A Diet Lacking Selenium, but Not Zinc, Copper or Manganese, Induces Anticancer Activity in Mice with Metastatic Cancers.

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53-/- murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers.

A rapid inventory of amphibians, squamates, and bats of Mata de Plátano Field Station and Nature Reserve, Arecibo, Puerto Rico.

Puerto Rico harbors a diverse vertebrate fauna with high levels of endemism. However, while several books for vertebrate diversity and local checklists for birds have been published, checklists of amphibians, reptiles, and bats are lacking or nonexistent at both local and regional scales. In this study, we documented the amphibian, reptile, and bat faunas at Mata de Plátano Field Station and Nature Reserve, in Arecibo, Puerto Rico. We document four species of amphibians, seven lizards, three snakes, and nine bats. Despite prior works using samples from this nature reserve, this represents the first vertebrate checklist for the Mata de Plátano Field Station and Nature Reserve. We provide additional natural history observations based on our survey results and highlight the importance of including local and regional checklists of species for downstream research and conservation.

Reliability of predictive models based on the mesiodistal and buccolingual diameters of permanent canine teeth for sex estimation in forensic contexts: A systematic review and meta-analysis.

This study aimed to assess the reliability of predictive models for sex estimation based on permanent canine size. A systematic literature review was performed by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Six electronic databases were searched as the primary source of information. As a secondary source of information, a manual search was performed to identify additional relevant studies not captured in the initial search. After assessing the methodological quality and risk of bias with the Joanna Briggs Institute Critical Appraisal Tools for Systematic Reviews, the data were subjected to statistical tests for a meta-analysis of diagnostic test accuracy and Higgin's I2 statistic to evaluate the heterogeneity between the eligible studies. The systematic search resulted in 21 studies for qualitative synthesis, and 13 of them were selected for quantitative analysis. The analysis of 25 univariate predictive models showed an estimated sensitivity of 77.2 % and specificity of 67.1 %. Meta-regression analyses were performed for dental arch, the type of diameter and dental region outcomes for these univariate predictive models. Dental arch (p = 0.029) and the dental region of measurement (p = 0.001) were significant modifiers. The analysis of 25 multivariate predictive models showed an estimated sensitivity of 82.6 % and specificity of 70.1 %. There were significant methodological limitations and substantial heterogeneity among the included studies. Based on the results, there is insufficient high-quality scientific evidence to support the safe use of predictive models based on permanent canine measurements as the exclusive method for sex estimation in forensic settings.

Digital matching of palatal rugae patterns for forensic identification in edentulous denture wearers.

Identifying edentulous victims in forensic contexts poses a significant challenge. It has been reported that having a denture to reproduce and compare Palatal Rugae (PR) patterns is crucial for identifying edentulous individuals, yet there are no validated protocols for conducting this procedure. In this study, a new method was developed and validated for plaster molding of the internal surface of upper dentures, along with a protocol involving focus-stacked photographs and reference scales. Thirty-eight edentulous subjects participated in the study, obtaining plaster models of the patients (PM), and their dentures (AM) were standardized. The AM/PM model was highlighted and photographed with ten shots in different z-focuses for each model, using standard lighting and aligning the position of the PR perpendicular to the photographic axis using tubular spirit levels and modeling clay. The images were processed using the stacking technique and analyzed by three observers through the proposed protocol using Adobe® Photoshop®. The results were analyzed based on the intra-observer and inter-observer agreement levels, with a 95% confidence interval. This study demonstrated high-precision intra-observer and inter-observer agreement (k = 1) in the matching of Palatal Rugae (PR) and maxillary morphology obtained from participants and their dentures. The protocol is simple, cost-effective, and precise. It enables standardization of the technique for obtaining plaster models, and the exposure of PR and photographic protocol minimizes the presence of artifacts in the images, thereby reducing the likelihood of errors and promoting the reproducibility of both the recording technique and the comparison of the PR.

Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents-In Vitro Evaluation against Breast Cancer Cells.

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.

Evaluation of Anticancer Activity of 76 Plant Species Collected in Andalusia (Spain) against Lung Cancer Cells.

Every year, cancer kills millions of people around the world. Finding more selective anticancer agents is essential to improve the low survival rates of patients with metastatic cancers. Since the research of natural products is a valuable approach to the discovery of new compounds and the Iberian flora offers a rich source of unstudied plants, we have carried out a random screening of 76 plant species from 43 families collected in Andalusia (South of Spain). Using non-malignant cells (HaCaT) and lung cancer cells (A549), we found that the extract from Arum italicum Mill. subsp. italicum (Araceae), Mandragora autumnalis Bertol. (Solanaceae), Rhamnus alaternus L. (Rhamnaceae), and Lomelosia simplex (Desf.) Raf. subsp. dentata (Jord. & Fourr.) Greuter & Burdet (Dipsacaceae) showed selective cytotoxicity against lung cancer cells. Extracts of plant species belonging to the Iridaceae family showed high selective activity against cancer cells, highlighting that the Xiphion xiphium (L.) M.B. Crespo, Mart.-Azorín & Mavrodiev flower extract was more selective against lung cancer cells than the standard anticancer drugs, cisplatin and 5-fluorouracil. This extract also showed modest selective cytotoxicity against bladder carcinoma cells (T24). The number of cells in the G1 phase increased after treatment with the extract from Xiphion xiphium. Our research indicates that various plants are potential sources for the isolation and development of new anticancer drugs.

Use of dimensions in posterior dentition for sex estimation in forensic contexts: A systematic review and meta-analysis.

OBJECTIVE: This study assessed the validity of dimensions in posterior dentition for sex estimation in forensic contexts. DESIGN: A systematic review was established following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). After assessing the risk of bias and methodological quality with the QUADAS-2 system, the data were subjected to statistical tests for a meta-analysis of diagnostic accuracy and I2 to verify the heterogeneity. RESULTS: The search resulted in 15 studies that underwent qualitative testing, all were selected for quantitative analysis. The papers included: the mesiodistal of the upper first molar, lower first molar, and upper second molar, and the buccolingual of the upper first molar and upper second molar. The results showed that sensitivity and specificity rates were lower with the mesiodistal diameter, with rates of 0.577 for the lower first molar, 0.674 for the upper first molar, and 0.698 for the upper second molar, while the rates were higher with the buccolingual diameter, with 0.724 for the upper first molar, and 0.743 for the upper second molar. The power to estimate sex is greater for males than for females. High heterogeneity was detected among the studies of almost all dimensions, except sensibility for the lower first molar and specificity for the upper second molar. CONCLUSIONS: None of the dimensions reached an accuracy of ≥80%, however, so they are not a reliable method for sex estimation in forensic practice.

Dietary Manipulation of Amino Acids for Cancer Therapy.

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs in challenging metabolic environments. However, since normal diets provide all AAs at relatively constant levels and ratios, these potentially lethal genetic and metabolic defects are eventually harmless to cancer cells. If we temporarily replace the normal diet of cancer patients with artificial diets in which the levels of specific AAs are manipulated, cancer cells may be unable to proliferate and survive. This article reviews in vivo studies that have evaluated the antitumor activity of diets restricted in or supplemented with the 20 proteinogenic AAs, individually and in combination. It also reviews our recent studies that show that manipulating the levels of several AAs simultaneously can lead to marked survival improvements in mice with metastatic cancers.

Age estimation by evaluation of obliteration of the palatine sutures: a scoping review.

The age estimation (AE) of human remains is a challenging task since it is dependent on the state in which these remains are found. Since the macroscopic evaluation of palatal sutures has been proposed as a method for AE, the aim of this study was to review the literature on this method, considering that the cases of edentulous elderly are among the greatest challenges in anthropological and forensic contexts. A scoping review was performed using a specific search strategy in PubMed, Web of Science, SciELO, LILACS, and Google Scholar. The search identified 13 articles, among which the USA yielded the most information with 3 articles. Only 1 study was identified in Latin America (Peru). There was great diversity regarding the origin of samples, and the studies were carried out on both historical and modern populations. Only 6 articles exceeded the average sample size (168.08) and 4 articles studied samples of fewer than 100 individuals. Although 6 different methods were identified, Mann et al.'s revised method was the most used. The selection of appropriate methods for AE depends on what skeletal elements are present and the general age of the specimens. Although evaluation of the obliteration of the palatal sutures has been found to be simple and promising for AE in individuals over 60 years of age, this method has been reported to have less precision than other more complex methods, which makes the use of a combination of methods necessary to increase the level of confidence and the percentage of success. Further research could resolve this weakness, and methodological refinement (perhaps the digitization and automation of processes, or the application of Bayesian methodology) could provide the necessary solidity to comply with international standards in the forensic scenario.

Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were also tested in this model. AA manipulation led to modest improvements in mice survival when the levels of lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Some mice fed the artificial diets as monotherapy lived much longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Artificial Diets with Altered Levels of Sulfur Amino Acids Induce Anticancer Activity in Mice with Metastatic Colon Cancer, Ovarian Cancer and Renal Cell Carcinoma.

Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53-/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

Undergraduate dental students and their potential role in disaster victim identification procedures: A scoping review under a Chilean perspective.

BACKGROUND: A mass fatality incident is an unexpected event that can cause the death of many people, which has motivated careful analysis and development of appropriate strategies for planning and response with all available resources. As these events involve multiple victims, their identities must be confirmed using the highest possible quality standards. Forensic Odontology (FO) has proven to be a scientific resource for disaster victim identification (DVI) procedures; however, it is highly dependent on the proper management not only of material resources but also of human resources. Chile is a country recognised as prone to natural disasters, but an insufficient number of forensic odontologists has been reported. The aim of the study was to review the literature on a dental undergraduate (UG) student's potential value in a DVI process. METHODOLOGY: A scoping review was performed using a specific search strategy in PubMed/Medline, Web of Science, Scopus, SciELO and EBSCO databases. RESULTS: The search identified 27 articles in which the basic dental degree, the necessary training and the need for human resources are variables considered in different priorities by those articles. DISCUSSION: It is vital to assess the local needs of Chile based on its UGs, considering that FO is an underestimated resource that should be included early on in dental curriculums. Furthermore, it should align with public policies to ensure viability and inclusion in standardised protocols. CONCLUSION: Although there is "potential" usage of UG dental students in DVI is not ideal, circumstances will dictate their use. The better trained they are as students, the more valuable their "potential" contribution will be.

Forensic odontology and dental age estimation research: a scoping review a decade after the NAS report on strengthening forensic science.

Dental age estimation (DAE) is one of the most reliable and useful scientific methods employed by forensic odontology (FO) for human identification. In 2009, the US National Academy of Sciences (NAS) report highlighted the need to deepen research in many disciplines, among which FO received strong criticism for specific expertise. The aim of this review is to provide a comprehensive overview in order to systematically map the latest original research done in FO, as well as identify DAE within this field. A systematic search was performed from 2014 to 2019. In total, 644 studies were identified for qualitative analysis: DAE was the most studied topic (41.30%). Asia was the most productive continent with 58.27% of the global production on DAE; India was the most productive Asian country, with 32.33% and 55.48% of global and Asian production, respectively. The University of Macerata (Italy), KU Leuven (Belgium), University of Split (Croatia), and University of São Paulo (Brazil) led DAE research. Authors from leading countries on DAE research demonstrated great individual productivity, which is evidence of their scientific efforts, but also possible risks if the continuity of this line of research depends on them. Although FO has significantly focused its research on DAE, the absence of publications on controversial topics but necessary for research according to the NAS report shows the possible lack of interest of authors or journals to address them.

Radix entomolaris: A morphological variable of human dentition with anthropological relevance. A study on a Chilean population.

The existence of a third root in the mandibular first molars may have implications for certain dental treatments; however, its greatest relevance could be in anthropological and forensic sciences, because its prevalence varies significantly according to ethnic groups. The purpose of this research was to determine the prevalence of radix entomolaris (RE) in a sample of Chilean people. A random sample of 1330 digital periapical radiographs of endodontically treated mandibular first molars (551 males and 779 females, aged between 18 and 87 years) were evaluated. The prevalence of RE, its distribution by sex and root canal lengths were determined. Evidence demonstrated that the formation of RE is associated with ancestry and its frequency is variable according to populations studied, being more frequent in Asians and Native Americans. The prevalence of RE in the studied people was 3.16%, similar to frequencies reported in European individuals (3.4%-4.2%). The 61.90% of RE were located at the right side of the mandible and 38.10% at the left side. The average working length of RE was 19.52 mm. No statistically significant differences in frequencies were observed by sex (p = 0.19). The prevalence of RE varies among continental population groups. However, due to human migration, the frequency of this physical trait could be modified in specific geographic regions. The observed prevalence of RE in the study group was similar to the prevalence ranges observed for European ancestry populations and it was considerably lower than the data reported for non-Europeans. The absence of sexual dimorphism is consistent with results of previous studies performed worldwide.

Rituximab pharmacokinetic and pharmacokinetic-pharmacodynamic evaluation based on a study in diffuse large B-cell lymphoma: Influence of tumor size on pharmacokinetic and assessment of pharmacokinetic similarity.

Dr. Reddy's Laboratories rituximab (DRL_RI; Dr. Reddy's Laboratories SA, Basel, Switzerland) is under development as a rituximab biosimilar. Study RI-01-002 (Clinical Trials Registry - India/2012/11/003129), comparing DRL_RI to the reference medicinal product (RMP) MabThera® (Roche, Grenzach-Wyhlen, Germany), demonstrated pharmacokinetic (PK) equivalence and showed comparable pharmacodynamic, efficacy, safety, and immunogenicity profiles. We used data from the same study to perform population PK and PK-pharmacodynamic analyses: first exploring possible factors influencing the PK similarity assessment between products and then performing simulations to investigate the impact of tumor size on rituximab PK. Nonlinear mixed-effects models for PK, tumor size, tumor size-PK, and tumor response were developed independently. The final PK model included drug product as a dose-scaling parameter and predicted a 6.75% higher dose reaching the system in RMP-treated patients. However, when tumor size was included in the tumor size-PK model, the drug product effect was no longer observed. The model rather indicated that patients with larger tumor size have higher clearance. Further simulations confirmed that higher baseline tumor size is associated to slightly lower rituximab exposure. Tumor response, described by a continuous-time Markov model, did not differ between drug products. Both had higher effects during the first 20 weeks of treatment. Also, the model described a subpopulation of nonresponders to treatment (42%) with faster transitions to a worse state. The different rituximab exposure initially detected between drug products (6.75%) was shown using PK/PK-pharmacodynamic analysis to be attributed to a tumor size imbalance between treatment groups. PK/PK-pharmacodynamic analyses may contribute to PK similarity assessments.

Digital Reconstructions Using Linear Regression: How Well Can It Estimate Missing Shape Data from Small Damaged Areas?

Skeletal remains analyzed by anthropologists, paleontologists and forensic scientists are usually found fragmented or incomplete. Accurate estimations of the original morphologies are a challenge for which several digital reconstruction methods have been proposed. In this study, the accuracy of reconstructing bones based on multiple linear regression (RM) was tested. A total of 150 digital models from complete zygomatics from recent past populations (European and African American) were studied using high-density geometric morphometrics. Some landmarks (i.e., 2, 3 and 6) were coded as missing to simulate incomplete zygomatics and the missing landmarks were estimated with RM. In the zygomatics, this simulated damage affects a few square centimeters or less. Finally, the predicted and original shape data were compared. The results indicate that the predicted landmark coordinates were significantly different from the original ones, although this difference was less than the difference between the original zygomatic and the mean zygomatic in the sample. The performance of the method was affected by the location and the number of missing landmarks, with decreasing accuracy with increasing damaged area. We conclude that RM can accurately estimate the original appearance of the zygomatics when the damage is small.

Visualizing the historical COVID-19 shock in the US airline industry: A Data Mining approach for dynamic market surveillance.

One of the purposes of Artificial Intelligence tools is to ease the analysis of large amounts of data. In order to support the strategic decision-making process of the airlines, this paper proposes a Data Mining approach (focused on visualization) with the objective of extracting market knowledge from any database of industry players or competitors. The method combines two clustering techniques (Self-Organizing Maps, SOMs, and K-means) via unsupervised learning with promising dynamic applications in different sectors. As a case study, 30-year data from 18 diverse US passenger airlines is used to showcase the capabilities of this tool including the identification and assessment of market trends, M&A events or the COVID-19 consequences.

Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.