclusion
Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC.
Crimes without a body: reflections on a case series of online crimes
Authors: Barbieri Cristiano , Grattagliano Ignazio , Catanesi Roberto 
Published: September 2023

Abstract
There is a large volume of online crimes. The aim of this work is to reflect on virtual crimes that are apparently different but actually have commonalities. In these cases, the corporeal sphere that mediates interpersonal relationships is absent, and perceptions of the real world and emotional regulation may be altered, which poses the risk of destructive behaviours. From this standpoint, self/hetero-directed aggression is the result of a certain type of transition from the real to the virtual world, where the body either is not involved at all or is experienced in an aberrant manner. In this study, we present three cases that clearly illustrate this concept.
Dynamic Evolution of Bacterial Ligand Recognition by Formyl Peptide Receptors
Authors: Paterson Nicole M , Al-Zubieri Hussein , Ragona Joseph , Kohler Kristin M , Tirado Juan , Geisbrecht Brian V , Barber Matthew F 
Published: September 2023

Abstract
The detection of invasive pathogens is critical for host immune defense. Cell surface receptors play a key role in the recognition of diverse microbe-associated molecules, triggering leukocyte recruitment, phagocytosis, release of antimicrobial compounds, and cytokine production. The intense evolutionary forces acting on innate immune receptor genes have contributed to their rapid diversification across plants and animals. However, the functional consequences of immune receptor divergence are often unclear. Formyl peptide receptors (FPRs) comprise a family of animal G protein–coupled receptors which are activated in response to a variety of ligands including formylated bacterial peptides, pathogen virulence factors, and host-derived antimicrobial peptides. FPR activation in turn promotes inflammatory signaling and leukocyte migration to sites of infection. Here we investigate patterns of gene loss, diversification, and ligand recognition among FPRs in primates and carnivores. We find that FPR1, which plays a critical role in innate immune defense in humans, has been lost in New World primates. Amino acid variation in FPR1 and FPR2 among primates and carnivores is consistent with a history of repeated positive selection acting on extracellular domains involved in ligand recognition. To assess the consequences of FPR divergence on bacterial ligand interactions, we measured binding between primate FPRs and the FPR agonist Staphylococcus aureus enterotoxin B, as well as S. aureus FLIPr-like, an FPR inhibitor. We found that few rapidly evolving sites in primate FPRs are sufficient to modulate recognition of bacterial proteins, demonstrating how natural selection may serve to tune FPR activation in response to diverse microbial ligands.
Identification of Dementia in Medicare Claims Compared to Rigorous Clinical Assessments in African Americans
Authors: Grodstein Francine , James Bryan D , Chen Yi , Capuano Ana W , Power Melinda C , Bennett David A , Bynum Julie P W , Barnes Lisa L 
Published: September 2023

Abstract

Background
Evidence indicates the health care system disproportionately misses dementia in African American compared to White individuals. In preliminary data, we examined factors related to dementia identification by the health care system among African Americans.

Methods
We leveraged linked Medicare fee-for-service claims and detailed annual cohort evaluations in African Americans from 4 cohorts at Rush Alzheimer’s Disease Center.

Results
Among 88 African Americans with cognitive impairment (mean = 10 years follow-up), Medicare claims identified dementia &lt;2 years from cohort diagnosis in 55%; 27% were identified 2–9.9 years after cohort diagnosis, and in 18% there was either no claims diagnosis during the study period, or claims identified dementia 10+ years after cohort diagnosis. Claims identification of dementia was related to older age at cohort diagnosis (eg, &lt;2 years between cohort and claims: mean = 82 years; 10+ years/no diagnosis: mean = 77 years, p = .04), lower Mini-Mental State Examination (MMSE) score (&lt;2 years: mean = 24; 10+ years/no diagnosis: mean = 26, p = .04), more depressive symptoms (&lt;2 years: mean = 2.1 symptoms; 10+ years/no diagnosis: mean = 1.2, p = .04), and more comorbidity (&lt;2 years: mean = 5.6 comorbidities; 10+ years/no diagnosis, mean = 3.0, p = .02).

Conclusions
Among African Americans, preliminary data indicate the health care system most rapidly identifies dementia in older individuals, with worse cognitive and physical health. The health care system may miss opportunities for early support of African Americans with dementia, and caregivers.
Confound-leakage: confound removal in machine learning leads to leakage
Authors: Hamdan Sami , Love Bradley C , von Polier Georg G , Weis Susanne , Schwender Holger , Eickhoff Simon B , Patil Kaustubh R 
Published: September 2023

Abstract

Background
Machine learning (ML) approaches are a crucial component of modern data analysis in many fields, including epidemiology and medicine. Nonlinear ML methods often achieve accurate predictions, for instance, in personalized medicine, as they are capable of modeling complex relationships between features and the target. Problematically, ML models and their predictions can be biased by confounding information present in the features. To remove this spurious signal, researchers often employ featurewise linear confound regression (CR). While this is considered a standard approach for dealing with confounding, possible pitfalls of using CR in ML pipelines are not fully understood.

Results
We provide new evidence that, contrary to general expectations, linear confound regression can increase the risk of confounding when combined with nonlinear ML approaches. Using a simple framework that uses the target as a confound, we show that information leaked via CR can increase null or moderate effects to near-perfect prediction. By shuffling the features, we provide evidence that this increase is indeed due to confound-leakage and not due to revealing of information. We then demonstrate the danger of confound-leakage in a real-world clinical application where the accuracy of predicting attention-deficit/hyperactivity disorder is overestimated using speech-derived features when using depression as a confound.

Conclusions
Mishandling or even amplifying confounding effects when building ML models due to confound-leakage, as shown, can lead to untrustworthy, biased, and unfair predictions. Our expose of the confound-leakage pitfall and provided guidelines for dealing with it can help create more robust and trustworthy ML models.
Radial shear in the flow at the Earth’s core surface
Authors: Firsov I , Jault D , Gillet N , Aubert J , Mandea M 
Published: September 2023

SUMMARY
The Earth’s magnetic field at the core–mantle boundary is the gradient of a harmonic potential function if the mantle is electrically insulating, and the horizontal components of the field can be derived from its radial component in the mantle. Therefore, these components give no further observational information on the core dynamics. However, it can still be envisioned that the horizontal components of the induction equation at Earth’s core surface yield further knowledge on the fluid motions at the top of the core independently of the observations. Here, we show that they provide a linear relationship between the surface velocity and the surface shear (strain shear) that depends on the mantle electrical conductivity. This offers a protocol to calculate the surface shear that we validate with synthetics obtained from dynamo simulations in the limit of a weak mantle conductance. First, using numerical simulations with stress-free boundary condition at the core surface, we retrieve the expected relationship between the horizontal flow uΣ and the shear, ${\bf u}_\Sigma =r\partial _r {\bf u}_{\Sigma }$. Next, we investigate simulations with no-slip boundary condition and insulating mantle, and we obtain the same relationship, even though the shear is not imposed as a boundary condition. Finally, we calculate the flow shear at the top of the core from a magnetic field model based on satellite measurements. The application to geophysical data indicates larger values of the surface flow shear than in the synthetic case, suggesting a possible role of the mantle electrical conductivity. The surface flow shear, in the simulations, much differs from the radial shear in the flow, deeper in the core, which is influenced by the mostly quasi-geostrophic geometry. This implies that we cannot rely on the relationship between the flow and the radial shear for quasi-geostrophic motions to exploit the horizontal components of the induction equation and gain further information on the flow at the Earth’s core surface.
Whole-genome and genome-wide association studies improve key agricultural traits of safflower for industrial and medicinal use
Authors: Chen Jiang , Guo Shuai , Hu Xueli , Wang Rui , Jia Donghai , Li Qiang , Yin Xianmei , Liao Xuejiao , Hu Zunhong , Wang Peiqi , Ren Chaoxiang , Dong Shuai , Chen Chao , Chen Shilin , Xu Jiang , Pei Jin 
Published: September 2023

Abstract
Safflower (Carthamus tinctorius) is widely cultivated around the world for its seeds and flowers. The presence of linoleic acid (LA) in its seeds and hydroxysafflor yellow A (HSYA) in its flowers are the crucial traits that enable safflower to be used for industrial and medicinal purposes. Understanding the genetic control of these traits is essential for optimizing the quality of safflower and its breeding. To further this research, we present a chromosome-scale assembly of the genome of the safflower variety ‘Chuanhonghua 1’, which was achieved using an integrated strategy combining Illumina, Oxford Nanopore, and Hi-C sequencing. We obtained a 1.17-Gb assembly with a contig N50 of 1.08 Mb, and all assembled sequences were assigned to 12 pseudochromosomes. Safflower’s evolution involved the core eudicot γ-triplication event and a whole-genome duplication event, which led to large-scale genomic rearrangements. Extensive genomic shuffling has occurred since the divergence of the ancestor of dicotyledons. We conducted metabolite and transcriptome profiles with time- and part-dependent changes and screened candidate genes that significantly contribute to seed lipid biosynthesis. We also analyzed key gene families that participate in LA and HSYA biosynthesis. Additionally, we re-sequenced 220 safflower lines and carried out a genome-wide association study using high-quality SNP data for eight agronomic traits. We identified SNPs related to important traits in safflower. Besides, the candidate gene HH_034464 (CtCGT1) was shown to be involved in the biosynthesis of HSYA. Overall, we provide a high-quality reference genome and elucidate the genetic basis of LA and HSYA biosynthesis in safflower. This vast amount of data will benefit further research for functional gene mining and breeding in safflower.
International Criminal Court Standards in a Context of Transitional Justice
Authors: Gutiérrez-Rodríguez Carlos 
Published: September 2023

Abstract
On October 2021, Colombia and the Office of the Prosecutor (OTP) of the International Criminal Court (ICC) signed a Cooperation Agreement that closed the preliminary examination opened in 2004. This is the first agreement of its kind. This article analyses the evolution of the OTP’s reasoning in considering whether a state has genuinely administered justice in a transitional context. To do so, it chronologically analyses the Colombian case, which is the first peace process in the world developed entirely under the continued scrutiny of the ICC. Furthermore, the Colombian situation was the ICC’s most extended preliminary examination, influencing in turn, the transitional justice outcomes as well as the position of the OTP. The Cooperation Agreement offers, therefore, an outstanding opportunity to analyse from a practical point of view, debates that have been predominantly theoretical and will have future consequences elsewhere.
Carbohydrate or Electrolyte Rehydration Recovers Plasma Volume but Not Post-immersion Performance Compared to Water After Immersion Diuresis
Authors: Wheelock Courtney E , Lavoie Elizabeth M , Stooks Jocelyn , Schwob Jacqueline , Hess Hayden W , Pryor Riana R , Hostler David 
Published: September 2023

ABSTRACT

Introduction
We tested the hypothesis that a carbohydrate (CHO: 6.5%) or carbohydrate–electrolyte (CHO + E: 6.5% + 50 mmol/L NaCl) drink would better recover plasma volume (PV) and exercise performance compared to water (H2O) after immersion diuresis.

Methods
Twelve men (24 ± 2 years; 82.4 ± 15.5 kg; and V̇O2max: 49.8 ± 5.1 mL · kg−1 · min−1) completed four experimental visits: a no-immersion control (CON) and three 4-h cold-water (18.0 °C) immersion trials (H2O, CHO, and CHO + E) followed by exercise in a warm environment (30 °C, 50% relative humidity). The exercise was a 60-minute loaded march (20.4 kg; 55% VO2max) followed by a 10-minute intermittent running protocol. After immersion, subjects were rehydrated with 100% of body mass loss from immersion diuresis during the ruck march. PV is reported as a percent change after immersion, after the ruck march, and after the intermittent running protocol. The intermittent running protocol distance provided an index of exercise performance. Data are reported as mean ± SD.

Results
After immersion, body mass loss was 2.3 ± 0.7%, 2.3 ± 0.5%, and 2.3 ± 0.6% for H2O, CHO, and CHO + E. PV loss after immersion was 19.8 ± 8.5% in H2O, 18.2 ± 7.0% in CHO, and 13.9 ± 9.3% in CHO + E, which was reduced after the ruck march to 14.7 ± 4.7% (P = .13) in H2O, 8.8 ± 8.3% (P &lt; .01) in CHO, and 4.4 ± 10.9% (P = .02) in CHO + E. The intermittent running protocol distance was 1.4 ± 0.1 km in CON, 1.4 ± 0.2 km in H2O, 1.4 ± 0.1 km in CHO, and 1.4 ± 0.2 km in CHO + E (P = .28).

Conclusions
Although CHO and CHO + E better restored PV after immersion, post-immersion exercise performance was not augmented compared to H2O, highlighting that fluid replacement following immersion diuresis should focus on restoring volume lost rather than fluid constituents.
Star clusters in tidal debris
Authors: Rodruck Michael , Charlton Jane , Borthakur Sanchayeeta , Chitre Aparna , Durrell Patrick R , Elmegreen Debra , English Jayanne , Gallagher Sarah C , Gronwall Caryl , Knierman Karen , Konstantopoulos Iraklis , Li Yuexing , Maji Moupiya , Mullan Brendan , Trancho Gelys , Vacca William 
Published: September 2023

ABSTRACT
We present results of a Hubble Space Telescope (HST) UBVI-band study of star clusters in tidal tails, using new WFC3 and ACS imaging to complement existing WFPC2 data. We survey 12 tidal tails across seven merging systems, deriving ages and masses for 425 star cluster candidates (SCCs). The stacked mass distribution across all systems follows a power law of the form dN/dM ∝ Mβ, with β = −2.02 ± 0.15, consistent with what is seen in other star-forming environments. GALEX and Swift UV imaging provide star formation rates (SFRs) for our tidal tails, which when compared with ages and masses of our SCCs, allows for a determination of the cluster formation efficiency (CFE). We find the CFE increases with increasing SFR surface density, matching the theoretical model. We confirm this fit down at SFR densities lower than previously measured (log ΣSFR (M⊙ yr−1 kpc−2) ≈ −4.2), as related to the CFE. We determine the half-light radii for a refined sample of 57 SCCs with our HST WFC3 and ACS imaging, and calculate their dynamical age, finding the majority of them to be gravitationally bound. We also provide evidence of only low-mass (&lt;104 M⊙) cluster formation in our nearest galaxy, NGC 1487, consistent with the theory that this system is a dwarf merger.
Thermal self-similar disc winds: transonic nature
Authors: Fukue J 
Published: September 2023

ABSTRACT
Thermally driven two-dimensional disc winds are examined under the fully self-similar treatment, focusing the attention on the transonic nature. In the spherical potential, such as point-mass and logarithmic ones, the usual transonic solutions cannot be constructed, because the critical conditions themselves do not exist. That is, the flow can reach the sonic point in the polar direction, while there is no gravitational force in the polar direction, and the regularity condition does not hold. In the non-spherical potential, such as the Mestel self-gravitating one, the gravity works in the polar direction, and therefore, there are critical points in the flow. However, the usual transonic solutions do not exist, since the topology of the critical points is always centre (O-type). Hence, in the fully self-similar disc winds, the usual transonic solutions passing through the critical points do not exist, at least for typical cases. Instead, the new-type wind solutions are found in the point-mass case. In contrast to the usual transonic flows, the new-type solutions are continuously accelerated along the streamline by the thermal pressure, and eventually become supersonic in the streamline direction without passing through the critical points. These new-type solutions are possible, when the density distribution is centrally concentrated, and when the initial subsonic velocity is not so large to avoid singularities.
Uric acid and diabetes mellitus: an update
Authors: Singh Shailendra K , Singh Rina , Singh Santosh K , Iquebal Mir A , Jaiswal Sarika , Rai Pradeep K 
Published: September 2023

Abstract
The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid–lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.
Hispanic Men’s Earnings Mobility Across Immigrant Generations: Estimates Using Tax Records
Authors: Villarreal Andrés , Tamborini Christopher R 
Published: September 2023

Abstract
Whether immigrants and their descendants are catching up socioeconomically with the rest of society is a fundamental question in the study of immigrant assimilation. In this paper, we examine the progress that Hispanic immigrant men make catching up with the earnings of later-generation Whites across generations. We rely on data from multiple years of the Current Population Survey linked with individuals’ tax earnings. This unique dataset allows us to overcome some important limitations of previous studies that employ a synthetic generation approach in which individuals born approximately one generation earlier are used as proxies for actual parents. Our matching strategy also enables us to identify the exact third generation and evaluate the contribution of ethnic attrition to estimates of intergenerational mobility. Second-generation Hispanic men are found to experience lower mobility than later-generation Whites for most values of parental earnings. However, their lower mobility can be explained by their immigrant parents’ lower education levels. In contrast, third-generation Hispanic men experience lower mobility even after accounting for parental education and ethnic attrition. This finding is consistent with a stalling or reversal in the socioeconomic progress of Hispanics beyond the second generation.
Alternatives for purposeful stewardship and wealth planning in Canada
Authors: Cross Pamela 
Published: September 2023

Abstract
There has been a global shift in client demands from tax-focused transactional planning to planning which accommodates using family wealth to address social and community purposes. These purposes may not be limited to charitable purposes or restricted to a geographic region. Stewardship structures are being used in new ways, and new structures are being introduced to accommodate these client needs. The author discusses the Canadian landscape and how Canadian laws may accommodate (or not) such stewardship models.1