bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory therapy of atherosclerosis: focusing on IKKβ
Authors: Gan Jiali , Guo Lin , Zhang Xiaolu , Yu Qun , Yang Qiuyue , Zhang Yilin , Zeng Wenyun , Jiang Xijuan , Guo Maojuan 
Published: February 2023

AbstractChronic low-grade inflammation has been identified as a major contributor in the development of atherosclerosis. Nuclear Factor-κappa B (NF-κB) is a critical transcription factors family of the inflammatory pathway. As a major catalytic subunit of the IKK complex, IκB kinase β (IKKβ) drives canonical activation of NF-κB and is implicated in the link between inflammation and atherosclerosis, making it a promising therapeutic target. Various natural product derivatives, extracts, and synthetic, show anti-atherogenic potential by inhibiting IKKβ-mediated inflammation. This review focuses on the latest knowledge and current research landscape surrounding anti-atherosclerotic drugs that inhibit IKKβ. There will be more opportunities to fully understand the complex functions of IKKβ in atherogenesis and develop new effective therapies in the future.
Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation
Authors: Liu Kaiyuan , Zhang Li , Lu Hengli , Wen Yingfei , Bi Bo , Wang Guocheng , Jiang Yingying , Zeng Leli , Zhao Jing 
Published: February 2023

Abstract
Background
Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT.

Results
Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT.

Conclusions
Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.

Graphical Abstract
Low-intensity pulsed ultrasound triggers a beneficial neuromodulation in dementia mice with chronic cerebral hypoperfusion via activation of hippocampal Fndc5/irisin signaling
Authors: Song Degang , Chen Xiaomin , Zhou Na , Yuan Yi , Geng Shuo , Zhang Cong , Zhao Zhe , Wang Xingran , Bao Xinran , Lan Xifa , Zhang Xiangjian 
Published: February 2023

Abstract
Background
Exercise-related signaling Fndc5/irisin expresses in brain and acts as a crucial regulator of cognitive function, but its detailed roles in vascular dementia (VaD) are still unclear. Low intensity pulsed ultrasound (LIPUS), a novel brain stimulation approach, has been suggested as a promising treatment for dementia. Here, we investigated the activity and efficacy of Fndc5/irisin in experimental VaD, further explored whether the potential effects of LIPUS on VaD is related to Fndc5/irisin.

Methods
Mouse model of VaD was established with chronic cerebral hypoperfusion (CCH) using bilateral common carotid arteries stenosis (BCAS). Transcranial LIPUS was applied 24 h after BCAS and subsequently daily with a stimulation time of 5 min at an ultrasound pressure of 0.51 MPa for a period of 28 days. The levels of Fndc5/irisin in different brain regions, the hippocampal long-term potentiation and anti-inflammatory cytokines were investigated at day 28 after cognitive evaluation. Global Fndc5 knock-out (F5KO), forced expression or knockdown of Fndc5, and recombinant irisin application were respectively employed for mechanism exploration. The neuron dendritic spine density and astrocyte phenotype were detected in vitro.

Results
Fndc5/irisin was reduced in hippocampus of BCAS mice, forced expression hippocampal Fndc5 or bilateral intrahippocampal injection of recombinant irisin respectively improved hippocampal synaptic plasticity or inflammatory microenvironment, and then alleviated the cognitive impairments. LIPUS existed a positive efficacy in enhancing hippocampal Fndc5/irisin in BCAS mice, thus triggering a beneficial neuromodulation for VaD protection. Importantly, the neurorestorative effects of LIPUS on CCH-induced damages were totally reversed by knockdown the expression of hippocampal Fndc5 in WT mice, or in F5KO mice. Moreover, Fndc5 mediated the upregulated effects of LIPUS on spine density as well as irisin secretion of hippocampal neurons. The neuron-secreted irisin further drove reactive astrocytes to a neuroprotective phenotype.

Conclusion
LIPUS induced a neurorestorative stimulation against VaD may be through upregulation of the hippocampal Fndc5/irisin levels. Hippocampal Fndc5/irisin signaling might be a promising strategic target for VaD.
The critical role of KLF4 in regulating the activation of A1/A2 reactive astrocytes following ischemic stroke
Authors: Wang Cong , Li Longxuan 
Published: February 2023

Abstract
Background
We have previously demonstrated that the expression of kruppel-like transcription factor-4 (KLF-4) is upregulated in astrocytes following acute ischemic stroke (AIS) and found that KLF4 confers vascular protection against cerebral ischemic injury. However, the functional role of KLF4 in astrocyte after AIS is far from clear.

Methods
The intrinsic relationship between KLF4 and A1/A2 reactive astrocytes and the impact of astrocytic KLF4 on the activation of A1/A2 subtype astrocytes were evaluated in middle cerebral artery occlusion (MCAO) mice and oxygen–glucose deprivation and restoration (OGD/R) astrocytes.

Results
Our results demonstrated that astrocytic KLF4 expression and complement C3-positive A1 and S100 calcium binding protein A10 (S100A10)-positive A2 astrocytes were induced in the ischemic penumbra following focal cerebral ischemia, and the time course of upregulation of astrocytic KLF4 correlated closely with the activation of A2 astrocytes. The dual immunofluorescent studies displayed that in the ischemic hemisphere, where the high levels of KLF4 were expressed, there were relatively low levels of C3 expressed in the reactive astrocytes and vice versa, but KLF4 was always co-stained well with S100A10. Mechanistic analyses revealed that astrocytic KLF4 inhibited the activation of A1 astrocyte but promoted A2 astrocyte polarization after OGD/R by modulating expressions of nuclear factor-kB.

Conclusions
Astrocyte-derived KLF4 has a critical role in regulating the activation of A1/A2 reactive astrocytes following AIS.
Stereotactic body radiation therapy for prostate cancer: a study comparing 3-year genitourinary toxicity between CyberKnife and volumetric-modulated arc therapy by propensity score analysis
Authors: Ito Makoto , Yoshioka Yasuo , Takase Yuuki , Suzuki Junji , Takahashi Hironori , Minami Yoshitaka , Sakuragi Ami , Oshima Yukihiko , Okuda Takahito , Suzuki Kojiro 
Published: February 2023

Abstract
Background
To investigate whether the rate of stereotactic body radiation therapy-related (SBRT-related) genitourinary (GU) toxicity is lower in patients with prostate cancer treated with CyberKnife.

Methods
We retrospectively reviewed the medical records of patients with nonmetastatic prostate cancer at two institutions between 2017 and 2020. We analyzed 70 patients who were extracted by propensity score matching based on age, pre-treatment International Prostate Symptom Score (IPSS), and prostate volume. The patients were treated with SBRT, with a total dose of 36.25 Gy in five fractions over five consecutive weekdays, using CyberKnife or volumetric-modulated arc therapy (VMAT).

Results
The low-, medium-, and high-risk patients were 2, 19, and 14, respectively, in the CyberKnife group and 4, 17, and 14, respectively, in the VMAT group. The median follow-up time in both groups was 3 years. One patient with CyberKnife died of unrelated causes. No biochemical or clinical recurrence, distant metastases, or death from prostate cancer was observed.
The peak values of IPSS in the acute phase (< 3 months) were significantly lower in the CyberKnife than in the VMAT group (CyberKnife:16.2 vs VMAT:20.2, p = 0.025). In multiple regression analyses, the treatment modality (p = 0.03), age (p = 0.01), bladder medication pre-irradiation (p = 0.03), and neoadjuvant androgen deprivation therapy (p = 0.04) contributed to the peak value of the acute-phase IPSS. The incidence of treatment-related grade 2 acute GU toxicity tended to be lower in the CyberKnife than the VMAT group (CyberKnife: 22.9% vs. VMAT: 45.7%, p = 0.077). No difference was noted between the groups with regard to late IPSS or GU toxicity and gastrointestinal toxicity in all phases. Toxicities of grade ≥ 3 have not been observed to date.

Conclusions
Regardless of treatment modality, SBRT is effective in treating prostate cancer without serious toxicity. However, CyberKnife has an advantage over VMAT in terms of acute prostate symptoms.
Ten simple rules for providing bioinformatics support within a hospital
Authors: Chicco Davide , Jurman Giuseppe 
Published: February 2023

AbstractBioinformatics has become a key aspect of the biomedical research programmes of many hospitals’ scientific centres, and the establishment of bioinformatics facilities within hospitals has become a common practice worldwide. Bioinformaticians working in these facilities provide computational biology support to medical doctors and principal investigators who are daily dealing with data of patients to analyze. These bioinformatics analysts, although pivotal, usually do not receive formal training for this job. We therefore propose these ten simple rules to guide these bioinformaticians in their work: ten pieces of advice on how to provide bioinformatics support to medical doctors in hospitals. We believe these simple rules can help bioinformatics facility analysts in producing better scientific results and work in a serene and fruitful environment.
Association between serum uric acid levels and long-term mortality of metabolic dysfunction-associated fatty liver disease: a nationwide cohort study
Authors: Liu Zhening , Wang Qinqiu , Huang Hangkai , Wang Xinyu , Xu Chengfu 
Published: February 2023

AbstractBackgroundThe association between hyperuricemia and metabolic dysfunction-associated fatty liver disease (MAFLD) remains undetermined. This study aimed to examine the association of serum uric acid (SUA) levels with prevalence and long-term mortality of MAFLD in a nationally representative sample of US adults.MethodsThis analysis included 11,177 participants from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) with matched mortality data until 2019. We used logistic regression models to estimate the adjusted odd ratios (ORs) for factors associated with risk of MAFLD, and applied restricted cubic spline (RCS) regression to assess the non-linear associations of SUA levels with all-cause and cause-specific mortality of MAFLD. We also used Cox proportional hazards regression analysis to estimate hazard ratios (HRs) for the mortality.ResultsA higher SUA level contributed to a significant increased risk of MAFLD. every 1 mg/dL increment of SUA level was related to 17% (95% CI 9–24%) increased risk of MAFLD. Furthermore, a U-shaped association for males and a J-shaped association for females was discovered between SUA levels and all-cause mortality in participants with MAFLD. Specifically, among males, when SUA > 6.7 mg/dL, the higher SUA showed increased risk of cardio-cerebrovascular disease (CVD) mortality [HR (95% CI): 1.29 (1.05–1.58)]. As for females, only when SUA > 5.5 mg/dL, it showed a significantly positive association with risk of CVD and cancer mortality [HR (95% CI) 1.62 (1.24–2.13) and 1.95 (1.41–2.68)].ConclusionsElevated SUA level is significantly associated with an increased risk of MAFLD. Besides, SUA level is also a predictor of long-term mortality of MAFLD.
Graph isomorphism-based algorithm for cross-checking chemical and crystallographic descriptions
Authors: Merkys Andrius , Vaitkus Antanas , Grybauskas Algirdas , Konovalovas Aleksandras , Quirós Miguel , Gražulis Saulius 
Published: February 2023

AbstractPublished reports of chemical compounds often contain multiple machine-readable descriptions which may supplement each other in order to yield coherent and complete chemical representations. This publication presents a method to cross-check such descriptions using a canonical representation and isomorphism of molecular graphs. If immediate agreement between compound descriptions is not found, the algorithm derives the minimal set of simplifications required for both descriptions to arrive to a matching form (if any). The proposed algorithm is used to cross-check chemical descriptions from the Crystallography Open Database to identify coherently described entries as well as those requiring further curation.
Reconstruction of lossless molecular representations from fingerprints
Authors: Ucak Umit V. , Ashyrmamatov Islambek , Lee Juyong 
Published: February 2023

AbstractThe simplified molecular-input line-entry system (SMILES) is the most prevalent molecular representation used in AI-based chemical applications. However, there are innate limitations associated with the internal structure of SMILES representations. In this context, this study exploits the resolution and robustness of unique molecular representations, i.e., SMILES and SELFIES (SELF-referencIng Embedded strings), reconstructed from a set of structural fingerprints, which are proposed and used herein as vital representational tools for chemical and natural language processing (NLP) applications. This is achieved by restoring the connectivity information lost during fingerprint transformation with high accuracy. Notably, the results reveal that seemingly irreversible molecule-to-fingerprint conversion is feasible. More specifically, four structural fingerprints, extended connectivity, topological torsion, atom pairs, and atomic environments can be used as inputs and outputs of chemical NLP applications. Therefore, this comprehensive study addresses the major limitation of structural fingerprints that precludes their use in NLP models. Our findings will facilitate the development of text- or fingerprint-based chemoinformatic models for generative and translational tasks.
Insights on the effects of antimicrobial and heavy metal usage on the antimicrobial resistance profiles of pigs based on culture-independent studies
Authors: Ekhlas Daniel , Argüello Héctor , Leonard Finola C. , Manzanilla Edgar G. , Burgess Catherine M. 
Published: February 2023

AbstractAntimicrobial resistance is a global threat to human, animal, and environmental health. In pig production, antimicrobials and heavy metals such as zinc oxide are commonly used for treatment and prevention of disease. Nevertheless, the effects of antimicrobials and heavy metals on the porcine resistome composition and the factors influencing this resistance profile are not fully understood. Advances in technologies to determine the presence of antimicrobial resistance genes in diverse sample types have enabled a more complete understanding of the resistome and the factors which influence its composition. The aim of this review is to provide a greater understanding of the influence of antimicrobial and heavy metal usage on the development and transmission of antimicrobial resistance on pig farms. Furthermore, this review aims to identify additional factors that can affect the porcine resistome. Relevant literature that used high-throughput sequencing or quantitative PCR methods to examine links between antimicrobial resistance and antimicrobial and heavy metal use was identified using a systematic approach with PubMed (NCBI), Scopus (Elsevier), and Web of Science (Clarivate Analytics) databases. In total, 247 unique records were found and 28 publications were identified as eligible for inclusion in this review. Based on these, there is clear evidence that antimicrobial and heavy metal use are positively linked with antimicrobial resistance in pigs. Moreover, associations of genes conferring antimicrobial resistance with mobile genetic elements, the microbiome, and the virome were reported, which were further influenced by the host, the environment, or the treatment itself.
Bacterial chondronecrosis with osteomyelitis related Enterococcus cecorum isolates are genetically distinct from the commensal population and are more virulent in an embryo mortality model
Authors: Huang Yue , Eeckhaut Venessa , Goossens Evy , Rasschaert Geertrui , Van Erum Johan , Roovers Geert , Ducatelle Richard , Antonissen Gunther , Van Immerseel Filip 
Published: February 2023

AbstractBacterial chondronecrosis with osteomyelitis (BCO) is a common cause of broiler lameness. Bacteria that are found in BCO lesions are intestinal bacteria that are proposed to have translocated through the intestinal epithelium and have spread systemically. One of the specific bacterial species frequently isolated in BCO cases is Enterococcus cecorum. In the current study, caecal isolates were obtained from birds derived from healthy flocks (12 isolates from 6 flocks), while isolates derived from caeca, colon, pericardium, caudal thoracic vertebrae, coxo-femoral joint, knee joint and intertarsal joint (hock) were obtained from broilers derived from BCO outbreaks (111 isolates from 10 flocks). Pulsed field gel electrophoresis was performed to determine similarity. Clonal E. cecorum populations were isolated from different bones/joints and pericardium from animals within the same flock, with intestinal strains carrying the same pulsotype, pointing to the intestinal origin of the systemically present bacteria. Isolates from the intestinal tract of birds from healthy flocks clustered away from the BCO strains. Isolates from the gut, bones/joints and pericardium of affected animals contained a set of genes that were absent in isolates from the gut of healthy animals, such as genes encoding for enterococcal polysaccharide antigens (epa genes), cell wall structural components and nutrient transporters. Isolates derived from the affected birds induced a significant higher mortality in the embryo mortality model as compared to the isolates from the gut of healthy birds, pointing to an increased virulence.
Capacity-building and continuing professional development in healthcare and rehabilitation in low- and middle-income countries—a scoping review protocol
Authors: Deprez Dalton , Busch Angela J. , Ramirez Paola Andrea , Pedrozo Araque Eliany , Bidonde Julia 
Published: February 2023

Abstract
Background
A recent world health report suggests that there is a growing rehabilitation human resource crisis. This review focuses on the capacity-building needed to meet present and future rehabilitation challenges in low- and middle-income countries (LMICs). Capacity-building is the process by which individuals and organizations obtain, improve, and retain the skills, knowledge, tools, equipment, and other resources needed to do their jobs competently. The objectives of this review are (1) to determine how capacity-building has been defined, implemented, and evaluated in LMICs and (2) to provide an overview of the effectiveness of capacity-building initiatives.

Methods
In the first of seven stages, we will refine and delimit the research. Then, we will identify relevant studies by searching five biomedical databases, two rehabilitation databases, three regional databases, and three databases of gray literature. Two independent reviewers will then select the studies using a priori selection criteria. We will exclude incomplete records, records published prior to 2000 for databases and 2010 for gray literature, and records written in languages other than English or Spanish. We will also exclude records focusing on entry-to-practice programs in academic settings. For Objective 1, using qualitative analysis software, we will extract and analyze text from included records that define or explains capacity building. For Objective 2, using an online file-sharing platform, one reviewer will extract data describing the effectiveness of capacity-building interventions and a second reviewer will verify the accuracy, with disagreements resolved by consensus. The results will be collated using tables and charts. After synthesizing the results, we will discuss the practicality and applicability of the findings with partners from Honduras and Colombia. We will use several formats and venues including presentations and publications in English and Spanish to present our results.

Discussion
To our knowledge, this will be the first attempt to systematically identify knowledge of capacity-building and rehabilitation in LMICs. This scoping review results will offer unique insights concerning the breadth and depth of literature in the area. It is anticipated that results from this scoping review will guide efforts in future capacity-building efforts in rehabilitation in LMICs.

Review registration
Busch AJ, Deprez D, Bidonde J, Ramírez PA, Araque EP. Capacity building and continuing professional development in healthcare and rehabilitation in low- and middle-income countries—a scoping review. 2021. https://doi.org/10.17605/OSF.IO/7VGXU.
Sea urchin (Diadema savignyi) extract as a novel protective agent against cisplatin induced neurotoxicity in rats
Authors: Khalil Eman A. , Swelim Hamdy , El-Tantawi Hala , Abdellatif Ahmed 
Published: February 2023

AbstractNeurotoxicity is a severe side effect of platinum compounds used for cancer chemotherapy such as Cisplatin. This neurotoxicity leads to severe cognitive and nervous dysfunction, therefore, limiting the dose of Cisplatin and compromising the treatment protocol.The present study investigates the neuroprotective effect of Sea Urchins which is a marine animal known for its rich bioactive compounds. Male Sprague Dawley rats received Cisplatin (2 mg/kg body weight) for 4 weeks, two times per week, followed by Sea Urchin extracts (50 and 100 mg/kg body weight) twice weekly for 4 weeks.Results show that rats treated with Urchin’s extracts showed a significant improvement in the thermal (heat and cold) sensitivity compared to untreated rats. Liver enzymes Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and Urea levels were also significantly decreased back to normal following treatment with sea urchin extracts. Brain tissue oxidative stress marker Nitric oxide (NO) and lipid peroxidation marker Malondialdehyde (MDA) increased significantly in the cisplatin-treated rats while the reduced glutathione levels (GSH) and catalase activity (CAT) showed a significant decrease. Treatment with sea Urchin extracts reversed these changes.Histological and immunohistochemical examination of the cerebral cortex reveled degenerative changes such as karyopyknosis and shrunken necrotic ghost like neurons in the cisplatin treated groups. There was also strong positive Glial fibrillary acidic protein (GFAP) reactivity and a negative B-cell leukemia/lymphoma 2 protein (Bcl2) reaction in most apparent neurons, indicating strong apoptotic changes. Treatment with Urchin extracts reversed these changes. Quantification of cerebral cortex neurons also revealed the strong effect of the extracts. Cisplatin treated groups showed 3708 cells/ mm3 compared to 8091 cells/mm3 in the normal rats. Extract treatment increased the neuronal numbers to almost normal levels. Quantification of the Immuno-histochemical expression of GFAP showed an increase by 10-folds after cisplatin administration. A remarkable decline from the cisplatin group was seen in the extract treated groups.In Conclusion, Sea Urchins extracts possess a strong neuroprotective activity and could provide a novel therapeutic method to prevent Cisplatin-induced neurotoxicity.