bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of CYP2D6 pharmacogenetic phenotype and phenoconversion on serum concentrations of antidepressants and antipsychotics: a retrospective cohort study
Authors: Scherf-Clavel Maike , Frantz Amelie , Eckert Andreas , Weber Heike , Unterecker Stefan , Deckert Jürgen , Reif Andreas , Hahn Martina 
Published: May 2023

Abstract
Background
Pharmacogenetics (PGx), especially in regard to CYP2D6, is gaining more importance in routine clinical settings. Including phenoconversion effects (PC) in result interpretation could maximize its potential benefits. However, studies on genetics of pharmacokinetic genes including the functional enzyme status are lacking.

Aim
The retrospective analyses of clinical routine data aimed to investigating how the CYP2D6 functional enzyme status affects serum concentrations and metabolite-to-parent ratios of seven common psychotropic drugs and allows an evaluation of the relevance of this information for patient care.

Method
Two patient cohorts (total n = 316; 44.2 ± 15.4 years) were investigated for the CYP2D6 functional enzyme status and its associations with drug exposure and metabolism of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone and quetiapine.

Results
We found an increase in intermediate and poor metabolizers, as well as a decrease in normal metabolizers of CYP2D6 when including PC. Moreover, we found associations between amitriptyline exposure with the phenoconversion-corrected activity score of CYP2D6 (Spearman correlation; p = 0.03), and risperidone exposure with CYP2D6 functional enzyme status (Kruskal–Wallis test; p = 0.01), as well as between metabolite-to-parent ratio of venlafaxine and risperidone with CYP2D6 functional enzyme status (Kruskal–Wallis test; p < 0.001; p = 0.05).

Conclusion
The data stress the relevance of PC-informed PGx in psychopharmacological treatment and suggest that PC should be included in PGx result interpretation when PGx is implemented in routine clinical care, especially before initiating amitriptyline- or risperidone-treatment, to start with a dose adequate to the respective CYP2D6 functional enzyme status. Moreover, PGx and therapeutic drug monitoring should be used complementary but not alternatively.
Laser Treatment of Pilonidal Disease — Immediate and Mid-term Results
Authors: Nuutinen Henrik , Savikkomaa Elina , Tyrväinen Emmi , Myllykangas Heidi 
Published: May 2023

AbstractDifferent forms of treatment of pilonidal disease include traditional open surgery with or without flap reconstruction, phenolization, and laser treatment. However, no significantly large series have been published about the laser method. This case series analysis consisted of 69 consecutive pilonidal disease patients, who were operated upon with a Fistula-tract laser Closure in the plastic surgery department of a single academic teaching hospital between August 2019 and December 2021. The follow-up was done by phone at 2 weeks and 4 weeks. The outpatient clinic follow-ups were at 6 weeks and 6 months postoperatively. The mean number of sick leave days was 6.2 ± 8.9 days. The mean number of outpatient clinic visits (including phone calls) was 3.4 ± 3.9. The mean secretion time was 22.1 ± 20.3 days. During the follow-up, 54 (81.8%) patients wounds healed. Eight (12.1%) patients had postoperative wound infection. There were no other complications. The mean follow-up time was 15.3 ± 7.7 months. Laser treatment for sinus pilonidal is promising and minimally invasive procedure. The procedure can be performed under local anesthesia. A re-operation comes into question if the operation area does not heal in the primary operation.
Discovery of novel anticancer candidates based on a combination strategy of synthesis, characterization, biological activity evaluation, consensus docking and molecular modeling
Authors: Atlam Faten M. , Hekal Hend A. 
Published: May 2023

AbstractThrough the Kabachnic-Fields three-component reaction of 3(2-amino-acetyl)-quinazolin-4(3H)-one, compound III, various aromatic aldehydes, triphenyl phosphite, and lithium perchlorate as Lewis acid catalyst, new α-amino phosphonates molecules, IVa-f have been produced in a high yield. FT-IR, 1H-NMR, elemental analysis, and mass spectral data were used to determine the structures of the newly synthesized chemicals. Examined phosphonates, Iva–f, have been tested for their in vitro anticancer effects on the five cell lines HePG-2, MCF-7, Hela, HCT-116, PC-3, and normal cell, WI-38. Newly synthesized compounds' antioxidant activities were also covered. The novel-created α-amino phosphonate compounds have been evaluated on six cell lines and exhibit good anti-proliferative properties. The IVc molecule is the most effective antioxidant and anticancer candidate. Utilizing DFT/B3LYP/6-311G (d, p) method, the electronic and geometric characteristics derived from the stable structure of the studied compounds were examined. Additionally, there are outcomes for HOMO–LUMO, molecule electrostatic potential, and quantum chemical parameters. The stability of the most active phosphonate molecule, IVc, is attributed to hyper-conjugative interactions and charge delocalization. This was investigated using NBO analysis. Theoretical FT-IR and 1H-NMR measurements were applied to demonstrate the relationship between theory and experiment. An excellent concurrence between experimental and theoretical data was discovered. A docking simulation study was applied to forecast the inhibitory mode of action of the most active substance inside the cavity of estrogen receptor-positive (ER +) MCF-7 breast cancer.
Designing a deep-tech venture builder to address grand challenges and overcome the valley of death
Authors: Romme A. Georges L. , Bell John , Frericks Guus 
Published: May 2023

AbstractA vital problem of the European economy has long been its limited capacity to transform technological inventions and breakthroughs into successful new companies that help solve grand challenges in, for example, climate change, energy production, and poverty. Various measures and initiatives addressing this problem have not yet resulted in increasing numbers of successful ventures overcoming the so-called valley of death, especially in the case of deep-tech innovations arising from technological breakthroughs in, for example, new materials, mechatronics, high-precision engineering, and photonics. In this paper, we adopt a design perspective on crafting a Deep-Tech Venture (DTV) builder that creates, supports, and develops new ventures arising from deep-tech breakthroughs accomplished in leading research institutes in Europe. This approach to building DTVs incorporates key elements of extant theories and tools in the field of entrepreneurship but also moves beyond the contemporary body of knowledge. As such, the DTV approach provides a comprehensive system for creating and scaling deep-tech ventures—the most complex and risky, yet most impactful breed of ventures. The DTV blueprint was implemented and further developed in a venture builder that sources technologies from leading research institutes, such as CERN and European Space Agency. The initial results are highly promising. The main contribution of this study involves a comprehensive system design for building deep-tech ventures that help solve the SDGs, one that is (a) grounded in the literature on technology sourcing, entrepreneurship, ecosystems, entrepreneurial finance, and talent acquisition and (b) tested in a major European venture builder.
Wine rankings and the Borda method
Authors: Barberà Salvador , Bossert Walter , Moreno-Ternero Juan D. 
Published: May 2023

AbstractWe propose to establish wine rankings using scores that depend on the differences between favorable and unfavorable opinions about each wine, according to the Borda rule. Unlike alternative approaches and specifications, this method is well-defined even if the panelists’ quality relations are not required to exhibit demanding properties such as transitivity or acyclicity. As an illustration, we apply the method to rank wines assessed by different experts and compare the resulting ranking with that obtained according to Condorcet's method of majority voting.
Transcriptome sequencing analysis revealing the potential mechanism of seed germination in Pulsatilla chinensis (Bunge) Regel
Authors: Dong Yanjing , Zhang Shouwen , Qin Qian , Cai Yating , Wu Danyang 
Published: May 2023

AbstractPulsatilla chinensis (Bunge) Regel has been widely used in the pharmaceutical industry. With the deepening of clinical application, the research on its plant resources has attracted much attention. However, the underlying molecular mechanisms of distinct germination during Pulsatilla seed development are still mostly unknown. Therefore, in this study, four germination stages of P. chinensis seeds, with obvious differences in seed appearance traits, were used as materials. Transcriptome sequencing technology was used to analyse the molecular mechanisms of seed germination. A total of 27,601 differentially expressed genes (DEGs) (six different groups) were determined. KEGG enrichment analysis revealed that the up-regulated DEGs were enriched in phenylpropanoid biosynthesis, photosynthesis, photosynthesis–antenna proteins, plant hormone signal transduction, flavonoid biosynthesis and other pathways. A total of 87 DEGs was enriched in phytohormone signal transduction pathways, including auxin (25), abscisic acid (13), gibberellin (6), ethylene (9) and cytokinin (7). Furthermore, a protein–protein interaction network was constructed using these DEGs. Some DEGs were validated by qRT-PCR analysis. This comprehensive analysis provided basic information on the key genes of plant hormone signal transduction pathways involved in the seed germination process of P. chinensis (Bunge) Regel.
Linear optimization over homogeneous matrix cones
Authors: Tunçel Levent , Vandenberghe Lieven 
Published: May 2023

A convex cone is homogeneous if its automorphism group acts transitively on the interior of the cone. Cones that are homogeneous and self-dual are called symmetric. Conic optimization problems over symmetric cones have been extensively studied, particularly in the literature on interior-point algorithms, and as the foundation of modelling tools for convex optimization. In this paper we consider the less well-studied conic optimization problems over cones that are homogeneous but not necessarily self-dual.We start with cones of positive semidefinite symmetric matrices with a given sparsity pattern. Homogeneous cones in this class are characterized by nested block-arrow sparsity patterns, a subset of the chordal sparsity patterns. Chordal sparsity guarantees that positive define matrices in the cone have zero-fill Cholesky factorizations. The stronger properties that make the cone homogeneous guarantee that the inverse Cholesky factors have the same zero-fill pattern. We describe transitive subsets of the cone automorphism groups, and important properties of the composition of log-det barriers with the automorphisms.Next, we consider extensions to linear slices of the positive semidefinite cone, and review conditions that make such cones homogeneous. An important example is the matrix norm cone, the epigraph of a quadratic-over-linear matrix function. The properties of homogeneous sparse matrix cones are shown to extend to this more general class of homogeneous matrix cones.We then give an overview of the algebraic theory of homogeneous cones due to Vinberg and Rothaus. A fundamental consequence of this theory is that every homogeneous cone admits a spectrahedral (linear matrix inequality) representation.We conclude by discussing the role of homogeneous structure in primal–dual symmetric interior-point methods, contrasting this with the well-developed algorithms for symmetric cones that exploit the strong properties of self-scaled barriers, and with symmetric primal–dual methods for general convex cones.
Temporal and Spatial Synchronicity in West Nile Virus Cases Along the Central Flyway, USA
Authors: Hort H. M. , Ibaraki M. , Schwartz F. W. 
Published: May 2023

AbstractThis study of West Nile virus (WNV) examined the possibility of avian transmission to explain synchronicity in the year‐to‐year variability of WNV case numbers from Texas northward to the Dakotas, and reasons for the large case numbers on the northern Great Plains. We determined correlation coefficients between annual disease incidence per 100,000 people among states within the Great Plains Region, as well as the Central Flyway. There was spatial and temporal synchronicity, as evidenced by Pearson “r,” with values along the core of the Central Flyway (Oklahoma, Kansas, Nebraska, and South Dakota) varying between 0.69 and 0.79. Correlations for North Dakota (r = 0.6), however, were affected by local conditions. The concept of relative amplification is helpful in explaining why northerly states along the Central Flyway have larger annual case numbers per 100,000 than Texas but preserve the temporal signal. States differed in their capacity for amplifying the temporal signal in case numbers. For example, Nebraska, South Dakota, and North Dakota case numbers were commonly amplified relative to Texas, with Oklahoma and Kansas deamplified. Relative amplification factors for all states increased as a function of increasing case numbers in Texas. Thus, increased numbers of initially infected birds in Texas likely led to the rapid intensification of the zoonotic cycle as compared to more typical years. The study also confirmed the importance of winter weather in locally modulating disease cases. North Dakota appeared most impacted by these factors to the extent of reducing WNV case numbers in colder years and years with deep snow.
Intermediate Infrared Spectroscopy of Pyroxene: Determination of Ca‐Mg‐Fe Composition in the 4–8 Micron Wavelength Range
Authors: Kremer Christopher H. , Mustard John. F. , Pieters Carlé M. 
Published: May 2023

AbstractAlthough pyroxene has been detected remotely across the Solar System, limited information is available from infrared remote sensing about the Mg‐Fe composition of pyroxene, and distinguishing between augite (20 < CaSiO3 < 45) and diopside‐hedenbergite (CaSiO3 > 45) remains challenging. The characteristics of pyroxene in the intermediate infrared range (4–8 μm), meanwhile, have not been documented. Using reflectance spectra of 72 samples ranging across the pyroxene quadrilateral, we investigate the effect of variations in Mg# (Mg/[Mg + Fe] × 100) and Ca‐content on the positions of strong and well‐defined spectral bands at ∼5.1 and ∼5.3 μm in high‐Ca pyroxene and ∼5.2 in low‐Ca pyroxene. We find that the 5.1, 5.2, and 5.3 μm bands move to shorter wavelengths as Mg# increases, whereas Ca‐content does not significantly affect the positions of these bands, enabling the determination of pyroxene Mg# directly from band positions alone. We also find that the ∼5.1 μm band is significantly more distinctive in diopside‐hedenbergite and the ∼5.3 μm band significantly more so in augite. Therefore, the 5.1, 5.2, and 5.3 μm spectral bands enable discrimination among diopside‐hedenbergite, low‐Ca pyroxene, and augite. Additionally, the 5.1, 5.2, and 5.3 μm bands enable direct determination of Mg# of diopside‐hedenbergite, low‐Ca pyroxene, and augite within ±23, ±10, and ±29 mol% Mg‐Fe, respectively.
TMS-EEG perturbation biomarkers for Alzheimer’s disease patients classification
Authors: Tăuƫan Alexandra-Maria , Casula Elias P. , Pellicciari Maria Concetta , Borghi Ilaria , Maiella Michele , Bonni Sonia , Minei Marilena , Assogna Martina , Palmisano Annalisa , Smeralda Carmelo , Romanella Sara M. , Ionescu Bogdan , Koch Giacomo , Santarnecchi Emiliano 
Published: May 2023

AbstractThe combination of TMS and EEG has the potential to capture relevant features of Alzheimer’s disease (AD) pathophysiology. We used a machine learning framework to explore time-domain features characterizing AD patients compared to age-matched healthy controls (HC). More than 150 time-domain features including some related to local and distributed evoked activity were extracted from TMS-EEG data and fed into a Random Forest (RF) classifier using a leave-one-subject out validation approach. The best classification accuracy, sensitivity, specificity and F1 score were of 92.95%, 96.15%, 87.94% and 92.03% respectively when using a balanced dataset of features computed globally across the brain. The feature importance and statistical analysis revealed that the maximum amplitude of the post-TMS signal, its Hjorth complexity and the amplitude of the TEP calculated in the window 45–80 ms after the TMS-pulse were the most relevant features differentiating AD patients from HC. TMS-EEG metrics can be used as a non-invasive tool to further understand the AD pathophysiology and possibly contribute to patients’ classification as well as longitudinal disease tracking.
Evaluation of administrative case definitions for hypertension in Canadian children
Authors: Dart Allison , Singer Alexander , Chanchlani Rahul , Ferguson Thomas , Tangri Navdeep , Zappitelli Michael 
Published: May 2023

AbstractHypertension is increasing in children and warrants disease surveillance. We therefore sought to evaluate the validity of case definitions to identify pediatric hypertension in administrative healthcare data. Cases of hypertension in children 3–18 years of age were identified utilizing blood pressures recorded in the Manitoba Primary Care Research Network (MaPCReN) electronic medical record from 2014 to 2016. Prevalence of hypertension and associated clinical characteristics were determined. We then evaluated the validity of 18 case definitions combining outpatient physician visits (ICD9CM codes), hospital claims (ICD9CM/ICD10 codes) and antihypertensive use within 1–3 years of data housed at the Manitoba Centre for Health Policy. The MaPCReN database identified 241 children with hypertension and 4090 without (prevalence = 5.6%). The sensitivity of algorithms ranged between 0.18 and 0.51 and the specificity between 0.98 and 1.00. Pharmaceutical use increased the sensitivity of algorithms significantly. The algorithms with the highest sensitivity and area under the ROC curve were 1 or more hospitalization OR 1 or more physician claim OR 1 or more pharmaceutical record. Evaluating 2 years of data is recommended. Administrative data alone reflects diagnosis of hypertension with high specificity, but underestimate the true prevalence of this disease. Alternative data sources are therefore required for disease surveillance.
Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA)
Authors: Yanagimori Marcela , Fernandes Mariana D. , Garcia Michelle L. , Scudeller Paula G. , Carvalho Carlos R. R. , Edwards Bradley , Lorenzi-Filho Geraldo , Genta Pedro R. 
Published: May 2023

AbstractInsomnia and obstructive sleep apnea (OSA) are common sleep disorders and frequently coexist (COMISA). Arousals from sleep may be a common link explaining the frequent comorbidity of both disorders. Respiratory arousal threshold (AT) is a physiologic measurement of the level of respiratory effort to trigger an arousal from sleep. The impact of COMISA on AT is not known. We hypothesized that a low AT is more common among COMISA than among patients with OSA without insomnia. Participants referred for OSA diagnosis underwent a type 3 sleep study and answered the insomnia severity index (ISI) questionnaire and the Epworth sleepiness scale. Participants with an ISI score ≥ 15 were defined as having insomnia. Sleep apnea was defined as an apnea hypopnea index (AHI) ≥ 15 events/h. Low AT was determined using a previously validated score based on 3 polysomnography variables (AHI, nadir SpO2 and the frequency of hypopneas). OSA-only (n = 51) and COMISA (n = 52) participants had similar age (61[52–68] vs 60[53–65] years), body-mass index (31.3[27.7–36.2] vs 32.2[29.5–38.3] kg/m2) and OSA severity (40.2[27.5–60] vs 37.55[27.9–65.2] events/h): all p = NS. OSA-only group had significantly more males than the COMISA group (58% vs 33%, p = 0.013. The proportion of participants with a low AT among OSA-only and COMISA groups was similar (29 vs 33%, p = NS). The similar proportion of low AT among COMISA and patients with OSA suggests that the respiratory arousal threshold may not be related to the increased arousability of insomnia.
Vacuolar control of stomatal opening revealed by 3D imaging of the guard cells
Authors: Mirasole Filippo Maria , Nastasi Sara Paola , Cubero-Font Paloma , De Angeli Alexis 
Published: May 2023

AbstractLand plants regulate their photosynthesis and water transpiration by exchanging gases (CO2 and H2Ovapour) with the atmosphere. These exchanges take place through microscopic valves, called stomata, on the leaf surface. The opening of the stomata is regulated by two guard cells that actively and reversibly modify their turgor pressure to modulate the opening of the stomatal pores. Stomatal function depends on the regulation of the ion transport capacities of cell membranes as well as on the modification of the subcellular organisation of guard cells. Here we report how the vacuolar and cytosolic compartments of guard cells quantitatively participate in stomatal opening. We used a genetically encoded biosensor to visualise changes in ionic concentration during stomatal opening. The 3D reconstruction of living guard cells shows that the vacuole is the responsible for the change in guard cell volume required for stomatal opening.
A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion
Authors: Paranjape Neha , Lin Yu-Hsiu T. , Flores-Ramirez Quetzal , Sarin Vishesh , Johnson Amanda Brooke , Chu Julia , Paredes Mercedes , Wiita Arun P. 
Published: May 2023

Abstract22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb “A-D” deletion at this locus. The ~ 1.5 Mb “A-B” deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 “A-B” deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.