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Abstract Background A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. Methods We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. Results Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p

ABSTRACT Timber bridges in Brazil, intended for rural roads and rural areas, present several problems due to the lack of design, structural calculation, and periodic maintenance by municipal administrations. This study evaluated a total of 10 timber bridges with a deck of sawn planks connected by nails to natural round beams, aiming to identify their main pathologies and provide minimum pre-sizing values for the used sections. The bridges were inspected on-site to measure the parts and identify the main problems. Subsequently, based on the Manual de Projeto e Construção de Pontes de Madeira and ABNT NBR 7190-1 (2022), we verified whether the diameter of the round beams found on site was adequate from the point of view of structural sizing using an Excel spreadsheet. Most of the analyzed bridges had spans of up to 15 m and problems related to the degradation of the timber and metal connections, reducing their useful life. As a result, the main construction recommendations for bridges are the use of timber treated with chromated copper arsenate (CCA) and galvanized connections to prevent corrosion. The use of the proposed pre-sizing tables is recommended to ensure minimum calculation values, considering the design vehicle classes and the minimum dimensions for the timber sections. This study aims to guide Brazilian municipal administrations and other interested parties in the construction of timber bridges for rural areas, obtaining safe, low-cost, and highly durable structures.

Abstract. neighboring countries. Recently, an increase in biological surveys and access to natural preserves has led to a better understanding of species distributions in Nicaragua and across Central America. Here, we provide new departmental records for three species of didelphid, 18 chiropterans (Phyllostomidae, Molossidae, Vespertilionidae), one geomyid, and one mustelid from 21 sites across the country. This work underscores the need for additional sampling across Nicaragua to fill gaps in the known distribution of many species. This information can facilitate or inform conservation actions in established and proposed preserves in Nicaragua.

Air bubbles in the upper ocean are generated mainly by waves breaking at the air–sea interface. As such, after the waves break, entrained air bubbles evolve in the form of plumes in the turbulent flow, exchange gas with the surrounding water, and may eventually rise to the surface. To shed light on the short-term response of entrained bubbles in different stormy conditions and to assess the link between bubble plume penetration depth, mechanical and thermal forcings, and the air–sea transfer velocity of CO2, a field experiment was conducted from an oceanographic research tower in the north Adriatic Sea. Air bubble plumes were observed using high-resolution echosounder data from an upward-looking 1000 kHz sonar. The backscatter signal strength was sampled at a high resolution, 0.5 s in time and 2.5 cm along the vertical direction. Time series profiles of the bubble plume depth were established using a variable threshold procedure applied to the backscatter strength. The data show the occurrence of bubbles organized into vertical plume-like structures, drawn downwards by wave-generated turbulence and other near-surface circulations, and reaching the seabed at 17 m depth under strong forcing. We verify that bubble plumes adapt rapidly to wind and wave conditions and have depths that scale approximately linearly with wind speed. Scaling with the wind–wave Reynolds number is also proposed to account for the sea-state severity in the plume depth prediction. Results show a correlation between measured bubble depths and theoretical air–sea CO2 transfer velocity parametrized with wind-only and wind/wave formulations. Further, our measurements corroborate previous results suggesting that the sinking of newly formed cold-water masses helps bring bubbles to greater depths than those reached in stable conditions for the water column. The temperature difference between air and sea seems sufficient for describing this intensification at the leading order of magnitude. The results presented in this study are relevant for air–sea interaction studies and pave the way for progress in CO2 gas exchange formulations.

This paper addresses the problem of activity scheduling and operator assignment in workstations of aerospace assembly lines. The problem is modelled as a new variant of the Multi-Mode Resource Constrained Project Scheduling Problem (MRCPSP), which incorporates practical features from aerospace workstations in assembly lines. These workstations have a substantial number of activities to be scheduled within a given assembly cycle time. It introduces particularities which are not usually addressed such as considering additional workers for performing activities, different workers’ proficiency, and spatial limitations in work zones. The objective is to schedule the activities of an aerospace workstation, minimising the total labour cost, while satisfying the cycle time and the zone’s limitations. The problem is initially formulated by employing mixed-integer linear programming methods with mathematical modelling and solved using two different algorithms: an Ant Colony System (ACS) and a memetic ACS. Given the novelty of the problem presented, new sets of benchmark cases of different sizes for this problem are also proposed and solved. To assess the performance of the algorithms, the solutions for the small-sized instances are compared in terms of deviation with the results obtained by an optimisation modelling software. Further experimentation with the algorithms is carried out with medium and large instances, showing good performance and providing reasonably good results in realistic problems.

Abstract Background Oritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE). Methods We conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance. Results Overall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient). Conclusions The use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Ionospheric disturbances induced by seismic activity have been studied in recent years by many authors, showing an impact both before and after the occurrence of earthquakes. In this study, the ionospheric scintillation produced by the 2021 La Palma volcano eruption is analyzed. The Cumbre Vieja volcano was active from 19 September to 13 December 2021, and many earthquakes of magnitude 3–4 were recorded, with some of them reaching magnitude 5. Three methods, GNSS reference monitoring, GNSS reflectometry (GNSS-R) from NASA CYGNSS, and GNSS radio occultation (GNSS-RO) from COSMIC and Spire constellations, are used to compare and evaluate their sensitivity as proxies of earthquakes associated with the volcanic eruption. To compare the seismic activity with ionospheric scintillation, seismic energy release, and 95th percentile of the intensity scintillation parameter (S4), measurements have been computed at 6 h intervals for the whole duration of the volcanic eruption. GNSS-RO has shown the best correlation between earthquake energy and S4, with values up to 0.09 when the perturbations occur around 18 h after the seismic activity. GNSS reference monitoring station data also show some correlation 18 h and 7–8 d after. As expected, GNSS-R is the one that shows the smallest correlation, as the ionospheric signatures get masked by the signature of the surface where the reflection is taking place. Additionally, the three methods show a smaller correlation during the week before earthquakes. Given the small magnitude of the seismic activity, the correlation is barely detectable in this situation, and thus would be difficult to use in any application to find earthquake proxies.

ABSTRACT: Objectives: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. Methods: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. Results: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P

Abstract Objectives To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb‐eligible patients with coronavirus disease 2019 (COVID‐19). Methods This retrospective observational cohort study of ED patients utilized a propensity score‐matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID‐19 control patients in November–December 2021. The primary outcome was all‐cause hospitalization within 28 days, and secondary outcomes were 90‐day hospitalization, 28‐ and 90‐day mortality, and ED length of stay (LOS). Results Of 1340 patients included in the analysis, 490 received subcutaneous casirivimab and imdevimab, and 850 did not received them. There was no difference observed for 28‐day hospitalization (8.4% vs. 10.6%; adjusted odds ratio [aOR] 0.79, 95% confidence intervals [CI] 0.53–1.17) or 90‐day hospitalization (11.6% vs. 12.5%; aOR 0.93, 95% CI 0.65–1.31). However, mortality at both the 28‐day and 90‐day timepoints was substantially lower in the treated group (28‐day 0.6% vs. 3.1%; aOR 0.18, 95% CI 0.08–0.41; 90‐day 0.6% vs. 3.9%; aOR 0.14, 95% CI 0.06–0.36). Among hospitalized patients, treated patients had shorter hospital LOS (5.7 vs. 11.4 days; adjusted rate ratio [aRR] 0.47, 95% CI 0.33–0.69), shorter intensive care unit LOS (3.8 vs. 10.2 days; aRR 0.22, 95% CI 0.14–0.35), and the severity of hospitalization was lower (aOR 0.45, 95% CI 0.21–0.97) compared to untreated. Conclusions Among ED patients who presented for symptomatic COVID‐19 during the Delta variant phase, ED subcutaneous casirivimab/imdevimab treatment was not associated with a decrease in hospitalizations. However, treatment was associated with lower mortality at 28 and 90 days, hospital LOS, and overall severity of illness.

Background: Severe gram-positive infections are frequent in people who inject drugs, and successful completion of treatment presents unique challenges in this population. Objectives: We aimed to evaluate the feasibility of a long-acting antibiotic, dalbavancin, as an alternative to standard-of-care antibiotics for severe infections due to vancomycin-susceptible pathogens requiring ⩾2 weeks of therapy. Design: We designed an investigator-initiated single-arm unblinded prospective cohort study to evaluate the safety and efficacy of an early switch to dalbavancin in two doses administered 1 week apart. Methods: We screened patients admitted with bloodstream infection, osteomyelitis, septic arthritis, infective endocarditis or deep abscesses, and comorbid substance use disorder (SUD) for eligibility. Consenting patients were switched to dalbavancin within 7 days from their index culture. They were monitored in the hospital for efficacy and safety of the treatment until the second dose of dalbavancin 7 days later and then discharged if stable. Study participants were evaluated with a decision support engine for a hypothetical appropriate level of care regarding their SUD after discharge. Their follow-up was planned for 12 months from the index culture, either in-person or via telehealth/telephone. Results: The enrollment was terminated early due to significant loss-to-follow-up. In all, 11 patients were enrolled, 4 completed 12 months of follow-up, 2 completed 8 months of follow-up, and 1 was seen once after discharge. The remaining five patients were lost to follow-up immediately after discharge. All 11 patients continued to improve after switching to dalbavancin between the first and second doses. There were two per-protocol failures of treatment. Dalbavancin was well tolerated, though some adverse events were reported. Conclusion: Dalbavancin may be a safe and effective alternative for an early switch in treating severe gram-positive infections. Trial registration: The trial was registered as NCT04847921 with clinicaltrials.gov.

ABSTRACT Eravacycline is a synthetic fluorocycline approved by the U.S. Food and Drug Administration in 2018. This study aimed to describe clinical and microbiological outcomes in addition to associated adverse effects of eravacycline used in U.S. hospitals. Real-world, observational study involving patients receiving ≥72 h of eravacycline at 19 medical centers located in all 5 regions of the United States between October 2018 and August 2022. The primary outcome was clinical success, defined as survival and absence of microbiological recurrence at 30 days from the end of eravacycline therapy and clinical improvement within 96 h of eravacycline initiation. In total, 416 patients met study criteria and were evaluated. Index culture specimens were most often isolated from the respiratory tract (24.8%, n = 103/416), wound(s) (20.9%, n = 87/416), or blood (19.5%, n = 81/416). As definitive therapy, eravacycline was most often used to treat infections caused by Enterobacterales spp. (42.3%, n = 176/416; 24.4%, n = 43/176 carbapenem-resistant), Enterococci spp. (24.0%, n = 100/416; 49.0%, 49/100 vancomycin-resistant), and Acinetobacter spp. (23.3%, n = 97/416; 47.4%, n = 46/97 carbapenem-resistant). Clinical success occurred in 75.7% of patients (n = 315/416). Thirty-nine (9.4%, n = 39/416) patients experienced a treatment emergent adverse event (TEAE) potentially related to eravacycline with the majority (51.3%, n = 20/39) being gastrointestinal intolerance. Only 27 isolates (6.5%, n = 27/416) underwent eravacycline susceptibility testing. Eravacycline is being used to treat a broad range of Gram-negative and Gram-positive bacteria in the United States including those demonstrating multidrug-resistance with consistently low reported drug-related TEAE; however, antimicrobial susceptibility testing and subsequent in vitro susceptibility data of clinical isolates was sparingly performed. IMPORTANCE The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline’s efficacy in addressing the pressing global challenge of MDR bacterial infections.

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

The current study investigates the final unresolved cosmopolitan species of Marphysa in South Africa, Marphysa corallina, collected from KwaZulu Natal, Eastern and Western Cape provinces, together with another species collected from northern KwaZulu Natal. Morphological and genetic data prove that M. corallina, originally described from Hawaii, does not occur in South Africa. The curvature of the inner base on maxilla I, the elevated inner base of maxilla II, and the ventral cirrus as a transverse welt with a rounded tip allow us to identify it as a new species of Treadwellphysa, T. izinqa sp. nov. (common name: brown wonderworm). Characteristic traits include the basal reddish and distal golden colour of the subacicular hook, the ear-shaped postchaetal lobe, and tridentate falcigers which is reported for the first time for the genus. This species is harvested as bait on the south coast of SA, although less frequently than the more common blood wonderworm, Marphysa haemasona Quatrefages, 1866, and can be distinguished by its more uniform brown colouration and white-tipped antennae. A second species, Marphysa mzingazia sp. nov., is characterized by red eyes, six branchial filaments extending to the posterior end, the golden aciculae in posterior chaetigers, weakly bidentate yellow/brown subacicular hooks, and the presence of similar sized spinigers along the body. A molecular analysis based on cytochrome oxidase I fragments confirm both taxa as different species. A key for all South African species of Marphysa is included.

ABSTRACT: Objectives: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021, to March 10, 2022, using electronic health records from a statewide health system. We propensity-matched patients not receiving authorized treatment for each patient treated with sotrovimab. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. We also propensity-matched sotrovimab-treated patients from the Omicron and Delta phases. Logistic regression was used to determine sotrovimab effectiveness during Omicron and between variant phases. Results: Of 30,247 SARS-CoV-2 Omicron variant infected outpatients, we matched 1542 receiving sotrovimab to 3663 not receiving treatment. Sotrovimab treatment was not associated with reduced odds of 28-day hospitalization (2.5% vs 3.2%; adjusted odds ratio [OR] 0.82, 95% CI 0.55, 1.19) or mortality (0.1% vs 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). Between phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs 0.39, respectively; interaction P-value = 0.053). Conclusion: Real-world evidence demonstrated that sotrovimab was not associated with reduced 28-day hospitalization or mortality among COVID-19 outpatients during the Omicron BA.1 phase.

Abstract Background Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. Methods This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. Results COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52–5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01–3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20–3.82), obesity (OR 1.79, 95% CI 1.36–2.34), one comorbidity (OR 1.68, 95% CI 1.11–2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13–2.35), and male sex (OR 1.56, 95% CI 1.21–2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). Conclusions Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

Alcohol consumption has been linked to numerous pathologic conditions, including infectious diseases and several types of cancer. Alcohol exerts its modulatory effects on the immune system (IS) in a dose- and time-dependent manner. Numerous studies indicate that these alterations affect responses such as peripheral inflammation or decreased antibody production and promote chronic inflammation, leading to cell death. The molecular mechanisms underlying these effects involve generating an oxidative tissue environment, producing cell damage-associated molecular patterns (DAMPs), and activating pattern recognition receptors. In particular, toll-like receptors and their signaling system emerge as central elements whose activity is altered by alcohol intake. There is also some epidemiological evidence demonstrating the causal role of alcohol in the development of various types of cancer, such as head-and-neck cancer, esophageal cancer, colorectal cancer, liver cancer, and breast cancer. Most recent evidence suggests that factors related to alcohol consumption and cancer include increased levels of acetaldehyde, production of reactive oxygen species, alteration in DNA methylation, and modifications in retinoid metabolism. In addition, changes associated with alcohol use on the IS and intestinal microbiota may favor the growth of some types of tumors.

Background: HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality. Objective: We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality. Methods: We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis ( n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis. Results: 1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p

We conducted a literature review to identify commonly used recruitment and retention strategies in research among adolescent and young adult (AYA) cancer survivors 15-39 years of age and examine the effectiveness of these strategies based on the reported recruitment and retention rates. We identified 18 publications published after 2010, including 14 articles describing recruitment strategies and four articles discussing retention strategies and addressing reasons for AYA cancer patients dropping out of the studies. In terms of recruitment, Internet and social networking strategies were used most frequently and resulted in higher participation rates of AYA cancer survivors compared to other conventional methods, such as hospital-based outreach, mailings, and phone calls. In terms of retention, investigators used monetary incentives in all four studies and regular emails in two studies. There was no association between the number of strategies employed and the overall recruitment (p = 0.09) and retention rates (p = 0.33). Future research and planned studies testing recruitment and retention strategies are needed to identify optimal, modern communication procedures to increase AYA participation and adherence. More education should be provided to AYAs to increase their knowledge of research studies and strengthen the connection between AYA cancer survivors and their health providers.

ABSTRACT Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Aiming to provide greater visibility for the wood species Acrocarpus fraxinifolius, the present study sought to analyze the influence of heat treatment on an industrial scale applied to wood species, also popularly known as Indian cedar. The heat treatment was carried out in an autoclave, with temperature and pressure control, and with saturated steam injection, for temperatures 155 ºC, 165 ºC, 175 ºC, and 185 ºC. Physical, chemical, and mechanical tests were carried out for the analyzed wood. The content of holocellulose and total lignin decreased, while the content of extractives showed a substantial increase. The density increased after the heat treatment, however the treated wood showed cracks, and these cracks influenced the significant loss of the values of the mechanical properties of compression, tension, and flexion. The shear showed strength gain for the temperature of 155 ºC, and the wood treated at 165 ºC was equivalent to untreated wood. The woods submitted to temperatures of 175 ºC and 185 ºC presented strength losses. The heat treatment in question contributes to increase the visibility, use and market value of wood.

Foodborne trematodiasis is a neglected tropical disease (NTD) caused by zoonotic trematodes that persist mainly in impoverished areas in the Asia-Pacific region. Globally, about 2 million disability life years (DALYs) are lost due to these parasitic infections. Four groups of foodborne trematodes are known to cause significant illness: fish-borne liver fluke infections caused by Opisthorchis and Clonorchis spp.; water vegetable-borne Fasciola spp. infections; crustacean-vectored paragonimiasis; and those caused by intestinal trematodes. In the Philippines, endemic foodborne trematodes of public health concern include Paragonimus westermani, some members of Heterophyidae and Echinostomatidae, and Fasciola hepatica/ F. gigantica. Opisthorchis viverrini and Clonorchis sinensis have also been reported in the country. Data on the epidemiology of these zoonotic illnesses remain scarce and in need of research attention in the Philippines. Culturally rooted eating behaviors in endemic areas are important risk factors to acquiring and perpetuating foodborne trematodiasis. The combination of mass drug administration (MDA), provision of clean water and maintenance of good sanitation and hygiene (WASH), community health education towards modification of risky behaviors, surveillance, and veterinary public health interventions have been shown to be effective in combatting these zoonotic parasitoses. An integrated control and prevention program anchored on the One Health paradigm is a must to address these illnesses. This paper aims to review the biology and epidemiology of, and public health interventions against zoonotic foodborne trematodiasis in the Philippines and its neighboring countries.

Seismic reflection data (normal incidence and wide angle) are unique assets for solid Earth sciences as they provide critical information about the physical properties and structure of the lithosphere as well as about the shallow subsurface for exploration purposes. The resolution of these seismic data is highly appreciated; however they are logistically complex and expensive to acquire, and their geographical coverage is limited. Therefore, it is essential to make the most of the data that have already been acquired. The collation and dissemination of seismic open-access data are then key to promote accurate and innovative research and to enhance new interpretations of legacy data. This work presents the Seismic DAta REpository (SeisDARE), which is, to our knowledge, one of the first comprehensive open-access online databases that stores seismic data registered with a permanent identifier (DOI). The datasets included here are openly accessible online and guarantee the FAIR (findable, accessible, interoperable, reusable) principles of data management, granting the inclusion of each dataset in a statistics referencing database so its impact can be measured. SeisDARE includes seismic data acquired in the last 4 decades in the Iberian Peninsula and Morocco. These areas have attracted the attention of international researchers in the fields of geology and geophysics due to the exceptional outcrops of the Variscan and Alpine orogens and wide foreland basins, the crustal structure of the offshore margins that resulted from a complex plate kinematic evolution, and the vast quantities of natural resources contained within. This database has been built thanks to a network of national and international institutions, promoting a multidisciplinary research and is open for international data exchange and collaborations. As part of this international collaboration, and as a model for inclusion of other global seismic datasets, SeisDARE also hosts seismic data acquired in Hardeman County, Texas (USA), within the COCORP project (Consortium for Continental Reflection Profiling). SeisDARE aims to make easily accessible old and recently acquired seismic data and to establish a framework for future seismic data management plans. SeisDARE is freely available at https://digital.csic.es/handle/10261/101879 (a detailed list of the datasets can be found in Table 1), bringing endless research and teaching opportunities to the scientific, industrial, and educational communities.

An exploratory study is presented on the family networks of positive cases to SARS-CoV-2 with the objective of characterizing the families and their members in the period from March 11 to June 1, 2020. The distribution of family networks is identified of positive cases by provinces and it is emphasized in Havana, as the epicenter of the epidemic in Cuba until that period. The results are shown according to sociodemographic variables such as population density, age, sex, family relationship. The results are contrasted with evidence from other international investigations. The importance of analysis of co-residence patterns and relationships between generations is shown for understanding the transmissibility of COVID-19. / RESUMEN Se presenta un estudio exploratorio sobre las redes familiares de casos positivos al SARS-CoV-2 con el objetivo de caracterizar las familias y sus miembros en el período del 11 de marzo al 1 de junio de 2020. Se identifica la distribución de las redes familiares de los casos positivos por provincias y se enfatiza en La Habana, como epicentro de la epidemia en Cuba hasta ese período. Se muestran lo resultados según variables sociodemográficas como densidad poblacional, edad, sexo, parentesco familiar. Se contrastan los resultados con evidencias de otras investigaciones internacionales. Se muestra la importancia del análisis de los patrones de co-residencia y las relaciones entre generaciones para la comprensión de la transmisibilidad de la COVID-19.

Orbital images have been increasingly refined spatially as spectrally as that is the case with those provided by satellite Earth observation WorldView-3 used in this paper. However, the images are very susceptible to noise interference, so it is difficult to identify and characterize objects. Therefore, it is essential to use techniques to minimize them. Thus, through increasingly innovative processing, it is possible to carry out detailed characterization mainly of urban areas. This work aims to perform the classification of images Worldview-3 using the advanced methods of classification Random Forest and Deep Learning for the region of Botafogo in the municipality of Rio de Janeiro, Brazil. Such classifications were performed for four different data sets, including the spectral bands and transformations (MNF and PCA) resulting from the original images. The results demonstrate that the use of transformations resulting from the original images as input data for the extraction of attributes in conjunction with the spectral bands improves the accuracy of the classifications generated by the Random Forest and Deep Learning method.

Background and Aim: Schistosomiasis is one of the seven neglected tropical diseases that are of public health concern in the Philippines. The disease is prevalent in few of the barangays (communities) in Koronadal City, Philippines. Status of the Schistosoma japonicum infections in domestic animal reservoir host has yet to be explored in these endemic communities. The study aimed to determine the prevalence and infection intensity of the disease in cattle and water buffaloes of endemic communities of Koronadal City. Materials and Methods: Schistosomiasis was investigated in 70 cattle and 38 water buffaloes from three endemic communities in Koronadal City. The copro-parasitological technique used was the formalin-ethyl acetate sedimentation method. Results: S. japonicum infection was observed in 48.6% of cattle and 60.5% in water buffaloes. The bovine contamination index indicated that all infected animals released 3,505,500 eggs/day. On average, infected cattle released 1,674,500 eggs daily, while infected water buffaloes liberated 1,932,000 eggs in the environment daily. Conclusion: Cattle and water buffaloes in these endemic areas are infected with S. japonicum. These animals release large numbers of eggs in the environment daily; hence, played an important role in disease transmission. Those living and working in endemic areas should be aware of the inherent dangers of the disease.

Generation of oligodendrocytes in the adult brain enables both adaptive changes in neural circuits and regeneration of myelin sheaths destroyed by injury, disease, and normal aging. This transformation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes requires processing of distinct mRNAs at different stages of cell maturation. Although mislocalization and aggregation of the RNA-binding protein, TDP-43, occur in both neurons and glia in neurodegenerative diseases, the consequences of TDP-43 loss within different stages of the oligodendrocyte lineage are not well understood. By performing stage-specific genetic inactivation of Tardbp in vivo, we show that oligodendrocyte lineage cells are differentially sensitive to loss of TDP-43. While OPCs depend on TDP-43 for survival, with conditional deletion resulting in cascading cell loss followed by rapid regeneration to restore their density, oligodendrocytes become less sensitive to TDP-43 depletion as they mature. Deletion of TDP-43 early in the maturation process led to eventual oligodendrocyte degeneration, seizures, and premature lethality, while oligodendrocytes that experienced late deletion survived and mice exhibited a normal lifespan. At both stages, TDP-43-deficient oligodendrocytes formed fewer and thinner myelin sheaths and extended new processes that inappropriately wrapped neuronal somata and blood vessels. Transcriptional analysis revealed that in the absence of TDP-43, key proteins involved in oligodendrocyte maturation and myelination were misspliced, leading to aberrant incorporation of cryptic exons. Inducible deletion of TDP-43 from oligodendrocytes in the adult central nervous system (CNS) induced the same progressive morphological changes and mice acquired profound hindlimb weakness, suggesting that loss of TDP-43 function in oligodendrocytes may contribute to neuronal dysfunction in neurodegenerative disease.

ABSTRACT Urinary tract infections (UTIs) are the second most frequent bacterial infections worldwide, with Escherichia coli being the main causative agent. The increase of antibiotic-resistance determinants among isolates from clinical samples, including UTIs, makes the development of novel therapeutic strategies a necessity. In this context, the use of bacteriophages as a therapeutic alternative has been proposed, due to their ability to efficiently kill bacteria. In this work, we isolated and characterized three novel bacteriophages, microbes laboratory phage 1 (MLP1), MLP2, and MLP3, belonging to the Chaseviridae, Myoviridae, and Podoviridae families, respectively. These phages efficiently infect and kill laboratory reference strains and multidrug-resistant clinical E. coli isolates from patients with diagnosed UTIs. Interestingly, these phages are also able to infect intestinal pathogenic Escherichia coli strains, such as enteroaggregative E. coli and diffusely adherent E. coli. Our data show that the MLP phages recognize different regions of the lipopolysaccharide (LPS) molecule, an important virulence factor in bacteria that is also highly variable among different E. coli strains. Altogether, our results suggest that these phages may represent an interesting alternative for the treatment of antibiotic-resistant E. coli. IMPORTANCE Urinary tract infections affect approximately 150 million people annually. The current antibiotic resistance crisis demands the development of novel therapeutic alternatives. Our results show that three novel phages, MLP1, MLP2, and MLP3 are able to infect both laboratory and multidrug-resistant clinical isolates of Escherichia coli. Since these phages (i) efficiently kill antibiotic-resistant clinical isolates of uropathogenic Escherichia coli (UPEC), (ii) recognize different portions of the LPS molecule, and (iii) are able to efficiently infect intestinal pathogenic Escherichia coli hosts, we believe that these novel phages are good candidates to be used as a therapeutic alternative to treat antibiotic-resistant E. coli strains generating urinary tract and/or intestinal infections.

Indian cedar (Acrocarpus fraxinifolius) is a wood species that occurs naturally in India, Myanmar (Burma) and Bangladesh, and has a high commercial value, with characteristics like mahogany and native cedars. The planting of Indian cedar has been undertaken in Brazil, but there is little information available regarding the characterization of the species. Therefore, considering its timber potential and its possibility of development in the country, the present work aimed to evaluate the physical, chemical, and mechanical properties of 9-year-old Indian cedar wood, planted in the southern region of Brazil. A low specific mass (502 kg/m³), low average dimensional stability (anisotropy coefficient of 2,09 %) was observed, in addition to the low content of extractives (1,94 %). From the mechanical characterization, an average value for the elastic modulus of 8963 MPa was obtained, and for the compressive strength parallel to the grain the average and characteristic values ​​were 32,14 MPa and 21,46 MPa, respectively. This indicates that this wood belongs to resistance class C20 (dicotyledons). The results obtained classify the wood for use in light, external, or internal civil construction.

We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).

Background: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. Methods: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. Results: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: −0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). Conclusions: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge.

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

ABSTRACT Natural transformation is a broadly conserved mechanism of horizontal gene transfer (HGT) in bacteria that can shape their evolution through the acquisition of genes that promote virulence, antibiotic resistance, and other traits. Recent work has established that neighbor predation via type VI secretion systems, bacteriocins, and virulent phages plays an important role in promoting HGT. Here, we demonstrate that in chitin estuary microcosms, Vibrio cholerae K139 lysogens exhibit prophage-dependent neighbor predation of nonlysogens to enhance HGT. Through predation of nonlysogens, K139 lysogens also have a fitness advantage under these microcosm conditions. The ecological strategy revealed by our work provides a better understanding of the evolutionary mechanisms used by bacteria to adapt in their natural setting and contributes to our understanding of the selective pressures that may drive prophage maintenance in bacterial genomes. IMPORTANCE Prophages are nearly ubiquitous in bacterial species. These integrated phage elements have previously been implicated in horizontal gene transfer (HGT) largely through their ability to carry out transduction (generalized or specialized). Here, we show that prophage-encoded viral particles promote neighbor predation leading to enhanced HGT by natural transformation in the waterborne pathogen Vibrio cholerae. Our findings contribute to a comprehensive understanding of the dynamic forces involved in prophage maintenance which ultimately drive the evolution of naturally competent bacteria in their natural environment.

A vast polychaete fauna is hidden behind complexes of cryptic and pseudo-cryptic species, which has greatly hindered our understanding of species diversity in several regions worldwide. Among the eunicids, Marphysa sanguinea Montagu, 1813 is a typical example, recorded in three oceans and with various species considered its junior synonyms. In South Africa, specimens previously misidentified as M. sanguinea are now known as Marphysa elityeni Lewis & Karageorgopoulos, 2008. Of the six Marphysa Quatrefages, 1865a species recorded from the same region, three have their distributions restricted to South Africa while the others are considered to have worldwide distributions. Here, we evaluated the taxonomic status of the indigenous M. elityeni and investigated the presence of the widespread species Marphysa macintoshi Crossland, 1903 and Marphysa depressa Schmarda, 1861 in South Africa using morphological and molecular data. Our results reveal that M. elityeni is a junior synonym of Marphysa haemasoma, a species previously described from South Africa which is herein reinstated as a valid species. Both M. macintoshi and M. depressa are not present in South Africa and their status as being distributed worldwide deserves further investigation. Marphysa durbanensis Day, 1934 and the new species described here, M. sherlockae n. sp., had been misidentified as M. macintoshi and M. depressa respectively. Thus, the number of Marphysa species with distributions restricted to South Africa increased from three to five. This study reiterates the importance of implementing an integrated taxonomic framework to unravel local biodiversity.

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here, we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

The apoplast, i.e. the cellular compartment external to the plasma membrane, undergoes important changes during senescence. Apoplastic fluid volume increases quite significantly in senescing leaves, thereby diluting its contents. Its pH elevates by about 0.8 units, similar to the apoplast alkalization in response to abiotic stresses. The levels of 159 proteins decrease, whereas 24 proteins increase in relative abundance in the apoplast of senescing leaves. Around half of the apoplastic proteins of non-senescent leaves contain a N-terminal signal peptide for secretion, while all the identified senescence-associated apoplastic proteins contain the signal peptide. Several of the apoplastic proteins that accumulate during senescence also accumulate in stress responses, suggesting that the apoplast may constitute a compartment where developmental and stress-related programs overlap. Other senescence-related apoplastic proteins are involved in cell wall modifications, proteolysis, carbohydrate, ROS and amino acid metabolism, signaling, lipid transport, etc. The most abundant senescence-associated apoplastic proteins, PR2 and PR5 (e.g. pathogenesis related proteins PR2 and PR5) are related to leaf aging rather than to the chloroplast degradation program, as their levels increase only in leaves undergoing developmental senescence, but not in dark-induced senescent leaves. Changes in the apoplastic space may be relevant for signaling and molecular trafficking underlying senescence.

T cells can be activated by a small, two-digit, number of antigen peptide molecules even though the receptor for antigen (TCR) is of low affinity. Here the authors present evidence that all TCRs within a nanocluster can become activated when only a subset is bound to antigen.

El artículo aborda la importancia de la educación en población en la actualidad cubana y la necesidad de generar metodologías que garanticen la calidad de este proceso. Se muestra la educación en población como uno de los campos de conexión de la demografía con la psicología, lo que evidencia el enfoque multidisciplinario de los estudios de población y su necesidad constante de interrelación con otras ciencias. Se presenta, entonces, la supervisión psicológica como una herramienta metodológica para avanzar en este propósito. The article addresses the importance of education in the Cuban population today and the need to generate methodologies that guarantee the quality of this process. The connection of population education as one of the fields of demography with psychology is shown, which demonstrates the multidisciplinary approach of population studies and their constant need for interrelation with other sciences. Psychological supervision is then presented as a methodological tool to advance this purpose.

Context: The synthetic insecticides used to control Diptera are harmful to the environment and humans. Extracts and compounds from plants are a more sustainable source for the development of bio-insecticides. Aims: To evaluate the efficacy of a hydroalcoholic extract of Persea americana Mill seeds as an alternative control of the species Musca domestica. Methods: The extracts were obtained by two methods, the Shaker (S) and the Soxhlet extraction (SE) method, using 94% ethanol as the solvent. Also, the qualitative chemical composition was determined by phytochemical screening. The effect of the two extracts on the post-embryonic development of the fly as well as the adulticidal effect was evaluated. Results: Phytochemical analysis revealed the presence of metabolites such as alkaloids, coumarins, tannins, flavonoids, sugars and amino acids. The influence on the post-embryonic development of M. domestica was demonstrated, especially on the viability of larvae and neolarvae to adults; however, the effect on the weight and duration of each period was low. The adulticidal effects of the extracts were determined by the lethal concentration 50(LC50) of 2.910 mg/100 mL and 3.944 mg/100 mL for the S and SE extracts, respectively. Conclusions: Both extracts showed their insecticidal effects against Musca domestica, but the extract elaborated by S method showed greater influence diminishing viability and better adulticidal effect.