bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competing endogenous RNA network analysis of Turner syndrome patient-specific iPSC-derived cardiomyocytes reveals dysregulation of autosomal heart development genes by altered dosages of X-inactivation escaping non-coding RNAs
Authors: Luo Yumei , Chen Yapei , Ge Lingxia , Zhou Guanqing , Chen Yaoyong , Zhu Detu 
Published: December 2023

Abstract
Background
A 45,X monosomy (Turner syndrome, TS) is the only chromosome haploinsufficiency compatible with life. Nevertheless, the surviving TS patients still suffer from increased morbidity and mortality, with around one-third of them subjecting to heart abnormalities. How loss of one X chromosome drive these conditions remains largely unknown.

Methods
Here, we have generated cardiomyocytes (CMs) from wild-type and TS patient-specific induced pluripotent stem cells and profiled the mRNA, lncRNA and circRNA expression in these cells.

Results
We observed lower beating frequencies and higher mitochondrial DNA copies per nucleus in TS-CMs. Moreover, we have identified a global transcriptome dysregulation of both coding and non-coding RNAs in TS-CMs. The differentially expressed mRNAs were enriched of heart development genes. Further competing endogenous RNA network analysis revealed putative regulatory circuit of autosomal genes relevant with mitochondrial respiratory chain and heart development, such as COQ10A, RARB and WNT2, mediated by X-inactivation escaping lnc/circRNAs, such as lnc-KDM5C-4:1, hsa_circ_0090421 and hsa_circ_0090392. The aberrant expressions of these genes in TS-CMs were verified by qPCR. Further knockdown of lnc-KDM5C-4:1 in wild-type CMs exhibited significantly reduced beating frequencies.

Conclusions
Our study has revealed a genomewide ripple effect of X chromosome halpoinsufficiency at post-transcriptional level and provided insights into the molecular mechanisms underlying heart abnormalities in TS patients.
Dynamics of Staphylococcus aureus in patients and the hospital environment in a tertiary care hospital in the Netherlands
Authors: van der Schoor Adriënne S. , Voor in ’t holt Anne F. , Zandijk Willemien H.A. , Bruno Marco J. , Gommers Diederik , van den Akker Johannes P.C. , Hendriks Johanna M. , Severin Juliëtte A. , Klaassen Corné H.W. , Vos Margreet C. 
Published: December 2023

Abstract
Background
The dynamics of Staphylococcus aureus in patients and the hospital environment are relatively unknown. We studied these dynamics in a tertiary care hospital in the Netherlands.

Methods
Nasal samples were taken from adult patients at admission and discharge. Isolates cultured from clinical samples taken before and during hospitalization from these patients were included. Environmental samples of patient rooms were taken over a three-year period. Finally, isolates from clinical samples from patients with an epidemiological link to S. aureus positive rooms were included. Staphylococcal protein A (spa) typing was performed.

Results
Nasal samples were taken from 673 patients. One hundred eighteen (17.5%) were positive at admission and discharge, 15 (2.2%) patients acquired S. aureus during hospitalization. Nineteen patients had a positive clinical sample during hospitalization, 15.9% of the S. aureus were considered as from an exogenous source. One hundred and forty (2.8%) environmental samples were S. aureus positive. No persistent contamination of surfaces was observed. Isolates were highly diverse: spa typing was performed for 893 isolates, identifying 278 different spa types, 161 of these spa types were observed only once.

Conclusion
Limited transmission could be identified between patients and the hospital environment, and from patient-to-patient. Exogenous acquisition was assumed to occur in 15% of clinical samples. Environmental contamination was infrequent, temporarily, and coincided with the strain from the patient admitted to the room at that time. MRSA was rare and not found in the environment.
Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway
Authors: He Zhaoqi , Zhao Caijun , He Yuhong , Liu Zhuoyu , Fan Guyue , Zhu Kun , Wang Yiqi , Zhang Naisheng , Fu Yunhe , Hu Xiaoyu 
Published: December 2023

Abstract
Background
Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.

Results
First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.

Conclusions
In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
Precise tilt measurement by seafloor borehole tiltmeters at the Nankai Trough subduction zone
Authors: Tsuji Shuhei , Araki Eiichiro , Yokobiki Takashi , Nishida Shuhei , Machida Yuya , Zumberge Mark , Takahashi Keisuke 
Published: December 2023

AbstractIn this study, geodetic and seismic phenomena occurring in the subduction zone were observed with two tiltmeters that were installed in seafloor boreholes drilled in the Kumano Basin in the Nankai Trough, southwest Japan. We used one electrolytic-type tiltmeter and one pendulum-type tiltmeter installed 6 and 19 m below the seafloor, respectively. The two tiltmeters have been continuously operated since 2019 and 2021, respectively. The records of the two tiltmeters showed microseisms, seismic signals of normal earthquakes, and variations that correlated well with the M2 tide (tidal response). The noise environment relative to existing seafloor observatories was assessed by comparing the power spectral densities of the tiltmeters and broadband seismometers in the seismic frequency band. The two tiltmeters and the seismometers showed similar spectral peaks in the microseism band, and at lower frequencies below 10–2 Hz, the pendulum tiltmeter had a noise level that was up to 20 dB lower than that of the broadband seismometers. The tidal responses of the tiltmeters were analyzed to reveal corresponding mechanisms because a large amplitude of the tidal response makes it difficult to detect geodetic phenomena. Considerable azimuthal dependence was observed in the NW–SE direction for both tiltmeters. The principal direction was approximately the same as the down-slope direction of the local bathymetry. This tendency was thus interpreted to be caused by the differences in the thickness of the sedimentary layer along the direction of the slope. Furthermore, the validity of the tilt measurements for the two tiltmeters was demonstrated by in-situ loading experiments, where the theoretical response of an elastic half-space medium was computed and compared with the experimental results. The results of the loading experiments can be explained using theoretical values with a set of realistic elastic moduli.
Graphical Abstract
Efficacy and safety of praziquantel treatment against Schistosoma mansoni infection among pre-school age children in southern Ethiopia
Authors: Tadele Tafese , Astatkie Ayalew , Tadesse Birkneh Tilahun , Makonnen Eyasu , Aklillu Eleni , Abay Solomon Mequanente 
Published: December 2023

Abstract
Background
Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control and eliminate schistosomiasis as a public health problem. This intervention mainly targets school age children, and pre-school age children (pre-SAC) are excluded from receiving preventive chemotherapy, partly due to scarcity of data on praziquantel treatment outcomes.

Methods
We conducted active efficacy and safety surveillance of praziquantel treatment among 240 Schistosoma mansoni-infected pre-SAC who received a single dose of praziquantel (40 mg/kg) in southern Ethiopia. The study outcomes were egg reduction rates (ERR) and cure rates (CRs) four weeks after treatment using the Kato–Katz technique and treatment-associated adverse events (AEs) that occurred within 8 days post-treatment.

Results
The overall ERR was 93.3% (WHO reference threshold ≥ 90%), while the CR was 85.2% (95% CI = 80.0–89.5%). Baseline S. mansoni infection intensity was significantly associated with CRs, 100% among light infected than moderate (83.4%) or heavy (29.4%) infected children. An increase of 100 in baseline S. mansoni egg count per gram of stool resulted in a 26% (95% CI: 17%, 34%) reduction in the odds of cure. The incidence of experiencing at least one type of AE was 23.1% (95% CI: 18.0%, 29.0%). Stomachache, diarrhea, and nausea were the most common AEs. AEs were mild-to-moderate grade and transient. Pre-treatment moderate (ARR = 3.2, 95% CI: 1.69, 6.14) or heavy infection intensity (ARR = 6.5, 95% CI: 3.62, 11.52) was a significant predictor of AEs (p < 0.001). Sex, age, or soil-transmitted helminth coinfections were not significant predictors of CR or AEs.

Conclusions
Single-dose praziquantel is tolerable and effective against S. mansoni infection among pre-SAC, and associated AEs are mostly mild-to-moderate and transient. However, the reduced CR in heavily infected and AEs in one-fourth of S. mansoni-infected pre-SAC underscores the need for safety and efficacy monitoring, especially in moderate-to-high infection settings. Integrating pre-SACs in the national deworming programs is recommended to accelerate the elimination of schistosomiasis as a public health problem.
The role of leadership level in college students’ facial emotion recognition: evidence from event-related potential analysis
Authors: Gu Huang , Du Shunshun , Jin Peipei , Wang Chengming , He Hui , Zhao Mingnan 
Published: December 2023

AbstractWhile the role of emotion in leadership practice is well-acknowledged, there is still a lack of clarity regarding the behavioral distinctions between individuals with varying levels of leadership and the underlying neurocognitive mechanisms at play. This study utilizes facial emotion recognition in conjunction with electroencephalograms to explore the temporal dynamics of facial emotion recognition processes among college students with high and low levels of leadership. The results showed no significant differences in the amplitude of P1 during the early stage of facial emotion recognition between the two groups. In the middle stage of facial emotion recognition, the main effect of group was significant on the N170 component, with higher N170 amplitude evoked in high-leadership students than low-leadership students. In the late stage of facial emotion recognition, low-leadership students evoked greater LPP amplitude in the temporal-parietal lobe when recognizing happy facial emotions compared to high-leadership students. In addition, time–frequency results revealed a difference in the alpha frequency band, with high-leadership students exhibiting lower alpha power than low-leadership students. The results suggest differences in the brain temporal courses of facial emotion recognition between students with different leadership levels, which are mainly manifested in the middle stage of structural encoding and the late stage of delicate emotional processing during facial emotion recognition.
Nanoemulsion drug delivery system loaded with imiquimod: a QbD-based strategy for augmenting anti-cancer effects
Authors: Jadhav Shital Tanaji , Salunkhe Vijay Rajaram , Bhinge Somnath Devidas 
Published: December 2023

Abstract
Background
Skin cancer is becoming a public health concern due to increased exposure to environmental pollutants and UV rays, among other factors. In India, skin neoplasms constitute 2–3% of all human cancer cases, whereas in the USA, 2–3 million cases of non-melanoma skin cancer are reported annually. Various drugs are available in the market for treating skin cancer. Imiquimod (IMQ) is one such drug approved by the USFDA for managing basal cell malignancy, external genital warts, and actinic keratosis. The conventional dosage form of IMQ cream has several side effects that can lead to therapy interruption. Therefore, the present work aims to develop an IMQ nanoemulsion with improved solubility, in vitro drug release and stability. Nanoemulsion was formulated using oleic acid/rose oil, with polysorbate 20/propylene glycol selected as the oil phase and Smix, respectively. Optimization carried out using a 32 factorial design with the aid of a quadratic model. Characterization was conducted for parameters, namely viscosity, pH, drug content, globule size, zeta potential and entrapment efficiency. Thermodynamic stability studies were conducted to assess the stability of the formulation. Furthermore, the optimized system was subjected to TEM analysis, in vitro drug release and in vitro cytotoxicity assay (MTT assay).

Results
Nanoemulsions were found to be in the size range of 152.80–470.13 nm and exhibited a spherical shape. Zeta potential values ranged from − 28.93 to − 58.48 mV. DSC measurements indicated the complete solubilization of IMQ in the nanoemulsion system. The optimized formulation F1 displayed the following characteristics: a globule size < 200 nm, a zeta potential > − 55 mV, a polydispersity index < 0.2, % drug content of 102.89 ± 1.06, % entrapment efficiency of 97.59 ± 0.24, a pH of 4.77 ± 0.06, and a viscosity of 4.06 ± 0.06 poise. In vitro IMQ release studies of nanoemulsion and commercial cream showed approximately 70% and 34% drug release, respectively, at the end of 8 h. Moreover, the in vitro cytotoxicity assay depicted that F1 exhibited greater cytotoxic potential compared to the commercial formulation against the A431 cell line.

Conclusion
The present investigation showed a significant improvement in in vitro drug release of the BCS class IV drug IMQ and enhanced cytotoxic activity against cancerous cells. IMQ-loaded nanoemulsion represents a promising vehicle for delivering treatment to the skin for treating skin cancer.

Graphical abstract
Molecular and physiological responses to salt stress in salinity-sensitive and tolerant Hibiscus rosa-sinensis cultivars
Authors: Trivellini Alice , Carmassi Giulia , Scatena Guido , Vernieri Paolo , Ferrante Antonio 
Published: December 2023

AbstractOrnamental plants are used to decorate urban and peri-urban areas, and during their cultivation or utilisation, they can be exposed to abiotic stress. Salinity is an abiotic stress factor that limits plant growth and reduces the ornamental value of sensitive species. In this study, transcriptomic analysis was conducted to identify genes associated with tolerance or sensitivity to salinity in two hibiscus (Hibiscus rosa-sinensis L.) cultivars, ‘Porto’ and ‘Sunny wind’. The physiological and biochemical parameters of plants exposed to 50, 100, or 200 mM NaCl and water (control) were monitored. Salinity treatments were applied for six weeks. After four weeks, differences between cultivars were clearly evident and ‘Porto’ was more tolerant than ‘Sunny wind’. The tolerant cultivar showed lower electrolyte leakage and ABA concentrations, and higher proline content in the leaves. Accumulation of Na in different organs was lower in the flower organs of ‘Porto’. At the molecular level, several differential expressed genes were observed between the cultivars and flower organs. Among the highly expressed DEGs, coat protein, alcohol dehydrogenase, and AP2/EREBP transcription factor ERF-1. Among the downregulated genes, GH3 and NCED were the most interesting. The differential expression of these genes may explain the salt stress tolerance of ‘Porto’.
Graphical Abstract
Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia
Authors: Shim Jaeyoon , Ahn Chang Ho , Park Seung Shin , Noh Jongsung , Lee Chaelin , Lee Sang Won , Kim Jung Hee , Choi Man Ho 
Published: December 2023

Abstract

Context
Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are limited to differentiate subtypes.

Objective
We explored metabolic characterizations and identified multiple diagnostic biomarkers specific to individual subtypes of CAH.

Methods
Liquid chromatography-mass spectrometry-based profiling of 33 adrenal steroids was developed and applied to serum samples obtained from 67 CAH patients and 38 healthy volunteers.

Results
Within- and between-run precisions were 95.4% to 108.3% and 94.1% to 110.0%, respectively, while all accuracies were &lt;12% and the correlation coefficients (r2) were &gt; 0.910. Metabolic ratios corresponding to 21-hydroxylase characterized 21-hydroxylase deficiency (21-OHD; n = 63) from healthy controls (area under the curve = 1.0, P &lt; 1 × 10−18 for all) and other patients with CAH in addition to significantly increased serum 17α-hydroxyprogesterone (P &lt; 1 × 10−16) and 21-deoxycortisol (P &lt; 1 × 10−15) levels. Higher levels of mineralocorticoids, such as corticosterone (B) and 18-hydroxyB, were observed in 17α-hydroxylase deficiency (17α-OHD; N = 3), while metabolic ratio of dehydroepiandrosterone sulfate to pregnenolone sulfate was remarkably decreased against all subjects. A patient with 11β-hydroxylase deficiency (11β-OHD) demonstrated significantly elevated 11-deoxycortisol and its metabolite tetrahydroxy-11-deoxyF, with reduced metabolic ratios of 11β-hydroxytestosterone/testosterone and 11β-hydroxyandrostenedione/androstenedione. The steroid profiles resulted in significantly decreased cortisol metabolism in both 21-OHD and 17α-OHD but not in 11β-OHD.

Conclusion
The metabolic signatures with specific steroids and their corresponding metabolic ratios may reveal individual CAH subtypes. Further investigations with more substantial sample sizes should be explored to enhance the clinical validity.
A Sequential Follower Refinement Algorithm for Robust Surgery Scheduling
Authors: Bansal Ankit , Richard Jean-Philippe , Berg Bjorn P. , Huang Yu-Li 
Published: December 2023

An algorithm for the two-stage robust optimization surgery-to-operating room allocation problem is presented. The second-stage problem is an integer linear program whose convex hull is approximated using three types of specialized valid inequalities and Chvátal-Gomory cuts. The resulting linear relaxation of the second-stage problem is then dualized and integrated into the first-stage problem. The resulting mixed integer linear program, which is an approximation of the original problem, is then solved using a commercial solver. If the solution of this model is not optimal for the second-stage problem, valid inequalities for the second-stage problem are generated, yielding a type of column-generation based approach that we refer to as the sequential follower refinement (SFR) algorithm. Data from an academic medical center are used to compare the computational performance of SFR with the constraint and column generation (C&CG) algorithm, which is the only exact approach that has been specifically applied for this problem in the literature. An extensive numerical study of SFR and its computational characteristics is presented that shows that SFR yields better-quality solutions compared with C&CG, even as the termination criterion of SFR is met much sooner, especially for problems involving higher number of surgeries.History: Accepted by Paul Brooks, Area Editor for Applications in Biology, Medicine, & Healthcare.Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0191 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0191 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Low loss and ultra-broadband design of an integrated 3  dB power splitter centered at 2  µm
Authors: Liu Zhiming , Dong Yue , Xu Yin , Zhang Bo , Ni Yi 
Published: December 2023

Because chemical gas is sensitive to absorption in the 2 µm band, and 2 µm matches the absorption band of the remote sensing material, many remote sensors and optical sensors are designed to operate in the 2 µm wavelength region. In this paper, we designed an integrated 3 dB power splitter centered at 2 µm. The study of this device is built on a silicon-on-insulator (SOI) platform. We introduced a subwavelength grating (SWG) to improve the performance of the device. We used the three-dimensional finite-difference time-domain (3D FDTD) method to analyze the effect of the structure on the power splitter. The insertion loss (IL) of the fundamental TE mode is only 0.04 dB at 2 µm and its bandwidth of IL <0.45dB is 940 nm (1570–2510 nm). It is suitable for multidomain and all-band photonic integrated circuits at 2 µm.