Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel ß-coronavirus to cause significant human mortality in the last two decades. Although vaccines are available, too few have been administered worldwide to keep the virus in check and to prevent mutations leading to immune escape. To determine if antibodies could be identified with universal coronavirus activity, plasma from convalescent subjects was screened for IgG against a stabilized pre-fusion SARS-CoV-2 spike S2 domain, which is highly conserved between human ß-coronavirus. From these subjects, several S2-specific human monoclonal antibodies (hmAbs) were developed that neutralized SARS-CoV-2 with recognition of all variants of concern (VoC) tested (Beta, Gamma, Delta, Epsilon, and Omicron). The hmAb 1249A8 emerged as the most potent and broad hmAb, able to recognize all human ß-coronavirus and neutralize SARS-CoV and MERS-CoV. 1249A8 demonstrated significant prophylactic activity in K18 hACE2 mice infected with SARS-CoV-2 lineage A and lineage B Beta, and Omicron VoC. 1249A8 delivered as a single 4 mg/kg intranasal (i.n.) dose to hamsters 12 hours following infection with SARS-CoV-2 Delta protected them from weight loss, with therapeutic activity further enhanced when combined with 1213H7, an S1-specific neutralizing hmAb. As little as 2 mg/kg of 1249A8 i.n. dose 12 hours following infection with SARS-CoV Urbani strain, protected hamsters from weight loss and significantly reduced upper and lower respiratory viral burden. These results indicate in vivo cooperativity between S1 and S2 specific neutralizing hmAbs and that potent universal coronavirus neutralizing mAbs with therapeutic potential can be induced in humans and can guide universal coronavirus vaccine development.

A dolabralexin-deficient mutant provides insight into specialized diterpenoid metabolism in maize.

Two major groups of specialized metabolites in maize (Zea mays), termed kauralexins and dolabralexins, serve as known or predicted diterpenoid defenses against pathogens, herbivores, and other environmental stressors. To consider the physiological roles of the recently discovered dolabralexin pathway, we examined dolabralexin structural diversity, tissue-specificity, and stress-elicited production in a defined biosynthetic pathway mutant. Metabolomics analyses support a larger number of dolabralexin pathway products than previously known. We identified dolabradienol as a previously undetected pathway metabolite and characterized its enzymatic production. Transcript and metabolite profiling showed that dolabralexin biosynthesis and accumulation predominantly occur in primary roots and show quantitative variation across genetically diverse inbred lines. Generation and analysis of CRISPR-Cas9-derived loss-of-function Kaurene Synthase-Like 4 (Zmksl4) mutants demonstrated dolabralexin production deficiency, thus supporting ZmKSL4 as the diterpene synthase responsible for the conversion of geranylgeranyl pyrophosphate precursors into dolabradiene and downstream pathway products. Zmksl4 mutants further display altered root-to-shoot ratios and root architecture in response to water deficit. Collectively, these results demonstrate dolabralexin biosynthesis via ZmKSL4 as a committed pathway node biochemically separating kauralexin and dolabralexin metabolism, and suggest an interactive role of maize dolabralexins in plant vigor during abiotic stress.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Tailored horseshoe-shaped nicotinonitrile scaffold as dual promising c-Met and Pim-1 inhibitors: Design, synthesis, SAR and in silico study.

For the horseshoe tactic to succeed in inhibiting c-Met and Pim-1, the nicotinonitrile derivatives (2a-n) were produced in high quantities by coupling acetyl phenylpyrazole (1) with the proper aldehydes and ethyl cyanoacetate under basic conditions. Consistent basic and spectroscopic data (NMR, IR, Mass, and HPLC) supported the new products' structural findings. With IC50 potency in nanomolar ranges, these compounds had effectively repressed them, particularly compounds 2d and 2 h, with IC50 values below 200 nM. The most potent compounds (2d and 2 h) were tested for their antitumor effects against prostate (PC-3), colon (HCT-116), and breast (MDA-MB-231) and were evaluated in comparison to the anticancer drug tivantinib using the MTT assay. Similar to tivantinib, these compounds showed good antiproliferative properties against the HCT-116 tumor cells while having low cytotoxicity towards healthy fetal colon (FHC) cells. In the HCT-116 cell line, their ability to trigger the apoptotic cascade was also investigated by looking at the level of Bax and Bcl-2 as well as the activation of the proteolytic caspase cascade. When HCT-116 cells were exposed to compounds 2d and 2 h in comparison to the control, active caspase-3 levels increased. The HCT-116 cell line also upregulated Bcl-2 protein levels and downregulated Bax levels. Additionally, when treated with compound 2d, the HCT-116 cell cycle was primarily stopped at the S phase. Compared to the control, compound 2d treatment significantly inhibited the protein expression levels of c-Met and Pim-1 kinases in the treated HCT-116 cells. Thorough molecular modeling analyses, such as molecular docking and dynamic simulation, were performed to ascertain the binding mechanism and stability of the target compounds.

Reduced intestinal lipid absorption improves glucose metabolism in aged G2-Terc knockout mice.

BACKGROUND: Biological aging is an important factor leading to the development of pathologies associated with metabolic dysregulation, including type 2 diabetes, cancer, cardiovascular and neurodegenerative diseases. Telomere length, a central feature of aging, has additionally been identified as inversely associated with glucose tolerance and the development of type 2 diabetes. However, the effects of shortened telomeres on body weight and metabolism remain incompletely understood. Here, we studied the metabolic consequences of moderate telomere shortening using second generation loss of telomerase activity in mice. RESULTS: Aged male and female G2 Terc-/- mice and controls were characterized with respect to body weight and composition, glucose homeostasis, insulin sensitivity and metabolic activity. This was complemented with molecular and histological analysis of adipose tissue, liver and the intestine as well as microbiota analysis. We show that moderate telomere shortening leads to improved insulin sensitivity and glucose tolerance in aged male and female G2 Terc-/- mice. This is accompanied by reduced fat and lean mass in both sexes. Mechanistically, the metabolic improvement results from reduced dietary lipid uptake in the intestine, characterized by reduced gene expression of fatty acid transporters in enterocytes of the small intestine. Furthermore, G2-Terc-/- mice showed significant alterations in the composition of gut microbiota, potentially contributing to the improved glucose metabolism. CONCLUSIONS: Our study shows that moderate telomere shortening reduces intestinal lipid absorption, resulting in reduced adiposity and improved glucose metabolism in aged mice. These findings will guide future murine and human aging studies and provide important insights into the age associated development of type 2 diabetes and metabolic syndrome.

Identification of 3-(5-cyano-6-oxo-pyridin-2-yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity.

New 5-cyano-6-oxo-pyridine-based sulfonamides (6a-m and 8a-d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5-cyanopyridine derivatives 6e and 6l on cell-cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

Recent advancements in wastewater treatment via anaerobic fermentation process: A systematic review.

This manuscript delves into the realm of wastewater treatment, with a particular emphasis on anaerobic fermentation processes, especially dark, photo, and dark-photo fermentation processes, which have not been covered and overviewed previously in the literature regarding the treatment of wastewater. Moreover, the study conducts a bibliometric analysis for the first time to elucidate the research landscape of anaerobic fermentation utilization in wastewater purification. Furthermore, microorganisms, ranging from microalgae to bacteria and fungi, emphasizing the integration of these agents for enhanced efficiency, are all discussed and compared. Various bioreactors, such as dark and photo fermentation bioreactors, including tubular photo bioreactors, are scrutinized for their design and operational intricacies. The results illustrated that using clostridium pasteurianum CH4 and Rhodopseudomonas palustris WP3-5 in a combined dark-photo fermentation process can treat wastewater to a pH of nearly 7 with over 90% COD removal. Also, integrating Chlorella sp and Activated sludge can potentially treat synthetic wastewater to COD, P, and N percentage removal rates of 99%,86%, and 79%, respectively. Finally, the paper extends to discuss the limitations and future prospects of dark-photo fermentation processes, offering insights into the road ahead for researchers and scientists.

Bimetallic bis-Aroyldihydrazone-Isatin Complexes of High O=V(IV) and Low Cu(II) Valent Ions as Effective Biological Reagents for Antimicrobial and Anticancer Assays.

Due to the versatile bioreactivity of aroyldihydrazone complexes as cost-effective alternatives with different transition metals, two novel bimetallic homo-complexes (VOLph and CuLph) were prepared via the coordination of a terephthalic dihydrazone diisatin ligand (H2Lph) with VO2+ and Cu2+ ions, respectively. The structure elucidation was confirmed by alternative spectral methods. Biologically, the H2Lph ligand and its MLph complexes (M2+ = VO2+ or Cu2+) were investigated as antimicrobial and anticancer agents. Their biochemical activities towards ctDNA (calf thymus DNA) were estimated using measurable titration viscometrically and spectrophotometrically, as well as the gel electrophoresis technique. The growth inhibition of both VOLph and CuLph complexes against microbial and cancer cells was measured, and the inhibition action, MIC, and IC50 were compared to the inhibition action of the free H2Lph ligand. Both VOLph and CuLph showed remarkable interactive binding with ctDNA compared to the free ligand H2Lph, based on Kb = 16.31, 16.04 and 12.41 × 107 mol-1 dm3 and ΔGb≠ = 47.11, -46.89, and -44.05 kJ mol-1 for VOLph, CuLph, and H2Lph, respectively, due to the central metal ion (VIVO and CuII ions). VOLph (with a higher oxidation state of the V4+ ion and oxo-ligand) exhibited enhanced interaction with the ctDNA molecule compared to CuLph, demonstrating the role and type of the central metal ion within the performed electronegative and electrophilic characters.

Newly emerged genotypes of highly pathogenic H5N8 avian influenza viruses in Kagoshima prefecture, Japan during winter 2020/21.

During the 2020/21 winter season, 29 and 10 H5N8 high pathogenicity avian influenza viruses (HPAIVs) were isolated from environmental water and wild birds, respectively, in Kagoshima prefecture, Japan. Furthermore, seven subtypes of low pathogenicity avian influenza viruses (LPAIVs) were also isolated; H1N1, H2N9, H3N2, H3N6, H3N8, H4N6, and H6N6 subtypes. While the H5 hemagglutinin (HA) genes of the G1 cluster were isolated throughout the winter season, those of the G2 cluster were also detected in late winter, suggesting that H5 HPAIVs possessing H5 HA genes from the two different clusters were individually introduced into Kagoshima prefecture. Intriguingly, genetic constellations revealed that the H5N8 HPAIVs could be classified into six genotypes, including four previously reported genotypes (E1, E2, E3, and E7), and two new genotypes (tentatively named E8 and E9). The PB1 and PA gene segments of genotypes E8 and E9 shared high similarity with those of LPAIVs, whereas the remaining gene segments were close to those of genotype E1. Furthermore, LPAIVs whose PA gene segment was close to that of genotype E9 were isolated from the environmental water. Overall, we revealed that various HPAIV genotypes circulated in Kagoshima prefecture during the 2020/21 winter season. This study highlights the importance of monitoring both HPAIV and LPAIV to better understand AIV ecology in migratory waterfowl populations.

Reproducibility of cerebral perfusion measurements using BOLD delay.

BOLD delay is an emerging, noninvasive method for assessing cerebral perfusion that does not require the use of intravenous contrast agents and is thus particularly suited for longitudinal monitoring. In this study, we assess the reproducibility of BOLD delay using data from 136 subjects with normal cerebral perfusion scanned on two separate occasions with scanners, sequence parameters, and intervals between scans varying between subjects. The effects of various factors on the reproducibility of BOLD delay, defined here as the differences in BOLD delay values between the scanning sessions, were investigated using a linear mixed model. Reproducibility was additionally assessed using the intraclass correlation coefficient of BOLD delay between sessions. Reproducibility was highest in the posterior cerebral artery territory. The mean BOLD delay test-retest difference after accounting for the aforementioned factors was 1.2 s (95% CI = 1.0 to 1.4 s). Overall, BOLD delay shows good reproducibility, but care should be taken when interpreting longitudinal BOLD delay changes that are either very small or are located in certain brain regions.

Polysaccharides from Spirulina platensis (PSP): promising biostimulants for the green synthesis of silver nanoparticles and their potential application in the treatment of cancer tumors.

Photosynthetic cyanobacterial components are gaining great economic importance as prospective low-cost biostimulants for the green synthesis of metal nanoparticles with valuable medical and industrial applications. The current study comprises the biological synthesis of silver nanoparticles (Ag-NPs) using soluble polysaccharides isolated from Spirulina platensis (PSP) as reducing and capping agents. FTIR spectra showed major functional groups of PSP and biogenic silver nanoparticles including O-H, C-H (CH2), C-H (CH3), C=O, amide, and COO- groups. The UV/Vis spectroscopy scan analyses of the extracted PSP showed absorption spectra in the range of 200-400 nm, whereas the biogenic Ag-NPs showed a maximum spectrum at 285 nm. Transmission electron microscopy (TEM) analysis of the synthesized Ag-NPs showed spherical nanoparticles with mean size between 12 and 15.3 nm. The extracted PSP and Ag-NPs exhibited effective cytotoxic activity against Hep-G2 (human hepatocellular carcinoma). The IC50 for PSP and Ag-NPs were 65.4 and 24.5 µg/mL, respectively. Moreover, cell apoptosis assays for PSP and Ag-NPs against the growth of Hep-G2 cells revealed superior growth inhibitory effects of the green synthesized Ag-NPs that encouraged tracing the apoptotic signalling pathway. In conclusion, the current study demonstrated an unprecedented approach for the green synthesis of silver nanoparticles (NPs), using the polysaccharide of Spirulina platensis as reducing and capping agents, with superior anticancer activity against a hepatocellular carcinoma cell line.

Avian paramyxovirus serotype-1 isolation from migratory birds and environmental water in southern Japan: An epidemiological survey during the 2018/19-2021/2022 winter seasons.

Newcastle disease caused by highly pathogenic viruses of avian paramyxovirus serotype-1 (APMV-1) is a highly contagious poultry disease. Although a large-scale epidemic of Newcastle disease had occurred in Japan between the 1950s and the 2000s, there have been no outbreaks anywhere since 2010. In addition, there are no reports of epidemiological surveys of APMV-1 in wild birds in Japan in the last 10 years. We conducted the first epidemiological survey of APMV-1 in the Izumi plain, Kagoshima prefecture of southern Japan from the winter of 2018 to 2022. A total of 15 APMV-1 strains were isolated, and isolation rates from roosting water and duck fecal samples were 2.51% and 0.10%, respectively. These results indicate that the isolation method from environmental water may be useful for efficient surveillance of APMV-1 in wild birds. Furthermore, this is the first report on the success of APMV-1 isolation from environmental water samples. Genetic analysis of the Fusion (F) gene showed that all APMV-1 isolates were closely related to virus strains circulating among waterfowl in Far East Asian countries. All isolates have avirulent motifs in their cleavage site of F genes, all of which were presumed to be low pathogenic viruses in poultry. However, pathogenicity test using embryonated chicken eggs demonstrated that some isolates killed all chicken embryos regardless of viral doses inoculated (102 -106 50% egg infectious dose). These results indicated that APMV-1 strains, which are potentially pathogenic to chickens, are continuously brought into the Izumi plain by migrating wild birds.

Unusual, hierarchically structured composite of sugarcane pulp bagasse biochar loaded with Cu/Ni bimetallic nanoparticles for dye removal.

Biochar-supported nanocatalysts emerged as unique materials for environmental remediation. Herein, sugarcane pulp bagasse (SCPB) was wet-impregnated with Cu(NO3)23H2O and Ni(NO3)26H2O, then pyrolyzed at 500 °C, under N2, for 1 h. We specifically focused on sugarcane pulp instead of SCB and biochar materials. The metal nitrate to biomass ratio was set at 0.5, 1, and 2 mmol/g, with Cu/Ni initial ratio = 1. The process provided hierarchically structured porous biochar, topped with evenly dispersed 40 nm-sized CuNi alloy nanoparticles (SCPBB@CuNi). The biochar exhibited an unusual fishing net-like structure induced by nickel, with slits having a length in the 3-12 µm range. Such a fishing net-like porous structure was obtained without any harsh acidic or basic treatment of the biomass. It was induced, during pyrolysis, by the nanocatalysts or their precursors. The CuNi nanoparticles form true alloy as proved by XRD, and are prone to agglomeration at high initial metal nitrate concentration (2 mmol/g). Stepwise metal loading was probed by XPS versus the initial metal nitrate concentration. This is also reflected in the thermal gravimetric analyses. The SCPBB@CuNi/H2O2 (catalyst dose: 0.25 g/L) system served for the catalyzed removal of Malachite Green (MG), Methylene Blue (MB), and Methyl Orange (MO) dyes (concentration = 0.01 mmol/L). Both single and mixed dye solutions were treated in this advanced oxidation process (AOP). The dyes were removed in less than 30 min for MG and 3 h for MB, respectively, but 8 h for MO, therefore showing selectivity for the degradation of MG, under optimized degradation conditions. The catalysts could be collected with a magnet and reused three times, without any significant loss of activity (∼85%). AOP conditions did not induce any nanocatalyst leaching. To sum up, we provide a simple wet impregnation route that permitted to design highly active Fenton-like biochar@CuNi composite catalyst for the degradation of organic pollutants, under daylight conditions.

Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents.

Mutant isocitrate dehydrogenase (IDH) 2 "IDH2m" acquires a neo-enzymatic activity reducing α-ketoglutarate to an oncometabolite, D-2-hydroxyglutarate (2-HG). Three s-triazine series were designed and synthesised using enasidenib as a lead compound. In vitro anticancer screening via National Cancer Institute "NCI" revealed that analogues 6a, 6c, 6d, 7g, and 7l were most potent, with mean growth inhibition percentage "GI%" = 66.07, 66.00, 53.70, 35.10, and 81.15, respectively, followed by five-dose screening. Compounds 6c, 6e, and 7c were established as the best IDH2R140Q inhibitors compared to enasidenib, reporting IC50 = 101.70, 67.01, 88.93, and 75.51 nM, respectively. More importantly, 6c, 6e, and 7c displayed poor activity against the wild-type IDH2, IC50 = 2928, 2295, and 3128 nM, respectively, which implementing high selectivity and accordingly safety. Furthermore, 6c was screened for cell cycle arrest, apoptosis induction, and western blot analysis. Finally, computational tools were applied to predict physicochemical properties and binding poses in IDH2R140Q allosteric site.

Central hepatectomy versus major hepatectomy for patients with centrally located hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: For those with a centrally located HCC, the two types of liver sectionectomy that can be performed are extended hepatectomy (EH) and central hepatectomy (CH). This meta-analysis aimed to compare the short- and long-term outcomes between patients treated with CH and patients treated with EH for those with centrally located HCC. METHOD: We searched PubMed, Scopus, Web of Science, and Cochrane library for eligible studies from inception to 1 April 2022 and a systematic review and meta-analysis were done to compare the outcomes between the two groups. RESULTS: we included 9 studies with a total of 1674 patients in this study. The pooled results in this meta-analysis showed equal long-term overall survival, Disease-free survival, recurrence and mortality between the two groups (5-year OS, RR = 1.14, 95% CI = 0.96-1.35, P = 0.12; I2 = 56%), (5-year DFS, RR = 0.81, 95% CI = 0.61-1.08, P = 0.15; I2 = 60%), (Recurrence, RR = 1.04, 95% CI = 0.94-1.15, P = 0.45; I2 = 27%), and (Mortality, RR = 0.55, 95% CI = 0.26-1.15, P = 0.11; I2 = 0%). In addition to that, no significant difference could be detected in the overall incidence of complications between the two groups (Complications, RR = 0.94, 95% CI = 0.76-1.16, P = 0.57; I2 = 0%). However, CH is associated with a remarkable increase in the rate of biliary fistula (Biliary fistula, RR = 1.90, 95% CI = 1.07-3.40, P = 0.03; I2 = 0%). And Liver cell failure was higher in the case of EH (LCF, RR = 0.47, 95% CI = 0.30-0.76, P = 0.002; I2 = 0%). Regarding the operative details, CH is associated with longer operative time (Time of the operation, Mean difference = 0.82, 95% CI = 0.36, 1.27, P = 0.0004; I2 = 57%). CONCLUSION: No significant difference in the short and long-term survival and recurrence between CH and MH for CL-HCC. However, CH is associated with greater future remnant liver volume that decreases the incidence of LCF and provides more opportunities for a repeat hepatectomy after tumour recurrence.

Is There Evidence of P-Hacking in Imaging Research?

BACKGROUND: P-hacking, the tendency to run selective analyses until they become significant, is prevalent in many scientific disciplines. PURPOSE: This study aims to assess if p-hacking exists in imaging research. METHODS: Protocol, data, and code available here https://osf.io/xz9ku/?view_only=a9f7c2d841684cb7a3616f567db273fa. We searched imaging journals Ovid MEDLINE from 1972 to 2021. Text mining using Python script was used to collect metadata: journal, publication year, title, abstract, and P-values from abstracts. One P-value was randomly sampled per abstract. We assessed for evidence of p-hacking using a p-curve, by evaluating for a concentration of P-values just below .05. We conducted a one-tailed binomial test (α = .05 level of significance) to assess whether there were more P-values falling in the upper range (e.g., .045 < P < .05) than in the lower range (e.g., .04 < P < .045). To assess variation in results introduced by our random sampling of a single P-value per abstract, we repeated the random sampling process 1000 times and pooled results across the samples. Analysis was done (divided into 10-year periods) to determine if p-hacking practices evolved over time. RESULTS: Our search of 136 journals identified 967,981 abstracts. Text mining identified 293,687 P-values, and a total of 4105 randomly sampled P-values were included in the p-hacking analysis. The number of journals and abstracts that were included in the analysis as a fraction and percentage of the total number was, respectively, 108/136 (80%) and 4105/967,981 (.4%). P-values did not concentrate just under .05; in fact, there were more P-values falling in the lower range (e.g., .04 < P < .045) than falling just below .05 (e.g., .045 < P < .05), indicating lack of evidence for p-hacking. Time trend analysis did not identify p-hacking in any of the five 10-year periods. CONCLUSION: We did not identify evidence of p-hacking in abstracts published in over 100 imaging journals since 1972. These analyses cannot detect all forms of p-hacking, and other forms of bias may exist in imaging research such as publication bias and selective outcome reporting.

Cross-Sectional Evaluation of Open Science Practices at Imaging Journals: A Meta-Research Study.

Objective: To evaluate open science policies of imaging journals, and compliance to these policies in published articles. Methods: From imaging journals listed we extracted open science policy details: protocol registration, reporting guidelines, funding, ethics and conflicts of interest (COI), data sharing, and open access publishing. The 10 most recently published studies from each journal were assessed to determine adherence to these policies. We calculated the proportion of open science policies into an Open Science Score (OSS) for all journals and articles. We evaluated relationships between OSS and journal/article level variables. Results: 82 journals/820 articles were included. The OSS of journals and articles was 58.3% and 31.8%, respectively. Of the journals, 65.9% had registration and 78.1% had reporting guideline policies. 79.3% of journals were members of COPE, 81.7% had plagiarism policies, 100% required disclosure of funding, and 97.6% required disclosure of COI and ethics approval. 81.7% had data sharing policies and 15.9% were fully open access. 7.8% of articles had a registered protocol, 8.4% followed a reporting guideline, 77.4% disclosed funding, 88.7% disclosed COI, and 85.6% reported ethics approval. 12.3% of articles shared their data. 51% of articles were available through open access or as a preprint. OSS was higher for journal with DOAJ membership (80% vs 54.2%; P < .0001). Impact factor was not correlated with journal OSS. Knowledge synthesis articles has a higher OSS scores (44.5%) than prospective/retrospective studies (32.6%, 30.0%, P < .0001). Conclusion: Imaging journals endorsed just over half of open science practices considered; however, the application of these practices at the article level was lower.

University students' awareness of e-waste and its disposal practices in Pakistan: a construction of the conceptual framework.

Pakistan is among the few countries generating and receiving enormous e-waste, which posits a threat to its future generations. A systematic literature review also suggests exploring e-waste awareness in Asia to understand awareness and behavior. Therefore, the present study explored university students' awareness of e-waste and the factors hindering the disposal of laptops, personal computers, and cellphones and suggested a conceptual framework. The study used the qualitative research approach and non-probability sampling. We collected data through four focus group discussions (FGDs) with students at a Pakistani university. After data saturation, we developed themes from FGDs and found computer sciences and engineering students with better awareness than others. The factors hindering e-waste disposal were lower monetary benefits for disposal, breach of sensitive information, nostalgic association with devices, and non-availability of disposal facilities. Other variables like lower resale value and high family sharing increased the storage of e-devices and reduced e-waste disposal. The research is among a few initial attempts to explore e-waste awareness and factors hindering disposal behavior in e-waste-receiving countries (e.g., Pakistan) and provides evidence from students who are the primary users. Our findings are crucial for policymakers to take corrective actions, introduce monetary benefits, and secure disposal to reduce e-waste.

DNA damage repair gene germline profiling for metastatic prostate cancer patients of different ancestries.

BACKGROUND: Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries. METHODS: Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.1% of cases with an African origin. RESULTS: Forty-seven germline mutations in 11 DDR genes were identified in 46 patients of the total cohort (8.3%). BRCA2 (4.1%) and ATM (2.0%) were the most frequently mutated genes. There was no difference in DDRg mutation frequency between mPC patients of European ancestry and those of African origin. Germline mutations of BRCA2 were associated with a positive family history of breast cancer (p = 0.02). The mean age at metastatic stage (59.7 vs. 67.0; p = 0.0003) and the mean age at death (65.2 vs. 73.9; p = 0.0003) were significantly earlier for carriers of BRCA2 mutation than for non-carriers. Moreover, the Cox model showed that BRCA2 positive status was statistically associated with poorer survival (hazard ratio: 0.29; 95% confidence interval 0.18-0.48; p < 0.0001). CONCLUSION: We showed that, in France, BRCA2 and ATM are the main predisposing DDR genes in mPC patients, with a particular aggressiveness for BRCA2 leading to early metastatic stage and death.