bluuebunny/crossref_metadata_2025_split huggingface dataset:
MammalMethylClock R package: software for DNA methylation-based epigenetic clocks in mammals
Authors: Zoller Joseph , Horvath Steve 
Published: April 2024

Abstract

Motivation
Epigenetic clocks are prediction methods based on DNA methylation levels in a given species or set of species. Defined as multivariate regression models, these DNA methylation-based biomarkers of age or mortality risk are useful in species conservation efforts and in preclinical studies.

Results
We present an R package called MammalMethylClock for the construction, assessment, and application of epigenetic clocks in different mammalian species. The R package includes the utility for implementing pre-existing mammalian clocks from the Mammalian Methylation Consortium.

Availability and implementation
The source code and documentation manual for MammalMethylClock, and clock coefficient .csv files that are included within this software package, can be found on Zenodo at https://doi.org/10.5281/zenodo.10971037.
The sound of fear is heritable
Authors: Blumstein Daniel T , Vu Natalie , Edic Megan , Vo Linh , Martin Julien G A 
Published: April 2024

Abstract
The nonlinearity and fear hypothesis predicts that highly aroused vocal mammals and birds produce vocalizations (notably alarm calls and screams) which contain a variety of nonlinear phenomena (NLP). Such vocalizations often sound “noisy” because vocal production systems are over-blown when animals are highly aroused. While much is known about the conditions under which animals produce vocalizations containing NLP and how species respond to them, there is little research about the heritability of such behavioral traits. Using the quantitative genetic animal model, we estimated the genetic basis of “noise” in alarm calls produced by females and found significant heritability in call entropy—our measure of the noisiness. About 9% of the variance in noisiness can be accounted for by genetic differences. Taken together, these findings suggest that the degree to which marmots produce noisy calls is modestly heritable and can be thus subject to further evolution via natural selection.
Integrative liquid chromatography–tandem mass spectrometry metabolomics and high-throughput sequencing technology reveal physicochemical characteristics and bacterial diversity of traditionally pickled mustard tuber from different regions of China
Authors: Liu Siyu , Luo Jiaqi , Liu Xiayu , Shi Ying , Chen Qihe 
Published: April 2024

Abstract

Objectives
This work aimed to investigate and compare the physicochemical properties and bacterial diversity of traditionally pickled mustard tuber from different regions in China.

Materials and Methods
Pickles were obtained from Ningbo (NB), Nei Mongol (NMG), and Harbin (HEB). The pH was monitored by a pH meter. Titratable acidity and salinity were determined via titrimetric analysis. Nitrite content was measured using N-(1-naphthyl)-ethylenediamine dihydrochloride spectrophotometric method. Organic acids were detected by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Bacterial diversity was conducted through the Illumina high-throughput sequencing platform.

Results
There were significant differences in the physicochemical properties of pickled mustard tuber from various locations, with the NB pickles having the highest pH, salinity, and nitrite content and the lowest titratable acidity. Importantly, pickles with higher titratable acidity levels had relatively lower nitrite and salinity contents. A total of 63 organic acids were detected, with lactic acid and succinic acid being the most prevalent. Moreover, the organic acid compositions of the NMG and HEB samples were more similar than those of the NB pickles. Additionally, bioinformatic analysis revealed that Firmicutes and Proteobacteria were the predominant bacterial phyla in all the samples. Among these, Lactobacillus was the major genus. The most abundant bacteria were found in the HEB pickles. Further correlation analysis revealed a strong correlation between bacterial community and 11 internal physicochemical parameters.

Conclusions
This study could contribute to a better understanding of the physicochemical characteristics and bacterial diversity of pickled mustard tuber from different locations.
Domesticating Wealth Inequality
Authors: Pouliot Vincent , Patterson Scott Robert 
Published: April 2024

AbstractRelative wealth inequality between countries of the North and South has not improved since the era of decolonization, yet the LIO's economic regime has scarcely been challenged since the 1970s' New International Economic Order. This paper seeks to explain this puzzle by theorizing and empirically tracking a pervasive pattern of rhetorical “domestication” through which wealth inequality was framed as a domestic instead of an international problem. As part of a rhetorical process of “containment,” the NIEO challenge was met with two alternative, liberal discourses from the 1980s through the present: a “responsive” discourse embodied by the Brandt report and its social-democratic middle ground; and a “resisting” one typified by a speech delivered by Ronald Reagan in Cancun in 1983. Our empirical demonstration illustrates how LIO proponents discursively contained NIEO contestation through the spread of a domesticated rhetoric. Using a corpus of General Assembly annual debates from 1971 to 2018, our machine learning textual analysis reveals how a growing proportion of diverse countries address economic development in an increasingly managerial way. By tracking rhetorical tropes, we document a groundswell movement away from structural and political contestation of the LIO. Overall, our original methodology—based on an inductive and relational approach to machine learning text analysis—allows us to capture the many euphemisms that containment diplomacy at the UN entails, and more generally, how key political problems get muffled in global debates.
First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug
Authors: Pieren Michel , Abáigar Gutiérrez-Solana Ana , Antonijoan Arbós Rosa María , Boyle Gary W , Davila Myriam , Davy Maria , Gitzinger Marc , Husband Lisa , Martínez-Martínez María S , Mazarro Dolores Ochoa , Pefani Eleni , Penman Sophie L , Remuiñán Modesto J , Vlasakakis Georgios , Zeitlinger Markus , Dale Glenn E 
Published: April 2024

Abstract

Background
The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.

Objectives
A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).

Methods
Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0.5 to 40 mg) were tested under fasted and fed (10 mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30 mg) were administered once daily for 7 days in three sequential cohorts.

Results
No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events. Alpibectir showed rapid absorption after single dose (mean Tmax range of 0.88 to 1.53 h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3.87 h), a lower Cmax (−17.7%) and increased AUC0–t (+19.6%) compared with the fasted condition. Following repeat dosing, dose proportionality was shown for both Cmax and AUC0–tau. Accumulation of alpibectir was observed across all doses, with a more profound effect on AUC during a dosing interval (AUC0–tau) compared with Cmax (1.8- and 1.3-fold on average), respectively. Steady state was considered to have been achieved by Day 7 of dosing.

Conclusions
Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food.
Antimicrobial susceptibility testing data analysis over 3 years at the Yaoundé General Hospital, Cameroon
Authors: Ngogang Marie Paule , Nkoth Abel fils , Ngaleu Welysiane , Mfouapon Heroine , Ekoume Priscille , Nibeye Yannick , Medi Sike Christiane , Voundi Esther Voundi , Mouliom Mouiche Mohammed Moctar , Fonkoua Marie Christine , Toukam Michel , Mbopi-Keou Francois-Xavier 
Published: April 2024

Abstract

Background
Antimicrobial resistance (AMR) is a major health concern with high rates in low-income countries. Bacteriology laboratories sustain the fight against AMR by providing antibiotic susceptibility testing (AST) results to ensure appropriate therapies. These laboratories generate a lot of data, which are usually used for prospective interventions. Our study conducted in a lower-middle-income hospital setting aimed to describe the profile of bacteria isolated from the specimens received over 3 years, assess their susceptibility profile and identify potential gaps or area of improvement from the analysis of our data.

Methods
Monthly data were retrieved from registers for all specimens received between January 2020 until December 2022. Data were compiled and analysed using the R and WHONET software.

Results
Out of 3582 specimens received, 797 were culture positive (22.3%). Escherichia coli and Klebsiella pneumoniae were frequently isolated (30.5% and 24.2%, respectively). AST results analysis showed high resistance of Gram-negative bacteria to penams and cephems, whereas low resistance was observed to carbapenems. Susceptibility to antibiotics based on the AWaRe antibiotic classification was variable. The bacteriological profile in the various types of specimen was established and rational information to design a therapeutic protocol adapted to our hospital setting was obtained.

Conclusions
AST results may not only be used for prospective guidance for treatment, but rather cumulative data analysis can contribute to design effective antibiotic prescriptions and improve general practices at the laboratory. This is, however, dependent on a good record-keeping, standardization of practices and collaboration between clinicians and laboratory scientists.
Comparing indicators of disease severity among patients presenting to hospital for urinary tract infections before and during the COVID-19 pandemic
Authors: Patel Selina , Gill Martin , Hayward Andrew , Hopkins Susan , Copas Andrew , Shallcross Laura 
Published: April 2024

Abstract

Background
During the COVID-19 pandemic, patients may have delayed seeking healthcare for urinary tract infections (UTIs). This could have resulted in more severe presentation to hospital and different antibiotic usage.

Objectives
We explored evidence for such changes through existing national indicators of prescribing, and routine clinical data collected in the electronic health record (EHR).

Methods
We carried out a retrospective cohort study of patients presenting to two UK hospitals for UTIs, comparing two indicators of disease severity on admission before and during the pandemic: intravenous (IV) antibiotic use, and National Early Warning Score 2 (NEWS2). We developed regression models to estimate the effect of the pandemic on each outcome, adjusting for age, sex, ethnicity and index of multiple deprivation.

Results
During the pandemic, patients were less likely to present to hospital for UTI with NEWS2 of 0 or 1 [adjusted odds ratio (aOR): 0.66; 95% confidence interval (CI): 0.52–0.85] compared with before, more likely to present with score 2 (aOR: 1.52; 95% CI: 1.18–1.94), whereas the likelihood of presenting with a NEWS2 of &gt;2 remained the same (aOR: 1.06; 95% CI: 0.87–1.29). We did not find evidence that this limited increase in disease severity resulted in changes to IV antibiotic use on admission (adjusted risk ratio: 1.02; 95% CI: 0.91–1.15).

Conclusions
There may have been a small increase in disease severity at hospital presentation for UTI during the pandemic, which can be detected using routine data and not through national indicators of prescribing. Further research is required to validate these findings and understand whether routine data could support a more nuanced understanding of local antimicrobial prescribing practices.
Performance of a Norfentanyl Immunoassay in Specimens with Low Concentrations of Fentanyl and/or Norfentanyl
Authors: Uljon Sacha , Tolan Nicole V , Mahowald Grace K , Khaliq Tahira , Urwiller Elizabeth D , Fernandes Maria Daluz , Basu Sankha S , Kang Phillip , Erickson Timothy B , Hayes Bryan D , Chai Peter R , Melanson Stacy E F 
Published: April 2024

Abstract

Background
Many fentanyl immunoassays are limited in their ability to detect norfentanyl. Urine specimens collected from individuals who have been exposed to fentanyl frequently have detectable concentrations of norfentanyl (≥2 ng/mL) but low concentrations of fentanyl (&lt;2 ng/mL) by LC-MS/MS. The Lin-Zhi Fentanyl II Immunoassay (Lin-Zhi) claims 100% cross-reactivity with norfentanyl and therefore may detect exposure missed by other assays.

Methods
In addition to verifying the manufacturer's analytical sensitivity claims, we selected 92 urine specimens with low-positive Lin-Zhi results (1–99 absorbance units, lowest 10%) for analysis by the Immunalysis Health Equity Impact Assessment and ARK II fentanyl methods. The accuracy of the 3 immunoassays was compared to LC-MS/MS as the reference method.

Results
Spiking studies using purified fentanyl and norfentanyl and a set of 100 consecutive specimens confirmed the manufacturer's claims of limit of detection for fentanyl (3.8 ng/mL) and norfentanyl (5.0 ng/mL). However, the 92 low-positive patient specimens demonstrated concentrations of norfentanyl and fentanyl below 2.0 ng/mL by LC-MS/MS, with 47 (51%) having only norfentanyl detected. When comparing Lin-Zhi to the Immunalysis and ARK II immunoassays, only 27 (29%) of the 92 specimens were concordant. Fifty-two (57%) of the specimens were positive by LC-MS/MS and Lin-Zhi but false negative by one or both other immunoassays. Seven specimens (8%) were positive by Lin-Zhi but negative by the other immunoassays and had undetectable concentrations (&lt;2 ng/mL) of fentanyl and norfentanyl by LC-MS/MS.

Conclusions
The clinical sensitivity of the Lin-Zhi exceeds the manufacturer’s claims, providing results comparable to LC-MS/MS methods.
Re-examining the compatibility of US fair use with Korean copyright law: challenges and suggestions for Korean fair use
Authors: Kim Hyojung 
Published: April 2024

Abstract
Korea introduced the fair use provision into the Korean Copyright Act following the model of the US system. Despite its adoption into the Korean Copyright Act, it has not been significantly relied upon by the courts of Korea. This article asserts that strong and robust fair use is crucial for achieving the objectives of Korean copyright law, which is a cultivating culture through copyright protection and facilitating the fair use of copyrighted works. Particularly important in the digital era, fair use serves as a pivotal tool for adapting the copyright system to rapid technological changes. Taking a legal transplant theory perspective, this paper evaluates the process of transplanting US fair use into Korean copyright law. It contends that the oversight of essential considerations during this process has led to a lack of balance between certainty and flexibility in Korean fair use. Following this analysis, this article offers recommendations to refine Korean fair use within the context of successful legal transplants. These recommendations will cover legislative revision, the roles of the courts and the involvement of legal experts to enhance legal certainty, ensure appropriate flexibility, and ultimately, promote the widespread use of Korean fair use.
3D DLP-printed cannabinoid microneedles patch and its pharmacokinetic evaluation in rats
Authors: Bagde Arvind , Mosley-Kellum Keb , Spencer Shawn , Singh Mandip 
Published: April 2024

Abstract

Objective
The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system.

Methods
CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile.

Key findings
Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P &lt; .0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P &lt; .05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control).

Conclusion
Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system.
Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis
Authors: Tao Sha-Sha , Fang Xi , Xu Liang-Zi , Zhang Ruo-Di , Luo Qing-Qing , Tang Jian , Dai Xiao-Fan , Xu Shu-Zhen , Yang Xiao-Ke , Pana Hai-Feng 
Published: April 2024

Abstract

Background
Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA.

Methods
We enrolled 457 RA patients and 551 healthy controls and conducted a case–control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann–Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value &lt;.05 was considered statistically significant.

Results
The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = −4.497, P &lt; .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = −0.262, P = .018), white blood cell count (rs = −0.382, P = .004), platelet (rs = −0.293, P = .030), and disease activity score in 28 joints (rs = −0.271, P = .016) in RA patients.

Conclusions
This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.
Amorphous curcumin-based hydrogels to reduce the incidence of post-surgical intrauterine adhesions
Authors: Zhang Wenya , He Yuxin , Chu Yun , Zhai Yuanxin , Qian Song , Wang Xinhui , Jiang Pengju , Cui Pengfei , Zhang Yin , Wang Jianhao 
Published: April 2024

Abstract
The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing IUAs, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.