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Biology education is crucial for living in a volatile, uncertain, complex, ambiguous, disruptive, and diverse environment. Moreover, most literature suggested developing learning activities for students based on the knowledge, attitudes, and skills competency gaps. Thus, this study assessed the academic performance in terms of their examination scores among the 150 randomly selected Grade Eight Biology students in different public schools in a rural municipality in Cebu, Philippines. It employed a descriptive research methodology. The test questionnaire was anchored on the Department of Education Learning Guide in determining the student's academic performance in Biology. The respondents' data were gathered from their Biology teachers and were expressed in frequencies and percentages. Data were computed using SPSS Statistics 27. The majority of the student's academic performance in Biology for Digestive System (n=65, 43.33%), Biodiversity (n=68, 45.33%), and Ecosystem (n=56, 37.34%) competencies indicate that the majority of the respondents' scores did not meet expectations. Our findings strongly recommend that teachers carefully plan and provide necessary learning activities based on the needs and knowledge gaps of the students in their instructional practices to give their students a thorough grasp of the topics covered in the Biology class.

Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog of triptolide, has demonstrated potent antiinflammatory and antitumor activity in several preclinical models and has proven both safe and efficacious in clinical trials for advanced gastrointestinal malignancies. Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared with posttransplant cyclophosphamide (PTCy). Strikingly, we found Minnelide improved survival, weight loss, and clinical scores in an MHC-mismatched model of aHSCT. These benefits were also apparent in minor MHC-matched aHSCT and xenogeneic HSCT models. Minnelide was comparable to PTCy in terms of survival, GVHD clinical score, and colonic length. Notably, in addition to decreased donor T cell infiltration early after aHSCT, several regulatory cell populations, including Tregs, ILC2s, and myeloid-derived stem cells in the colon were increased, which together may account for Minnelides GVHD suppression after aHSCT. Importantly, Minnelides GVHD prevention was accompanied by preservation of graft-versus-tumor activity. As Minnelide possesses anti-acute myeloid leukemia (anti-AML) activity and is being applied in clinical trials, together with the present findings, we conclude that this compound might provide a new approach for patients with AML undergoing aHSCT.

Abstract Background Theileria haneyi is one of the three known causative agents of equine piroplasmosis. While imidocarb is generally effective in the clearance of the highly pathogenic Theileria equi, it is ineffective in the treatment of T. haneyi. Moreover, co-infection with T. haneyi has been shown to impede the successful treatment of T. equi. Furthermore, tulathromycin and diclazuril have demonstrated inefficacy in eradicating T. haneyi. The absence of an effective therapeutic agent against this parasite represents a significant obstacle in managing equine piroplasmosis. Methods To address this issue, we evaluated the efficacy of buparvaquone in the treatment of T. haneyi in chronically infected horses. Results Our findings showed that treatment of horses with the recommended dose of 2.5 mg/kg of buparvaquone led to a rapid abatement of T. haneyi levels, to a level where the parasites were not detectable by nested PCR. Following treatment, the horses remained PCR negative for a minimum of seven weeks until recrudescence occurred. Subsequent re-administration of buparvaquone at an increased dosage of 6 mg/kg upon recrudescence failed to exert a theilericidal effect on T. haneyi. Throughout the treatment regimen, the hematological parameters of the horses and most components of the chemistry panel remained within the normal range, except for blood urea nitrogen levels, which fell below the normal range in certain instances. conclusions BPQ at 2.5 mg/kg and 6 mg/kg had a robust theilericidal effect but was ineffective in the clearance of the T. haneyi infection in persistently infected animals. Graphical Abstract

Managing health and well-being issues can be challenging for college students. Alternative supports, such as online programs, have been identified as cost-effective and efficient methods of providing inclusive support to college students, removing numerous barriers to health and well-being promotion. The article summarized a novel, evidence-based approach to developing an online health and well-being program. The program is based on Cognitive Behavioral Therapy (CBT), the positive emotion, engagement, relationships, meaning, and accomplishments (PERMA) construct, and the analysis, design, development, implementation, and evaluation (ADDIE) model. It discusses future directions in the evaluation, assessment, and documentation of the fitness-for-purpose process.

BACKGROUND: 3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R. METHODS: We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs. FINDINGS: We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found. INTERPRETATION: In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Abstract Background Access to an on-demand pericoital oral contraceptive pill – used to prevent pregnancy within a defined window around sexual intercourse – could offer women more reproductive agency. A contraceptive with this indication is not currently available in any market. This review aims to understand international user appeal for an on-demand pericoital oral contraceptive pill. Methods Systematic scoping review, comprising 30 peer-reviewed papers published between 2014–2023. Results Data from 30 papers reporting on research from 16 countries across five World Health Organisation regions suggests widespread user appeal for on-demand oral contraceptive pills that can be used peri- or post-coitally, especially among women who are younger, more educated or who have less frequent sex. Women of varying age, wealth, employment or relationship status, and with different prior experience of using modern contraceptives, were also interested. Women identified clear rationale for use and preference of these types of product: close alignment with women’s sexual lives that comprised unplanned, spontaneous or occasional sex; perceived convenience and effectiveness; discreet use of pills to negotiate contextual circumstances that constrained their reproductive agency. Factors inhibiting use included knowledge barriers and attitudes of service providers, a lack of knowledge and misinformation among end-users, women’s dislike of menstrual side effects and myths related to the effects of hormone content on future fertility. Conclusions Introduction of an on-demand pericoital oral contraceptive pill could expand contraceptive choice for diverse women experiencing unmet need for modern contraception and constrained sexual and reproductive agency. Priorities for future research include: broadening the geographical scope of evidence to include SE Asia and the Pacific, and international rural and peri-urban settings; documenting the perspectives of adolescents and unmarried young people; identifying opportunities for innovation in the supply channels to enhance appropriate, affordable access to on-demand oral contraceptives; and unpacking how to bring new pericoital contraceptives to the market in a variety of international settings.

Schools have been postulated as ideal environments to encourage physical activity (PA). This study aimed to assess the relationship between PA in school hours, motor competence, and screen time in a sample of Spanish preschool children. Fifty-seven 4-5-year-old preschoolers (n = 32 girls) participated. The Garmin Vivofit wristband was used to measure the PA levels during school hours in a week. Sedentary behavior was estimated through screen-time hours reported by preschoolers' families and motor competence was assessed by the Athletic Skills Track. The anthropometry (weight/height) and demographic data were also collected. We found that motor competence was significantly associated with PA both in minutes and in steps. Therefore, increased motor competence was related to higher engagement in PA during school hours. No association was found between screen time and PA or proficiency of motor competence. No gender differences were found in any variable assessed. Based on the relationship between motor competence proficiency and the amount of PA in preschool children, our findings support the need for specific strategies to promote fundamental movement skills and increase PA practice from early childhood.

UNLABELLED: We have shown that KRAS-TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS-TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell-dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF-TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell-neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC. SIGNIFICANCE: By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell-excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer. This article is highlighted in the In This Issue feature, p. 1275.

Summary: Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis.

IntroductionThis study evaluates the effectiveness of the Project SCORE intervention in fostering Positive Youth Development (PYD) within competitive youth sport settings in Portugal. Project SCORE is an online PYD-focused tool developed to assist coaches in promoting the 4Cs—competence, confidence, connection, and character—within their coaching.MethodsThe research involved 13 coaches and 70 youth athletes from football and rowing teams. Methodologically, this study analyzed the pre- and post- Project SCORE intervention data, assessing the perceptions of coaches and athletes towards the development of the 4Cs.ResultsResults indicated significant improvements in athletes' perceptions of 4Cs post-intervention, and among coaches' perceptions, there was a significant improvement in the practice and transfer of life skills. Particularly, coaches showed enhanced abilities in fostering life skills and facilitating the transfer of these skills to competitive environments, although some dimensions like sport climate did not sustain positive changes.DiscussionThe findings highlight the benefits of customized PYD-based programs in competitive youth sports and suggest the need for further research to enhance their widespread and consistent implementation.

Abstract Ocean warming and acidification, decreases in dissolved oxygen concentrations, and changes in primary production are causing an unprecedented global redistribution of marine life. The identification of underlying ecological processes underpinning marine species turnover, particularly the prevalence of increases of warm-water species or declines of cold-water species, has been recently debated in the context of ocean warming. Here, we track changes in the mean thermal affinity of marine communities across European seas by calculating the Community Temperature Index for 65 biodiversity time series collected over four decades and containing 1,817 species from different communities (zooplankton, coastal benthos, pelagic and demersal invertebrates and fish). We show that most communities and sites have clearly responded to ongoing ocean warming via abundance increases of warm-water species (tropicalization, 54%) and decreases of cold-water species (deborealization, 18%). Tropicalization dominated Atlantic sites compared to semi-enclosed basins such as the Mediterranean and Baltic Seas, probably due to physical barrier constraints to connectivity and species colonization. Semi-enclosed basins appeared to be particularly vulnerable to ocean warming, experiencing the fastest rates of warming and biodiversity loss through deborealization.

This study delves into the evolutionary path of food and agricultural research and development organizations, aligning with the ambitious climate-change objectives outlined in the Paris Agreement. Our exploration revolves around advancing the triple goals of creating sustainable, low-emission food systems, enhancing nutrition, and ensuring food security. A pivotal consideration emerges from the recent United Nations Framework Convention on Climate Change's Conference of the Parties, where civil society advocacy gained momentum, emphasizing the need to seamlessly integrate food and nutrition security within climate-change mitigation initiatives. The objective of this study is therefore to examine how agriculture and food research organizations incorporate climate-change mitigation to address food security, health, and environmental sustainability challenges. In light of this, we undertook an examination of CGIAR's published articles, existing research initiatives, and a curated selection of innovations, with a focus on regional climate-change priorities. Our analysis not only underscores CGIAR's commitment to climate-change research, but also evaluates its contribution to reducing greenhouse gas emissions within food systems. Noteworthy is the discernible shift in CGIAR's research portfolio, reflecting a response to the escalating demand for environmental sustainability and an increased awareness of the interconnected nature of malnutrition and food security. While CGIAR has made significant strides in climate-change adaptation efforts, our analysis indicates an incomplete integration of food-systems perspectives for mitigating climate change. Our proposed approach advocates a comprehensive strategy that harmonizes adaptation and mitigation research, encourages cross-CGIAR collaboration through institutional changes, and underscores the importance of scaling innovations. This holistic endeavor highlights the type of research CGIAR is developing, seamlessly integrating the food-systems approach into the broader climate-change research agenda.

Background: Stenotrophomonas maltophilia is an opportunistic pathogen found in healthcare settings. During April–September 2022, nine S. maltophilia bloodstream infections (BSIs) were identified among intensive care unit (ICU) patients at a hospital in Alameda County, California. Whole genome sequencing found isolates to be highly related. Despite implementation of infection prevention and control (IPC) interventions, four additional S. maltophilia BSIs were identified during June–September 2023. We investigated to identify risk factors for infection and stop transmission. Methods: We conducted a matched case-control study. A case was defined as S. maltophilia isolated from a blood culture from an ICU patient with a fever during April 2022–September 2023; control-patient subjects were patients admitted to the ICU during the same period with hospital stay greater than or equal to their matched case. Three control subjects were matched to each case. We extracted information on risk factors for infection from medical charts and observed IPC practices in hospital locations of interest. We collected environmental samples from the ICU, radiology unit, and emergency department. Results: Among 13 cases and 39 control subjects, patients exposed to iodinated contrast Omnipaque-300 (odds ratio [OR]: 5.7; 95% CI: 1.2–28.0), injectable propofol (OR: 12.2; 95% CI: 1.5–101.4), or fentanyl (OR: 9.2; 95% CI: 1.8–Inf.) were more likely to have a S. maltophilia BSI, compared with control-subjects. IPC deficiencies included improper cleaning and storage of medical equipment, including the contrast injection system, and patient care supplies. The outbreak strain of S. maltophilia was not isolated from environmental samples. Conclusions: Although a point-source was not identified, S. maltophilia was likely transmitted through improper IPC practices involving injectable contrast or anesthesia. Recommendations on proper cleaning and disinfection of the contrast injection system and proper storage, preparation, and administration of medications were made to reduce risk for contamination.

IntroductionTheileria orientalis, an economically significant tick-borne hemoparasite, infects cattle globally. The T. orientalis Ikeda genotype, transmitted by Haemaphysalis longicornis ticks, is associated with clinical manifestations characterized by anemia, abortions, and mortality, although subclinical infections prevail. Despite the common occurrence of subclinical infections, therapeutic interventions targeting T. orientalis Ikeda in such cases are currently lacking, impeding effective parasite control measures. To address this critical knowledge gap, we assessed the efficacy of buparvaquone (BPQ) in eliminating the T. orientalis Ikeda, US isolate, in sub-clinically infected cattle.MethodsTwelve sub-clinically infected calves, identified by the presence of T. orientalis in peripheral blood alongside the absence of fever and anemia, were enrolled in the study. Six calves received two treatments of the BPQ label dose (2.5 mg/kg) at a 48-h interval, while additional three calves received the drug at a dosage of 6 mg/kg following the same regimen. Three untreated calves served as controls.Results and discussionEndpoint and quantitative PCR analyses revealed that BPQ exerted a transient effect on T. orientalis parasitemia. Parasites remained undetectable in peripheral blood until weeks 4 and 11 post-treatment in animals administered 2.5 mg/kg and 6 mg/kg of BPQ, respectively. Intriguingly, following recrudescence, administering 6 mg/kg to animals previously treated with 2.5 mg/kg did not result in a reduction in parasite load. Pharmacokinetic analysis data suggested that escalating the dosage led to a less than proportional increase in serum concentrations of BPQ. Moreover, a significant yet reversible decrease (p

Abstract Introduction Silica‐sprayed tubes (SSTs) are often used to transport synovial fluid samples in equine practice. They promote the coagulation of the sample. The objective of the study is to evaluate the effect of SST on bacterial culture. Materials and methods The study was divided into two parts: sterile saline (Part A) and synovial fluid (Part B). Four common bacteria associated with equine synovial sepsis were used: Streptococcus pyogenes, Escherichia coli, Staphylococcus aureus and methicillin‐resistant S. aureus (MRSA). Three collection tubes were used: STT, plain (no‐additives) and brain and heart infusion (BHI) broth. Bacteria were cultured in horse blood agar plates for 48 h. Outcome variables were negative culture, positive culture and total number of colony‐forming units (CFUs). Statistical analysis was performed using Mann–Whitney U test, and significance was set at p

During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell-mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with Mycobacterium tuberculosis (Mtb) triggers HIF1A-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase inhibitor oxamate and the HIF1A inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.

IntroductionSerum symmetric dimethylarginine (SDMA) and creatinine are commonly used biomarkers of renal function in cats. We hypothesize that the serum analytes creatinine and SDMA are equally effective at detecting impaired renal function caused by meloxicam-induced renal injury in cats. Our primary objective was to compare serum concentrations of SDMA and creatinine in cats before, during, and after induction of renal injury from repeated dosages of meloxicam in the context of a small pilot study.MethodsThis follow-up study results from data collected in a well-controlled study that included 12 healthy female adult purpose-bred cats. Cats in the treatment group received meloxicam 0.3 mg/kg subcutaneously (SC) every 24 h for 31 days. Cats in the control group received saline (0.1 mL SC). Renal injury was defined as the presence of tubular damage, basement membrane damage, and/or interstitial inflammation in histological sections of kidney tissue. Serum creatinine and SDMA concentration were measured every 4 days.ResultsIn the control group, no cats developed renal azotemia. In the treatment group, four out of six cats developed elevated serum creatinine and histopathological evidence of renal injury. Three of these cats developed an elevation in serum SDMA. The time to the development of renal azotemia using serum creatinine or SDMA was not significantly different (p > 0.05).DiscussionIn this pilot study, there was no evidence that serum SDMA was superior to serum creatinine at detecting impaired renal function caused by meloxicam-induced renal injury in cats.

Introduction:B. bovis is an apicomplexan parasite responsible for bovine babesiosis, a tick-borne disease with a worldwide impact. The disease remains inefficiently controlled, and few effective drugs, including imidocarb dipropionate (ID), are currently available in endemic areas. The objective of this study was to evaluate whether buparvaquone (BPQ), a drug currently used to treat cattle infected with the Babesia-related Theileria spp. parasites, could be active against Babesia parasites. Herein, we compared the effect of ID and BPQ on B. bovis growth in vitro erythrocyte culture.Methods:We compared the effect of ID and BPQ on the culture-adapted Texas T2Bo strain of B. bovis. In vitro cultured parasites were incubated with ID and BPQ at two starting parasitemia levels (PPE), 0.2% and 1%. In vitro cultured parasites were treated with ID or BPQ at concentrations ranging from 10 to 300 nM, during 4 consecutive days. Parasitemia levels were daily evaluated using microscopic examination. Data was compared using the independent Student’s t-test.Results and discussion:Both ID and BPQ significantly inhibited (p < 0.05) the growth of B. bovis, regardless of the initial parasitemia used. At 1% parasitemia, BPQ had lower calculated inhibitory concentration 50 (IC50: 50.01) values than ID (IC50: 117.3). No parasites were found in wells with 0.2% starting parasitemia, treated previously with 50 nM of BPQ or ID, after 2 days of culture without drugs. At 1% parasitemia, no parasite survival was detected at 150 nM of BPQ or 300 nM of ID, suggesting that both drugs acted as babesiacidals.Conclusion:Overall, the data suggests that BPQ is effective against B. bovis and shows a residual effect that seems superior to ID, which is currently the first-line drug for treating bovine babesiosis globally.

With the appearance of physical literacy, a new approach to physical education has emerged, aimed at promoting lifelong physical activity. With the intention of exploring whether physical education teacher training programmes are in line with this trend, we analysed the conceptions of pre-service teachers. The aim of this study was to design and validate a questionnaire analysing the conceptions of students taking the degree course in the Science of Physical Activity and Sport with regard to what it means to be a physically well-educated student. A questionnaire was designed for data collection. A chi-square test was used to analyse the statistically significant differences and Cramer's V was used to quantify the degree of association. The results show that pre-service teachers consider a physically well-educated student to be one who maintains a healthy lifestyle and has overall motor competence and self-awareness. Differences have been found between the conceptions of pre-service teachers, between universities and between the beginning and the end of training programs. A valid and reliable instrument has been obtained for analysing the conceptions of pre-service teachers. The studies reinforce the conceptions related to an active lifestyle and overall motor competence. The conceptions of pre-service teachers are within closer range of physical literacy after their studies.

Abstract Background The nationally determined contribution (NDC) presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Convention on Climate Change (UNFCCC) on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation (REDD+). In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon (SOC) stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under climate variability due to a lack of information. The objectives of this study were: (i) to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and (ii) to relate SOC stocks with spatial–temporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high inter-annual climate variability. Methods We used 1040 forest soil samples (0–30 cm) to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covariates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google Earth Engine cloud-based computing platform for subsequent modelling. To determine the biodiversity threats from high inter-annual climate variability, we employed the spatial–temporal satellite-derived indices based on Enhanced Vegetation Index (EVI) and land surface temperature (LST) images from Landsat imagery. Results SOC model (0–30 cm depth) prediction accounted for 69% of the variation of this soil property across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C (2.71–2.84 Pg C with a probability of 90%) for a total area of 460,790 km2, where Chaco forests represented 58.4% of total SOC stored, followed by Andean Patagonian forests (16.7%) and Espinal forests (10.0%). SOC stock model was fitted as a function of regional climate, which greatly influenced forest ecosystems, including precipitation (annual mean precipitation and precipitation of warmest quarter) and temperature (day land surface temperature, seasonality, maximum temperature of warmest month, month of maximum temperature, night land surface temperature, and monthly minimum temperature). Biodiversity was influenced by the SOC levels and the forest regions. Conclusions In the framework of the Kyoto Protocol and REDD+, information derived in the present work from the estimate of SOC in native forests can be incorporated into the annual National Inventory Report of Argentina to assist forest management proposals. It also gives insight into how native forests can be more resilient to reduce the impact of biodiversity loss.

La lateralidad es un constructo relevante por su repercusión en el desarrollo motor, los procesos de aprendizaje y el rendimiento deportivo. Existe una serie de estudios que han identificado una relación entre determinados perfiles de lateralidad y una mayor versatilidad en las acciones motoras. Dicha relación no se ha explorado en el ámbito escolar ni con personas en las primeras etapas del desarrollo deportivo. Este estudio pretendía describir la distribución porcentual de los tipos de preferencia lateral (ocular, de dirección, de giro, manual, de pie, cruzada) en una muestra de escolares (deportistas vs. no deportistas) y explorar su posible relación con la creatividad motora (fluidez y originalidad). Participaron en el estudio 500 escolares (220 niñas y 280 niños) de 9.05 ± 1.86 años. El ojo dominante y la dirección de rotación se identificaron mediante pruebas estandarizadas. La preferencia lateral de manos y pies se evaluó mediante la observación durante la participación en juegos deportivos. Se utilizaron dos situaciones de prueba durante el juego (GTS, por sus siglas en inglés) para evaluar los parámetros de creatividad motora (fluidez y originalidad). El porcentaje de lateralidad izquierda y cruzada fue significativamente mayor en el grupo de escolares que practicaban deporte. Las pruebas t revelaron un rendimiento creativo superior (fluidez y originalidad) en los escolares con preferencia por el sentido de rotación hacia el lado izquierdo o con lateralidad cruzada. Los valores d de Cohen muestran vinculación cuando la creatividad se evalúa a través de situaciones de juego con interacción directa de los jugadores. Los resultados sugieren una vinculación entre la preferencia lateral y una mayor fluidez de movimientos y originalidad, lo cual sería interesante para detectar talentos y diseñar programas.

Abstract Background Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. Methods The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. Results We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. Conclusions Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.

Abstract Background Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. Results Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m $$^2$$ 2 by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC $$_{\text {0-last}}$$ 0-last was 890 h $$\cdot$$ · ng/ml (range 750-1100 h $$\cdot$$ · ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. Conclusions Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.

Abstract Suboptimal vaccine response is a significant concern in patients with Inflammatory Bowel Disease (IBD) receiving biologic drugs. This single-center observational study involved 754 patients with IBD. In Phase I (October 2020-April 2021), 754 IBD participants who had not previously received the SARS-CoV-2 vaccine, underwent blood extraction to assess the seroprevalence of SARS-CoV-2 infection and IBD-related factors. Phase II (May 2021-October 2021) included a subgroup of 52 IBD participants with confirmed previous SARS-CoV-2 infection, who were studied for humoral and cellular response to the SARS-CoV-2 vaccine. In Phase I, treatment with anti-TNF was associated with lower rates of seroconversion (aOR 0.25 95% CI [0.10–0.61]). In Phase II, a significant increase in post-vaccination IgG levels was observed regardless of biologic treatment. However, patients treated with anti-TNF exhibited significantly lower IgG levels compared to those without IBD therapy (5.32 ± 2.47 vs. 7.99 ± 2.59 U/ml, p = 0.042). Following vaccination, a lymphocyte, monocyte, and NK cell activation pattern was observed, with no significant differences between patients receiving biologic drugs and those without IBD treatment. Despite lower seroprevalence and humoral response to the SARS-CoV-2 vaccine in patients treated with anti-TNF, the cellular response to the vaccine did not differ significantly from that patients without IBD therapy.