bluuebunny/crossref_metadata_2025_split huggingface dataset:
To Tweak or Not to Tweak. How Exploiting Flexibilities in Gene Set Analysis Leads to Overoptimism
Authors: Wünsch Milena , Sauer Christina , Herrmann Moritz , Hinske Ludwig Christian , Boulesteix Anne‐Laure 
Published: December 2024

ABSTRACTGene set analysis, a popular approach for analyzing high‐throughput gene expression data, aims to identify sets of genes that show enriched expression patterns between two conditions. In addition to the multitude of methods available for this task, users are typically left with many options when creating the required input and specifying the internal parameters of the chosen method. This flexibility can lead to uncertainty about the “right” choice, further reinforced by a lack of evidence‐based guidance. Especially when their statistical experience is scarce, this uncertainty might entice users to produce preferable results using a “trial‐and‐error” approach. While it may seem unproblematic at first glance, this practice can be viewed as a form of “cherry‐picking” and cause an optimistic bias, rendering the results nonreplicable on independent data. After this problem has attracted a lot of attention in the context of classical hypothesis testing, we now aim to raise awareness of such overoptimism in the different and more complex context of gene set analyses. We mimic a hypothetical researcher who systematically selects the analysis variants yielding their preferred results, thereby considering three distinct goals they might pursue. Using a selection of popular gene set analysis methods, we tweak the results in this way for two frequently used benchmark gene expression data sets. Our study indicates that the potential for overoptimism is particularly high for a group of methods frequently used despite being commonly criticized. We conclude by providing practical recommendations to counter overoptimism in research findings in gene set analysis and beyond.
Green Synchronous Spectrofluorimetric Method for Simultaneous Determination of Trifluridine and Tipiracil Used for Treatment of Colorectal Cancer in Pharmaceutical Products and Spiked Human Biological Fluids
Authors: Salem Hesham , Abdelgaleel Mahmoud , Emad Nadeen , Moftah Soheir E. , Samir Basmala , Hassan Esraa M. , Abdelaziz Amany 
Published: December 2024

ABSTRACTTrifluridine and tipiracil can now be determined simultaneously thanks to a novel, quick, sensitive, selective, environmentally friendly, and extremely sensitive approach. To determine the medications under study, the first derivative synchronous spectrofluorimetric technique was used. Trifluridine and tipiracil's first derivative amplitudes have been measured at their respective zero crossing points of 260 and 250 nm. The range of linearity was discovered to be of 5.0–30.0 ng mL−1 for each trifluridine and tipiracil. The limits of detection were found to be 0.834 and 0.376 ng mL−1, while the quantitation limits were 2.53 and 1.14 ng mL−1 for trifluridine and tipiracil, in respective order. The technique worked well for figuring out both medications in their lab‐made mixes in various dosage forms and in spiked human biological fluids (spiked human plasma and urine). The outcomes were contrasted with those of HPLC techniques used in comparison. We employed ethanol as a green solvent. Trifluridine and tipiracil can be ascertained with a sufficient level of precision and accuracy using the suggested procedure: AGREE and Eco‐scale. In comparison to HPLC procedures, the suggested method is inexpensive and straightforward.
New Shikimic Acid Derivatives From the Marine‐Derived Actinomycete Streptomyces sp. G666 and Their Antimicrobial Activities
Authors: Do Thi Quynh , Van Trinh Thi Thanh , Phi Thi Dao , Nguyen Thuy Linh , Vu Thi Quyen , Le Thi Hong Minh , Murphy Brian T. , Doan Thi Mai Huong , Pham Van Cuong 
Published: December 2024

ABSTRACTAnalysis of an antimicrobial extract from the agar‐based culture of the marine‐derived actinomycete Streptomyces sp. G666 led to the isolation of three new shikimic acid derivatives, streptomine A‐C (1–3), along with five known compounds (4–8). Their structures were established by their spectral data analyses, including MS and NMR. All the isolated compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Three new compounds 1–3 demonstrated selective antimicrobial activity against Gram‐positive Enterococcus faecalis with MIC values ranging from 32 to 64 µg/mL. Compound 3 exhibited the highest inhibitory effect against E. faecalis with an MIC value of 32 µg/mL. Compound 4 selectively inhibited Escherichia coli with an MIC value of 128 µg/mL. In addition, compounds 1–3 moderately inhibited the yeast Candida albicans with the same MIC value of 16 µg/mL. Unfortunately, most of isolated compounds were inactive against Gram‐negative bacteria E. coli, Pseudomonas aeruginosa, and Salmonella enterica.
Enantio‐Recognition and Charge Transfer Complex Formation Involving Tetrathiafulvalene‐Appended Chiral 1,2‐Cyclohexane‐Diamine: An Integrated Experimental and Theoretical Study
Authors: Ferrari Camilla , Bogdan Alexandra , Pop Flavia , Curto Cosimo , Carella Alberta , Rossella Francesco , Avarvari Narcis , Fontanesi Claudio 
Published: December 2024

ABSTRACTIn this work, we exploit the electronic features of tetrathiafulvalene (TTF) as a backbone in synthesizing chiral derivatives. The aim is to make use of TTF's well‐known and unique redox and semiconducting properties in the fields of enantio‐selective recognition and chiral charge transfer (CT) complex preparation, with the ultimate objective of obtaining devices with various potential applications, ranging from plasmonics to quantum computing. In particular, both cyclohexane‐bis (TTF‐amide)–based enantiomers 1‐(S,S) and 1‐(R,R), stable under an oxidation regime, have been selected, and under these conditions, the electrochemical enantiospecific response of the four possible systems, coming from the combination with L‐ and D‐tartaric acid, respectively, was tested. The 1:tartaric acid adducts show lower oxidation potentials than the pristine 1, together with clear enantio‐discrimination demonstrated by sizeable potential differences in the range of 29–46 mV between the diastereomeric adducts. Because the oxidation potential of 1 suggests the possibility of the formation of CT complexes, impedance and FT‐IR spectra were recorded to confirm this hypothesis in the case of the CT complex 1:I2. The experimental results obtained through the FT‐IR analysis were also compared with the theoretical results deriving from the DFT‐based calculations.
Exploring the Lifeline: Unpacking the Complexities of Placental Vascular Function in Normal and Preeclamptic Pregnancies
Authors: Schliefsteiner Carolin , Wadsack Christian , Allerkamp Hanna H. 
Published: December 2024

Abstract

The proper development and function of the placenta are essential for the success of pregnancy and the well‐being of both the fetus and the mother. Placental vascular function facilitates efficient fetal development during pregnancy by ensuring adequate gas exchange with low vascular resistance. This review focuses on how placental vascular function can be compromised in the pregnancy pathology preeclampsia, and conversely, how placental vascular dysfunction might contribute to this condition. While the maternal endothelium is widely recognized as a key focus in preeclampsia research, this review emphasizes the importance of understanding how this condition affects the development and function of the fetal placental vasculature. The placental vascular bed, consisting of microvasculature and macrovasculature, is discussed in detail, as well as structural and functional changes associated with preeclampsia. The complexity of placental vascular reactivity and function, its mediators, its impact on placental exchange and blood distribution, and how these factors are most affected in early‐onset preeclampsia are further explored. These factors include foremost lipoproteins and their cargo, oxygen levels and oxidative stress, biomechanics, and shear stress. Challenges in studying placental pathophysiology are discussed, highlighting the necessity of innovative research methodologies, including
ex vivo
experiments,
in vivo
imaging tools, and computational modeling. Finally, an outlook on the potential of drug interventions targeting the placental endothelium to improve placental vascular function in preeclampsia is provided. Overall, this review highlights the need for further research and the development of models and tools to better understand and address the challenges posed by preeclampsia and its effects on placental vascular function to improve short‐ and long‐term outcomes for the offspring of preeclamptic pregnancies. © 2024 American Physiological Society.
Compr Physiol
14:5763‐5787, 2024.
Neuromechanical Circuits of the Spinal Motor Apparatus
Authors: Nichols T. Richard 
Published: December 2024

Abstract

The evolution of mechanisms for terrestrial locomotion has resulted in multi‐segmented limbs that allow navigation on irregular terrains, changing of direction, manipulation of external objects, and control over the mechanical properties of limbs important for interaction with the environment, with corresponding changes in neural pathways in the spinal cord. This article is focused on the organization of these pathways, their interactions with the musculoskeletal system, and the integration of these neuromechanical circuits with supraspinal mechanisms to control limb impedance. It is argued that neural pathways from muscle spindles and Golgi tendon organs form a distributive impedance controller in the spinal cord that controls limb impedance and coordination during responses to external disturbances. These pathways include both monosynaptic and polysynaptic components. Autogenic, monosynaptic pathways serve to control the spring‐like properties of muscles preserving the nonlinear relationship between stiffness and force. Intermuscular monosynaptic pathways compensate for inertial disparities between the inertial properties of limb segments and help to control inertial coupling between joints and axes of rotation. Reciprocal inhibition controls joint stiffness in conjunction with feedforward cocontraction commands. Excitatory force feedback becomes operational during locomotion and increases muscular stiffness to accommodate the higher inertial loads. Inhibitory force feedback is widely distributed among muscles. It is integrated with excitatory pathways from muscle spindles and Golgi tendon organs to determine limb stiffness and interjoint coordination during interactions with the environment. The intermuscular distribution of force feedback is variable and serves to modulate limb stiffness to meet the physical demands of different motor tasks. © 2024 American Physiological Society.
Compr Physiol
14:5789‐5838, 2024.
Cellulite & Skin Tightening: A Review of Pathophysiology and Topical Treatment
Authors: Castellanos‐García Isabella , Ramírez‐Zuluaga Luisa Valentina , Páez‐Cárdenas Laura Sofia , Villalba‐Moreno Dennys Lintsay , Caicedo‐León María Daniela , Singer Elisha , Pincelli Thais , Bruce Alison J. , Aristizabal Miguel A. 
Published: December 2024

ABSTRACTBackgroundCellulite is a localized skin condition that affects many women, particularly after puberty. It results from a complex interplay of several factors that lead to the characteristic dimpled appearance of the skin. Cellulite may cause psychological stress and negatively impact quality of life. Additionally, body skin laxity may further exacerbate cosmetic concerns in these patients. Consequently, multiple therapeutic options, including topical treatments, have been explored to address both cellulite and skin laxity.ObjectivesTo review the pathophysiology of cellulite and skin laxity, as well as topical skincare options for their management.MethodsA literature search from 2000 to 2024 was conducted using the databases PubMed, EBSCOhost, Scopus, and Google Scholar, with the key terms “cellulite,” “cellulite management,” “cellulite topical treatment,” “skin sagging,” “skin laxity,” and “loose skin.” The search included clinical trials, observational studies, book chapters, and review articles in English and Spanish.ResultsThe pathophysiologic mechanisms underlying cellulite involve a combination of histological, hormonal, genetic, and lifestyle factors. Several topical agents, including retinoids and methylxanthines, have shown potential in improving the cosmetic appearance of cellulite and may contribute to localized fat reduction. Emerging botanical extracts hold promise as topical treatments for cellulite and skin tightening.ConclusionsCellulite and skin laxity are prevalent cosmetic concerns with multifactorial and complex pathophysiologic origins. Topical treatments for cellulite and skin tightening require further investigation. Although some studies have demonstrated positive outcomes with skincare products and topicals, robust evidence and studies with extended follow‐up are still lacking. Additional research is necessary to evaluate the long‐term efficacy of topical treatments as standalone therapies for cellulite and skin tightening.
Effects of Mycoplasma ovipneumoniae, abundance, and climate conditions on bighorn sheep lamb:ewe ratios in New Mexico
Authors: Padilla Colton J. , Ruhl Caitlin Q. , Cain James W. , Gompper Matthew E. 
Published: December 2024

AbstractMycoplasma ovipneumoniae is a primary causative agent responsible for initiating polymicrobial pneumonia in bighorn sheep (Ovis canadensis). Infections of bighorn sheep populations are typically characterized by initial all‐age epizootics followed by long‐term periods of repressed juvenile (lamb) survival. Populations of bighorn sheep in New Mexico, USA, were thought to be free of this pathogen prior to 2017 but recent infection of multiple herds raised concerns regarding impacts on population size and juvenile:female ratios. Using aerial survey, survival, and disease sampling data in an exploratory framework, we (1) characterize age‐related differences in M. ovipneumoniae prevalence and seroprevalence, (2) quantify differences in lamb:ewe ratios pre‐ and post‐M. ovipneumoniae detection, and (3) investigate differences in survival between previously exposed and naïve individuals. From 2007 to 2022, we sampled 466 bighorn sheep across 19 populations in New Mexico for M. ovipneumoniae exposure. While the timing of initial herd infections varied across populations, one population sustained active infections for over 15 years. We found reduced juvenile:female ratios post M. ovipneumoniae exposure for both desert (O. c. mexicana) and Rocky Mountain (O. c. canadensis) bighorn sheep populations. Post‐exposure ratio declines ranged from 20% to 69%. Evaluation of population size and environmental condition effects on juvenile:female ratios indicated varying impacts for each subspecies. Notably, population size was negatively related to Rocky Mountain juvenile:female ratios only after populations were exposed to M. ovipneumoniae. Additionally, climatic conditions in the previous lambing season and pre‐parturition time frame were associated with juvenile:female ratios for Rocky Mountain populations, while juvenile:female ratios of desert bighorn appeared to only be affected by pre‐parturition climatic conditions. Kaplan–Meier survival estimation of previously exposed, but putatively recovered, individuals (n = 31) and naïve individuals (n = 70) revealed lower (75%; 95% CI: 62%–93%) but not statistically significant (p = 0.2) 1‐year survival rates for individuals that were seropositive but not actively infected, when compared to seronegative individuals (88%; 95% CI: 81%–97%). These results collectively suggest that following M. ovipneumoniae introduction, bighorn sheep populations in New Mexico could be limited by lamb survival.
Biomass allocation and root topology alteration of an introduced amphibious plant in response to cultural eutrophication
Authors: Huang Xiaolong , Zhao Yu , Xu Hai , Yin Chunyu , Shen Ruijie , Guan Baohua , Mao Zhigang , He Hu , Yu Jinlei , Li Kuanyi 
Published: December 2024

AbstractParrot feather (Myriophyllum aquaticum) is an introduced, noninvasive amphibious plant found in coastal provinces, but it has the potential to become an invasive species in China. The plant is heterophyllous, with both emergent (aerial) and submerged (aquatic) leaves, and has two distinct root types: aquatic (adventitious) and edaphic (sediment) root systems. This morphological plasticity allows M. aquaticum to effectively absorb nutrients from different layers of the environment, making it a suitable model plant for exploring nutrient dynamics in both water and soil systems and investigating how wetland plants respond to cultural eutrophication. We designed an outdoor mesocosm experiment to assess plant growth traits and root topological indices in response to different nitrogen (N) and phosphorus (P) concentrations. The results indicated that the plant has a high tolerance to N loading. In contrast, the P content had greater impacts than the N content on plant growth and root topological indices, indicating that the P content was the main influencing factor affecting and suppressing the development of M. aquaticum. The aquatic or edaphic root branching did not change, but the aquatic root topology of M. aquaticum exhibited similar stable trends with increasing P concentration, indicating typical herringbone branching; additionally, its edaphic roots exhibited decreasing topological indices, indicating more typical dichotomous branching with increasing P concentration. The plant has a high tolerance to N, and it may become invasive following the current trend of increasing cultural eutrophication.
Efficacy of Pendulum Tuned Mass Dampers in Reducing Overturning Risk of Rocking Blocks Subjected to Artificial Accelerograms
Authors: Edwin Duque , José Inaudi 
Published: December 2024

ABSTRACTThis study presents a comprehensive statistical analysis of the efficacy of pendulum tuned mass dampers (PTMD) in mitigating the overturning risk of rigid blocks subjected to artificial seismic loads. The block is modeled as a rigid parallelepiped undergoing rocking motion, with the PTMD characterized by its mass, length, and viscous damping properties, mounted on top of the block. The analysis includes the derivation of the differential equations of motion for the coupled system, which are numerically integrated. The seismic accelerograms are synthetically generated as realizations of a stationary random process characterized in the frequency domain by its power spectral density (PSD). Second‐order white‐noise filters are used for sample generation. A Monte Carlo simulation is performed to conduct a parametric analysis, determining the sensitivity of the PTMD parameters to seismic intensity and block slenderness. The results indicate that the efficacy of the PTMD in reducing overturning risk strongly depends on the block's slenderness and the intensity of ground motion. The TMD demonstrates robust performance for moderate ground motion and block slenderness. Although the design parameters do not exhibit systematic trends with respect to mass ratio of PTMD and block due to the inherent nonlinearity of the coupled system, stabilizing, and optimal parameter ranges can still be identified to minimize the overturning risk. Significant reduction of overturning risk can be achieved with respect to the block without PTMD.
Integration of In Vitro and In Silico Results From Chemical and Biological Assays of Rheum turkestanicum and Calendula officinalis Flower Extracts
Authors: Korpayev Serdar , Zengin Gokhan , Ak Gunes , Glamočlija Jasmina , Soković Marina , Aničić Neda , Gašić Uroš , Stojković Dejan , Agamyradov Mirap , Cetiz Mehmet Veysi , Agamyradova Guljan 
Published: December 2024

ABSTRACTIn this study, we conducted a thorough analysis of Rheum turkestanicum (RT) and Calendula officinalis flowers (COF) extracts with varying polarities using LC–MS chemical profiling and biological tests (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic effects). The highest level of total phenolic content in the ethanol extract of RT with 75.82 mg GAE/g, followed by the infusions of RT (65.00 mg GAE/g) and COF (40.99 mg GAE/g). A total of 20 bioactive compounds were identified and quantified. The ethanol extract of COF was rich in terms of 5‐O‐caffeoylquinic acid (2780.56 μg/g), isorhamnetin‐O‐rutinoside (1653.59 μg/g), and rutin (1356.97 μg/g). However, RF extracts were rich in catechin gallate (21.66–80.01 μg/g) and 5‐O‐caffeoylquinic acid. Except for metal chelating ability, the ethanol extract of RT exhibited the strongest ability (DPPH: 171.5 mg TE/g; ABTS: 387.35 mg TE/g; CUPRAC: 449.80 mg TE/g; FRAP: 195.60 mg TE/g; and PBD: 1.52 mmol TE/g). In the enzyme inhibition tests, the tested ethanol extracts for both species were more active than the infusion. The highest values for tyrosinase were recorded as 72.47 mg KAE/g (in RT extracts) and 71.74 mg KAE/g (in COF extracts). Furthermore, all extracts underwent assessment for their antibacterial and antifungal properties, targeting both Gram‐positive and Gram‐negative bacteria, as well as clinical yeast and fungal microorganisms. In silico studies yielded valuable insights into the potential therapeutic applications of the bioactive compounds identified in COF and RT extracts. Stable interactions were observed between key compounds, such as isorhamnetin 3‐O‐glucoside and 3‐O‐caffeoylquinic acid, with crucial target proteins (AChE, BChE, and MurE). These compounds formed stable hydrogen bonds with minimal root mean square deviation (RMSD) fluctuations, particularly in the isorhamnetin 3‐O‐glucoside‐Staphylococcus aureus MurE and 3‐O‐caffeoylquinic acid‐MurE of S. aureus complexes. These findings further underscore the potential of these compounds as promising candidates for therapeutic development.
From Inhibition to Exciting Science
Authors: Buzsáki György 
Published: December 2024

ABSTRACTI am lucky to be part of the hippocampus story, if not from the beginning but at least in its formative decades. Being part of this community is a true privilege. As I try to illustrate below, science is made by scientists. My fierce competitors over the years have become my close friends. I hope the field of hippocampus research will stay that way forever.