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Objective: The diagnosis of a mood-related psychiatric disorder (MRPD) among patients with cancer has been associated with decreased quality of life and lower cancer survival. This study aimed to understand the risk of a new MRPD after cancer diagnosis by individual risk behaviors, with a specific focus on tobacco use and the presence of a human papillomavirus (HPV)-associated cancer., Methods: Single-center retrospective cohort study of 11,712 patients diagnosed with cancer between 2009 and 2020. We identified predictors of a new MRPD after cancer diagnosis using a time-to-event analysis and Cox proportional hazards model including demographics, disease characteristics, and tobacco use and HPV-associated tumors., Results: Univariate analyses revealed lower hazard ratios (HRs) of a new MRPD among individuals that identified as Asian/Pacific Islanders and among the older age groups (> 51 years). Univariate analyses additionally demonstrated higher HRs of MRPD among females; sexual minorities; former and current smokers; individuals with HPV-associated cancers; and individuals diagnosed at later stages. These relationships were observed in the multivariate model when adjusting for covariates. Shorter time-to-MRPD was observed when stratifying by individual behavioral risk factors, with active smokers and individuals with an HPV-associated cancer being at the highest risk., Conclusions: Individual behavioral risk factors increase risk of new MRPD after being diagnosed with cancer. These findings build on past studies by linking tobacco use and HPV-associated cancers with MRPD risk in oncology and can be used to identify patients at risk of developing new MRPDs post-cancer diagnosis and engaging them in treatment., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation" sites are of significant ecological, socio-economic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world (>50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The direct approach for determining reference intervals (RIs) is not always practical. This study aimed to generate evidence that a real-world data (RWD) approach could be applied to transfer free thyroxine RIs determined in one population to a second population, presenting an alternative to performing multiple RI determinations., Design and Methods: Two datasets (US, n = 10,000; Europe, n = 10,000) were created from existing RWD. Descriptive statistics, density plots and cumulative distributions were produced for each data set and comparisons made. Cumulative probabilities at the lower and upper limits of the RIs were identified using an empirical cumulative distribution function. According to these probabilities, estimated percentiles for each dataset and estimated differences between the two sets of percentiles were obtained by case resampling bootstrapping. The estimated differences were then evaluated against a pre-determined acceptance criterion of ≤7.8% (inter-individual biological variability). The direct approach was used to validate the RWD approach., Results: The RWD approach provided similar descriptive statistics for both populations (mean: US = 16.1 pmol/L, Europe = 16.4 pmol/L; median: US = 15.4 pmol/L, Europe = 15.8 pmol/L). Differences between the estimated percentiles at the upper and lower limits of the RIs fulfilled the pre-determined acceptance criterion and the density plots and cumulative distributions demonstrated population homogeneity. Similar RI distributions were observed using the direct approach., Conclusions: This study provides evidence that a RWD approach can be used to transfer RIs determined in one population to another., Competing Interests: Hedwig Kurka, Peter Dilba, Thorsten Rehberg, Benedikt Weber, Horst Donner and Anja Thorenz are employees of Roche Diagnostics GmbH. Alex Katayev and André Valcour are employees of Laboratory Corporation of America Holdings (Labcorp). Ignacio Gadea Gironés, Carlos Castillo Perez, Peter Findeisen and Laura Rodríguez Alonso have no conflict of interest to declare., (© 2024 The Authors.)

COVID-19, a disease caused by SARS-CoV-2, was declared a pandemic in 2020 and created a global crisis in health systems, with more than 545 million confirmed cases and 6.33 million deaths. In this sense, this work aims to identify possible inhibitors of the SARS-CoV-2 RdRp enzyme using in silico approaches. RdRp is a crucial enzyme in the replication and assembly cycle of new viral particles and a critical pharmacological target in the treatment of COVID-19. We performed a virtual screening based on molecular docking from our in-house chemical library, which contains a diversity of 313 structures from different chemical classes. Nine compounds were selected since they showed important interactions with the active site from RdRp. Next, the ADME-Tox in silico predictions served as a filter and selected the three most promising compounds: a coumarin LMed-052 , a hydantoin LMed-087 , and a guanidine LMed-250 . Molecular dynamics simulations revealed details such as changes in the positions of ligands and catalytic residues during the simulations compared to the complex from molecular docking studies. Binding free energy analysis was performed using the MMGBSA method, demonstrating that LMed-052 and LMed-087 have better affinities for the RdRp by energetic contributions to the stability of the complexes when compared to LMed-250 . Furthermore, LMed-052 showed significant in vitro inhibition against MHV-3, decreasing 99% of viral titers. Finally, these findings are useful to guide structural modifications aiming to improve the potential of these compounds to act as inhibitors of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

The coronavirus disease-2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), became the highest public health crisis nowadays. Although the use of approved vaccines for emergency immunization and the reuse of FDA-approved drugs remains at the forefront, the search for new, more selective, and potent drug candidates from synthetic compounds is also a viable alternative to combat this viral disease. In this context, the present study employed a computational virtual screening approach based on molecular docking and molecular dynamics (MD) simulation to identify possible inhibitors for SARS-CoV-2 M pro (main protease), an important molecular target required for the maturation of the various polyproteins involved in viral replication. The virtual screening approach selected four potential inhibitors against SARS-CoV-2 M pro . In addition, MD simulation studies revealed changes in the positions of the ligands during the simulations compared to the complex obtained in the molecular docking studies, showing the benzoylguanidines LMed-110 and LMed-136 have a higher affinity for the active site compared to the other structures that tended to leave the active site. Besides, there was a better understanding of the formation and stability of the existing H-bonds in the formed complexes and the energetic contributions to the stability of the target-ligand molecular complexes. Finally, the in silico prediction of the ADME profile suggested that LMed-136 has drug-like characteristics and good pharmacokinetic properties. Therefore, from the present study, it can be suggested that these structures can inhibit SARS-CoV-2 M pro . Nevertheless, further studies are needed in vitro assays to investigate the antiviral properties of these structures against SARS-CoV-2.

Leishmaniases are infectious diseases caused by flagellated protozoan parasites belonging to the genus Leishmania that infect cells of the mononuclear phagocytic system. These parasites are transmitted to humans by biting an infected female sandfly belonging to the genera Phlebotomus in the Old World and Lutzomyia in the New World. Despite representing a major public health problem, the therapeutic options are old and have several disadvantages. Given this scenario, developing vaccines or drugs for oral administration is necessary. Therefore, integrating computational and experimental strategies into the studies on molecular targets essential for the survival and virulence of the parasite is fundamental in researching and developing new treatments for leishmaniasis. In the effort to develop new vaccines and drugs, molecular docking methods are widely used as they explore the adopted conformations of small molecules within the binding sites of macromolecular targets and estimate the free energy of target-ligand binding. Privileged structures have been widely used as an effective model in medicinal chemistry for drug discovery. Chalcones are a common simple scaffold found in many compounds of natural and synthetic origin, where studies demonstrate the great pharmacological potential in treating leishmaniasis. This review is based on scientific articles published in the last ten years on molecular docking of chalcone derivatives for essential molecular targets of Leishmania . Thus, this review emphasizes how versatile chalcone derivatives can be used in developing new inhibitors of important molecular targets involved in the survival, growth, cell differentiation, and infectivity of the parasites that cause leishmaniasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Adding nitrogen fertilizers to agricultural soils contributes to increasing concentrations of nitrous oxide (N 2 O) in the atmosphere. However, the impacts of N addition on soil organic matter (SOM) turnover, SOM availability, and the ensuing SOM-derived N 2 O emissions remain elusive. Within this context, the net change in direction and rate of SOM-derived N 2 O production triggered by added N is termed the N 2 O priming effect. This incubation study examined the sources and priming of N 2 O production as a function of urea addition and multiple moisture contents in a soil with high SOM (55 g organic C kg -1 ). We assessed four water-filled pore space (WFPS) conditions: 28, 40, 52, and 64%. Relative to controls receiving no N, urea addition increased N 2 O production by 2.6 times (P < .001). Cumulative N 2 O production correlated well with nitrification rates (r = .75; P = .03). We used 15 N-labeled urea to trace the added urea into N 2 O. Of the N added via urea, the recovery as N 2 O-N shifted from 0.02 to 0.17% when WFPS increased from 28 to 64% (P < .05). We also partitioned the N 2 O production into urea vs. SOM sources. More N 2 O was sourced from SOM than urea, with 59 ± 2% N 2 O originating from SOM. The magnitude of SOM-derived N 2 O under urea was larger than that of the control, revealing that positive N 2 O priming was triggered by urea addition. Upon subtracting the controls, the primed N 2 O was a consistent 19 ± 2% of the total N 2 O produced by urea-amended soils. Nevertheless, the priming magnitude rose sharply with increasing moisture by more than one order of magnitude from 4 to 48 μg N 2 O-N kg -1 soil and in exponential mode (R 2   = .98). Soil moisture, SOM, and nitrification interacted to drive the sources and priming of N 2 O., (© 2020 The Authors. Journal of Environmental Quality © 2020 American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Objective: To analyse the prevalence of myopia among a sample of more than 6000 children in Spain as well as to determine the impact of risk factors in its progression., Methodology: A total of 6,152 children aged from 5 to 7 were examined. The participants underwent an eye examination that included visual acuity, refraction without cycloplegia, and tests of accommodative and binocular function. In addition, a questionnaire regarding their lifestyle, family history, and geographical data was carried out. Finally, data were analysed using the SPSS version 25 program., Results: The prevalence of myopia in the sample of children studied has increased from 17% in 2016 to 20% in 2017. Likewise, the number of children with high myopia has also increased, from 1.7% in 2016 to 3.6% in 2017. 43.3% of the participants spent more than 3 hours a day doing near activities, and 48.9% of this group spent more than 50% of this time using electronic devices. In addition, only 9.7% spent more than 2.5 hours outdoors each day., Conclusion: Myopia prevalence appears to be increasing in Spain. Lifestyle factors appear to be increasing the risk of myopia., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

A long-standing objective in neuroscience has been to image distributed neuronal activity in freely behaving animals. Here we introduce NeuBtracker, a tracking microscope for simultaneous imaging of neuronal activity and behavior of freely swimming fluorescent reporter fish. We showcase the value of NeuBtracker for screening neurostimulants with respect to their combined neuronal and behavioral effects and for determining spontaneous and stimulus-induced spatiotemporal patterns of neuronal activation during naturalistic behavior.

Reconstructing a three-dimensional scene from multiple simultaneously acquired perspectives (the light field) is an elegant scanless imaging concept that can exceed the temporal resolution of currently available scanning-based imaging methods for capturing fast cellular processes. We tested the performance of commercially available light field cameras on a fluorescent microscopy setup for monitoring calcium activity in the brain of awake and behaving reporter zebrafish larvae. The plenoptic imaging system could volumetrically resolve diverse neuronal response profiles throughout the zebrafish brain upon stimulation with an aversive odorant. Behavioral responses of the reporter fish could be captured simultaneously together with depth-resolved neuronal activity. Overall, our assessment showed that with some optimizations for fluorescence microscopy applications, commercial light field cameras have the potential of becoming an attractive alternative to custom-built systems to accelerate molecular imaging research on cellular dynamics.

An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F. Casearin X degraded to the corresponding dialdehyde when stored in CDCl(3). The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC(50) values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity.