The new record of drought and warmth in the Amazon in 2023 related to regional and global climatic features.

In 2023 Amazonia experienced both historical drought and warm conditions. On October 26th 2023 the water levels at the port of Manaus reached its lowest record since 1902 (12.70 m). In this region, October monthly maximum and minimum temperature anomalies also surpassed previous record values registered in 2015 (+ 3 °C above the normal considering the 1981-2020 average). Here we show that this historical dry and warm situation in Amazonia is associated with two main atmospheric mechanisms: (i) the November 2022-February 2023 southern anomaly of vertical integrated moisture flux (VIMF), related to VIMF divergence and extreme rainfall deficit over southwestern Amazonia, and (ii) the June-August 2023 downward motion over northern Amazonia related to extreme rainfall deficit and warm conditions over this region. Anomalies of both atmospheric mechanisms reached record values during this event. The first mechanism is significantly correlated to negative sea surface temperature (SST) anomalies in the equatorial Pacific (November-February La Niña events). The second mechanism is significantly correlated to positive SST anomalies in the equatorial Pacific, related to the impacts of June-September El Niño on the Walker Circulation. While previous extreme droughts were linked to El Niño (warmer North Tropical Atlantic SST) during the austral summer (winter and spring), the transition from La Niña 2022-23 to El Niño 2023 appears to be a key climatic driver in this record-breaking dry and warm situation, combined to a widespread anomalous warming over the worldwide ocean.

Factors associated with ablation-related thrombus extension following microfoam versus radiofrequency saphenous vein closure.

OBJECTIVE: Polidocanol endovenous microfoam ablation (MFA) is approved by the US Food and Drug Administration for great saphenous vein (GSV) closure, yet there are few published data on the subsequent risk of ablation-related thrombus extension (ARTE). Recent societal practice guidelines recommend against routine postprocedure duplex ultrasound (DU) examination after thermal ablation of the GSV in asymptomatic patients. At present, limited data do not allow this recommendation to extend to MFA. Our aim is to identify characteristics and outcomes associated with ARTE following MFA vs radiofrequency ablation (RFA). METHODS: A retrospective review of a prospectively maintained database was conducted of patients who underwent MFA and RFA closure of incompetent above-knee GSVs. Patients treated for isolated tributary vein treatment or did not have a postprocedure DU examination within 48 to 72 hours were not included. Patients were classified into two groups: ARTE and no ARTE. Demographic data, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, operative details, postprocedure (48-72 hours) DU findings, and adverse events were analyzed. Variables that were significant on univariate analysis were evaluated using multivariate logistic regression with the primary outcome being development of ARTE. RESULTS: Between June 2018 and February 2023, 800 limbs were treated with either MFA (n = 224) or RFA (n = 576). Ninety-six GSVs treated with MFA met the study criteria. One hundred fifty successive GSVs treated with RFA during the same period were included as a comparison group. There was no statistically significant difference in baseline demographics between the two groups. Six patients (2.4%) demonstrated ARTE on postoperative DU examination at 48 to 72 hours (MFA, n = 5 [5.2%]; RFA, n = 1 [0.7%]; P = .02). Saphenous vein ablation with MFA (P = .045) and a vein diameter of >10 mm (P = .017) were associated with ARTE on both univariable and multivariable analysis. All patients who developed ARTE were treated with oral anticoagulants (mean, 15.6 days). Body mass index, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, microfoam volume, operative time, and prior deep venous thrombosis were not predictive of ARTE. CONCLUSIONS: ARTE after above-knee GSV closure occurred more frequently after MFA. Our results suggest that a saphenous vein diameter of >10 mm may be associated with ARTE. Despite this finding, all patients with ARTE were treated with short-term anticoagulation with no related complications. Until larger studies with high-risk subgroups have been studied after MFA, DU examination should be performed routinely after this procedure and patients with ARTE anticoagulated until the thrombus retracts caudal to the saphenofemoral junction or is no longer present on DU examination. Current societal guidelines recommending against routine post-thermal ablation DU examination should not be applied to similar patients after saphenous nonthermal MFA ablation.

Increased body mass index and vein diameter are associated with incomplete target vein closure following microfoam ablation of incompetent saphenous veins.

OBJECTIVE: Patient characteristics and risk factors for incomplete or non-closure following thermal saphenous vein ablation have been reported. However, similar findings have not been clearly described following commercially manufactured polidocanol microfoam ablation (MFA). The objective of our study is to identify predictive factors and outcomes associated with non-closure following MFA of symptomatic, refluxing saphenous veins. METHODS: A retrospective review of a prospectively maintained patient database was performed from procedures in our Ambulatory Procedure Unit. All consecutive patients who underwent MFA with commercially manufactured 1% polidocanol microfoam for symptomatic superficial vein reflux between June 2018 and September 2022 were identified. Patients treated for tributary veins only, without truncal vein ablation, were excluded. Patients were then stratified into groups: complete closure (Group I) and non-closure (Group II). Preoperative demographics, procedural details, and postoperative outcomes were analyzed. Preoperative variables that were significant on univariate analysis (prior deep venous thrombosis [DVT], body mass index [BMI] ≥30 kg/m2, and vein diameter) were entered into a multivariate logistic regression model with the primary outcome being vein non-closure. RESULTS: Between June 2018 and September 2022, a total of 224 limbs underwent MFA in our ambulatory venous center. Of these, 127 limbs in 103 patients met study inclusion criteria. Truncal veins treated included the above-knee great saphenous vein (Group I: n = 89, 77% vs Group II: n = 7, 58%; P = .14), below-knee great saphenous vein (Group I: n = 7, 6% vs Group II: n = 0; P = .38), anterior accessory saphenous vein (Group I: n = 17, 15% vs Group II: n = 4, 33%; P = .12, and small saphenous vein (Group I: n = 4, 4% vs Group II: n = 1, 8%; P = .41). Complete closure (Group I) occurred in 115 limbs, and 12 limbs did not close (Group II) based on postoperative duplex ultrasound screening. The mean BMI in Group II (36.1 ± 6.4 kg/m2) was significantly greater than Group I (28.6 ± 6.1 kg/m2) (P < .001). Vein diameter of ≥10.2 mm was independently associated with truncal vein non-closure with an odds ratio of 4.8. The overall mean foam volume was 6.2 ± 2.7 ml and not different between the two cohorts (Group I: 6.2 ± 2.6 ml vs Group II: 6.3 + 3.5 ml; P = .89). Post MFA improvement in symptoms was higher in Group I (96.9%) compared with Group II (66.7%) (P = .001). The mean postoperative Venous Clinical Severity Score was also lower in Group I (8.0 ± 3.0) compared with Group II (9.9 ± 4.2) (P = .048). The overall incidences of ablation-related thrombus extension and DVT were 4.7% (n = 6) and 1.6% (n = 2), and all occurred in Group I. All were asymptomatic and resolved with anticoagulation. CONCLUSIONS: Microfoam ablation of symptomatic, refluxing truncal veins results in excellent overall closure rates and symptomatic relief. BMI ≥30 kg/m2 and increased vein diameter are associated with an increased risk of saphenous vein non-closure following MFA. Non-closure is associated with less symptomatic improvement and a lower post-procedure reduction in Venous Clinical Severity Score. Despite the incidence of ablation-related thrombus extension and DVT in this study being higher than reported rates following thermal ablation, MFA is safe for patients with early postoperative duplex ultrasound surveillance and selective short-term anticoagulation.

Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey.

BACKGROUND: National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002-2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission. METHODS: In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to 'next-generation sequencing workflow' (11), 'variant classification' (3) and 'phenotypical context' (4). RESULTS: Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored. CONCLUSION: The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation.

Short-term mortality and revisions to promote maturation after arteriovenous fistula creation.

OBJECTIVE: Arteriovenous fistula (AVF) for hemodialysis access is traditionally considered superior to grafts due to infection resistance and purported improved patency. However, challenges to AVF maturation and limited patient survival may reduce AVF benefits. The objective of this study is to identify factors associated with risk of AVF requiring revision before maturation and/or mortality within 2 years of creation. METHODS: We performed a retrospective review of 250 AVFs created between May 2017 and November 2020 at a single institution. Maturation was defined as the date the surgeon deemed the AVF ready for use or the patient successfully used the AVF for dialysis. The Risk Analysis Index was used to calculate frailty. The primary outcome was a composite of endovascular/surgical revision to promote maturation and/or mortality within 2 years of AVF creation (REVDEAD). The primary outcome was categorized as met if the patient required a revision to promote maturation or if the patient experienced mortality within 2 years of AVF creation, or if both occurred. REVDEAD was compared with those who did not meet the primary outcome and will be referred to as NOREVDEAD. RESULTS: Survival at 2 years after AVF creation was 82%, and 54 (22%) patients underwent AVF revision. Of those, 31 (59%) patients progressed to AVF maturation. Of the 250 AVFs, 91 (36%) met the primary outcome of REVDEAD and 159 (64%) did not (NOREVDEAD). There was no difference between the REVDEAD and NOREVDEAD groups in age (P = .18), sex (P = .75), White race (P = .97), Hispanic ethnicity (P = .62), obesity (P = .76), coronary artery disease (P = .07), congestive heart failure (P = .29), diabetes mellitus (P = .78), chronic obstructive pulmonary disease (P = .10), dialysis status (P = .63), hypertension (P = .32), peripheral arterial disease (P = .34), or dysrhythmia (P = .13). There was no difference between the groups in the forearm vs the upper arm location of AVF (P = .42) or the vein diameter (P = .58). Forearm access, as opposed to upper arm AVF creation, was associated with higher rate of revision before maturation (P = .05). More patients in REVDEAD were frail or very frail (60% vs 48%, P = .05). Of the AVFs that matured, maturation required longer time in REVDEAD at 110.0 ± 9.1 days vs 78.8 ± 5.6 days (mean ± standard deviation) (P = .003). Adjusted for the vein diameter and the forearm vs the upper arm, frailty increased the odds of REVDEAD by 1.9 (95% confidence interval: 1.1, 3.3). CONCLUSIONS: Frail patients who underwent AVF were significantly more likely to die within 2 years of AVF creation with no significant association between frailty and the need for revisions to promote maturation. Forearm AVFs were more likely to require revisions; in patients who are frail, with a high likelihood of 2-year mortality, graft may be more appropriate than AVF. If AVF is being considered in a frail patient, upper arm AVFs should be prioritized over forearm AVFs.

The Barriers to Deprescription in Older Patients: A Survey of Spanish Clinicians.

BACKGROUND AND OBJECTIVE: There are barriers to deprescription that hinder its implementation in clinical practice. The objective of this study was to analyse the main barriers and limitations of the deprescription process perceived by physicians who care for multipathological patients. MATERIALS AND METHODS: The "deprescription questionnaire of elderly patients" was adapted to an online format and sent to physicians in geriatrics. Question 1 is a reference to establish agreement or disagreement with this practice. The influence of different aspects of deprescription was analysed via the demographic characteristics of the clinicians and perceptions of the various barriers (questions 2-9) by means of bivariate analysis. Based on the latter, a multivariate model was carried out to demonstrate the relationship between barriers and the degree of deprescription agreement among respondents. RESULTS: Of the 72 respondents, 72.2% were in favour of deprescribing. Regarding the analyses, the demographic characteristics did not influence rankings. The deprescription of preventive drugs and consensus with patients were associated with a positive attitude towards deprescribing, while withdrawing drugs prescribed by other professionals, time constraints and patient reluctance emerged as possible barriers. The only factor independently associated with deprescribing was lack of time. CONCLUSIONS: Time was found to be the main barrier to deprescription. Training, the creation of multidisciplinary teams and integrated health systems are key facilitators.

Early results following comparison of radiofrequency and microfoam ablation of large diameter truncal veins demonstrate high closure rates and symptomatic relief.

OBJECTIVE: Endovenous closure of truncal veins with a large diameter (LD) (≥8 mm) has been associated with higher risk of post ablation thrombus propagation into the deep venous system. Similar findings after Varithena microfoam ablation (MFA) have not been characterized. The study objective was to analyze outcomes after both radiofrequency ablation (RFA) and MFA and of LD truncal veins. METHODS: A retrospective review of a prospectively maintained database was performed. All patients who underwent MFA and RFA for LD symptomatic truncal vein reflux (≥8 mm) were identified. All patients had postoperative duplex (48-72 hours) scanning. Patients underwent subsequent clinical follow-up at 3 to 6 weeks. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, adverse thrombotic events, and follow-up data were abstracted. RESULTS: Between June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent truncal vein (great, accessory, and small saphenous) closure for symptomatic reflux. Sixty-six limbs in the MFA group met inclusion criteria. Sixty-six consecutive limbs treated with RFA during the same time period were included as a comparison group. The mean truncal vein diameter treated was 10.5 mm (RFA, 10.0 mm; MFA, 10.9 mm). Twenty-nine limbs (44%) in the RFA group underwent concomitant phlebectomy. Tributary veins were concomitantly sclerosed in 34 MFA limbs (52%). Total procedural times were shorter in the MFA group (MFA, 31.6 minutes vs RFA, 55.7 minutes) (P < .001). Immediate closure rates were 100% and 95% in the RFA and MFA groups, respectively. Venous Clinical Severity Scores improved after treatment in both groups (RFA, from 9.5 to 7.8; P ≤ .001) (MFA, from 11.3 to 9.0; P ≤ .001). In the RFA and MFA groups, 83% and 79% of venous ulcers healed during the study period, respectively. Symptomatic superficial phlebitis occurred after RFA in 11% and 17% MFA. The incidence of postablation proximal deep venous thrombus extension was 3.0% in the RFA group and 6.1% in the MFA group, which was not statistically significant. All resolved with short-term oral anticoagulant therapy. No remote deep venous thromboses or pulmonary emboli occurred in either group. CONCLUSIONS: High early closure rates, symptom relief and ulcer healing rates can be achieved after RFA and MFA of LD saphenous veins. Both techniques can be used safely across a wide array of CEAP classes. Longer term studies are required to characterize the durability of MFA closure and sustained symptom relief in LD truncal veins.

Comparison of outcomes following polidocanol microfoam and radiofrequency ablation of incompetent thigh great and accessory saphenous veins.

BACKGROUND: Microfoam ablation (MFA) and radiofrequency ablation (RFA) are both approved by the Food and Drug Administration for treatment of proximal saphenous truncal veins. The objective of our study was to compare early postoperative outcomes between MFA and RFA following treatment of incompetent thigh saphenous veins. METHODS: A retrospective review of a prospectively maintained database was conducted of patients who underwent treatment of incompetent great saphenous veins (GSVs) or anterior accessory saphenous veins (AASVs) in the thigh. All the patients underwent duplex ultrasound of the treated leg at 48 to 72 hours postoperatively. Patients were excluded from analysis if concomitant stab phlebectomy was performed. Demographic data, CEAP (clinical, etiologic, anatomic, pathophysiologic) class, venous clinical severity score (VCSS), and adverse events were recorded. RESULTS: Between June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent venous closure for symptomatic reflux. A total of 200 consecutive thigh GSVs and ASVs treated within the study period using either MFA (n = 100) or RFA (n = 100) were identified. The patients were predominantly women (69%) with a mean age of 64 years. The preoperative CEAP classification was similar between the MFA and RFA groups. The mean preoperative VCSS was 9.4 ± 2.6 for the RFA patients and 9.9 ± 3.3 for the MFA patients. Among the RFA patients, the GSV was treated in 98% and the AASV in 2% compared with the GSV in 83% and the AASV in 17% in the MFA group (P < .001). The mean operative time was 42.4 ± 15.4 minutes in the RFA group and 33.8 ±16.9 minutes in the MFA group (P < .001). The median follow-up was 64 days for the study cohort. The mean postoperative VCSS declined to 7.3 ± 2.1 in the RFA group and 7.8 ± 2.9 in the MFA group. Complete closure occurred in 100% of the limbs after RFA and 90% after MFA (P = .005). Eight veins were partially closed and two remained patent following MFA. The incidence of superficial phlebitis was 6% and 15% (P = .06) after RFA and MFA, respectively. Overall, symptomatic relief was 90% following RFA and 89.5% following MFA. The complete ulcer healing rate for the entire cohort was 77.8%. Deep venous proximal thrombus extension (RFA, 1%; vs MFA, 4%; P = .37) and remote deep vein thrombosis (RFA, 0%; vs MFA, 2%; P = .5) showed a trend toward being higher following MFA but the difference did not reach statistical significance. All were asymptomatic and resolved with short-term anticoagulation therapy. CONCLUSIONS: MFA and RFA are both safe and effective for treating incompetent thigh saphenous veins, with excellent symptomatic relief and a low incidence of postprocedure adverse thrombotic events. RFA resulted in improved complete closure rates following initial treatment compared with MFA. The operative times were shorter with MFA. Both modalities can be used for patients with active venous ulcers with good healing rates. Longer term studies are required to characterize the durability of MFA closure for above knee truncal veins.

Modeling the interaction between donor-derived regulatory T cells and effector T cells early after allogeneic hematopoietic stem cell transplantation.

While allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative therapy against hematological malignancies, modulation of donor T cell alloreactivity is required to enhance the graft-versus-leukemia (GVL) effect and control graft-versus-host-disease (GVHD) after allo-HSCT. Donor-derived regulatory CD4+CD25+Foxp3+ T cells (Tregs) play a central role in establishing of immune tolerance after allo-HSCT. They could be a key target to be modulated for increasing the GVL effect and control of GVHD. We constructed an ordinary differential equation model incorporating bidirectional interactions between Tregs and effector CD4+ T cells (Teffs) as a mechanism for control of Treg cell concentration. The goal is to elucidate how the interaction between Tregs and Teffs is modulated in order to get insights into fine tuning of alloreactivity after allo-HSCT. The model was calibrated with respect to published Treg and Teff recovery data after allo-HSCT. The calibrated model exhibits perfect or near-perfect adaptation to stepwise perturbations between Treg and Teff interactions, as seen in Treg cell populations when patients with relapsed malignancy were treated with anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen 4). In addition, the model predicts observed shifts of Tregs and Teffs concentrations after co-stimulatory receptor IL-2R or TNFR2 blockade with allo-HSCT. The present results suggest simultaneous blockades of co-stimulatory and co-inhibitory receptors as a potential treatment for enhancing the GVL effect after allo-HSCT without developing GVHD.

Half a century of rising extinction risk of coral reef sharks and rays.

Sharks and rays are key functional components of coral reef ecosystems, yet many populations of a few species exhibit signs of depletion and local extinctions. The question is whether these declines forewarn of a global extinction crisis. We use IUCN Red List to quantify the status, trajectory, and threats to all coral reef sharks and rays worldwide. Here, we show that nearly two-thirds (59%) of the 134 coral-reef associated shark and ray species are threatened with extinction. Alongside marine mammals, sharks and rays are among the most threatened groups found on coral reefs. Overfishing is the main cause of elevated extinction risk, compounded by climate change and habitat degradation. Risk is greatest for species that are larger-bodied (less resilient and higher trophic level), widely distributed across several national jurisdictions (subject to a patchwork of management), and in nations with greater fishing pressure and weaker governance. Population declines have occurred over more than half a century, with greatest declines prior to 2005. Immediate action through local protections, combined with broad-scale fisheries management and Marine Protected Areas, is required to avoid extinctions and the loss of critical ecosystem function condemning reefs to a loss of shark and ray biodiversity and ecosystem services, limiting livelihoods and food security.

Relation between the Dam's Weight on Superficial Temperature of Her Puppies at Different Stages of the Post-Partum.

The thermal stability of newborns is an essential parameter that can be recorded to evaluate neonatal care. Knowing the thermal windows to evaluate and maintain a constant temperature helps significantly reduce neonatal mortality. This study aimed to assess the superficial temperature alterations in the distinct thermal windows of puppies with mothers of diverse weights and their repercussions. We evaluated the superficial temperature using infrared thermography at eight thermal windows and seven different times: when wet due to the fetal fluid immediately after birth until 24 h of life in newborn puppies from bitches divided into four bodyweight groups. The results revealed a positive correlation between the dam's weight and the ability to achieve thermostability in the newborn puppies in all the evaluated thermal windows. The time effect showed the lowest temperatures when the puppies were still wet, a gradual increase, and the highest temperature at 24 h after birth. The thermal windows with the highest temperatures were abdominal, thoracic, nasal, and upper left palpebral, and those with the lowest were the thoracic limb brachial biceps, thoracic limb elbow, metacarpal, and femoral pelvic limb. A significant increase in the temperatures in the thermal windows of the abdominal, thoracic, and upper left palpebral immediately after ingesting colostrum was observed. The weight of the dams is an important factor that positively intervenes in the thermoregulatory capacity of the puppies, especially when newborns are dry and have been passed 24 h after birth.

Severe symptomatic nickel allergy following stent graft implantation requiring excision and external iliac artery reconstruction.

Although nickel allergy is a common cause of contact dermatitis, systemic reactions to nitinol stents are rare. A 61-year-old woman had presented with a nonhealing toe wound. Angiography revealed an external iliac artery stenosis, which was treated with a nitinol stent graft. However, she developed severe truncal pruritus, and within 3 months, her external iliac stent graft had thrombosed. Allergy testing revealed nickel sensitivity. After medical therapy had failed, stent graft removal was performed, resulting in complete resolution of her symptoms. The present case demonstrates a rare allergic reaction to the nitinol in commercially available stent grafts. Pruritus and rash are rare reactions to stenting; however, a nitinol allergy should be considered for patients with no other identifiable primary source.

Diversity and determinants of bitterness, astringency, and fat content in cultivated Nacional and native Amazonian cocoa accessions from Ecuador.

Cocoa (Theobroma cacao L.) is the only tree that can produce cocoa. Cocoa beans are highly sought after by chocolate makers to produce chocolate. Cocoa can be fine aromatic, characterized by floral and fruity notes, or it can be described as standard cocoa with a more pronounced cocoa aroma and bitterness. In this study, the genetic and biochemical determinants of sensorial notes and nonvolatile compounds related to bitterness, astringency, fat content, and protein content will be investigated in two populations: a cultivated modern Nacional population and a population of cocoa accessions collected recently in the Ecuadorian South Amazonia area of origin of the Nacional ancestral variety. For this purpose, a genome-wide association study (GWAS) was carried out on both populations, with results of biochemical compounds evaluated by near-infrared spectroscopy (NIRS) assays and with sensory evaluations. Twenty areas of associations were detected for sensorial data especially bitterness and astringency. Fifty-three areas of associations were detected linked to nonvolatile compounds. A total of 81 candidate genes could be identified in the areas of the association.

Glucose consumption rate-dependent transcriptome profiling of Escherichia coli provides insight on performance as microbial factories.

BACKGROUND: The modification of glucose import capacity is an engineering strategy that has been shown to improve the characteristics of Escherichia coli as a microbial factory. A reduction in glucose import capacity can have a positive effect on production strain performance, however, this is not always the case. In this study, E. coli W3110 and a group of four isogenic derivative strains, harboring single or multiple deletions of genes encoding phosphoenolpyruvate:sugar phosphotransferase system (PTS)-dependent transporters as well as non-PTS transporters were characterized by determining their transcriptomic response to reduced glucose import capacity. RESULTS: These strains were grown in bioreactors with M9 mineral salts medium containing 20 g/L of glucose, where they displayed specific growth rates ranging from 0.67 to 0.27 h-1, and specific glucose consumption rates (qs) ranging from 1.78 to 0.37 g/g h. RNA-seq analysis revealed a transcriptional response consistent with carbon source limitation among all the mutant strains, involving functions related to transport and metabolism of alternate carbon sources and characterized by a decrease in genes encoding glycolytic enzymes and an increase in gluconeogenic functions. A total of 107 and 185 genes displayed positive and negative correlations with qs, respectively. Functions displaying positive correlation included energy generation, amino acid biosynthesis, and sugar import. CONCLUSION: Changes in gene expression of E. coli strains with impaired glucose import capacity could be correlated with qs values and this allowed an inference of the physiological state of each mutant. In strains with lower qs values, a gene expression pattern is consistent with energy limitation and entry into the stationary phase. This physiological state could explain why these strains display a lower capacity to produce recombinant protein, even when they show very low rates of acetate production. The comparison of the transcriptomes of the engineered strains employed as microbial factories is an effective approach for identifying favorable phenotypes with the potential to improve the synthesis of biotechnological products.

Global transcriptomic response of Escherichia coli to p-coumaric acid.

The aromatic compound p-coumaric acid (p-CA) is a secondary metabolite produced by plants. This aromatic acid and derived compounds have positive effects on human health, so there is interest in producing them in biotechnological processes with recombinant Escherichia coli strains. To determine the physiologic response of E. coli W3110 to p-CA, dynamic expression analysis of selected genes fused to a fluorescent protein reporter as well as RNA-seq and RT-qPCR were performed. The observed transcriptional profile revealed the induction of genes involved in functions related to p-CA active export, synthesis of cell wall and membrane components, synthesis of amino acids, detoxification of formaldehyde, phosphate limitation, acid stress, protein folding and degradation. Downregulation of genes encoding proteins involved in energy production, carbohydrate import and metabolism, as well as several outer and plasma membrane proteins was detected. This response is indicative of cell envelope damage causing the leakage of intracellular components including amino acids and phosphate-containing compounds. The cellular functions responding to p-CA that were identified in this study will help in defining targets for production strains improvement.

Predicting 30-Day Readmission Risk for Patients With Chronic Obstructive Pulmonary Disease Through a Federated Machine Learning Architecture on Findable, Accessible, Interoperable, and Reusable (FAIR) Data: Development and Validation Study.

BACKGROUND: Owing to the nature of health data, their sharing and reuse for research are limited by legal, technical, and ethical implications. In this sense, to address that challenge and facilitate and promote the discovery of scientific knowledge, the Findable, Accessible, Interoperable, and Reusable (FAIR) principles help organizations to share research data in a secure, appropriate, and useful way for other researchers. OBJECTIVE: The objective of this study was the FAIRification of existing health research data sets and applying a federated machine learning architecture on top of the FAIRified data sets of different health research performing organizations. The entire FAIR4Health solution was validated through the assessment of a federated model for real-time prediction of 30-day readmission risk in patients with chronic obstructive pulmonary disease (COPD). METHODS: The application of the FAIR principles on health research data sets in 3 different health care settings enabled a retrospective multicenter study for the development of specific federated machine learning models for the early prediction of 30-day readmission risk in patients with COPD. This predictive model was generated upon the FAIR4Health platform. Finally, an observational prospective study with 30 days follow-up was conducted in 2 health care centers from different countries. The same inclusion and exclusion criteria were used in both retrospective and prospective studies. RESULTS: Clinical validation was demonstrated through the implementation of federated machine learning models on top of the FAIRified data sets from different health research performing organizations. The federated model for predicting the 30-day hospital readmission risk was trained using retrospective data from 4.944 patients with COPD. The assessment of the predictive model was performed using the data of 100 recruited (22 from Spain and 78 from Serbia) out of 2070 observed (records viewed) patients during the observational prospective study, which was executed from April 2021 to September 2021. Significant accuracy (0.98) and precision (0.25) of the predictive model generated upon the FAIR4Health platform were observed. Therefore, the generated prediction of 30-day readmission risk was confirmed in 87% (87/100) of cases. CONCLUSIONS: Implementing a FAIR data policy in health research performing organizations to facilitate data sharing and reuse is relevant and needed, following the discovery, access, integration, and analysis of health research data. The FAIR4Health project proposes a technological solution in the health domain to facilitate alignment with the FAIR principles.

Regional variation in multiple paternity in the brown smooth-hound shark Mustelus henlei from the northeastern Pacific.

Multiple paternity (MP) in the brown smooth-hound shark (Mustelus henlei) was assessed in 15 litters (15 mothers and 97 embryos) collected in the northern Gulf of California of which 86.7% were sired by more than one male (i.e., from 2 to 4 sires). When taken together with results from previous studies, this record indicates that there is regional variation in MP in M. henlei in the northeastern Pacific. This pattern is associated with variations in the reproductive traits of each population (e.g., female size and litter size). In the Gulf of California, the results of a generalized linear model (GLZ) indicated that the litters of larger females had a higher probability of MP compared to those of smaller females.

Papel de los estímulos ambientales asociados a la droga en el desarrollo de tolerancia cruzada a los efectos de taquicardia de la nicotina y el alcohol en humanos / Role of drug-associated environmental stimuli in the development of cross-tolerance to the tachycardic effects of nicotine and alcohol in humans

De acuerdo con el modelo de condicionamiento pavloviano, las claves ambientales asociadas a la droga modulan la tolerancia a las drogas. Este estudio evaluó la contribución de las claves asociadas a la droga en el desarrollo de tolerancia cruzada a los efectos taquicárdicos de la nicotina de tabaco y el alcohol en sujetos humanos. En este experimento participaron cuarenta estudiantes universitarios. Cada estudiante fue asignado aleatoriamente a una de dos condiciones experimentales. Veinte estudiantes fumaron cigarros con nicotina en el Contexto A y placebo en el Contexto B y veinte estudiantes fumaron cigarros con nicotina en el Contexto B y placebo en el Contexto A. La prueba de tolerancia cruzada fue llevada a cabo dividiendo a los participantes de cada condición en dos subgrupos (n = 10), cada subgrupo consumió alcohol en cada uno de los contextos (A y B). Los resultados de este experimento muestran que la tolerancia cruzada entre nicotina y alcohol se presentó únicamente cuando la prueba de tolerancia cruzada se realizó en el mismo contexto donde se desarrolló la tolerancia a la nicotina del tabaco. Estos resultados concuerdan con la hipótesis de que los estímulos ambientales asociados a la droga juegan un papel modulador en el desarrollo de la tolerancia cruzada entre la nicotina del tabaco y el alcohol.(AU)

According to the Pavlovian conditioning model, drug tolerance is modulated by drug-associated environmental cues. This study evaluated the contribution of drug-associated cues in the development of cross-tolerance to the tachycardic effects of nicotine from tobacco and alcohol in human subjects. Forty undergraduate students were recruited for this experiment, and each student was randomly assigned to one of two experimental conditions. Twenty students smoked nicotine-containing cigarettes in context A and placebo cigarettes in context B, and twenty students smoked nicotine-containing cigarettes in context B and placebo cigarettes in context A. A cross-tolerance test was carried out by dividing the subjects in each condition into two subgroups (n = 10). Each subgroup consumed alcohol in both contexts (A and B). The results of this experiment showed that cross-tolerance between nicotine and alcohol was exhibited only if the cross-tolerance test was carried out in the same context where tolerance had developed to the nicotine from tobacco. These results support the hypothesis that drug-associated environmental stimuli play a modulatory role in the development of cross-tolerance between nicotine from tobacco and alcohol.(AU)

Between uncertainty and hope: Young leaders as agents of change in sustainable small-scale fisheries.

The path to sustainable small-scale fisheries (SSF) is based on multiple learning processes that must transcend generational changes. To understand young leaders from communities with sustainable SSF management practices in Mexico, we used in-depth interviews to identify their shared motivations and perceptions for accepting their fishing heritage. These possible future decision-makers act as agents of change due to their organizational and technological abilities. However, young people are currently at a crossroads. Many inherited a passion for the sea and want to improve and diversify the fishing sector, yet young leaders do not want to accept a legacy of complicated socioenvironmental conditions that can limit their futures. These future leaders are especially concerned by the uncertainty caused by climate change. If fishing and generational change are not valued in planning processes, the continuity of fisheries, the success of conservation actions, and the lifestyles of young fishers will remain uncertain.

Integration of GWAS, metabolomics, and sensorial analyses to reveal novel metabolic pathways involved in cocoa fruity aroma GWAS of fruity aroma in Theobroma cacao.

Nacional is a variety of cocoa tree known for its "Arriba" aroma characterised mainly by fruity, floral, and spicy aromatic notes. In this study, the genetic basis of the fruity aroma of modern Nacional cocoa was investigated. GWAS studies have been conducted on biochemical and sensorial fruity traits and allowed to identify a large number of association zones. These areas are linked to both the volatile compounds known to provide fruity flavours and present in the beans before and after roasting, and to the fruity notes detected by sensorial analysis. Five main metabolic pathways were identified as involved in the fruity traits of the Nacional population: the protein degradation pathway, the sugar degradation pathway, the fatty acid degradation pathway, the monoterpene pathway, and the L-phenylalanine pathway. Candidate genes involved in the biosynthetic pathways of volatile compounds identified in association areas were detected for a large number of associations.