A novel algorithm for optimizing hydrocyclone operations in the decontamination of potentially toxic elements in soils.

We present the Three-Parameter Penalized Attributive Analysis for Upgrading (3PPAA-U) method as a tool for selecting the Best Upgrading Condition (BUC) in process engineering. Conventional approaches tend to consider only maximizing recovery (ε) and minimizing yield (γc); in contrast, the proposed 3PPAA-U introduces and seeks to maximize a third parameter, the grade (λ). This multi-parameter approach has not yet been explored in existing literature. In addition to controlling multiple parameters, the method is also superior to others as it includes inverse standard deviation weighting to avoid the distortion of results due to data dispersion. This reduces the possibility of drawing conclusions based on extreme values. Furthermore, the method can be used with a target-to-distance correction to optimize separation for multi-component feeds. To illustrate our method, we present a practical application of 3PPAA-U. Soil contaminated with potentially toxic elements (PTEs) was subject to hydrocycloning under 12 different experimental conditions. Results of these 12 experiments were compared using 3PPAA-U and conventional methods to identify the best upgrading conditions (BUC). Analysis reveals that the 3PPAA-U approach offers a simple and effective criterion for selecting BUC. Furthermore, 3PPAA-U has uses beyond soil remediation. It offers a versatile tool for optimizing operations across various processing and manufacturing environments offering a way to manage factors such as concentration, temperature, pressure, pH, Eh, grain size, and even broader environmental and economic considerations.

Update on the status of the contamination by organotin compounds in sediment of Nuevo Gulf, Argentina. Insights from field and experimental studies.

Organotin compounds are persistent pollutants and are considered chemicals of high environmental concern. In the present study, the distribution and degradation of tributyltin were evaluated in field sediments and through an ex situ experiment. For this, sediment samples from two locations were analysed: Luis Piedrabuena Harbour, with higher maritime traffic, and Cerro Avanzado, which receives less impact from anthropogenic activities. The results indicated that pollution levels at Luis Piedrabuena Harbour have decreased compared with studies performed 9 years ago for the same area. On the contrary, traces of organotin compounds have been found for the first time at Cerro Avanzado. Moreover, the butyltin degradation index indicated that organotin compounds undergo an advanced degradation process in the collected samples at both sites. Ex situ experiments revealed a limited capacity of sediments to retain tributyltin, and suggested an active role of bioturbation activity in the degradation of these compounds. In addition, visualisation using chemometric techniques (principal components analysis) allowed a simpler analysis of two sediment characteristics: the degree of contamination and the degradation levels of organotin compounds.

Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study. / Percepción de la mujer con psoriasis en la planificación familiar: Estudio descriptivo, transversal y multicéntrico.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

[Translated article] Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

Lanthanide-dependent isolation of phyllosphere methylotrophs selects for a phylogenetically conserved but metabolically diverse community.

The influence of lanthanide biochemistry during methylotrophy demands a reassessment of how the composition and metabolic potential of methylotrophic phyllosphere communities are affected by the presence of these metals. To investigate this, methylotrophs were isolated from soybean leaves by selecting for bacteria capable of methanol oxidation with lanthanide cofactors. Of the 344 pink-pigmented facultative methylotroph isolates, none were obligately lanthanide-dependent. Phylogenetic analyses revealed that all strains were nearly identical to each other and to model strains from the extorquens clade of Methylobacterium, with rpoB providing higher resolution than 16s rRNA for strain-specific identification. Despite the low species diversity, the metabolic capabilities of the community diverged greatly. Strains encoding identical PQQ-dependent alcohol dehydrogenases displayed significantly different growth from each other on alcohols in the presence and absence of lanthanides. Several strains also lacked well-characterized lanthanide-associated genes thought to be important for phyllosphere colonization. Additionally, 3% of our isolates were capable of growth on sugars and 23% were capable of growth on aromatic acids, substantially expanding the range of multicarbon substrates utilized by members of the extorquens clade in the phyllosphere. Whole genome sequences of eleven novel strains are reported. Our findings suggest that the expansion of metabolic capabilities, as well as differential usage of lanthanides and their influence on metabolism among closely related strains, point to evolution of niche partitioning strategies to promote colonization of the phyllosphere.

Comparative analysis of short-term outcomes and oncological results between robotic-assisted and laparoscopic surgery for rectal cancer by multiple surgeon implementation: a propensity score-matched analysis.

Robotic-assisted surgery (RAS) is becoming increasingly common for the surgical treatment of rectal cancer. However, the use and implementation of robotic surgery remains controversial. This study aimed to compare the short-term outcomes of robotic surgery, focusing on pathological results and disease-free survival (DFS), in our cohort with initial robotic experience by multiple surgeon implementation. This retrospective study enrolled 571 patients diagnosed with rectal cancer, who were treated with chemoradiotherapy and surgery between January 2015 and December 2021. Surgical outcomes after RAS and laparoscopic surgery (LS) were compared using a propensity score-matching (PSM) analysis. After matching, 200 patients (100 in each group) were included. The median operative time was significantly longer in the RAS group than in the LS group (p < 0.001). The conversion and morbidity rates were similar between the groups. A significantly higher rate of complete mesorectal excision (92% vs. 72%; p = 0.001) and number of lymph nodes harvested (p = 0.009) was observed in the RAS group. There were no statistically significant differences between the groups regarding circumferential and distal resection margin involvement. The 3-year overall and disease-free survival rate was similar between the two groups (p = 0.849 and p = 0.582, respectively). Two patients in the LS group developed local recurrence and 27 patients (15.4%) developed metastatic disease. Multivariate analysis showed that tumor stage III was the only factor associated with disease-free survival (HR, 9.34; (95% CI 1.13-77.1), p = 0.038). RAS and LS showed similar outcomes in terms of perioperative, anatomopathological, and disease-free survival, after multiple surgeon implementations.

Clinical and thyroid profile in patients with COVID-19 hospitalized in an intensive care unit.

OBJECTIVE: This study aimed to summarize the epidemiological and clinical features of thyroid function in COVID-19 patients in the intensive care unit (ICU) of Civil Fray Antonio Alcalde Hospital in Mexico. PATIENTS AND METHODS: This is a cross-sectional study that included 63 ICU patients with COVID-19 from August 2021 to December 2021. Thyroid function was evaluated through the TSH, T4, T3, and FT3 measures. Comorbidities such as diabetes mellitus type 2 (T2DM), arterial hypertension (HT), body mass index (BMI), and biochemical biomarkers, including procalcitonin (PCT) and C reactive protein (CRP), were also analyzed. RESULTS: A total of 63 patients with COVID-19 were hospitalized in the ICU; 42 (67%) were male, and 21 (33%) were female, with a mean age of 47 (range of 26-76 years). A total of 49 (78%) patients were non-vaccinated, 5 (8%) had an incomplete vaccination schedule, and 4 (6%) had completed the vaccination schedule. Regarding BMI, 10 (16%) were overweight, and 26 (40%) reported obesity. When assessing thyroid function, 8 (13%) patients were euthyroid, and 55 (87%) showed alterations on the thyroid hormonal axis, mainly a low concentration of TSH (0.56±0.79; p=0.0001) and FT3 (2.34±0.52; p=0.0006). In addition, increased PCT concentrations were associated with a higher risk to decease (1.22 vs. 8.21; p=0.0001) in this group of patients. CONCLUSIONS: Based on our findings, it appears that COVID-19 patients with low TSH and FT3 levels, who have not been vaccinated against SARS-CoV-2, are overweight or obese, and exhibit high levels of PCT are more likely to experience a poor prognosis and even mortality.

[Sociodemographic, clinical and ultrasound characterization of thyroid nodule pathology and its association with malignancy in a Colombian high-complexity center]. / Caracterización sociodemográfica, clínica y ecográfica de la enfermedad de nódulos tiroideos y su relación con la malignidad en un centro de alta complejidad colombiano.

BACKGROUND AND OBJECTIVE: Thyroid nodules are among the most frequent conditions, with a 10% risk of malignancy. The objective is to describe the frequency of demographic, clinical, and ultrasonographic characteristics of thyroid nodule pathology in adults and to explore the relationship with tumor malignancy. METHODS: An analytical, retrospective cross-sectional study in adults with thyroid nodules and nodular fine-needle aspiration performed in adult patients from a Colombian reference center between 2009-2019. Data were obtained from the clinical history, descriptive measures of the patient's demographic, clinical, and ultrasound variables were estimated, and their relationship with the malignancy of the tumor was explored. RESULTS: A total of 445 patients and 515 nodules were included. The median age was 55 years (IQR 44-64), 86.8% of women, and 54.8% had a single lesion. Percentages of 80.2 and 19.8 were benign and malignant nodules, with a median of 15.7mm (IQR 11-25) and 12.7mm (IQR 8.5-18.3), respectively (p<0.001). Hypothyroidism and levothyroxine consumption were higher in those with malignant nodules (p<0.001). The echographic characteristics were statistically different between the nodules. In the malignant ones, there was a higher frequency of solid composition, hypoechogenicity, and irregular margins. In contrast, in the benign ones, the absence of echogenic focus stood out (p<0.001). CONCLUSION: The ultrasound characteristics are essential to define the risk of malignancy of a thyroid nodule. Therefore, considering the most frequent ones can help in the most appropriate approach to primary care.

Minor Actinides Can Replace Essential Lanthanides in Bacterial Life.

Certain f-block elements-the lanthanides-have biological relevance in the context of methylotrophic bacteria. The respective strains incorporate these 4 f elements into the active site of one of their key metabolic enzymes, a lanthanide-dependent methanol dehydrogenase. In this study, we investigated whether actinides, the radioactive 5 f elements, can replace the essential 4 f elements in lanthanide-dependent bacterial metabolism. Growth studies with Methylacidiphilum fumariolicum SolV and the Methylobacterium extorquens AM1 ΔmxaF mutant demonstrate that americium and curium support growth in the absence of lanthanides. Moreover, strain SolV favors these actinides over late lanthanides when presented with a mixture of equal amounts of lanthanides together with americium and curium. Our combined in vivo and in vitro results establish that methylotrophic bacteria can utilize actinides instead of lanthanides to sustain their one-carbon metabolism if they possess the correct size and a +III oxidation state.

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020.

Alzheimer's disease (AD) is the most common form of dementia. There is currently no cure, and the available pharmacological treatment focuses on treating the symptoms. This study aimed to analyze the pharmacological treatments for AD protected in the US Patent Office. The Matheo Patent software was used to search for patents granted in the 2010-2020 period in the USPTO database. The search strategy «Alzheimer¼ was used in title and abstract and the International Patent Classification (IPC) codes A61P* and A61K*. The selected patents were divided into six categories according to therapeutic target. Complementary information from scientific databases was used to determine the stage of investigation and efficacy of the patented molecules. In the analyzed period, 58 patents were granted: 10 directed to Aß peptide metabolism and deposition, three to tau, seven to inflammation, nine to cholinergic, two to glutamatergic and 27 to other targets. More than 80.0% belong to holders from the USA, France, and Japan. The molecules Elenbecestat and LY3202626 decreased the burden of Aß plaques without significant cognitive improvement, Donanemab is in Phase 3 clinical trial, and the FDA has designated it Breakthrough Therapy. CPC-201 and PXT864 demonstrated, in Phase 2, good tolerability and improvement of AD symptoms. Most of the inventions are focused on treating the earliest phase of AD. The most advanced treatments in their research are those focused on treating Aß accumulation. More studies are needed to prove the efficacy of the patented molecules.

A Novel Protein for the Bioremediation of Gadolinium Waste.

Several hundreds of tons of gadolinium-based contrast agents (GBCAs) are being dumped into the environment every year. Although macrocyclic GBCAs exhibit superior stability compared to their linear counterparts, we have found that the structural integrity of chelates are susceptible to ultraviolet light, regardless of configuration. In this study, we present a synthetic protein termed GLamouR that binds and reports gadolinium in an intensiometric manner. We then explore the extraction of gadolinium from GBCA-spiked artificial urine samples and investigate if the low picomolar concentrations reported in gadolinium-contaminated water sources pose a barrier for bioremediation. Based on promising results, we anticipate GLamouR can be used for detecting and mining REEs beyond gadolinium as well and hope to expand the biological toolbox for such applications.

Evaluation of potential biomarkers to determine adequate colostrum provision in male dairy-beef calves upon arrival at the rearing facility beyond 14 days of age.

Colostrum consumption is crucial for passive immunization and development of the newborn calf. However, the incidence on failed transfer of passive immunity in male calves destined to dairy-beef production remains high to date. In addition, the lack of an automated procedure to validate the immunization status upon arrival at rearing facilities in calves beyond 14 d of age impedes the identification of failed transfer of passive immunity, and therefore, of those calves at high risk of suffering diseases. For this study, 82 newborn male Holstein calves (43.3 ± 0.86 kg of body weight; mean ± standard error) from a commercial dairy farm were used to investigate potential serum biomarkers of colostrum provision. The potential biomarkers selected were IgG, IgG1, cholesterol, alkaline phosphatase, gamma-glutamyl transferase (GGT), and total protein (TP). Treatments were as follows: high-colostrum (HC; n = 49), in which calves received 4 L of colostrum within the first 2 h after birth and 2 L of colostrum in the next 3 feedings within the first 24 h after birth, for a total of 10 L of colostrum; and low-colostrum (LC; n = 33), in which calves received only 2 L of colostrum within the first 2 h after birth. After colostrum consumption, calves were allocated to individual hutches and fed 2 L of milk replacer twice daily at a concentration of 125 g/L as fed. Starter feed and water were offered ad libitum. At approximately 14 d of age (14.2 ± 0.81 d of age; mean ± standard error) calves were transported 2.5 h to a research unit at IRTA (Torre Marimon, Spain) simulating the arrival to a rearing facility. Blood samples were collected before feeding at birth, 48 h after birth, and at arrival to the rearing facility. Results on the serum concentrations of the potential biomarkers at arrival to the rearing facility showed that IgG, IgG1, GGT, and TP were greater for the HC calves compared with the LC calves. Serum concentrations of cholesterol and alkaline phosphatase did not show differences between treatment groups. Additionally, body weight losses from birth until arrival to the rearing facility were greater for the LC treatment compared with the HC. Because of their low cost, quickness, and ease of measurement, GGT and TP were good indicators of colostrum intake in calves arriving at rearing facilities beyond 14 d of age.

Intercritical photophobia in the migrainous patient. Proposal for diagnostic criteria.

INTRODUCTION: Photophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology. BASIC PROCEDURE: This article focuses on 30 clinical cases with isolated intense photophobia and on the review of the literature. OBJECTIVE: The purpose of this article is to establish diagnostic criteria for photophobia. RESULTS: The etiology of photophobia appears to be at the level of the intrinsically photosensitive retinal ganglion cells known as melanopsin cells and at a neurochemical level mediated by calcitonin-related peptide and the pituitary activating peptide cyclase. CONCLUSION: The treatment of photophobia could consist of monoclonal antibodies against calcitonin-related peptide and/or pituitary activating peptide cyclase.

Sexist Attitudes in Adolescents: Prevalence and Associated Factors.

Gender violence is a major public health issue. The aim of this study was to determine the prevalence of sexist attitudes that could be associated with said violence, and to identify some sociodemographic variables that predict sexism. A cross-sectional observational study was conducted with 723 adolescents between the ages of 14 to 19. Their explicit sexist attitudes were measured with the EVAMVE and EARG scales, and their implicit attitudes were measured with a series of assessment items regarding the behavior of the protagonists of a video and a story in which a young couple interacts. Explicit and implicit sexist attitudes were detected in adolescents of both sexes. Qualitatively, the assessment of the behavior of the female protagonist is striking. Regarding the sexism predictors, it was found that male adolescents, those born outside of Spain, those who were studying in a public school, those whose parents did not have university studies, and those who consumed the most pornography presented attitudes that were significantly more sexist. These results suggest that it is necessary to strengthen education in equality and prevention of gender violence in adolescents, and to develop affective-sexual education programs.

Methylothon: a Versatile Course-Based High School Research Experience in Microbiology and Bioinformatics with Pink Bacteria.

Methylothon is an inquiry-based high school learning module in microbial ecology, molecular biology, and bioinformatics that centers around pink-pigmented plant-associated methylotrophic bacteria. Here, we present an overview of the module's learning goals, describe course resources (available for public use at http://methylothon.com), and relate lessons learned from adapting Methylothon for remote learning during the pandemic in spring of 2021. This curriculum description is intended not only for instructors but also for microbial ecology researchers with an interest in conducting K-12 outreach. The original in-person version of the module allows students to isolate their own strains of methylotrophic bacteria from plants they sample from the environment, to identify these using PCR, sequencing, and phylogenetic analysis, and to contribute their strains to original research in a university lab. The adapted version strengthens the focus on bioinformatics and increases its flexibility and accessibility by making the lab portion optional and adopting free web-based tools. Student feedback and graded assignments from spring 2021 revealed that the lesson was especially effective at introducing the concepts of BLAST and phylogenetic trees and that students valued and felt inspired by the opportunity to conduct hands-on work and to participate in community science.

A perspective on the role of lanthanides in biology: Discovery, open questions and possible applications.

Because of their use in high technologies like computers, smartphones and renewable energy applications, lanthanides (belonging to the group of rare earth elements) are essential for our daily lives. A range of applications in medicine and biochemical research made use of their photo-physical properties. The discovery of a biological role for lanthanides has boosted research in this new field. Several methanotrophs and methylotrophs are strictly dependent on the presence of lanthanides in the growth medium while others show a regulatory response. After the first demonstration of a lanthanide in the active site of the XoxF-type pyrroloquinoline quinone methanol dehydrogenases, follow-up studies showed the same for other pyrroloquinoline quinone-containing enzymes. In addition, research focused on the effect of lanthanides on regulation of gene expression and uptake mechanism into bacterial cells. This review briefly describes the discovery of the role of lanthanides in biology and focuses on open questions in biological lanthanide research and possible application of lanthanide-containing bacteria and enzymes in recovery of these special elements.

Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis.

INTRODUCTION: Genomic studies have identified numerous genetic variants associated with susceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of the risk of developing the disease. These variants are located in genes involved in specific pathways, which supports the hypothesis that the risk of developing MS may be linked to alterations in these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene, which encodes one of the TNF-α receptors involved in a signaling pathway previously linked to autoimmune disease. METHODS: We included 138 individuals from 23 families including at least 2 members with MS, and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing. We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584 (-g.6442643C > G, NM_001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligodendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labeling was used to locate the protein within cells. We also analyzed the ability of transfected HOG cells to proliferate and differentiate into oligodendrocytes. RESULTS: Variant rs4149584 was found in 2 patients with MS (3.85%), one patient with another autoimmune disease (7.6%), and in 5 unaffected individuals (7.46%). The 2 patients with MS and variant rs4149584 were homozygous carriers and belonged to the same family, whereas the remaining individuals presented the variant in heterozygosis. The study of HOG cells transfected with the mutation showed that the protein does not reach the cell membrane, but rather accumulates in the cytoplasm, particularly in the endoplasmic reticulum and near the nucleus; this suggests that, in the cells presenting the mutation, TNFRSF1 does not act as a transmembrane protein, which may alter its signaling pathway. The study of cell proliferation and differentiation found that transfected cells continue to be able to differentiate into oligodendrocytes and are probably still capable of producing myelin, although they present a lower rate of proliferation than wild-type cells. CONCLUSIONS: Variant rs4149584 is associated with risk of developing MS. We analyzed its functional role in oligodendrocyte lineage cells and found an association with MS in homozygous carriers. However, the associated molecular alterations do not influence the differentiation into oligodendrocytes; we were therefore unable to confirm whether this variant alone is pathogenic in MS, at least in heterozygosis.

Comprehensive Phylogenomics of Methylobacterium Reveals Four Evolutionary Distinct Groups and Underappreciated Phyllosphere Diversity.

Methylobacterium is a group of methylotrophic microbes associated with soil, fresh water, and particularly the phyllosphere, the aerial part of plants that has been well studied in terms of physiology but whose evolutionary history and taxonomy are unclear. Recent work has suggested that Methylobacterium is much more diverse than thought previously, questioning its status as an ecologically and phylogenetically coherent taxonomic genus. However, taxonomic and evolutionary studies of Methylobacterium have mostly been restricted to model species, often isolated from habitats other than the phyllosphere and have yet to utilize comprehensive phylogenomic methods to examine gene trees, gene content, or synteny. By analyzing 189 Methylobacterium genomes from a wide range of habitats, including the phyllosphere, we inferred a robust phylogenetic tree while explicitly accounting for the impact of horizontal gene transfer (HGT). We showed that Methylobacterium contains four evolutionarily distinct groups of bacteria (namely A, B, C, D), characterized by different genome size, GC content, gene content, and genome architecture, revealing the dynamic nature of Methylobacterium genomes. In addition to recovering 59 described species, we identified 45 candidate species, mostly phyllosphere-associated, stressing the significance of plants as a reservoir of Methylobacterium diversity. We inferred an ancient transition from a free-living lifestyle to association with plant roots in Methylobacteriaceae ancestor, followed by phyllosphere association of three of the major groups (A, B, D), whose early branching in Methylobacterium history has been heavily obscured by HGT. Together, our work lays the foundations for a thorough redefinition of Methylobacterium taxonomy, beginning with the abandonment of Methylorubrum.