bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demographic Features and Laboratory Parameters Among Hospitalized Vaccinated Patients With COVID-19 in Istanbul, Turkey
Authors: Yagci Ayşegul Karahasan , Alci Gamze , Guncu Mehmet Mucahit , Yilmaz Omer Bugrahan , Tekin Eranalp , Cakir Safa Emre , Cebe Burak , Ozturk Cem , Sirikci Onder 
Published: April 2023

Background
The number of COVID-19 cases has been decreasing recently, and the restrictions are waived in many countries. The data about vaccine efficacy are essential to be prepared for the future even if the pandemic ends and the disease becomes endemic.

Aims
The aim of this study was to define demographic and laboratory data for disease severity among vaccinated COVID-19 cases who were hospitalized.

Study Design
This is a retrospective cohort study.

Methods
SARS-CoV-2 polymerase chain reaction–positive patients who were fully vaccinated (2 doses of vaccines and 3 doses of vaccines) and had been hospitalized at least 15 days after the last vaccine dose were enrolled in this study. Patients' data including laboratory parameters were retrieved, and descriptive statistics and comparison of variables were calculated.

Results
Between September 1, 2021, and February 28, 2022, 685 patients (mean age, 67.84 years; 50.8% female) were hospitalized. Inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac) had been administered to 467 of the patients (68.4%), BNT162b2 mRNA vaccine (Pfizer-Pfizer-BioNTech) had been administered to 107 of the patients (15.6%), and to 111 of the patients (16%), a combination of 2 vaccines had been administered. At least 1 comorbidity was present in 160 participants (23%) and more than 4 comorbidities in 46 patients (6.6%). The most common comorbidity was hypertension (349, 50.2%). The presence of comorbidities was significantly higher in patients having 3 doses of vaccine. Increased ferritin levels were determined in 56.4% of the patients, increased D-dimer levels in 69.9% of the patients, increased C-reactive protein levels in 79.7% of the patients, and increased procalcitonin levels in 61.5% of the patients. A total of 36.4% of the patients had decreased lymphocyte counts, 20% had low lymphocyte/monocyte ratio, and 22% had decreased neutrophil/lymphocyte ratio. The only parameter that was significantly higher in patients having 3 vaccine doses was procalcitonin. Mean duration of hospitalization was 9.68 ± 7.29 days. In the CoronaVac and Pfizer-BioNTech groups, 68.5% and 21.4%, respectively, of the patients were older than 65 years. Seventeen (3.6%) patients in the CoronaVac group, 6 (5.4%) patients in the combination group, and 3 (2.8%) patients in Pfizer-BioNTech group had been admitted to the intensive care unit. Mortality rate was 0.3% (2 of 685 patients).

Conclusions
The incidence of severe COVID-19 disease among fully vaccinated patients is low even in the presence of comorbidities, older age, and presence of abnormal laboratory parameters, regardless of the vaccine type.
Extended pelvic lymph node dissection in muscle invasive bladder cancer
Authors: Katims Andrew B. , Bochner Bernard H. 
Published: April 2023

Purpose of review
Bilateral pelvic lymph node dissection (PLND) at the time of radical cystectomy (RC) provides important staging information and oncologic benefit in patients with bladder cancer. The optimal extent of the PLND remains controversial. Our aim is to highlight nodal mapping studies and the data that guides optimization of both staging and oncologic outcomes. We then review contemporary randomized trials studying the extent of PLND.

Recent findings
A recent randomized trial (RCT) powered for a 15% improvement in recurrence-free survival (RFS) of extended (e) over limited (l)PLND was completed but failed to identify this large difference in outcome. Concerns over study design limit the ability to interpret the oncologic results. Importantly, ePLND minimally changed surgical morbidity. An ongoing, similar RCT (SWOG S1011) powered to detect a 10% difference in RFS has completed accrual, but no published outcomes are available.

Summary
RC and ePLND can provide cure in 33% of LN positive bladder cancer patients. Current data support a 5% improvement in RFS if ePLND is routinely used in MIBC patients. Two randomized trials powered to identify much larger (15 and 10%) improvements in RFS are unlikely to identify such an ambitious benefit by extending the PLND.
Effect of the olive leaf extract in chronic spinal cord injury model: an experimental research
Authors: Nasution Iqbal P.A. , Ibrahim Sabri , Riawan Wibi 
Published: April 2023

Introduction:
Posttraumatic myelopathy is defined as a spinal cord injury (SCI) that results in varying degrees of motor and sensory deficits. The degree of ‘secondary damage,’ which is caused by a variety of cellular, molecular, and biochemical cascades is linked to the outcome of SCI. According to research, the beneficial effects of oleuropein and its derivatives have been linked to radical scavenging/antioxidant actions and anti-inflammatory effects.

Materials and Methods:
This study was divided into six groups: control negative (sham-operated) group, control positive 1 and 2 (early chronic and chronic), treatment groups 1, 2, and 3 (prophylactic, concomitant, and late). Olive leaf extract (OLE) given dose was 350 mg/kg body weight. Blood was taken from the left corotic artery before the animals were terminated, seromarker assessment, enzyme-linked immunosorbent assay of IL-6, TNF-α, brain-derived neurotrophic factor (BDNF), and assessment of functional motoric outcome before the animal was terminated.

Results:
Chronic spinal cord compression increased serum levels of IL-6, TNF-α, and decreased serum level of BDNF. OLE 350 mg/kg body weight decreased serum levels of IL-6, TNF-α and increased functional motoric outcome, especially in prophylactic and concomitant therapy.

Discussion:
These findings indicate that OLE may be effective in protecting chronic SCI model.

Conclusion:
Oleuropein has a potential effect to reduce the IL-6 and TNF-α in rabbit model of SCI, and the BDNF value risen after the administration of Oleuropein.
DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation
Authors: Mullen Nicholas J. , Shukla Surendra K. , Thakur Ravi , Kollala Sai Sundeep , Wang Dezhen , Chaika Nina , Santana Juan F. , Miklavcic William R. , LaBreck Drew A. , Mallareddy Jayapal Reddy , Price David H. , Natarajan Amarnath , Mehla Kamiya , Sykes David B. , Hollingsworth Michael A. , Singh Pankaj K. 
Published: April 2023

AbstractPyrimidine nucleotide biosynthesis is a druggable metabolic dependency of cancer cells, and chemotherapy agents targeting pyrimidine metabolism are the backbone of treatment for many cancers. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine biosynthesis pathway that can be targeted by clinically approved inhibitors. However, despite robust preclinical anticancer efficacy, DHODH inhibitors have shown limited single-agent activity in phase 1 and 2 clinical trials. Therefore, novel combination therapy strategies are necessary to realize the potential of these drugs. To search for therapeutic vulnerabilities induced by DHODH inhibition, we examined gene expression changes in cancer cells treated with the potent and selective DHODH inhibitor brequinar (BQ). This revealed that BQ treatment causes upregulation of antigen presentation pathway genes and cell surface MHC class I expression. Mechanistic studies showed that this effect is 1) strictly dependent on pyrimidine nucleotide depletion, 2) independent of canonical antigen presentation pathway transcriptional regulators, and 3) mediated by RNA polymerase II elongation control by positive transcription elongation factor B (P-TEFb). Furthermore, BQ showed impressive single-agent efficacy in the immunocompetent B16F10 melanoma model, and combination treatment with BQ and dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1) significantly prolonged mouse survival compared to either therapy alone. Our results have important implications for the clinical development of DHODH inhibitors and provide a rationale for combination therapy with BQ and immune checkpoint blockade.
Algal symbioses with fire corals demonstrate host genotype specificity and niche adaptation at subspecies resolution
Authors: Dubé Caroline E , Hume Benjamin CC , Boissin Emilie , Mercière Alexandre , Bourmaud Chloé A-F , Ziegler Maren , Voolstra Christian R 
Published: April 2023

AbstractCorals share an intimate relationship with photosynthetic dinoflagellates that contribute to the biology of the emerging metaorganism. While many coral-algal associations exhibit high host fidelity, the extent of this specificity under environmental change remains to be fully understood and is a prerequisite to forecasting the adaptive potential of this obligate symbiosis. Here, we disentangled the contribution of host genotype and environment on governing coral-algae associations by working at subspecies resolution. We used fine-scale genotyping of algal symbionts from 198 fire coral colonies (Milleporacf.platyphylla)that map to ten distinct sexually produced clonal host genotypes across three environmentally distinct reef habitats. Based on microalgal ITS2 genotyping, we show that algal-host specificity extends down to the Symbiodiniaceae subspecies level in a natural reef environment. Closely relatedSymbiodinium(A7)-dominated algal assemblages almost perfectly mapped to fire coral host genotype. Furthermore, identification of host genotype- and habitat-specificSymbiodiniumalga suggest the presence of algal phenotypic diversity even at this taxonomic resolution (i.e., withinSymbiodiniumA7), which may aid environmental niche adaptation of the metaorganism. Our results suggest that the here-identifiedMillepora-Symbiodiniumassociations are co-evolved to match their prevailing environment. Thus, despite the presence of rarer host generalistCladocopiumalgae, scope for environmentally induced modification of the cnidarian-algal association is likely constrained by host genotype.
Effects of VCD-induced ovarian failure on single muscle fiber contractility in a mouse model of menopause
Authors: Mashouri Parastoo , Saboune Jinan , Glen Pyle W. , Power Geoffrey A. 
Published: April 2023

AbstractObjectiveMenopause is associated with impairments in muscle contractile function. The temporal and mechanistic basis of this dysfunction are not known. Using a mouse model of menopause we identified how gradual ovarian failure affects single muscle fiber contractility.Study designMice were injected with VCD over 15 days and ovarian failure developed over 120 days. Mice were then sacrificed and slow-type soleus (SOL) and fast-type extensor digitorum longus (EDL) muscles were dissected and chemically permeabilized for mechanical testing.Main outcome measuresMuscle fiber contractility was assessed via: force, rate of force redevelopment, instantaneous stiffness, and calcium sensitivity across three relative force levels (pCa10,pCa50,pCa90).ResultsPeak force and cross-sectional area (CSA) of the SOL were ∼33% and ∼24% greater in the VCD group as compared with controls (P<0.05), respectively, with no differences in force produced by the EDL fibers across groups (P>0.05). Upon normalizing force to CSA there were no differences across groups (P>0.05). Rate of force development was ∼33% faster for SOL in the VCD group compared to control. Ca2+sensitivity did not differ between groups for either muscle at pCa50(P>0.05). In the VCD group, Ca2+sensitivity was higher for EDL, but lower for SOL at pCa10and pCa90(P<0.05), respectively.ConclusionsIn our mouse model of menopause, alterations to muscle contractility were much less evident as compared with ovariectomized models. This divergence across models highlights the importance of better approximating the natural trajectory of menopause during and after the transitional phase of ovarian failure on neuromuscular function.
Characterization of mitotic phenotypes associated with a MYC synthetic lethal compound
Authors: Shi Qiong , Liu Xuemei , Kalashova Julia , Yang Chenglu , Li Hongmei , Long Yan , Zhang Ting , Zhang Shenqiu , Lv Gang , Huang Jian , Liu Hong , Zhang Jing , Allen Thaddeus D. , Yang Dun 
Published: April 2023

AbstractTherapeutic targeting of MYC directly has proven difficult, but several means to target MYC indirectly using a synthetic lethal drug approach have been proposed. Synthetic lethal approaches for MYC have sought to take advantage of vulnerabilities MYC imposes related to either metabolic reprogramming, apoptotic signaling or the cycling of cancer cells. Here, we describe in detail the cell division phenotypes induced by a MYC synthetic lethal compound, dimethylfasudil (diMF). DiMF is a known ROCK inhibitor, but structurally related ROCK inhibitors are not synthetic lethal with MYC, so the activity of diMF is not related to blockade of this family of kinases. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe-induced death and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as CENP-F, failed to localize at the metaphase plate, confirming a deficit in centromere assembly. This, presumably, contributed to the development of segregation anomalies in diMF-treated cells. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the centralspindlin complex and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death phenotypes induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.
Inter-user comparison for quantification of superparamagnetic iron oxides with magnetic particle imaging across two institutions highlights a need for standardized approaches
Authors: Good Hayden J. , Sehl Olivia C. , Gevaert Julia J. , Yu Bo , Berih Maryam A. , Montero Sebastian A. , Rinaldi-Ramos Carlos M. , Foster Paula J. 
Published: April 2023

AbstractPurposeMagnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions.ProceduresSix users (3 from each institute) imaged a known amount of Vivotrax+ (10 μg Fe), diluted in a small (10 μL) or large (500 μL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users x triplicate samples x 2 sample volumes x 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax+ quantification, and ROI selection was compared across users, within and across institutions.ResultsMPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax+. Overall quantification yielded measurements that were within ± 20% from ground truth, however SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples.ConclusionsThis study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental set up, image acquisition parameters, and ROI selection analysis.
How Connecting the Legs with a Spring Improves Human Running Economy
Authors: Stingel Jon P. , Hicks Jennifer L. , Uhlrich Scott D. , Delp Scott L. 
Published: April 2023

AbstractConnecting the legs with a spring attached to the shoelaces reduces the energy cost of running, but how the spring reduces the energy burden of individual muscles remains unknown. We generated muscle-driven simulations of seven individuals running with and without the spring to discern whether savings occurred during the stance phase or the swing phase, and to identify which muscles contributed to energy savings. We computed differences in muscle-level energy consumption, muscle activations, and changes in muscle-fiber velocity and force between running with and without the spring. Across participants, running with the spring reduced the measured rate of energy expenditure by 0.9 W/kg (8.3%). Simulations predicted a 1.4 W/kg (12.0%) reduction in the average rate of energy expenditure and correctly identified that the spring reduced rates of energy expenditure for all participants. Simulations showed most of the savings occurred during stance (1.5 W/kg), though the rate of energy expenditure was also reduced during swing (0.3 W/kg). The energetic savings were distributed across the quadriceps, hip flexor, hip abductor, hamstring, hip adductor, and hip extensor muscle groups, whereas no changes in the rate of energy expenditure were observed in the plantarflexor or dorsiflexor muscles. Energetic savings were facilitated by reductions in the rate of mechanical work performed by muscles and their estimated rate of heat production. The simulations provide insight into muscle-level changes that occur when utilizing an assistive device and the mechanisms by which a spring connecting the legs improves running economy.
Meta-analysis of gene activity (MAGA) contributions and correlation with gene expression, through GAGAM
Authors: Martini Lorenzo , Bardini Roberta , Savino Alessandro , Di Carlo Stefano 
Published: April 2023

AbstractIt is well-known how sequencing technologies propelled cellular biology research in the latest years, giving an incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with Single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to perform the mentioned sequencing modalities simultaneously on the same cells. Yet, there still needs to be a clear and dedicated way to analyze this multi-modal data. One of the current methods is to calculate the Gene Activity Matrix, which summarizes the accessibility of the genes at the genomic level, to have a more direct link with the transcriptomic data. However, this concept is not well-defined, and it is unclear how various accessible regions impact the expression of the genes. Therefore, this work presents a meta-analysis of the Gene Activity matrix based on the Genomic-Annotated Gene Activity Matrix model, aiming to investigate the different influences of its contributions on the activity and their correlation with the expression. This allows having a better grasp on how the different functional regions of the genome affect not only the activity but also the expression of the genes.
Aberrant centrosome biogenesis disrupts nephron progenitor cell renewal and fate resulting in fibrocystic kidney disease
Authors: Cheng Tao , Agwu Chidera , Shim Kyuhwan , Wang Baolin , Jain Sanjay , Mahjoub Moe R. 
Published: April 2023

SummaryMutations that disrupt centrosome structure or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet, it remains unclear how mutations in proteins essential for centrosome biogenesis impact embryonic kidney development. Here, we examined the consequences of conditional deletion of a ciliopathy gene,Cep120, in the two nephron progenitor niches of the embryonic kidney.Cep120loss led to reduced abundance of both metanephric mesenchyme and ureteric bud progenitor populations. This was due to a combination of delayed mitosis, increased apoptosis, and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis, and decline in filtration function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in pathways essential for branching morphogenesis, cystogenesis and fibrosis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney development, and identifies new therapeutic targets for renal centrosomopathies.Graphical AbstractHighlightsDefective centrosome biogenesis in nephron progenitors causes:Reduced abundance of metanephric mesenchyme and premature differentiation into tubular structuresAbnormal branching morphogenesis leading to reduced nephron endowment and smaller kidneysChanges in cell-autonomous and paracrine signaling that drive cystogenesis and fibrosisUnique cellular and developmental defects when compared to Pkd1 knockout models
Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate
Authors: Ertunc Onur , Smearman Erica , Zheng Qizhi , Hicks Jessica L. , Brosnan-Cashman Jacqueline A. , Jones Tracy , Gomes-Alexandre Carolina , Trabzonlu Levent , Meeker Alan K. , De Marzo Angelo M. , Heaphy Christopher M. 
Published: April 2023

ABSTRACTTelomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenicin situhybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay (“Telo-CISH”) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.