bluuebunny/crossref_metadata_2025_split huggingface dataset:
The preparation, biodistribution, and human’s absorbed dose evaluation of Radio-Scandium-HYNIC-TOC for somatostatin-receptor-positive neuroendocrine tumors therapy by animal study
Authors: Deilami-nezhad Leila , Moghaddam-Banaem Leila , Sadeghi Mahdi 
Published: June 2022

Background
Most of the neuroendocrine tumors (NETs) express Somatostatin receptors (SSTr), which are the main bases for the development of several radiopharmaceuticals for therapy and imaging of these types of tumors. In this study, 46Scandium nuclide was used to label a peptide compound via hydrazinonicotinyl-Tyr3-Octreotide (HYNIC-TOC) and researched further for somatostatin-receptor NETs treatment.

Methods and materials
The labeling procedure was conducted at 95°C for 10 min. The compound stability was tested in the environment of human serum at 37°C. The biodistribution of compound was investigated in balb/c normal mice and mice bearing AR4-2J tumor. Absorbed Doses of Human Organs were estimated by extrapolation of the biokinetics data of compound in mice to human’s organs and then the absorbed doses were estimated by application of MATLAB and MIRDOSE software.

Results
Labeling yield was more than 90% with 555 MBq/mg specific activity. The radio-labeled compound expressed well consistency in human serum. The tumor uptake reached 3.831 ID/g% until 4 h post-injection and increased to 5.564%ID/g until 24 h post-injection.

Conclusion
The main achievement of this study was high tumor uptake of 46Sc-HYNIC-TOC which may be therapeutically valuable for the therapy of NETs. The estimation of the absorbed dose of human from 47Scandium-HYNIC-TOC showed low absorbed doses in critical organs and the elimination of the radiopharmaceutical was through the gastrointestinal tract.
Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents With Eosinophilic Esophagitis
Authors: Gupta Sandeep K. , Hill Malcolm , Vitanza Joanne M. , Farber Robert H. , Desai Nirav K. , Williams James , Song Ivy H. 
Published: June 2022

The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE) (MPI 101-01/NCT00762073).
Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2–9 or 10–18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution, and bodyweight and body mass index were also evaluated.
Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post dose and the half-life of budesonide was 3.3–3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.
Protein Profiling of Mechanically Processed Lipoaspirates: Discovering Wound Healing and Antifibrotic Biomarkers in Nanofat
Authors: Sanchez-Macedo Nadia , McLuckie Michelle , Grünherz Lisanne , Lindenblatt Nicole 
Published: June 2022

Background:
Nanofat is an injectable oily emulsion, rich in adipose-derived stem cells and growth factors. It is prepared from lipoaspirates through mechanical emulsification and filtration. Despite being successfully used in several procedures in regenerative medicine such as scar attenuation, skin rejuvenation, and treatment of chronic wounds, little is known about exactly how nanofat induces regeneration in treated skin at the molecular level.

Methods:
Microfat and nanofat samples were isolated from 18 healthy patients. Proteomic profiling was performed through untargeted mass spectrometry proteomics and multiplex antibody arrays. Pathway enrichment analysis of differentially expressed proteins between microfat and nanofat was performed using Gene Ontology, Reactome, and Kyoto Encyclopaedia of Genes and Genomes as reference databases.

Results:
Untargeted proteomics showed that up-regulated genes in nanofat are involved in innate immunity responses, coagulation, and wound healing, whereas down-regulated genes were linked to cellular migration and extracellular matrix production. Secretome array screening of microfat and nanofat samples showed no significantly different expression, which strongly suggests that the mechanical emulsification step does not affect the concentration of tissue regeneration biomarkers. The identified proteins are involved in wound healing, cellular migration, extracellular matrix remodeling, angiogenesis, stress response, and immune response.

Conclusions:
Mechanical processing of lipoaspirates into nanofat significantly influences the proteome profile by enhancing inflammation, antimicrobial, and wound healing pathways. Nanofat is extremely rich in tissue repair and tissue remodeling factors. This study shows that the effects of microfat and nanofat treatment are based on up-regulated inflammation, antimicrobial, and wound healing pathways. Mechanical emulsification does not alter the concentration of tissue regeneration biomarkers.

Clinical Relevance Statement:
In addition to adipose-derived stems cells, nanofat contains distinct tissue repair and remodelling factors, which explains its beneficial effects on tissue regeneration.
Technique for Minimally Invasive Face and Neck Contouring with Bipolar Radiofrequency Devices
Authors: Rohrich Rod J. , Chamata Edward S. , Bellamy Justin L. , Alleyne Brendan 
Published: June 2022

Summary:
Radiofrequency devices have grown in popularity as minimally invasive options for the treatment of skin laxity in the face and neck. These treatments are often combined with liposuction procedures to provide enhanced tissue contraction alongside the reduction in adiposity. Proper patient selection and intraoperative technique are crucial to achieving the desired outcomes in a safe manner. In this article, the authors discuss their indications and technique for the treatment of the face and neck with bipolar radiofrequency devices.
Brief Report: Impact of COVID-19 on Cabotegravir Plus Rilpivirine Long-Acting Dosing Across 6 Ongoing Global Phase IIb and III Clinical Trials
Authors: Czarnogorski Maggie , Benn Paul , McCoig Cindy , Nwafor Toyin , Griffith Sandy , Sutton Ken , Harrington Conn , Saggu Parminder , Yague Itziar , Williams Will , Español Carlos M. , Goodchild Jessica , Fricker Jane , Patel Parul , D'Amico Ronald 
Published: June 2022

Background:
Cabotegravir + rilpivirine long-acting (LA) is a novel antiretroviral therapy (ART) administered intramuscularly monthly or every 2 months by a health care provider. The COVID-19 pandemic presents a potential challenge to patients' ability to attend scheduled clinic visits for dosing administration.

Setting:
This analysis evaluated implementation fidelity across 6 phase IIb/III/IIIb cabotegravir + rilpivirine LA clinical trials in 16 countries during the COVID-19 pandemic.

Methods:
COVID-19-impacted visits were defined as modified dosing visits for which oral therapy was provided to participants unable to attend the clinic or injection visits that were rescheduled. Data from December 1, 2019, to March 1, 2021, were aggregated and analyzed using descriptive statistics.

Results:
Of 2127 participants in cabotegravir + rilpivirine LA trials, 1997 (94%) had LA dosing visits proceed as planned during the COVID-19 pandemic. Of 130 (6%) participants with injection visits affected by COVID-19, most were from North America (57%) and Europe (26%). Most participants with COVID-19-impacted visits used oral therapy with cabotegravir + rilpivirine (75%) or alternative oral standard-of-care ART (21%) to maintain continuous ART. The most common reasons for missed visits were clinic closure/staffing constraints (48%) and COVID-19-related travel restrictions (23%). Most (98%) participants who used oral ART maintained virologic suppression; 2 participants had viral load between 50 and 100 copies/mL.

Conclusion:
During the COVID-19 pandemic, most trial participants maintained their LA dosing schedules. Flexibility of the LA dosing regimen, with the ability to switch to oral therapy, facilitated continuous ART provision and implementation fidelity.
Drivers of melioidosis endemicity: epidemiological transition, zoonosis, and climate change
Authors: Birnie Emma , Biemond Jason J. , Wiersinga W. Joost 
Published: June 2022

Purpose of review
Melioidosis, caused by the soil-dwelling bacterium Burkholderia pseudomallei, is a tropical infection associated with high morbidity and mortality. This review summarizes current insights into melioidosis’ endemicity, focusing on epidemiological transitions, zoonosis, and climate change.

Recent findings
Estimates of the global burden of melioidosis affirm the significance of hot-spots in Australia and Thailand. However, it also highlights the paucity of systematic data from South Asia, The Americas, and Africa. Globally, the growing incidence of diabetes, chronic renal and (alcoholic) liver diseases further increase the susceptibility of individuals to B. pseudomallei infection. Recent outbreaks in nonendemic regions have exposed the hazard from the trade of animals and products as potential reservoirs for B. pseudomallei. Lastly, global warming will increase precipitation, severe weather events, soil salinity and anthrosol, all associated with the occurrence of B. pseudomallei.

Summary
Epidemiological transitions, zoonotic hazards, and climate change are all contributing to the emergence of novel melioidosis-endemic areas. The adoption of the One Health approach involving multidisciplinary collaboration is important in unraveling the real incidence of B. pseudomallei, as well as reducing the spread and associated mortality.
Wireless interfaces for brain neurotechnologies
Authors: Kim Han-Joon , Ho John S. 
Published: June 2022

Wireless interfaces enable brain-implanted devices to remotely interact with the external world. They are critical components in modern research and clinical neurotechnologies and play a central role in determining their overall size, lifetime and functionality. Wireless interfaces use a wide range of modalities—including radio-frequency fields, acoustic waves and light—to transfer energy and data to and from an implanted device. These forms of energy interact with living tissue through distinct mechanisms and therefore lead to systems with vastly different form factors, operating characteristics, and safety considerations. This paper reviews recent advances in the development of wireless interfaces for brain neurotechnologies. We summarize the requirements that state-of-the-art brain-implanted devices impose on the wireless interface, and discuss the working principles and applications of wireless interfaces based on each modality. We also investigate challenges associated with wireless brain neurotechnologies and discuss emerging solutions permitted by recent developments in electrical engineering and materials science.
This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.
The interplay between sulfur assimilation and biodesulfurization phenotype in Rhodococcus qingshengii IGTS8: Insights into a regulatory role of the reverse transsulfuration pathway
Authors: Martzoukou Olga , Glekas Panayiotis , Avgeris Margaritis , Mamma Diomi , Scorilas Andreas , Kekos Dimitris , Amillis Sotiris , Hatzinikolaou Dimitris G. 
Published: June 2022

AbstractBiodesulfurization (BDS) is a process that selectively removes sulfur from dibenzothiophene and its derivatives. Several mesophilic natural biocatalysts have been isolated, harboring the highly conserved desulfurization operon dszABC. Even though the desulfurization phenotype is known to be significantly repressed by methionine, cysteine, and inorganic sulfate, the available information on the metabolic regulation of gene expression is still limited. In this study, scarless knockouts of the sulfur metabolism-related cbs and metB genes are constructed in the desulfurizing strain Rhodococcus sp. IGTS8. We provide sequence analyses for both enzymes of the reverse transsulfuration pathway and report their involvement in the sulfate- and methionine-dependent repression of the biodesulfurization phenotype, based on desulfurization assays in the presence of different sulfur sources. Additionally, the positive effect of cbs and metB gene deletions on dsz gene expression in the presence of both sulfate and methionine, but not cysteine, is uncovered and highlighted.
Bridging the gap: A qualitative analysis of online public forum with healthcare professionals in bursting myths about weight management
Authors: Bhatti R , Joumaa M , Bereczky B 
Published: June 2022

AbstractBackgroundObesity has increased rapidly worldwide in last few decades. According to World Obesity Federation 2018, the prevalence of obesity in UAE amongst Emirati aged 18-69 years has been reported as 32.2% vs 38.5% living with obesity vs overweight in men and 41.8% vs 29.3% living with obesity vs overweight in women. There are many myths amongst general public about obesity.AimThe objective of the study was to address public questions through online forum regarding weight management.MethodsIn this cross-sectional observational study qualitative analysis was done. It was conducted quarterly at Mediclinic City and Parkview Hospital in Dubai from August 2020-September 2021. An online zoom meeting was made available to the public. People who wanted to attend the session registered via dedicated email address. A certified dietician, endocrinologist and bariatric surgeon were available to answer people’s questions.Results6 online forums have been conducted. 163 (range 10-90) people attended. Three themes were constructed during data analysis. 1-Diet: what’s the best diet and about caloric intake. 2-Insulin resistance or hormone imbalance is responsible for weight gain. 3-Misinformation and unrealistic expectations about bariatric surgery. Feedback from audience was ‘it was interactive, fun and informative session’, ‘it’s good to know that it’s not my fault and I need to get help’.ConclusionOur results show that patients need support throughout their weight management journey. Healthcare professionals need to be more aware of patient’s perceptions about weight management so that they can be addressed in consultations. We need more online support sessions facilitated by healthcare professionals.
Prosthesis hand grasp control following targeted muscle reinnervation in individuals with transradial amputation
Authors: Simon Ann M. , Turner Kristi L. , Miller Laura A. , Dumanian Gregory A. , Potter Benjamin K. , Beachler Mark D. , Hargrove Levi J. , Kuiken Todd A. 
Published: June 2022

AbstractTransradial amputation is the most common level of major upper limb amputation. Despite the growing availability of multifunctional prosthetic hands, users’ control of these hands and overall functional abilities remain limited. The combination of pattern recognition control and targeted muscle reinnervation (TMR) surgery, an innovative technique where amputated nerves are transferred to reinnervate new muscle targets in the residual limb, has been used to improve prosthesis control of individuals with more proximal upper limb amputation levels (i.e., shoulder disarticulation and transhumeral amputation). The goal of this study was to determine if similar prosthesis control improvements could be seen for individuals with amputations at the transradial level. Participants controlled 3-5 grips with a multi-articulating hand prosthesis under myoelectric pattern recognition control for at least 8 weeks at home pre- and post-TMR surgery. Users gained some significant functional control benefits using a multi-articulating hand prosthesis with pattern recognition at 9-12 months post-TMR surgery. Additionally, a majority of subjects noted an improvement in their residual limb and phantom limb sensations post-TMR. An additional offline EMG analysis showed a decrease in grip classification error post-TMR surgery compared to pre-TMR surgery.
User-centred Design of a Clinical Decision Support System for Palliative Care: Insights from Healthcare Professionals
Authors: Blanes-Selva Vicent , Asensio-Cuesta Sabina , Doñate-Martínez Ascensión , Mesquita Felipe Pereira , García-Gómez Juan M. 
Published: June 2022

AbstractClinical Decision Support Systems (CDSSs) could offer many benefits to clinical practice, but they present several adoption barriers regarding their acceptance and usability by professionals. Our objective in this study is to validate a Palliative Care CDSS, The Aleph, through a user-centred methodology, considering the predictions of the AI core, the usability, and the user experience. We performed two rounds of individual evaluation sessions with potential users. Each session included a model evaluation, a task test and a usability and user experience assessment. The Machine Learning predictive models outperformed the participants in the three predictive tasks. SUS reported 62.7± 14.1 and 65 ± 26.2 on a 100-point rating scale for both rounds, respectively, while UEQ-S scores were 1.42 and 1.5 on the –3 to 3 scale. Think-aloud methodology and the inclusion of the user-experience dimension allowed us to identify most of the workflow implementation issues.
Associations Between Depression, Anxiety, and Multiple Disease Outcomes: A Phenotype x Phenome-Wide Association Study in Electronic Health Records
Authors: Gao Y. Nina , Coombes Brandon , Ryu Euijung , Pazdernik Vanessa , Jenkins Gregory , Pendegraft Richard , Biernacka Joanna , Olfson Mark 
Published: June 2022

Unstructured AbstractAnxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of isolated depression, isolated anxiety, or both. Using electronic health records for 14,994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype x phenome-wide association study (Phe2WAS) was performed to test for differences between these groups. Additional Phe2WAS were performed restricting analyses to diagnoses occurring before or after a diagnosis of depression or anxiety to determine the temporal sequencing of diagnoses. Compared to isolated anxiety, isolated depression was more strongly associated with obesity (OR=1.61; p=3e-22), sleep apnea (OR=1.71; p=1e-22), type II diabetes (OR=1.74; p=9e-18), and neurological disorders (OR=1.54; p=6e-10); these differences were most pronounced for medical diagnoses made after first depression or anxiety diagnosis. In relation to isolated depression, isolated anxiety was more strongly related to palpitations (OR=1.91; p=2e-25), skin neoplasms (OR=1.61; p=2e-17), cardiac dysrhythmias (OR=1.45; p=2e-12), and degenerative skin conditions (OR=1.41; p=1e-10); these differences were most pronounced for medical diagnoses made before a first depression or anxiety diagnosis. Patients with the comorbid depression and anxiety had stronger associations with other mental health disorders, substance use disorders, sleep problems, and digestive problems relative to those with isolated depression or anxiety. While depression and anxiety are closely related, this study suggests that improving phenotypic characterization within the broad categories of depression and anxiety could improve clinical care and provide future directions for research.
Community assessment of methods to deconvolve cellular composition from bulk gene expression
Authors: White Brian S. , de Reyniès Aurélien , Newman Aaron M. , Waterfall Joshua J. , Lamb Andrew , Petitprez Florent , Lin Yating , Yu Rongshan , Guerrero-Gimenez Martin E , Domanskyi Sergii , Monaco Gianni , Chung Verena , Banerjee Jineta , Derrick Daniel , Valdeolivas Alberto , Li Haojun , Xiao Xu , Wang Shun , Zheng Frank , Yang Wenxian , Catania Carlos A. , Lang Benjamin J. , Bertus Thomas J. , Piermarocchi Carlo , Caruso Francesca P. , Ceccarelli Michele , Yu Thomas , Guo Xindi , Bletz Julie , Coller John , Maecker Holden , Duault Caroline , Shokoohi Vida , Patel Shailja , Liliental Joanna E. , Simon Stockard ,   Tumor Deconvolution DREAM Challenge consortium, Saez-Rodriguez Julio , Heiser Laura M. , Guinney Justin , Gentles Andrew J. 
Published: June 2022

AbstractWe evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods usingin vitroandin silicotranscriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.
CRISPR/Cas9 screen reveals a role of purine synthesis for estrogen receptor α activity and tamoxifen resistance of breast cancer cells
Authors: Hany Dina , Vafeiadou Vasiliki , Picard Didier 
Published: June 2022

AbstractIn breast cancer, resistance to endocrine therapies that target estrogen receptor α (ERα), such as tamoxifen and fulvestrant, remains a major clinical problem. Whether and how ERα+ breast cancers switch from being estrogen-dependent to -independent remains unclear. With a genome-wide CRISPR/Cas9 knockout screen, we identified new biomarkers and potential therapeutic targets of endocrine resistance. We demonstrate that high levels of PAICS, an enzyme involved in thede novobiosynthesis of purines, can shift the balance of ERα activity to be more estrogen-independent and tamoxifen-resistant. We indicate that this is due to an elevated activity of cAMP-activated protein kinase A and mammalian target of rapamycin, kinases known to phosphorylate ERα specifically and to stimulate its activity. Genetic or pharmacological targeting of PAICS sensitizes tamoxifen-resistant cells to tamoxifen. Based on these findings, we propose the combined targeting of PAICS and ERα as a new, effective, and potentially safe therapeutic regimen.