bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pamoic acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia
Authors: De Leo Federica , Rossi Alice , De Marchis Francesco , Cigana Cristina , Melessike Medede , Quilici Giacomo , De Fino Ida , Mantonico Malisa Vittoria , Fabris Chantal , Bragonzi Alessandra , Bianchi Marco Emilio , Musco Giovanna 
Published: September 2022

Abstract
Background
High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear protein that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 is significantly elevated during Pseudomonas aeruginosa infections and has a clinical relevance in respiratory diseases such as Cystic Fibrosis (CF). Salicylates are HMGB1 inhibitors. To address pharmacological inhibition of HMGB1 with small molecules, we explored the therapeutic potential of pamoic acid (PAM), a salicylate with limited ability to cross epithelial barriers.

Methods
PAM binding to HMGB1 and CXCL12 was tested by Nuclear Magnetic Resonance Spectroscopy using chemical shift perturbation methods, and inhibition of HMGB1·CXCL12-dependent chemotaxis was investigated by cell migration experiments. Aerosol delivery of PAM, with single or repeated administrations, was tested in murine models of acute and chronic P. aeruginosa pulmonary infection in C57Bl/6NCrlBR mice. PAM efficacy was evaluated by read-outs including weight loss, bacterial load and inflammatory response in lung and bronco-alveolar lavage fluid.

Results
Our data and three-dimensional models show that PAM is a direct ligand of both HMGB1 and CXCL12. We also showed that PAM is able to interfere with heterocomplex formation and the related chemotaxis in vitro. Importantly, PAM treatment by aerosol was effective in reducing acute and chronic airway murine inflammation and damage induced by P. aeruginosa. The results indicated that PAM reduces leukocyte recruitment in the airways, in particular neutrophils, suggesting an impaired in vivo chemotaxis. This was associated with decreased myeloperoxidase and neutrophil elastase levels. Modestly increased bacterial burdens were recorded with single administration of PAM in acute infection; however, repeated administration in chronic infection did not affect bacterial burdens, indicating that the interference of PAM with the immune system has a limited risk of pulmonary exacerbation.

Conclusions
This work established the efficacy of treating inflammation in chronic respiratory diseases, including bacterial infections, by topical delivery in the lung of PAM, an inhibitor of HMGB1.
Identification of a small-molecule RPL11 mimetic that inhibits tumor growth by targeting MDM2-p53 pathway
Authors: Wang Bingwu , Gao Jian , Zhao Zhongjun , Zhong Xuefei , Cui Hao , Hou Hui , Zhang Yanping , Zheng Junnian , Di Jiehui , Liu Yong 
Published: September 2022

Abstract
Background
Targeting ribosome biogenesis to activate p53 has recently emerged as a therapeutic strategy in human cancer. Among various ribosomal proteins, RPL11 centralizes the nucleolar stress-sensing pathway by binding MDM2, leading to MDM2 inactivation and p53 activation. Therefore, the identification of MDM2-binding RPL11-mimetics would be valuable for anti-cancer therapeutics.

Methods
Based on the crystal structure of the interface between RPL11 and MDM2, we have identified 15 potential allosteric modulators of MDM2 through the virtual screening.

Results
One of these compounds, named S9, directly binds MDM2 and competitively inhibits the interaction between RPL11 and MDM2, leading to p53 stabilization and activation. Moreover, S9 inhibits cancer cell proliferation in vitro and in vivo. Mechanistic study reveals that MDM2 is required for S9-induced G2 cell cycle arrest and apoptosis, whereas p53 contributes to S9-induced apoptosis.

Conclusions
Putting together, S9 may serve as a lead compound for the development of an anticancer drug that specifically targets RPL11-MDM2-p53 pathway.
Quantitative proteome profiling reveals molecular hallmarks of egg quality in Atlantic halibut: impairments of transcription and protein folding impede protein and energy homeostasis during early development
Authors: Yilmaz Ozlem , Jensen Anders Mangor , Harboe Torstein , Møgster Margareth , Jensen Ragnfrid Mangor , Mjaavatten Olav , Birkeland Even , Spriet Endy , Sandven Linda , Furmanek Tomasz , Berven Frode S. , Wargelius Anna , Norberg Birgitta 
Published: September 2022

Abstract
Background
Tandem mass tag spectrometry (TMT labeling-LC-MS/MS) was utilized to examine the global proteomes of Atlantic halibut eggs at the 1-cell-stage post fertilization. Comparisons were made between eggs judged to be of good quality (GQ) versus poor quality (BQ) as evidenced by their subsequent rates of survival for 12 days. Altered abundance of selected proteins in BQ eggs was confirmed by parallel reaction monitoring spectrometry (PRM-LC-MS/MS). Correspondence of protein levels to expression of related gene transcripts was examined via qPCR. Potential mitochondrial differences between GQ and BQ eggs were assessed by transmission electron microscopy (TEM) and measurements of mitochondrial DNA (mtDNA) levels.

Results
A total of 115 proteins were found to be differentially abundant between GQ and BQ eggs. Frequency distributions of these proteins indicated higher protein folding activity in GQ eggs compared to higher transcription and protein degradation activities in BQ eggs. BQ eggs were also significantly enriched with proteins related to mitochondrial structure and biogenesis. Quantitative differences in abundance of several proteins with parallel differences in their transcript levels were confirmed in egg samples obtained over three consecutive reproductive seasons. The observed disparities in global proteome profiles suggest impairment of protein and energy homeostasis related to unfolded protein response and mitochondrial stress in BQ eggs. TEM revealed BQ eggs to contain significantly higher numbers of mitochondria, but differences in corresponding genomic mtDNA (mt-nd5 and mt-atp6) levels were not significant. Mitochondria from BQ eggs were significantly smaller with a more irregular shape and a higher number of cristae than those from GQ eggs.

Conclusion
The results of this study indicate that BQ Atlantic halibut eggs are impaired at both transcription and translation levels leading to endoplasmic reticulum and mitochondrial disorders. Observation of these irregularities over three consecutive reproductive seasons in BQ eggs from females of diverse background, age and reproductive experience indicates that they are a hallmark of poor egg quality. Additional research is needed to discover when in oogenesis and under what circumstances these defects may arise. The prevalence of this suite of markers in BQ eggs of diverse vertebrate species also begs investigation.
How to persuade more primary care professionals to adopt a valued smoking cessation referral aid: a cross-sectional study of facilitators and barriers
Authors: Zijlstra Daniëlle N , Bolman Catherine AW , Muris Jean WM , de Vries Hein 
Published: September 2022

Abstract
Background
To study the factors associated with the intention of primary care professionals (PCPs) to use or not use a referral aid (RA) for selecting an evidence-based smoking cessation intervention (EBSCI).

Methods
Participants (n = 85) were recruited from June to September 2020 to complete an online questionnaire based on the I-Change Model to assess the factors associated with the adoption of RA. The differences between PCPs with (n = 37) and without (n = 48) the intention to adopt in terms of demographics, motivational factors, and post-motivational factors were subsequently assessed. Correlation and logistic regression analyses were conducted to investigate the factors associated with the intention to adopt.

Results
Both groups indicated that they highly appreciated the RA. However, PCPs without the intention to adopt expressed a more negative attitude towards the RA, experienced less social support, showed low self-efficacy, and encountered barriers such as lack of time and skills. The factors most strongly associated with the intention to adopt were advantages, disadvantages, self-efficacy, less barriers, working in a solo practice and age.

Conclusions
The adoption of RA can be facilitated in two ways. The first one is by increasing the added value of the tool through a second round of co-creation focusing on the adoptability of the RA in practice. The second approach is by communicating the added value of referring to EBSCIS and thereby using the RA by implementing it in smoking cessation training for PCPs, which could also help to improve the attitude, social support, self-efficacy, and perceived skills in terms of RA usage among PCPs.

Impact
This study is the first work in the Netherlands to investigate the willingness of PCPs to actively refer patients to other EBSCIs in addition to providing face-to-face counseling themselves.

Trial registration
The study was registered at the Netherlands Trial Register (NL7020, https://www.trialregister.nl/trial/7020).
Development and validation of a risk prediction model for lost to follow-up among adults on active antiretroviral therapy in Ethiopia: a retrospective follow-up study
Authors: Fentie Dawit Tefera , Kassa Getahun Molla , Tiruneh Sofonyas Abebaw , Muche Achenef Asmamaw 
Published: September 2022

Abstract
Background
Over 420,000 people have initiated life-saving antiretroviral therapy (ART) in Ethiopia; however, lost-to-follow-up (LTFU) rates continues to be high. A clinical decision tool is needed to identify patients at higher risk for LTFU to provide individualized risk prediction to intervention. Therefore, this study aimed to develop and validate a statistical risk prediction tool that predicts the probability of LTFU among adult clients on ART.

Methods
A retrospective follow-up study was conducted among 432 clients on ART in Gondar Town, northwest, Ethiopia. Prognostic determinates included in the analysis were determined by multivariable logistic regression. The area under the receiver operating characteristic (AUROC) and calibration plot were used to assess the model discriminative ability and predictive accuracy, respectively. Individual risk prediction for LTFU was determined using both regression formula and score chart rule. Youden index value was used to determine the cut-point for risk classification. The clinical utility of the model was evaluated using decision curve analysis (DCA).

Results
The incidence of LTFU was 11.19 (95% CI 8.95–13.99) per 100-persons years of observation. Potential prognostic determinants for LTFU were rural residence, not using prophylaxis (either cotrimoxazole or Isoniazid or both), patient on appointment spacing model (ASM), poor drug adherence level, normal Body mass index (BMI), and high viral load (viral copies > 1000 copies/ml). The AUROC was 85.9% (95% CI 82.0–89.6) for the prediction model and the risk score was 81.0% (95% CI 76.7–85.3) which was a good discrimination probability. The maximum sensitivity and specificity of the probability of LTFU using the prediction model were 72.07% and 83.49%, respectively. The calibration plot of the model was good (p-value = 0.350). The DCA indicated that the model provides a higher net benefit following patients based on the risk prediction tool.

Conclusion
The incidence of LTFU among clients on ART in Gondar town was high (> 3%). The risk prediction model presents an accurate and easily applicable prognostic prediction tool for clients on ART. A prospective follow-up study and external validation of the model is warranted before using the model.
Excess hospitalizations and mortality associated with seasonal influenza in Portugal, 2008–2018
Authors: Froes Filipe , Carmo Mafalda , Lopes Hugo , Bizouard Geoffray , Gomes Catarina , Martins Margarida , Bricout Hélène , de Courville Caroline , de Sousa Jaime Correia , Rabaçal Carlos , Raposo João F. , Cordeiro Carlos Robalo 
Published: September 2022

Abstract
Background
Influenza can have a domino effect, triggering severe conditions and leading to hospitalization or even death. Since influenza testing is not routinely performed, statistical modeling techniques are increasingly being used to estimate annual hospitalizations and deaths associated with influenza, to overcome the known underestimation from registers coded with influenza-specific diagnosis. The aim of this study was to estimate the clinical and economic burden of severe influenza in Portugal.

Methods
The study comprised ten epidemic seasons (2008/09–2017/18) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization incidence, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487–488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480–488, 517.1; ICD-10: J09–J18), respiratory (ICD-9: 460–519; ICD-10: J00–J99), respiratory or cardiovascular (R&C, ICD-9: 390–459, 460–519; ICD-10: I00–I99, J00–J99), and all-cause. Means are reported excluding the H1N1pdm09 pandemic (2009/10).

Results
The mean number of hospitalizations coded as due to influenza per season was 1,207, resulting in 11.6 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €3.9 million, of which 78.6% was generated by patients with comorbidities. Mean annual influenza-associated R&C hospitalizations were estimated at 5356 (min: 456; max: 8776), corresponding to 51.5 cases per 100,000 (95% CI: 40.9–62.0) for all age groups and 199.6 (95% CI: 163.9–235.8) for the population aged ≥ 65 years. The mean direct annual cost of the estimated excess R&C hospitalizations was €15.2 million for all age groups and €12.8 million for the population aged ≥ 65 years. Mean annual influenza-associated all-cause deaths per 100,000 people were estimated at 22.7 for all age groups.

Conclusions
The study findings suggest that there is an under-detection of influenza in the Portuguese population. A high burden of severe influenza remains to be addressed, not only in the elderly population but also in younger people.
Anti-phospholipase A2 receptor antibody levels at diagnosis predicts outcome of TAC-based treatment for idiopathic membranous nephropathy patients
Authors: Wang Bihua , Zhu Zhidan , Huang Feng , Huang Haowen , Tu Luxia , Wang Ying , Zheng Linfeng , Zhou Jing , Wei Xin 
Published: September 2022

Abstract
Background
Idiopathic membranous nephropathy (iMN) is recognized as an organ-specific autoimmune disease, mainly caused by anti-PLA2R antibody. This study aimed to study between anti-PLA2R antibody level at diagnosis and the response to tacrolimus (TAC)-based treatment in iMN patients.

Methods
This was a retrospective cohort study including 94 kidney biopsy-proven MN patients with positive anti-PLA2R antibody at diagnosis from May 2017 to September 2021 in our center. All iMN patients received the TAC regimen as the initial immunosuppressive therapy. All patients were divided into two groups according to anti-PLA2R antibody titer at diagnosis: high-level group (> 150 RU/ml; n = 42) and low-level group (≤ 150 RU/ml; n = 52). The association between anti-PLA2R antibody levels and clinical outcomes was assessed using the Kaplan–Meier method.

Results
The low density lipoprotein in the high-level group was significantly higher than low-level group at diagnosis, otherwise, serum albumin was significantly lower than low-level group; however, there was no significant difference in creatinine levels between two groups. The remission rates were significantly higher in the low-level group than high-level group after treatment with TAC for 12, 18, or 24 months (all P < 0.05). After 12 months of treatment with TAC, 82.7% of the patients in the low-level group achieved complete remission (CR) or partial remission (PR) (mean, 6.52 ± 0.53 months). However, 38.1% of the patients in high-level group achieved CR or PR (mean, 9.86 ± 0.51 months). Moreover, CR rate at 12 months in the high-level group was only 4.7% (mean, 11.88 ± 0.63 months). The infection frequency in the high-level group (35.6%) was higher than the low-level group (20%) during the TAC treatment, although there was no significant difference (P = 0.065). There were 19% patients who had end-stage kidney disease (ESKD), and 7.1% of patients died of ESKD in the high-level group during the follow-up period.

Conclusion
Anti-PLA2R antibody level above 150 RU/ml at diagnosis can predict a poor treatment response and outcome of TAC treatment in iMN patients, who may not benefit from TAC or other calcineurin inhibitor regimens as the initial treatment.
Impact of maternal dietary carbohydrate intake and vitamin D-related genetic risk score on birth length: the Vitamin D Pregnant Mother (VDPM) cohort study
Authors: Aji Arif Sabta , Lipoeto Nur Indrawaty , Yusrawati Yusrawati , Malik Safarina G. , Kusmayanti Nur Aini , Susanto Isman , Nurunniyah Siti , Alfiana Ratih Devi , Wahyuningsih Wahyuningsih , Majidah Nur Mukhlishoh , Vimaleswaran Karani Santhanakrishnan 
Published: September 2022

Abstract
Background
Our objectives were to investigate the relationship between maternal vitamin D status and IGF-1 levels in healthy Minangkabau pregnant mothers and their impact on newborn anthropometry outcomes and to examine whether this relationship was modified by dietary intake using a nutrigenetic approach.

Methods
Healthy singleton pregnant mother and infant pairs (n = 183) were recruited. We created three genetic risk scores (GRSs): a six-SNP GRS based on six vitamin D-related single nucleotide polymorphisms (SNPs) involved in the synthesis of vitamin D (vitamin D-GRS), a two-SNP GRS using SNPs in VDR genes (VDR-GRS) and a four-SNP GRS using SNPs from DHCR7, GC, CYP24A1 and CYP2R1 genes (non-VDR GRS). The effect of the GRSs on IGF-1, vitamin D and newborn anthropometry and the interaction between the GRSs and dietary factors were tested using linear regression analysis.

Results
The vitamin D- and non-VDR GRSs were significantly associated with lower 25(OH)D concentration (p = 0.005 and p = 0.001, respectively); however, there was no significant association with IGF-1, and newborn anthropometry outcomes. However, there was a significant interaction of VDR-GRS with carbohydrate intake on birth length outcome (Pinteraction = 0.032). Pregnant mothers who had higher carbohydrate intake (405.88 ± 57.16 g/day) and who carried ≥ 2 risk alleles of VDR-GRS gave birth to babies with significantly lower birth lengths compared to babies born to mothers with < 2 risk alleles (p = 0.008).

Conclusion
This study identified a novel interaction between VDR-GRS and carbohydrate intake on birth length outcome. These findings suggest that reducing the intake of carbohydrates during pregnancy, particularly for those who have a higher genetic susceptibility, might be an effective approach for preventing foetal growth abnormalities.
Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial
Authors: Allahyari Abolghasem , Ehsanpour Ali , Najafi Behrouz , Ansarinejad Nafiseh , Mehrzad Valiollah , Kalantari Behjat , Raafat Jahangir , Ghadiany Mojtaba , Shahi Farhad , Gharib Behrooz , Moazed Vahid , Khosravi Adnan , Mirpour Mir Hossein , Salari Sina , Mortazavizadeh Seyedmohammadreza , Nekoyi Amirabbas , Khani Mohsen , Sadeghi Alireza , Gharib Sirus , Bary Alireza , Mirzania Mehrzad , Haghighat Shirin , Razavi Seyed Mohsen , Emami Seyed Amir Hossein , Hosseinzadeh Mehran , Mirbolouk Mahdi , Sadighi Sanambar , Shahrasbi Abdolali , Esfahani Ali , Gity Masoumeh , Anjidani Nassim , Kafi Hamidreza , Najafi Safa 
Published: September 2022

Abstract
Background
Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab.

Methods
This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity.

Results
Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of − 0.04 (95% CI: − 0.16, 0.09). Secondary endpoints were also comparable between the two groups.

Conclusions
The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.
Implantable collamer lens sizing based on measurement of the sulcus-to-sulcus distance in ultrasound biomicroscopy video clips and ZZ ICL formula
Authors: Zhang Jun , Shao Jie , Zheng Li , Zhao Xia , Chen Shu 
Published: September 2022

AbstractBackgroundTo evaluate a new method of implantable collamer lens (ICL) sizing based on ultrasound biomicroscopy (UBM) video clips.MethodsThis observational study included consecutive patients with myopia and myopic astigmatism scheduled for V4c toric ICL (TICL) implantation (STAAR) at Hangzhou MSK Eye Hospital (October 2020 to November 2020). Sulcus-to-sulcus (STS) distance, lens thickness (LT), and clinical refraction were measured preoperatively. The ZZ ICL formula (provides the predicted vault height and refraction based on TICL size, intraocular meridian, power, and eye parameters, including STS distance and LT) was used to select TICL size and predict vault height and residual refraction, which was also compared with the STAAR software recommended. Vault and residual refraction were measured at 3 months postoperatively.ResultsThe analysis included 168 eyes in 84 patients. Postoperative vault size was comparable to that predicted by the ZZ ICL formula (528 ± 193 vs. 545 ± 156 μm,P = 0.227). Vault prediction error (PE) by the ZZ ICL formula was within 100, 300, and 500 μm in 40.48%, 88.10%, and 100% of eyes, respectively. Spherical equivalent (SE) and absolute cylindrical refractive error were 0.36 ± 0.48 and 0.40 ± 0.31 D at 3 months postoperatively. The SE PE, absolute cylindrical PE, and percentages of eyes with an absolute cylindrical PE within ± 0.50 D and ± 1.00 D were lower for the ZZ ICL formula than for the STAAR software (P < 0.01).ConclusionsCombining measurements obtained in UBM video clips with the ZZ ICL formula provides an effective method of sizing TICLs and predicting vault height and residual refractive error.