bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model
Authors: Ta Wenjing , Wang Jie , Song Jihong , Li Xingyue , Wang Jianxiang , Lu Wen 
Published: January 2024

Abstract
Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs’ intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.
Deuterium fractionation in cold dense cores in the low-mass star-forming region L1688
Authors: Petrashkevich I V , Punanova A F , Caselli P , Sipilä O , Pineda J E , Friesen R K , Korotaeva M G , Vasyunin A I 
Published: January 2024

ABSTRACT
In this work, we study deuterium fractionation in four starless cores in the low-mass star-forming region L1688 in the Ophiuchus molecular cloud. We study how the deuterium fraction (RD) changes with environment, compare deuteration of ions and neutrals, core centre and its envelope, and attempt to reproduce the observed results with a gas–grain chemical model. We chose high and low gas density tracers to study both core centre and the envelope. With the IRAM 30 m antenna, we mapped N2H+(1–0), N2D+(1–0), H13CO+ (1–0) and (2–1), DCO+(2–1), and p-NH2D(111–101) towards the chosen cores. The missing p-NH3 and N2H+(1–0) data were taken from the literature. To measure the molecular hydrogen column density, dust and gas temperature within the cores, we used the Herschel/SPIRE dust continuum emission data, the Green Bank Ammonia Survey data (NH3), and the COMPLETE survey data to estimate the upper limit on CO depletion. We present the deuterium fraction maps for three species towards four starless cores. Deuterium fraction of the core envelopes traced by DCO+/H13CO+ is one order of magnitude lower (∼0.08) than that of the core central parts traced by the nitrogen-bearing species (∼0.5). Deuterium fraction increases with the gas density as indicated by high deuterium fraction of high gas density tracers and low deuterium fraction of lower gas density tracers and by the decrease of RD with core radii, consistent with the predictions of the chemical model. Our model results show a good agreement with observations for RD(N2D+/N2H+) and RD(DCO+/HCO+) and underestimate the RD(NH2D/NH3).
GMF G214.5-1.8 as traced by CO: I – cloud-scale CO freeze-out as a result of a low cosmic-ray ionization rate
Authors: Clarke S D , Makeev V A , Sánchez-Monge Á , Williams G M , Tang Y -W , Walch S , Higgins R , Nürnberger P C , Suri S 
Published: January 2024

ABSTRACT
We present an analysis of the outer Galaxy giant molecular filament (GMF) G214.5-1.8 (G214.5) using IRAM 30m data of 12CO, 13CO, and C18O. We find that the 12CO (1-0) and (2-1) derived excitation temperatures are near identical and are very low, with a median of 8.2 K, showing that the gas is extremely cold across the whole cloud. Investigating the abundance of 13CO across G214.5, we find that there is a significantly lower abundance along the entire 13 pc spine of the filament, extending out to a radius of ∼0.8 pc, corresponding to Av ≳ 2 mag and Tdust ≲ 13.5 K. Due to this, we attribute the decrease in abundance to CO freeze-out, making G214.5 the largest scale example of freeze-out yet. We construct an axisymmetric model of G214.5’s 13CO volume density considering freeze-out and find that to reproduce the observed profile significant depletion is required beginning at low volume densities, n ≳ 2000 cm−3. Freeze-out at this low number density is possible only if the cosmic-ray ionization rate is ∼1.9 × 10−18 s−1, an order of magnitude below the typical value. Using time scale arguments, we posit that such a low ionization rate may lead to ambipolar diffusion being an important physical process along G214.5’s entire spine. We suggest that if low cosmic-ray ionization rates are more common in the outer Galaxy, and other quiescent regions, cloud-scale CO freeze-out occurring at low column and number densities may also be more prevalent, having consequences for CO observations and their interpretation.
Modelling stellar variability in archival HARPS data: I - Rotation and activity properties with multidimensional Gaussian processes
Authors: Yu Haochuan , Aigrain Suzanne , Klein Baptiste , Barragán Oscar , Mortier Annelies , O’Sullivan Niamh K , Cretignier Michael 
Published: January 2024

ABSTRACT
Although instruments for measuring the radial velocities (RVs) of stars now routinely reach sub-metre per second accuracy, the detection of low-mass planets is still very challenging. The rotational modulation and evolution of spots and/or faculae can induce variations in the RVs at the level of a few m s–1 in Sun-like stars. To overcome this, a multidimensional Gaussian Process framework has been developed to model the stellar activity signal using spectroscopic activity indicators together with the RVs. A recently published computationally efficient implementation of this framework, S + LEAF 2, enables the rapid analysis of large samples of targets with sizeable data sets. In this work, we apply this framework to HARPS observations of 268 well-observed targets with precisely determined stellar parameters. Our long-term goal is to quantify the effectiveness of this framework to model and mitigate activity signals for stars of different spectral types and activity levels. In this first paper in the series, we initially focus on the activity indicators (S-index and Bisector Inverse Slope), and use them to (a) measure rotation periods for 49 slow rotators in our sample, (b) explore the impact of these results on the spin-down of middle-aged late F, G, and K stars, and (c) explore indirectly how the spot to facular ratio varies across our sample. Our results should provide valuable clues for planning future RV planet surveys such as the Terra Hunting Experiment or the PLATO ground-based follow-up observations programme, and help fine-tune current stellar structure and evolution models.
Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro
Authors: Qiu Chenxi , Arora Payal , Malik Indranil , Laperuta Amber J , Pavlovic Emily M , Ugochukwu Scott , Naik Mandar , Kaplan Craig D 
Published: January 2024

Abstract
Thiolutin is a natural product transcription inhibitor with an unresolved mode of action. Thiolutin and the related dithiolopyrrolone holomycin chelate Zn2+ and previous studies have concluded that RNA Polymerase II (Pol II) inhibition in vivo is indirect. Here, we present chemicogenetic and biochemical approaches to investigate thiolutin's mode of action in Saccharomyces cerevisiae. We identify mutants that alter sensitivity to thiolutin. We provide genetic evidence that thiolutin causes oxidation of thioredoxins in vivo and that thiolutin both induces oxidative stress and interacts functionally with multiple metals including Mn2+ and Cu2+, and not just Zn2+. Finally, we show direct inhibition of RNA polymerase II (Pol II) transcription initiation by thiolutin in vitro in support of classical studies that thiolutin can directly inhibit transcription in vitro. Inhibition requires both Mn2+ and appropriate reduction of thiolutin as excess DTT abrogates its effects. Pause prone, defective elongation can be observed in vitro if inhibition is bypassed. Thiolutin effects on Pol II occupancy in vivo are widespread but major effects are consistent with prior observations for Tor pathway inhibition and stress induction, suggesting that thiolutin use in vivo should be restricted to studies on its modes of action and not as an experimental tool.
Outcomes of Ceftriaxone Compared With Cefazolin or Nafcillin/Oxacillin for Outpatient Therapy for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infections: Results From a Large United States Claims Database
Authors: Hamad Yasir , Nickel Katelin B , Olsen Margaret A , George Ige A 
Published: January 2024

Abstract

Background
Ceftriaxone is a convenient option for methicillin-sensitive Staphylococcus aureus (MSSA) outpatient parenteral antimicrobial therapy (OPAT), but population-based studies for its effectiveness are lacking.

Methods
In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models.

Results
Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61–64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01–2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81–3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18–2.23]), central line–associated BSI (aOR, 1.72 [95% CI, 1.33–2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18–2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI, .67–1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI, .66–1.10]) when compared with oxacillin/nafcillin/cefazolin.

Conclusions
In this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin.
You Might be an Anarchist if …
Authors: Ehrenberg Kenneth M 
Published: January 2024

Abstract
I show that conceptual philosophical anarchism, the claim that law cannot give reasons for action, is entailed by several popular theories about law. Reductionists about practical authority believe that all supposedly legitimate practical authority reduces to forms of theoretical authority. They tend to embrace anarchism, but some readers might not be clear why. Trigger theorists about reason-giving believe that all reason-giving merely activates pre-existing conditional reasons. Natural lawyers hold that all legal reasons are sourced in the natural law, which entails that positive law cannot provide reasons for action. If you are attracted to any of these theories and still think that positive law creates new practical reasons, you might have to give up one or the other position. If anarchism is entailed by believing the normativity in law’s directives pre-dates the directive, only a few may be able to avoid it, Hans Kelsen, Mark Greenberg, and Joseph Raz being the most likely.
Telemedicine in Peru: origin, implementation, pandemic escalation, and prospects in the new normal
Authors: Rees Gareth H , Peralta Felipe 
Published: January 2024

Abstract
For many countries telemedicine was speedily adopted as a result of the COVID-19 pandemic, though for some countries telemedicine may have been implemented in a context of limited regulations or few plans or strategies to scale quickly. This article recounts how telemedicine was developed in Peru as a measure to support the country's Universal Health Coverage and service access to rural and locations with low workforce numbers and its deployment. From a range of data, we find that Peru's development of telehealth began before the pandemic, which by 2020 was sufficient to be able to foster a rapid and wider deployment and while the telemedicine service volumes quickly grew from the pandemic onset, these numbers then begin to reduce suggesting that telemedicine was considered more as a pandemic emergency measure rather than a change to the mix of health provision. From these data we offer two lessons, (i) that Peru's preparedness in terms of telemedicine policy and regulation were helpful to rapidly expand telemedicine at a time of necessity and (ii) that due to this investment and with a better understanding, Peru now has a short-run window of opportunity for the Peruvian Government to continue its regulatory development and investment to further deploy telemedicine services as a UHC improvement measure and to better align the health system to the country’s health needs.
X-ray iron absorption line in Swift J1858.6−0814
Authors: Asai Kazumi , Mihara Tatehiro , Sakai Kento , Kubota Aya 
Published: January 2024

Abstract
We present the spectral analysis of bright steady states in an outburst of the transient neutron star low-mass X-ray binary Swift J1858.6−0814 observed with the Neutron star Interior Composition Explorer (NICER). We detected an ionized iron K absorption line (H-like Fe) at 6.97 keV in the spectrum. We estimate the photoionization parameter using the ratio of the equivalent widths of the Fe xxvi (H-like) (17 ± 5 eV) and Fe xxv (He-like) (&lt;3 eV) and discuss the origin of the iron absorption line. The irradiated gas producing the absorption line would locate within (3–6) × 109 cm of the X-ray source. We suggest that the observed H-like Fe absorption line originates from the highly ionized gas in the inner accretion disk in Swift J1858.6−0814.
Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights
Authors: Verma Deepak , Kapoor Shruti , Kumari Sarita , Sharma Disha , Singh Jay , Benjamin Mercilena , Bakhshi Sameer , Seth Rachna , Nayak Baibaswata , Sharma Atul , Pramanik Raja , Palanichamy Jayanth Kumar , Sivasubbu Sridhar , Scaria Vinod , Arora Mohit , Kumar Rajive , Chopra Anita 
Published: January 2024

Abstract
T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes—BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers—DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)—XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.
Leveraging metabolic modeling and machine learning to uncover modulators of quiescence depth
Authors: Eames Alec , Chandrasekaran Sriram 
Published: January 2024

Abstract
Quiescence, a temporary withdrawal from the cell cycle, plays a key role in tissue homeostasis and regeneration. Quiescence is increasingly viewed as a continuum between shallow and deep quiescence, reflecting different potentials to proliferate. The depth of quiescence is altered in a range of diseases and during aging. Here, we leveraged genome-scale metabolic modeling (GEM) to define the metabolic and epigenetic changes that take place with quiescence deepening. We discovered contrasting changes in lipid catabolism and anabolism and diverging trends in histone methylation and acetylation. We then built a multi-cell type machine learning model that accurately predicts quiescence depth in diverse biological contexts. Using both machine learning and genome-scale flux simulations, we performed high-throughput screening of chemical and genetic modulators of quiescence and identified novel small molecule and genetic modulators with relevance to cancer and aging.
The Voynich Manuscript, Dr Johannes Hartlieb and the Encipherment of Women’s Secrets
Authors: Brewer Keagan , Lewis Michelle L 
Published: January 2024

Summary
The Voynich manuscript is a famous European enciphered manuscript of the early fifteenth century featuring herbal, pharmaceutical, astrological and anatomical illustrations, including hundreds of naked women. Some hold objects adjacent to or unambiguously pointed towards their genitalia. This paper therefore investigates the culture of self-censorship, erasure and encipherment of women’s secrets, with a focus on Dr Johannes Hartlieb (c. 1410–68). Hartlieb had enduring apprehensions about the propagation of women’s secrets in vernacular Bavarian, which culminated in a call for ‘secret letters’ to hide recipes for abortifacients and contraceptives. Other cases of encipherment relating to sexual intercourse and genitalia will be described. On the basis of this evidence, we propose that the Rosettes, the largest and most complex illustration in the Voynich manuscript, represents coitus and conception. This hypothesis explains many of the illustration’s features and establishes a variety of future research possibilities.
Mathematical modeling of fluid dynamics in in vitro gut fermentation systems: A new tool to improve the interpretation of microbial metabolism
Authors: Lessard‐Lord Jacob , Lupien‐Meilleur Joseph , Roussel Charlène , Gosselin‐Cliche Benjamin , Silvestri Cristoforo , Di Marzo Vincenzo , Roy Denis , Rousseau Elsa , Desjardins Yves 
Published: January 2024

AbstractIn vitro systems are widely employed to assess the impact of dietary compounds on the gut microbiota and their conversion into beneficial bacterial metabolites. However, the complex fluid dynamics and multi‐segmented nature of these systems can complicate the comprehensive analysis of dietary compound fate, potentially confounding physical dilution or washout with microbial catabolism. In this study, we developed fluid dynamics models based on sets of ordinary differential equations to simulate the behavior of an inert compound within two commonly used in vitro systems: the continuous two‐stage PolyFermS system and the semi‐continuous multi‐segmented SHIME® system as well as into various declinations of those systems. The models were validated by investigating the fate of blue dextran, demonstrating excellent agreement between experimental and modeling data (with r2 values ranging from 0.996 to 0.86 for different approaches). As a proof of concept for the utility of fluid dynamics models in in vitro system, we applied generated models to interpret metabolomic data of procyanidin A2 (ProA2) generated from the addition of proanthocyanidin (PAC)‐rich cranberry extract to both the PolyFermS and SHIME® systems. The results suggested ProA2 degradation by the gut microbiota when compared to the modeling of an inert compound. Models of fluid dynamics developed in this study provide a foundation for comprehensive analysis of gut metabolic data in commonly utilized in vitro PolyFermS and SHIME® bioreactor systems and can enable a more accurate understanding of the contribution of bacterial metabolism to the variability in the concentration of target metabolites.
Cervical Kyphosis
Authors: Lee Yu-Po , Liang Jason 
Published: January 2024

Abstract
Kyphosis of the cervical spine can have many causes. The most common causes include degeneration of the cervical spine, infection, trauma, inflammatory diseases, tumors, and iatrogenic causes. Cervical kyphosis can be associated with myelopathy and radiculopathy, so it is important to look for signs and symptoms of spinal cord and nerve root compression as well. As the kyphosis worsens, patients can experience problems with horizontal gaze, swallowing, and even breathing. The first line of treatment for cervical kyphosis is rest and lifestyle modifications. Cervical kyphosis can cause muscular strain best treated with rest and avoidance of re-injuring the muscles and tendons. Nonsurgical treatments for cervical kyphosis also includes physical therapy and pain management procedures, and is attempted if there are no findings of sensory loss, motor weakness, bowel or bladder dysfunction, or spinal cord impingement signs. Many factors play a role in the decision-making process for surgical intervention, which include level of pain, degree of physical impairment, and the amount of cervical kyphosis present. The optimal surgical approach is not always clear but can include an anterior, posterior, or combined anterior and posterior approach.
CE: Our Journey to Pass a Surgical Plume Evacuation Law
Authors: Vortman Rebecca K. , Smalley Penny J. 
Published: January 2024

ABSTRACT
Surgical plume is produced when heat-generating instruments are used to cut, cauterize, or vaporize tissue during surgery. Surgical plume can rapidly diffuse, and without the use of plume evacuators to ensure it is captured, filtered, and removed, health care workers and patients are at risk for inhalation exposure to airborne contaminants, including smoke and biological hazards. The use of surgical plume evacuators in health care facilities is inconsistent across the United States. This article describes the experience of two nurses who led a grassroots coalition to pass a surgical plume evacuation law in Illinois. It also outlines strategies they used in the legislative process that nurses can apply to their own efforts to advocate for health policy change at the state level.