bluuebunny/crossref_metadata_2025_split huggingface dataset:
scFv biofunctionalized nanoparticles to effective and safe targeting of CEA-expressing colorectal cancer cells
Authors: Silveira Maria José , Martins Cláudia , Cruz Tânia , Castro Flávia , Amorim-Costa Ângela , Chester Kerry , Oliveira Maria José , Sarmento Bruno 
Published: October 2023

AbstractColorectal cancer (CRC) is one of the deadliest cancers worldwide, with the 5 year survival rate in metastatic cases limited to 12%. The design of targeted and effective therapeutics remains a major unmet clinical need in CRC treatment. Carcinoembryonic antigen (CEA), a glycoprotein overexpressed in most colorectal tumors, may constitute a promising molecule for generating novel CEA-targeted therapeutic strategies for CRC treatment. Here, we developed a smart nanoplatform based on chemical conjugation of an anti-CEA single-chain variable fragment (scFv), MFE-23, with PLGA-PEG polymers to deliver the standard 5-Fluorouracil (5-FU) chemotherapy to CRC cells. We confirmed the specificity of the developed CEA-targeted NPs on the internalization by CEA-expressing CRC cells, with an enhance of threefold in the cell uptake. Additionally, CEA-targeted NPs loaded with 5-FU induced higher cytotoxicity in CEA-expressing cells, after 24 h and 48 h of treatment, reinforcing the specificity of the targeted NPs. Lastly, the safety of CEA-targeted NPs loaded with 5-FU was evaluated in donor-isolated macrophages, with no relevant impact on their metabolic activity nor polarization. Altogether, this proof of concept supports the CEA-mediated internalization of targeted NPs as a promising chemotherapeutic strategy for further investigation in different CEA-associated cancers and respective metastatic sites.Authors: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Maria José] Last name [Silveira]. Author 7 Given name: [Maria José] Last name [Oliveira]. Also, kindly confirm the details in the metadata are correctokAffiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.ok
Graphical Abstract
“Flying a plane and building it at the same time”: Lessons learned from the dynamic implementation of mass vaccination clinics in the Region of Waterloo, Ontario, Canada
Authors: Tetui Moses , Tennant Ryan , Adil Maisha , Bala Arthi , Burns Catherine , Waite Nancy , Grindrod Kelly 
Published: October 2023

Abstract
Background
Vaccination plays a critical role during pandemics, and mass vaccination clinics are often an imperative public health measure. These clinics usually consist of multi-disciplinary teams, which can pose significant coordination challenges, yet also present an opportunity for collectively contributing towards mitigating the impact of infection within communities. This study explores the coordination dynamics of the Region of Waterloo’s coronavirus disease of 2019 (COVID-19) mass vaccination clinics in Ontario, Canada, between July 2021 and April 2022.

Methods
This qualitative study included 16 purposively selected participants working in mass vaccination clinics. Participants were individually interviewed for 40–60 min. An inductive and iterative thematic analysis was undertaken, including open coding, grouping, labelling, regrouping and making sense of the themes.

Results
Three interrelated themes were created: (1) unpredictable work environment, which was comprised of changing clinic processes and the impact of clinic adjustments to the running of the clinics; (2) clinic cohesion challenges, which included staff role disparities, limited job preparation and clinic system silos; and (3) adaptable and supportive work environment, which was comprised of staff adaptability, dispositional flexibility and a supportive work environment. While the first two themes created a precarious situation in the clinics, the third countered it, leading to a largely successful clinic implementation.

Conclusions
The rapid evolution and high transmissibility of COVID-19 in communities required a public health response that felt like flying and building a plane simultaneously – a seemingly impossible yet necessary task. However, an adaptable and supportive work environment was critical for establishing an atmosphere that can overcome challenges from a constantly changing pandemic and the guidance of public health officials. Such lessons gained from understanding the dynamic experiences in mass vaccination clinics are essential for improving the development and operation of future immunization campaigns.
Transient intracranial pressure elevations (B waves) are associated with sleep apnea
Authors: Riedel Casper Schwartz , Martinez-Tejada Isabel , Andresen Morten , Wilhjelm Jens E. , Jennum Poul , Juhler Marianne 
Published: October 2023

Abstract
Background
Repetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies a general association between ICP macropatterns and sleep apnea remains unknown.

Methods
We included 34 patients with hydrocephalus, or idiopathic intracranial hypertension (IIH), who were referred to the Neurosurgical Department, Copenhagen, Denmark, from 2017 to 2021. Every patient underwent diagnostic overnight ICP monitoring for clinical indications, with simultaneous polysomnography (PSG) sleep studies. All transient ICP elevations were objectively quantified in all patients. Three patients were monitored with continuous positive airway pressure (CPAP) treatment for an additional night.

Results
All patients had transient ICP elevations associated with sleep apnea. The mean temporal delay from sleep apnea to transient ICP elevations for all patients was 3.6 s (SEM 0.2 s). Ramp-type transient ICP elevations with a large increase in ICP were associated with rapid eye movement (REM) sleep and sinusoidal-type elevations with non-REM (NREM) sleep. In three patients treated with CPAP, the treatment reduced the number of transient ICP elevations with a mean of 37%. CPAP treatment resulted in insignificant changes in the average ICP in two patients but elevated the average ICP during sleep in one patient by 5.6 mmHg.

Conclusion
The findings suggest that sleep apnea causes a significant proportion of transient ICP elevations, such as B-waves, and sleep apnea should be considered in ICP evaluation. Treatment of sleep apnea with CPAP can reduce the occurrence of transient ICP elevations. More research is needed on the impact of slow oscillating mechanisms on transient ICP elevations during high ICP and REM sleep.
Community-engaged optimization of COVID-19 rapid evaluation and testing experiences: roll-out implementation optimization trial
Authors: Stadnick Nicole A. , Laurent Louise C. , Cain Kelli L. , Seifert Marva , Burola Maria Linda , Salgin Linda , Watson Paul , Oswald William , Munoz Fatima A. , Velasquez Sharon F. , Smith Justin D. , Zou Jingjing , Rabin Borsika A. 
Published: October 2023

Abstract
Background
There continues to be a need for COVID-19 testing that is pragmatic, community-centered, and sustainable. This study will refine and test implementation strategies prioritized by community partners: (1) walk-up no-cost testing, (2) community health worker (promotores)-facilitated testing and preventive care counseling, (3) vending machines that dispense no-cost, self-testing kits.

Methods
A co-designed Theory of Change from an earlier study phase and the Practical, Robust Implementation and Sustainment Model (PRISM) will guide the study design, measures selection, and evaluation. The first aim is to refine and operationalize a multi-component implementation strategy bundle and outcome measures for COVID-19 testing. A Community and Scientific Advisory Board (CSAB) will be established and include community members, clinical providers/staff from the partnering Federally Qualified Health Center (FQHC), public health researchers, policymakers, and a county health department ambassador. Engagement of CSAB members will be assessed through structured ethnography and a survey about the quality and quantity of engagement practices. The second aim is to implement and evaluate the impact of the implementation strategy bundle to optimize COVID-19 testing in communities using a roll-out implementation optimization (ROIO) design. Seven thousand and five hundred community members will be enrolled across four FQHC clinics over 18 months. Participants will be invited to complete an electronic survey about their demographics, health, and COVID-19 testing results and experiences. CSAB members and clinic partners will participate in PRISM fit and determinant assessments prior to each clinic rollout and post-trial. Interviews will be conducted with 60 community participants and 12 providers/staff following a 3-month rollout period at each clinic, inquiring about their experiences with the implementation strategies. Quantitative data will be analyzed using hierarchical multilevel models to determine the impact of implementation strategies. Qualitative data will be analyzed using rapid qualitative approaches to summarize implementation experiences and identify necessary changes prior to subsequent rollouts. A matrix approach will be used to triangulate data from quantitative and qualitative sources based on PRISM domains.

Discussion
This is one of the first pragmatic implementation trials to use a ROIO design and aims to co-create a sustainable and equitable COVID-19 testing program. Findings are likely to generalize to other public health prevention efforts.

Trial registration
NCT05894655 March 2, 2023.
MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma
Authors: Van Ommen Fasco , le Quellenec Gaelle A.T. , Willemsen-Bosman Mirjam E. , van Noesel Max M. , van den Heuvel-Eibrink Marry M. , Seravalli Enrica , Kroon Petra S. , Janssens Geert O. 
Published: October 2023

Abstract
Background
In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT).

Materials and methods
Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position.

Results
The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from − 3.5 to 5.8 Gy for the pancreatic tail and − 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation.

Conclusion
Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.
Follow-up of pre-motor symptoms of Parkinson’s disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF
Authors: Wilke Matheus Vernet Machado Bressan , Poswar Fabiano , Borelli Wyllians Vendramini , Michelin Tirelli Kristiane , Randon Dévora Natalia , Lopes Franciele Fátima , Pasetto Fernanda Bender , Sebastião Fernanda Medeiros , Iop Gabrielle Dineck , Faqueti Larissa , da Silva Layzon Antonio , Kubaski Francyne , Schuh Artur Francisco Schumacher , Giugliani Roberto , Schwartz Ida Vanessa Doederlein 
Published: October 2023

Abstract
Background
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Its classic motor symptoms may be preceded by non-motor symptoms (NMS). Population studies have identified GBA variants as risk factors for idiopathic PD. The increased risk of PD has also been suggested in other Lysosomal Storage Disorders (LSDs). Objective: To assess the evolution of the prevalence of NMS compatible with PD in a cohort of South Brazilian adult patients with Gaucher Disease (GD) type 1, already evaluated 3 years ago (2018). Cerebrospinal Fluid (CSF) was collected to assess the levels of LSD enzymes (beta-hexosaminidases, beta-glucuronidase) and biomarker of macrophage activation (chitotriosidase, ChT), compared to controls (metachromatic leukodystrophy, MLD). Cognition was evaluated by the Montreal Cognitive Assessment (MoCA) questionnaire, daytime sleepiness by the Epworth Sleepiness Scale (ESS), depression by Beck´s Inventory, constipation by the Unified Multiple System Atrophy Rating Scale (UMSARS) scale, and REM sleep behavior disorder by the single-question screen. Hyposmia was assessed with Sniffin’ Sticks (SST).

Results
Nineteen patients completed the follow-up (mean age of the sample was 44 years; range, 26–71). The patient with the highest number of NMS at the baseline (4 including the lowest SST score) was diagnosed with PD four years later. Apart from an improvement in the ESS score, no other statistical significance was found between the number of NMS between the first and second evaluation, nor between patients with one L444P variant (n = 5) and the rest of the cohort. CSF was collected in five patients (mean age of the sample was 40 years, range 30–53. A significant difference was found in the mean CSF activity levels of beta-hexosaminidases and beta-glucuronidase between GD1 and MLD patients. Mean ChT (CSF) was 62 nmol/h/mL in GD patients and 142 in MLD (n = 6) patients.

Conclusions
The patient with the highest number of NMS in our 2018 cohort was the one that developed PD, corroborating with the importance of this longitudinal follow-up. CSF and plasma analysis might allow a better understanding of the neurodegenerative processes connecting PD and the lysosomal environment. Further analysis is needed to understand this relationship.
Biosynthesis of ternary NiCoFe2O4 nanoflowers: investigating their 3D structure and potential use in gene delivery
Authors: Alijani Hajar Q. , Khatami Mehrdad , Torkzadeh-Mahani Masoud , Michalička Jan , Wang Wu , Wang Di , Heydari Abolfazl 
Published: October 2023

AbstractMulticomponent nanoparticle systems are known for their varied properties and functions, and have shown potential as gene nanocarriers. This study aims to synthesize and characterize ternary nickel–cobalt-ferrite (NiCoFe2O4) nanoparticles with the potential to serve as gene nanocarriers for cancer/gene therapy. The biogenic nanocarriers were prepared using a simple and eco-friendly method following green chemistry principles. The physicochemical properties of the nanoparticles were analyzed by X-ray diffraction, vibrating sample magnetometer, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller. To evaluate the morphology of the nanoparticles, the field emission scanning electron microscopy with energy dispersive X-Ray spectroscopy, high-resolution transmission electron microscopy imaging, and electron tomography were conducted. Results indicate the nanoparticles have a nanoflower morphology with a mesoporous nature and a cubic spinel structure, where the rod and spherical nanoparticles became rose-like with a specific orientation. These nanoparticles were found to have minimal toxicity in human embryonic kidney 293 (HEK-293 T) cells at concentrations of 1 to 250 µg·mL–1. We also demonstrated that the nanoparticles could be used as gene nanocarriers for delivering genes to HEK-293 T cells using an external magnetic field, with optimal transfection efficiency achieved at an N/P ratio of 2.5. The study suggests that biogenic multicomponent nanocarriers show potential for safe and efficient gene delivery in cancer/gene therapy.
Graphical Abstract
Interplay between ESR1/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): comprehensive circulating tumor DNA (ctDNA) analysis
Authors: Gerratana Lorenzo , Davis Andrew A. , Velimirovic Marko , Clifton Katherine , Hensing Whitney L. , Shah Ami N. , Dai Charles S. , Reduzzi Carolina , D’Amico Paolo , Wehbe Firas , Medford Arielle , Wander Seth A. , Gradishar William J. , Behdad Amir , Puglisi Fabio , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo 
Published: October 2023

Abstract
Background
although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice.

Methods
The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored.

Results
The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases.

Conclusions
The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making.
The impact of an oral nutritional supplement on body weight gain in older adults with malnutrition: an open-label randomized controlled trial
Authors: Jayawardena Ranil , Wickramawardhane Prasani , Dalpatadu Chamila , Hills Andrew P. , Ranasinghe Priyanga 
Published: October 2023

Abstract
Background
The global aging population is expanding rapidly and many individuals have a particularly higher risk of malnutrition. Malnutrition can lead to impaired body function, morbidity, and mortality. Meeting nutritional requirements is a key strategy to minimize multiple debilitating adverse outcomes associated with malnutrition in the elderly.
Oral nutritional supplements (ONS) have been widely used as a dietary intervention for malnutrition in older adults. These supplements provide additional nutrients and calories to support nutritional requirements and have been shown to improve nutritional status, physical function, and quality of life in malnourished older adults.

Methods
This is an open-label, randomized controlled, parallel-group study including 50 institutionalized older adults (aged > 60 years) with malnutrition or at risk of malnutrition, living in a selected elderly care institution in Colombo, Sri Lanka. The aim is to assess improvement in healthy body weight gain and body composition in older adults with malnutrition at risk of malnutrition by using an ONS. Older adults will be screened for malnutrition using the Mini Nutrition Assessment (MNA) tool and eligible participants randomized using the simple random sampling technique to intervention and control groups (1:1 allocation ratio). The intervention group will consume 200 mL of ONS before bed continuously for 12 weeks. The primary outcome is the percentage who achieved at least 5% weight gain in the intervention group compared to the control group. Nutritional status (anthropometric, biochemical, clinical, and dietary), body composition (dual-energy X-ray absorptiometry), frailty, functional capacity (hand grip strength, knee extension, and Barthel index) cognitive status (Montreal Cognitive Assessment), and physical activity will be assessed as secondary outcomes at baseline and at the end of the 12-week intervention. Some measurements (anthropometry, dietary, and functional assessments) will also be performed at the end of the 4th week. Data will be analyzed using SPSS V-23.

Discussion
This study will determine whether the use of an ONS is effective in promoting healthy weight gain in older adults with malnutrition or at risk of malnutrition. In addition, investigating the impact of an ONS on multiple outcomes via clinical, nutritional, functional, and cognitive function will provide a more comprehensive understanding of the potential benefits of these supplements.

Trial registration
Sri Lanka Clinical Trail Registry SLCTR/2022/021. Oct. 6, 2022.
A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial
Authors: Pan Mang-Mang , Zhang Chi , Shen Long , Sha Jing-Jing , Shen Hui , Yan Yi-Dan , Wang Jia , Wang Xin , Lin Hou-Wen , Gu Zhi-Chun 
Published: October 2023

Abstract
Background
Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF.

Methods
The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction.

Discussion
This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries.

Trial registration
ChiCTR ChiCTR2200062123. Registered on 23 July 2022.