The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia. Full article

Background. Cancer is the leading cause of disease-related death among children of more than 1 year of age. However, childhood cancer risk factors and etiology are yet to be fully understood. The goal of this study is to identify geographic variation among children and adolescents diagnosed with pediatric tumors between 2001 and 2018 in the province of Quebec. Methods. We analyzed pediatric patients less than 15 years of age from the Cancer in Young People in Canada (CYP-C) surveillance system who were diagnosed between 2001 and 2018 with cancer in the province of Quebec. The age-standardized age-adjusted incidence rates (AAIR) per 100,000 person years were calculated for all childhood cancers by cancer subgroups, Quebec Health regions, and age groups. Results. Overall, 3904 pediatric patients less than 15 years old were diagnosed with cancer in the province of Quebec in 2001–2018. The overall incidence rate (IR) in the province of Quebec was 16.14 (95%CL [15.56–16.73]) per 100,000 person years. For childhood cancers, regions that presented a higher AAIR were Chaudière-Appalaches and Capitale-Nationale with 18.2 and 17.5 per 100,000 person years, respectively. The incidence rates (IRs) in Chaudière-Appalaches (95% CI 1.0439–1.3532) and in Capitale-Nationale (95% CI 1.0124–1.2942) were statistically higher than the incidence in the province of Quebec (p = 0.0090 and p = 0.0310, respectively). When comparing the AAIR of the CNS tumor subgroup in Chaudière-Appalaches and in Capitale-Nationale, with the provincial average, we noticed a statistically higher incidence in Chaudière-Appalaches and a trend for Capitale-Nationale (p < 0.0001 and p = 0.0602, respectively). Conclusion. There is evidence of spatial clusters in Chaudière-Appalaches and Capitale-Nationale as areas for all childhood cancers. Further studies should be performed to investigate potential risk factors in these regions. Full article

Background: Ischaemic heart disease, including myocardial infarction, is one of the main causes leading to heart failure as a consequence of ischaemic myocardial damage. In recent years, survival in the acute phase of myocardial infarction has improved significantly, but the high mortality rate within 12 months of hospital discharge (reaching up to 9.8% in Poland) remains a challenge. Therefore, the KOS-Zawał (MC-AMI) comprehensive 12-month post-MI care programme was introduced in Poland in 2017. Aim: This study aimed to assess body composition (including, but not limited to, the phase angle, visceral fat, total body fat, redistribution between intracellular and extracellular fluid in the body, and metabolic age) using a bioelectrical impedance analysis (BIA) in post-MI patients before and after early post-MI rehabilitation who were participating in the KOS-Zawał (MC-AMI) programme. Methods: This study involved an examination (before rehabilitation) of 94 post-myocardial infarction patients who were referred to a cardiology appointment within 7–10 days of hospital discharge, during which a clinical assessment, electrocardiogram, and biochemical blood tests (complete blood count, CRP, and serum creatinine) were performed. For various reasons (death, qualification for device implantation, non-completion of rehabilitation, failure to attend a follow-up BIA), data from 55 patients who were examined twice (before and after rehabilitation) were used for the final analysis. Measurements were taken using a high-grade Tanita MC-780 BIA body composition analyser, which measured the resistance of tissues to a low-intensity electrical impulse (not perceptible to the subject). Results: Participation in rehabilitation as part of the KOS-Zawał (MC-AMI) programme was associated with a decrease in metabolic age in patients, with a reduction in visceral fat levels and levels of adipose tissue in the lower and upper limbs. Moreover, a clinically beneficial reduction in the ratio of extracellular water to total body water was also observed. These changes were statistically significant (p < 0.005). In contrast, there were no statistically significant differences in the change in phase angle values in the subjects before and after the 5-week post-infarction rehabilitation. Conclusions: Participation in early post-myocardial infarction rehabilitation as part of the KOS-Zawał (MC-AMI) programme (25 training sessions) is associated with significant improvements in body composition parameters, such as visceral adipose tissue, limb fat, and water redistribution, and, consequently, a reduction in metabolic age, despite no significant increase in phase angle values. It was hypothesised that the good baseline condition of the subjects might explain the lack of significant change in the phase angle over the short observation period. For further analysis, it would be worthwhile to increase the number of patients with baseline reduced phase angle values and monitor changes in this parameter throughout rehabilitation and the entire MC-AMI programme, because changes in the phase angle may also be influenced by other programme components such as dietary or psychological education. It is worth considering implementing a regular BIA assessment in patients in the programme as a motivating stimulus for diligent exercise and extending rehabilitation to be followed by telerehabilitation or hybrid telerehabilitation. Full article

One of the traditional observations about English derivational morphology is that prefixes behave differently from suffixes and are rather close to lexemes. A word-based analysis of prefixes based on this observation has been proposed, but it faces a challenge raised by the seemingly category-changing property of the comparative verb-forming prefix out-. This study aims to solve this problem in a framework that enriches the traditional generative word-based morphology with the concept of the Abstract Lexical Unit. In analyzing data, I pay attention to the degree semantics of comparative out-prefixed verbs and show that the so-called “denominal or deadjectival” out-verbs are produced as hyponyms of already existing out-verbs with sparse semantics. A pseudonym experiment demonstrates that this type of out-verb has a number/rank/action comparative interpretation, and the nouns or adjectives that occupy the head position further specify the object that is counted. The problematic type is related to its base word via head replacement rather than concatenative affixation. Drawing on these new perspective and observations, this paper shows that the traditional finding about the status of English prefixes can be maintained in a word-based approach. Full article

Cocaine use is associated with negative health outcomes: cocaine use disorders, speedballing, and overdose deaths. Currently, treatments for cocaine use disorders and overdose are non-existent when compared to opioid use disorders, and current standard cocaine use disorder treatments have high dropout and recidivism rates. Physical exercise has been shown to attenuate addiction behavior as well as modulate brain activity. This study examined the differential effects of chronic cocaine use between exercised and sedentary rats. The effects of exercise on brain glucose metabolism (BGluM) following chronic cocaine exposure were assessed using Positron Emission Tomography (PET) and [18F]-Fluorodeoxyglucose (FDG). Compared to sedentary animals, exercise decreased metabolism in the SIBF primary somatosensory cortex. Activation occurred in the amygdalopiriform and piriform cortex, trigeminothalamic tract, rhinal and perirhinal cortex, and visual cortex. BGluM changes may help ameliorate various aspects of cocaine abuse and reinstatement. Further investigation is needed into the underlying neuronal circuits involved in BGluM changes and their association with addiction behaviors. Full article

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy. Full article

Introduction: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. Methods: Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. Results: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23–74 years; mean number of UTI episodes in previous year 6.1 +/− 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. Conclusion: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients’ long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system. Full article

The quality of Ti alloy casing is crucial for the safe and stable operation of aero engines. However, the fluctuation of key process parameters during the investment casting process of titanium alloy casings has a significant influence on the volume and number of porosity defects, and this influence cannot be effectively suppressed at present. Therefore, this paper proposes a strategy to control the influence of process parameters on shrinkage volume and number. This study constructed multiple regression prediction models and neural network prediction models of porosity volume and number for a ZTC4 casing by simulating the gravity investment casting process. The results show that the multiple regression prediction model and neural network prediction model of shrinkage cavity total volume have an accuracy of over 99%. The accuracy of the neural network prediction model is higher than that of the multiple regression model, and the neural network model realizes the accurate prediction of shrinkage defect volume and defect number through pouring temperature, pouring time, and mold shell temperature. The sensitivity degree of casing defects to key process parameters, from high to low, is as follows: pouring temperature, pouring time, and mold temperature. Further optimizing the key process parameter window reduces the influence of process parameter fluctuation on the volume and number of porosity defects in casing castings. This study provides a reference for actual production control process parameters to reduce shrinkage cavity and loose defects. Full article

The occurrence of Supraglacial Lakes (SGLs) may influence the signals acquired with microwave radiometers, which may result in a degree of uncertainty when employing microwave radiometer data for the detection of surface melt. Accurate monitoring of surface melting requires a reasonable assessment of this uncertainty. However, there is a scarcity of research in this field. Therefore, in this study, we computed surface melt in the vicinity of Automatic Weather Stations (AWSs) by employing Defense Meteorological Satellite Program (DMSP) Ka-band data and Soil Moisture and Ocean Salinity (SMOS) satellite L-band data and extracted SGL pixels by utilizing Sentinel-2 data. A comparison between surface melt results derived from AWS air temperature estimates and those obtained with remote sensing inversion in the two different bands was conducted for sites below the mean snowline elevation during the summers of 2016 to 2020. Compared with sites with no SGLs, the commission error (CO) of DMSP morning and evening data at sites where these water bodies were present increased by 36% and 30%, respectively, and the number of days with CO increased by 12 and 3 days, respectively. The omission error (OM) of SMOS morning and evening data increased by 33% and 32%, respectively, and the number of days with OM increased by 17 and 21 days, respectively. Identifying the source of error is a prerequisite for the improvement of surface melt algorithms, for which this study provides a basis. Full article

Background: Gaucher disease (GD) is a rare, autosomal, recessive condition characterized by hepatosplenomegaly, thrombocytopenia, anemia, and bone abnormalities, often requiring life-long treatment. Velaglucerase alfa has improved hematologic and visceral parameters in clinical trials; however, limited long-term efficacy and safety data are available. Methods: The Gaucher Outcome Survey (GOS), a structured and validated international registry for patients with confirmed GD, provides an opportunity to evaluate long-term data from patients receiving velaglucerase alfa. Results: This analysis included 376 treatment-naïve children and adults with GD enrolled in GOS, including 20 with type 3 GD, who initiated velaglucerase alfa through participation in clinical trials or as part of their clinical management and continued treatment for a mean (range) time of 6.6 (0.003–18.6) years. Initial improvements in hematologic and visceral parameters and the biomarkers glucosylsphingosine (lyso-GL1) and chitotriosidase were observed after one year of treatment and were maintained throughout the follow-up period. Of 129 (34.3%) patients who developed adverse events during the follow-up period, events were considered related to treatment in 33 (8.8%). None led to treatment discontinuation. There were 21 deaths overall, none of which were considered related to treatment. Conclusions: This analysis of data from the GOS registry supports the safety and efficacy of velaglucerase alfa in patients with GD. Full article

Previous research has been limited in examining the causal relationship between green transformational leadership (GTL) and green supply chain management (GSCM), with the intermediary influence of green human resource management (GHRM), within the pharmaceutical sector of the Kingdom of Saudi Arabia (KSA). This gap persisted despite the recognition in Saudi Vision 2030 of logistics, specifically, supply chain management (SCM), as fundamental to the national development agenda, given that contemporary competitiveness lies in the efficacy of supply chains (SCs) rather than individual companies. Moreover, the achievement of economic progress hinges significantly on how well these accomplishments align with sustainability demands and obstacles. This paper aims to investigate the extent to which GTL fosters GRHM practices to enhance the maturity of GSCM performance in the pharmaceutical industry in the KSA. In other words, the research goal is to explain the variance of GSCM due to GHRM and GTL. Drawing upon the Resource-Based View (RBV) and the Ability–Motivation–Opportunity theory (AMO), GTL can enhance many aspects of GHRM, such as employee performance measurement, training content design, recruitment criteria, and green-based rewards policies, which positively influence GSCM practices. The methodology employed is deductive and translated into a questionnaire derived from a comprehensive review of the existing literature. This questionnaire was subsequently tested through the collection of 111 responses from pharmaceutical companies operating in the KSA. The results show the critical effects of GTL and GHRM on GSCM in this sector. The research provides fresh theoretical perspectives and actionable recommendations based on the outcomes. As for originality, this research explores the contribution of transformational leadership and green human resource management in enhancing SC sustainability. The research provides directions for future research to investigate the mediating or moderating impacts of other significant factors, such as green thinking or eco-friendly behaviour, on SCM sustainability. As for practical implications, this research came up with an in-depth understanding of SC managers and professionals regarding their practices related to sustainability. Full article

In this systematic literature review, the intersection of deep learning applications within the aphasia domain is meticulously explored, acknowledging the condition’s complex nature and the nuanced challenges it presents for language comprehension and expression. By harnessing data from primary databases and employing advanced query methodologies, this study synthesizes findings from 28 relevant documents, unveiling a landscape marked by significant advancements and persistent challenges. Through a methodological lens grounded in the PRISMA framework (Version 2020) and Machine Learning-driven tools like VosViewer (Version 1.6.20) and Litmaps (Free Version), the research delineates the high variability in speech patterns, the intricacies of speech recognition, and the hurdles posed by limited and diverse datasets as core obstacles. Innovative solutions such as specialized deep learning models, data augmentation strategies, and the pivotal role of interdisciplinary collaboration in dataset annotation emerge as vital contributions to this field. The analysis culminates in identifying theoretical and practical pathways for surmounting these barriers, highlighting the potential of deep learning technologies to revolutionize aphasia assessment and treatment. This review not only consolidates current knowledge but also charts a course for future research, emphasizing the need for comprehensive datasets, model optimization, and integration into clinical workflows to enhance patient care. Ultimately, this work underscores the transformative power of deep learning in advancing aphasia diagnosis, treatment, and support, heralding a new era of innovation and interdisciplinary collaboration in addressing this challenging disorder. Full article

Background and Objectives: The aim of the study was to evaluate the health status of professional athletes after recovering from COVID-19 and the impact that SARS-CoV-2 had on their overall cardiorespiratory fitness, which was done by conducting cardiopulmonary exercise testing (CPET). Materials and Methods: A total of twenty-seven professional basketball players (Euroleague Basketball and the ABA League) participated in the study. CPET was performed before (as part of their regular preparticipation exam, during the pre-season period), as well as after SARS-CoV-2 infection (after two weeks of home isolation, during the competitive part of the season). CPET was performed on a treadmill, while cardiovascular, respiratory, and metabolic functions were evaluated by using a breath-by-breath analysis technique (Quark CPET system manufactured by Cosmed, Rome, Italy). Results: Maximal oxygen consumption and aerobic efficiency were significantly reduced after SARS-CoV-2 infection (p = 0.000). An obvious decrease in oxygen pulse was observed during CPET after recovering from COVID-19 (p = 0.001), as was deterioration of ventilatory efficiency. Internal respiration was the most negatively affected. An early transition from aerobic to anaerobic mechanisms of creating energy for work and intensive metabolic fatigue were obvious after SARS-CoV-2 infection. Conclusions: Although it was believed that SARS-CoV-2 only affects the cardiopulmonary status of the elderly population and people with associated comorbidities, it is clear from this research that professional athletes can also be at certain risk. Even though no pathological cardiovascular and respiratory changes were found in athletes after COVID-19, results showed significantly decreased cardiorespiratory fitness, with an emphasis on internal respiration. Full article

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques. Full article

The “Yangtze River Economic Belt Development Strategy” is one of China’s three major national development strategies. Enhancing the protection and quality of arable land in the Yangtze River Economic Belt (YEB) is pivotal for fostering regional growth. In this study, land use data spanning the years 1980 to 2020 in the YEB were extracted from the national land use database maintained by the Resource and Environment Data Center of the Chinese Academy of Sciences. Employing Geographic Information System (GIS) spatial analysis techniques and arable land change metrics, the study delineated the spatiotemporal characteristics of arable land alterations across the YEB for the period. Additionally, using grain output data at the prefecture level from 2011 to 2020, the paper calculated provincial grain output to analyze the impact of arable land changes over the last four decades on grain output. The findings revealed that: (1) From 1980 to 2020, the total arable land area in the YEB decreased by approximately 41,775 square kilometers, with the most significant decrease occurring in the downstream region. (2) From 1980 to 1990, the primary factor contributing to the decrease in arable land area was the expansion of water bodies, while from 1990 to 2020, the principal reason for the reduction in arable land area was the expansion of construction land. (3) From 1980 to 2020, the decrease in arable land area resulted in a net reduction of approximately 25.12 million tons in total grain output, with the largest decline observed in the downstream regions and the smallest decline in the upstream regions. (4) Consistent with the trends in arable land area reduction, the main reason for the decline in grain output from 1980 to 1990 was the expansion of water bodies encroaching upon arable land, whereas from 2000 to 2010, the primary cause of arable land reduction was the expansion of construction land areas. In conclusion, the research suggested that over the past four decades, the primary driver behind the reduction in arable land within the YEB has been the expansion of construction land areas. Particularly noteworthy was the period from 2000 to 2010, during which the impact of arable land reduction on grain output was most pronounced. This period coincided with the rapid economic development and accelerated urbanization process within the YEB. Full article

Aquaculture is a rapidly expanding agri-food industry that faces substantial economic losses due to infectious disease outbreaks, such as bacterial infections. These outbreaks cause disruptions and high mortalities at various stages of the rearing process, especially in the larval stages. Probiotic bacteria are emerging as promising and sustainable alternative or complementary strategies to vaccination and the use of antibiotics in aquaculture. In this study, potential probiotic candidates for larviculture were isolated from a rotifer-rearing tank used as the first live feed for turbot larvae. Two Lacticaseibacillus paracasei and two Lactiplantibacillus plantarum isolates were selected for further characterization due to their wide and strong antimicrobial activity against several ichthyopathogens, both Gram-positive and Gram-negative. An extensive in vitro safety assessment of these four isolates revealed the absence of harmful traits, such as acquired antimicrobial resistance and other virulence factors (i.e., hemolytic and gelatinase activities, bile salt deconjugation, and mucin degradation, as well as PCR detection of biogenic amine production). Moreover, Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR) analyses unveiled their genetic relatedness, revealing two divergent clusters within each species. To our knowledge, this work reports for the first time the isolation and characterization of Lactic Acid Bacteria (LAB) with potential use as probiotics in aquaculture from rotifer-rearing tanks, which have the potential to optimize turbot larviculture and to introduce novel microbial management approaches for a sustainable aquaculture. Full article

Three-dimensional cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to possess anticancer effects. In this work, we used B16F1 mouse melanoma cells in two-dimensional (2D) monolayer cultures and three-dimensional (3D) spheroids to test the effect of PTX and NCTD over the p62 expression. We analyzed the effect on p62 expression through Western blot and immunofluorescence assays. Our results indicate that PTX decreases p62 expression in both cell culture models, while Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease. Full article

Background: Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF) by significantly reducing the risk of stroke. Direct oral anticoagulants (DOAC) became preferred over warfarin due to their superior safety and efficacy profile. Assessing adherence to anticoagulation therapy is necessary in clinical practice for optimising patient outcomes and treatment efficacy, thus emphasising its significance. Methods: A retrospective study utilised the Latvian National Health Service reimbursement prescriptions database, covering prescriptions for AF and flutter from January 2012 to December 2022. The proportion of days covered method was selected for adherence assessment, categorising it into three groups: (1) below 80%, (2) between 80% and 90%, and (3) above 90%. Results: A total of 1,646,648 prescriptions were analysed. Dabigatran prescriptions started declining after 2020, coinciding with a decrease in warfarin prescriptions since 2018. The total adherence levels to DOAC therapy were 69.4%. Only 44.2% of users achieved an adherence level exceeding 80%. The rate of paper prescriptions decreased from 98.5% in 2017 to 1.3% in 2022. Additionally, the utilisation of international non-proprietary names reached 79.7% in 2022. Specifically, 16.7% of patients selected a single pharmacy, whereas 27.7% visited one or two pharmacies. Meanwhile, other patients obtained medicines from multiple pharmacies. Conclusions: The total adherence level to DOAC therapy is evaluated as low and there was no significant difference in age, gender, or “switcher” status among adherence groups. Physicians’ prescribing habits have changed over a decade. Full article

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs. Full article

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial–mesenchymal cell co-culture models in the air–liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism. Full article

Blisks subjected to rough machining for channel creation must undergo finishing processes, and such processes must achieve the required tolerance limits. A high-quality surface finish and predictable long tool life are critical for the finish milling of blisks. Accordingly, the aim of this study was to optimize parameters for the finish machining of an Inconel 718 alloy monolithic blisk. Ball-cone mills were used to machine the blade surface at a constant depth. A sensory tool holder was used to collect cutting force signals during machining, and a digital microscope was used to examine tool wear. The surface texture measuring instrument was used to measure blisk blade surface roughness to evaluate processing quality. This study manipulated two cutting parameters, namely cutting speed and feed per tooth, and investigated their effects. The relationship between cutting conditions and machining efficiency was analyzed. According to the experimental results, we identified a set of optimal parameters at effective cutting speeds of 46.53 m/min, feed per tooth of 0.1 mm/tooth, and depth of cut of 0.05 mm for marginal tool wear and fast cutting speeds. Then the corresponding tool life was estimated by using the derived parameters. Full article

People with HIV exhibit persistent inflammation that correlates with HIV-associated comorbidities including accelerated aging, increased risk of cardiovascular disease, and neuroinflammation. Mechanisms that perpetuate chronic inflammation in people with HIV undergoing antiretroviral treatments are poorly understood. One hypothesis is that the persistent low-level expression of HIV proviruses, including RNAs generated from defective proviral genomes, drives the immune dysfunction that is responsible for chronic HIV pathogenesis. We explore factors during HIV infection that contribute to the generation of a pool of defective proviruses as well as how HIV-1 mRNA and proteins alter immune function in people living with HIV. Full article