bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae
Authors: Zhao Meirong , Ma Jianfan , Zhang Lei , Qi Haishan 
Published: January 2024

AbstractMicrobial proteins are promising substitutes for animal- and plant-based proteins. S. cerevisiae, a generally recognized as safe (GRAS) microorganism, has been frequently employed to generate heterologous proteins. However, constructing a universal yeast chassis for efficient protein production is still a challenge due to the varying properties of different proteins. With progress in synthetic biology, a multitude of molecular biology tools and metabolic engineering strategies have been employed to alleviate these issues. This review first analyses the advantages of protein production by S. cerevisiae. The most recent advances in improving heterologous protein yield are summarized and discussed in terms of protein hyperexpression systems, protein secretion engineering, glycosylation pathway engineering and systems metabolic engineering. Furthermore, the prospects for efficient and sustainable heterologous protein production by S. cerevisiae are also provided.
Impact of a spatial repellent intervention on Anopheles kdr insecticide resistance allele in Sumba, Indonesia
Authors: Syahrani Lepa , Asih Puji B. S. , Bowolaksono Anom , Dwiranti Astari , Zubaidah Siti , Rozi Ismail E. , Permana Dendi H. , Bøgh Claus , Bangs Michael J. , Grieco John P. , Achee Nicole L. , Lobo Neil F. , Syafruddin Din 
Published: January 2024

Abstract
Background
The emergence of insecticide resistance and outdoor transmission in malaria-endemic areas underlines the urgent need to develop innovative tools, such as spatial repellents (SR), that may circumvent this residual transmission. With limited options for effective insecticides, regular resistance monitoring is warranted for selecting and using appropriate tools. This study evaluates the pyrethroid knockdown resistance (kdr) allele before and after implementing a transfluthrin-based spatial repellent (SR) intervention in placebo-treated clusters.

Methods
This study looks at the frequency distribution of the kdr allele in Sumba Island from June 2015 to August 2018. Insecticide susceptibility tests were carried out on female Anopheles sp. aged 3–5 days against permethrin 21.5 μg/ml, deltamethrin 12.5 μg/ml, and transfluthrin 10 μg/ml using CDC bottle assay. PCR sequencing of representative samples from adult mosquito collections and insecticide tests revealed the presence of kdr mutations (L1014F and L1014S) in the VGSC gene.

Results
A total of 12 Anopheles species, Anopheles tesselatus, Anopheles. aconitus, Anopheles barbirostris, Anopheles kochi, Anopheles annularis, Anopheles maculatus, Anopheles sundaicus, Anopheles flavirostris, Anopheles balabacensis, Anopheles indefinitus, Anopheles subpictus, and Anopheles vagus were analysed. Anopheles vagus and An. sundaicus predominated in the larval populations. Susceptibility assays for all insecticides identified fully susceptible phenotypes in all species examined. Anopheles increasing frequency of kdr mutant alleles during the 3 year SR deployment was observed in both SR-treated and placebo areas, a statistically significant increase occurred in each arm. However, it is unclear how significant SR is in causing the increase in mutant alleles. The L1014S, knockdown resistance east type (kdr-e) allele was detected for the first time among the mosquito samples in this study. The L1014F, knockdown resistance west type (kdr-w) allele and heteroduplex form (wild-type—mutant) were found in almost all Anopheles species examined, including An. vagus, An. aconitus, An. subpictus, An. tesselatus, An. annularis, An. flavirostris and An. sundaicus.

Conclusion
The presence of fully susceptible phenotypes over time, along with an increase in the frequency distribution of the L1014F/S mutations post-intervention, suggest drivers of resistance external to the study, including pyrethroid use in agriculture and long-lasting insecticidal nets (LLINs). However, this does not negate possible SR impacts that support resistance. More studies that enable the comprehension of possible SR-based drivers of resistance in mosquitoes need to be conducted.
The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia
Authors: Barshidi Asal , Ardeshiri Keivan , Ebrahimi Farbod , Alian Fatemeh , Shekarchi Ali Akbar , Hojjat-Farsangi Mohammad , Jadidi-Niaragh Farhad 
Published: January 2024

AbstractThe immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies.
A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma
Authors: Huang Tao , You Qi , Huang Dengjun , Zhang Yan , He Zhijie , Shen Xuguang , Li Fei , Shen Qiang , Onyebuchi Ifeanyi Christian , Wu Chengwei , Liu Feng , Zhu Shaojin 
Published: January 2024

Abstract
Background
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins.

Methods
The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms.

Results
PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription.

Conclusions
Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.
Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis
Authors: Ji Xiao-Yu , Guo Yu-Xin , Wang Li-Bin , Wu Wen-Cheng , Wang Jia-Qi , He Jin , Gao Rui , Rasouli Javad , Gao Meng-Yuan , Wang Zhen-Hai , Xiao Dan , Zhang Wei-Feng , Ciric Bogoljub , Zhang Yuan , Li Xing 
Published: January 2024

AbstractDemyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3′UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.
Satisfaction of antiretroviral therapy services and its associated factors among adult clients attending antiretroviral therapy in Woliso town, Ethiopia
Authors: Abdissa Bayisa , Abdissa Rahel , Derega Jiregna , Wake Senahara Korsa 
Published: January 2024

Abstract
Background
Antiretroviral therapy client satisfaction is a significant tool that enables to strengthen the quality of life of the clients. The study aimed to assess the satisfaction of clients with antiretroviral therapy services and its associated factors among adult clients attending antiretroviral therapy.

Methods
A cross-sectional study was undertaken from 28 August to 27 October 2022. Data were analyzed by using Logistic regression.

Result
Clients who did not attend formal education and attended health education information were significantly associated with satisfaction on antiretroviral therapy services.

Conclusion
HIV care services should introduce systematic health education programs to improve satisfaction with antiretroviral therapy services.
Comparison of the efficacy of Oxford unicondylar replacement for the treatment of spontaneous osteonecrosis of the knee versus medial knee osteoarthritis: a meta-analysis
Authors: Liu Pengyu , Li Liangliang , Yang Jiaju , Li Hao , Feng Yuhua , Qin Zhipeng , Zhang Min 
Published: January 2024

Abstract
Objective
Meta-analysis of the comparative efficacy of Oxford unicompartmental knee arthroplasty (OUKA) for the treatment of spontaneous osteonecrosis of the knee (SONK) and medial knee osteoarthritis (MKOA).

Methods
A computerized search was conducted for literature related to OUKA treatments of SONK and MKOA across various databases, including the China National Knowledge Infrastructure, WAN FANG, VIP, SinoMed, Cochrane Library, PubMed, Embase, and Web of Science, covering the period from each database's inception to September 2023. Literature screening, quality assessment and data extraction were performed according to the inclusion and exclusion criteria. After extracting the literature data, RevMan 5.4 software was applied to analyse the postoperative knee function score, postoperative knee mobility, postoperative pain, bearing dislocation rate, aseptic loosening, postoperative progression of posterolateral arthritis, and revision rate.

Result
A total of 9 studies were included, including 6 cohort studies and 3 matched case‒control studies. A total of 1544 knees were included, including 183 in the SONK group and 1361 in the MKOA group. The meta-analysis results showed that the SONK and MKOA groups showed a significant difference in postoperative knee function scores [MD = 0.16, 95% CI (− 1.20, 1.51), P = 0.82], postoperative knee mobility [MD = − 0.05, 95% CI (− 1.99. 1.89), P = 0.96], postoperative pain [OR = 0.89, 95% CI (0.23, 3.45), P = 0.87], rate of bearing dislocation [OR = 1.28, 95% CI (0.34, 4.81), P = 0.71], aseptic loosening [OR = 2.22, 95% CI (0.56, 8.82), P = 0.26], postoperative posterolateral arthritis progression [OR = 2.14, 95% CI (0.47, 9.86), P = 0.33], and revision rate [OR = 1.28, 95% CI (0.53, 3.04), P = 0.58] were not statistically significant.

Conclusion
OUKA treatment with SONK and MKOA can achieve similar satisfactory clinical results.
The epidemiology and the pathogen distribution of pediatric dacryocystitis in Chinese population 2017–2022
Authors: Sun Zhihong , Li Mingchao , Sun Huiqing 
Published: January 2024

Abstract
Background
Dacryocystitis is a common disease in pediatric ophthalmology. Analysis of basic information, flora distribution, and characteristics of information on drug-resistant bacteria in children with dacryocystitis for 6 years, providing evidence for ophthalmologic infection prevention and clinical management strategies.

Methods
A retrospective cohort study was conducted to evaluate the demographics of dacryocystitis in children and microbiological characteristics of secretion cultures, and to analyze the basic information, distribution of pathogenic bacteria, drug resistance, and to plot trendsand distribution pie charts according to the years.

Results
This study recruited 5791 specimens. Decreased incidence of dacryocystitis from 2020 to 2022 (including the COVID-19 pandemic). The age of highest incidence of dacryocystitis is infancy, followed by the neonatal period, and the incidence decreased with age. Streptococcus pneumoniae had the highest percentage in 2017, and the overall trend was decreasing, the difference was statistically significant (p < 0.001); Streptococcus mitis showed an overall increasing trend, with the highest incidence in 2022 and the lowest in 2017, with a statistically significant difference (p < 0.001); Haemophilus influenzae was the most common gram-negative bacteria with an overall decreasing trend (p < 0.001); The incidence of Catamoeba and Stenotrophomonas varied from year to year, with statistically significant differences (p = 0.010, p = 0.033, respectively). Methicillin-resistant Staphylococcus aureus (MRSA) had the lowest incidence in 2017 and 2022 the highest incidence in 2022, with a statistically significant difference in incidence between years (p = 0.003); β-lactamase-positive was the most common type of resistance, and MRSA was the second, with statistically significant differences between years (p = 0.003, p < 0.001, respectively). Streptococcus pneumoniae is a common etiologic agent of dacryocystitis in all age groups.

Conclusions
Dacryocystitis in children is significantly associated with age characteristics and infection-related pathogens, and infection prevention and control can help reduce the infection of related pathogens and the increase of new drug-resistant strains. Close monitoring of changes in pathogen distribution in ocular secretion cultures can help in early intervention and treatment of infectious dacryocystitis.
Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial
Authors: Obling Laust E. R. , Beske Rasmus P. , Meyer Martin A. S. , Grand Johannes , Wiberg Sebastian , Mohr Thomas , Damm-Hejmdal Anders , Forman Julie L. , Frikke-Schmidt Ruth , Folke Fredrik , Møller Jacob E. , Kjaergaard Jesper , Hassager Christian 
Published: January 2024

Abstract
Background
Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients.

Methods
The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times.

Results
A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference − 0.04 mcg/kg/min, 95% CI − 0.07 to − 0.01, p = 0.02). Moreover, after 12–24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from − 4.2 to − 3.8, 95% CIs from − 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from − 0.10 to − 0.07, 95% CIs from − 0.16 to − 0.01), while there were no major differences in heart rate (mean differences from − 4 to − 3, 95% CIs from − 11 to 3). These treatment differences between groups were also present 30–48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups.

Conclusions
Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients.
Trial registration: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776.

Graphic Abstract
PICALO: principal interaction component analysis for the identification of discrete technical, cell-type, and environmental factors that mediate eQTLs
Authors: Vochteloo Martijn , Deelen Patrick , Vink Britt ,   BIOS Consortium, Tsai Ellen A. , Runz Heiko , Andreu-Sánchez Sergio , Fu Jingyuan , Zhernakova Alexandra , Westra Harm-Jan , Franke Lude 
Published: January 2024

AbstractExpression quantitative trait loci (eQTL) offer insights into the regulatory mechanisms of trait-associated variants, but their effects often rely on contexts that are unknown or unmeasured. We introduce PICALO, a method for hidden variable inference of eQTL contexts. PICALO identifies and disentangles technical from biological context in heterogeneous blood and brain bulk eQTL datasets. These contexts are biologically informative and reproducible, outperforming cell counts or expression-based principal components. Furthermore, we show that RNA quality and cell type proportions interact with thousands of eQTLs. Knowledge of hidden eQTL contexts may aid in the inference of functional mechanisms underlying disease variants.
AQbD TLC-densitometric method approach along with green fingerprint and whiteness assessment for quantifying two combined antihypertensive agents and their impurities
Authors: Nagieb Hend M. , Abdelwahab Nada S. , Abdelrahman Maha M. , Zaazaa Hala E. , Ghoniem Nermine S. 
Published: January 2024

AbstractPreserving the environment, reducing the amount of waste resulting from chemical trials, and reducing the amount of energy consumed have currently become a pivotal global trend. An analytical quality by design (AQbD) based eco-friendly TLC-densitometric method was implemented for quantifying two antihypertensive agents, captopril (CPL) and hydrochlorothiazide (HCZ), along with their impurities; captopril disulphide (CDS), chlorothiazide (CTZ) and salamide (SMD). The analytical target profile (ATP) was first identified, followed by selecting the critical analytical attributes (CAAs), such as retardation factors and resolution between the separated peaks. Critical method parameters (CMPs) that may have a crucial influence on CAAs were identified and emanated through the quality risk assessment phase. A literature survey-based preliminary studies were performed, followed by optimization of the selected CMPs through a custom experimental design to attain the highest resolution with optimum retardation factors. Moreover, method robustness was also tested by testing the design space. Complete separation of the drugs and their impurities was achieved using ethyl acetate: glacial acetic acid (6: 0.6, v/v) as a developing system applied to a 12 cm length TLC plate at room temperature with UV scanning at 215 nm. Calibration graphs were found to be linear in the ranges of (0.70–6.00), (0.10–2.00), (0.20–1.00), (0.07–1.50) and (0.05–1.00) µg/band corresponding to CPL, HCZ, CDS, CTZ, and SMD, respectively. Four different green metric tools were used to evaluate the greenness profile of the proposed method, and results showed that it is greener than the reported HPLC method. Method whiteness assessment was also conducted. Moreover, the method performance was evaluated following the ICH guidelines, and the outcomes fell within the acceptable limits. The developed method could be approved for routine assay of the cited components in their pharmaceutical formulations and bulk powder without interference from the reported impurities. The issue of concern is saving money, especially in developing countries.