bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of brachytherapy clinical trials: a cross-sectional analysis of ClinicalTrials.gov
Authors: Chen David , Parsa Rod , Chauhan Kabir , Lukovic Jelena , Han Kathy , Taggar Amandeep , Raman Srinivas 
Published: February 2024

Abstract
Introduction
Characterizing the landscape of clinical trials including brachytherapy can provide an overview of the current status and research trends which may guide further areas of investigation.

Method
We queried 449,849 clinical trials from the ClinicalTrials.gov registry using brachytherapy-related keywords from 1980 to 2023, yielding 245 multi-arm and 201 single-arm, brachytherapy trials. Multi-arm and single-arm brachytherapy trials were compared using 12 trial protocol elements.

Results
The number of trials including brachytherapy has increased over time, with over 60% of trials registered in 2010 onwards. The majority of clinical trials were Phase 2 or 3, evaluated both safety and efficacy, and were funded by academic sponsors. The most common tumor sites evaluated in brachytherapy clinical trials include prostate, cervix, liver, endometrium, and breast.

Conclusion
There remains continued interest in clinical trials including brachytherapy focused on evaluation of novel delivery systems, treatment planning, and new indications. More brachytherapy clinical trials are needed to define the optimal clinical utilization and advance prospective research in this field.
Interfractional variation in whole-breast VMAT irradiation: a dosimetric study with complementary SGRT and CBCT patient setup
Authors: Mankinen M. , Virén T. , Seppälä J. , Koivumäki T. 
Published: February 2024

Abstract
Background
The dosimetric effect of setup uncertainty and tissue deformations in left-sided whole-breast irradiation with complementary surface-guided radiotherapy (SGRT) and cone-beam computed tomography (CBCT) setup was evaluated.

Method
Treatment courses of 40.05 Gy prescribed dose in 15 fractions were simulated for 29 patients by calculating the dose on deformed CT images, that were based on daily CBCT images, and deforming and accumulating the dose onto the planning CT image. Variability in clinical target volume (CTV) position and shape was assessed as the 95% Hausdorff distance (HD95) between the planning CTV and deformed CTV structures. DVH metrics were evaluated between the planned and simulated cumulative dose distributions using two treatment techniques: tangential volumetric modulated arc therapy (tVMAT) and conventional 3D-conformal radiotherapy (3D-CRT).

Results
Based on the HD95 values, the variations in CTV shape and position were enclosed by the 5 mm CTV-PTV margin in 85% of treatment fractions using complementary CBCT and SGRT setup. A residual error of 8.6 mm was observed between the initial SGRT setup and CBCT setup. The median CTV V95% coverage was 98.1% (range 93.1–99.8%) with tVMAT and 98.2% (range 84.5–99.7%) with 3D-CRT techniques with CBCT setup. With the initial SGRT-only setup, the corresponding coverages were 96.3% (range 92.6–99.4%) and 96.6% (range 84.2–99.4%), respectively. However, a considerable bias in vertical residual error between initial SGRT setup and CBCT setup was observed. Clinically relevant changes between the planned and cumulative doses to organs-at-risk (OARs) were not observed.

Conclusions
The CTV-to-PTV margin should not be reduced below 5 mm even with daily CBCT setup. Both tVMAT and 3D-CRT techniques were robust in terms of dose coverage to the target and OARs. Based on the shifts between setup methods, CBCT setup is recommended as a complementary method with SGRT.
CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration
Authors: Mravinacová Sára , Alanko Vilma , Bergström Sofia , Bridel Claire , Pijnenburg Yolande , Hagman Göran , Kivipelto Miia , Teunissen Charlotte , Nilsson Peter , Matton Anna , Månberg Anna 
Published: February 2024

Abstract
Background
Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates.

Method
We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins.

Results
The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort.

Conclusions
Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.
Increased bronchiolitis burden and severity after the pandemic: a national multicentric study
Authors: Ghirardo Sergio , Ullmann Nicola , Zago Alessandro , Ghezzi Michele , Minute Marta , Madini Barbara , D’Auria Enza , Basile Cecilia , Castelletti Francesca , Chironi Federica , Capodiferro Agata , Andrenacci Beatrice , Risso Francesco Maria , Aversa Salvatore , Dotta Laura , Coretti Antonella , Vittucci Anna Chiara , Badolato Raffaele , Amaddeo Alessandro , Barbi Egidio , Cutrera Renato 
Published: February 2024

Abstract
Background
The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020–2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology.

Methods
We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law.

Results
Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021–2022, 34 in 2020–2021, 395 in 2019–2020 and 483 in 2018–2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022–2023), compared to 5.7 ± 4 in 2021–2022, 5.3 ± 4 in 2020–2021, 6.4 ± 5 in 2019–2020 and 5.5 ± 4 in 2018–2019 (p < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021–2022, 0 in 2020–2021, 11 (2%) in 2019–2020 and 6 (1%) in 2018–2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021–2022, 1 (33%) in 2020–2021, 68 (23%) in 2019–2020, 61 (28%) in 2018–2019 (p = 0.001).

Conclusions
This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years.
An immunoinformatics and structural vaccinology approach to design a novel and potent multi-epitope base vaccine targeting Zika virus
Authors: Hakami Mohammed Ageeli 
Published: February 2024

AbstractZika virus is an infectious virus, that belongs to Flaviviridae family, which is transferred to humans through mosquito vectors and severely threatens human health; but, apart from available resources, no effective and secure vaccine is present against Zika virus, to prevent such infections. In current study, we employed structural vaccinology approach to design an epitope-based vaccine against Zika virus, which is biocompatible, and secure and might trigger an adaptive and innate immune response by using computational approaches. We first retrieved the protein sequence from National Center for Biotechnology Information (NCBI) database and carried out for BLAST P. After BLAST P, predicted protein sequences were shortlisted and checked for allergic features and antigenic properties. Final sequence of Zika virus, with accession number (APO40588.1) was selected based on high antigenic score and non-allergenicity. Final protein sequence used various computational approaches including antigenicity testing, toxicity evaluation, allergenicity, and conservancy assessment to identify superior B-cell and T-cell epitopes. Two B-cell epitopes, five MHC-six MHC-II epitopes and I were used to construct an immunogenic multi-epitope-based vaccine by using suitable linkers. A 50S ribosomal protein was added at N terminal to improve the immunogenicity of vaccine. In molecular docking, strong interactions were presented between constructed vaccine and Toll-like receptor 9 (− 1100.6 kcal/mol), suggesting their possible relevance in the immunological response to vaccine. The molecular dynamics simulations ensure the dynamic and structural stability of constructed vaccine. The results of C-immune simulation revealed that constructed vaccine activate B and T lymphocytes which induce high level of antibodies and cytokines to combat Zika infection. The constructed vaccine is an effective biomarker with non-sensitization, nontoxicity; nonallergic, good immunogenicity, and antigenicity, however, experimental assays are required to verify the results of present study.
Early signs of myocardial systolic dysfunction in patients with type 2 diabetes are strongly associated with myocardial microvascular dysfunction independent of myocardial fibrosis: a prospective cohort study
Authors: Bojer Annemie S. , Sørensen Martin H. , Madsen Stine H. , Broadbent David A. , Plein Sven , Gæde Peter , Madsen Per L. 
Published: February 2024

Abstract
Background
Patients with diabetes demonstrate early left ventricular systolic dysfunction. Notably reduced global longitudinal strain (GLS) is related to poor outcomes, the underlying pathophysiology is however still not clearly understood. We hypothesized that pathophysiologic changes with microvascular dysfunction and interstitial fibrosis contribute to reduced strain.

Methods
211 patients with type 2 diabetes and 25 control subjects underwent comprehensive cardiovascular phenotyping by magnetic resonance imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), extracellular volume (ECV), and 3D feature tracking GLS and global circumferential (GCS) and radial strain (GRS) were quantified.

Results
Patients (median age 57 [IQR 50, 67] years, 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. Compared to control subjects GLS, GCS, and GRS were reduced in the total diabetes cohort, and GLS was also reduced in the sub-group of patients without diabetic complications compared to control subjects (controls − 13.9 ± 2.0%, total cohort − 11.6 ± 3.0%; subgroup − 12.3 ± 2.6%, all p < 0.05). Reduced GLS, but not GCS or GRS, was associated with classic diabetes complications of albuminuria (UACR ≥ 30 mg/g) [β (95% CI) 1.09 (0.22–1.96)] and autonomic neuropathy [β (95% CI) 1.43 (0.54–2.31)] but GLS was not associated with retinopathy or peripheral neuropathy. Independently of ECV, a 10% increase in MBF at stress and MPR was associated with higher GLS [multivariable regression adjusted for age, sex, hypertension, smoking, and ECV: MBF stress (β (95% CI) − 0.2 (− 0.3 to − 0.08), MPR (β (95% CI) − 0.5 (− 0.8 to − 0.3), p < 0.001 for both]. A 10% increase in ECV was associated with a decrease in GLS in univariable [β (95% CI) 0.6 (0.2 to 1.1)] and multivariable regression, but this was abolished when adjusted for MPR [multivariable regression adjusted for age, sex, hypertension, smoking, and MPR (β (95% CI) 0.1 (− 0.3 to 0.6)]. On the receiver operating characteristics curve, GLS showed a moderate ability to discriminate a significantly lowered stress MBF (AUC 0.72) and MPR (AUC 0.73).

Conclusions
Myocardial microvascular dysfunction was independent of ECV, a biomarker of myocardial fibrosis, associated with GLS. Further, 3D GLS could be a potential screening tool for myocardial microvascular dysfunction. Future directions should focus on confirming these results in longitudinal and/or interventional studies.
Impact of dexamethasone in severe COVID-19-induced acute kidney injury: a multicenter cohort study
Authors: Rubin Sébastien , Orieux Arthur , Prezelin-Reydit Mathilde , Garric Antoine , Picard Yoann , Mellati Nouchan , Le Gall Lisa , Dewitte Antoine , Prevel Renaud , Gruson Didier , Louis Guillaume , Boyer Alexandre ,   for the Groupe Recherche Rein Réanimation (G3R)
Published: February 2024

Abstract
Background
Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study (n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI. This study aimed to investigate the preventive impact of DXM on AKI in a multicenter study of patients with severe COVID-19.

Methods
We conducted a multicenter study in three French ICUs from March 2020 to August 2021. All patients admitted to ICU for severe COVID-19 were included. Individuals with preexistent AKI or DXM administration before admission to ICU were excluded. While never used during the first wave, DXM was used subsequently at ICU entry, providing two treatment groups. Multivariate Cause-specific Cox models taking into account changes in ICU practices over time, were utilized to determine the association between DXM and occurrence of AKI.

Results
Seven hundred and ninety-eight patients were included. Mean age was 62.6 ± 12.1 years, 402/798 (50%) patients had hypertension, and 46/798 (6%) had previous chronic kidney disease. Median SOFA was 4 [3–6] and 420/798 (53%) required invasive mechanical ventilation. ICU mortality was 208/798 (26%). AKI was present in 598/798 (75%) patients: 266/598 (38%), 163/598 (27%), and 210/598 (35%) had, respectively, AKI KDIGO 1, 2, 3, and 61/598 (10%) patients required renal replacement therapy. Patients receiving DXM had a significantly decreased hazard of AKI occurrence compared to patients without DXM (HR 0.67; 95CI 0.55–0.81). These results were consistent in analyses that (1) excluded patients with DXM administration to AKI onset delay of less than 12 h, (2) incorporating the different ‘waves’ of the COVID-19 pandemic.

Conclusions
DXM was associated with a decrease in the risk of AKI in severe COVID-19 patients admitted to ICU. This supports the hypothesis that the inflammatory injury of AKI may be preventable.
Orthodontic camouflage treatment for a patient with bilateral cleft lip and palate, bilateral crossbite, and microdontic maxillary lateral incisors
Authors: Cheng Lanxin , Xia Kai , Sun Wentian , Yu Liyuan , Zhao Zhihe , Liu Jun 
Published: February 2024

AbstractCleft lip and palate is a congenital craniofacial anomaly that affects the lip and oral cavity. The management and orthodontic treatment of this anomaly is important but challenging. This article reports the successful treatment of a patient with bilateral cleft lip and palate, Class III malocclusion, bilateral crossbite, crowding and microdontic maxillary lateral incisors. One mandible incisor was extracted, and three miniscrew anchorages were utilized to distalize the maxillary left dental arch and retract the mandibular arch. After treatment, ideal occlusion and a better profile were established, and long-term stability was confirmed by a 4-year follow-up. This article represents a successful attempt of orthodontic camouflage treatment of severe dentofacial discrepancy, as an important part of the series treatment of cleft lip and palate, to provide some insight into the clinical field.
A comprehensive review on ecology, life cycle and use of Tecoma stans (bignoneaceae)
Authors: Singh Simrat , Miller Chad Thomas , Singh Parminder , Sharma Rishu , Rana Nepu , Dhakad Ashok Kumar , Dubey Rajesh Kumar 
Published: February 2024

AbstractTecoma stans is a widely distributed tall ornamental shrub in the plains of Indian subcontinent and is considered an invasive species across Argentina, Australia, South Africa, Pacific Islands and tropical regions of Asia. Besides having an ornamental significance, T. stans has been extensively investigated for its pharmaceutical applications as a source of bioactive compounds. In addition, the shrub is cultivated commercially as a potted flowering plant. We believe that T. stans, being a hardy, invasive and aggressively growing species, holds a considerable potential and a promising solution for re-greening waste and degraded lands outside its invasive range, due to its wider adaptability and drought tolerant characteristics. The shrub is an excellent source of pollen and nectar, that attracts diverse insect-pollinators and several species of birds. The prudent plantation of this shrub has the potential to restore the ecology of barren landscapes, that can change its perspective of ‘being invasive’ to ‘being ecologically healthy’ across the tropical, semi-arid and subtropical regions worldwide. This paper reviews the current updates on ecology, life cycle including morphology, plant growth characteristics, flowering phenology, reproductive biology, breeding system and fruiting of T. stans. In addition, details on insect-pollinator diversity and natural regeneration potential have also been discussed, besides highlighting its therapeutic and landscape use.
Impact of ChatGPT on ESL students’ academic writing skills: a mixed methods intervention study
Authors: Mahapatra Santosh 
Published: February 2024

AbstractThis paper presents a study on the impact of ChatGPT as a formative feedback tool on the writing skills of undergraduate ESL students. Since artificial intelligence-driven automated writing evaluation tools positively impact students’ writing, ChatGPT, a generative artificial intelligence-propelled tool, can be expected to have a more substantial positive impact. However, very little empirical evidence regarding the impact of ChatGPT on writing is available. The current mixed methods intervention study tried to address this gap. Data were collected from tertiary level ESL students through three tests and as many focus group discussions. The findings indicate a significant positive impact of ChatGPT on students' academic writing skills, and students’ perceptions of the impact were also overwhelmingly positive. The study strengthens and advances theories of feedback as a dialogic tool and ChatGPT as a reliable writing tool, and has practical implications. With proper student training, ChatGPT can be a good feedback tool in large-size writing classes. Future researchers can investigate the impact of ChatGPT on various specific genres and micro aspects of writing.
Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury
Authors: Nishijima Takayuki , Okuyama Kentaro , Shibata Shinsuke , Kimura Hiroo , Shinozaki Munehisa , Ouchi Takehito , Mabuchi Yo , Ohno Tatsukuni , Nakayama Junpei , Hayatsu Manabu , Uchiyama Keiko , Shindo Tomoko , Niiyama Eri , Toita Sayaka , Kawada Jiro , Iwamoto Takuji , Nakamura Masaya , Okano Hideyuki , Nagoshi Narihito 
Published: February 2024

Abstract
Background
Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected.

Methods
Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing.

Result
After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system’s role in recovery.

Conclusion
The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.