bluuebunny/crossref_metadata_2025 huggingface dataset:
Ramification of COVID-19 pandemic : Occurrence and impact of fungal infections in a tertiary care hospital
Authors: Kaur Ravinder , Rawat Deepti , William Ashish , Singh Pradeep Kumar , Kandir Neelam S.S. , Sharma Akanksha
Published: June 2023

Coronavirus disease 2019 (COVID-19) pandemic has been prevailing for more than a year associated with increased number of opportunistic invasive fungal infections in patients who have been critically ill or immunocompromised. In this retrospective study, details of various clinical specimens received from suspected patients of fungal infections were processed according to standard protocol were studied. The fungal infections were present in 64% (51/79) COVID-19 positive patients and 43% (163/381) COVID-19 negative patients) during the year 2021 during the second wave of COVID-19. Among COVID-19 infected patients, the fungal infection mostly observed was Candidiasis (63%) followed by Aspergillosis (15% ) and Mucormycosis (6%). The maximum samples positive in COVID-19 patients were urine samples followed by Serum (for Aspergillus Galactomannan). Among the urine and respiratory samples (BAL, Tracheal aspirate, Sputum) in COVID-19 positive patients, maximum positivity of Candida species was seen. Mucormycosis in COVID-19 positive patients was isolated in Nasal samples followed by tissue sample with Rhizopus arrhizus and Rhizopus homothallicus. There has been an increase in fungal co-infections during the COVID-19 pandemic which is a matter of great concern. Early diagnosis is essential for effective management of these patients.
Detection of wolf spider courtship signals against complex chromatic backgrounds by intended and unintended receivers
Authors: Uetz George W , Gilbert Rachel , Wilson Rebecca , Mann Jacqueline , Clark David L.
Published: June 2023

We used video digitization and playback of courting male Schizocosa ocreata wolf spiders to examine responses of intended receivers and eavesdroppers viewing manipulated spider color displayed against background treatments of complex litter with different chromatic contrast. Intended receivers (female S. ocreata) were more likely to detect males with higher background intensity contrast, while a different pattern for receptivity suggests chromatic contrast matters more for mate recognition. Social eavesdroppers (conspecific males) were similar but had a significant interaction of spider color x background, suggesting possible differences in color perception between sexes. Interceptive eavesdroppers (predators) differed across taxa in some respects but were similar in others. Vertebrates (toads) were quicker to orient than invertebrates (spider predators). Toads took longer to respond to control spiders on complex color backgrounds but were quicker with the same spider against complex greyscale backgrounds. Color differences among prey stimuli appear to be less important than contrast for both toads and wolf spiders with dichromatic vision. However, color of the prey spider stimulus matters more for jumping spiders with trichromatic vision, as they respond more quickly to natural color and RGB average color than gray monochrome stimuli. Analyses of chromatic and luminance intensity contrast values for spiders and backgrounds suggest that for both intended female receivers and eavesdroppers, intensity and chromatic contrast influence detection and mate recognition in complex and subtle ways. These results support the hypothesis that receivers with different visual sensory capacities vary in response to color and contrast of courting male spiders against complex backgrounds.
C-H-activated Csp2-Csp3 diastereoselective gridization enables ultraviolet-emitting stereo-molecular nanohydrocarbons with mulitple H•••H interactions
Authors: Wei Ying , Zhong Chunxiao , Sun Yue , Ma Shuwei , Wu Xiangping , Yan Yongxia , Yang Lei , Khodov Ilya A. , Ge Jiaoyang , Li Yang , Lin Dongqing , Wang Yongxia , Bao Qiujing , Zhang He , Wang Shasha , Song Juan , Huang Wei , Xie Linghai
Published: June 2023

Gridization is an emerging molecular integration technology that enables the creation of cross-scale materials by facilitating the generation and their networks of molecular nanohydrocarbon through precise and stepwise linkages. Despite the fact that Friedel-Crafts gridization of fluorenols is powerful, direct linkage among fluorene molecules is challenging owing to the limitation of the Csp2-Csp3 coupling reactions. Herein, we reported an achiral Pd-PPh3-cataylized diastereoselective (> 99:1 d.r.) gridization based on the C-H-activation at the fluorene the 9-position to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). The cis-cis-TWGs exhibit unique intramolecular and multiple H•••H interactions with a low field shift to 8.51 ppm, which is rare for hydrocarbon aromatics. Furthermore, these non-conjugated nanogrids show ultraviolet emission behaviors with emission peaks at 361-393 nm in film and 356-373 nm in crystal state, representing the first report of ultraviolet-emitting macrocycles. These nanogrids offer potential nanoscafflolds for ultraviolet organic light-emitting diodes and lasing applications.
BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: A cohort study
Authors: Yung Chee Fu , Bert Nina Le , Kam Kai Qian , Saffari Seyed Ehsan , Tan Chee Wah , Mah Yun Yan , Zhang Jinyan , Yeoh Aileen Ying-Yan , Zhu Feng , Hariharaputran Smrithi , Chong Chia Yin , Bertoletti Antonio , Wang Linfa
Published: June 2023

There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2(10mcg) vaccination cohort study of healthy children 5–11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD: 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR:16.5 to 30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.
Joint toxicity of Cadmium (II) and microplastic leachates on wheat seed germination and seedling growth
Authors: Du Ling , Wu Dongming , Yang Xi , Xu Li , Tian Xu , Li Youping , Liu Yanmei
Published: June 2023

Cadmium (Cd) and microplastics are widely distributed in soil and pose potential threats to agricultural production and human health. However, the joint toxicity of Cd and microplastics on crop growth remain largely unknown. In this study, the toxic effects of Cd2+ solution and two kinds of microplastic leachates, polyvinyl chloride (PVC) and low-density polyethylene (LDPE), on wheat seeds germination and seedlings’ growth were explored under the single and combined conditions. The results showed that Cd2+ solution and two kinds of microplastic leachates stimulated wheat seeds germination process but inhibited the germination rate by 0–8.6%. The combined treatments promoted wheat seeds germination but inhibited the growth of wheat seedlings on different degree. In especial, the combination of 2.0 mg L-1 Cd2+ and 1.0 mgC L-1 PVC could promote both wheat seeds germination and seedlings’ growth, but they synergistically increased the antioxidant enzyme activity of seedlings. The physiological and biochemical indicators showed that the possible mechanism through which Cd2+ and microplastics leachates and their combination affected wheat seedlings involved oxidative stress. The toxicity of the PVC leachate to wheat seedlings was stronger than LDPE leachate. The addition of Cd2+ could alleviate the toxicity of PVC leachate on wheat seedlings, and reduce the toxicity of LDPE leachate on wheat seedlings under the same concentration class combinations but aggravated stress under different concentration class combinations, consistent with the effect on wheat seedlings’ growth. Overall, our study has important implications for the joint toxicity of Cd2+ solution and microplastic leachates in agriculture.
Assessment of the wind power density over South America simulated by CMIP6 models in the present and future climate
Authors: Ferreira Glauber , Reboita Michelle , Ribeiro João Gabriel , Carvalho Vanessa , Santiago Maria , Silva Pedro , Baldoni Thales , Souza Christie
Published: June 2023

Expanding the South American renewable energy matrix to ensure more sustainable socio-economic development, mitigate the climate change effects, and meet the targets set in the Paris Agreement is crucial. Hence, this study sought to estimate South America’s wind speed and wind power density alterations projected by eight global climate models (GCMs) from Coupled Model Intercomparison Project – Phase 6 (CMIP6). To this end, we applied statistical downscaling and bias correction to the GCMs outputs through the Quantile Delta Mapping method and assessed the projected changes in wind power in future climate under the Shared Socioeconomic Pathways (SSPs) SSP2-4.5 and SSP5-8.5 emission scenarios. ERA5 reanalysis data from 1995–2014 validated the models’ historical simulations. The CMIP6 multimodel ensemble indicated an approximate 25–50% increase in wind power density in sectors such as Northeast and South Brazil and growing wind power in regions such as Argentine Patagonia, northern Venezuela, and portions of Uruguay, Bolivia, and Paraguay. Estimates of the wind power growth for the 21st century in those regions reiterated their potential performance in the historical period. For the SSP5-8.5 emission scenario, the ensemble projections indicated even more favorable wind power conditions in the sectors mentioned. However, individual projections of wind intensity anomalies obtained by each ensemble member showed a large spread among the GCMs, evidencing the uncertainties associated with the prospects of change in wind power on the continent. Furthermore, this study has presented a first analysis of CMIP6 projections for South American wind power generation, providing relevant information to the energy sector decision-makers.
Synthesis and Use of Nano Particles for Enhancing the Self-Cleaning Effects in White-Cement
Authors: Alshoaibi Adil , Hussain Fayaz , Aslam Muhammad , Zubairi Hareem , Aijaz Anabia , Majeeed Faryal , Khan Iqra
Published: June 2023

A major ingredient of concrete, tiles and other materials used for architectural and decorative purposes is white cement. Self-cleaning would be a sustainable and environmental-friendly approach to resolve the cleaning issues of building surfaces as well as to overcome the cost of time, energy, labour and materials. So this study has explored the synthesis of anatase-TiO2, Ag and ZnO nanoparticles, and their photo-catalytical properties to enhance the self-cleaning effects in white-cement at different ratios of composition. The doped formulations were mixed and coated on bricks to check the ink-stains degradation concerning the time under sunlight exposure concerning the time. The self-cleaning ability of prepared samples was evaluated under UV radiations from sunlight. - The white cement containing TiO2 co-doped with 0.2% Ag and 0.2% ZnO, mixed into the cement in a ratio of 0.2 (co-doped TiO2 to Cement) has proved to be the best combination. This ratio combination has also recorded the maximum dye (ink) degradation, the highest rate of absorption, and enhanced the degree of whiteness as compared to the remaining samples. They were characterized by XRD, UV Spectroscopy and Stereo micrographs and the maximum degradation is obtained in the 0 TiO2 co-doped with 0.2% Ag and 0.2% ZnO samples.
Study of biochar for salinity adsorption in barly plant
Authors: Norolahi Zahra , farasati masumeh , moghaddam ali nakhzari
Published: June 2023

The aim of research was investigation of biochar effect on reducing of salinity in mung bean plant. The experiment was performed in a randomized complete block design with three replications and three treatments of saline, non-saline and saline + biochar. A silty soil was used for the plant substrate while calcium chloride and sodium chloride salts were employed in order to create the salinity levels in it. The results of analysis variance associated with the studied traits showed that the simple effects of salinity and plant organs as well as the interaction of salinity×plant organs on the calcium, magnesium, chlorine, sodium, potassium levels are significant at a level of 1%. Also, the results of comparing the mean interaction of salinity×organ indicated that the highest calcium content in most cases is associated with leaf. The biochar consumption has been found to reduce the calcium absorption at high salinity in leaves and roots and increase it in the stem and pod. Increasing the calcium chloride and sodium chloride salinities in plant organs, the concentration of potassium decreased compared to calcium and with increasing salinity levels, the concentration of all mentioned elements increased in most treatments. According to the results, effect of organ, salinity and organ× salinity on all characteristics was significant. From the above results, it can be inferred that although high salinity reduces the growth of barly plant, this plant is resistant to low salinity levels. It has been found that the salinity resistance mechanism of this plant is the salt tolerance through the accumulation of ions in its organs. Therefore, it can be used in the improvement of saline soils, for the optimal use of soil resources and saline waters. Also, in order to prepare biochar, the type of plant and the conversion temperature of the plant to biochar should be considered.
The Proteasome Modulates Endocytosis in a Glomerular Cell Type Specific Modality to Secure Kidney Filtration
Authors: Sachs Wiebke , Blume Lukas , Loreth Desiree , Schebsdat Lisa , Hatje Favian , Köhler Sybille , Wedekind Uta , Sachs Marlies , Zielinski Stephanie , Brand Johannes , Conze Christian , Florea Bogdan , Heppner Frank , Krüger Elke , Rinschen Markus , Kretz Oliver , Thünauer Roland , Meyer-Schwesinger Catherine
Published: June 2023

Kidney filtration is ensured in the glomerulus by the interaction of podocytes, endothelial and mesangial cells. In comparison to autophagy and mitochondrial function, the proteasome system represents a completely unexplored aspect of cellular metabolism especially in kidney cells, even though it is getting more and more clear that proteasome alterations are central to many glomerular metabolic and immune pathologies. Here we identify the proteasome to be critical in a conserved cell type specific modality. Combining genetic and inhibitor-based human, pig, mouse, and Drosophila models we demonstrate that the proteasome ensures filtration barrier integrity, with podocyte metabolism depending on the constitutive proteasome whereas glomerular endothelial cells depend on the immunoproteasome. Endothelial immunoproteasome deficiency as well as proteasome inhibition disrupt the filtration barrier in mice, resulting in pathologic immunoglobulin deposition under the slit diaphragm and glomerular basement membrane alterations. Mechanistically, a reduced endocytic activity was identified, which relates to altered membrane recycling and turnover of endocytic receptors for collagen 4 and immunoglobulins.
Our findings expand the concept of the (immuno)proteasome as a control protease for protein degradation and antigen presentation to an orchestrator of endocytosis and will lead to new therapeutic principles in targeting disease-associated glomerular protein accumulations.
Transmembrane Stem Factor Nanodiscs Enhanced Revascularization in a Hind Limb Ischemia Model in Diabetic, Hyperlipidemic Rabbits
Authors: Takematsu Eri , Massidda Miles , Howe Gretchen , Goldman Julia , Felli Patricia , Mei Lei , Callahan Gregory , Sligar Andrew , Smalling Richard , Baker Aaron
Published: June 2023

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.
Bayesian inference elucidates fault-system anatomy and resurgent earthquakes induced by continuing saltwater disposal
Authors: Vasyura-Bathke Hannes , Biegel Katherine , Salvage Rebecca , Eaton David , Ackerley Nick , Samsonov Sergey , Dettmer Jan
Published: June 2023

A sequence of injection-induced earthquakes in western Canada demonstrates a resurgent response of a fault system to persistent, post-mainshock saltwater disposal. Compared with independent analysis, joint inference of InSAR and seismic waveform data significantly reduces uncertainty in source parameters, showing that the mainshock nucleated at 5-km depth, propagating up-dip towards the injection source, arresting at 1.9-km depth. Precise hypocenter relocations, combined with Bayesian inference, reveal that four subparallel faults were reactivated, likely part of a regional, basement-rooted graben system. The reactivated faults appear to be truncated by a conjugate fault that is misoriented for slip in the present-day stress regime. The nearest saltwater disposal well targets a permeable Devonian reef that is in direct contact with Precambrian basement, atop a ridge-like uplift. Our observations show that a fault system can be activated more than a decade after initiation of saltwater disposal, and continued disposal may lead to resurgence of seismicity.
Bioluminescence imaging of Cyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung
Authors: Veland Nicolas , Gleneadie Hannah , Brown Karen , Sardini Alessandro , Pombo Joaquim , Dimond Andrew , Burns Vanessa , Sarkisyan Karen , Schiering Chris , Webster Zoe , Merkenschlager Matthias , Fisher Amanda
Published: June 2023

Aryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal and Cyp1a1 expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustained Cyp1a1 expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespoke Cyp1a1-Fluc reporters to longitudinally monitor AHR activity in vivo.
The association of mortality with vaccination and underlying disease among COVID-19 patients in long term care hospitals at Daegu and Gyeonsangbuk-do in Korea
Authors: Park Hanul , Park Chungmin , Choi Seong-Ju , Jung Yeon Haw , Hwang Myung-Jae , Son Junseock , Seo Inyeong , Park Taeyeon , Kim You Kyung , Seong Ji-Seon , Son Taejong
Published: June 2023

Background
This study aimed to estimate the effects of vaccine on reducing the mortality rate and the relationship between underlying diseases and death among long term care hospital residents during the Omicron epidemic.
Methods
This study included 2,507 inpatients at 18 long term care hospitals that experienced COVID-19 outbreaks more than twice in Daegu Metropolitan City and Gyeongsangbuk-do in Korea, from January 2022 to August 2022. Descriptive statistics were used to analyze participants’ demographic characteristics and mortality, which were expressed as percentages (%). Logistic regression analysis was performed to compare mortality, and the crude risk ratio (cRR) and adjusted risk risk (aRR) were estimated. The analysis model was adjusted for sex, age, region, history of Paxlovid priscription, vaccine status, reinfection, and presence, type, and number of underlying diseases.
Results
In terms of vaccination status, the aRR in the group with < 90 days after the 3 doses was 0.20 (CI:0.09–0.45) and ≥ 90 days was 0.14 (CI:0.06–0.32), that in the group with < 90 days after 4 doses was 0.18 (CI:0.06–0.43), compared with the non-vaccinated group. The fatality rate in the group prescribed Paxlovid was higher than that in the non-prescribed group. However, the difference was not statistically significant. The aRR of hypothyroidism was 5.75 (CI:1.10–30.13) and that of COPD and asthma were 2.84 (CI:1.15–6.99), compared with the group that did not have each underlying disease.
Conclusion
We confirmed the preventive effects of vaccination on death and the high risk of death from hypothyroidism, COPD, and asthma in COVID-19-confirmed patients in long term care hospitals.
CMIP6 precipitation and temperature projections for Chile
Authors: Salazar Alvaro , Thatcher Marcus , Goubanova Katerina , Bernal Patricio , Gutiérrez Julio , Squeo Francisco
Published: June 2023

Precipitation and near-surface temperature and from an ensemble of 36 new state-of‐the‐art climate models under the Coupled Model Inter‐comparison Project phase 6 (CMIP6) are evaluated over Chile´s climate. The analysis is focused on four distinct climatic subregions: Northern Chile, Central Chile, Northern Patagonia, and Southern Patagonia. Over each of the subregions, first, we evaluate the performance of individual global climate models (GCMs) against a suit of precipitation and temperature observation-based gridded datasets over the historical period (1986–2014) and then we analyze the models’ projections for the end of the century (2080–2099) for four different shared socioeconomic pathways scenarios (SSP). Although the models are characterized by general wet and warm mean bias, they reproduce realistically the main spatiotemporal climatic variability over different subregions. However, none of the models is best across all subregions for both precipitation and temperature. Moreover, among the best performing models defined based on a Taylor skill score, one finds the so-called “hot models” likely exhibiting an overestimated climate sensitivity, which suggest caution in using these models for accessing the future change in Chile. We found robust (90% of models agree in the direction of change) projected end-of-the-century reductions in mean annual precipitation for Central Chile (~-20% to ~-40%) and Northern Patagonia (~-10% to ~-30%) under scenario SSP585, but changes are strong from scenario SSP245 onwards, where precipitation is reduced by 10–20%. Northern Chile and Southern Patagonia show non-robust changes across the models. Future near-surface temperature warming presented high inter-model agreement across subregions with the greatest increments occurring along the Andes Mountains. Northern Chile displays the strongest increment of up to ~ 6°C in SSP585, followed by Central Chile (up to ~ 5°C), both Northern and Southern Patagonia show a corresponding increment by up to ~ 4°C. We also briefly discuss the environmental and socio-economic implications of these future changes for Chile.
Diagnostic model for Alzheimer's disease based on PANoptosis-related genes
Authors: Zhang Erdong , Dai Fengqiu , Chen Tingting , Tao Ling , Shen Xiangchun
Published: June 2023

Background:The pathophysiology of Alzheimer's disease (AD) involves the interplay of three different processes: pyroptosis, apoptosis, and necroptosis. However, the role of PANoptosis, a novel pro-inflammatory programmed cell death pathway, in AD remains unexplored.Result:Our study utilized tissue expression profile data from AD patients to construct three distinct PANoptosis patterns, each with unique molecular and clinical characteristics. We have created a risk scoring system called the PANscore, which can analyze patterns specific to each AD patient. Additionally, we observed significantly lower levels of follicular helper T cells (Tfh) in the high PANscore and AD patients. Further analysis revealed a significant negative correlation of Tfh withGSDMDandMLKL.Conclusion:These findings provide a roadmap for personalized patient stratification, enabling clinicians to develop personalized treatment plans for AD patients and advance the field of precision medicine.
Protocol for a Prospective Study Evaluating Circulating Tumour Cells Status to Predict Radical ProstatectomyTreatment Failure in Localised Prostate Cancer Patients (C- ProMeta-1)
Authors: Al-Hammouri Tarek , Almeida-Magana Ricardo , Lawrence Rachel , Duffy Tom , White Laura , Burke Edwina , Kudahetti Sakunthala , Collins Justin , Rajan Prabhakar , Berney Daniel , Gabe Rhian , Shaw Greg , Lu Yong-Jie
Published: June 2023

Background: Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence.
Methods: We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood sample (20ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time.
Discussion: CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment.
Trial registration: ISRCTN17332543
What is important to the GP in recognizing acute appendicitis in children: a Delphi study
Authors: Blok Guus C.G.H. , Berger Marjolein Y. , Holtman Gea A.
Published: June 2023

BACKGROUND: For diagnostic research on appendicitis in registration data, insight is needed in the way GPs generate medical records. We aimed to reach a consensus on the features that GPs consider important in the consultation and medical records when evaluating a child with suspected appendicitis.
METHODS: We performed a three-round Delphi study among Dutch GPs selected by purposive sampling. An initial feature list was created based on a literature search and features in the relevant Dutch guideline. Finally, using a vignette describing a child who needed later reassessment, we asked participants to complete an online questionnaire about which consultation features should be addressed and recorded.
RESULTS: A literature review and Dutch guideline yielded 95 consultation features. All three rounds were completed by 22 GPs, with the final consensus list containing 26 symptoms, 29 physical assessments and signs, 2 additional tests, and 8 further actions (including safety-netting, i.e., informing the patient about when to contact the GP again). Of these, participants reached consensus that 37 should be actively addressed and that 20 need to be recorded if findings are negative.
CONCLUSIONS:
GPs agreed that negative findings do not need to be recorded for most features and that records should include the prognostic and safety-netting advice given. The results have implications in three main domains: for research, that negative findings are likely to be missing; for medicolegal purposes, that documentation cannot be expected to be complete; and for clinical practice, that safety-netting advice should be given and documented.
The relationship between circulating stem cells and stromal cell derived factor-1 with disease severity in patients with liver cirrhosis
Authors: Mansoursamaei Ali , Forough Zahra , Sadeghi Amir Mohammad , Abhari Hani Khalili , Vahedi Hamid , Atashi Amir
Published: June 2023

Introduction:
Stem cells have the ability to regenerate and transform into different cells. The chemokine stromal cell-derived factor 1 (SDF-1) plays an important role in hematopoietic stem cell mobilization, implantation, survival, and proliferation. In this study, we aimed to investigate the relationship between the number of stem cells in the blood and the blood concentration of stromal cell-derived factor 1 with disease severity in cirrhotic patients.
Methods
15 patients with cirrhosis and 15 healthy individuals aged 18 to 65 years were randomly selected between January 2016 and July 2017. The number of circulating stem cells and SDF-1 levels were compared in the patient group and the healthy control group. The correlation between circulating stem cells and SDF-1 concentration with disease severity was evaluated.
Results
33% of cirrhotic patients were classified as severity B and 67% as severity C by the Child-Pugh method. The percentage of stem cells and mean SDF-1 concentration in patients with cirrhosis was approximately 2.8 (p < 0.00) and 1.81 (P < 0.001) times higher than in healthy individuals, respectively. Although, there was no significant association between disease severity and the percentage of circulating stem cells in cirrhotic patients (P = 0.46), a significantly higher concentrations of SDF-1 was observed in more severe forms of the disease (p = 0.04).
Conclusion
The percentage of stem cells and the concentration of SDF-1 in the serum of patients with cirrhosis were higher in patients with cirrhosis. The severity of the disease was significantly related to the SDF-1 concentration.
Comparison of Machine Learning Models in Predicting In-hospital Mortality of Patients with Acute Paraquat Poisoning
Authors: Tang Guo , Jiang Zhen , Wei Wei , Yang Ying , Yang Sha , Yao Rong
Published: June 2023

Aims
To evaluate the predictive capabilities of various machine learning models for in-hospital mortality in patients diagnosed with acute paraquat poisoning(APP).
Methods
From September 2010 to January 2022, patients were identified retrospectively from the emergency departments of West China Hospital, Sichuan University, People's Republic of China. A total of 724 patients were randomly divided into a training set (80% of subjects) and a validation set (20% of subjects). The least absolute shrinkage and selection operator (LASSO) method was utilized to identify significant features associated with APP, and nine machine learning models were constructed. Model evaluation was carried out in the validation set, using a range of evaluation metrics such as accuracy, precision, recall, F-measure, the area under the receiver operating characteristic curve(AUC), Precision-Recall curve (PRC), and Clinical decision curve analysis(DCA). The CatBoost model was employed to predict in-hospital mortality in patients with APP, and the ibreakdown and SHapley Additive exPlanations (SHAP) package in R were used to interpret the CatBoost model.
Results
A group of 724 individuals who had suffered from APP were enrolled, of whom 360 had passed away. During feature selection, six variables were chosen as predictive indicators for the model. In feature selection, 6 variables were selected as model predicting indicators. Compared with Adaptive Boosting(AdaBoost), CatBoost, Decision Tree(DT), Gradient Boosting Decision Tree(GBDT), Light Gradient Boosting Machine(LightGBM), Logistic Classification, Random Forest(RF), Support Vector Machine(SVM), eXtremeGradient Boosting(XGBoost) improved the classification prediction performance, respectively. CatBoost was the best-performing model (accuracy = 1, precision = 1, recall = 1, F-measure = 1, and AUC = 1). Furthermore, PRC and DCA indicated that the model had a excellent predictive performance.
Conclusions
By utilizing machine learning models, the likelihood of in-hospital mortality in patients with APP can be predicted with precision and dependability. Of the various ensemble learning models tested, including RF, AdaBoost, CatBoost, GBDT, LightGBM, and XGBoost, CatBoost exhibited nearly flawless performance. These results demonstrate the feasibility of integrating machine learning models into electronic health records to facilitate informed care and service planning.
A network pharmacology for predicting the key targets and potential mechanism of Paxlovid in treating COVID-19
Authors: Liu Heng-Jian , Lin Yuan , Qian Pei-Xia , He Jiang
Published: June 2023

Background: Paxlovid has been widely used to treat COVID-19 in global pandemics. The aim of this study is to discover the main targets of SARS-CoV-2 and to explore therapeutic mechanism of Paxlovid.
Methods: The targets of Paxlovid were predicted by SwissTargetPrediction. Meanwhile, COVID-19 related targets were collected from GeneCards and OMIM. Then, PPI networks, GO and KEGG enrichment analysis were constructed to discover the potential mechanism by STRING, Cytoscape and DAVID. Finally, AutoDock Vina and Pymol were performed to visualize the interactions between Paxlovid and targets.
Results: A total of 22 Paxlovid-related targets of were collected, and 1191 remained therapeutic genes for COVID-19. 23 targets were retained for the further study by PPI network and data integration. The GO and KEGG indicated that 23 targets were significantly enriched to inflammatory response, immune response and so forth. Paxlovid was successfully docked to the active of ALB, CXCL8, HLA-A, IL1B, IL6, KNG1, TNF, VEGFA, CD8A and CTSL. In addition, Paxlovid easily bind with the active pocket of3CLpro and PLpro.
Conclusions: Paxlovid could directly target 3CLproand PLpro, and also regulate the immune system. Meanwhile, it may affect the interaction between spike protein RBD and ACE2.
The relationship between self-esteem and problematic smartphone use: the mediating role of aggressiveness
Authors: Zhang Lihua , Yang Bo , Zhu He
Published: June 2023

Background: Problematic smartphone use can negatively affect people on a cognitive and behavioral level. Some studies found a negative association between self-esteem and problematic smartphone use but there are different results. This may be due to a lack of differentiation between explicit and implicit self-esteem. Previous studies have also examined the relationship between self-esteem, aggressiveness, and problematic smartphone use, but it is unclear if aggressiveness plays a mediating role in self-esteem and problematic smartphone use. To address these gaps in knowledge, we conducted a study where we separately analyzed the relationships between explicit and implicit self-esteem and problematic smartphone use, and investigated whether aggressiveness acts as a mediator between them.
Method:A cross-sectional study with167 College students was carried out. The Rosenberg Self-Esteem Scale was used to measure the participants' explicit self-esteem. The Implicit Association Test was used to measure implicit self-esteem. The Smartphone Addiction Scale-Short Version was used to measure the participants' problematic smartphone use. The Chinese College Students' Version of the Buss-Perry Aggression Questionnaire was used to measure aggressiveness.
Results: The findings show a negative correlation between problematic smartphone use and explicit self-esteem, but not implicit self-esteem. The connection between explicit self-esteem and problematic smartphone use is totally mediated by aggressiveness.
Conclusion: This study emphasize the important role of aggressiveness in problematic smartphone use behaviors of people with low explicit self-esteem. Aggressiveness plays a completely mediating role between explicit self-esteem and problematic smartphone use. Our study provides a basis for future interventions for problematic smartphone use.
Systemic lupus erythematosus increases the risk of knee osteoarthritis: A Mendelian randomization study
Authors: Li Jin , Zhang Liheng , Li Jie , Jin Xi , Liu Sheng , Leng Xiangyang
Published: June 2023

Patients with systemic lupus erythematosus (SLE) often present with musculoskeletal system involvement, but the existence of a causal association between SLE and osteoarthritis remains unclear. Knee osteoarthritis (KOA) is the most common form of osteoarthritis. We used two-sample Mendelian randomization to analyze the potential causal relationship between SLE and KOA risk. We downloaded summary data on SLE and KOA from the IEU Open genome-wide association studies database and selected 52 single nucleotide polymorphisms that were independently associated with SLE as genetic IVs. Inverse variance weighted, MR-Egger, weighted median, simple model, and weighted model methods were selected for two-sample Mendelian randomization analysis. Pleiotropy was estimated using MR-Egger regression, MR-PRESSO, and Cochran's Q tests. Finally, sensitivity analysis was performed using the leave-one-out method. The results of all five models showed a significant causal association between SLE and KOA. SLE increased the risk of KOA (odds ratio = 1.012, 95% confidence interval = 1.002–1.023, P = 0.017 using inverse variance weighted analysis), and no significant polymorphism was found. Sensitivity analysis supported that the results were robust. In summary, our study reveals that SLE is an important risk factor for KOA and a potential causal association exists between SLE and KOA. Therefore, controlling SLE may be important for the prevention of KOA.
Framing protocol optimization in oncological Patlak parametric imaging with uKinetics
Authors: Ye Qing , Zeng Hao , Zhao Yizhang , Zhang Weiguang , Dong Yun , Fan Wei , Lu Yihuan
Published: June 2023

Purpose

Total-body PET imaging with ultra-high sensitivity makes high-temporal-resolution framing protocols possible for the first time, which allows to capture rapid tracer dynamic changes. However, whether protocols with higher number of temporal frames can justify the efficacy with substantially added computation burden for clinical application remains unclear. We have developed a kinetic modeling software package (uKinetics). The aim of this work is to verify the uKinetics with PMOD and to perform framing protocol optimization for the oncological Patlak parametric imaging.

Methods

Six different protocols with 100, 61, 48, 29, 19 and 12 temporal frames were applied to analyzing 60-min dynamic 18F-FDG PET scans of 10 patients, respectively. Voxel-based Patlak analysis coupled with image-derived input function was applied to generate parametric images. Normal tissues and lesions were segmented to perform correlation analysis and Bland-Altman plots. Different protocols were compared with the protocol of 100 frames as reference.

Results

Minor differences were found between uKinetics and PMOD in the Patlak parametric imaging. Compared with the protocol with 100 frames, the relative difference of the input function and quantitative kinetic parameters remained low for protocols with at least 29 frames, but increased for the protocols with 19 and 12 frames. Significant difference of lesion Ki values was found between the protocols with 100 frames and 12 frames.

Conclusion

uKinetics was proved providing equivalent oncological Patlak parametric imaging comparing to PMOD. Minor differences were found between protocols with 100 and 29 frames, which indicated that 29 frames is sufficient and efficient for the oncological 18F-FDG Patlak applications, and the protocols with more frames are not needed. The protocol with 19 frames yielded acceptable results, while that with 12 frames is not recommended.
The Impact of Learning Curve on Surgical Performance focused on Achieving Medial Support in Proximal Humeral Fracture: ORIF using locking plate for complex proximal humeral fracture
Authors: Lim Tae Kang , Koh Kyoung Hwan , Kim Hwa Pyung , Shon Min Soo
Published: June 2023

Background: Although the optimal treatment for proximal humeral fractures has not been established yet, open reduction and internal fixation (ORIF) using a locking plate is currently recommended as a viable option. However, such procedures in some cases are technically in demand, and it is more difficult than expected for less experienced beginner surgeons. This study aimed to evaluate with respect to whether the surgical performance, focused on achieving medial support, improved during their learning periods of novice surgeons for open reduction and internal fixation (ORIF) using locking plate of complex proximal humeral fracture.
Methods: This retrospective study was performed on 62 patients who underwent ORIF for complex proximal humeral fractures from three fellowship-trained shoulder specialists in same training institution, who had just started their own clinics in one of the three different institutions. Based on the periodic splitting of 2 groups between the first and subsequent 1-year during the learning curve, we assessed the achievement of medial support as a primary variable. Patient demographics, clinical outcomes, radiological outcomes including technical errors, and complications were also evaluated.
Results: Group A (32 patients) in the first and group B (30 patients) in subsequent 1-year of experience were included in this study. There were no statistically significant differences between the two groups in the demographic data, the distribution of fracture type, and the presence of medial comminution at the time of the injury. The interesting finding was that significant increases in cases that were achieved the medial support (p=0.027) and adequate position of the plate (p=0.008) were seen in Group B than in Group A. However, the periodic splitting of the two groups showed no difference in the clinical results and postoperative stiffness in the final follow-up.
Conclusions: The study showed that the surgical performance regarding the achievement of medial support was improved during the learning curve of the inexperienced surgeon for locking plate fixation in complex proximal humeral fracture. Its recognition as a reference for a significant learning curve effect will play a role in emphasizing the need to focus faster and safely overcome the learning curve.
Advance care planning and a structured palliative plan in primary health care decrease cancer deaths in hospital: A prospective controlled non-randomized intervention trial
Authors: Driller Bardo , Talseth-Palmer Bente , Strømskag Kjell Erik , Hole Torstein , Brenne Anne-Tove
Published: June 2023

Background: Advance care planning (ACP) enables patients to define goals and preferences, reflecting a person’s wishes and current medical condition. Spending less time in hospital and not dying in hospital are advocated to be desirable outcomes in palliative care (PC). In 2015, 36% of cancer patients died in hospital and 13% died at home in Norway.
Method: From 2015 to 2022 this prospective controlled non-randomized intervention trial included and observed 151 cancer patients from the Romsdal region with or without an organized ACP conversation with a conclusive and structured palliative plan in primary health care (ClinicalTrials.gov Identifier: NCT02170168, June 23, 2014). The patients were identified through their contact with the local hospital, cancer outpatient clinic or hospital-based PC team.
Results: During the observation period, 135 patients died. Of these, 74 patients had a structured palliative plan (intervention (I) group) and 61 had not (control (C) group). Dying in hospital was significantly less common for patients in the I group compared to the C group (16.2% vs 34.4%; p=0.014; X2 (1, n = 135) = 6.00). Patients with the intervention were more likely to die at home (33.8% vs 29.5%) or in nursing home (50.0% vs 36.1%). There were no statistically significant differences between the groups according to days at home, in nursing home, or in hospital during the last 90 days of life. Observed differences between the groups when it came fulfilment of preferred place of death (PPOD) and actual place of death (APOD) on 109 patients (42.2% in I group and 26.7% in C group) did not reach statistical significance (p=0.096).
Conclusion: Organized ACP conversations with a conclusive and structured palliative plan in primary health care decreased the number of cancer deaths in hospital in our study. A structured ACP approach integrating palliative care into oncology within primary health care, supports patients´ preferences by changing the current care profile to a more outpatient care and is feasible within the Norwegian health care system.