bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing treatments for migraine: a headache for decision-makers
Authors: Mistry Hema , Naghdi Seyran , Underwood Martin , Duncan Callum , Madan Jason , Matharu Manjit
Published: December 2023

Background

Migraine is the world’s second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.

Aim

To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.

Methods

We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.

Results

Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.

Conclusions

Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
What to do with non-responders to CGRP(r) monoclonal antibodies: switch to another or move to gepants?
Authors: Waliszewska-Prosół Marta , Vuralli Doga , Martelletti Paolo
Published: December 2023

In this editorial we aim to provide potential therapeutic options in patients who do not benefit from treatment with CGRP(r) monoclonal antibodies. Based on current real-life studies and analysis of practical and economic aspects, we will analyze the potential benefits of changing CGRP-targeted treatment.
The implementation of the substitution principle in European chemical legislation: a comparative analysis
Authors: Slunge Daniel , Miguel Mécia , Lindahl Lina , Backhaus Thomas
Published: December 2023

Background

The substitution of hazardous chemicals with safer alternatives is an important objective in European chemical policy, but implementation has been slower than expected. We conduct a comprehensive analysis and comparison of the implementation of the substitution principle in European regulations for pesticides, biocides, and industrial chemicals. Specifically, we examine and compare the criteria and processes associated with the identification of candidates for substitution and the assessment of alternatives.

Results

We find only minor differences in the criteria applied to identify candidates for substitution amongst pesticides, biocides, and industrial chemicals, but larger differences concerning the processes used. While all substances that are to be approved as a pesticide and biocide are systematically evaluated against the established criteria for substitution, the substitution process for industrial chemicals only focuses on those substances identified as substances of very high concern. The main reason candidates for substitution remain on the market is the lack of identified safer chemical alternatives and the insufficient consideration of non-chemical alternatives, caused, at least to a large extent, by the comparatively weak incentives provided by current regulations.

Conclusions

The systematic approach for the identification of industrial substances of very high concern (SVHC) under ECHAs “Integrated Regulatory Strategy” is much welcome. However, no final conclusion on SVHC properties or the need for regulatory action has been drawn for approximately 90% of the REACH-registered substances, as often even basic hazard and exposure data are missing. Hence, at least a screening-level evaluation of SVHC properties should become a mandatory part of the substance registration under REACH. To reduce the risk of strategic behaviour in the search for alternatives to industrial chemicals identified as SVHC, a setup in which regulatory authorities play a larger role as information and knowledge brokers should be considered. Investments in innovation as well as improved sharing of information and a better distribution of the workloads amongst European authorities might also improve the identification of safer alternatives. However, without stronger incentives, making it more costly for companies to continue using hazardous substances relative to safer alternatives, initiatives to promote substitution are likely to have limited success.
Daily intake of 30 mg duloxetine is effective in decreasing premature ejaculation severity: a prospective randomized placebo-controlled cross over clinical trial
Authors: Zaazaa Adham , Nasr Eldin Mohamed , GamalEl Din Sameh Fayek , Zeidan Ashraf , Saleh Mohamed Yassin Mohamed , Adel Ahmed , Shokr Mohamed
Published: December 2023

Background

Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE).

Results

The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all).

Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all).

Conclusion

Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it’s efficacy and superiority.
Association between opioid abuse and COVID-19 susceptibility: a propensity score matched study
Authors: Hedayatyaghoobi Mojtaba , Azizmohammad Looha Mehdi , Shafiee Arman , Jafarabady Kyana , Safari Omid , Alirezaei Amirhesam , Bakhtiyari Mahmood
Published: December 2023

Background

Opioid use disorder (OUD) has been associated with adverse health outcomes, and its potential impact on COVID-19 outcomes is of significant concern. This study aimed to assess the susceptibility and clinical outcomes of hospitalized COVID-19 patients with OUD using a propensity score-matched design.

Methods

A historical cohort study was conducted in Alborz province, Iran, during the early months of the COVID-19 pandemic. Patients aged 18 years and above with confirmed COVID-19 were included in the study. OUD was defined as a compulsive urge to use opioids or opioid-derivative drugs. Non-opioid abusers with COVID-19 were selected as the control group. Data on demographics, clinical characteristics, laboratory factors, comorbidities, and vital signs were collected. Propensity score matching (PSM) was used to balance the groups and assess the impact of OUD on ICU admission, mortality, the need for intubation, and the severity of pulmonary involvement on CT scans.

Results

A total of 442 patients were included in the study, with 351 discharged and 34 deceased. The PSM analysis showed that OUD was not significantly associated with ICU admission (OR: 1.87, 95% CI: 0.22–2.91, p = 0.631). However, opium users had an increased risk of mortality (OR: 2.38, 95% CI: 1.30–4.35, p = 0.005) and a higher likelihood of requiring intubation (OR: 3.57, 95% CI: 1.38–9.39, p = 0.009) compared to non-opioid abusers. The severity of pulmonary involvement on CT scans did not show a significant association with OUD.

Conclusion

OUD among hospitalized COVID-19 patients was associated with an increased risk of mortality and the need for intubation. These findings highlight the importance of addressing OUD as a potential risk factor in the management and treatment of COVID-19 patients. Further research is warranted to explore the underlying mechanisms and develop appropriate interventions to mitigate the impact of OUD on COVID-19 outcomes.
The diagnostic dilemma for atypical presentation of progressive human Mpox
Authors: Sahra Syeda , Villalobos Raul Orozco , Scott Brian M. , Bowman Deidra J. , Sassine Joseph , Salvaggio Michelle , Drevets Douglas A. , Higuita Nelson Iván Agudelo
Published: December 2023

Background

Human mpox has increasingly been reported worldwide since May 2022, with higher incidence in men who have sex with men (MSM) and persons living with HIV (PLHIV) with presentation typical for generalized macules and papules.

Case presentation

We are describing a case of human mpox, which presented as widespread, atypical round verrucous lesions that went undiagnosed in the community for six months and was treated with antibacterials and antifungals given the similarity to skin manifestations associated with endemic mycoses.

Conclusions

Suspicion for human mpox should be high in young MSM and PLHIV who present with rash and mpox should be ruled out earlier.
Correlation between gut microbiome and cognitive impairment in patients undergoing peritoneal dialysis
Authors: Wang Jingjing , Wu Siyang , Zhang Jin , Li Yuanyuan , Wu Yonggui , Qi Xiangming
Published: December 2023

Background

Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment.

Methods

A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients.

Results

The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera.

Conclusion

Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.
Association between composite dietary antioxidant index and coronary heart disease among US adults: a cross-sectional analysis
Authors: Ma Ruicong , Zhou Xinyang , Zhang Guolin , Wu Hongying , Lu Yi , Liu Fengyi , Chang Yeting , Ding Yanchun
Published: December 2023

Background

The Composite Dietary Antioxidant Index (CDAI) is a dietary antioxidant score that plays a protective role in many diseases, including depression, osteoporosis, papillomavirus infection, etc. However, the association between CDAI and coronary heart disease (CHD) is currently unclear. We aim to explore the correlations between CDAI and the risk of CHD.

Methods

Eligible participants were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. All participants in this cross-sectional study are required to undergo two separate 24-h dietary recall interviews. Average daily intakes of dietary antioxidants were used to calculate CDAI. CHD status was determined through a questionnaire. Weighted multiple logistic regression models were used to evaluate the relationship between CDAI and CHD. Moreover, we also used restricted cubic spline to explore Non-linear correlations. Sensitivity analysis using unweighted logistic analysis and subgroup analysis were used to demonstrate the stability of the results.

Results

A total of 34,699 participants were eligible for analysis.Compared to the participants without CHD, the participants with CHD showed lower levels of CDAI. After adjusting confounding factors in the multivariate weighted logistic regression model, CDAI was inversely associated with CHD (Q4 vs. Q1, OR = 0.65 (0.51–0.82, P < 0.001). Restricted cubic spline showed that there was a negative non-linear correlation (L-shaped) between CDAI and CHD, suggesting a potential saturation effect at higher CDAI levels, with the inflection point of 0.16. Sensitivity analysis showed that the results were stable. No significant statistically interaction was showed in subgroup analysis.

Conclusions

There was a negative non-linear correlation between CDAI and CHD in US adults. However, further prospective studies are still needed to reveal their relationship.
Development and validation of two nomograms for predicting overall survival and Cancer-specific survival in prostate cancer patients with bone metastases: a population-based study
Authors: Li Baochao , Xing Jiajun , Wang Zhongyuan , Gong Zixuan , Wang Zengjun , Xu Aiming
Published: December 2023

Background

Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis.

Methods

From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared.

Results

There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System.

Conclusion

Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.
Change in surface properties of two different dental resin composites after using various beverages and brushing
Authors: Elmalawany Lamia M. , El-Refai Dina A. , Alian Ghada A.
Published: December 2023

Background

The study aimed to evaluate the influence of various beverages; with and without brushing; on the surface mechanical properties of two resin composites.

Methods

A total of 160 disc-shaped specimens were prepared for each of the following dental composites; nanohybrid ormocer (Admira fusion, VOCO GmbH, Cuxhaven, Germany) and nanohybrid resin composite (Grandio, VOCO GmbH, Cuxhaven, Germany). The baseline surface hardness and roughness measurements were carried out after 24 h. The composite samples were randomly distributed into one of the two groups; brushing and non-brushing, which were further divided into one of the four subgroups (n = 10); artificial saliva as control, coffee, red wine, and soft drink. In the non-brushing group, the specimens were immersed in the different beverages for five minutes three times daily for 30 days. The same procedure was done for the brushing group, in addition to brushing the specimens for five seconds. The surface hardness and roughness measurements were repeated after 30 days. One-way ANOVA and independent t-tests were used for statistical analysis.

Results

The soft drink had the most deteriorating effect and artificial saliva had the least. The change in surface properties was higher in the brushing subgroups. Grandio exhibited a higher change in surface microhardness while Admira fusion exhibited a higher change in surface roughness.

Conclusions

The surface properties of both dental resin composites were negatively affected by using beverages and brushing.
Antioxidant and antidiabetic flavonoids from the leaves of Dypsis pembana (H.E.Moore) Beentje & J.Dransf., Arecaceae: in vitro and molecular docking studies
Authors: Abdelrahim Mohamed S. , Abdel-Baky Afaf M. , Bayoumi Soad A.L. , Backheet Enaam Y.
Published: December 2023

Background

Oxidative stress and diabetes are medical conditions that have a growing prevalence worldwide, significantly impacting our bodies. Thus, it is essential to develop new natural antioxidant and antidiabetic agents.Dypsis pembana(H.E.Moore) Beentje & J.Dransf (DP) is an ornamental palm of the family Arecaceae. This study aimed to broaden the understanding of this plant’s biological properties by evaluating its in vitro antioxidant and antidiabetic activities.

Methods

The in vitro antioxidant activities of the crude extract, fractions, and selected isolates were evaluated by DPPH method. While the in vitro antidiabetic activities of these samples were evaluated by assessing the degree of inhibition of α-glucosidase. Additionally, molecular docking analysis was performed to investigate the interactions of tested compounds with two potential targets, the cytochrome c peroxidase and alpha glucosidase.

Results

The crude extract displayed the highest antioxidant activity (IC50of 11.56 µg/ml), whereas among the fractions, the EtOAc fraction was the most potent (IC50of 14.20 µg/ml). Among tested compounds, isoquercetrin (10) demonstrated the highest potency, with an IC50value of 3.30 µg/ml, followed by rutin (8) (IC50of 3.61 µg/ml). Regarding antidiabetic activity, the EtOAc (IC50of 60.4 µg/ml) and CH2Cl2fractions (IC50of 214.9 µg/ml) showed activity, while the other fractions did not demonstrate significant antidiabetic effects. Among tested compounds, kaempferol-3-O-neohesperidoside (9) showed the highest antidiabetic activity, with an IC50value of 18.38 µg/ml, followed by kaempferol (4) (IC50of 37.19 µg/ml). These experimental findings were further supported by molecular docking analysis, which revealed that isoquercetrin and kaempferol-3-O-neohesperidoside exhibited strong enzyme-binding affinities to the studied enzyme targets. This analysis provided insights into the structure-activity relationships among the investigated flavonol-O-glycosides.

Conclusion

The biological and computational findings revealed that isoquercetrin and kaempferol-3-O-neohesperidoside have potential as lead compounds for inhibiting cytochrome c peroxidase and alpha glucosidase enzymes, respectively.
Dying at “home” - a qualitative study of end-of-life care in rural Northern Norway from the perspective of health care professionals
Authors: Ervik Bente , Dønnem Tom , Johansen May-Lill
Published: December 2023

Background

‘Most patients want to die at home’ is a familiar statement in palliative care. The rate of home deaths is therefore often used as a success criterion. However, providing palliative care and enabling patients to die at home in rural and remote areas may be challenging due to limited health care resources and geographical factors. In this study we explored health care professionals’ experiences and reflections on providing palliative care to patients at the end of life in rural Northern Norway.

Methods

This is a qualitative focus group and interview study in rural Northern Norway including 52 health care professionals. Five uni-professional focus group discussions were followed by five interprofessional focus group discussions and six individual interviews. Transcripts were analysed thematically.

Results

Health care professionals did their utmost to fulfil patients’ wishes to die at home. They described pros and cons of providing palliative care in rural communities, especially their dual roles as health care professionals and neighbours, friends or even relatives of patients. Continuity and carers’ important contributions were underlined. When home death was considered difficult or impossible, nurses expressed a pragmatic attitude, and the concept of home was extended to include ‘home place’ in the form of local health care facilities.

Conclusions

Providing palliative care in patients’ homes is professionally and ethically challenging, and health care professionals’ dual roles in rural areas may lead to additional pressure. These factors need to be considered and addressed in discussions of the organization of care. Nurses’ pragmatic attitude when transfer to a local health care facility was necessary underlines the importance of building on local knowledge and collaboration. Systematic use of advance care planning may be one way of facilitating discussions between patients, family carers and health care professionals with the aim of achieving mutual understanding of what is feasible in a rural context.
Challenges and prospects of yeast-based microbial oil production within a biorefinery concept
Authors: Gallego-García María , Susmozas Ana , Negro María José , Moreno Antonio D.
Published: December 2023

Biodiesel, unlike to its fossil-based homologue (diesel), is renewable. Its use contributes to greater sustainability in the energy sector, mainly by reducing greenhouse gas emissions. Current biodiesel production relies on plant- and animal-related feedstocks, resulting in high final costs to the prices of those raw materials. In addition, the production of those materials competes for arable land and has provoked a heated debate involving their use food vs. fuel. As an alternative, single-cell oils (SCOs) obtained from oleaginous microorganisms are attractive sources as a biofuel precursor due to their high lipid content, and composition similar to vegetable oils and animal fats. To make SCOs competitive from an economic point of view, the use of readily available low-cost substrates becomes essential. This work reviews the most recent advances in microbial oil production from non-synthetic sugar-rich media, particularly sugars from lignocellulosic wastes, highlighting the main challenges and prospects for deploying this technology fully in the framework of a Biorefinery concept.
BMP signaling in cancer stemness and differentiation
Authors: Zhou Wei , Yan Kun , Xi Qiaoran
Published: December 2023

The BMP (Bone morphogenetic protein) signaling pathway plays a central role in metazoan biology, intricately shaping embryonic development, maintaining tissue homeostasis, and influencing disease progression. In the context of cancer, BMP signaling exhibits context-dependent dynamics, spanning from tumor suppression to promotion. Cancer stem cells (CSCs), a modest subset of neoplastic cells with stem-like attributes, exert substantial influence by steering tumor growth, orchestrating therapy resistance, and contributing to relapse. A comprehensive grasp of the intricate interplay between CSCs and their microenvironment is pivotal for effective therapeutic strategies. Among the web of signaling pathways orchestrating cellular dynamics within CSCs, BMP signaling emerges as a vital conductor, overseeing CSC self-renewal, differentiation dynamics, and the intricate symphony within the tumor microenvironment. Moreover, BMP signaling’s influence in cancer extends beyond CSCs, intricately regulating cellular migration, invasion, and metastasis. This multifaceted role underscores the imperative of comprehending BMP signaling’s contributions to cancer, serving as the foundation for crafting precise therapies to navigate multifaceted challenges posed not only by CSCs but also by various dimensions of cancer progression. This article succinctly encapsulates the diverse roles of the BMP signaling pathway across different cancers, spanning glioblastoma multiforme (GBM), diffuse intrinsic pontine glioma (DIPG), colorectal cancer, acute myeloid leukemia (AML), lung cancer, prostate cancer, and osteosarcoma. It underscores the necessity of unraveling underlying mechanisms and molecular interactions. By delving into the intricate tapestry of BMP signaling’s engagement in cancers, researchers pave the way for meticulously tailored therapies, adroitly leveraging its dualistic aspects—whether as a suppressor or promoter—to effectively counter the relentless march of tumor progression.
Low HDL-C can be a biomarker to predict persistent severe AKI in septic patients? A retrospective cohort study
Authors: Jiang Wei , Song Lin , Gong Weilei , Zhang Yaosheng , Shi Kerang , Liao Ting , Zhang Chuanqing , Yu Jiangquan , Zheng Ruiqiang
Published: December 2023

Purposes

Low HDL-C is associated with an increased risk of sepsis-associated AKI and subsequent decline in eGFR. HDL-C possesses anti-inflammatory, antioxidant, and endothelial repair-promoting properties. The use of Apo A-I mimetic peptides, which are the main structural components of HDL-C, has been shown to improve renal function in animal models of sepsis. However, the diagnostic value of low HDL-C in persistent sepsis-associated AKI remains unclear.

Methods

This is a retrospective cohort study based on MIMIC IV (V 2.2). The study population consisted of all adult septic patients admitted to the Beth Israel Deaconess Medical Center Intensive Care Unit from 2008 to 2019, with plasma HDL-C measured within 24 h of ICU admission. The primary endpoint was persistent severe sepsis-associated acute kidney injury (SA-AKI) and the secondary endpoint is kidney replacement therapy (KRT). Logistic regression was used to assess the correlation between HDL-C and persistent severe SA-AKI and KRT, and receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive ability.

Results

A total of 604 cases of SA-AKI patients were included in the analysis, among which 88 cases (14.5%) experienced persistent severe SA-AKI. The median (IQR) HDL-C level in the group with persistent severe SA-AKI was lower (33.0 [24.0–45.5]) compared to the non-persistent severe SA-AKI group (42.0 [31.0–53.0]). However, HDL-C showed poor discriminatory ability with an AUROC [95%CI] of 0.62 [0.56–0.69]. Clinical prediction models based on serum creatinine concentration, 24-h creatinine change, APSIIIscore, lactate levels, APTT, and heart rate performed well in predicting persistent severe SA-AKI with an AUROC [95%CI] of 0.876 [0.84–0.91]. However, adding HDL-C to this model did not improve predictive performance.

Conclusions

The plasma HDL-C measured within 24 h after admission to the ICU does not provide a good prediction for persistent severe SA-AKI, and it does not improve the clinical predictive ability compared to conventional variables.
An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker
Authors: Yang Yaocheng , Tang Xianzhe , Lin Zhengjun , Zheng Tao , Zhang Sheng , Liu Tang , Yang Xiaolun
Published: December 2023

Background

The gene TIMELESS, which is involved in the circadian clock and the cell cycle, has recently been linked to various human cancers. Nevertheless, the association between TIMELESS expression and the prognosis of individuals afflicted with pan-cancer remains largely unknown.

Objectives

The present study aims to exhaustively scrutinize the expression patterns, functional attributes, prognostic implications, and immunological contributions of TIMELESS across diverse types of human cancer.

Methods

The expression of TIMELESS in normal and malignant tissues was examined, as well as their clinicopathologic and survival data. The characteristics of genetic alteration and molecular subtypes of cancers were also investigated. In addition, the relationship of TIMELESS with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity was illustrated. Immunohistochemistry (IHC) was used to validate the expression of TIMELESS in clinical patients with several types of cancer.

Results

In contrast to the matching normal controls, most tumor types were found to often overexpress TIMELESS. Abnormal expression of TIMELESS was significantly related to more advanced tumor stage and poorer prognosis of breast cancer, as well as infiltrating immune cells such as cancer-associated fibroblast infiltration in various tumors. Multiple cancer types exhibited abnormal expression of TIMELESS, which was also highly correlated with MSI and TMB. More crucially, TIMELESS showed promise in predicting the effectiveness of immunotherapy and medication sensitivity in cancer therapy. Moreover, cell cycle, DNA replication, circadian rhythm, and mismatch repair were involved in the functional mechanisms of TIMELESS on carcinogenesis. Furthermore, immunohistochemical results manifested that the TIMELESS expression was abnormal in some cancers.

Conclusions

This study provides new insights into the link between the circadian gene TIMELESS and the development of various malignant tumors. The findings suggest that TIMELESS could be a prospective prognostic and immunological biomarker for pan-cancer.
Defining hip cartilage repair: a modified delphi study to establish the Magnetic Resonance Evaluation of the Repair of Cartilage in the Hip (MERCH) score
Authors:   The Magnetic Resonance Evaluation of the Repair of Cartilage in the Hip (MERCH) Investigators and The Canadian Hip Preservation Research Collaborative (CHIPR), Ayeni Olufemi R.
Published: December 2023

Purpose

To develop a standardized scoring system to evaluate pre‐ to post‐operative repair or reconstruction of hip cartilage using magnetic resonance imaging (MRI).

Methods

A two‐phase modified Delphi study was conducted. Phase 1 involved a survey with suggested criteria and diagrams to define various stages of articular cartilage repair and phase 2 involved an expert consensus meeting that discussed the survey responses and voted on final scoring criteria. The survey was emailed to members of the Canadian Hip Preservation Research Collaborative (CHIPR) and respondents included both board certified orthopedic surgeons as well as musculoskeletal radiologists.

Results

Overall, there were 17 survey respondents from Canada and most (47%, 8/17) participants agreed that the minimum MRI protocol needed to evaluate cartilage repair was a 3.0 T MRI and 94% (17/18) agreed that the minimum time post‐operatively that they felt they would be able to accurately evaluate cartilage repair on an MRI was 12 months. Following phases 1 and 2, the final Magnetic Resonance Evaluation of the Repair of Cartilage in the Hip (MERCH) score was developed with 7 domains, 3 criteria per domain: 1) volume fill of cartilage defect, 2) integration into adjacent cartilage, 3) surface of the repair tissue, 4) structure of the repair tissue, 5) bony overgrowth, 6) subchondral changes, and 7) delamination. The score ranges from 60 (optimal) to ‐20 points (worst/none).

Conclusions

This consensus project established a new MRI scoring system to evaluate post‐operative cartilage restoration of the hip. The implementation of the MERCH score is essential in our ability to guide patient management and expectations in a rapidly evolving field and will help with standardizing our evaluation of cartilage repair in future research trials.

Level of Evidence

Level II Diagnostic.
Optimisation of the air fraction correction for lung PET/CT: addressing resolution mismatch
Authors: Leek Francesca , Anderson Cameron , Robinson Andrew P. , Moss Robert M. , Porter Joanna C. , Garthwaite Helen S. , Groves Ashley M. , Hutton Brian F. , Thielemans Kris
Published: December 2023

Background

Increased pulmonary$$^{18}{}$$18F-FDG metabolism in patients with idiopathic pulmonary fibrosis, and other forms of diffuse parenchymal lung disease, can predict measurements of health and lung physiology. To improve PET quantification, voxel-wise air fractions (AF) determined from CT can be used to correct for variable air content in lung PET/CT. However, resolution mismatches between PET and CT can cause artefacts in the AF-corrected image.

Methods

Three methodologies for determining the optimal kernel to smooth the CT are compared with noiseless simulations and non-TOF MLEM reconstructions of a patient-realistic digital phantom: (i) the point source insertion-and-subtraction method,$$h_{pts}$$hpts; (ii) AF-correcting with varyingly smoothed CT to achieve the lowest RMSE with respect to the ground truth (GT) AF-corrected volume of interest (VOI),$$h_{AFC}$$hAFC; iii) smoothing the GT image to match the reconstruction within the VOI,$$h_{PVC}$$hPVC. The methods were evaluated both using VOI-specific kernels, and a single global kernel optimised for the six VOIs combined. Furthermore,$$h_{PVC}$$hPVCwas implemented on thorax phantom data measured on two clinical PET/CT scanners with various reconstruction protocols.

Results

The simulations demonstrated that at$$<200$$<200iterations (200 i), the kernel width was dependent on iteration number and VOI position in the lung. The$$h_{pts}$$hptsmethod estimated a lower, more uniform, kernel width in all parts of the lung investigated. However, all three methods resulted in approximately equivalent AF-corrected VOI RMSEs (<10%) at$$\ge$$≥200i. The insensitivity of AF-corrected quantification to kernel width suggests that a single global kernel could be used. For all three methodologies, the computed global kernel resulted in an AF-corrected lung RMSE <10%  at$$\ge$$≥200i, while larger lung RMSEs were observed for the VOI–specific kernels. The global kernel approach was then employed with the$$h_{PVC}$$hPVCmethod on measured data. The optimally smoothed GT emission matched the reconstructed image well, both within the VOI and the lung background. VOI RMSE was <10%, pre-AFC, for all reconstructions investigated.

Conclusions

Simulations for non-TOF PET indicated that around 200i were needed to approach image resolution stability in the lung. In addition, at this iteration number, a single global kernel, determined from several VOIs, for AFC, performed well over the whole lung. The$$h_{PVC}$$hPVCmethod has the potential to be used to determine the kernel for AFC from scans of phantoms on clinical scanners.
Repeated exposure of wheat to the fungal root pathogen Bipolaris sorokiniana modulates rhizosphere microbiome assembly and disease suppressiveness
Authors: Costa Lilian S. Abreu Soares , de Faria Mírian Rabelo , Chiaramonte Josiane Barros , Mendes Lucas W. , Sepo Edis , de Hollander Mattias , Fernandes José Maurício Cunha , Carrión Víctor J. , Bettiol Wagner , Mauchline Tim H. , Raaijmakers Jos M. , Mendes Rodrigo
Published: December 2023

Background

Disease suppressiveness of soils to fungal root pathogens is typically induced in the field by repeated infections of the host plant and concomitant changes in the taxonomic composition and functional traits of the rhizosphere microbiome. Here, we studied this remarkable phenomenon for Bipolaris sorokiniana in two wheat cultivars differing in resistance to this fungal root pathogen.

Results

The results showed that repeated exposure of the susceptible wheat cultivar to the pathogen led to a significant reduction in disease severity after five successive growth cycles. Surprisingly, the resistant wheat cultivar, initially included as a control, showed the opposite pattern with an increase in disease severity after repeated pathogen exposure. Amplicon analyses revealed that the bacterial families Chitinophagaceae, Anaerolineaceae and Nitrosomonadaceae were associated with disease suppressiveness in the susceptible wheat cultivar; disease suppressiveness in the resistant wheat cultivar was also associated with Chitinophagaceae and a higher abundance of Comamonadaceae. Metagenome analysis led to the selection of 604 Biosynthetic Gene Clusters (BGCs), out of a total of 2,571 identified by AntiSMASH analysis, that were overrepresented when the soil entered the disease suppressive state. These BGCs are involved in the biosynthesis of terpenes, non-ribosomal peptides, polyketides, aryl polyenes and post-translationally modified peptides.

Conclusion

Combining taxonomic and functional profiling we identified key changes in the rhizosphere microbiome during disease suppression. This illustrates how the host plant relies on the rhizosphere microbiome as the first line of defense to fight soil-borne pathogens. Microbial taxa and functions identified here can be used in novel strategies to control soil-borne fungal pathogens.
Comparative analysis of Hmx expression and the distribution of neuronal somata in the trigeminal ganglion in lamprey and shark: insights into the homology of the trigeminal nerve branches and the evolutionary origin of the vertebrate jaw
Authors: Tamura Motoki , Ishikawa Ryota , Nakanishi Yuki , Pascual-Anaya Juan , Fukui Makiko , Saitou Takashi , Sugahara Fumiaki , Rijli Filippo M. , Kuratani Shigeru , Suzuki Daichi G. , Murakami Yasunori
Published: December 2023

The evolutionary origin of the jaw remains one of the most enigmatic events in vertebrate evolution. The trigeminal nerve is a key component for understanding jaw evolution, as it plays a crucial role as a sensorimotor interface for the effective manipulation of the jaw. This nerve is also found in the lamprey, an extant jawless vertebrate. The trigeminal nerve has three major branches in both the lamprey and jawed vertebrates. Although each of these branches was classically thought to be homologous between these two taxa, this homology is now in doubt. In the present study, we compared expression patterns of Hmx, a candidate genetic marker of the mandibular nerve (rV3, the third branch of the trigeminal nerve in jawed vertebrates), and the distribution of neuronal somata of trigeminal nerve branches in the trigeminal ganglion in lamprey and shark. We first confirmed the conserved expression pattern of Hmx1 in the shark rV3 neuronal somata, which are distributed in the caudal part of the trigeminal ganglion. By contrast, lamprey Hmx genes showed peculiar expression patterns, with expression in the ventrocaudal part of the trigeminal ganglion similar to Hmx1 expression in jawed vertebrates, which labeled the neuronal somata of the second branch. Based on these results, we propose two alternative hypotheses regarding the homology of the trigeminal nerve branches, providing new insights into the evolutionary origin of the vertebrate jaw.
Predictive underestimation of difficult direct laryngoscopy in a patient with rheumatoid arthritis-associated immobilized craniocervical junction
Authors: Matsuyama Hirotaka , Hara Masato , Seto Atsushi , Hiraki Teruyuki
Published: December 2023

Background

The upper cervical spine is a major focus of damage by rheumatoid arthritis (RA). Specific screening for mobility of the upper cervical spine, which is essential for direct laryngoscopy, is lacking. Herein, we present a case of RA with Cormack-Lehane grade IV, which was not predicted by preoperative examination.

Case presentation

A 66-year-old woman with RA was scheduled for a right total knee arthroplasty and right elbow synovectomy. She had a long history of RA without symptoms related to the cervical spine or spinal cord. Although physical examination suggested moderate risk of difficult intubation with preserved cervical retroflexion, her Cormack-Lehane classification was grade IV under muscle relaxation. Bony integration of the occiput to axis was considered to be the main cause of difficult direct laryngoscopy, and restricted neck rotation was found postoperatively.

Conclusions

RA patients may have limited upper cervical spine motion despite normal cervical retroflexion.
Replicability and reproducibility of predictive models for diagnosis of depression among young adults using Electronic Health Records
Authors: Nickson David , Singmann Henrik , Meyer Caroline , Toro Carla , Walasek Lukasz
Published: December 2023

Background

Recent advances in machine learning combined with the growing availability of digitized health records offer new opportunities for improving early diagnosis of depression. An emerging body of research shows that Electronic Health Records can be used to accurately predict cases of depression on the basis of individual’s primary care records. The successes of these studies are undeniable, but there is a growing concern that their results may not be replicable, which could cast doubt on their clinical usefulness.

Methods

To address this issue in the present paper, we set out to reproduce and replicate the work by Nichols et al. (2018), who trained predictive models of depression among young adults using Electronic Healthcare Records. Our contribution consists of three parts. First, we attempt to replicate the methodology used by the original authors, acquiring a more up-to-date set of primary health care records to the same specification and reproducing their data processing and analysis. Second, we test models presented in the original paper on our own data, thus providing out-of-sample prediction of the predictive models. Third, we extend past work by considering several novel machine-learning approaches in an attempt to improve the predictive accuracy achieved in the original work.

Results

In summary, our results demonstrate that the work of Nichols et al. is largely reproducible and replicable. This was the case both for the replication of the original model and the out-of-sample replication applying NRCBM coefficients to our new EHRs data. Although alternative predictive models did not improve model performance over standard logistic regression, our results indicate that stepwise variable selection is not stable even in the case of large data sets.

Conclusion

We discuss the challenges associated with the research on mental health and Electronic Health Records, including the need to produce interpretable and robust models. We demonstrated some potential issues associated with the reliance on EHRs, including changes in the regulations and guidelines (such as the QOF guidelines in the UK) and reliance on visits to GP as a predictor of specific disorders.
Healthy lives and well-being for all at all ages: expanding representations of determinants of health within systems dynamics and integrated assessment models
Authors: Weber Eartha , Downward George , Pinho Maria G. M. , Van Vuuren Detlef P.
Published: December 2023

Integrated Assessment Models (IAMs) and System Dynamic Models (SDMs) are starting to incorporate representations of the impact of environmental changes on health and socio-economic development into their modelling frameworks. We use this brief review to provide an overview of how health and well-being are currently represented in IAMs and SDMs. A grey literature search on 12 selected model host websites and their corresponding Wiki pages was conducted. Model descriptions, coverage and publications were then tabulated. Additional potential determinants related to health were then suggested based on emerging environmental health literature. Based on these tabulations, it was determined that many individual health outcomes are not represented and thus not analyzed. Social well-being is not represented at all. Additionally, potentially health relevant determinants such as chemical or metal exposure and water pollution are rarely represented in models. Most models have representations of climate, outdoor air pollution and food availability. Air pollution was the most analyzed determinant, especially in relation to its respiratory effects. We suggest that future modelers incorporate more representations of environmental determinants influencing health, and to analyze all available determinants in relation to a wider array of health outcomes. Perhaps, if and when broader determinants of health are represented in IAMs and SDMs, then a composite of these determinants could be used to determine a population’s ability to achieve elements that also contribute to social well-being.
Towards the transferable audio adversarial attack via ensemble methods
Authors: Guo Feng , Sun Zheng , Chen Yuxuan , Ju Lei
Published: December 2023

In recent years, deep learning (DL) models have achieved significant progress in many domains, such as autonomous driving, facial recognition, and speech recognition. However, the vulnerability of deep learning models to adversarial attacks has raised serious concerns in the community because of their insufficient robustness and generalization. Also, transferable attacks have become a prominent method for black-box attacks. In this work, we explore the potential factors that impact adversarial examples (AEs) transferability in DL-based speech recognition. We also discuss the vulnerability of different DL systems and the irregular nature of decision boundaries. Our results show a remarkable difference in the transferability of AEs between speech and images, with the data relevance being low in images but opposite in speech recognition. Motivated by dropout-based ensemble approaches, we propose random gradient ensembles and dynamic gradient-weighted ensembles, and we evaluate the impact of ensembles on the transferability of AEs. The results show that the AEs created by both approaches are valid for transfer to the black box API.