bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis
Authors: Fu Jennifer , Tabbara Najla , Tomlinson George , Murphy Kellie E , Hamilton Jill , Feig Denice S
Published: January 2025

Objective

The study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.

Design

Systematic review and meta-analysis.

Data sources

Medline, Embase and Cochrane Central were searched from inception to 4 October 2024.

Eligibility criteria for selecting studies

Follow-up studies of randomised-controlled trials and observational studies involving metformin use in pregnancy for any insulin-resistant maternal condition were included.

Data extraction and synthesis

Two reviewers independently extracted data and completed risk-of-bias assessments using either Cochrane Risk-Of-Bias tool V.2 or Risk of Bias in Non-Randomised Studies of Exposure depending on study design. Meta-analyses were conducted using the generic inversed variance method in a random-effects model. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess certainty of evidence.

Results

18 studies reporting on 7975 children with metformin exposure in utero and over 1 million children without metformin exposure were included. At the oldest age of follow-up reported (weighted mean age of 4.4 years), children with metformin exposure for any maternal indication had comparable body mass index (BMI) with their non-exposed peers (standardised mean difference (SMD) −0.02; 95% CI: −0.11, 0.07; low certainty). When stratified by age at follow-up, while metformin-exposed children had slightly higher BMI at 1–3 years of age (SMD 0.15; 95% CI: 0.04, 0.27; low certainty), no difference remained between the two groups by ages 3–6 and 6–11 years. When stratified by maternal diagnosis, no difference in BMI was found in the diabetes and obesity subgroups, while in the polycystic ovary syndrome subgroup metformin-exposed children were heavier than non-exposed peers (SMD 0.31; 95% CI: 0, 0.62; low certainty). No difference was seen in overweight, obesity or waist circumference.

Conclusions

Metformin-exposed children did not differ in adiposity measures compared with their non-exposed peers in later childhood. This adds to the growing body of evidence supporting the long-term safety of metformin use in pregnancy.

PROSPERO registration number

CRD42023394464.
Application of core functions and forms in complex health intervention research: a scoping review protocol
Authors: Fox Katelyn , Passey Debbie , Kang Eunyoung , Zeigen Laura , Kenzie Erin , Austin Jessica D , Meadows Rachel J , Fernandez Maria E , Perez Jolles Monica
Published: January 2025

Introduction

The ability of healthcare, community and public health systems to effectively implement and disseminate research innovations depends on contextual factors at multiple interconnected levels of influence (eg, the innovation, individual, provider/implementor, organisation and health system). Recently, there has been an increase in the development of complex interventions designed to target multiple levels, designed for or adapted to the context in which they are delivered. Two concepts from complex systems thinking have been increasingly used to operationalise such interventions—core functions (theory and evidence-driven purposes of interventions) and forms (adaptable activities that perform each core function). However, there is a gap in the literature regarding how these concepts are being applied in intervention design and evaluation and implementation strategies. To fill this gap and advance understanding of complex health interventions, this scoping review will:

Identify how functions and forms are defined and operationalised across complex health implementation research studies.

Describe methodological approaches to identify or apply the concepts of core functions and forms to the design and evaluation of complex health interventions and implementation strategies.

Methods and analysis

This review will follow the methodological approach of Arksey and O’Malley. The search strategy will include electronic databases (PubMed, Scopus, Embase, CINAHL and Web of Science) and reference lists and citations of exemplar papers in the field. The literature search will be designed to capture research applying the concepts of core functions and forms in healthcare and public health complex interventions. The search will be restricted to studies published in English in peer-reviewed academic journals. Two coders will screen study titles and abstracts, followed by full-text reviews. One researcher will extract the data and a second will review it for any omissions or errors. An inductive content analysis will be used to categorise the nature of how studies define and operationalise core functions and forms. The scope of the work in this area and methodology (eg, measures selection and analytic approaches) will be described narratively. Results will be presented to experts in the field and their input will be used to further contextualise the findings.

Ethics and dissemination

This project does not require ethics approval. We will share the findings and data results will be shared via peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/YQFP7
miR-21 and cathepsin B in familial Mediterranean fever: novel findings regarding their impact on disease severity
Authors: Durmus Sinem , Gelisgen Remise , Hajiyeva Ramila , Adrovic Amra , Yildiz Mehmet , Yucesan Emrah , Barut Kenan , Kasapcopur Ozgur , Uzun Hafize
Published: January 2025

Objective

The limited predictive effect of genotype on familial Mediterranean fever (FMF) phenotype suggests that epigenetic factors and alternative mechanisms that may cause IL-1β release could contribute to phenotypic heterogeneity. The objective of this study was to examine the role of IL-1β levels and miR-21-5p, cathepsin B and pyrin levels, which were identified as potential factors causing IL-1β release through the use of bioinformatics tools, in the pathogenesis of FMF and their relationship with disease severity.

Materials and methods

50 paediatric patients with FMF and 40 healthy children were enrolled in this study. Patients were divided into subgroups according to Pras disease severity score. Serum miR-21-5p expression levels were assessed by qRT-PCR, while serum pyrin, IL-1β and cathepsin B levels were determined by ELISA.

Results

Serum miR-21-5p was significantly downregulated in FMF patients compared with the control group (p<0.001), while serum pyrin, IL-1β and cathepsin B levels were markedly elevated (p<0.001 for each). Only miR-21-5p was negatively correlated with IL-1β (r=−0.855; p<0.001). In moderately severe FMF patients, miR-21-5p exhibited a statistically significant downregulation (p<0.001), whereas IL-1β and cathepsin B showed a statistically significant increase (p<0.001 and p<0.05, respectively). Furthermore, the Pras score showed a strong negative correlation (r=−0.738; p<0.001) with miR-21-5p levels. Multivariate logistic regression showed that in FMF, a one-unit decrease in miR-21 increased disease severity risk 6.76-fold, while a one-unit increase in cathepsin B raised it 1.71-fold.

Conclusion

This might be considered one of the mechanisms for subclinical inflammation in paediatric FMF patients through increased activation of cytokines via the downregulation of miR-21-5p. Our findings suggest that miR-21-5p and IL-1β play key roles in subclinical inflammation, and these molecules might be a potential therapeutic target.
Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing
Authors: Taube Janis M , Sunshine Joel C , Angelo Michael , Akturk Guray , Eminizer Margaret , Engle Logan L , Ferreira Cláudia S , Gnjatic Sacha , Green Benjamin , Greenbaum Shirley , Greenwald Noah F , Hedvat Cyrus V , Hollmann Travis J , Jiménez-Sánchez Daniel , Korski Konstanty , Lako Ana , Parra Edwin R , Rebelatto Marlon C , Rimm David L , Rodig Scott J , Rodriguez-Canales Jamie , Roskes Jeffrey S , Schalper Kurt A , Schenck Emanuel , Steele Keith E , Surace Michael J , Szalay Alexander S , Tetzlaff Michael T , Wistuba Ignacio I , Yearley Jennifer H , Bifulco Carlo B
Published: January 2025

Objectives

Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force. The current effort represents a complementary manuscript for mIHC/IF analysis focused on the associated image analysis and data management.

Methods

The Society for Immunotherapy of Cancer convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the quantitative image analysis of mIHC/IF output and data management considerations.

Results

Best-practice approaches for image acquisition, color deconvolution and spectral unmixing, tissue and cell segmentation, phenotyping, and algorithm verification are reviewed. Additional quality control (QC) measures such as batch-to-batch correction and QC for assembled images are also discussed. Recommendations for sharing raw outputs, processed results, key analysis programs and source code, and representative photomicrographs from mIHC/IF assays are included. Lastly, multi-institutional harmonization efforts are described.

Conclusions

mIHC/IF technologies are maturing and are routinely included in research studies and moving towards clinical use. Guidelines for how to perform and standardize image analysis on mIHC/IF-stained slides will likely contribute to more comparable results across laboratories and pave the way for clinical implementation. A checklist encompassing these two-part guidelines for the generation of robust data from quantitative mIHC/IF assays will be provided in a third publication from this task force. While the current effort is mainly focused on best practices for characterizing the tumor microenvironment, these principles are broadly applicable to any mIHC/IF assay and associated image analysis.
Challenges and prospects in implementing the Generational Endgame policy: Malaysia and global perspectives
Authors: Phoa Picholas Kian Ann , Wee Lei Hum , Wong Yin How , Siau Ching Sin , Chan Caryn Mei Hsien , Dain Chrisminder , Mohamed Mohamad Haniki Nik
Published: January 2025

In Malaysia, tobacco smoking continues to be one of the leading public health concerns; hence, the tobacco control community aims to see a generation free of tobacco use by 2040. Drafted and presented to the parliament, the Malaysian Control of Smoking Products for Public Health Bill 2022 highlighted the Generational Endgame (GEG) policy, which forbids the use and sale of tobacco products and smoking substances to individuals born on or after 1 January 2007. Stakeholders, including government and non-governmental organisations, policymakers, healthcare professionals, tobacco industry representatives and retailers, have expressed differing opinions indicating non-support of the policy. The Attorney General Chamber deemed the policy as ‘unconstitutional’ for discriminating against those within the implementation age range, which prompted its omission from the revised Control of Smoking Products for Public Health 2023 Bill. This paper discusses the obstacles and possible implications of the GEG policy implementation in Malaysia and details its implementation in other countries. This paper also proposes several recommendations for future directions in tackling the obstacles mentioned more effectively.
Prospective association of tobacco retailer density and neighbourhood walkability with youth vaping initiation in California, USA
Authors: Harlow Alyssa F , Thompson Laura K , Eckel Sandrah P , Leventhal Adam M , Haley Danielle F , Roberts Megan E , Cockburn Myles G , Barrington-Trimis Jessica L
Published: January 2025

Background

Tobacco retailer density might influence youth e-cigarette use due to increased access and exposure to point-of-sale marketing. There is a need for longitudinal investigations on the association of tobacco retailer density with youth e-cigarette use, with consideration of contextual factors such as neighbourhood walkability that could enhance retailer exposure.

Methods

Five semi-annual waves (Fall 2021-Fall 2023) of a Southern California school-based cohort of youth who never vaped at baseline (n=3401; mean baseline age=15 years [range=12–17]) were merged with spatial data on tobacco retailers corresponding to each school year. Time-varying measures of retailer exposures included count of retailers within circular home buffers (800 m/1600 m buffers) and retailer density/km2within home census tracts. Discrete-time survival analyses estimated associations of time-lagged and time-varying retailer exposures with vaping initiation at each 6-month follow-up, adjusting for race/ethnicity, parental education, neighbourhood walkability and an Area Deprivation Index. Secondary analyses examined moderation by neighbourhood walkability based on a National Walkability Index.

Results

The incident rate of vaping initiation was 3.8% per 6-month follow-up. After covariate adjustment, only associations with census tract retail density were statistically significant (risk ratio (RR) highest vs lowest quartile=1.36, 95% CI=1.01 to 1.84). In moderation analyses, count of retailers within 800 m home buffers was positively associated with vaping initiation for youth who lived in the most walkable neighbourhoods (RR=1.08, 95% CI: 1.01 to 1.16), with no association for youth in less walkable neighbourhoods (RR=1.00, 95% CI:0.95 to 1.05; interaction p-value=0.0238).

Conclusion

Findings highlight the potential role of restricting retailer density in preventing youth vaping, particularly in areas characterised by both greater walkability and tobacco retailer density.
Balancing specialization and adaptation in a transforming scientific landscape
Authors: Gautheron Lucas
Published: January 2025

How do scientists navigate between the need to capitalize on their prior knowledge through specialization, and the urge to adapt to evolving research opportunities? Drawing from diverse perspectives on adaptation, this paper proposes an unsupervised Bayesian approach motivated by Optimal Transport of the evolution of scientists’ research portfolios in response to transformations in their field. The model relies on $186{,}162$
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scientific abstracts and authorship data to evaluate the influence of intellectual, social, and institutional resources on scientists’ trajectories within a cohort of 2108 high-energy physicists between 2000 and 2019. Using Inverse Optimal Transport, the reallocation of research efforts is shown to be shaped by learning costs, thus enhancing the utility of the scientific capital disseminated among scientists. Two dimensions of social capital, namely “diversity” and “power”, have opposite associations with the magnitude of change in scientists’ research interests: while “diversity” is associated with greater change and expansion of research portfolios, “power” is associated with more stable research agendas. Social capital plays a more crucial role in shifts between cognitively distant research areas. More generally, this work suggests new approaches for understanding, measuring and modeling collective adaptation using Optimal Transport.
Nerve Capping Using Renerve® Synthetic Collagen Conduits for Hand Amputation Neuroma Pain
Authors: TAKEDA Shinsuke , KURIMOTO Shigeru , SHIBATA Ryutaro , MITSUYA So , OKAMOTO Hideki , MURAKAMI Hideki
Published: January 2025

Background: Amputated neuromas, a common consequence of peripheral nerve injury, can cause significant pain and may impair daily life. Herein, we conducted a retrospective study on patients who underwent a nerve-capping technique using the bioabsorbable nerve conduit Renerve®, with a minimum follow-up period of 6 months.

Methods: We conducted a retrospective study to assess patients with amputation neuromas of the finger or palm who underwent surgical treatment using the capping technique with the Renerve® conduit between October 2018 and September 2022. The data on demographics, operative details, pre- and postoperative evaluations (visual analogue scale [VAS] pain scores and Tinel sign) and complications were analysed.

Results: Seven patients (seven nerves) with a median age of 51 years (three men and four women) were assessed. The median follow-up duration was 15 months. Renerve® conduits of varying sizes (1.0–2.3 mm) and lengths (15–25 mm) were used. The median duration until surgery was 195 days. After the procedure, VAS pain scores significantly decreased from a baseline of 53.1 mm to 5.7 mm at the 6-month follow-up. Tinel sign persisted in four patients, and no postoperative complications occurred.

Conclusions: Our study demonstrates the clinical usefulness of the Renerve® conduit as a nerve-capping technique for amputation neuroma. Considering the limited availability of real-world data on Renerve® conduits for nerve capping, our findings provide valuable insights for clinical practitioners.

Level of Evidence: Level IV (Therapeutic)
The Higher Positive Amyloid Deposition in Electrophysiologically Proven Idiopathic Carpal Tunnel Syndrome Patients
Authors: MAEHARA Haruka , TADOKORO Nobuaki , UEBA Hiroaki , IKEUCHI Masahiko
Published: January 2025

Background: Carpal tunnel syndrome (CTS) due to amyloid deposition was reported to precede fatal cardiac amyloidosis by several years. Although nerve conduction study (NCS) supports CTS diagnosis, the incidence of positive amyloid deposition in electrophysiologically proven CTS is unclear.

Methods: We retrospectively analysed the demographic data including age, gender, bilateral hand involvement, amyloid deposition and NCS results, of 111 consecutive CTS patients with postoperative symptom improvement (mean 71.1 years old, male/female ratio: 44/67) who simultaneously underwent carpal tunnel release (CTR) and biopsy for amyloid deposition.

Results: Electrophysiologically proven CTS patients were 102 (91.9%) out of 111 patients. Amyloid deposition was detected in 62 hands (55.9%), of which 51 were transthyretin amyloid. The NCS severity was associated with a higher prevalence of positive amyloid deposition (p < 0.01). The NCS severity also showed an increased trend between reported risk factors for positive amyloid deposition such as older age, male gender and bilateral hand symptoms (p < 0.01).

Conclusions: The prevalence of positive amyloid deposition was higher than previous reports in this study. Abnormal NCS findings in CTS, such as an increased distal motor latency (DML) of abductor pollicis brevis compound muscle action potentials (APB-CMAP) or absent APB-CMAP, may help to increase the pre-test probability of amyloid deposition in tenosynovial biopsy.

Level of Evidence: Level IV (Diagnostic Study)
Effectiveness of Nerve Wrapping and Capping with a Nerve Conduit and Blocking Splint Therapy for a Painful Neuroma at the Metacarpophalangeal Joint
Authors: SHINTANI Kosuke , KUBOTA Yutaka , MATSUDA Daisaku
Published: January 2025

A 42-year-old man suffered an avulsion amputation of his right middle finger. He had undergone several surgeries since the age of 24, including amputation plasty and implantation of the injured nerve into fat and bone, but had difficulty returning to work due to persistent severe pain. He underwent nerve capping with an artificial nerve conduit at a university hospital, and his symptoms improved slightly, but immediately flared up again. Therefore, he was referred to our hospital and was treated with a blocking splint in addition to resection of the traumatic neuroma, covering with an artificial nerve conduit and wrapping with an adiposal flap. The lumen of the conduit was observed without collapse until it was resorbed, and he returned to work without pain 10 months after surgery. The blocking splint to an angle that preserves the lumen of the conduit was useful for artificial nerve surgery near the joint.

Level of Evidence: Level V (Therapeutic)
Shady Science: The Role of Shadows in Non-Line-of-Sight Imaging
Authors: Saunders Charles
Published: January 2025

What secrets do shadows hold? Perhaps more than you might expect. They can help us see around obstacles, brightening the future of autonomous driving safety and other technologies.
Lung Endothelial Cell Heterogeneity in Health and Pulmonary Vascular Disease
Authors: Mora Massad K. , Dai Z. , Petrache I. , Ventetuolo C. E. , Lahm T.
Published: January 2025

Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH). In this mini-review, we explore the evolving understanding of lung EC heterogeneity, particularly through the lens of single-cell RNA sequencing (scRNA-seq) technologies. These advances have provided unprecedented insights into the diverse EC subpopulations, their specific roles, and the disturbances in their homeostatic functions that contribute to PH pathogenesis. In particular, these studies identified novel and functionally distinct cell types such as aerocytes and general capillary ECs that are critical for maintaining lung function in health and disease. In addition, multiple novel pathways and mechanisms have been identified that contribute to aberrant pulmonary vascular remodeling in PH. Emerging techniques like single-nucleus RNA sequencing and spatial transcriptomics have further pushed the field forward by discovering novel disease mediators. As research continues to leverage these advanced techniques, the field is poised to uncover novel EC subtypes and disease mechanisms, paving the way for new therapeutic targets in PH and other lung diseases.
Early auditory and adult mating experiences interact with singer identity to shape neural responses to song in female zebra finches
Authors: Catalano Isabella , Woolley Sarah Cushing
Published: January 2025

Social and sensory experiences across the lifespan can shape social interactions, however, experiencedependent plasticity is widely studied within discrete life stages. In the socially monogamous zebra finch, in which females use learned vocal signals to identify individuals and form long‐lasting pair bonds, developmental exposure to song is key for females to show species‐typical song perception and preferences. While adult mating experience can still lead to pair‐bonding and song preference learning even in birds with limited previous song exposure (“song‐naïve”), whether similarities in adult behavioral plasticity between normally‐reared and song‐naïve females reflect convergent patterns of neural activity is unknown. We investigated this using expression of a marker of neural activity and plasticity (phosphorylated S6) in mated normally‐reared and song‐naïve females in response to song from either their mate, a neighbor, or an unfamiliar male. We found that, in portions of a secondary auditory region (the caudomedial nidopallium, NCM) and in dopaminergic neurons of the caudal ventral tegmental area, hearing the mate’s song significantly increased pS6 expression in females from both rearing conditions. In contrast, within other NCM subregions, song identity drove different patterns of pS6 expression depending on the rearing condition. These data suggest that developmental experiences can have long‐lasting impacts on the neural signatures of behaviors acquired in adulthood and that socially‐driven behavioral plasticity in adults may arise through both shared and divergent neural circuits depending on an individual’s developmental experiences.
Real Life Blood Management Practices in Thalassemia and Myelodysplastic Syndrome Patients
Authors: Aydin Muruvvet S. , Cengiz Esra
Published: January 2025

The effect of pretransfusion hemoglobin on transfusion burden, thrombosis, and mortality in thalassemia and myelodysplastic syndrome is unclear. We aimed to study the pretransfusion hemoglobin and erythrocyte transfusion burden and investigate the effects of these variables on each other in real‐life in thalassemia and myelodysplastic syndrome. Adult patients with thalassemia and myelodysplastic syndrome who received at least one erythrocyte concentrate unit outpatient at Sanliurfa Mehmet Akif Inan Training and Research Hospital during 1 year were included in the study. The data were retrospectively obtained. Ethical approval was obtained for the study. Ninety‐two patients were included in the study. In thalassemia major, pretransfusion hemoglobin ≥ 9 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (15 vs. 27) and median annual number of transfusion sessions (11 vs. 14) p = 0.002, p = 0.009, respectively). In myelodysplastic syndrome, a pretransfusion hemoglobin level ≥ 8 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (6 vs. 24) (p = 0.016). In thalassemia major with an intact spleen, pretransfusion hemoglobin ≥ 8 g/dL was associated with an increased median annual number of transfused erythrocyte concentrate units (32 vs. 27) and median annual number of transfusion sessions (18 vs. 14) (p = 0.046, p = 0.038, respectively). In conclusion, higher pretransfusion hemoglobin levels were related to a lower transfusion burden in thalassemia major and myelodysplastic syndrome.
The Effects of Different Constitutive Compression Models of Concrete on the FRP–Concrete Bonded Interface
Authors: An Feng-Chen
Published: January 2025

This study presents the selection process of an approximate constitutive compression model of concrete in the simulations of a fiber‐reinforced polymer (FRP)–concrete bonded interface because significant effects of compressive strain energy have been found on the ultimate load at the FRP–concrete bonded interface through a reliable finite element (FE) model. In this study, a number of constitutive compression models of concrete are comprehensively reviewed first and then compared to the experimental data from short concrete columns with different compressive strengths, revealing that the models in the third group are in the best agreement with those in physical tests. The effect of residual stress through different cut‐off schemes is then investigated on the basis of the FE model validated by the corresponding testing data of the FRP–concrete bonded interface. The aforementioned constitutive compression models with appropriate values for residual stress are employed to investigate their effects on the mechanical behavior in the simulations of the FRP–concrete bonded interface through the validated FE model. Once again, it suggests that the models in the third group are most suitable to simulate the mechanical behavior of concrete at the FRP–concrete bonded interface.
Nutritional Composition, Bioactive Compounds and Antioxidant Potential of Pineapple Rind Flour as Functional Food Ingredient
Authors: Emmanuella Bai , Ijeoma Nwafor , Sunday Adoga , Ogo Ogo , Ogbene Igbum
Published: January 2025

The global drive toward transformative food systems has intensified focus on value addition and the development of functional foods from agricultural by‐products. Pineapple processing significantly contributes to the food industry yet generates substantial waste, primarily in the form of peels. These by‐products are often discarded, representing an untapped resource for potential functional food ingredients. This study aimed to comprehensively evaluate the nutritional and chemical composition of pineapple rind flour (PRF) as a novel functional ingredient. PRF was prepared by dehydrating fresh pineapple rinds at 50°C for 12 h using a 21S01 DOOSAT air fryer oven. The flour was subjected to various analyses including proximate composition, vitamin and mineral profiling, essential amino acid quantification, phytochemical characterization, physicochemical property assessment and antioxidant capacity evaluation using standard analytical procedures. The results revealed that PRF contains significant nutritional components: 5.99% protein, 3.92% crude fibre and 3.81% ash. Furthermore, mineral analysis showed high concentrations of potassium (941 mg/100 g), zinc (16.04 mg/100 g) and iron (36.22 mg/100 g). Vitamins A (6.52 mg/100 g) and C (28.82 mg/100 g) were present in appreciable quantities, with B‐vitamins ranging from 2.33 mg/100 g to 4.16 mg/100 g. Also, PRF showed significant essential fatty acid including oleic (65.77 mg/100 g), linoleic (172.00 mg/100 g) and arachidonic acids (169.04 mg/100 g). Additionally, phytochemical analysis revealed substantial amounts of total phenols (131.32 mgGAE/g), flavonoids (97.08 mgQE/g) and cardiac glycosides (64.26 mg/g). The antioxidant capacity of PRF as measured by FRAP, DPPH and ABTS was 181.31 μmol FeSO4/g), 96.47% and 88.22 μmol TE/g DW, respectively. Importantly, antinutritional factors were present in low concentrations. These findings demonstrate the potential of PRF as a nutrient‐dense functional food ingredient, suggesting that its incorporation into food products could contribute to improved their nutritional profiles while concurrently offering a sustainable solution to agricultural waste management.
Time‐Series Forecasting Using SVMD‐LSTM: A Hybrid Approach for Stock Market Prediction
Authors: Agarwal Sanskar , Sharma Shivam , Faisal Kazi Newaj , Sharma Rishi Raj
Published: January 2025

The fluctuations in the stock market serve as an indicator of societal and economic progress. To enhance the forecasting of financial time series data, this paper introduces a novel hybrid model that integrates successive variational mode decomposition (SVMD) with a long short‐term memory (LSTM) network. SVMD is used as a data‐decomposition technique to facilitate the division of complex original series into its decomposed intrinsic mode functions in order to reduce nonstationarity. This approach has been analyzed for both synthetic signals and financial time series data. LSTM is utilized to analyze each signal and take into consideration the influence of historical data in order to enhance prediction accuracy. The final predicted results are derived by reconstructing each predicted time series. To evaluate the model, financial time‐series data from global stock market have been selected for analysis, i.e., the Hong Kong Hang Seng Index (HSI), Stock Exchange Sensitive Index (SENSEX), Standard and Poor’s 500 (S&P500), and North America West Texas Intermediate (WTI). The proposed model has shown improved prediction results based on the performance metrics when compared with single models and other existing hybrid models.
Somatosensory‐Evoked Potentials and Clinical Assessments of Sensory Function Over Time in Patients With Subacute Stroke
Authors: Fuseya Hiroshi , Tashiro Syoichi , Takahashi Osamu , Kobayashi Yukiko , Tsuji Tetsuya , Mizuno Katsuhiro
Published: January 2025

Objective: To demonstrate the utility of somatosensory evoked potentials (SEPs) following median nerve stimulation for chronological assessment of sensory function in patients with subacute stroke during rehabilitation.

Design: Retrospective study.

Patients: Forty‐seven patients with hemiparesis due to stroke during the subacute phase.

Methods: We screened 363 patients who underwent SEP measurements at a rehabilitation hospital. Among them, 47 who underwent SEP measurements within 1 week after admission and at least 2 weeks after the initial assessment were included in this study. Sensorimotor assessments, including the Semmes−Weinstein monofilament test (SWMT), pain sensation, position sensation, two‐point discrimination, and Stroke Impairment Assessment Set (SIAS) motor tests simultaneously with SEP measurements were available for 20 of the 47 patients. The relationship between the SEP peak count and each sensorimotor assessment was examined.

Results: SEP amplitudes and latencies showed no significant differences between the initial and second assessments (paired t‐test, p  > 0.05). However, the counts of SEP peaks after NI (N20) increased (Wilcoxon signed‐rank test, p  < 0.05), indicating changes in the SEP waveform. Furthermore, strong correlations were observed between SEP peak counts, stage, and all functional assessments (counts and SWMT, RS = −0.77, p < 0.001; counts and pain sensation, RS = −0.71, p < 0.001; counts and position sensation, RS = 0.75, p < 0.001; counts and two‐point discrimination, RS = −0.74, p < 0.001; stage and SWMT, RS = −0.74, p < 0.001; stage and pain sensation, RS = −0.69, p < 0.001; stage and position sensation, RS = 0.74, p < 0.001; and stage and two‐point discrimination, RS = −0.75, p < 0.001; all Spearman’s rank correlation coefficients).

Conclusion: Despite the limitations of the retrospective study design, our study highlights the utility of SEPs for evaluating sensory function in patients with subacute stroke, setting the foundation for further investigations on the use of SEPs to assess functional changes in patients with subacute stroke undergoing rehabilitation.
Oxidative Phosphorylation is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer
Authors: Tau Steven , Chamberlin Mary D. , Yang Huijuan , Marotti Jonathan D. , Muskus Patricia C. , Roberts Alyssa M. , Carmichael Melissa M. , Cressey Lauren , Dragnev Christo Philip C. , Demidenko Eugene , Hampsch Riley A. , Soucy Shannon M. , Kolling Fred W. , Samkoe Kimberley S. , Alvarez James V. , Kettenbach Arminja N. , Miller Todd W.
Published: January 2025

Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease. Using CRISPR-Cas9 genome-wide knockout screening in ER+ breast cancer cells, we identified a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration in endocrine-tolerant persister cells. Quantitative proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters where oxidative phosphorylation was required to generate ATP. A phase II clinical trial was conducted to evaluate changes in mitochondrial markers in primary ER+/HER2- breast tumors induced by neoadjuvant endocrine therapy (NCT04568616). In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content. Genetic profiling and barcode lineage tracing showed that endocrine-tolerant persistence occurred stochastically without genetic predisposition. Pharmacological inhibition of mitochondrial complex I suppressed the tumor-forming potential of persisters in mice and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts. These findings indicate that mitochondrial metabolism is essential in endocrine-tolerant persister ER+ breast cancer cells and warrant the development of treatment strategies to leverage this vulnerability for treating breast cancer.
Supplementary Figures S1-S14 from Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma
Authors: Fandrei David , Seiffert Sabine , Rade Michael , Rieprecht Susanne , Gagelmann Nico , Born Patrick , Wiemers Thomas , Weidner Heike , Kreuz Markus , Schassberger Tamara , Koßmann Jannik , Mangold Marlene , Fürst Daniel , Fischer Luise , Baber Ronny , Heyn Simone , Wang Song Yau , Bach Enrica , Hoffmann Sandra , Metzeler Klaus H. , Herling Marco , Jentzsch Madlen , Franke Georg-Nikolaus , Köhl Ulrike , Friedrich Maik , Boldt Andreas , Reiche Kristin , Platzbecker Uwe , Vucinic Vladan , Merz Maximilian
Published: January 2025

Fig. S1: PFS analysis of the BsAb vs other bridging groups. Fig. S2: Quantification of CAR-T cells using MFC vs PCR. Fig. S3: Correlation of sBCMA levels with IMWG response criteria. Fig. S4: PFS analysis of patients with higher vs lower than median sBCMA on the day of CAR-T infusion. Fig. S5: Impact of bridging with BsAb vs other BT groups on absolute counts of T cell subsets. Fig. S6: Absolute numbers of CAR-T cells in the bridging groups. Fig. S7: Proportions of CAR-T cells in the samples used for the in vitro cytotoxicity assay per bridging group. Fig. S8: Proportions of naive and memory Tregs in the bridging groups. Fig. S9: Overview of T cell subsets stratified by response to bridging. Fig. S10: Alluvials of T cell subsets among the bridging groups. Fig. S11: Checkpoint marker expression stratified by response to bridging therapy. Fig. S12: Proportions of PD-1+CD4+ and PD-1+CD8+ non-transduced T cells amongst the bridging groups. Fig. S13: Overview of sample numbers in the bridging groups included for single-cell multi-omics sequencing. Fig. S14: Numbers of circulating plasma cells.
Figure 4 from Autofluorescence Virtual Staining System for H&E Histology and Multiplex Immunofluorescence Applied to Immuno-Oncology Biomarkers in Lung Cancer
Authors: Loo Jessica , Robbins Marc , McNeil Carson , Yoshitake Tadayuki , Santori Charles , Shan Chuanhe (Jay) , Vyawahare Saurabh , Patel Hardik , Wang Tzu Chien , Findlater Robert , Steiner David F. , Rao Sudha , Gutierrez Michael , Wang Yang , Sanchez Adrian C. , Yin Raymund , Velez Vanessa , Sigman Julia S. , Coutinho de Souza Patricia , Chandrupatla Hareesh , Scott Liam , Weaver Shamira S. , Lee Chung-Wein , Rivlin Ehud , Goldenberg Roman , Couto Suzana S. , Cimermancic Peter , Wong Pok Fai
Published: January 2025

A, Example of real (left) and virtual (right) stains showing the WSI composite for all mIF stains. B–E, Examples of real (left) and virtual (right) stains from the individual models for DAPI + PanCK, PD-L1, CD3, and CD8 at several regions across the WSI.
Associations of Causes of Chronic Kidney Disease with Disease Progression and Mortality: Insights from the Fukuoka Kidney disease Registry (FKR) Study
Authors: Kitamura Hiromasa , Tanaka Shigeru , Hiyamuta Hiroto , Tsuruya Kazuhiko , Kitazono Takanari , Nakano Toshiaki
Published: January 2025

Introduction: The Kidney Disease: Improving Global Outcomes guidelines recognize the importance of causes of chronic kidney disease (CKD), glomerular filtration rate, and albuminuria as predictors of kidney outcome and prognosis. However, compared with biopsy-proven causes, there has been limited research regarding the relationship between clinically diagnosed causes of CKD and patient prognosis.
Methods: We examined 3,119 patients with non-dialysis-dependent CKD who participated in the Fukuoka Kidney disease Registry Study, a multicenter prospective cohort study. Patients were divided into six groups: IgA nephropathy, chronic glomerulonephritis (non-biopsy-proven), diabetic nephropathy, hypertensive nephrosclerosis, chronic interstitial nephritis, and polycystic kidney disease. The primary outcomes included a composite kidney outcome, defined as a 1.5-fold increase in serum creatinine and/or the development of end-stage kidney disease, and all-cause mortality. The risks of these outcomes were estimated using a Fine–Gray proportional subdistribution hazards model. Patients with IgA nephropathy, the most prevalent primary glomerulonephritis, served as the reference group.
Results: During the median follow-up period of 5 years, 1,221 patients developed the composite kidney outcome, and 346 patients died. Compared with IgA nephropathy, the multivariable-adjusted subdistribution hazard ratios (sHRs) for the composite kidney outcome were significantly higher in diabetic nephropathy (sHR 1.45) and polycystic kidney disease (sHR 2.07) groups, whereas the chronic interstitial nephritis group had a significantly lower risk (sHR 0.71). The risk of all-cause mortality was significantly higher in the hypertensive nephrosclerosis group (sHR 1.90).
Conclusion: The causes of CKD were associated with risks of the composite kidney outcome and all-cause mortality, highlighting their clinical relevance in predicting prognosis. These findings suggest that different causes of CKD have distinct impacts on patient outcomes, emphasizing the importance of tailoring management strategies according to the underlying causes.
Ponderações sobre o branqueamento em processos de restauração de papel: um panorama químico e teórico do procedimento
Authors: Amaral Luiza Batista , Camargos Camilla Henriques Maia de
Published: January 2025

Bleaching is a commonly used procedure in the field of paper restoration. It is often performed with the justification of benefiting, enhancing, or "rescuing" the aesthetic quality of the treated work, offering a subjectively new, aseptic, and pristine appearance to previously yellowed or stained paper. Even in less biased justifications, based on a possible recovery of legibility and improvement of aesthetic enjoyment of works of art on paper, the argument in agreement with executing this restorative approach also prevails. Focusing on this controversial procedure, the aim of this article is to provide an overview of bleaching methods, including conventional, less conventional, or alternative ones, discussing their methodological principles and key physico-chemical aspects. Through this critical-methodological review, which also includes an introduction to the fundamental chemical phenomena related to the action of bleaching on key chromophores present in yellowed cellulose, a careful exposition of the pros and cons of the procedure in question is presented, comparing the restoration theory debate with the discussion presented by Irene Brückler and Ute Henniges in their systematic article "Thoughts on Bleaching Guidelines". The proposal is to contribute to the debate on bleaching, also in Portuguese, providing conservators-restorers with information on the main criteria to be considered and the various methods for safely and rationally performing the procedure.
Tendências de adoção de comportamentos de risco em pessoas idosas nas capitais do nordeste brasileiro: ênfase na inatividade física e comportamento sedentário no período 2009-2019
Authors: Gusmão Bárbara Marcelly Tavares de , Wanderley Flavia Accioly Canuto
Published: January 2025

It is an epidemiological study with a serial cross-sectional design that examined secondary data from the results of Vigitel, in the period between the years 2009 to 2019, referring to the elderly population (≥ 60 years) living in the capitals of northeastern Brazil. It aimed to analyze the trend towards the adoption of risky health behaviors (alcohol abuse; smoking, physical inactivity); frequency of overweight and obesity; physical activity (physical exercise); Referred morbidity (hypertension and diabetes) in elderly people in the capitals of northeastern Brazil. Among the risk factors analyzed, we observed: 1) the trend of increasing prevalence of obesity (p = 0.001) and diabetes (p = 0.010), especially for women (obesity: p = 0.016; diabetes: p = 0.013), 2) men showed a tendency to reduce physical inactivity (p = 0.030), 3) the variables screen time greater than 3h / day and hypertension remained stable. It appears that it is necessary to expand the incentive to public policies and specific programs that encourage healthy lifestyles including the practice of physical activity and combating sedentary behaviors. It is suggested to follow the trends for these variables in order to direct the management of health services and public policies aimed at this population.
“L'ouvrière, mot impie, sordide.”...o discurso da economia política francesa sobre as operárias (1840-1960)
Authors: Ramos Viviane , Perosa Graziela Serroni , Scott Joan W.
Published: January 2025

L'ouvrière, mot impie, sordide”... O discurso da economia política francesa sobre as operárias (1840-1960) é uma tradução inédita no Brasil, e publicada pela primeira vez em língua portuguesa, de um ensaio escrito pela historiadora Joan Scott, atualmente professora do Institute for Advanced Study in Princeton (EUA). O texto foi originalmente publicado em inglês como sétimo capítulo do famoso livro Gender and the politics of history em 1988. Em 1990, foi traduzido e publicado em francês na Revue Actes de la recherche en sciences sociales por Pierre Bourdieu. A expressão “L’ouvrière mot impie, sordide” do título foi mantida em francês também na versão em inglês. O ensaio aborda o discurso da economia política francesa sobre as operárias, a partir do século XIX - período marcado por uma intensa aceleração da industrialização – , discutindo a posição de homens públicos e economistas políticos em relação ao crescimento do trabalho feminino, visto com preocupação e pessimismo.
Olhar da personagem feminina, paternalismo e tradição patriarcal: um motivo machadiano
Authors: Fraia Maurício Fernandes Di
Published: January 2025

Este artigo busca indicar, na obra de Machado de Assis, uma relação entre a conduta dos olhos de personagens femininas e a elaboração literária do paternalismo brasileiro do século XIX. Este microelemento de enredo – que envolve oposição de gênero e geralmente de classe nas relações intersubjetivas – gera uma contradição (movimento livre dos olhos enquanto imagem de autonomia do indivíduo vs. estrita subordinação personalista) que parece constituir um ponto privilegiado de figuração de um processo social marcado pelo domínio não mediado, que precisa coibir índices de igualdade. Após uma tentativa de apreensão do conceito de paternalismo, são expostos alguns casos deste efetivo motivo machadiano, seguidos por um comentário geral. Em seguida, propõe-se um caminho de revinculação da questão ao quadro da literatura europeia – quadro que a modernidade pós-1848 parece deslocar, o que dá ensejo à retomada crítica da tradição. O artigo busca rastrear essa retomada na própria obra machadiana, e conclui com um comentário sobre “Noite de almirante”, que assume um lugar talvez excepcional neste conjunto.
A poesia de Paul Celan e “Sobre verdades e mentiras no sentido extra-moral”, de Nietzsche: aproximações
Authors: Beretta Laysa
Published: January 2025

Em Crepúsculo dos Ídolos: ou como se filosofa com o martelo (1889), último livro escrito antes da enfermidade, Nietzsche estabelece, e de modo bastante elucidativo, o lugar da moral e da verdade para a construção do niilismo enquanto conceito. O filósofo entende que a moral, principalmente a cristã, nega a vida presente em favor de um ideal transcendental, tornando-se um "mal-entendido" que oferece consolo, mas também aprisiona a verdade em conceitos estáticos e ilusórios. Além disso, mas não menos importante, Nietzsche questiona a linguagem, a principal potência do homem, como instrumento para a cristalização desses conceitos. Assim, pretendo observar o texto “Verdade e mentira no sentido extra-moral” (1873), ensaio em que Nietzsche, além de salientar a incessante busca do homem pela verdade – sem deixar, é claro, de observar a ilusão inerente ao ato –, discorre sobre o intelecto humano, desmantela o conceito tradicional de verdade e questiona os limites da linguagem, a matéria-prima do intelecto. Ademais, dedico-me, à luz das considerações presentes no ensaio mencionado, à análise de alguns poemas de Paul Celan (1920-1970), em que um movimento bastante semelhante àquele proposto por Nietzsche salta aos nossos olhos, pois a linguagem é manejada como ferramenta fluida que pode apontar para verdades complexas e intuições profundas, mas nunca capturá-las completamente.