bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering a modular 44Ti/44Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry
Authors: Benabdallah Nadia , Zhang Hanwen , Unnerstall Ryan , Fears Amanda , Summer Lucy , Fassbender Michael , Rodgers Buck E. , Abou Diane , Radchenko Valery , Thorek Daniel L. J. 
Published: March 2023

Abstract
Background
44Sc/47Sc is an attractive theranostic pair for targeted in vivo positron emission tomographic (PET) imaging and beta-particle treatment of cancer. The 44Ti/44Sc generator allows daily onsite production of this diagnostic isotope, which may provide an attractive alternative for PET facilities that lack in-house irradiation capabilities. Early animal and patient studies have demonstrated the utility of 44Sc. In our current study, we built and evaluated a novel clinical-scale 44Ti/44Sc generator, explored the pharmacokinetic profiles of 44ScCl3, [44Sc]-citrate and [44Sc]-NODAGA (1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid) in naïve mice, and estimated the radiation burden of 44ScCl3 in humans.

Methods
44Ti/44Sc (101.2 MBq) in 6 M HCl solution was utilized to assemble a modular ZR resin containing generator. After assembly, 44Sc was eluted with 0.05 M HCl for further PET imaging and biodistribution studies in female Swiss Webster mice. Based on the biodistribution data, absorbed doses of 44/47ScCl3 in human adults were calculated for 18 organs and tissues using the IDAC-Dose software.

Results
44Ti in 6 M HCl was loaded onto the organic resin generator with a yield of 99.97%. After loading and initial stabilization, 44ScCl3 was eluted with 0.05 M HCl in typical yields of 82.9 ± 5.3% (N = 16), which was normalized to the estimated generator capacity. Estimated generator capacity was computed based on elution time interval and the total amount of 44Ti loaded on the generator. Run in forward and reverse directions, the 44Sc/44Ti ratio from a primary column was significantly improved from 1038 ± 440 to 3557 ± 680 (Bq/Bq) when a secondary, replaceable, ZR resin cartridge was employed at the flow outlet. In vivo imaging and ex vivo distribution studies of the reversible modular generator for 44ScCl3, [44Sc]-citrate and [44Sc]-NODAGA show that free 44Sc remained in the circulation significantly longer than the chelated 44Sc. The dose estimation of 44ScCl3 reveals that the radiation burden is 0.146 mSv/MBq for a 70 kg adult male and 0.179 mSv/MBq for a 57 kg adult female. Liver, spleen and heart wall will receive the highest absorbed dose: 0.524, 0.502, and 0.303 mGy/MBq, respectively, for the adult male.

Conclusions
A clinical-scale 44Ti/44Sc generator system with a modular design was developed to supply 44ScCl3 in 0.05 M HCl, which is suitable for further radiolabeling and in vivo use. Our data demonstrated that free 44ScCl3 remained in the circulation for extended periods, which resulted in approximately 10 times greater radiation burden than stably chelated 44Sc. Stable 44Sc/47Sc-complexation will be more favorable for in vivo use and for clinical utility.
Identification and verification of feature biomarkers associated with immune cells in neonatal sepsis
Authors: Liao Weiqiang , Xiao Huimin , He Jinning , Huang Lili , Liao Yanxia , Qin Jiaohong , Yang Qiuping , Qu Liuhong , Ma Fei , Li Sitao 
Published: March 2023

Abstract
Background
Neonatal sepsis (NS), a life-threatening condition, is characterized by organ dysfunction and is the most common cause of neonatal death. However, the pathogenesis of NS is unclear and the clinical inflammatory markers currently used are not ideal for diagnosis of NS. Thus, exploring the link between immune responses in NS pathogenesis, elucidating the molecular mechanisms involved, and identifying potential therapeutic targets is of great significance in clinical practice. Herein, our study aimed to explore immune-related genes in NS and identify potential diagnostic biomarkers. Datasets for patients with NS and healthy controls were downloaded from the GEO database; GSE69686 and GSE25504 were used as the analysis and validation datasets, respectively. Differentially expressed genes (DEGs) were identified and Gene Set Enrichment Analysis (GSEA) was performed to determine their biological functions. Composition of immune cells was determined and immune-related genes (IRGs) between the two clusters were identified and their metabolic pathways were determined. Key genes with correlation coefficient > 0.5 and p < 0.05 were selected as screening biomarkers. Logistic regression models were constructed based on the selected biomarkers, and the diagnostic models were validated.

Results
Fifty-two DEGs were identified, and GSEA indicated involvement in acute inflammatory response, bacterial detection, and regulation of macrophage activation. Most infiltrating immune cells, including activated CD8 + T cells, were significantly different in patients with NS compared to the healthy controls. Fifty-four IRGs were identified, and GSEA indicated involvement in immune response and macrophage activation and regulation of T cell activation. Diagnostic models of DEGs containing five genes (PROS1, TDRD9, RETN, LOC728401, and METTL7B) and IRG with one gene (NSUN7) constructed using LASSO algorithm were validated using the GPL6947 and GPL13667 subset datasets, respectively. The IRG model outperformed the DEG model. Additionally, statistical analysis suggested that risk scores may be related to gestational age and birth weight, regardless of sex.

Conclusions
We identified six IRGs as potential diagnostic biomarkers for NS and developed diagnostic models for NS. Our findings provide a new perspective for future research on NS pathogenesis.
Integration of omics studies indicates that species-dependent molecular mechanisms govern male fertility
Authors: Park Yoo-Jin , Pang Won-Ki , Pang Myung-Geol 
Published: March 2023

Abstract
Background
Comparative and comprehensive omics studies have recently been conducted to provide a comprehensive understanding of the biological mechanisms underlying infertility. However, because these huge omics datasets often contain irrelevant information, editing strategies for summarizing and filtering the data are necessary prerequisite steps for identifying biomarkers of male fertility. Here, we attempted to integrate omics data from spermatozoa with normal and below-normal fertility from boars and bulls, including transcriptomic, proteomic, and metabolomic data. Pathway enrichment analysis was conducted and visualized using g:Profiler, Cytoscape, EnrichmentMap, and AutoAnnotation to determine fertility-related biological functions according to species.

Results
In particular, gamete production and protein biogenesis-associated pathways were enriched in bull spermatozoa with below-normal fertility, whereas mitochondrial-associated metabolic pathways were enriched in boar spermatozoa with normal fertility. These results indicate that below-normal fertility may be determined by aberrant regulation of protein synthesis during spermatogenesis, and the modulation of reactive oxygen species generation to maintain capacitation and the acrosome reaction governs boar sperm fertility.

Conclusion
Overall, this approach demonstrated that distinct molecular pathways drive sperm fertility in mammals in a species-dependent manner. Moreover, we anticipate that searching for species-specific signaling pathways may aid in the discovery of fertility-related biomarkers within large omics datasets.
Gut microbiome is linked to functions of peripheral immune cells in transition cows during excessive lipolysis
Authors: Gu Fengfei , Zhu Senlin , Tang Yifan , Liu Xiaohan , Jia Minghui , Malmuthuge Nilusha , Valencak Teresa G. , McFadden Joseph W. , Liu Jian-Xin , Sun Hui-Zeng 
Published: March 2023

Abstract
Background
Postpartum dairy cows experiencing excessive lipolysis are prone to severe immunosuppression. Despite the extensive understanding of the gut microbial regulation of host immunity and metabolism, its role during excessive lipolysis in cows is largely unknown. Herein, we investigated the potential links between the gut microbiome and postpartum immunosuppression in periparturient dairy cows with excessive lipolysis using single immune cell transcriptome, 16S amplicon sequencing, metagenomics, and targeted metabolomics.

Results
The use of single-cell RNA sequencing identified 26 clusters that were annotated to 10 different immune cell types. Enrichment of functions of these clusters revealed a downregulation of functions in immune cells isolated from a cow with excessive lipolysis compared to a cow with low/normal lipolysis. The results of metagenomic sequencing and targeted metabolome analysis together revealed that secondary bile acid (SBA) biosynthesis was significantly activated in the cows with excessive lipolysis. Moreover, the relative abundance of gut Bacteroides sp. OF04 − 15BH, Paraprevotella clara, Paraprevotella xylaniphila, and Treponema sp. JC4 was mainly associated with SBA synthesis. The use of an integrated analysis showed that the reduction of plasma glycolithocholic acid and taurolithocholic acid could contribute to the immunosuppression of monocytes (CD14+MON) during excessive lipolysis by decreasing the expression of GPBAR1.

Conclusions
Our results suggest that alterations in the gut microbiota and their functions related to SBA synthesis suppressed the functions of monocytes during excessive lipolysis in transition dairy cows. Therefore, we concluded that altered microbial SBA synthesis during excessive lipolysis could lead to postpartum immunosuppression in transition cows.
JAK inhibition ameliorates bone destruction by simultaneously targeting mature osteoclasts and their precursors
Authors: Yari Shinya , Kikuta Junichi , Shigyo Hotaka , Miyamoto Yu , Okuzaki Daisuke , Furusawa Yuki , Minoshima Masafumi , Kikuchi Kazuya , Ishii Masaru 
Published: March 2023

Abstract
Background
Rheumatoid arthritis (RA) is characterized by chronic inflammation and resultant cartilage/bone destruction because of aberrantly activated osteoclasts. Recently, novel treatments with several Janus kinase (JAK) inhibitors have been shown to successfully ameliorate arthritis-related inflammation and bone erosion, although their mechanisms of action for limiting bone destruction remain unclear. Here, we examined the effects of a JAK inhibitor on mature osteoclasts and their precursors by intravital multiphoton imaging.

Methods
Inflammatory bone destruction was induced by local injection of lipopolysaccharides into transgenic mice carrying reporters for mature osteoclasts or their precursors. Mice were treated with the JAK inhibitor, ABT-317, which selectively inhibits the activation of JAK1, and then subjected to intravital imaging with multiphoton microscopy. We also used RNA sequencing (RNA-Seq) analysis to investigate the molecular mechanism underlying the effects of the JAK inhibitor on osteoclasts.

Results
The JAK inhibitor, ABT-317, suppressed bone resorption by blocking the function of mature osteoclasts and by targeting the migratory behaviors of osteoclast precursors to the bone surface. Further exhaustive RNA-Seq analysis demonstrated that Ccr1 expression on osteoclast precursors was suppressed in the JAK inhibitor-treated mice; the CCR1 antagonist, J-113863, altered the migratory behaviors of osteoclast precursors, which led to the inhibition of bone destruction under inflammatory conditions.

Conclusions
This is the first study to determine the pharmacological actions by which a JAK inhibitor blocks bone destruction under inflammatory conditions; this inhibition is beneficial because of its dual effects on both mature osteoclasts and immature osteoclast precursors.
Acceptability and feasibility of a mobile health application for enhancing public private mix for TB care among healthcare Workers in Southwestern Uganda
Authors: Tumuhimbise Wilson , Atwine Daniel , Kaggwa Fred , Musiimenta Angella 
Published: March 2023

Abstract
Background
Mobile health interventions can potentially enhance public–private linkage for tuberculosis care. However, evidence about their acceptability and feasibility is lacking. This study sought to assess the initial acceptability and feasibility of a mobile health application for following up on presumptive tuberculosis patients referred from private to public hospitals. Twenty-two healthcare workers from three private hospitals and a public hospital in southwestern Uganda received the Tuuka mobile application for 1 month for testing. Testing focused on referring patients by healthcare workers from private hospitals and receiving referred patients by public healthcare workers and sending SMS reminders to the referred patients by filling out the digital referral forms inbuilt within the app. Study participants participated in qualitative semi-structured in-depth interviews on the acceptability and feasibility of this app. An inductive, content analytic approach, framed by the unified theory of acceptance and use of technology model, was used to analyze qualitative data. Quantitative feasibility metrics and the quantitative assessment of acceptability were analyzed descriptively using STATA.

Results
Healthcare workers found the Tuuka application acceptable and feasible, with a mean total system usability scale score of 98 (SD 1.97). The majority believed that the app would help them make quicker medical decisions (91%), communicate with other healthcare workers (96%), facilitate partnerships with other hospitals (100%), and enhance quick TB case notification (96%). The application was perceived to be useful in reminding referred patients to adhere to referral appointments, notifying public hospital healthcare workers about the incoming referred patients, facilitating communication across facilities, and enhancing patient-based care.

Conclusion
The Tuuka mobile health application is acceptable and feasible for following up on referred presumptive tuberculosis patients referred from private to public hospitals in southwestern Uganda. Future efforts should focus on incorporating incentives to motivate and enable sustained use among healthcare workers.
Estimating two groups of fracture weaknesses using azimuthal differences in partially incidence-angle-stacked seismic amplitudes
Authors: Chen Huaizhen , Innanen Kristopher A. 
Published: March 2023

Geophysical and geologic data, e.g., results obtained using rock cores, outcrops, and borehole images, reveal the presence of multiple sets of fractures in rock. To analyze how fracture interactions affect seismic anisotropy and dispersion, we consider an effective model that contains two sets of orthogonal fractures. In seismic amplitude analysis, we focus on the case of subsurface target zones containing a fracture network composed of primary and secondary fracture sets. Focusing on gas-bearing rocks with small fracture densities, we formulate simplified stiffness parameters in terms of two groups of fracture weaknesses, which are related to the primary and secondary fractures, respectively. Using the simplified stiffness parameters, we derive the PP-wave reflection coefficient and the azimuthal elastic impedance (AEI) as functions of the two groups of normal and tangential fracture weaknesses. Based on the derived PP-wave reflection coefficient and AEI, we propose a method and workflow in which the azimuthal variations of the partial incidence-angle-stacked seismic data are used to estimate the AEI and differences in AEI (which we refer to as DEI) is input to a nonlinear inversion for two groups of fracture weaknesses. In the nonlinear inversion, the initial values of fracture weaknesses are obtained based on a two-term approximation of the PP-wave reflection coefficient. First- and second-order derivatives of DEI with respect to fracture weakness parameters are calculated to generate the update in the unknown parameter vector. Synthetic seismic gathers with varying signal-to-noise ratios are used to validate the robustness of the estimation. Applying the inversion method to a real data set, we obtain what we interpret to be reliable fracture weakness estimates that produce azimuthal amplitude differences matching those extracted from real seismic data. The results provide a potential tool for determining if two sets of fractures have developed in a reservoir.
Neoadjuvant Arterial Embolization of Spine Metastases Associated With Improved Local Control in Patients Receiving Surgical Decompression and Stereotactic Body Radiotherapy
Authors: Damante Mark A. , Gibbs David , Dibs Khaled , Palmer Joshua D. , Raval Raju , Scharschmidt Thomas , Chakravarti Arnab , Bourekas Eric , Boulter Daniel , Thomas Evan , Grecula John , Beyer Sasha , Xu David , Nimjee Shahid , Youssef Patrick , Lonser Russell , Blakaj Dukagjin M. , Elder J. Bradley 
Published: March 2023

BACKGROUND:
Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control.

OBJECTIVE:
To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT).

METHOD:
A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level.

RESULTS:
Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort (P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization (P < .001).

CONCLUSION:
Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.
Dynamics of horizontal walking and vertical climbing in the Australian green tree frog (Ranoidea caerulea)
Authors: Young Melody W. , Flaim Nicholas D. , Yarbro Johnathan , Ragupathi Ashwin , Guru Navjot , Dickinson Edwin , Granatosky Michael C. 
Published: March 2023

ABSTRACTDespite the high mechanical demands associated with climbing, the ability to ascend vertically has evolved independently in most major animal lineages. However, little is known about the kinetics, mechanical energy profiles or spatiotemporal gait characteristics of this locomotor mode. In this study, we explored the dynamics of horizontal locomotion and vertical climbing on both flat substrates and narrow poles in five Australian green tree frogs (Ranoidea caerulea). Vertical climbing is associated with slow, deliberate movements (i.e. reduced speed and stride frequency and increased duty factors) and propulsive fore–aft impulses in both the forelimb and hindlimb. By comparison, horizontal walking was characterized by a braking forelimb and a propulsive hindlimb. In the normal plane, tree frogs mirrored other taxa in exhibiting a net pulling forelimb and a net pushing hindlimb during vertical climbing. In terms of mechanical energy, tree frogs matched theoretical predictions of climbing dynamics (i.e. the total mechanical energetic cost of vertical climbing was predominantly driven by potential energy, with negligible kinetic contributions). Utilizing power as a means of estimating efficiency, we also demonstrate that Australian green tree frogs show total mechanical power costs only slightly above the minimum mechanical power necessary to climb, highlighting their highly effective locomotor mechanics. This study provides new data on climbing dynamics in a slow-moving arboreal tetrapod and raises new testable hypotheses about how natural selection can act upon a locomotor behavior that is notably constrained by external physical forces.
Genetic diversity and population structure of Capitulum mitella (Linnaeus, 1767) in Fujian (China) revealed by mtDNA COI sequences
Authors: Sun Rouxin , Zhang Zhilan , Wu Qiong , Xiang Peng , Wang Yanguo , Xing Bingpeng 
Published: March 2023

Background: Capitulum mitella is a widely distributed and ecologically important stalked barnacle that settles extensively on rocky shores. This species contributes to the structural complexity of intertidal habitats and plays a critical role in the marine ecosystem. This study aimed to reveal the genetic diversity and population structure of C. mitella by analyzing the mitochondrial cytochrome oxidase I (COI) gene. Methods: A 683bp fragment of the COI gene was sequenced from 390 individuals sampled from six localities in Fujian, China. Results: A total of 84 distinct haplotypes were identified through the analysis of 82 polymorphic sites, resulting in an average haplotype diversity (h) of 0.660 and nucleotide diversity (π) of 0.00182. Analysis of molecular variance (AMOVA) and pairwise FST statistics showed no significant population structure. Neutrality tests and mismatch distributions provided evidence of recent population expansion for the species. Conclusions: We suggest that the species' high dispersal ability, and ocean currents coupled with limited physical barriers in the region, contribute to its current phylogeographic structure. These findings enhance our comprehension of the genetic diversity and population structure of C. mitella, providing valuable insights for future conservation efforts.
DAY-CASE PARTIAL AND TOTAL KNEE ARTHROPLASTY: A DISTRICT GENERAL HOSPITAL EXPERIENCE
Authors: Mathai N. , Guro R. , Chandratreya A. , Kotwal R. 
Published: March 2023

There has been a significant increase in the demand for arthroplasty as a result of the Covid 19 pandemic and lack of beds on the green pathway. The average length of in-hospital stay following knee replacements has been successfully reduced over the years following introduction and adoption of enhanced recovery protocols. Day case arthroplasty has the potential to be efficient as well as cost-effective. We present our day case pathway for elective knee arthroplasty and early results of its adoption at a district general hospital.Our pathway was developed through a multidisciplinary input from surgeons, anaesthetists, physiotherapists, nursing staff, administrative staff, surgical care practitioners and pharmacists. Inclusion criteria were defined to identify patients suitable for cay case arthroplasty. Results of 32 patients who underwent day case partial and total knee replacement at our institution between 2018 to 2022 are presented.31 out of 32 (97%) were discharged safely on the day of surgery. Patients were discharged at a mean of 7 hours following surgery. There were no re-admissions following discharge. There were no surgical complications at a mean follow-up of 2 years. Patient feedback revealed high levels of satisfaction and that they would recommend the pathway to others. Cost analysis revealed savings towards bed costs.Our early results demonstrate day case knee arthroplasty to be safe and cost effective. With limited resources to tackle the enormous backlog of arthroplasty, it offers the potential to make theatre utilization efficient.