bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of medicinal plants during COVID-19 pandemic in Brazil
Authors: da Silva Alciellen Mendes , Horsth Ana Luísa , Timóteo Élida da Silva , Faria Ronaldo José , Bazoni Patrícia Silva , Meira Eduardo Frizzera , dos Santos Jéssica Barreto Ribeiro , da Silva Michael Ruberson Ribeiro 
Published: October 2023

AbstractMedicinal plants are an integrative and complementary health practice widely used by the population. However, its use is not without risks. This study assessed the profile and associated factors with the traditional use of medicinal plants. To this end, a cross-sectional survey study was conducted in a southeastern Brazilian city. Descriptive analysis was performed by frequency distribution and median and interquartile range. Associated factors with the use of medicinal plants were analyzed using Poisson regression with robust variance. A total of 641 people were interviewed, of whom 258 (40.2%) reported using medicinal plants. A total of 79 distinct plants were identified, of whom Melissa officinalis (31.0%), Peumus boldus (24.4%), Mentha spicata (20.9%), Matricaria recutita L. (18.2%), Rosmarinus officinalis (17.0%), and Foeniculum vulgare (14.7%) were the most used. There were no reports of medicinal plants used to treat COVID-19. However, anxiety was the most frequently cited indication for using medicinal plants, a health condition exacerbated by the COVID-19 pandemic. Furthermore, the use of medicinal plants for treating respiratory and gastrointestinal symptoms similar to those in COVID-19 has been identified. There was an association between the use of medicinal plants and females, non-white, lower schooling, higher income, and comorbidities.
In-silico and in-vitro study reveals ziprasidone as a potential aromatase inhibitor against breast carcinoma
Authors: Sahu Ankita , Ahmad Shaban , Imtiyaz Khalid , Kizhakkeppurath Kumaran Ajeeshkumar , Islam Mojahidul , Raza Khalid , Easwaran Murugesh , Kurukkan Kunnath Asha , Rizvi Moshahid A. , Verma Saurabh 
Published: October 2023

AbstractAromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL708 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates for therapeutic use in breast cancer.
ESX1 gene as a potential candidate responsible for male infertility in nonobstructive azoospermia
Authors: Malcher Agnieszka , Graczyk Zuzanna , Bauer Hermann , Stokowy Tomasz , Berman Andrea , Smolibowski Mikołaj , Blaszczyk Dominika , Jedrzejczak Piotr , Yatsenko Alexander N. , Kurpisz Maciej 
Published: October 2023

AbstractInfertility is a problem that affects approximately 15% of couples, and male infertility is responsible for 40–50% of these cases. The cause of male infertility is still poorly diagnosed and treated. One of the prominent causes of male infertility is disturbed spermatogenesis, which can lead to nonobstructive azoospermia (NOA). Whole-genome sequencing (WGS) allows us to identify novel rare variants in potentially NOA-associated genes, among others, in the ESX1 gene. The aim of this study was to activate the ESX1 gene using CRISPRa technology in human germ cells (testicular seminoma cells—TCam-2). Successful activation of the ESX1 gene in TCam-2 cells using the CRISPRa system was achieved, and the expression level of the ESX1 gene was significantly higher in modified TCam-2 cells than in WT cells or the negative control with nontargeted gRNA (p < 0.01). Using RNA-seq, a network of over 50 genes potentially regulated by the ESX1 gene was determined. Finally, 6 genes, NANOG, CXCR4, RPS6KA5, CCND1, PDE1C, and LINC00662, participating in cell proliferation and differentiation were verified in azoospermic patients with and without a mutation in the ESX1 gene as well as in men with normal spermatogenesis, where inverse correlations in the expression levels of the observed genes were noted.
Characterisation of strength and deformation characteristics of alkali-activated rice husk ash filler-assemblage perimeter rock
Authors: Zhao Wenhua , He Ruilin , Sun Qi , Gu Qi 
Published: October 2023

AbstractIn this study, the strength characteristics, deformation characteristics and damage characteristics of three kinds of specimens, namely, surrounding rock, cemented paste backfill (CPB) and a surrounding rock-CPB combination, were studied by uniaxial compression testing using rice husk ash and slag as cementing materials, and the mechanical properties of the combination specimens with different height ratios were also analyzed. The results showed that the surrounding rock specimens were the strongest, followed by the composite body, and the CPB was the weakest. The relationship between different height ratios of the assemblage and the cut line modulus was found according to the fitted curves. The CPB specimens and the surrounding rock specimens showed ductile damage, while the assemblage specimens showed brittle damage.
A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo
Authors: Giannakopoulou Eirini , Lehander Madeleine , Virding Culleton Stina , Yang Weiwen , Li Yingqian , Karpanen Terhi , Yoshizato Tetsuichi , Rustad Even H. , Nielsen Morten Milek , Bollineni Ravi Chand , Tran Trung T. , Delic-Sarac Marina , Gjerdingen Thea Johanne , Douvlataniotis Karolos , Laos Maarja , Ali Muhammad , Hillen Amy , Mazzi Stefania , Chin Desmond Wai Loon , Mehta Adi , Holm Jeppe Sejerø , Bentzen Amalie Kai , Bill Marie , Griffioen Marieke , Gedde-Dahl Tobias , Lehmann Sören , Jacobsen Sten Eirik W. , Woll Petter S. , Olweus Johanna 
Published: October 2023

AbstractAcute myeloid leukemia (AML), the most frequent leukemia in adults, is driven by recurrent somatically acquired genetic lesions in a restricted number of genes. Treatment with tyrosine kinase inhibitors has demonstrated that targeting of prevalent FMS-related receptor tyrosine kinase 3 (FLT3) gain-of-function mutations can provide significant survival benefits for patients, although the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable. We identified a T cell receptor (TCR) reactive to the recurrent D835Y driver mutation in the FLT3 tyrosine kinase domain (TCRFLT3D/Y). TCRFLT3D/Y-redirected T cells selectively eliminated primary human AML cells harboring the FLT3D835Y mutation in vitro and in vivo. TCRFLT3D/Y cells rejected both CD34+ and CD34− AML in mice engrafted with primary leukemia from patients, reaching minimal residual disease-negative levels, and eliminated primary CD34+ AML leukemia-propagating cells in vivo. Thus, T cells targeting a single shared mutation can provide efficient immunotherapy toward selective elimination of clonally involved primary AML cells in vivo.
Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial
Authors: Liebers Nora , Bruch Peter-Martin , Terzer Tobias , Hernandez-Hernandez Miguel , Paramasivam Nagarajan , Fitzgerald Donnacha , Altmann Heidi , Roider Tobias , Kolb Carolin , Knoll Mareike , Lenze Angela , Platzbecker Uwe , Röllig Christoph , Baldus Claudia , Serve Hubert , Bornhäuser Martin , Hübschmann Daniel , Müller-Tidow Carsten , Stölzel Friedrich , Huber Wolfgang , Benner Axel , Zenz Thorsten , Lu Junyan , Dietrich Sascha 
Published: October 2023

AbstractEx vivo drug response profiling is a powerful tool to study genotype–drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial,NCT03488641). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers.
Writers and readers of H3K9me2 form distinct protein networks during the cell cycle that include candidates for H3K9 mimicry
Authors: Pollin Gareth , De Assuncao Thiago M. , Doria Jorge Salomao , Chi Young-In , Charlesworth M. Cristine , Madden Benjamin , Iovanna Juan , Zimmermann Michael T. , Urrutia Raul , Lomberk Gwen 
Published: October 2023

Abstract
Histone H3 lysine 9 methylation (H3K9me), which is written by the Euchromatic Histone Lysine Methyltransferases EHMT1 and EHMT2 and read by the heterochromatin protein 1 (HP1) chromobox (CBX) protein family, is dysregulated in many types of cancers. Approaches to inhibit regulators of this pathway are currently being evaluated for therapeutic purposes. Thus, knowledge of the complexes supporting the function of these writers and readers during the process of cell proliferation is critical for our understanding of their role in carcinogenesis. Here, we immunopurified each of these proteins and used mass spectrometry to define their associated non-histone proteins, individually and at two different phases of the cell cycle, namely G1/S and G2/M. Our findings identify novel binding proteins for these writers and readers, as well as corroborate known interactors, to show the formation of distinct protein complex networks in a cell cycle phase-specific manner. Furthermore, there is an organizational switch between cell cycle phases for interactions among specific writer–reader pairs. Through a multi-tiered bioinformatics-based approach, we reveal that many interacting proteins exhibit histone mimicry, based on an H3K9-like linear motif. Gene ontology analyses, pathway enrichment, and network reconstruction inferred that these comprehensive EHMT and CBX-associated interacting protein networks participate in various functions, including transcription, DNA repair, splicing, and membrane disassembly. Combined, our data reveals novel complexes that provide insight into key functions of cell cycle-associated epigenomic processes that are highly relevant for better understanding these chromatin-modifying proteins during cell cycle and carcinogenesis.
Adverse effects of ovarian cryopreservation and auto-transplantation on ovarian grafts and quality of produced oocytes in a mouse model
Authors: Wu Que , Ru Gaizhen , Xiao Wanfen , Wang Qian , Li Zhiling 
Published: October 2023

Abstract
The process of ovarian cryopreservation and transplantation is the only feasible fertility preservation method for prepubertal girls and female patients with cancer who cannot delay radiotherapy and chemotherapy. However, basic research on this technique is lacking. To better understand ovarian function and oocyte quality after ovarian tissue (OT) transplantation, we characterised the appearance, angiogenesis, and endocrine function of ovarian grafts in a murine model; the mitochondrial function and DNA damage in oocytes isolated from the OT; and the development of embryos after in vitro fertilisation. The results showed a decrease in oocyte numbers in the transplanted OT, abnormal endocrine function of ovarian grafts, as well as dysfunctional mitochondria and DNA damage in the oocytes, which could adversely affect subsequent embryonic development. However, these adverse phenotypes were partially or completely resolved within 21 days of transplantation, suggesting that ovulation induction and assisted pregnancy treatment should not be conducted too soon after OT transfer to ensure optimal patient and offspring outcomes.
Constraints on the multiplicity of the most massive stars known: R136 a1, a2, a3, and c
Authors: Shenar T. , Sana H. , Crowther P. A. , Bostroem K. A. , Mahy L. , Najarro F. , Oskinova L. , Sander A. A. C. 
Published: October 2023

Context. The upper stellar mass limit is a fundamental parameter for simulations of star formation, galactic chemical evolution, and stellar feedback. An empirical bound on this parameter is therefore highly valuable. The most massive stars known to date are R 136 a1, a2, a3, and c, with reported masses in excess of 150–200 M⊙ and initial masses of up to ≈300 M⊙. They are located within the central cluster R 136a of the Tarantula nebula in the Large Magellanic Cloud (LMC), However, the mass estimation of these stars relies on the assumption that they are single.
Aims. Via multi-epoch spectroscopy, we provide, for the first time, constraints on the presence of close stellar companions to the most massive stars known for orbital periods of up to ≈10 yr.
Methods. We collected three epochs of spectroscopy for R 136 a1, a2, a3, and c with the Space Telescope Imaging Spectrograph (STIS) of the Hubble Space Telescope (HST) in the years 2020–2021 to probe potential radial-velocity (RV) variations. We combined these epochs with an additional HST/STIS observation taken in 2012. For R 136 c, we also used archival spectroscopy obtained with the Very Large Telescope (VLT). We used cross-correlation to quantify the RVs and establish constraints on possible companions to these stars up to periods of ≈10 yr. Objects are classified as binaries when the peak-to-peak RV shifts exceed 50 km s−1 and when the RV shift is significant with respect to errors.
Results. R 136 a1, a2, and a3 do not satisfy the binary criteria and are thus classified as putatively single, although formal peak-to-peak RV variability on the level 40 km s−1 is noted for a3. Only R 136 c is classified as a binary, in agreement with the literature. We can generally rule out massive companions (M2 ≳ 50 M⊙) to R 136 a1, a2, and a3 out to orbital periods of ≲1 yr (separations ≲5 au) at 95% confidence, or out to tens of years (separations ≲100 au) at 50% confidence. Highly eccentric binaries (e ≳ 0.9) or twin companions with similar spectra could evade detection down to shorter periods (≳10 days), though their presence is not supported by the relative X-ray faintness of R 136 a1, a2, and a3. We derive a preliminary orbital solution with a 17.2 days period for the X-ray-bright binary R 136 c, though more data are needed to conclusively derive its orbit.
Conclusions. Our study supports a lower bound of 150–200 M⊙ on the upper-mass limit at LMC metallicity.
Prediction of Minimal Ventilation Requirements for Oxygenation in a Bubble and Membrane Blood Oxygenator During Cardiopulmonary Bypass
Authors: Riley J. B. , Walker C. T , Kauffman J. N. , Rigatti R. L. , Young M. R. , Daly W. L. 
Published: October 2023

2300 Optiflo II and 80 Sci-Med blood oxygenator cardiopulmonary operative records were studied to define the semilogarithmic relationship between the PaO2 and the gas-to-blood flow ratio or the percent FIO2 respectively. A mathematical model was developed to consider the linear effects of oxygenator blood residence time, temperature, hematocrit and the continuously monitored venous inlet % O2 saturation of hemoglobin on the slope and Y -intercept of the device semilog PaO2 function curve.
The ventilation of five Optiflo II patient circuits (37 blood gas determinations) and five Sci-Med patient circuits (40 blood gases) ventilation was controlled by intrabypass evaluation of a mathematical statement as each of the four continuously monitored independent variables were altered. The formulae were solved to generate gas-to-blood flow ratios and FIO2’s to yield PaO2’s of 150 mmHg. The average resulting PaO2 in the Optiflo II group = 158 ± 55 mmHg (mean ± 1 S.D.), the PaO2 falling within 150 ± 60 mmHg 70.3% of the time. The average resulting PaO2 in the Sci-Med group = 180 ± 59 mmHg, the PaO2 falling within 150 ± 60 mmHg 67.5% of the time.
The minimal ventilation requirements to achieve blood oxygenation were quantitated, formulated, and tested with success.
Development of a two-way mentorship scale focusing on next-generation core competencies
Authors: Chen Yin-Che , Chai Ching-Ching 
Published: October 2023

AbstractWith society and technology developing rapidly and the new generation of young adults entering the workforce, the core competencies that must be possessed by employees are changing along with factors such as changes in the external environment and enterprises’ internal demands; consequently, the characteristics of mentorship are also subject to change. This study investigated two-way mentorship and the core competencies necessary for workers in an organization. After rigorous testing and compilation processes, this study developed a two-way mentorship scale for assessing the three dimensions of career development, psychosocial support, and role modeling. The data analysis revealed that the internal consistency values for career development, psychosocial support, and role modeling were 0.911, 0.879, and 0.791, respectively. The factor loading of all items exceeded 0.50 and thereby conformed to the theoretical model. Confirmatory factor analysis revealed that the goodness-of-fit indices of the scale met the corresponding standards. The average variance extracted was 0.342–0.497, the composite reliability was 0.591–0.911, and the square root of the average variance extracted was 0.584–0.704. Finally, managerial, practical, and academic suggestions are proposed on the basis of the study results, and the research limitations are identified.
Signatures of elongated and compact configurations in the fusion barrier distribution of deformed nuclei
Authors: Fareed F A , Seif W M , Adel A , Abdul-Magead I A M 
Published: October 2023

Abstract
The fusion barrier distributions (BD) of 11 fusion reactions are investigated to understand the role of orientation as a degree of freedom in the fusion mechanism involving deformed nuclei, and seeking signatures of cold and hot fusion. We compared the experimentally extracted BD with those calculated using the coupled-channel method, starting from orientation-dependent folding potentials based on M3Y-Reid nucleon–nucleon interaction, with coupling to the anticipated vibrational and rotational excitations in projectile and target nuclei. We found that the signature of the hot fusion process within the compact configuration of the participating deformed nuclei is always evident in the extracted fusion barrier distribution. The different peaks appearing in the extracted BD can be individually assigned to the elongated-cold or compact-hot fusion process. The imprint of the compact-hot fusion may also manifest itself as a little increase in the value of the BD at certain related energy, compared with the preceding and succeeding values.
Modeling the effects of transcranial magnetic stimulation on spatial attention
Authors: Jing Ying , Numssen Ole , Weise Konstantin , Kalloch Benjamin , Buchberger Lena , Haueisen Jens , Hartwigsen Gesa , Knösche Thomas R 
Published: October 2023

Abstract

Objectives. Transcranial magnetic stimulation (TMS) has been widely used to modulate brain activity in healthy and diseased brains, but the underlying mechanisms are not fully understood. Previous research leveraged biophysical modeling of the induced electric field (E-field) to map causal structure–function relationships in the primary motor cortex. This study aims at transferring this localization approach to spatial attention, which helps to understand the TMS effects on cognitive functions, and may ultimately optimize stimulation schemes. Approach. Thirty right-handed healthy participants underwent a functional magnetic imaging (fMRI) experiment, and seventeen of them participated in a TMS experiment. The individual fMRI activation peak within the right inferior parietal lobule (rIPL) during a Posner-like attention task defined the center target for TMS. Thereafter, participants underwent 500 Posner task trials. During each trial, a 5-pulse burst of 10 Hz repetitive TMS (rTMS) was given over the rIPL to modulate attentional processing. The TMS-induced E-fields for every cortical target were correlated with the behavioral modulation to identify relevant cortical regions for attentional orientation and reorientation. Main results. We did not observe a robust correlation between E-field strength and behavioral outcomes, highlighting the challenges of transferring the localization method to cognitive functions with high neural response variability and complex network interactions. Nevertheless, TMS selectively inhibited attentional reorienting in five out of seventeen subjects, resulting in task-specific behavioral impairments. The BOLD-measured neuronal activity and TMS-evoked neuronal effects showed different patterns, which emphasizes the principal distinction between the neural activity being correlated with (or maybe even caused by) particular paradigms, and the activity of neural populations exerting a causal influence on the behavioral outcome. Significance. This study is the first to explore the mechanisms of TMS-induced attentional modulation through electrical field modeling. Our findings highlight the complexity of cognitive functions and provide a basis for optimizing attentional stimulation protocols.
Completion of 25.2 T ultrahigh magnetic field NMR user facility in China
Authors: Wang Yaohui , Liu Jianhua , Zhou Benzhe , Wang Kangshuai , Liu Hui , Wang Hui , Chen Shunzhong , Liu Feng , Wang Weimin , Wang Qiuliang 
Published: October 2023

Abstract
Significant scientific breakthroughs often arise from research conducted under extreme conditions, such as ultrahigh magnetic fields. Ultrahigh field nuclear magnetic resonance (NMR) provides a cutting-edge platform for studying material properties under extreme conditions. However, pursuing ultrahigh NMR presents considerable challenges, with only a few institutions worldwide having the requisite technical capabilities. After several years of research and development, we have successfully created the world’s first high-temperature superconducting (HTS) NMR experimental instrument under low-temperature measurement with a field strength exceeding 25 T using the Bi-2223 HTS double-pancake winding technique. The instrument has demonstrated exceptional performance, and stable operation, fully satisfying the demands of the user facility. The open operation of this experimental facility will significantly support basic scientific research in China and around the world.