bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway
Authors: Dai Lei , Chen Yu , Wu Jinhua , He Zhen , Zhang Yueqi , Zhang Wenjun , Xie Yang , Zeng Hesong , Zhong Xiaodan 
Published: February 2024

Abstract
Background
Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model.

Methods
We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1β and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously.

Results
C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1β and IL-18) release. Besides, C3a enhanced IL-1β activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro.

Conclusion
Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.
Intranasal delivery of mitochondria targeted neuroprotective compounds for traumatic brain injury: screening based on pharmacological and physiological properties
Authors: Pandya Jignesh D. , Musyaju Sudeep , Modi Hiren R. , Okada-Rising Starlyn L. , Bailey Zachary S. , Scultetus Anke H. , Shear Deborah A. 
Published: February 2024

AbstractTargeting drugs to the mitochondrial level shows great promise for acute and chronic treatment of traumatic brain injury (TBI) in both military and civilian sectors. Perhaps the greatest obstacle to the successful delivery of drug therapies is the blood brain barrier (BBB). Intracerebroventricular and intraparenchymal routes may provide effective delivery of small and large molecule therapies for preclinical neuroprotection studies. However, clinically these delivery methods are invasive, and risk inadequate exposure to injured brain regions due to the rapid turnover of cerebral spinal fluid. The direct intranasal drug delivery approach to therapeutics holds great promise for the treatment of central nervous system (CNS) disorders, as this route is non-invasive, bypasses the BBB, enhances the bioavailability, facilitates drug dose reduction, and reduces adverse systemic effects. Using the intranasal method in animal models, researchers have successfully reduced stroke damage, reversed Alzheimer’s neurodegeneration, reduced anxiety, improved memory, and delivered neurotrophic factors and neural stem cells to the brain. Based on literature spanning the past several decades, this review aims to highlight the advantages of intranasal administration over conventional routes for TBI, and other CNS disorders. More specifically, we have identified and compiled a list of most relevant mitochondria-targeted neuroprotective compounds for intranasal administration based on their mechanisms of action and pharmacological properties. Further, this review also discusses key considerations when selecting and testing future mitochondria-targeted drugs given intranasally for TBI.
Graphical Abstract
Antibacterial activities of titanium dioxide (TiO2) nanotube with planar titanium silver (TiAg) to prevent orthopedic implant infection
Authors: Zhang Lihong , Jin Zhihui 
Published: February 2024

Abstract
Background
Orthopedic implant infection has become a common catastrophic complication after various orthopedic implants, which can lead to prolonged use of antibiotics and even surgical failure. The quality of care (QoC) of orthopedic implant infection is very important.

Methods
Titanium dioxide (TiO2) nanotube array with planar TiAg was prepared, and their antibacterial rates were tested. 400 patients hospitalized in the Department of Orthopedics of Wuhan Fourth Hospital from May 2019 to May 2020 were selected as controls (before QoC evaluation system of orthopedics), and 400 patients hospitalized from June 2020 to June 2021 were selected as observation group (after QoC evaluation system of orthopedics).

Results
Regardless of Staphylococcus aureus or Escherichia coli, the antibacterial rate of TiO2 nanotube array with planar TiAg was clearly higher than that of pure iron film on the 10th and 20th days (P < 0.05). The accuracy of hospitalization assessment, disease assessment, adverse event intervention, nursing record filing and nursing satisfaction in observation group were higher as against controls (P < 0.05).

Conclusion
The TiO2 nanotube array with planar TiAg has good antibacterial property, which can effectively prevent orthopedic implant infection. The construction of QoC evaluation system for orthopedic specialists can effectively improve the QoC of orthopedic specialists.
Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease
Authors: Liu Pei-Yu , Hong Kin-Fong , Liu Ya-Di , Sun Zhong-Yan , Zhao Ting-Ting , Li Xu-Ling , Lao Chi-Chou , Tan Shu-Feng , Zhang Hai-Ying , Zhao Yong-Hua , Xie Ying , Xu You-Hua 
Published: February 2024

Abstract
Background
Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear.

Methods
In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods.

Results
Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress.

Conclusion
Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.
The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis
Authors: Ma Jing , Zhang Huiqiu , Liang Feng , Li Guanxi , Pang Xiaomin , Zhao Rongjuan , Wang Juan , Chang Xueli , Guo Junhong , Zhang Wei 
Published: February 2024

Abstract
Background
Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally.

Methods
In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR.

Results
Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05).

Conclusions
Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.
Administration of methylene blue in septic shock: pros and cons
Authors: Arias-Ortiz Julian , Vincent Jean-Louis 
Published: February 2024

AbstractSeptic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.
RUBICON: a framework for designing efficient deep learning-based genomic basecallers
Authors: Singh Gagandeep , Alser Mohammed , Denolf Kristof , Firtina Can , Khodamoradi Alireza , Cavlak Meryem Banu , Corporaal Henk , Mutlu Onur 
Published: February 2024

AbstractNanopore sequencing generates noisy electrical signals that need to be converted into a standard string of DNA nucleotide bases using a computational step called basecalling. The performance of basecalling has critical implications for all later steps in genome analysis. Therefore, there is a need to reduce the computation and memory cost of basecalling while maintaining accuracy. We present , a framework to develop efficient hardware-optimized basecallers. We demonstrate the effectiveness of by developing , the first hardware-optimized mixed-precision basecaller that performs efficient basecalling, outperforming the state-of-the-art basecallers. We believe offers a promising path to develop future hardware-optimized basecallers.
Effectiveness of IT-supported patient recruitment: study protocol for an interrupted time series study at ten German university hospitals
Authors: Boeker Martin , Zöller Daniela , Blasini Romina , Macho Philipp , Helfer Sven , Behrens Max , Prokosch Hans-Ulrich , Gulden Christian 
Published: February 2024

Abstract
Background
As part of the German Medical Informatics Initiative, the MIRACUM project establishes data integration centers across ten German university hospitals. The embedded MIRACUM Use Case “Alerting in Care - IT Support for Patient Recruitment”, aims to support the recruitment into clinical trials by automatically querying the repositories for patients satisfying eligibility criteria and presenting them as screening candidates. The objective of this study is to investigate whether the developed recruitment tool has a positive effect on study recruitment within a multi-center environment by increasing the number of participants. Its secondary objective is the measurement of organizational burden and user satisfaction of the provided IT solution.

Methods
The study uses an Interrupted Time Series Design with a duration of 15 months. All trials start in the control phase of randomized length with regular recruitment and change to the intervention phase with additional IT support. The intervention consists of the application of a recruitment-support system which uses patient data collected in general care for screening according to specific criteria. The inclusion and exclusion criteria of all selected trials are translated into a machine-readable format using the OHDSI ATLAS tool. All patient data from the data integration centers is regularly checked against these criteria. The primary outcome is the number of participants recruited per trial and week standardized by the targeted number of participants per week and the expected recruitment duration of the specific trial. Secondary outcomes are usability, usefulness, and efficacy of the recruitment support. Sample size calculation based on simple parallel group assumption can demonstrate an effect size of d=0.57 on a significance level of 5% and a power of 80% with a total number of 100 trials (10 per site). Data describing the included trials and the recruitment process is collected at each site. The primary analysis will be conducted using linear mixed models with the actual recruitment number per week and trial standardized by the expected recruitment number per week and trial as the dependent variable.

Discussion
The application of an IT-supported recruitment solution developed in the MIRACUM consortium leads to an increased number of recruited participants in studies at German university hospitals. It supports employees engaged in the recruitment of trial participants and is easy to integrate in their daily work.
Novel tetrahydroisoquinolines as DHFR and CDK2 inhibitors: synthesis, characterization, anticancer activity and antioxidant properties
Authors: Sayed Eman M. , Bakhite Etify A. , Hassanien Reda , Farhan Nasser , Aly Hanan F. , Morsy Salma G. , Hassan Nivin A. 
Published: February 2024

AbstractIn this study, we synthesized new 5,6,7,8-tetrahydroisoquinolines and 6,7,8,9-tetrahydrothieno[2,3-c]isoquinolines based on 4-(N,N-dimethylamino)phenyl moiety as expected anticancer and/or antioxidant agents. The structure of all synthesized compounds were confirmed by spectral date (FT-IR, 1H NMR, 13C NMR) and elemental analysis. We evaluated the anticancer activity of these compounds toward two cell lines: A459 cell line (lung cancer cells) and MCF7 cell line (breast cancer cells). All tested compounds showed moderate to strong anti-cancer activity towards the two cell lines. Compound 7e exhibited the most potent cytotoxic activity against A549 cell line (IC50: 0.155 µM) while compound 8d showed the most potent one against MCF7 cell line (IC50: 0.170 µM) in comparison with doxorubicin. In addition, we examined the effect of compounds 7e and 8d regarding the growth of A549 and MCF7 cell lines, employing flow cytometry and Annexin V-FITC apoptotic assay. Our results showed that compound 7e caused cell cycle arrest at the G2/M phase with a 79-fold increase in apoptosis of A459 cell line. Moreover, compound 8d caused cell cycle arrest at the S phase with a 69-fold increase in apoptosis of MCF7 cell line. Furthermore, we studied the activity of these compounds as enzyme inhibitors against several enzymes. Our findings by docking and experimental studies that compound 7e is a potent CDK2 inhibitor with IC50 of 0.149 µM, compared to the Roscovitine control drug with IC50 of 0.380 µM. We also found that compound 8d is a significant DHFR inhibitor with an IC50 of 0.199 µM, compared to Methotrexate control drug with IC50 of 0.131 µM. Evaluation of the antioxidant properties of ten compounds was also studied in comparison with Vitamin C. Compounds 1, 3, 6, 7c and 8e have higher antioxidant activity than Vitamin C which mean that these compounds can used as potent antioxidant drugs.
Graphical Abstract
Pembrolizumab-induced secondary adrenal insufficiency due to adrenocorticotrophic hormone deficiency in a patient with non-small-cell lung carcinoma: a case report
Authors: Fujimiya Tatsuhiro , Azuma Kanako , Togashi Yuki , Kuwata Koji , Unezaki Sakae , Takeuchi Hironori 
Published: February 2024

Abstract
Background
Pembrolizumab can cause immune-related adverse events such as adrenal insufficiency (AI). However, there is no consensus regarding appropriate monitoring of adrenal function during subsequent chemotherapy in patients who have received immune checkpoint inhibitors (ICIs) such as pembrolizumab.

Case presentation
In this report, we discuss the case of a 60s-year-old male patient with non-small cell lung cancer receiving chemotherapy who developed secondary AI due to adrenocorticotrophic hormone (ACTH) deficiency 8 months after the discontinuation of pembrolizumab, which was 17 months after the initiation of pembrolizumab immunotherapy. After 5 months of chemotherapy, he developed fever and diarrhoea, after which chemotherapy was discontinued. Thereafter, he was hospitalised owing to the development of general fatigue and anorexia. Although cortisol and ACTH levels were not measured during chemotherapy, they were measured before hospitalisation, and secondary AI was suspected. After admission, a detailed endocrine workup was performed, and the patient was diagnosed with secondary AI due to ACTH deficiency. Treatment with hydrocortisone was initiated, which markedly improved his general fatigue and anorexia. The patient showed no evidence of progressive disease 9 months after the discontinuation of pembrolizumab.

Conclusions
Although rare, the possibility of AI should be considered in patients who have received ICIs when nonspecific symptoms develop during or after subsequent chemotherapy, and measurements of endocrine function (including cortisol and ACTH levels) should be performed.
A guide for social science journal editors on easing into open science
Authors: Silverstein Priya , Elman Colin , Montoya Amanda , McGillivray Barbara , Pennington Charlotte R. , Harrison Chase H. , Steltenpohl Crystal N. , Röer Jan Philipp , Corker Katherine S. , Charron Lisa M. , Elsherif Mahmoud , Malicki Mario , Hayes-Harb Rachel , Grinschgl Sandra , Neal Tess , Evans Thomas Rhys , Karhulahti Veli-Matti , Krenzer William L. D. , Belaus Anabel , Moreau David , Burin Debora I. , Chin Elizabeth , Plomp Esther , Mayo-Wilson Evan , Lyle Jared , Adler Jonathan M. , Bottesini Julia G. , Lawson Katherine M. , Schmidt Kathleen , Reneau Kyrani , Vilhuber Lars , Waltman Ludo , Gernsbacher Morton Ann , Plonski Paul E. , Ghai Sakshi , Grant Sean , Christian Thu-Mai , Ngiam William , Syed Moin 
Published: February 2024

AbstractJournal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors:www.dpjedi.org) has collated several resources on embedding open science in journal editing (www.dpjedi.org/resources). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide:https://doi.org/10.31219/osf.io/hstcx).
How do humans learn about the reliability of automation?
Authors: Strickland Luke , Farrell Simon , Wilson Micah K. , Hutchinson Jack , Loft Shayne 
Published: February 2024

AbstractIn a range of settings, human operators make decisions with the assistance of automation, the reliability of which can vary depending upon context. Currently, the processes by which humans track the level of reliability of automation are unclear. In the current study, we test cognitive models of learning that could potentially explain how humans track automation reliability. We fitted several alternative cognitive models to a series of participants’ judgements of automation reliability observed in a maritime classification task in which participants were provided with automated advice. We examined three experiments including eight between-subjects conditions and 240 participants in total. Our results favoured a two-kernel delta-rule model of learning, which specifies that humans learn by prediction error, and respond according to a learning rate that is sensitive to environmental volatility. However, we found substantial heterogeneity in learning processes across participants. These outcomes speak to the learning processes underlying how humans estimate automation reliability and thus have implications for practice.
Machine translation: Turkish–English bilingual speakers’ accuracy detection of evidentiality and preference of MT
Authors: Tosun Sümeyra 
Published: February 2024

AbstractMachine translation (MT) is the automated process of translating text between different languages, encompassing a wide range of language pairs. This study focuses on non-professional bilingual speakers of Turkish and English, aiming to assess their ability to discern accuracy in machine translations and their preferences regarding MT. A particular emphasis is placed on the linguistically subtle yet semantically meaningful concept of evidentiality. In this experimental investigation, 36 Turkish–English bilinguals, comprising both early and late bilinguals, were presented with simple declarative sentences. These sentences varied in their evidential meaning, distinguishing between firsthand and non-firsthand evidence. The participants were then provided with MT of these sentences in both translation directions (Turkish to English and English to Turkish) and asked to identify the accuracy of these translations. Additionally, participants were queried about their preference for MT in four crucial domains: medical, legal, academic, and daily contexts. The findings of this study indicated that late bilinguals exhibited a superior ability to detect translation accuracy, particularly in the case of firsthand evidence translations, compared to their early bilingual counterparts. Concerning the preference for MT, age of acquisition and the accuracy detection of non-firsthand sentence translations emerged as significant predictors.