bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a risk assessment framework for micro- and nanoplastic particles for human health
Authors: Vogel Amelie , Tentschert Jutta , Pieters Raymond , Bennet Francesca , Dirven Hubert , van den Berg Annemijne , Lenssen Esther , Rietdijk Maartje , Broßell Dirk , Haase Andrea 
Published: November 2024

Abstract
Background
Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies. Moreover, several of their properties change over time due to aging/ weathering. Case-by-case assessment of each MNP type does not seem feasible, more straightforward methodologies are needed. However, conceptual approaches for human health risk assessment are rare, reliable methods for exposure and hazard assessment are largely missing, and meaningful data is scarce.

Methods
Here we reviewed the state-of-the-art concerning risk assessment of chemicals with a specific focus on polymers as well as on (nano-)particles and fibres. For this purpose, we broadly screened relevant knowledge including guidance documents, standards, scientific publications, publicly available reports. We identified several suitable concepts such as: (i) polymers of low concern (PLC), (ii) poorly soluble low toxicity particles (PSLT) and (iii) fibre pathogenicity paradigm (FPP). We also aimed to identify promising methods, which may serve as a reasonable starting point for a test strategy.

Results and conclusion
Here, we propose a state-of-the-art modular risk assessment framework for MNPs, focusing primarily on inhalation as a key exposure route for humans that combines several integrated approaches to testing and assessment (IATAs). The framework starts with basic physicochemical characterisation (step 1), followed by assessing the potential for inhalative exposure (step 2) and includes several modules for toxicological assessment (step 3). We provide guidance on how to apply the framework and suggest suitable methods for characterization of physicochemical properties, exposure and hazard assessment. We put special emphasis on new approach methodologies (NAMs) and included grouping, where adequate. The framework has been improved in several iterative cycles by taking into account expert feedback and is currently being tested in several case studies. Overall, it can be regarded as an important step forward to tackle human health risk assessment.
Shifting focus from ideality to reality: a qualitative study on how quality of life is defined by premanifest and manifest Huntington’s disease gene expansion carriers
Authors: van Lonkhuizen Pearl J. C. , Heemskerk Anne-Wil , Slutter Leanne , van Duijn Erik , de Bot Susanne T. , Chavannes Niels H. , Meijer Eline ,   on behalf of the HEALTHE-RND consortium, Vegt Niko , Chavannes Niels , Heemskerk Anne- Wil , de Bot Susanne T. , van Lonkhuizen Pearl J. C. , Vegt Niko , Feleus Stephanie , Arendts Esther C , Putman Amy , Landwehrmeyer G. Bernhard , Mühlbäck Alzbeta , Frank Wiebke , Steck Franziska , Klempíř Jiří , Konvalinková Romama , Bezuchová Eva , Dolečková Kristýna , Klempířová Olga , Roth Jan , Ulmanová Olga , Squitieri Ferdinando , Maffi Sabrina , Scaricamazza Eugenia , Migliore Simone , Giorgio Chiara , D’Alessio Barbara , Casella Melissa , Hoblyn Jennifer , Thangaramanujam Muthukumaran , Burke Tom , O’Malley Emer , McKenna Stephen , McKenna Ian , Thorpe Jeanette , Coffey Anna , Moldovan Ramona , Foley Peter , Kerr Jacqueline 
Published: November 2024

Abstract
Background
Understanding quality of life (QoL) is important in diseases for which there is no cure to date, such as Huntington’s disease (HD). A deeper level of understanding is, however, compromised by the lack of studies examining QoL from the perspectives of HD gene expansion carriers (HDGECs). Only a few qualitative studies on QoL in HD have been performed, yet none investigated how QoL is defined by HDGECs themselves.

Objective
This qualitative study explores how premanifest and manifest HDGECs define their QoL.

Methods
Online semi-structured interviews were conducted with 6 premanifest and 6 manifest HDGECs in the Netherlands. Qualitative content analysis was used to explore participants’ QoL definitions via inductive coding and the subsequent formulation of (sub)categories and (sub)themes.

Results
Premanifest and manifest HDGECs had a different focus when defining QoL. Two subthemes were identified for premanifest HDGECs: Thoughts about a meaningful life regardless of HD and Concerns about the future progression and impact of HD. For manifest HDGECs, two other subthemes were identified: Coming to terms with HD and Shifting perspectives due to the impact of HD. One overall theme was generated, reflecting the difference and adaptive shift in focus between premanifest and manifest HDGECs: Shifting focus from ideality to reality.

Conclusions
In providing optimal care, HDGECs should be considered as part of a complex, continuously changing environment, thereby taking into account their individual QoL experiences and tailoring care accordingly. HDGECs might benefit from forming helpful beliefs about future adaptability and resilience and developing adaptive coping strategies.
Seeding activity of skin misfolded tau as a biomarker for tauopathies
Authors: Wang Zerui , Wu Ling , Gerasimenko Maria , Gilliland Tricia , Shah Zahid Syed Ali , Lomax Evalynn , Yang Yirong , Gunzler Steven A. , Donadio Vincenzo , Liguori Rocco , Xu Bin , Zou Wen-Quan 
Published: November 2024

Abstract
Background
Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically hyperphosphorylated tau protein in the brain, leading to prion-like aggregation and propagation. They include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Currently, reliable diagnostic biomarkers that directly reflect the capability of propagation and spreading of misfolded tau aggregates in peripheral tissues and body fluids are lacking.

Methods
We utilized the seed-amplification assay (SAA) employing ultrasensitive real-time quaking-induced conversion (RT-QuIC) to assess the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies, including AD, PSP, CBD, and PiD, compared to normal controls.

Results
We found that the skin tau-SAA demonstrated a significantly higher sensitivity (75–80%) and specificity (95–100%) for detecting tauopathy, depending on the tau substrates used. Moreover, the increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients examined. Analysis of the end products of skin-tau SAA confirmed that the increased seeding activity was accompanied by the formation of tau aggregates with different physicochemical properties related to two different tau substrates used.

Conclusions
Overall, our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of misfolded tau in the skin could serve as a diagnostic biomarker for tauopathies.
Lung ultrasound for the diagnosis of subpleural consolidations - a review of the veterinary and human literature
Authors: Gajewski Michał 
Published: November 2024

AbstractLung ultrasound (LUS) is an imaging modality of growing importance in human medicine. LUS has been extensively applied to human patients. Guidelines have been created for internal medicine, describing ultrasonographic features of various lung pathologic processes. Such guidelines do not exist for veterinary medicine, and studies on the utility of LUS in companion animals are limited. Therefore, this review compares conclusions from veterinary studies to recommendations in human medicine for the detection of subpleural consolidations beyond the application of LUS as a point-of-care modality in emergency and critical care.
Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy
Authors: Lin Jianbang , Liu Jing , Zhang Qi , Liu Taian , Hong Zexuan , Lu Yi , Zhong Cheng , Lu Zhonghua , Li Yuantao , Hu Yu 
Published: November 2024

AbstractTemporal lobe epilepsy (TLE) is the most common form of medically-intractable epilepsy. Subicular hyperexcitability is frequently observed with TLE, presumably caused by impaired inhibition of local excitatory neurons. Here, we evaluated the effectiveness of silencing subicular pyramidal neurons to treat a rodent model of TLE. First, we generated a chronic TLE mouse model via initial intrahippocampal kainic acid (IHKA) injection. In the chronic state after first IHKA injection, behavioral seizures and histological abnormalities were reliably observed. We then injected an adeno-associated viral (AAV) vector carrying an inhibitory chemogenetic element, hM4Di, directly into the subiculum. Eight weeks after the first IHKA injection, acute seizures were induced by giving a second dose of kainic acid (KA), which mimicked generalized tonic–clonic seizures. Herein, precise control over generalized tonic–clonic seizure onset was achieved via this two-step process. We found that chemogenetic suppression of subicular pyramidal neurons had a robust anti-epileptogenesis effect in this acute-chronic model of TLE. These data confirm a crucial role of the subiculum in the propagation of hippocampal seizures and highlight the potential for using subicular chemogenetic manipulation to treat generalized tonic–clonic seizures.
AKT kinases as therapeutic targets
Authors: Hassan Dalal , Menges Craig W. , Testa Joseph R. , Bellacosa Alfonso 
Published: November 2024

AbstractAKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While some have recently garnered attention for their favorable profile, concern over resistance and off-target effects have continued to hinder their widespread adoption in the clinic, mandating a discussion on alternative modes of targeting. In this review, we discuss isoform-centric targeting that may be more effective and less toxic than traditional pan-AKT inhibitors and its significance for disease prevention and treatment, including immunotherapy. We also touch on the emerging mutant- or allele-selective covalent allosteric AKT inhibitors (CAAIs), as well as indirect, novel AKT-targeting approaches, and end with a briefing on the ongoing quest for more reliable biomarkers predicting sensitivity and response to AKT inhibitors, and their current state of affairs.
Decoding the synergy: unveiling gradient boosting regression model for multivariate quantitation of pioglitazone, alogliptin and glimepiride in pure and tablet dosage forms
Authors: Elkhoudary Mahmoud M. , Marie Aya A. , Hammad Sherin F. , Salim Mohamed M. , Kamal Amira H. 
Published: November 2024

AbstractThis study represents a comparison among the performances of four multivariate procedures: partial least square (PLS) and artificial neural networks (ANN) in addition to support vector regression (SVR) and extreme gradient boosting (XG Boost) algorithm for the determination of the anti-diabetic mixture of pioglitazone (PIO), alogliptin (ALG) and glimepiride (GLM) in pharmaceutical formulations with aid of UV spectrometry. Key wavelengths were selected using knowledge-based variable selection and various preprocessing methods (e.g., mean centering, orthogonal scatter correction, and principal component analysis) to minimize noise and improve model precision. XG Boost effectively enhanced computing speed and accuracy by focusing on specific spectral features rather than the entire spectrum, demonstrating its advantages in resolving complex, overlapping spectral data. The independent test results of different models demonstrated that XG Boost outperformed other methods. XG Boost achieved the lowest root mean squared error of prediction (RMSEP) and standard deviation (SD) values across all compounds, indicating minimal prediction error and variability. For PIO, XG Boost recorded an RMSEP of 0.100 and SD of 0.369, significantly better than PLS and ANN. For ALG, XG Boost showed near-perfect performance with an RMSEP of 0.001 and SD of 0.005, outperforming SVR and PLS, which had higher error rates. In the case of GLM, XG Boost also excelled with an RMSEP of 0.001 and SD of 0.018, demonstrating superior precision compared to the much higher errors seen in PLS and ANN. These results highlight XG Boost’s exceptional ability to handle complex, overlapping spectral data, making it the most reliable and accurate model in this study.
Non-metastatic causes of multiple pulmonary nodules
Authors: Akçiçek Esra , Durhan Gamze , Düzgün Selin Ardalı , Kurtulan Olcay , Akpınar Meltem Gülsün , Demirkazık Figen , Arıyürek Orhan Macit 
Published: November 2024

Abstract
Various processes, including benign or malignant (mostly metastasis) processes, contribute to the occurrence of multiple pulmonary nodules. For differential diagnosis, metastasis must be excluded as an etiological factor in patients who have multiple pulmonary nodules with a known primary malignancy. However, differential diagnosis of multiple pulmonary nodules caused by benign diseases and malignant processes is challenging. Multiple pulmonary nodules resulting from metastasis may mimic those resulting from infections, inflammatory processes, and rare benign diseases. Some rare diseases, such as pulmonary sclerosing pneumocytoma and pulmonary epithelioid hemangioendothelioma, or common diseases with a rare presentation of multiple nodules must be considered in the differential diagnosis of metastasis. In addition to the clinical and laboratory findings, radiological features are crucial for differential diagnosis. The size, density, location, and border characteristics (well-defined or poorly defined) of pulmonary nodules, as well as their internal structure (solid, subsolid, or ground glass nodule), growth rate during follow-up, and associated pulmonary and extrapulmonary findings are important for differential diagnosis along with clinical and laboratory data. This article summarizes the general features and imaging findings of these diseases, which less frequently present with multiple pulmonary nodules, and the clues that can be used to distinguish these diseases from metastasis.

Critical relevance statement
The radiological features, clinical findings, and temporal changes during follow-up are important in distinguishing non-metastatic causes of multiple pulmonary nodules from metastatic causes and guiding diagnosis and early treatment, especially in patients with primary malignancy.

Key Points

Multiple pulmonary nodules have a wide range of etiologies, including metastatic disease.

Metastasis as an etiology must be excluded in patients with multiple pulmonary nodules.

Correlation of radiological findings (nodule size, position, and associated findings) with clinical history is crucial for differential diagnosis.

Graphical Abstract
Identification of neural alterations in patients with Crohn’s disease with a novel multiparametric brain MRI-based radiomics model
Authors: Zhang Ruo-nan , Wang Yang-di , Wang Hai-jie , Ke Yao-qi , Shen Xiao-di , Huang Li , Lin Jin-jiang , He Wei-tao , Zhao Chen , Li Zhou-lei , Mao Ren , Wang Ye-jun , Yang Guang , Li Xue-hua 
Published: November 2024

Abstract
Objectives
Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn’s disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits.

Methods
This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs.

Results
In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975–1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881–1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG.

Conclusion
We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets.

Critical relevance statement
Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn’s disease. We validated this model’s effectiveness using multiomics data, making it a potential biomarker for better patient management.

Key Points

Utilizing multiparametric MRI and radiomics techniques could unveil Crohn’s disease’s neurophenotype.

The neurophenotype radiomics model is interpreted using multiomics data.

This model may serve as a novel biomarker for Crohn’s disease management.

Graphical Abstract
Modern contraceptive use among currently married non-pregnant women (aged 15–49 years) in West Bengal, India: a reflection from NFHS-5
Authors: Sen Susanta , Banerjee Amit , Ali Asif , Chakma Namita 
Published: November 2024

Abstract
Background
There is a dearth of research on modern family planning practices in high focus states like West Bengal in India with diverse population groups and distinct health needs. Thus, this study aims to investigate the latest picture of modern contraceptive use and its associated socio-demographic factors among currently married non-pregnant of reproductive aged (15–49 years) women in West Bengal.

Methods
The study is based on secondary data, collected from the fifth round of the National Family Health Survey (NFHS-5; 2019-20). A total of 15,841 currently married non-pregnant women were included into this study. With the overarching goal of understanding the determinants and patterns of modern contraceptive use, the study employed a combination of bi-variate and multivariate analyses, including logistic regression.

Results
The results reveal that female sterilization is the most common modern contraceptive method across the state. Contraceptive use varies by district, from 43% in Puruliya to 77.3% in Birbhum. Women aged 30–34 were significantly more likely to use contraception (OR = 1.47), while those aged 45–49 were less likely to use it (OR = 0.74). Women with mixed gender composition of living children (OR = 1.48) were more likely to use contraception, compared to women with no children (OR = 0.21) or daughters only (OR = 0.80). SC women (OR = 1.63) and Christians (OR = 2.17) showed higher usage. Wealthier women (OR = 1.26) and urban residents also reported higher use. Moreover, son preference continues and women married after 18 are less likely to adopt modern methods. These findings highlight the need to improve reproductive health outcomes and overcome barriers to increasing contraceptive uptake.

Conclusion
Targeted interventions focusing on education, awareness-building, and improving access to diverse contraceptive options are recommended to empower women in making informed reproductive choices and advancing reproductive rights and health equity. Also, effective modern contraceptive services must overcome legal policy, social, cultural and structural barriers to benefit more women.
Translation and cross-cultural adaptation of the Nepali version of Sexual Interest and Satisfaction Scale (SIS): a cross-sectional study
Authors: Nepal Govinda Mani , Maharjan Sonu , Sherpa Nima 
Published: November 2024

Abstract
Background and objective
Individuals with Spinal Cord Injury (SCI) rank regaining sexual function as their top priority. Sexual dissatisfaction often leads to low self-esteem, reduced intimacy, and relationship difficulties and hence forms an essential part of the rehabilitation process. In Nepal, where people generally hold fairly traditional views about sex and sexual health, a sexual outcome measure that is culturally sensitive is a must for addressing sexual problems. No study has yet been carried out to investigate the impact of SCI on sexual attitudes and satisfaction in Nepal. Therefore, this study aims to translate and cross-culturally adapt the Sexual Interest and Satisfaction Scale (SIS) in the Nepali language.

Methods
(1) Forward translation: Three translators translated the English version of SIS into Nepali. (2) Synthesis: The three translated versions were synthesized into a draft version. (3) Expert committee review: The expert committee meetings were held to reach a consensus for a sensible and applicable pre-final version of SIS. (4) Pre-test: The pre-final version of SIS was tested on 25 individuals with SCI. Their opinions and comprehension were documented for each question, and subsequent modifications were made to form the final version of Nepali SIS (SIS-NP). The internal consistency of SIS-NP was calculated using Cronbach’s alpha.

Results
The translation and cross-cultural adaptation segregated the questions into two divisions: first, which could be answered by everyone irrespective of their sexual partner status, and second, which could only be answered by those with a sexual partner. No changes were made to the original questions; however, essential clarifications and definitions were added. A total of 66 individuals with SCI participated to evaluate internal consistency with a median duration of injury of 9.5 years (IQR = 9.25). Unmarried participants accounted for 40% (n = 27). Internal consistency was found to be 0.74.

Conclusion
SIS was translated to Nepali, adapting standard recommended guidelines. SIS-NP demonstrated adequate internal consistency to be used in SCI.