bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic selection strategies for clonally propagated crops
Authors: Werner Christian R. , Gaynor R. Chris , Sargent Daniel J. , Lillo Alessandra , Gorjanc Gregor , Hickey John M. 
Published: March 2023

AbstractKey messageFor genomic selection in clonally propagated crops with diploid (-like) meiotic behavior to be effective, crossing parents should be selected based on genomic predicted cross-performance unless dominance is negligible.AbstractFor genomic selection (GS) in clonal breeding programs to be effective, parents should be selected based on genomic predicted cross-performance unless dominance is negligible. Genomic prediction of cross-performance enables efficient exploitation of the additive and dominance value simultaneously. Here, we compared different GS strategies for clonally propagated crops with diploid (-like) meiotic behavior, using strawberry as an example. We used stochastic simulation to evaluate six combinations of three breeding programs and two parent selection methods. The three breeding programs included (1) a breeding program that introduced GS in the first clonal stage, and (2) two variations of a two-part breeding program with one and three crossing cycles per year, respectively. The two parent selection methods were (1) parent selection based on genomic estimated breeding values (GEBVs) and (2) parent selection based on genomic predicted cross-performance (GPCP). Selection of parents based on GPCP produced faster genetic gain than selection of parents based on GEBVs because it reduced inbreeding when the dominance degree increased. The two-part breeding programs with one and three crossing cycles per year using GPCP always produced the most genetic gain unless dominance was negligible. We conclude that (1) in clonal breeding programs with GS, parents should be selected based on GPCP, and (2) a two-part breeding program with parent selection based on GPCP to rapidly drive population improvement has great potential to improve breeding clonally propagated crops.
Correlates of chronic depression in the general population: results from the CoLaus|PsyCoLaus study
Authors: Ambresin Gilles , Strippoli Marie-Pierre F. , Vandeleur Caroline L. , de Roten Yves , Despland Jean-Nicolas , Preisig Martin 
Published: March 2023

Abstract
Purpose
Previous population-based studies have partially provided inconsistent results regarding the co-variates of chronic depression, which were likely to be attributable to methodological limitations. The present paper that compared people with chronic major depressive disorder (MDD), non-chronic MDD and no mood disorder in the community focused on specific atypical and melancholic depression symptoms and subtypes of MDD, family history (FH) of mood disorders, measured physical cardio-vascular risk factors (CVRF), personality traits, coping style and adverse life-events.

Methods
Data stemmed from a population-based cohort including 3618 participants (female 53%, n=1918; mean age 50.9 years, s.d. 8.8 years). Among them 563 had a lifetime history of chronic MDD, 1060 of non-chronic MDD and 1995 of no mood disorder. Diagnostic and FH information were elicited through semi-structured interviews, CVRF were assessed through physical investigations.

Results
The major findings were that chronic MDD was associated with increase in appetite/weight and suicidal ideation/attempts during the most severe episode, higher exposure to life-events in adulthood, higher levels of neuroticism, lower levels of extraversion and lower levels of informal help-seeking behavior but less frequent FH of MDD compared to non-chronic MDD.

Conclusion
Chronic MDD is associated with a series of potential modifiable risk factors which are accessible via psychotherapeutic approaches that may improve the course of chronic MDD.
Integrated topology and controller optimization using the Nyquist curve
Authors: Delissen Arnoud , van Keulen Fred , Langelaar Matthijs 
Published: March 2023

AbstractThe design of high-performance mechatronic systems is very challenging, as it requires delicate balancing of system dynamics, the controller, and their closed-loop interaction. Topology optimization provides an automated way to obtain systems with superior performance, although extension to simultaneous optimization of both topology and controller has been limited. To allow for topology optimization of mechatronic systems for closed-loop performance, stability, and disturbance rejection (i.e. modulus margin), we introduce local approximations of the Nyquist curve using circles. These circular approximations enable simple geometrical constraints on the shape of the Nyquist curve, which is used to characterize the closed-loop performance. Additionally, a computationally efficient robust formulation is proposed for topology optimization of dynamic systems. Based on approximation of eigenmodes for perturbed designs, their dynamics can be described with sufficient accuracy for optimization, while preventing the usual threefold increase of additional computational effort. The designs optimized using the integrated approach have significantly better performance (up to 350% in terms of bandwidth) than sequentially optimized systems, where eigenfrequencies are first maximized and then the controller is tuned. The proposed approach enables new directions of integrated (topology) optimization, with effective control over the Nyquist curve and efficient implementation of the robust formulation.
Smoothing inertial method for worst-case robust topology optimization under load uncertainty
Authors: Nishioka Akatsuki , Kanno Yoshihiro 
Published: March 2023

AbstractWe consider a worst-case robust topology optimization problem under load uncertainty, which can be formulated as a minimization problem of the maximum eigenvalue of a symmetric matrix. The objective function is nondifferentiable where the multiplicity of maximum eigenvalues occurs. Nondifferentiability often causes some numerical instabilities in an optimization algorithm such as oscillation of the generated sequence and convergence to a non-optimal point. We use a smoothing method to tackle these issues. The proposed method is guaranteed to converge to a point satisfying the first-order optimality condition. In addition, it is a simple first-order optimization method and thus has low computational cost per iteration even in a large-scale problem. In numerical experiments, we show that the proposed method suppresses oscillation and converges faster than other existing methods.
Effects of DPTQ, a novel positive allosteric modulator of the dopamine D1 receptor, on spontaneous eye blink rate and spatial working memory in the nonhuman primate
Authors: Castner Stacy A. , Zhang Linli , Yang Charles R. , Hao Junliang , Cramer Jeffrey W. , Wang Xushan , Bruns Robert F. , Marston Hugh , Svensson Kjell A. , Williams Graham V. 
Published: March 2023

Abstract
Rationale
Dopamine (DA) signaling through the D1 receptor has been shown to be integral to multiple aspects of cognition, including the core process of working memory. The discovery of positive allosteric modulators (PAMs) of the D1 receptor has enabled treatment modalities that may have alternative benefits to orthosteric D1 agonists arising from a synergism of action with functional D1 receptor signaling.

Objectives
To investigate this potential, we have studied the effects of the novel D1 PAM DPTQ on a spatial delayed response working memory task in the rhesus monkey. Initial studies indicated that DPTQ binds to primate D1R with high affinity and selectivity and elevates spontaneous eye blink rate in rhesus monkeys in a dose-dependent manner consistent with plasma ligand exposures and central D1activation.

Results
Based on those results, DPTQ was tested at 2.5 mg/kg IM in the working memory task. No acute effect was observed 1 h after dosing, but performance was impaired 48 h later. Remarkably, this deficit was immediately followed by a significant enhancement in cognition over the next 3 days. In a second experiment in which DPTQ was administered on days 1 and 5, the early impairment was smaller and did not reach statistical significance, but statistically significant enhancement of performance was observed over the following week. Lower doses of 0.1 and 1.0 mg/kg were also capable of producing this protracted enhancement without inducing any transient impairment.

Conclusions
DPTQ exemplifies a class of D1PAMs that may be capable of providing long-term improvements in working memory.
Optimization of FK-506 production in Streptomyces tsukubaensis by modulation of Crp-mediated regulation
Authors: Schulz Susann , Sletta Håvard , Fløgstad Degnes Kristin , Krysenko Sergii , Williams Alicia , Olsen Silje Malene , Vernstad Kai , Mitulski Agnieszka , Wohlleben Wolfgang 
Published: March 2023

Abstract

FK-506 is a potent immunosuppressive macrocyclic polyketide with growing pharmaceutical interest, produced by Streptomyces tsukubaensis. However, due to low levels synthesized by the wild-type strain, biotechnological production of FK-506 is rather limited. Optimization strategies to enhance the productivity of S. tsukubaensis by means of genetic engineering have been established. In this work primarily global regulatory aspects with respect to the FK-506 biosynthesis have been investigated with the focus on the global Crp (cAMP receptor protein) regulator. In expression analyses and protein-DNA interaction studies, the role of Crp during FK-506 biosynthesis was elucidated. Overexpression of Crp resulted in two-fold enhancement of FK-506 production in S. tsukubaensis under laboratory conditions. Further optimizations using fermentors proved that the strategy described in this study can be transferred to industrial scale, presenting a new approach for biotechnological FK-506 production.

Key Points
• The role of the global Crp (cAMP receptor protein) regulator for FK-506 biosynthesis in S. tsukubaensis was demonstrated
• Crp overexpression in S. tsukubaensis was applied as an optimization strategy to enhance FK-506 and FK-520 production resulting in two-fold yield increase
Scaphoid kinematics in scapholunate instability: a dynamic CT study
Authors: Amarasooriya Melanie , Al-Dirini Rami , Bryant Kimberley , Bain Gregory Ian 
Published: March 2023

Abstract
Objective
The scaphoid is proposed to be driven by the distal carpal row in scapholunate instability (SLI) as it is dissociated from the proximal row. The aim of this study was to describe the 6 degrees of freedom kinematics of the scaphoid using dynamic CT in the normal and SLI wrists. We hypothesised that the SLI scaphoid would demonstrate kinematic evidence conforming to distal row motion.

Materials and methods
We studied dynamic CT scans of 17 SLI and 17 normal wrists during ulnar to radial deviation and extension to flexion. The radio-scaphoid angles in three anatomic planes were calculated in the wrist neutral position and during wrist motion. The centroid position was also calculated in the wrist neutral position and during wrist motion. The scapho-capitate motion index (SCI) was calculated as a ratio between the scaphoid and the capitate motion.

Results
In the neutral position of the wrist, the SLI scaphoid was flexed, internally rotated, and radially translated compared to the normal scaphoid. During wrist motion, the SLI scaphoid had more ‘in-plane’ motion and less ‘out-of-plane’ motion with a higher SCI during wrist neutral to radial deviation and extension to neutral.

Conclusion
We have described the malalignment of the SLI scaphoid in the neutral position of the wrist and 6 degrees of freedom kinematics during wrist motion of the SLI scaphoid compared to the normal. The SLI scaphoid conformed more to the distal row motion than the normal scaphoid. This information may help define the surgical reconstruction techniques for SLI.
Do female bluethroats without extra-pair offspring have more MHC-compatible social mates?
Authors: Rekdal Silje L. , Anmarkrud Jarl Andreas , Lifjeld Jan T. , Johnsen Arild 
Published: March 2023

Abstract
Genes of the major histocompatibility complex (MHC) are crucial for adaptive immunity in jawed vertebrates, and theory predicts that there should be mate choice for optimizing MHC constitution in the offspring. In a previous study, we demonstrated a non-random female choice of extra-pair males in the bluethroat (Luscinia svecica), yielding offspring that was closer to an intermediate MHC class II (MHCII) allele count than their within-pair halfsiblings. The present study tests whether social pairs with only within-pair young (WPY) in their brood, in the same study population, had a combined MHC-constitution closer to a presumed intermediate optimum, than social pairs with extra-pair young (EPY), with a corresponding pattern in their offspring. As expected, we found that WPY from pure WPY-broods were more MHC-optimal than WPY from mixed broods, but only in broods of young (second year) males. Correspondingly, there was a tendency for social pairs with only WPY in their brood to be more MHC-compatible than social pairs with EPY in their brood, when the male was young. Older bluethroat males have considerably larger testes than young males, and their higher sperm competitiveness could help them secure paternity in their own brood, also when they are not MHC-compatible. In other words, in the sexual conflict over paternity, females may be more likely to realise their preference for a MHC-compatible mate when paired to a young male. As a possible fitness indicator, immune responsiveness to an injected antigen (PHA) was elevated for offspring closer to “the golden mean” in MHCII allele count.

Significance statement
This study contributes to our understanding of MHC-based mate choice in extra-pair mating systems, by showing that female bluethroats (Luscinia svecica) with an MHCII-compatible social mate tend to have no extra-pair young in their brood, but only when the social male is young. This elucidates a possible sexual conflict, in which older social males are able to override female preferences and prevent other males from gaining paternity in their brood through higher sperm production. Studying systems in which extra-pair paternity occurs offers an insight into the genetic benefits of mate choice, as extra-pair males, in contrast to social males, generally contribute only sperm. Further, the strict and thorough genotyping scheme applied in this study enabled us to demonstrate a preference for “the golden mean” in MHC-diversity in a species with one of the highest MHC class II-diversity known to date.
Clinical significance of high-dose chemotherapy with autologous stem cell transplantation in the era of novel agents in patients older than 65 years with multiple myeloma
Authors: Sato Shuku , Tsunoda Shun , Kawahigashi Teiko , Kamata Wataru , Tamai Yotaro 
Published: March 2023

AbstractHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for symptomatic multiple myeloma (MM) in patients under 65 years of age. However, the performing of ASCT in older patients > 65 years without comorbidities or complications is controversial. Introduction of novel drugs, such as daratumumab, has improved the long-term survival of patients with MM who are ineligible for ASCT. This retrospective study aimed to evaluate the clinical significance of ASCT in older patients, even in the era of novel drugs. A total of 55 patients aged 65–74 years (15 ASCT recipients and 40 ASCT-ineligible patients) newly diagnosed with MM between March 2013 and October 2021 at our institution were analyzed in this study. There were no significant differences in the 3-year overall survival (84.6% vs. 90.6%, p = 0.72) and progression-free survival (PFS) (61.2% vs. 75.1%, p = 0.40) between ASCT recipients and ASCT-ineligible patients. There was also no significant difference in complete response (CR) with minimal residual disease (MRD)-negative rate between the two groups (27% vs. 33%, p = 1.0). Multivariate analysis showed that CR was an independent predictor of PFS (hazard ratio [HR], 0.26; 95% confidence interval, 0.08–0.76; p = 0.01). In this retrospective study, despite patients who were determined to be intolerant to ASCT, the non-ASCT group was non-inferior to the ASCT group in PFS and overall response rate. The results of this study confirm that the significance of ASCT is diminishing in patients 65 years of age and older because newer agents can achieve good responses without ASCT.
Separation of conjoined spinal cords in symmetrical pygopagus twins using intraoperative neuromonitoring: pearls and pitfalls
Authors: Mahmoud Mohamed Ashraf , Elshawady Sherif Bahaa , Korkar George H. , Hussein Samar M. , Elserry Tarek H. , Mahmoud Mohamed Wael S. 
Published: March 2023

Abstract
Pygopagus twin is a rare congenital malformation with a worldwide incidence of 1in 200,000. Few literature reports are published regarding the matter. In some cases, neuromonitoring is essential for safe surgical separation. We believe it is important to share our challenges and nuances in order to minimize obstacles one might encounter. We utilized neuromonitoring during our separation of both twins, and we planned a multidisciplinary approach and efficient communication system with the other teams in order to plan a successful, safe, and timely separation of the twins. We seek to highlight not our success but rather the obstacles and challenges we encountered during the separation of pygopagus twins in our institute using neuromonitoring for future reference.
On the role of wave climate temporal variability in bias correction of GCM-RCM wave simulations
Authors: Lira Loarca Andrea , Berg Peter , Baquerizo Asuncion , Besio Giovanni 
Published: March 2023

AbstractThis work presents the performance analysis of a multi-model ensemble of wave climate projections in the Mediterranean Sea against hindcast data. The wave projections were developed with the numerical model Wavewatch III forced by surface wind fields of 17 EURO-CORDEX GCM-RCMs providing time series of the main wave parameters on a 3-h and 10-km resolution. The performance of the wave GCM-RCM simulations during the baseline period (1979–2005) was assessed by means of the deterministic metrics RMSE and Bias. Different bias correction methodologies were analyzed by means of the application of the widespread Empirical Quantile Mapping method considering different time periods of significant wave height in order to analyze the ability of the bias-correcting methods to capture the different wave climate temporal scales ranging from storm events, monthly, seasonal and interannual variability. The results show that the use of the EQM method for the full-time series without taking into account other timescales, can lead to increased biases in some regions and seasons and that the use of time-dependent bias-correction techniques leads to an improved accurate characterization of biases considering the interannual temporal variability of significant wave height. More specifically the use of the EQM method for monthly data provides a good performance in capturing the correlation and interannual temporal variability of wave climate.
Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism
Authors: Agamia Naglaa Fathi , Sorror Osama Ahmed , Sayed Naglaa Mohamed , Ghazala Rasha Abdelmawla , Echy Sammar Mohamed , Moussa Doaa Helmy , Melnik Bodo Clemens 
Published: March 2023

AbstractHypoxia-inducible factor-1α (HIF-1α) is the master transcription factor of glycolysis, Th17 cell differentiation and suppression of regulatory T cells. In the skin and serum of patients with psoriasis vulgaris, increased expression of HIF-1α has been reported, whereas HIF-1α expression in the skin and serum of patients with hidradenitis suppurativa (HS) has not yet been studied. The objective of the study is to demonstrate is there a role for HIF-1α in the pathogenesis of hidradenitis suppurativa, and its relation to HS severity. Twenty patients suffering from hidradenitis suppurativa were included in the study. Punch biopsies were taken from lesional skin for the determination of HIF-1α expression by immunohistochemical staining, and HIF-1α gene expression by quantitative reverse transcription real time PCR. Quantification of HIF-1α protein concentration was done by enzyme-linked immunosorbent assay. Twenty socio-demographically cross-matched healthy volunteers served as controls. We found increased serum levels of HIF-1α. Literature-derived evidence indicates that the major clinical triggering factors of HS, obesity, and smoking are associated with hypoxia and enhanced HIF-1α expression. Pro-inflammatory cytokines such as tumor necrosis factor-$$a$$
a
via upregulation of nuclear factor $$\kappa$$
κ
B enhance HIF-1α expression. HIF-1α plays an important role for keratinocyte proliferation, especially for keratinocytes of the anagen hair follicle, which requires abundant glycolysis providing sufficient precursors molecules for biosynthetic pathways. Metformin via inhibition of mTORC1 as well as adalimumab attenuate HIF-1α expression, the key mediator between Th17-driven deviated immunity and keratinocyte hyperproliferation. In accordance with psoriasis, our study identifies HS as an HIF-1α-driven inflammatory skin disease and offers a new rationale for the prevention and treatment of HS by targeting HIF-1$$a$$
a
overexpression.
Comparative expression analysis of the Atoh7 gene regulatory network in the mouse and chicken auditory hindbrain
Authors: Saleh Ali Jason , Ahmed Yannis , Peters Lars-Oliver , Nothwang Hans Gerd 
Published: March 2023

AbstractThe mammalian and avian auditory brainstem likely arose by independent evolution. To compare the underlying molecular mechanisms, we focused on Atoh7, as its expression pattern in the mammalian hindbrain is restricted to bushy cells in the ventral cochlear nucleus. We thereby took advantage of an Atoh7 centered gene regulatory network (GRN) in the retina including upstream regulators, Hes1 and Pax6, and downstream targets, Ebf3 and Eya2. In situ hybridization demonstrated for the latter four genes broad expression in all three murine cochlear nuclei at postnatal days (P) 4 and P30, contrasting the restricted expression of Atoh7. In chicken, all five transcription factors were expressed in all auditory hindbrain nuclei at embryonic day (E) 13 and P14. Notably, all five genes showed graded expression in the embryonic nucleus magnocellularis (NM). Atoh7 was highly expressed in caudally located neurons, whereas the other four transcription factors were highly expressed in rostrally located neurons. Thus, Atoh7 shows a strikingly different expression between the mammalian and avian auditory hindbrain. This together with the consistent absence of graded expression of GRN components in developing mammalian nuclei provide the first molecular support to the current view of convergent evolution as a major mechanism in the amniote auditory hindbrain. The graded expression of five transcription factors specifically in the developing NM confirms this nucleus as a central organizer of tonotopic features in birds. Finally, the expression of all five retinal GRN components in the auditory system suggests co-options of genes for development of sensory systems of distinct modalities.