The Association of Genetic Markers Involved in Muscle Performance Responding to Lactate Levels during Physical Exercise Therapy by Nordic Walking in Patients with Long COVID Syndrome: A Nonrandomized Controlled Pilot Study.

Several genetic markers have shown associations with muscle performance and physical abilities, but the response to exercise therapy is still unknown. The aim of this study was to test the response of patients with long COVID through an aerobic physical therapy strategy by the Nordic walking program and how several genetic polymorphisms involved in muscle performance influence physical capabilities. Using a nonrandomized controlled pilot study, 29 patients who previously suffered from COVID-19 (long COVID = 13, COVID-19 = 16) performed a Nordic walking exercise therapy program for 12 sessions. The influence of the ACE (rs4646994), ACTN3 (rs1815739), AMPD1 (rs17602729), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms, genotyped by using single nucleotide primer extension (SNPE) in lactic acid concentration was established with a three-way ANOVA (group × genotype × sessions). For ACE polymorphism, the main effect was lactic acid (p = 0.019). In ACTN3 polymorphism, there were no main effects of lactic acid, group, or genotype. However, the posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CT and TT genotypes (all p < 0.05). For AMPD1 polymorphism, there were main effects of lactic acid, group, or genotype and lactic acid × genotype or lactic acid × group × genotype interactions (all p < 0.05). The posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CC and CT genotypes (all p < 0.05). Physical therapy strategy through Nordic walking enhanced physical capabilities during aerobic exercise in post-COVID19 patients with different genotypes in ACTN3 c.1729C>T and AMPD1 c.34C>T polymorphisms. These findings suggest that individuals who reported long COVID who presumably exercised less beforehand appeared to be less able to exercise, based on lactate levels, and the effect of aerobic physical exercise enhanced physical capabilities conditioned by several genetic markers in long COVID patients.

Impact of radiological follow-up frequency on resected lung cancer: a propensity score matching analysis.

Background: Despite advances in lung cancer treatment and the subsequent improvement in oncological outcomes, the optimal frequency of radiological follow-up remains unclear. Current recommendations lack consensus and do not consider individual patient characteristics and tumor factors. This study aimed to examine the impact of radiological follow-up frequency on oncological outcomes following lung cancer resection. Methods: A prospective multicenter study, involving patients who underwent anatomical lung resection in the GEVATS database between December 2016 and March 2018. The relationship between surveillance frequency and oncological outcomes was evaluated. Two groups were established based on follow-up frequency: low frequency (LF) and high frequency (HF). Subgroup analyses were performed based on tumor stage, histology, lymphadenectomy, and adjuvant therapy. Propensity score matching (PSM) was applied to balance the groups. Results: A total of 1,916 patients were included in the study, LF 444 (23.17%), HF 1,472 (76.83%). Factors associated with HF surveillance included higher stage, adjuvant chemotherapy and adjuvant radiotherapy. Subanalyses were performed after PSM for various factors, revealing significant differences between LF and HF groups in cancer-specific survival among who received adjuvant therapy {LF 53.021 months [95% confidence interval (CI): 48.622-57.421] vs. HF 58.836 months (95% CI: 55.343-62.330); HR 0.453, 95% CI: 0.242-0.849; P=0.013}, as well as overall survival for patients with squamous cell carcinoma [LF 54.394 months (95% CI: 51.424-57.364) vs. HF 61.578 months (95% CI: 59.091-64.065); HR 0.491, 95% CI: 0.299-0.806; P=0.005] and those who received adjuvant therapy LF 50.176 months [95% CI: 45.609-54.742) vs. HF 57.189 months (95% CI: 53.599-60.778); HR 0.503, 95% CI: 0.293-0.865; P=0.013]. Conclusions: Findings suggest that high-frequency surveillance only improves survival outcomes in lung cancer patients who received adjuvant treatment or had squamous cell carcinoma. Therefore, future guidelines for lung cancer follow-up should consider individualizing the frequency of radiological surveillance based on patients' risk profiles.

Assessing the Ecological Quality Status in tropical Indian estuaries: testing the applicability of benthic foraminiferal indices.

The ecological quality status (EcoQS) of Vellar and Uppanar estuaries (Southeast coast of India) has been monitored monthly, using a combination of foraminiferal (Foram Stress Index: FSI and exp(H'bc) indices and abiotic (Pollution Load Index: PLI, Dissolved Oxygen: DO, and Total Organic Carbon: TOC) parameters. The Uppanar Estuary shows relatively higher values of PLI and TOC and lower DO values than Vellar Estuary. The highest value of TOC and PLI are recorded during the monsoon season. These variations are well mirrored by the change in exp(H'bc) and FSI. The lowest values of exp(H'bc) are observed with the monsoon season and could be ascribed by an overall reduction of salinity, and to the highest level of TOC and PLI in response to enhanced river discharge. The FSI also exhibits great variability with significant higher values in the Vellar Estuary than in the Uppanar Estuary. The EcoQS evaluated by a combination of pollution- (i.e., PLI, TOC and DO) and foraminiferal-based [i.e., FSI and exp(H'bc)] indices are highly consistent (73.4%). The most frequent disagreement among indices is mostly associated to Uppanar Estuary and, particularly, in the inner stations. This difference might be related to a time-lag response of benthic foraminifera in terms of diversity and assemblages' compositions as well as of the pollution indicators in response to enhanced riverine input. This study further supports the application of foraminiferal-based indices in EcoQS assessment in transitional environments including tropical Indian estuaries. It also fills the gap of knowledge by providing a seasonal perspective on the variation of EcoQS based on a monthly-scale sampling.

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.

Implementation of the Versius robotic surgical system for thoracic surgery: first clinical evaluation of feasibility and performance.

OBJECTIVES: The aim of this study is to demonstrate the ability of the Versius surgical system to successfully and safely complete a range of thoracic procedures aligned with Stage 2a (Development) of the Idea, Development, Exploration, Assessment and Long-term follow-up framework for surgical innovation. METHODS: This prospective study included the first 30 consecutive patients who underwent robotic surgery with Versius by 2 surgeons without prior robotic experience between 1 April 2023 and 30 December 2023 [25 lung resections (wedge, segmentectomy and lobectomy) and 5 thymectomies]. There were no specific predetermined selection criteria for each case. The primary outcome was safe completion of the procedure without unplanned conversion. Secondary outcomes included intraoperative and postoperative complications, intraoperative device-related outcomes and pathology results. RESULTS: Twenty-eight (93.3%) cases were completed without conversion. Both conversions were to thoracoscopy, one due to a 'console alarm' and the other due to pulmonary artery bleeding. In lung resections, median console time was 103 (90-129) min. Five (20%) patients experienced postoperative complications, most frequent was persistent air leak (16%). Median length-of-stay was 3 (2-4) days. Neither readmissions nor mortality was observed. In thymectomies, no intraoperative or postoperative complications, readmissions, reinterventions or mortality were observed. Median console time was 77 (75-89) min and median length of stay was 1 (1-1) day. CONCLUSIONS: This phase 2a IDEAL-D study confirms lung resections and thymectomies are feasible with the use of Versius system, laying the foundation for larger phase 2b and 3 clinical studies within the IDEAL-D framework.

Reversibility of Neuropsychiatric Adverse Events after Switching to Darunavir/Cobicistat or Doravirine in Men on INSTI-Based Regimen.

Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks.

Quality of Life of Colorectal Cancer Survivors: Mapping the Key Indicators by Expert Consensus and Measures for Their Assessment.

Quality of life (QoL) assessments are integral to cancer care, yet their effectiveness in providing essential information for supporting survivors varies. This study aimed to elucidate key indicators of QoL among colorectal cancer survivors from the perspective of healthcare professionals, and to evaluate existing QoL questionnaires in relation to these indicators. Two studies were conducted: a Delphi study to identify key QoL indicators and a scoping review of questionnaires suitable for colorectal cancer survivors. Fifty-four healthcare professionals participated in the Delphi study's first round, with 25 in the second. The study identified two primary QoL domains (physical and psychological) and 17 subdomains deemed most critical. Additionally, a review of 12 questionnaires revealed two instruments assessing the most important general domains. The findings underscored a misalignment between existing assessment tools and healthcare professionals' clinical priorities in working with colorectal cancer survivors. To enhance support for survivors' QoL, efforts are needed to develop instruments that better align with the demands of routine QoL assessment in clinical practice.

Development of Flame-Retardant Polylactic Acid Formulations for Additive Manufacturing.

Polymeric materials, renowned for their lightweight attributes and design adaptability, play a pivotal role in augmenting fuel efficiency and cost-effectiveness in railway vehicle development. The tailored formulation of compounds, specifically designed for additive manufacturing, holds significant promise in expanding the use of these materials. This study centers on poly(lactic acid) (PLA), a natural-based biodegradable polymeric material incorporating diverse halogen-free flame retardants (FRs). Our investigation scrutinizes the printability and fire performance of these formulations, aligning with the European railway standard EN 45545-2. The findings underscore that FR in the condensed phase, including ammonium polyphosphate (APP), expandable graphite (EG), and intumescent systems, exhibit superior fire performance. Notably, FR-inducing hydrolytic degradation, such as aluminum hydroxide (ATH) or EG, reduces polymer molecular weight, significantly impacting PLA's mechanical performance. Achieving a delicate balance between fire resistance and mechanical properties, formulations with APP as the flame retardant emerge as optimal. This research contributes to understanding the fire performance and printability of 3D-printed PLA compounds, offering vital insights for the rail industry's adoption of polymeric materials.

LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model.

Postnatal development of the gastrointestinal tract involves the establishment of the commensal microbiota, the acquisition of immune tolerance via a balanced immune cell composition, and maturation of the intestinal epithelium. While studies have uncovered an interplay between the first two, less is known about the role of the maturing epithelium. Here we show that intestinal-epithelial intrinsic expression of lysine-specific demethylase 1A (LSD1) is necessary for the postnatal maturation of intestinal epithelium and maintenance of this developed state during adulthood. Using microbiota-depleted mice, we find plasma cells, innate lymphoid cells (ILCs), and a specific myeloid population to depend on LSD1-controlled epithelial maturation. We propose that LSD1 controls the expression of epithelial-derived chemokines, such as Cxcl16, and that this is a mode of action for this epithelial-immune cell interplay in local ILC2s but not ILC3s. Together, our findings suggest that the maturing epithelium plays a dominant role in regulating the local immune cell composition, thereby contributing to gut homeostasis.

Variability of the trophic state in a coastal reef system associated with submarine groundwater discharge in the Mexican Caribbean.

Submarine groundwater discharges (SGD) have been associated with important sources of nutrients between the land and oceans that can generate eutrophication conditions. This study aims to analyze the behavior of nitrogen and phosphorus using the mixing curve method, to examine the variation of the trophic state using the Karydis Index, and to evaluate the δ15N in benthic organisms to trace the origin of nitrogen in neap tide (November) and spring tide (January) in the Manatí Cenote, and Nohoch-Teek reef lagoon in the Mexican Caribbean. Nitrogen and phosphate enrichment was in the Manatí Cenote during neap and spring tides. This enrichment was particularly noticeable in the reef lagoon during low tides in the areas influenced by SGD. In the Cenote, differences in the nitrate trophic state were observed, indicating an eu-mesotrophic condition during neap tide and a mesotrophic condition during spring tide. However, no significant differences were observed for ammonium (oligo-mesotrophic), nitrites, or phosphate compounds (oligotrophic). The trophic state reef lagoon exhibited a similar pattern but with different spatial variations. In both systems, phosphorus was a limiting nutrient, while δ15N suggested anthropogenic nitrogen uptake by several benthic organisms.

Effects of Aerobic Exercise Therapy through Nordic Walking Program in Lactate Concentrations, Fatigue and Quality-of-Life in Patients with Long-COVID Syndrome: A Non-Randomized Parallel Controlled Trial.

BACKGROUND: Long-COVID syndrome comprises a variety of signs and symptoms that develop during or after infection with COVID-19 which may affect the physical capabilities. However, there is a lack of studies investigating the effects of Long-COVID syndrome in sport capabilities after suffering from COVID-19 infection. The purpose of the study was to evaluate and compare lactate concentration and quality of life (QoL) in patients with Long-COVID with those who have not developed non-Long-COVID during Nordic walking exercise therapy. METHODS: Twenty-nine patients (25.5 ± 7.1 years) took part in a non-randomized controlled trial, divided into two groups: a Long-COVID group (n = 16) and a non-Long-COVID control (n = 13). Patients were confirmed as having Long-COVID syndrome if they experienced fatigue or tiredness when performing daily activities and worsening of symptoms after vigorous physical or mental activity. All participants underwent a 12-week Nordic Walking program. Lactate concentration after exercise and distance covered during all sessions were measured. Pre- and Long-Nordic Walking program, the Modified Fatigue Impact Scale (MFIS), the Short Form 36 Health Survey (SF-36), and EURO QoL-5D (EQ-ED) were administered to assess fatigue and quality of life, respectively. RESULTS: There was a lactate concentration effect between groups (F = 5.604; p = 0.024). However, there was no significant effect as a result of the session (F = 3.521; p = 0.121) with no interaction of group × session (F = 1.345; p = 0.414). The group main effect (F = 23.088; p < 0.001), time effect (F = 6.625; p = 0.026), and group × time (F = 4.632; p = 0.002) interaction on the SF-36 scale were noted. Also, there were a significant group main effect (F = 38.372; p < 0.001), time effect (F = 12.424; p = 0.005), and group × time interaction (F = 4.340; p = 0.014) on EQ-5D. However, there was only a significant group main effect (F = 26.235; p < 0.001) with no effect on time (F = 2.265; p = 0.160) and group × time (F = 1.584; p = 0.234) interaction on the MFIS scale. CONCLUSIONS: The Long-COVID group showed higher lactate concentration compared with the control group during the 12 weeks of the Nordic Walking program. The Long-COVID group presented a decrease in fatigue with respect to the control group according to the MFIS scale, as well as improvement in quality of life after aerobic exercise therapy.

Digital Microscopy Augmented by Artificial Intelligence to Interpret Bone Marrow Samples for Hematological Diseases.

Analysis of bone marrow aspirates (BMAs) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on a visual examination of samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital microscopy system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store, and analyze BMA samples remotely but is also supported by an Artificial Intelligence (AI) pipeline that accelerates the differential cell counting process and reduces interobserver variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.

Sequential-contingent strategy for fallopian tube evaluation using hysterosalpingo foam sonography: a cost analysis.

Background: Tubal pathology is the etiological factor in 20% of couples with female infertility. Historically, diagnostic evaluation of the fallopian tubes has been performed by means of hysterosalpingography (HSG). Hysterosonosalpingography with EXEM® foam is a recent technique with supposedly comparable effectiveness to HSG, but with better tolerability for patients. Methods: Tubal patency was assessed in patients who were candidates for intrauterine insemination (IUI) between January 2020 and July 2021. (I) Hysterosonosalpingography with EXEM® foam. (II) If the patient had both tubes patent, IUI was proposed. In case of inconclusive or pathological results, HSG was performed. (III) If the HSG concludes tubal patency, IUI is proposed. On the other hand, if it results in tubal obstruction, in vitro fertilization (IVF) is proposed. Results: Assessment of tubal patency by HSG showed concordance with previous Hysterosonosalpingography with EXEM® foam results in 45.5% (n=15) of cases of unilateral obstruction and 66.7% (n=6) of cases of bilateral obstruction. When we compare the total cost of HSG (€54,899.46) with the sum of patients who only required Hysterosonosalpingography with EXEM® foam together with those who underwent both tests (€45,575.96), it shows that the latter represents a cost benefit strategy (cost difference €9,323.50). Conclusions: Our results suggest a benefit of €9,323.50 when performing the contingent sequential strategy, in case of pathological or inconclusive results, compared to performing a systematic HSG in all patients. Patients with an obstructive hysterosalpingogram with EXEM® and a patent hysterosalpingogram will be the subgroup that will benefit the most, as IUI can be proposed instead of IVF. In addition, there is a benefit in terms of optimizing the medical procedure, hospital visits and speeding up the time to start assisted reproductive technology (ART).

The prognostic impact of non-driver gene mutations and variant allele frequency in primary myelofibrosis.

Prognostic impact of non-MPN driver gene mutations in primary myelofibrosis. MIPSS70: Mutation-Enhanced International Prognostic Score System.

Azoic sediments and benthic foraminifera: Environmental quality in a subtropical coastal lagoon in the gulf of California.

Marine transitional environments play an important role in human sustainability. Around these ecosystems, coastal lagoons are subject to high anthropogenic pressure from population growth. The increased demand for goods and services is associated with the elevated discharge of untreated and treated wastewater into lagoon systems. The absence of benthic organisms in lagoon environments has been linked to extreme natural conditions and severe anthropogenic impact at both spatial and temporal scales. However, the mechanisms that lead to the presence of azoic sediments in lagoon environments have yet to be studied. This study aimed to determine the vertical variability of textural groups, geochemistry, and benthic foraminiferal fauna to understand how natural and anthropogenic components generate a vertical sediment sequence with low or absent benthic foraminifera in a subtropical coastal lagoon in the southwestern end of the Gulf of California. A 41 cm-long sediment core was collected from La Paz Lagoon at a 1-m depth. The core was sectioned every centimeter, and sediment subsamples were dried and homogenized for grain size, calcium carbonate, elemental and isotopic carbon and nitrogen analyses, and benthic foraminifera quantification. Muds with fine sands towards the core's base characterized the sedimentary sequence. Organic carbon and total nitrogen increased from the base (1.4% and 0.06%, respectively) to the core-top (CT, 3.0% and 0.14%, respectively), significant from the 27 cm interval. Calcium carbonate content was very low (<0.8%). The relationship of δ13C vs. C:N ratio indicated that sedimentary organic carbon was derived from the marine and sewage source mixture. The δ15N of organic matter increased by 3.7‰, starting from the 27 cm interval towards the CT. The nitrogen sewage input source was relatively more significant than nitrogen fixation. The few individuals (<18 ind. in 10 g) and genera (Ammonia and Elphidium), as well as the absence of foraminifera in 19 of 41 intervals in the core, indicated that environmental conditions were unfavorable, even for colonization of environmentally stress-tolerant genera. The frequency of azoic sediments was higher from the 25 cm interval to the CT vs. from the base to the 25 cm interval. Moreover, the AEI revealed severe to moderate hypoxia in the study area. The limited presence of benthic foraminifera and calcium carbonate preservation corroborated that the quality of the lagoon's environment has deteriorated along with population growth, which requires strategic programs to sustain this transitional ecosystem.

Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome.

Long COVID-19 syndrome is present in 5-10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infectionA total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility. The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521-8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785-6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19.

Phylogenetic classification of natural product biosynthetic gene clusters based on regulatory mechanisms.

The natural products (NPs) biosynthetic gene clusters (BGCs) represent the adapting biochemical toolkit for microorganisms to thrive different microenvironments. Despite their high diversity, particularly at the genomic level, detecting them in a shake-flask is challenging and remains the primary obstacle limiting our access to valuable chemicals. Studying the molecular mechanisms that regulate BGC expression is crucial to design of artificial conditions that derive on their expression. Here, we propose a phylogenetic analysis of regulatory elements linked to biosynthesis gene clusters, to classify BGCs to regulatory mechanisms based on protein domain information. We utilized Hidden Markov Models from the Pfam database to retrieve regulatory elements, such as histidine kinases and transcription factors, from BGCs in the MIBiG database, focusing on actinobacterial strains from three distinct environments: oligotrophic basins, rainforests, and marine environments. Despite the environmental variations, our isolated microorganisms share similar regulatory mechanisms, suggesting the potential to activate new BGCs using activators known to affect previously characterized BGCs.