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Abstract Machine learning has increasingly been applied to predict opioid-related harms due to its ability to handle complex interactions and generating actionable predictions. This review evaluated the types and quality of ML methods in opioid safety research, identifying 44 studies using supervised ML through searches of Ovid MEDLINE, PubMed and SCOPUS databases. Commonly predicted outcomes included postoperative opioid use (n = 15, 34%) opioid overdose (n = 8, 18%), opioid use disorder (n = 8, 18%) and persistent opioid use (n = 5, 11%) with varying definitions. Most studies (96%) originated from North America, with only 7% reporting external validation. Model performance was moderate to strong, but calibration was often missing (41%). Transparent reporting of model development was often incomplete, with key aspects such as calibration, imbalance correction, and handling of missing data absent. Infrequent external validation limited the generalizability of current models. Addressing these aspects is critical for transparency, interpretability, and future implementation of the results.

Abstract Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid. Thirty-three patients received BPX-601 with or without rimiducid, 24 patients with mPDAC and 9 with mCRPC. Two dose-limiting toxicities and two treatment-related deaths occurred in the highest-dose mCRPC cohort, after which the study was terminated, without determination of the RP2D. Two mCRPC patients experienced partial responses (one unconfirmed), and 56% of mCRPC patients achieved ≥50% reduction in prostate-specific antigen. BPX-601 cell expansion, long-term persistence in peripheral blood, and tumor infiltration were observed. Rimiducid increased circulating inflammatory cytokines/chemokines consistent with GoCAR-T® cell activation. These results suggest that pharmacological activation of GoCAR-T® cells is feasible and may offer a promising avenue to control chimeric antigen receptor-T cell activity with continued dose-optimization to improve tolerability.

Abstract Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion. As the lipid droplet grows, caveolae disassemble to release their membrane reservoir and increase cell surface area, and transfer specific caveolar components to the LD surface. Adipose tissue null for caveolae is stiffer, shows compromised deformability, and is prone to rupture under mechanical compression. Mechanistically, phosphoacceptor Cav1 Tyr14 is required for caveolae disassembly: adipocytes bearing a Tyr14Phe mutation at this residue are stiffer and smaller, leading to decreased adiposity in vivo; exhibit deficient transfer of Cav1 and EHD2 to the LD surface, and show distinct Cav1 molecular dynamics and tension adaptation. These results indicate that Cav1 phosphoregulation modulates caveolar dynamics as a relevant component of the homeostatic mechanoadaptation of the differentiated adipocyte.

Abstract By analogy with the formula for the massless string disk amplitudes, we define massive field-theory tree amplitudes and conjecture that the BRST cohomology structure of pure spinor superspace fixes their form. We give evidence by deriving the pure spinor superspace expression of the massive field-theory n-point tree amplitude with one first-level massive and n − 1 massless states in two ways: 1) from BRST cohomology arguments in pure spinor superspace and 2) from the α′2 correction to the massless string amplitudes by inverting the unitarity constraint in superspace.

Abstract Background Hybrids are expected to show greater phenotypic variation than their parental species, yet how hybrid phenotype expression varies with genetic distances in closely-related parental species remains surprisingly understudied. Here, we investigate pelage and morphometric trait variation in anthropogenic hybrids between four species of Brazilian Callithrix marmosets, a relatively recent primate radiation. Marmoset species are distinguishable by pelage phenotype and morphological specializations for eating tree exudates. In this work, we (1) describe qualitative phenotypic pelage differences between parental species and hybrids; (2) test whether significant quantitative differences exist between parental and hybrid morphometric phenotypes; and (3) determine which hybrid morphometic traits show heterosis, dysgenesis, trangression, or intermediacy relative to the parental trait. We investigated cranial and post-cranial morphometric traits, as most hybrid morphological studies focus on the former instead of the latter. Finally, we estimate mitogenomic distances between marmoset species from previously published data. Results Marmoset hybrid facial and overall body pelage variation reflected novel combinations of coloration and patterns present in parental species. In morphometric traits, C. jacchus and C. penicillata were the most similar, while C. aurita was the most distinct, and C. geoffroyi trait measures fell between these species. Only three traits in C. jacchus x C. penicillata hybrids showed heterosis. We observed heterosis and dysgenesis in several traits of C. penicillata x C. geoffroyi hybrids. Transgressive segregation was observed in hybrids of C. aurita and the other species. These hybrids were also C. aurita-like for a number of traits, including body length. Genetic distance was closest between C. jacchus and C. penicillata and farthest between C. aurita and the other species. Conclusion We attributed significant morphometric differences between marmoset species to variable levels of morphological specialization for exudivory in these species. Our results suggest that intermediate or parental species-like hybrid traits relative to the parental trait values are more likely in crosses between species with relatively lesser genetic distance. More extreme phenotypic variation is more likely in parental species with greater genetic distance, with transgressive traits appearing in hybrids of the most genetically distant parental species. We further suggest that fewer developmental disturbances can be expected in hybrids of more recently diverged parental species, and that future studies of hybrid phenotypic variation should investigate selective pressures on Callithrix cranial and post-cranial morphological traits.

Abstract The long-term practice of mulched drip irrigation (MDI) has significantly advanced cotton production in China’s arid regions. In this study, we conducted an evaluation of the changes to key soil environmental factors within cotton fields under MDI, providing a holistic assessment of MDI sustainability. Specifically, long-term MDI demonstrated numerous benefits including improved soil salinity management, nutrient retention, soil structure, and microbial functions. Collectively, these changes contribute to enhanced overall soil quality. Our research also confirms MDI as an effective integrated water-saving technology approach. Affirming the sustainability of widespread MDI promotion, our findings firmly support its potential as a sustainable and viable solution for oasis agriculture in arid lands, conferring long-term benefits to agricultural production in these regions.

Abstract Background Andalusia is the second largest region in Spain, and it has developed a comprehensive mental health (MH) plan that encourages the consolidation of the balanced care model. However, its geographical and socioeconomic disparity is a great challenge for a community-based MH system. Both the assessment of the implementation of the MH plan and the development of new tools to support decision-making can be considered critical. Objectives The present study aims (i) to assess how the integration of different types of MH care may influence system performance and (ii) to check the performance evolution of the integration process geographically regarding the small MH areas of Andalusia. Methods The performance of the Andalusian MH system was assessed by combining Monte Carlo simulation, fuzzy inference and data envelopment analysis. The relative technical efficiency was the main performance indicator. Results A correct integration of appropriate types of MH care, according to population needs, increases the performance of the Andalusian MH system both from global and regional perspectives. The spatial representation (based on small MH areas) of the results highlights how the performance depends on specific geographical characteristics. By analyzing the identified spatial clusters, defined by different management patterns depending on user and socioeconomic characteristics, benchmark areas and areas for improvement can be studied to design evidence-informed policies and interventions. Conclusions A global analysis of MH system performance was carried out, including both the successive integration of different types of care and its spatial evolution. Although an appropriate integration of different types of MH care has a positive effect on the Andalusian MH system, this process has different profiles depending on specific geographically based user and socioeconomic characteristics. The balanced care model can be considered the paradigm for assessing the performance of a large and populated territory such as Andalusia, which has a community-based MH system. This methodological approach (performance assessment and spatial analysis) may be used as a guide for developing future evidence-informed policies and managerial interventions.

Abstract The Antarctic Peninsula (West Antarctica) marine ecosystem has undergone substantial changes due to climate-induced shifts in atmospheric and oceanic temperatures since the 1950s. Using 25 years of satellite data (1998-2022), this study presents evidence that phytoplankton biomass and bloom phenology in the West Antarctic Peninsula are significantly changing as a response to anthropogenic climate change. Enhanced phytoplankton biomass was observed along the West Antarctic Peninsula, particularly in the early austral autumn, resulting in longer blooms. Long-term sea ice decline was identified as the main driver enabling phytoplankton growth in early spring and autumn, in parallel with a recent intensification of the Southern Annular Mode (2010-ongoing), which was observed to influence regional variability. Our findings contribute to the understanding of the complex interplay between environmental changes and phytoplankton responses in this climatically key region of the Southern Ocean and raise important questions regarding the far-reaching consequences that these ecological changes may have on global carbon sequestration and Antarctic food webs in the future.

Abstract Background Cervical cancer incidence is rising in Puerto Rico (PR). Whether the increase is real or reflective of increased diagnostic scrutiny remains unclear. Methods Using data from the PR Central Cancer Registry for 2001–2019, we estimated trends of hysterectomy-corrected cervical cancer incidence and mortality rates, overall, and by stage at diagnosis and age. Results Overall, cervical cancer incidence (per 100,000) increased 1.6%/year (95% CI, -0.5% to 3.8%) from 12.5 to 15.3, with a prominent increase in distant-stage disease (4.5%/year [95% CI, 1.6% to 8.0%]), particularly among screening age eligible (25–64-year-old) women (5.8%/year [95% CI, 2.1% to 10.6%]). Mortality rates in this age-group remained stable during the study period. Conclusions Increased occurrence of distant-stage disease among screening-eligible women is troubling and may reflect a real increase. Future research is needed to elucidate the factors underlying these trends. Improved prevention is also an urgent priority to reverse the rising cervical cancer incidence in PR.

Abstract Visual recognition is largely realized through neurons in the ventral stream, though recently, studies have suggested that ventrolateral prefrontal cortex (vlPFC) is also important for visual processing. While it is hypothesized that sensory and cognitive processes are integrated in vlPFC neurons, it is not clear how this mechanism benefits vision, or even if vlPFC neurons have properties essential for computations in visual cortex implemented via recurrence. Here, we investigated if vlPFC neurons in two male monkeys had functions comparable to visual cortex, including receptive fields, image selectivity, and the capacity to synthesize highly activating stimuli using generative networks. We found a subset of vlPFC sites show all properties, suggesting subpopulations of vlPFC neurons encode statistics about the world. Further, these vlPFC sites may be anatomically clustered, consistent with fMRI-identified functional organization. Our findings suggest that stable visual encoding in vlPFC may be a necessary condition for local and brain-wide computations.

Abstract Despite numerous efforts from numerical approaches to complement experimental measurements, several fundamental challenges have still hindered one’s ability to truly provide an atomistic picture of the nucleation process in nanocrystals. Among them, our study resolves three obstacles: (1) Machine-learning force fields including long-range interactions able to capture the finesse of the underlying atomic interactions, (2) Data-driven characterization of the local ordering in a complex structural landscape associated with several crystal polymorphs and (3) Comparing results from a large range of temperatures using both brute-force and rare-event sampling. Altogether, our simulation strategy has allowed us to study zinc oxide crystallization from nano-droplet melt. Remarkably, our results show that different nucleation pathways compete depending on the investigated degree of supercooling.

Obtaining accurate information regarding root zone soil moisture (RZSM) is a critical element of effective hydrological and agricultural management practices. Previous studies have relied on surface soil moisture (SSM) values, which are more easily measured, to estimate RZSM using the Soil Moisture Analytical Relationship (SMAR) model or regression method. However, the performance of these two types of methods in areas with complex topography still needs more exploration. Here, we assess the accuracy of these two types of methods in a forested mountainous catchment, using daily SSM measurements from 32 monitoring sites. The results show that both methods are capable of accurately estimating RZSM with a high NSE (>0.950) during the validation period. Additionally, they exhibit excellent model transferability at ungauged sites. Spatially, both methods perform better in drier areas than in wetter areas. Temporally, both methods are better in the wet–cold season than in the dry–warm season. Overall, both methods demonstrate comparable performance in the catchment, with NSE values of 0.986 and 0.951 during the validation period, respectively. The regression method is more suited to complex hydropedological environments characterized by long-term soil moisture monitoring and nonlinear hydropedological behaviors. Conversely, the SMAR model is better suited for flat areas and less spatial variability in microtopography. Moreover, the estimation of RZSM by both methods is influenced not only by soil moisture conditions but also by local factors including terrain topography, soil depth, and the degree of subsurface hydrological connectivity. This study adds to our understanding of RZSM estimation from SSM in complex terrain and will act as a reference for selecting appropriate methods of RZSM estimation. The results of this study underscore a discernible relationship between surface and deep soil moisture across varying spatial and temporal scales.

Category: Trauma; Ankle Introduction/Purpose: To compare the quality of syndesmotic reduction with the ankle in maximal dorsiflexion versus neutral plantarflexion (normal resting position). Methods: Two fellowship-trained orthopaedic surgeons disrupted syndesmoses of 10 cadaveric ankle specimens from 5 donors. All ankles were initially placed in neutral plantarflexion and were subsequently reduced and stabilized with one 0.062-inch K-wire in a quadricortical fashion. Post-reduction computed tomography (CT) scans were then obtained. This process was repeated with the ankles placed in maximal dorsiflexion. Post-reduction CT scans were compared to baseline CT imaging obtained prior to syndesmotic disruption. Mixed-effects linear regression was used to assess differences between baseline scans and reduction in neutral plantarflexion and maximal dorsiflexion with significance set at P< 0.05. Results: Syndesmotic reduction and stabilization in maximal dorsiflexion led to increased external rotation of the fibula compared to baseline scans [13.0 degrees ± 5.4 degrees (mean ± SD) vs. 7.5 degrees ± 2.4 degrees, P=0.002]. There was a tendency towards lateral translation of the fibula with the ankle placed in maximal dorsiflexion (3.3 mm ± 1.0 mm vs. 2.7 mm ± 0.7 mm, P=0.096). No other statistically significant differences between measurements of reduction with the ankle placed in neutral plantarflexion or maximal dorsiflexion and baseline were present (P>0.05). Conclusion: Reducing the syndesmosis with the ankle in maximal dorsiflexion leads to malreduction with external rotation of the fibula. There was no statistically significant difference in reduction quality with the ankle placed in neutral plantarflexion. Future studies should assess the clinical implications of ankle positioning during syndesmotic fixation.

Category: Ankle Arthritis; Trauma Introduction/Purpose: Intraarticular pilon fractures have a high rate of posttraumatic osteoarthritis (PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory proteins triggered by injury contribute to PTOA development.MicroRNAs (miRNA), regulators of gene expression, are dysregulated in the cartilage of osteoarthritic joints, and their modulation may deter cartilage destruction. Specifically, miRNA-146a is associated with normal cartilage development and prevents overexpression of inflammatory proteins in degenerative osteoarthritis but is yet to be studied in clinical PTOA. This novel study aims to determine the effect of acute intraarticular pilon fracture on miRNA-146a expression and its association with inflammatory proteins. Methods: Bilateral ankles of patients with unilateral pilon fracture were aspirated for synovial fluid at the time of external fixation and/or open reduction internal fixation (ORIF). After processing, synovial fluid samples were sequenced for small RNA analysis. Measured levels of miRNA-146a in injured ankles were compared to the contralateral uninjured ankles, which served as baseline controls. Results: Five patients with unilateral pilon fractures consented to participate in the study. miRNA-146a was readily detectable in all patient samples. Using uninjured ankles (n=5) as a control, mean fold miRNA-146a expression was 1.0 ±0.93 [Mean ± Standard Deviation (SD)]. In comparison, mean fold miRNA-146a in injured ankles (n=5) was 0.4 ± 0.53(p=0.07). Additional results will be analyzed and available to present at the 2024 AOFAS Annual Meeting. Conclusion: Though not statistically significant, our preliminary data demonstrated that miRNA-146a was lower in injured ankles when compared to uninjured ankles. This study aims to better characterize the effect of acute pilon fracture on miRNA-146 expression and its association with inflammatory proteins. Anticipated results will help elucidate the role of miRNA-146a in the pathogenesis of PTOA following pilon fracture, impacting future PTOA research on the diagnostic and therapeutic capabilities of miRNAs.

Abstract This paper explores how the world crisis currently affecting liberalism and democracy has impacted Brazil’s and Türkiye’s foreign policy in three multilateral issue areas: security, human rights, and climate change. Assuming that a country’s foreign policy echoes the interplay between international and domestic dynamics, it considers two cases of similar escalation of antidemocratic domestic politics – the Bolsonaro administration (2019-2022) and Erdogan’s first mandate as Türkiye’s president under presidentialism (2018-2023). By means of a comparative methodological framework, it showcases that Bolsonaro and Erdogan may look very similar in their opposition to some (not all) Western and liberal values; however, they adopt different strategies to express their opposition, and neither one rejects multilateralism. The paper analyses their distinct geopolitical motivations in foreign policy based on different conceptions of how states should act in and for development.

Introduction. High-dose antibiotic regimens are commonly employed to improve outcomes in critically ill patients with severe infections; however, their direct impact on antimicrobial resistance (AMR) remains underexplored. Methods. This systematic review analyzed randomized controlled trials (RCTs) published between 2020 and 2024, focusing on high-dose regimens for gram-negative bacterial infections, cellulitis, and ventilated hospital-acquired bacterial pneumonia (vHABP). A comprehensive search was conducted using the Web of Science and PubMed databases, yielding four studies that met the inclusion criteria. Results. The results suggest that while high-dose regimens reduce treatment failure and improve clinical outcomes, they are associated with higher adverse effects and may contribute to antibiotic-resistant bacteria. Notably, none of the studies directly assessed the molecular or epidemiological mechanisms linking high-dose regimens to AMR, underscoring a significant gap in the current literature. Conclusion. Further research is required to elucidate these mechanisms and establish evidence-based guidelines that balance immediate clinical benefits with long-term public health concerns.

A subset of children and adolescents experience recurrent or persistent symptoms following SARS-CoV-2 infection, known as postacute sequelae of COVID-19 (PASC), however, the clinical epidemiology within the United States (US) is not yet well understood. This scoping review aims to synthesize the clinical epidemiology of pediatric PASC in the US. A comprehensive literature search was conducted and databases were queried from inception until January 29, 2024. Studies including US children and adolescents

I am gladly sharing a few anecdotes of my interactions with Steven Weinberg during many years, from my student days to more recent times.

Se presenta el primer caso de embarazo abdominal secundario ocurrido en el Hospital San Juan de Dios del Callao y 14o. caso que se publica en el país. Se engloban los cuadros clínicos y exámenes toco-ginecológicos de los casos publicados y el nuestro, con el afán de encontrar signos frecuentes de embarazo abdominal. Se insiste sobre la importancia de la radiologla como método de diagnóstico certero. Recomendamos el estudio del tránsito intestinal en aquellos casos que presentan sintomatología sospechosa de abdominociesis. Se realiza el diagnóstico pre-operatorio y extirpación total de un embarazo abdominal de 6 meses con feto muerto, cuya placenta estaba insertada en el ligamento tubo-ovárico.

One of the negative effects of linear infrastructures is the formation of barriers to the movements for arboreal wildlife resulting in the reduction in connectivity between populations and thus increasing the risk of extinction. One of the most widely used ways to mitigate these barrier effects is canopy bridges. There is a lack of knowledge about how behavioral differences between species may affect the efficacy of canopy bridges. The purpose of this study was to evaluate the hypothesis that Leontopithecus rosalia (an endangered endemic species) and Callithrix spp. hybrids (introduced invasive species) perceive canopy bridges as sites with risk of predation. We compared the behavior of these species during attempts to cross four canopy bridges installed over oil and gas pipeline right-of-way strips, and another 4 bridges installed inside the forest near the pipeline bridges. The behavior was recorded from 30-second videos obtained from two camera traps installed at each end of the bridges. Of the 1917 crossing events identified, 356 events were randomly chosen for behavioral data collection. Of these, 173 were social group crossing events and 183 individual crossing events. There were few crossings (7.9%) with the two species present. The differences between the species were more quantitative than qualitative and may be related to interspecific differences in vulnerability to predation and anti-predatory tactics. Both species exhibited significantly more behaviors related to perception of risk of predation (vigilance, hesitation, rapid passage) in the pipeline bridges than in the forest bridges. One vigilance measure showed higher occurrence during the first months after installation of the cameras, especially for Callithrix spp., but in general there was little waning of the risk-assessment response. Alarm calls, scent marking and social and feeding behaviors were rare or absent. Low-cost simple canopy bridges may be an effective strategy to overcome the barrier effect of right-of-way strips over gas and oil pipelines. However, the results on perceived risk of predation raise the hypothesis that there may be a cost-benefit ratio between distance to be traveled and risk perception that would lead to a reduction in effectiveness of bridges in greater distance. We discuss the implications for conservation of an endangered species and management of an invasive species.

High elevation fossil deposits in Cuba have been poorly studied, and there is a limited understanding of how altitudinal changes could have affected the composition of faunal communities in the past. Here, we report fossils of 13 vertebrate species and an invertebrate from 11 late Quaternary cave deposits at elevations ranging from 532 to 1123 meters above sea level, located in the Guamuhaya Masiff in central Cuba. The composition of the vertebrate fauna assemblages recovered from these localities resembles that known from other lowland deposits and includes eight extinct, one extirpated, and four extant species. Furthermore, the specimens reported here record the highest elevation known for nine species recovered.

Abstract Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the SARS-CoV-2 pandemic. In this proof-of-concept study we adapted an original-D614G SARS-CoV-2 virus to Vero cell culture as a strategy to enhance inactivated vaccine manufacturing productivity. A passage 60 (P60) virus showed enhanced fitness and 50-fold increased virus yield in a bioreactor compared to the original-D614G virus. It further remained susceptible to neutralization by plasma from SARS-CoV-2 vaccinated and convalescent individuals, suggesting exposure of relevant epitopes. Monovalent inactivated P60 and bivalent inactivated P60/omicron BA.1 vaccines induced neutralizing responses against original-D614G and BA.1 viruses in mice and hamsters, demonstrating that the P60 virus is a suitable vaccine antigen. Antibodies further cross-neutralized delta and BA.5 viruses. Importantly, the inactivated P60 vaccine protected hamsters against disease upon challenge with original-D614G or BA.1 virus, with minimal lung pathology and lower virus loads in the upper and lower airways. Antigenicity of the P60 virus was thus retained compared to the original virus despite the acquisition of cell culture adaptive mutations. Consequently, cell culture adaptation may be a useful approach to increase yields in inactivated vaccine antigen production.

Abstract Background Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. Methods We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS

Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Background Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiated in mice with early sporadic lesions as compared with late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, impact TST function and liver cancer progression.Methods Mice with a germline floxed allele of the SV40 large T antigen (TAG) undergo spontaneous recombination and activation of the TAG oncogene, leading to rare early cancerous TAG-expressing lesions that inevitably progress to established liver cancer. We assessed the immunophenotype (CD44, PD1, TCF1, and TOX expression) and function (TNFα and IFNγ cytokine production) of tumor/TAG-specific CD8 T cells in mice with early and late liver lesions by flow cytometry. We vaccinated mice, either alone or in combination with ICB, to test whether these immunotherapeutic interventions could stop liver cancer progression and improve survival.Results In mice with early lesions, a subset of TST were PD1+ TCF1+ TOX− and could produce IFNγ while TST present in mice with late liver cancers were PD1+ TCF1lo/− TOX+ and unable to make effector cytokines. Strikingly, vaccination with attenuated TAG epitope-expressing Listeria monocytogenes (LMTAG) blocked liver cancer development and led to a population of TST that were PD1-heterogeneous, TCF1+ TOX− and polyfunctional cytokine producers. Vaccine-elicited TCF1+TST could self-renew and differentiate, establishing them as progenitor TST. In contrast, ICB administration did not slow cancer progression or improve LMTAG vaccine efficacy.Conclusion Vaccination, but not ICB, generated a population of functional progenitor TST and halted cancer progression in a clinically relevant model of sporadic liver cancer. In patients with early cancers or at high risk of cancer recurrence, immunization may be the most effective strategy.

PURPOSELung cancer remains one of the leading causes of cancer-related mortality worldwide. It is the third cause of death among patients with cancer in Puerto Rico (PR) and non–small cell lung cancer (NSCLC) is the most prevalent. This study aims to describe the first-line treatment (1LT) and health care resource utilization (HCRU) among patients with NSCLC in PR.METHODSA retrospective cohort study was conducted using the PR Central Cancer Registry Health Insurance Linkage Database to describe patients with NSCLC from 2012 to 2016. It describes sociodemographic and clinical characteristics on the basis of stage and histology and includes 1LT patterns and HCRU.RESULTSA total of 1,011 patients met the inclusion criteria. Most were male (57.1%), married (54.1%), and had no comorbidities (55.8%). A significant proportion of patients (71.1%) were diagnosed at stages III and IV, with nonsquamous cell carcinoma being the most prevalent histology group (75.9%). About 61.7% received systemic therapy, 36.7% received radiotherapy, and 21.9% underwent surgery. Platinum (Pt)-based combinations were the most common 1LT (82.9%). On average, patients had 4.7 emergency room visits, nearly six hospitalizations, and 22.4 outpatient visits annually. The mean frequencies of positron emission tomography, ultrasounds, computerized tomography scans, and magnetic resonance imaging were 0.95, 0.11, 4.88, and 0.91, respectively.CONCLUSIONTo our knowledge, this study provides the first description of 1LT patterns, HCRU, and sociodemographic information among patients with NSCLC in PR. A significant number of patients were diagnosed at stage III or higher and received Pt-based systemic therapy as their 1LT. More research is required to investigate treatment patterns beyond the 1LT and to gain a comprehensive understanding of optimal care interventions and factors associated with early NSCLC diagnosis.

Abstract Using NASA's Global‐scale Observations of the Limb and Disk (GOLD) imager, we report nightside ionospheric changes during the G5 super geomagnetic storm of 10 and 11 May 2024. Specifically, the nightside southern crest of the Equatorial Ionization Anomaly (EIA) was observed to merge with the aurora near the southern tip of South America. During the storm, the EIA southern crest was seen moving poleward as fast as 450 m/s. Furthermore, the aurora extended to mid‐latitudes reaching the southern tips of Africa and South America. The poleward shift of the equatorial ionospheric structure and equatorward motion of the aurora means there was no mid‐latitude ionosphere in this region. These observations offer unique insights into the ionospheric response to extreme geomagnetic disturbances, highlighting the complex interplay between solar activity and Earth's upper atmosphere.

ObjectivesTo characterize factors associated with parental willingness for their children participation in a COVID-19 vaccine trial, use of different COVID-19 vaccines and acceptance of a third vaccine dose.MethodsParents of children aged 12–17 years in Lima, Perú were asked to complete an online questionnaire via social networks, from November 9, 2021, to April 23, 2022. We calculated crude and adjusted prevalence ratios with 95% confidence intervals to compare factors with the mentioned outcomes.ResultsFrom 523 parents responding, 374 completed the survey. 90.4% would give their children a third vaccine dose, 36.6% would allow their children participation in a COVID-19 vaccine clinical trial, and 33.2% would accept different vaccine brands between doses. Parental belief that COVID-19 vaccine studies met quality standards was associated with acceptance of a third booster dose (adjusted PR 3.25; 95% CI1.57–6.74; p = 0.002), enrolment in a COVID-19 clinical trial (adjusted PR 4.49; 95% CI1.25–16.06; p = 0.02), and acceptance of different COVID-19 vaccine brands between doses (adjusted PR 10.02; 95% CI1.40–71.95; p = 0.02).ConclusionMost parents would accept a third vaccine booster dose, approximately a third would participate in COVID-19 vaccine trials. Believing COVID-19 vaccines studies fulfilled quality standards was associated with the study outcomes. It is necessary to inform about the rigorous processes for the development of COVID-19 vaccines to generate confidence in parents to accept these vaccine-related outcomes.

Abstract COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50

We report herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride.

Due to their ease of preparation, stability, and diverse reactivity, N-hydroxyphthalimide (NHPI) esters have found many applications as radical precursors. Mechanistically, NHPI esters undergo a reductive decarboxylative fragmentation to provide a substrate radical capable of engaging in diverse transformations. Their reduction via single-electron transfer (SET) can occur under thermal, photochemical, or electrochemical conditions and can be influenced by a number of factors, including the nature of the electron donor, the use of Brønsted and Lewis acids, and the possibility of forming charge-transfer complexes. Such versatility creates many opportunities to influence the reaction conditions, providing a number of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations.

Abstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.

Glyphosate is an herbicide used worldwide with harmful health effects, and efforts are currently being made to develop sensors capable of detecting its presence. In this work, an array of four interdigitated microwave sensors was used together with the multivariate statistical technique of principal component analysis, which allowed a well-defined pattern to be found that characterized waters for agricultural use extracted from the Bustillos lagoon. The variability due to differences between the samples was explained by the first principal component, amounting to 86.3% of the total variance, while the variability attributed to the measurements and sensors was explained through the second principal component, amounting to 13.2% of the total variance. The time evolution of measurements showed a clustering of data points as time passed, which was related to microwave–sample interaction, varied with the fluctuating dynamical structure of each sample, and tended to have a stable mean value.

Prunus serotina (black cherry) is native to America and has five subspecies: serotina, eximia, hirsuta, virens, and capuli. P. serotina subsp. capuli is found in Central and South America with superior fruits found in Ecuador. These have large, juicy, and tasty fruits used for human consumption. They are available in produce markets and have important nutraceutical properties. However, no commercial cultivars of capuli are currently available. The main goal of this research was to understand if different morphological characters can differentiate unique populations of P. serotina subsp. capuli present in Ecuador. Morphological traits (tree, leaf, and flower) of plants grown from the OP seeds of 44 capuli accessions collected from three provinces of Ecuador (Cotopaxi, Chimborazo, and Tungurahua) were characterized in 2019 and 2020. Tree measurements included the number of primary branches and growth habit. Leaf measurements included petiole length, leaf area, leaf height, leaf width, leaf apex angle, and leaf basal angle. Flower measurements included pedicel length, flower width, and flower length. Raceme length, number of racemes per branch, and number of flowers per raceme were also characterized. ANOVA were performed with significant differences observed among capuli accessions for all variables measured. No clear differences were observed across regions with PCA and cluster analysis that may support the presence of different populations.

Abstract A coronal mass ejection erupted from the Sun on 21 April 2023 and created a G4 geomagnetic storm on 23 April. NASA's global‐scale observations of the limb and disk (GOLD) imager observed bright equatorial ionization anomaly (EIA) crests at ∼25° Mlat, ∼11° poleward from their average locations, computed by averaging the EIA crests during the previous geomagnetic quiet days (18–22 April) between ∼15°W and 5°W Glon. Reversed C‐shape equatorial plasma bubbles (EPBs) were observed reaching ∼±36° Mlat (∼40°N and ∼30°S Glat) with apex altitudes ∼4,000 km and large westward tilts of ∼52°. Using GOLD's observations EPBs zonal motions are derived. It is observed that the EPBs zonal velocities are eastward near the equator and westward at mid‐latitudes. Model‐predicted prompt penetration electric fields indicate that they may have affected the postsunset pre‐reversal enhancement at equatorial latitudes. Zonal ion drifts from a defense meteorological satellite program satellite suggest that westward neutral winds and perturbed westward ion drifts over mid‐latitudes contributed to the observed latitudinal shear in zonal drifts.

IntroductionOur objective was to explore the effect of the reduction of saturated fat (SAF) intake on cardiovascular disease, mortality and other health-related outcomes in adults.MethodsWe conducted an umbrella review, searching Medline, Scopus, EMBASE, Cochrane Library, and LILACS databases for systematic reviews from December 1, 2012, to December 1, 2022. We have included meta-analyses of randomized controlled trials (RCTs) and cohort studies. We extracted effect sizes (95%CI), heterogeneity (I2), and evidence quality rating based on the population, intervention, comparator, and outcomes.Results21 meta-analyses were included (three were from RCTs, and 18 were from cohort studies). Among meta-analyses of RCTs, 15 of the 45 associations were significant. The effect of reduction in SAF intake on combined cardiovascular events (RR 0.79, 95%CI 0.66–0.93) was graded as having moderate certainty of evidence. We found no effect on all-cause mortality, cardiovascular mortality, cancer deaths, and other cardiovascular events. Among meta-analyses of cohort studies, five of the 19 associations were significant. There was an increase in coronary heart disease mortality (HR 1.10, 95% CI 1.01–1.21) and breast cancer mortality (HR 1.51, 95% CI 1.09–2.09) in participants with higher SFA intake compared to reduced SFA. We found no effect on all-cause mortality, cardiovascular mortality, and other cardiovascular events.ConclusionThis umbrella review found the reduction in SAF intake probably reduces cardiovascular events and other health outcomes. However, it has little or no effect on cardiovascular mortality and mortality from other causes. More high-quality clinical trials with long-term follow-up are needed.Systematic review registration: CRD42022380859.

Given the increasing pressure on water bodies, it is imperative to explore sustainable methodologies for wastewater treatment and reuse. The simultaneous presence of multiples contaminants in complex wastewater, such as the liquid effluents from biogas plants, can compromise biological treatment effectiveness for reclaiming water. Vertical subsurface flow constructed wetlands were established as low-cost decentralized wastewater treatment technologies to treat the liquid fraction of digestate from municipal organic waste with metals, antibiotics, and antibiotic resistance genes, to allow its reuse in irrigation. Twelve lab-scale planted constructed wetlands were assembled with gravel, light expanded clay aggregate and sand, testing four different treating conditions (liquid digestate spiked with oxytetracycline, sulfadiazine, or ofloxacin, at 100 μg/ L, or without dosing) during 3 months. Physicochemical parameters (pH, chemical oxygen demand (COD), nutrients, metals, and antibiotics), the microbial communities dynamics (through 16S high-throughput sequencing) and antibiotic resistance genes removal (qPCR) were monitored in influents and effluents. Systems removed 85.8%–96.9% of organic matter (as COD), over 98.1% of ammonium and phosphate ions, and 69.3%–99.4% of nitrate and nitrite ions, with no significant differences between the presence or absence of antibiotics. Removal of Fe, Mn, Zn, Cu, Pb and Cr exceeded 82% in all treatment cycles. The treatment also removed oxytetracycline, sulfadiazine and ofloxacin over 99%, and decreased intl1, tetA, tetW, sul1 and qnrS gene copies. Nonetheless, after 3 months of ofloxacin dosing, qnrS gene started being detected. Removal processes relied on high HRT (14 days) and various mechanisms including sorption, biodegradation, and precipitation. Microbial community diversity in liquid digestate changed significantly after treatment in constructed wetlands with a decrease in the initial Firmicutes dominance, but with no clear effect of antibiotics on the microbial community structure. Removals above 85% and 94% were observed for Streptococcus and Clostridium, respectively. Results suggest that vertical subsurface flow constructed wetlands were a suitable technology for treating the liquid digestate to reuse it in irrigation agricultural systems, contributing to the circular bioeconomy concept. However, a more profound understanding of effective wastewater treatment strategies is needed to avoid antibiotic resistance genes dissemination.

The Brazilian Pantanal is a remarkable ecosystem, encompassing vital aspects such as fish, fruit, and grain production, greenhouse gas emission regulation, temperature and precipitation modulation, and groundwater recharge. However, 2019 and 2020 experienced prolonged and severe drought that profoundly impacted the Pantanal region. Although these impacts are still under review, their effects on wildlife, vegetation, and the local population are undeniable. To enhance our understanding of the magnitude and consequences of the 2019/2020 drought, the present study conducted a comprehensive evaluation of drought occurrences in the Pantanal biome. Utilizing two well-established drought indices, the standard precipitation index (SPI) and the standard precipitation evapotranspiration index (SPEI), we analyzed the available observational data provided by the Climate Research Unit (CRU). Additionally, we endeavored to project droughts throughout the 21st century, thereby facilitating the visualization of potential reoccurrences of hazardous events in the Pantanal area. Two regional climate model (RCM) ensembles, the Eta ensemble (E1) and CORDEX ensemble (E2), along with representative concentration pathways (RCP4.5 and RCP8.5 scenarios) were used to project the severity of droughts in the Brazilian Pantanal until 2098/2099. The findings indicate that the hydrological year of 2019/2020 was the driest on record in the Pantanal over the past 80 years. The E1 ensemble did not project such an extreme event, whereas the E2 ensemble forecasted extreme droughts before the 2040s under the RCP4.5 and RCP8.5 scenarios. Using the SPEI, both ensembles showed similar results, with extreme droughts projected toward the end of the 21st century. Notably, the SPI demonstrated effectiveness in detecting short-term droughts, while the SPEI was more efficient for long-term assessments, projecting extreme drought events for the last two decades. The SPEI, employed with the Eta and CORDEX ensembles, can provide valuable insights into drought projections. Moreover, the potential recurrence of extreme droughts, characterized by significant below-average precipitation spanning vast areas throughout the hydrological year, poses a severe threat to the Pantanal biome in this century.

Faults in power distribution feeders cause damage to power utilities due to the deterioration of reliability and power quality indexes and the displacement of field maintenance teams to replace or repair power grid equipment. Additionally, consumer units have energy supply interruptions for an undetermined time. Studies in specialized literature usually detect, classify, and locate faults after they occur. In contrast, preventing faults by estimating areas vulnerable to them is crucial to mitigate all inconveniences and additional costs after they occur. Tree vegetation is an essential factor contributing to faults. In this sense, an enhanced method for tree vegetation mapping by areas is developed using multilayer perceptron neural networks trained on high-resolution images from Google Earth. A geographic space is incorporated to estimate the regions vulnerable to failures due to tree vegetation. Geographically weighted spatial analysis is applied from local variables aggregated by areas. Spatial data analysis is used to real faults and tree vegetation data from a medium-sized Brazilian city via QGIS and R programming environments. As a result, thematic maps are produced with the areas whose feeders are vulnerable to faults, where there is a moderate positive correlation by regions between the faults in distribution transformers and tree vegetation in the northeast and southwest areas of the city under study.

In-depth research has been done in the literature on applying sophisticated modulation and control systems for power converters, such as Feedback Quantizer and Predictive Control. This research aims to enhance the Feedback Quantizer, a closed-loop modulation technique used in three-phase voltage source inverters. This method naturally reduces harmonics at low frequencies, which harms electrical machinery like transformers and AC motors. This modulation technique achieves an excellent follow-up of the fundamental voltage reference. One of the disadvantages of Feedback Quantizer are the low sampling time to achieve a good waveform quality; in addition, as it is not a carrier-based method, the switching frequency is variable, resulting in a dispersed harmonic spectrum. The three-phase voltage source inverter has eight valid states to monitor the voltage reference; the proposal consists of modifying the feedback quantizer modulation using virtual vectors by discrete space vectors, which achieves a better follow-up. The proposal considers a simplified implementation of discrete space vectors in such a way as to reduce the computational cost to obtain voltage and current waveforms with low WTHD, THD distortion, and a defined harmonic spectrum but with a high sampling time. The proposed modulation scheme obtains a THD of less than 2% in the load current, reducing the noise produced by the traditional scheme of Feedback Quantizer and using a fixed switching frequency for a sampling time of ( $200~\mu $ s). The above is an improvement compared to the conventional Feedback Quantizer. Additionally, it was possible to reduce the mathematical operations of the algorithm by a factor of 5.38 by using strategies to simplify the algorithm of the suggested scheme. The proposed technique operates correctly, according to experimental tests.INDEX TERMS Feedback quantizer, discrete space vector modulation, total harmonic distortion, weighted total harmonic distortion, voltage source converter, modulation scheme.

Europe has a long history of non-native species introductions given its central role in global trade in recent centuries. Currently, approximately two hundred cerambycid species have been found in Europe, as the result of introductions between and within biogeographical regions; still, despite better monitoring and stronger restrictions, the arrivals and spread of non-native Cerambycidae continue.The aim of this contribution is to report and discuss the first European records of the non-native longhorn beetle Olenecamptus bilobus (Fabricius, 1801) on the basis of three specimens recorded almost simultaneously in Spain and Greece, respectively.

Coffee is one of the most consumed beverages worldwide. Its production generates a large amount of waste, and its use is of vital importance to prevent it from becoming a source of environmental pollution. Cuba is a country with a well-known coffee-growing tradition. Although coffee production has decreased, it is vitally important to use the waste generated in these productions to reduce environmental pollution. To know the possible use or application of coffee waste, it is necessary to know its composition. In this article, three Cuban Arabica coffee wastes (husk, parchment and spent coffee grounds) were characterized using chemical, physical and physicochemical methods. In the characterization of these wastes, SEM and EDX were used to determine their microscopic form and chemical composition. The Chesson–Datta method, ATR and TGA were used to determine whether these materials were lignocellulosic. Ash, pH and density of the waste were determined as characterization methods. The extractive content was determined and a phytochemical screening was performed to determine the groups of the secondary metabolites present.

Reactive oxygen species (ROS) is a general term that describes free radicals [e [...]

First-order phase transitions produce abrupt changes to the character of both ground and excited electronic states. Here we conduct electronic compressibility measurements to map the spin phase diagram and Landau level (LL) energies of monolayer WSe_{2} in a magnetic field. We resolve a sequence of first-order phase transitions between completely spin-polarized LLs and states with LLs of both spins. Unexpectedly, the LL gaps are roughly constant over a wide range of magnetic fields below the transitions, which we show reflects spin-polarized ground states with opposite spin excitations. These transitions also extend into compressible regimes, with a sawtooth boundary between full and partial spin polarization. We link these observations to the important influence of LL filling on the exchange energy beyond a smooth density-dependent contribution. Our results show that WSe_{2} realizes a unique hierarchy of energy scales where such effects induce reentrant magnetic phase transitions tuned by density and magnetic field.

Optimal veterinary care of managed elephant populations is vital due to the continued decline of wild populations. Appropriate health monitoring and accurate disease diagnosis include hematologic evaluation. Elephant hematology is distinctive in that elephants have high percentages of monocytes in health. Elephant monocytes also have unusual morphology, a feature shared with manatees and rock hyraxes. Manual white blood cell counting is used for elephant hematology, as analyzers are generally inaccurate. The aims of this study were to evaluate basic cell isolation and functional testing protocols for use in elephant monocyte research, and to test several available antibodies via flow cytometry for use in elephant monocyte identification. Peripheral blood samples from five Asian elephants (Elephas maximus) were used. Methods for monocyte isolation and evaluation of phagocytic function were established. Putative lymphocyte and monocyte populations were identified using a scatter on flow cytometry. Antibodies against CD11b, CD11c, CD14, and ionized calcium-binding adapter molecule 1 (IBA1) were tested, with IBA1 showing the highest apparent diagnostic utility in labeling monocytes. Combined flow cytometric scatter and IBA1 positivity appear to identify Asian elephant monocytes. These data provide a methodologic basis for further investigation into elephant monocyte function and immune response to infection.

The success of using active restoration in Mediterranean-type climate zones mostly depends on an appropriate matching of plant species and specific management prescriptions upon establishment. In this study, we assessed the early growth and short-term physiological acclimation of seven common species found in the sclerophyllous forests in central Chile to water restriction and shading. We established a nursery experiment that included three treatments (T0: sun-exposed and water-restricted, T1: sun-exposed and fully irrigated, and T2: shaded and fully irrigated) and seven tree species differing in their shade and drought tolerance (Quillaja saponaria Molina, Aristotelia chilensis (Mol.) Stuntz, Peumus boldus Molina, Lithraea caustica (Mol.) Hook. and Arn, Luma apiculata (DC.) Burret, Colliguaja odorifera Molina, and Escallonia pulverulenta (Ruiz and Prav.) Pers). We measured the increment in seedling height and different leaf morpho-physiological traits during two months in the dry season. Based on the measured traits, none of the species took advantage of the higher water availability in T1 relative to T0, but most of the species responded to the shade in T2, regardless of their shade or drought tolerance. Height increments due to shade varied from 0% in P. boldus to 203% in L. apiculata. Overall, all the species responded similarly to the treatments in specific leaf area, chlorophyll content index, photosynthetic rate, stomatal conductance, and intrinsic water use efficiency. This suggests that the species exhibited similar acclimation patterns of these parameters to shade and drought, even regarding the variation in midday xylem water potential found in the water-restricted treatment T0 (from −1.5 MPa in P. boldus to −3.1 MPa in E. pulverulenta). In this study, shading had a higher positive effect on the seedling performance of sclerophyllous species than watering, which at operational level highlights the need for investing in tree shelters when using these species in restoration programs.

Abstract Background Long-term mental health (MH) policies in Finland aimed at investing in community care and promoting reforms have led to a reduction in the number of psychiatric hospital beds. However, most resources are still allocated to hospital and community residential services due to various social, economic and political factors. Despite previous research focussing on the number and cost of these services, no study has evaluated the emerging patterns of use, their technical performance and the relationship with the workforce structure. Objective The purpose of this study was to observe the patterns of use and their technical performance (efficiency) of the main types of care of MH services in the Helsinki-Uusimaa region (Finland), and to analyse the potential relationship between technical performance and the corresponding workforce structure. Methods The sample included acute hospital residential care, non-hospital residential care and outpatient care services. The analysis was conducted using regression analysis, Monte Carlo simulation, fuzzy inference and data envelopment analysis. Results The analysis showed a statistically significant linear relationship between the number of service users and the length of stay, number of beds in non-hospital residential care and number of contacts in outpatient care services. The three service types displayed a similar pattern of technical performance, with high relative technical efficiency on average and a low probability of being efficient. The most efficient acute hospital and outpatient care services integrated multidisciplinary teams, while psychiatrists and nurses characterized non-hospital residential care. Conclusions The results indicated that the number of resources and utilization variables were linearly related to the number of users and that the relative technical efficiency of the services was similar across all types. This suggests homogenous MH management with small variations based on workforce allocation. Therefore, the distribution of workforce capacity should be considered in the development of effective policies and interventions in the southern Finnish MH system.

Abstract Gut microbiome disruptions may lead to adverse effects on wildlife fitness and viability, thus maintaining host microbiota biodiversity needs to become an integral part of wildlife conservation. The highly-endangered callitrichid golden lion tamarin (GLT-Leontopithecus rosalia) is a rare conservation success, but allochthonous callitrichid marmosets (Callithrix) serve as principle ecological GLT threats. However, incorporation of microbiome approaches to GLT conservation is impeded by limited gut microbiome studies of Brazilian primates. Here, we carried out analysis of gut metagenomic pools from 114 individuals of wild and captive GLTs and marmosets. More specifically, we analyzed the bacterial component of ultra filtered samples originally collected as part of a virome profiling study. The major findings of this study are consistent with previous studies in showing that Bifidobacterium, a bacterial species important for the metabolism of tree gums consumed by callitrichids, is an important component of the callitrichid gut microbiome - although GTLs and marmosets were enriched for different species of Bifidobacterium. Additionally, the composition of GLT and marmoset gut microbiota is sensitive to host environmental factors. Overall, our data expand baseline gut microbiome data for callitrichids to allow for the development of new tools to improve their management and conservation.

Abstract Actin, an important component of eukaryotic cell cytoskeleton, regulates cell shape and transport. The morphology and biochemical properties of actin filaments are determined by their structure and protein-protein contacts. Crowded environments can organize filaments into bundles, but less is known about how they affect F-actin structure. This study used 2D IR spectroscopy and spectral calculations to examine how crowding and bundling impact the secondary structure and local environments in filaments and weakly or strongly bundled networks. The results reveal that bundling induces changes in actin’s secondary structure, leading to a decrease in β-sheet and an increase in loop conformations. Strongly bundled networks exhibit a decrease in backbone solvent exposure, with less perturbed α-helices and nearly “locked” β-sheets. Similarly, the loops become less hydrated but maintain a dynamic environment. These findings highlight the role of loop structure in actin network morphology and stability under morphology control by PEG.