bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short- and long-term pathologic responses to quartz are induced by nearly free silanols formed during crystal fracturing
Authors: Pavan Cristina , Leinardi Riccardo , Benhida Anissa , Ibouraadaten Saloua , Yakoub Yousof , Brule Sybille van den , Lison Dominique , Turci Francesco , Huaux François 
Published: December 2024

Abstract
Background
Inhalation of respirable crystalline silica particles, including quartz, is associated with an increased risk of developing pathologies, including persistent lung inflammation, fibrosis, cancer, and systemic autoimmunity. We demonstrated that the nearly free silanols (NFS) generated upon quartz fracturing trigger the early molecular events determining quartz toxicity. Here, we address the involvement of NFS in driving short- and long-term pathogenic responses, including lung inflammation, fibrosis, cancer, and autoimmunity in multiple mouse models.

Results
In vivo pulmonary responses to as-grown NFS-poor quartz (gQ) and fractured NFS-rich quartz (gQ-f) of synthetic origin were compared to two NFS-rich reference quartz dusts (Min-U-Sil 5, mQ-f). Acute and persistent inflammation, as well as fibrosis, were assessed 3 and 60 days, respectively, after administering one dose of particles (2 mg) via oropharyngeal aspiration (o.p.a.) to C57BL/6 mice. The carcinogenic potential was assessed in a co-carcinogenicity study using A/J mice, which were pre-treated with 3-methylcholanthrene (3-MC) and administered four doses of quartz particles (4 × 1 mg, o.p.a.), then sacrificed after 10 months. Autoimmunity was evaluated in autoimmune-prone 129/Sv mice 4 months after particle administration (2 × 1.25 mg, o.p.a). Mice exposed to NFS-rich quartz exhibited a strong acute lung inflammatory response, characterized by pro-inflammatory cytokine release and leukocyte accumulation, which persisted for up to 60 days. No inflammatory effect was observed in mice treated with NFS-poor gQ. Fibrosis onset (i.e., increased levels of pro-fibrotic factors, hydroxyproline, and collagen) was prominent in mice exposed to NFS-rich but not to NFS-poor quartz. Additionally, lung cancer development (tumour numbers) and autoimmune responses (elevated IgG and anti-dsDNA autoantibody levels) were only observed after exposure to NFS-rich quartz.

Conclusions
Collectively, the results indicate that NFS, which occur upon fracturing of quartz particles, play a crucial role in the short- and long-term local and systemic responses to quartz. The assessment of NFS on amorphous or crystalline silica particles may help create a predictive model of silica pathogenicity.
Inhibition of the chemokine receptors CXCR1 and CXCR2 synergizes with docetaxel for effective tumor control and remodeling of the immune microenvironment of HPV-negative head and neck cancer models
Authors: Horn Lucas A. , Lind Hanne , Fousek Kristen , Qin Haiyan , Rajabian Nika , Angstadt Shantel , Hsiao-Sanchez Nicole , Medina-Enriquez Miriam M. , Kelly Marcus D. , Allen Clint T. , Hammoudeh Sarah M. , Weigert Roberto , Maeda Dean Y. , Zebala John A. , Palena Claudia 
Published: December 2024

Abstract
Background
Relapsed head and neck squamous cell carcinoma (HNSCC) unrelated to HPV infection carries a poor prognosis. Novel approaches are needed to improve the clinical outcome and prolong survival in this patient population which has poor long-term responses to immune checkpoint blockade. This study evaluated the chemokine receptors CXCR1 and CXCR2 as potential novel targets for the treatment of HPV-negative HNSCC.

Methods
Expression of IL-8, CXCR1, and CXCR2 was investigated in HNSCC tissues and human cell line models. Inhibition of CXCR1/2 with the clinical stage, small molecule inhibitor, SX-682, was evaluated in vitro and in vivo using human xenografts and murine models of HNSCC, both as a monotherapy and in combination with the taxane chemotherapy, docetaxel.

Results
High levels of IL-8, CXCR1, and CXCR2 expression were observed in HPV-negative compared to HPV-positive HNSCC tumors or cell lines. Treatment of HPV-negative HNSCC cell lines in vitro with SX-682 sensitized the tumor cells to the cytotoxic activity of docetaxel. In vivo, treatment of HNSCC xenograft models with the combination of SX-682 plus docetaxel led to strong anti-tumor control resulting in tumor cures. This phenomenon was associated with an increase of microRNA-200c and a decreased expression of its target, tubulin beta-3, a protein involved in resistance to microtubule-targeting chemotherapies. In vivo treatment of a murine syngeneic model of HNSCC with SX-682 plus docetaxel led to potent anti-tumor efficacy through a simultaneous decrease in suppressive CXCR2+ polymorphonuclear, myeloid-derived suppressor cells and an increase in cytotoxic CD8+ T cells in the combination therapy treated tumors compared to controls.

Conclusions
This study reports, for the first time, mechanistic findings through which the combination of CXCR1/2 inhibition and docetaxel chemotherapy exhibits synergy in models of HPV-negative HNSCC. These findings provide rationale for the use of this novel combination approach to treat HPV-negative HNSCC patients and for future combination studies of CXCR1/2 inhibition, docetaxel, and immune-based therapies.
Acceptability of midazolam and melatonin as premedications for anxious children undergoing general anaesthesia: a qualitative interview study with children, caregivers and health professionals participating in the MAGIC trial
Authors: Kettle Jennifer , Bolt Robert , Deery Chris , Papaioannou Diana , Rodd Helen , Hyslop Marie C. , Totton Nikki , Marshman Zoe 
Published: December 2024

Abstract
Background
The acceptability of a children’s premedication, prior to general anaesthesia (GA), is fundamental to ensuring positive clinical- and patient-reported outcomes. Midazolam, the current standard premedication, is known to have an unfavourable side-effects profile and presents a degree of risk which is accepted due to a need for compliance. Melatonin is a functionally diverse hormone with anxiolytic properties that offer potential benefits over midazolam. Little is currently known about how patients and health professionals view these two different premedications. This research aimed to explore the acceptability of midazolam and melatonin as premedications for anxious children undergoing GA, from the perspective of children, caregivers and health professionals involved in the Melatonin for Anxiety prior to General Anaesthesia In Children (MAGIC) trial.

Methods
Participants were children recruited to the MAGIC trial, their caregivers and health professionals involved in recruitment to the trial. In total, 37 participants (23 health professionals, 10 caregivers and 4 children) took part in semi-structured interviews relating to the MAGIC trial and acceptability of premedications. Interviews were carried out face-to-face, by telephone or online by a trained qualitative researcher. Interviews were transcribed verbatim and analysed using a framework approach.

Results
The acceptability of midazolam and melatonin is related to six main factors: effectiveness as premedication prior to GA; administration of premedication; experience of recovery; prior experiences of premedication; associations and evidence; and range of options for managing anxiety. Interviews highlighted the trade-offs involved and the relevance of the wider context in which premedications are provided. Barriers and facilitators were identified on the acceptability of premedications more generally.

Conclusions
Future clinical trials evaluating the effectiveness of premedications in children prior to general anaesthesia need to consider that premedication choice is multifactorial. The MAGIC study found that melatonin was less effective at reducing anxiety (pre-operative distress) when compared with the standard of care, midazolam. However, there remains a need for a premedication with a better side effects profile to midazolam. While children, caregivers and health professionals are open to alternatives to midazolam, this is likely to vary by subgroup and will involve trade-offs in terms of benefits.

Trial registration
ISCRCTN ISRCTN18296119. Registered on 10/01/2019.
Monitoring alpha-cypermethrin susceptibility of Phlebotomus argentipes, the vector of visceral leishmaniasis in India, using the CDC bottle bioassay
Authors: Chaubey Rahul , Shukla Ashish , Kushwaha Anurag Kumar , Singh Shakti Kumar , Singh Om Prakash , Kumar Rajiv , Lawyer Phillip , Rowton Edgar , Petersen Christine A. , Bernhardt Scott A. , Sundar Shyam 
Published: December 2024

Abstract
Background
Visceral leishmaniasis (VL), known as Kala-azar on the Indian subcontinent, is a parasitic disease caused by the flagellated protozoa Leishmania donovani and can be fatal if left untreated. The sand fly Phlebotomus argentipes is the only proven vector of VL in the Southeast Asia region, and VL control in this region has relied on the use of synthetic insecticides for indoor residual spraying (IRS). The use of DDT in VL control programmes has led to the development of resistance to this insecticide in sand flies, resulting in DDT being replaced with the insecticide alpha-cypermethrin. However, alpha-cypermethrin has a similar mode of action as DDT and, therefore, the risk of resistance development in sand flies increases under the pressure of regular exposure to this insecticide. In the present study we assessed the susceptibility status of wild-caught sand flies and F1 progeny using the CDC bottle bioassay.

Methods
Sand flies were collected from 10 villages in Muzaffarpur District, Bihar, India. Eight of these villages are receiving continuous IRS with alpha-cypermethrin, one village had discontinued IRS with alpha-cypermethrin and one village had never received IRS with alpha-cypermethrin. The collected sand flies were exposed to a pre-determined diagnostic dose for a specific time duration (3 µg/ml for 40 min), and knockdown and mortality at 24 h post-exposure were recorded.

Results
Knockdown ranged from 91.19% to 99.47% for wild-caught sand flies and from 91.70% to 98.89% for their F1 progeny. At 24 h post-exposure, mortality ranged from 89.34% to 98.93% for wild-caught sand flies and from 90.16% to 98.33% for F1 progeny.

Conclusions
The results of this study showed that P. argentipes is potentially developing resistance, signalling the need for continuous monitoring and vigilance to sustain the validation of elimination once achieved.

Graphical Abstract
An analysis of mitochondrial variation in cardiomyopathy patients from the 100,000 genomes cohort: m.4300A>G as a cause of genetically elusive hypertrophic cardiomyopathy
Authors: Lopes Luis R. , Macken William L. , Preez Seth Du , Kotwal Huafrin , Savvatis Konstantinos , Sekhri Neha , Mohiddin Saidi A. , Kabiljo Renata , Pitceathly Robert D. S. 
Published: December 2024

Abstract
Background
A significant proportion of cardiomyopathy patients remain genetically unsolved. Our aim was to use the large genomes cohort of the 100,000 genomes project (100KGP) to explore the proportion of potentially causal mitochondrial (mtDNA) variants in cardiomyopathy patients, particularly in genotype-elusive participants. The homoplasmic MT-TI 4300A>G is unusual in that it typically presents with a cardiac-only phenotype, but MT-TI is currently not part of the genes analysed for non-syndromic cardiomyopathies.

Results
We analysed 1363 cardiomyopathy genomes from the 100KGP project (of which only 172 had been previously solved) to detect disease causing mtDNA variants. MitoHPC was used to call variants. For controls, 1329 random subjects not recruited for a cardiomyopathy diagnosis and not related to any participant in the cardiomyopathy cohort were selected. We have additionally compared the frequency of detected variants with published UK Biobank data. Pathogenicity annotations were assigned based on MitoMap. Four patients, all with a diagnosis of hypertrophic cardiomyopathy (HCM) and without a previously identified genetic cause from the 100KGP clinical-standard analysis, were found to harbour the pathogenic MT-TI m.4300A>G variant (0.6% of HCM cases without a diagnosis).

Conclusion
These data support the inclusion of MT-TI in the initial genetic testing panel for (non-syndromic) HCM.
Performance assessment of interpolation methods for orbits of altimetry satellites
Authors: Zeitlhöfler Julian , Alkahal Riva , Rudenko Sergei , Bloßfeld Mathis , Seitz Florian 
Published: December 2024

AbstractGlobal and regional sea level variations are important indicators of climate change and are derived from accurate sea surface height measurements and precisely determined orbits of altimetry satellites. To validate and improve the quality of these orbits, comparisons with external solutions are important. Since orbit solutions of different institutions are not necessarily provided at the same time instants, interpolation is required for comparison. In this study, we investigate the appropriate interpolation method and its degree to reduce interpolation errors to sub-millimetre levels. We also assess the magnitude of errors occurring at transformations when expressing orbit differences not only in the terrestrial reference frame (Cartesian coordinates), but also in local orbital and ellipsoidal coordinates. The analyses conducted in this study provide good results for Hermite interpolation of degrees 7–11 and Newton interpolation of at least degree 9 with a three-dimensional interpolation error of 0.6 mm and a scattering of 0.2 mm on average for satellite coordinates given with an accuracy of 1 mm in the SP3 format. These interpolation settings limit transformation errors between coordinate systems to ±0.01 mm and incorrect mapping of interpolation errors into certain components in the target system to ±0.02 mm. The spectral analysis of orbit differences is affected up to 0.1 mm in magnitude with appropriate interpolation settings. Extending the number of decimal digits of the satellite position and velocity in SP3 files by one digit benefits the orbit comparisons and reduces the interpolation error by 90% from 0.6 to 0.06 mm. The results are obtained using piece-wise interpolation and a validity interval inside the interpolation interval to minimise the effects of the Runge phenomenon.
Graphical Abstract
Does septic arthritis after anterior cruciate ligament reconstruction lead to poor outcomes? A systematic review and meta-analysis of observational studies
Authors: Lin Ashleigh Peng , Nguyen Bao Tu Thai , Tran Son Quang , Kuo Yi-Jie , Huang Shu-Wei , Chen Yu-Pin 
Published: December 2024

Abstract
Background
Septic arthritis is a rare but devastating complication after anterior cruciate ligament reconstruction (ACLR). While early treatment can prevent significant graft complications, outcomes are often inferior to those in uncomplicated ACLR. Furthermore, whether to retain or remove the graft after infection remains debatable. Therefore, we sought to compare the outcomes of septic arthritis post ACLR with uncomplicated ACLR and evaluate graft retention versus removal in infected patients.

Methods
We conducted a systematic review and meta-analysis in which PubMed, Embase, and Cochrane Library databases were searched. Clinical studies were included if they compared patient-reported, clinician-reported, or radiographic outcomes (minimum follow-up of 12 months) between patients with post-ACLR septic arthritis and those with uncomplicated ACLR or that compared graft retention and removal in patients with post-ACLR septic arthritis.

Results
Thirteen studies were retrieved. Patients with post-ACLR septic arthritis reported inferior Lysholm Knee Scoring Scale scores (mean difference (MD) 7.53; 95% confidence interval (CI) 3.20–11.86; P = 0.0006), Tegner Activity Scale scores (MD, 1.42; 95% CI 1.07–1.76; P < .00001), and return to sports rates (53% versus 76%, respectively) to those of patients with uncomplicated ACLR. Patients with post-ACLR septic arthritis and those with uncomplicated ACLR did not differ in terms of the pooled estimate of various clinician-reported outcomes, such as the objective International Knee Documentation Committee score, anterior–posterior laxity, pivot shift, and Lachman test results. Furthermore, no significant difference was noted between the aforementioned patient groups regarding osteoarthritis (detected radiographically). Graft retention led to better patient- and clinician-reported outcomes than graft removal.

Conclusions
Despite similar clinician-reported outcomes and osteoarthritis rates, patients with post-ACLR septic arthritis reported worse outcomes than those with uncomplicated ACLR. Graft retention leads to improved patient- and clinician-reported outcomes compared with the outcomes of graft removal. Our findings may help develop realistic expectations and management strategies for this rare complication.
Externally validated clinical prediction models for estimating treatment outcomes for patients with a mood, anxiety or psychotic disorder: systematic review and meta-analysis
Authors: Burghoorn Desi G. , Booij Sanne H. , Schoevers Robert A. , Riese Harriëtte 
Published: December 2024

Background
Suboptimal treatment outcomes contribute to the high disease burden of mood, anxiety or psychotic disorders. Clinical prediction models could optimise treatment allocation, which may result in better outcomes. Whereas ample research on prediction models is performed, model performance in other clinical contexts (i.e. external validation) is rarely examined. This gap hampers generalisability and as such implementation in clinical practice.

Aims
Systematically appraise studies on externally validated clinical prediction models for estimated treatment outcomes for mood, anxiety and psychotic disorders by (1) reviewing methodological quality and applicability of studies and (2) investigating how model properties relate to differences in model performance.

Method
The review and meta-analysis protocol was prospectively registered with PROSPERO (registration number CRD42022307987). A search was conducted on 8 November 2021 in the databases PubMED, PsycINFO and EMBASE. Random-effects meta-analysis and meta-regression were conducted to examine between-study heterogeneity in discriminative performance and its relevant influencing factors.

Results
Twenty-eight studies were included. The majority of studies (n = 16) validated models for mood disorders. Clinical predictors (e.g. symptom severity) were most frequently included (n = 25). Low methodological and applicability concerns were found for two studies. The overall discrimination performance of the meta-analysis was fair with wide prediction intervals (0.72 [0.46; 0.89]). The between-study heterogeneity was not explained by number or type of predictors but by disorder diagnosis.

Conclusions
Few models seem ready for further implementation in clinical practice to aid treatment allocation. Besides the need for more external validation studies, we recommend close examination of the clinical setting before model implementation.
Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study
Authors: De Crescenzo Franco , De Giorgi Riccardo , Garriga Cesar , Liu Qiang , Fazel Seena , Efthimiou Orestis , Hippisley-Cox Julia , Cipriani Andrea 
Published: December 2024

Background
Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world.

Aims
To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

Method
We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

Results
A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Conclusions
Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.
Mesogenic Architectures for Advanced Drug Delivery: Interrogating Lyotropic and Thermotropic Liquid Crystals
Authors: Govindan Induja , Paul Angeeta , Rama Annamalai , Kailas Anjana A. , Abutwaibe K. A. , Annadurai Thamizharasan , Naha Anup 
Published: December 2024

Abstract
The possibility of precisely regulating and targeting drug release with mesophase or Liquid crystal drug delivery systems has drawn much attention recently. This review offers a thorough investigation of liquid crystal drug delivery systems with an emphasis on their mesogenic architecture. It describes the various liquid crystal forms such as thermotropic and lyotropic liquid crystals and their applicability in advanced drug delivery. Liquid crystals are used as excellent carriers due to their distinctive characteristics, such as stimuli-responsive drug delivery and sustained release patterns. Comprehending the materials that form mesophase provides insight into their distinct physiochemical characteristics and their use in drug delivery. This review highlights the important role lyotropic and thermotropic liquid crystals play in drug delivery, underscoring their considerable potential. The transition of thermotropic liquid crystals from their conventional technological applications to drug delivery has been studied. Nonetheless, a few challenges still need to be addressed, including formulation strategy refinement, regulating release rates, maximising the loading of hydrophilic drugs, and storage stability. In the pharmaceutical field, addressing these issues will open the door to a revolutionary paradigm that will revolutionise therapeutic outcomes and improve patient care.

Graphical Abstract