bluuebunny/crossref_metadata_2025 huggingface dataset:
Berberine Promotes A549 Cell Apoptosis and Autophagy via miR-144
Authors: Gao Zhiyan , Tan Chang , Sha Rula
Published: September 2022

Objective: To explore the effects of berberine on A549 lung cancer cells and corresponding changes in miR-144 expression, and the apoptosis and autophagy pathways. Methods: Cell proliferation was detected by cell counting Kit-8. The expression of miR-144 by quantitative PCR, caspase-3, caspase-3 cleaved, Bcl-2, Bax, beclin-1, LC3I, and LC3II were assessed using Western blot. Results: A549 proliferation was reduced with increasing berberine concentration. Berberine appeared to suppress A549 proliferation through apoptosis and autophagy, and, additionally, enhanced miR-144 expression. Berberine promoted A549 cell apoptosis by inhibiting caspase-3 cleavage and Bcl-2 expression and promoting Bax expression. Berberine also promoted A549 autophagy by raising the expression of beclin-1, LC3I, and LC3II. Conclusions: Berberine promotes A549 apoptosis and autophagy via miR-144.
Mechanical testing of frontal plane adaptability of commercially available prosthetic feet
Authors: Wernke Matthew M , Ficanha Evandro M , Thomas Zac , Maitland Murray E , Allyn Katheryn J , Albury Alex , Colvin James
Published: September 2022

Introduction

Prosthetic feet have limited adaptability in the frontal plane. Research shows walking on uneven terrain is difficult for many prosthesis users. A new prosthetic foot, the META Arc, was designed with a polycentric ankle joint that allows relatively free movement in the frontal plane to address this limitation. Previous simulations of the polycentric ankle mechanism found potential benefits such as reduced lateral movement of a proximal mass during forward progress and reduced forces being transferred upward from the ground through the foot.

Methods

Standard mechanical testing protocols were used to evaluate the Meta Arc prosthetic foot’s performance and six comparable feet commercially available.

Results

The results found the META Arc prosthetic foot had increased frontal plane adaptability as well as reduced lateral forces, and reduced inversion eversion moment compared to the six comparison feet on 10-degree cross-slope test conditions. All included prosthetic feet had similar results for the percent of energy return and dynamic force in the sagittal plane.

Conclusions

These results suggest the inclusion of the polycentric ankle within the META Arc foot will provide more stability without sacrificing forward walking performance.
Mycotic Pseudoaneurysm: Rare Complication of a Norwood/Sano Graft Stump
Authors: Krivenko Gabriel , Hsia Tain-Yen , Farias Michael , Tarulli Kathryn , DeCampli William M.
Published: September 2022

The Sano variant of the stage 1 Norwood procedure is commonly performed as initial palliation for hypoplastic left heart syndrome. We present a case of a 2-year-old who developed a mycotic pseudoaneurysm of the Sano graft and discuss the importance of imaging and operative management of this rare presentation. Localization and full description of the lesion require compulsive, often multimodality imaging.
Less Partisan and Less Aggressive? The Impact of Covid-19 on the Media Discourse of “El Clásico” on Spanish Radio
Authors: Martínez Corcuera Rául , Mauro Max
Published: September 2022

The football rivalry between Real Madrid CF and FC Barcelona is one of the most popular at club level globally. In Spain, where it is known as El Clásico (the Classic), it has an unrivalled status in the sports media industry. Its significance relies in part to the historical tension between Catalonia, the region of which Barcelona is the main centre, and Madrid, the capital of Spain. The exaltation of confrontation and partisanship is the central feature of highly popular radio programmes devoted to El Clásico. This study aimed to observe how the media discourse articulated by these programmes was affected by the fact that, during the Covid-19 pandemic, matches were played in empty venues. Through the comparisons of broadcasts of two games, one from 2017 and from 2020, the paper shows that the sensationalistic style is toned down, and a less polarised and partisan sports journalism is possible.
Covid-19 stigmatization: A systematic literature review
Authors: Kartono Rinikso , Salahudin  , Sihidi Iradhad Taqwa
Published: September 2022

Covid-19 has severe implications for the emergence of negative stigmatization of specific individuals and community groups. Due to labeling and discrimination, mental attacks cause psychological distress so seriously that it requires proper handling. Therefore, this study aims to conduct a systematic literature review on articles on COVID-19 stigmatization. This paper used descriptive analysis that 248 articles are from the Scopus database obtained by keyword Covid-19 stigmatization in the 2020–2021 time span were then processed and visualized using the Vosviewer software. The results reveal the three most dominant concepts studied: anxiety, isolation, and knowledge. The Covid-19 stigma arises due to low public knowledge, widespread Covid-19 disinformation, and lack of trust in the government. This research contributes to a description of the root causes and adverse effects of stigmatization during Covid-19 to help formulate recommendations for preventive and treatment actions that can be taken. Meanwhile, the limitation of this research is that the articles reviewed are only sourced from Scopus, so they do not have comparative data. Therefore, future studies require using a comparative analysis approach that uses a Web of Science (WoS) database.
Designing a Surveillance System to Monitor the Adverse Health Effect of Environmental Disasters: A Case Study of Drying Lake Urmia-Iran
Authors: Gharaee Hojatolah , Dewey Rebecca Susan , Rezapour Ramin , Derakhshani Naser , Azami-aghdash Saber
Published: September 2022

Background

Through designing a surveillance system, steps to policy making and designing measures needed to reduce the potential risks of environmental disasters on human health could be taken. Therefore, this study aimed to develop a model for Environmental Disasters Diseases Surveillance System (EDDS) to monitor Adverse Health Effects (AHEs) of Environmental Disasters (AHEEDs).

Methods

As the first step, the literature review was conducted to identify the AHEEDs. Then, using the results of the first step and analyzing the existing documents, the AHEEDs were identified, and, based on the experts’ opinions, high-priority effects were included in the EDDS. Then, using semi-structured interviews, 20 experts’ views on the appropriate model of EDDS were investigated. To design the initial model, a panel of experts was formed with six participants. Finally, the Delphi technique was used for expert opinion and model finalization.

Results

As a result of the literature review and document analysis, 41 hazards/diseases were identified. Finally, ten diseases were suggested to enter the EDDS. In the experts’ view, it is better that communicable diseases be reported actively and urgently and Non-Communicable Diseases (NCD) actively and non-urgently. From the participants’ point of view, the most significant achievements of the EDDS can be organizational and managerial, health promotion, and economic achievements.

Conclusion

Developing a dedicated EDDS for AHEEDs can be very helpful for better management of these effects. To this end, the model proposed in this study can serve as a guide for national and local policymakers to implement surveillance systems for AHEEDs.
Workforce Development to Improve Access to Pain Care for Veterans: A Qualitative Analysis of VA-ECHO Participant Experiences
Authors: Subramaniam Soumya , Stryczek Krysttel C. , Ball Sherry , Stevenson Lauren , Ho P. Michael , Aron David C.
Published: September 2022

Background/Objective

The prevalence of chronic pain and its links to the opioid epidemic have given way to widespread aims to improve pain management care and reduce opioid use, especially in rural areas. Pain Management Specialty Care Access Network-Extension for Community Health Outcomes (VA-ECHO) promotes increased pain care access to rural Veterans through knowledge sharing from specialists to primary care providers (PCPs). We explored PCP participants’ experiences in VA-ECHO and pain management care.

Methods

This qualitative study is based on a descriptive secondary analysis of semi-structured interviews (n = 10) and 3 focus groups with PCPs participating in VA-ECHO from 2017–2019. A rapid matrix analysis approach was used to analyze participants’ responses.

Results

VA-ECHO was an effective workforce development strategy for meeting PCPs’ training needs by providing pain management knowledge and skills training (eg alternative care approaches and communicating treatment options). Having protected time to participate in VA-ECHO was a challenge for many PCPs, mitigated by leadership and administrative support. Participants who volunteer to participate had more positive experiences than those required to attend.

Conclusions

VA-ECHO could be used for meeting the workforce development needs of PCPs. Respondents were satisfied with the program citing improvement in their practice and increased confidence in providing pain management care to Veterans despite some challenges to participation. These findings offer insight into using VA-ECHO to meet the VHA’s workforce development to improve Veterans’ access to pain management care. The ECHO model presents opportunities for workforce development in large complex healthcare systems and garnering ongoing support for this training model is necessary for promoting workforce development for PCPs.
Depression Among Patients with Chronic Pain, in Jimma Town Public Hospitals, Ethiopia
Authors: Serawit Tigist , Belay Yeshitila , Tesfaye Yonas , Mekoya Tsion , Yimam Ebrahim
Published: September 2022

Introduction

The co-occurrence of depression and chronic pain causes additive adverse effects on patients” outcomes, response to treatment, and poorer functioning. Despite this, there is a dearth of studies in developing countries. Therefore, this study aimed to provide a new insight into the understanding of the prevalence and associated factors between chronic pain and depression among patients with chronic pain in Jimma town public hospitals.

Methods

Institution-based cross-sectional study was conducted in Jimma town public hospitals. A total of 422 sampled patients with chronic pain participated in the study. Depression was assessed using the PHQ-9 scale. The coded data were entered to Epi Data version 3.1 and exported into SPSS version 23.0 for analysis. Logistic regression analysis model was used to identify factors independently associated with depression.

Result

The prevalence of depression among chronic pain patients was found to be 43.3%. The number of presenting compliant (AOR = 3.092, 95% CI: 1.684-5.678), history of depression (AOR = 0.319, CI: 0.133-0.766), pain intensity (AOR = 5.296, 95% CI: 2.018-13.901), pain location (AOR = 0.318, 95% CI: 0.158-0.638), pain persistence (AOR = 5.163, 95% CI: 2.784-9.576), the extent the pain compromised the respondent quality of life (AOR = 3.816, 95% CI: 1.685-8.643), and episodes of the pain associated with activities (AOR = 0.247, 95% CI: 0.138-0.442) were significantly associated with depression among patients with chronic pain.

Conclusion

This study has shown a high prevalence of depression among patients with chronic pain. Furthermore, depression was associated with various pain-related factors. Hence, effective screening and management of depression among chronic pain patients’ needs noteworthy attention.
El Niño without ‘El Niño’? Path dependency and the definition problem in El Niño Southern Oscillation research
Authors: Adamson George
Published: September 2022

The El Niño phenomenon – and its associated phenomena El Niño Southern Oscillation (ENSO) and La Niña – have become probably the most well-known forms of natural climatic variability. El Niño forecasts underpin regional Climate Outlook Forums in many parts of the world. The declaration of El Niño conditions can unlock development aid money and El Niño events commonly receive widespread media coverage. Yet ‘El Niño’ has not always meant what it does today. The name was originally applied to an annually-occurring ocean current that affected northern Peru and Ecuador, so called because it arrived at Christmas (the Christ Child). The transition in meaning to a complex global phenomenon was related as much to commercial and geopolitical priorities as to the oceanic and atmospheric observations that underpin theories of El Niño dynamics. In this paper, I argue that scientific conceptualisations of El Niño are an example of path dependency. Badging ocean-atmosphere variability as ‘El Niño’ is unnecessary either for the advancement of science or effective disaster risk reduction; in fact, current definitions are confusing and can create problems in preparing for El Niño-related hazards, as occurred with the 2017 ‘coastal’ El Niño in Peru. This paper outlines the historical processes that led to the current conceptualisations of El Niño and suggests an alternative way of understanding ocean-atmosphere dynamics in the Pacific and beyond. It then considers the implications of this path-dependency on El Niño’s ontological politics; that is, who gets to define El Niño, and to what end.
Managing the problem of too much capital: Coal power overcapacity, migrant labor sacrifice, and structural problems in contemporary Chinese political economy
Authors: Wang Xi
Published: September 2022

China's electricity sector suffers from significant overcapacity in coalfired generation. Between 2000 and 2020, China built more than 970 gigawatts of new coal power capacity, accounting for more than 70% of all new coal capacity worldwide. Building large amounts of coal and other generation capacity has continued despite clear indicators of overcapacity before the mid-2010s. This article uses a Marxian political economy theoretical framework to assert that generation overcapacity is a symptom of China's broader problem of capital overaccumulation. More specifically, it is the result of governance choices to deal with the overaccumulation problem. In so doing, this article presents a new conceptual pathway to understanding overcapacity in the electricity sector, which mainstream discourse attributes to bad planning and mistaken economic assumptions. Through the case of Chinese coal generation overcapacity, this article advocates for examining contemporary political economy issues through the conceptual lens of overaccumulation and devaluation management—in China and beyond. It proceeds by highlighting three central features of structural problems in contemporary Chinese political economy. The first is the expression of capital overaccumulation as massive coal generation overcapacity. The second is the structural bias toward overbuilding generation infrastructure; this is due both to the bulky and long-lived nature of electricity sector fixed capital and the sector's key role in circulating capital throughout the economy. The third feature is how—given insufficient consumption demand—capital is offloaded spatially, temporally, and biophysically onto migrant contract workers. Together, these features trace governance decisions made by state entities at different scales and times to deal with the imperatives of capital while maintaining economic, social, and political legitimacy. This framework highlights the ongoing management of overaccumulation and devaluation as a core governance imperative. This imperative undergirds current class warfare, and in this case of fossil fuel capital expansion, carries grim implications for climate change.
Heart Failure Due to Liver Involvement of Hereditary Hemorrhagic Telangiectasia, Diagnosed by Point-of-Care Ultrasonography
Authors: Cheong Issac
Published: September 2022

Osler-Weber-Rendu syndrome, also known as hereditary hemorrhagic telangiectasia (HHT), is a rare inherited disorder characterized by the presence of systemic arteriovenous malformations, which most commonly affects the liver. One of the most serious complications of liver compromise is high output heart failure (HOHF). In this case study, point-of-care ultrasonography is utilized as a means to describe the diagnostic findings of an intensive care unit patient diagnosed with liver involvement of HHT and the development of HOHF.
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

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

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

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

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

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

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

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

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

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

Background

To evaluate a new method of implantable collamer lens (ICL) sizing based on ultrasound biomicroscopy (UBM) video clips.

Methods

This 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.

Results

The 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).

Conclusions

Combining 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.
Impact of tight glycemic control and hypoglycemia after pediatric cardiac surgery on neurodevelopmental outcomes at three years of age: Findings from a randomized clinical trial
Authors: Sadhwani Anjali , Asaro Lisa A. , Goldberg Caren S. , Ware Janice , Butcher Jennifer , Gaies Michael , Smith Cynthia , Alexander Jamin L. , Wypij David , Agus Michael S. D.
Published: September 2022

Background

Studies examining the impact of randomization As per standard instruction, city is required for affiliations; however, this information is missing in affiliation 6. Please check if the provided city is correct and amend if necessary. to tight glycemic control (TGC) and resultant hypoglycemia on later neurodevelopmental outcomes have produced mixed results. Our study examined this association in children undergoing cardiac surgery.

Methods

Participants who were enrolled in the Safe Pediatric Euglycemia after Cardiac Surgery (SPECS) trial returned for neurodevelopmental (ND) follow-up between 30 to 42.5 months of age. ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. ND scores were compared between the TGC and standard care treatment groups and between patients with moderate to severe and no to mild hypoglycemia. As a secondary analysis, to increase sample size and power, we combined the three-year-old assessments with previously collected assessments done at < 30 months of age to further examine differences between groups longitudinally.

Results

Among the 269 participants who completed neurodevelopmental evaluation (in-person testing or questionnaires) at three years of age (follow-up rate, 31%), there were no statistically significant differences in ND outcomes according to treatment group or hypoglycemia status. In the combined analysis of all evaluations (from 9 to 42.5 months of age), we found no treatment group differences. However, in these longitudinal analyses, children who experienced moderate to severe hypoglycemia had lower scores on the Bayley-III cognitive and motor domains compared to children with no to mild hypoglycemia.

Conclusions

For infants undergoing cardiac surgery, there was no impact of tight glycemic control on neurodevelopmental outcomes. Moderate to severe hypoglycemia was associated with worse ND outcomes in longitudinal analyses.

Trial registration

ClinicalTrials.gov NCT00443599. Registered: November 2016.
Risk stratification of patients with acute respiratory distress syndrome complicated with sepsis using lactate trajectories
Authors: Zhang Haoyue , Li Ziping , Zheng Weiqiang , Zhang Linlin , Yang Tianqi , Xie Keliang , Yu Yonghao
Published: September 2022

Background

No consensus has been reached on an optimal blood lactate evaluation system although several approaches have been reported in the literature in recent years. A group-based trajectory modeling (GBTM) method could better stratify patients with acute respiratory distress syndrome (ARDS) complicated with sepsis in the intensive care unit (ICU).

Patients and methods

760 patients from the comprehensive ICU of Tianjin Medical University General Hospital with ARDS complicated with sepsis were eligible for analysis. Serial serum lactate levels were measured within 48 h of admission. In addition to the GBTM lactate groups, the initial lactate, peak lactate level, the area under the curve of serial lactate (lactate AUC), and lactate clearance were also considered for comparison. The short- and long-term outcomes were the 30- and 90-day mortality, respectively.

Results

Three lactate groups were identified based on GBTM, with group 3 exhibiting the worse short- [hazard ratio (HR) for 30-day mortality: 2.96, 95% confidence interval (CI) 1.79–4.87, P < 0.001] and long term (HR for 90-day mortality: 3.49, 95% CI 2.06–5.89, P < 0.001) outcomes followed by group 2 (HR for 30-day mortality: 2.05, 95% CI 1.48–2.84, P < 0.001 and HR for 90-day mortality: 1.99, 95% CI 1.48–2.67, P < 0.001). GBTM lactate groups exhibited significantly improved diagnostic performance of initial lactate + SOFA scores/APACHE II scores models. Based on the multivariable fractional polynomial interaction (MFPI) approach, GBTM lactate groups could better differentiate high-risk patients than the initial lactate groups in short- and long-term outcomes.

Conclusions

To the best of our knowledge, this is the first report that GBTM-based serial blood lactate evaluations significantly improve the diagnostic capacity of traditional critical care evaluation systems and bring many advantages over previously documented lactate evaluation systems.
Diaphragmatic ultrasonography-based rapid shallow breathing index for predicting weaning outcome during a pressure support ventilation spontaneous breathing trial
Authors: Song Jia , Qian Zhixian , Zhang Haixiang , Wang Minjia , Yu Yihua , Ye Cong , Hu Weihang , Gong Shijin
Published: September 2022

Background

The optimum timing to wean is crucial to avoid negative outcomes for mechanically ventilated patients. The rapid shallow breathing index (RSBI), a widely used weaning index, has limitations in predicting weaning outcomes. By replacing the tidal volume of the RSBI with diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) assessed by ultrasonography, we calculated two weaning indices, the diaphragmatic excursion rapid shallow breathing index (DE-RSBI, respiratory rate [RR]/DE) and the diaphragm thickening fraction rapid shallow breathing index (DTF-RSBI, RR/DTF). The aim of this study was to evaluate the predictive values of DTF-RSBI, DE-RSBI and traditional RSBI in weaning failure.

Methods

This prospective observational study included patients undergoing mechanical ventilation (MV) for > 48 h and who were readied for weaning. During a pressure support ventilation (PSV) spontaneous breathing trial (SBT), right hemidiaphragmatic excursion and DTF were measured by bedside ultrasonography as well as RSBI. Weaning failure was defined as: (1) failing the SBT and (2) SBT success but inability to maintain spontaneous breathing for more than 48 h without noninvasive or invasive ventilation. A receiver operator characteristic (ROC) curve was used for analyzing the diagnostic accuracy of RSBI, DE-RSBI, and DTF-RSBI.

Results

Of the 110 patients studied, 37 patients (33.6%) failed weaning. The area under the ROC (AUROC) curves for RSBI, DE-RSBI, and DTF-RSBI for predicting failed weaning were 0.639, 0.813, and 0.859, respectively. The AUROC curves for DE-RSBI and DTF-RSBI were significantly higher than for RSBI (P = 0.004 and P < 0.001, respectively). The best cut-off values for predicting failed weaning were RSBI > 51.2 breaths/min/L, DE-RSBI > 1.38 breaths/min/mm, and DTF-RSBI > 78.1 breaths/min/%.

Conclusions

In this study, two weaning indices determined by bedside ultrasonography, the DE-RSBI (RR/DE) and DTF-RSBI (RR/DTF), were shown to be more accurate than the traditional RSBI (RR/VT) in predicting weaning outcome during a PSV SBT.