Enhancing Cellulose and Lignin Fractionation from Acacia Wood: Optimized Parameters Using a Deep Eutectic Solvent System and Solvent Recovery.

Cellulose and lignin, sourced from biomass, hold potential for innovative bioprocesses and biomaterials. However, traditional fractionation and purification methods often rely on harmful chemicals and high temperatures, making these processes both hazardous and costly. This study introduces a sustainable approach for fractionating acacia wood, focusing on both cellulose and lignin extraction using a deep eutectic solvent (DES) composed of choline chloride (ChCl) and levulinic acid (LA). A design of experiment was employed for the optimization of the most relevant fractionation parameters: time and temperature. In the case of the lignin, both parameters were found to be significant variables in the fractionation process (p-values of 0.0128 and 0.0319 for time and temperature, respectively), with a positive influence. Likewise, in the cellulose case, time and temperature also demonstrated a positive effect, with p-values of 0.0103 and 0.028, respectively. An optimization study was finally conducted to determine the maximum fractionation yield of lignin and cellulose. The optimized conditions were found to be 15% (w/v) of the wood sample in 1:3 ChCl:LA under a treatment temperature of 160 °C for 8 h. The developed method was validated through repeatability and intermediate precision studies, which yielded a coefficient of variation lower than 5%. The recovery and reuse of DES were successfully evaluated, revealing remarkable fractionation yields even after five cycles. This work demonstrates the feasibility of selectively extracting lignin and cellulose from woody biomass using a sustainable solvent, thus paving the way for valorization of invasive species biomass.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

INTRODUCTION: Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. METHODS: Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. RESULTS: As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60 years and prevalent (2 years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68 years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. CONCLUSIONS: In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Pulmonary arterial hypertension (PAH) is a disease that gets worse over time. To make decisions about treatment, we need to know the stage of the disease. We can do this by measuring the patient's risk of death during the next few years. Selexipag is a medication for PAH. This analysis included patients living in Europe and Canada who started treatment with selexipag for their PAH disease. Our findings suggest that the monitoring of patients' health and the timing of starting selexipag can be improved. This analysis includes 698 patients taking part in the EXPOSURE study (EUPAS19085), which looks at the real-life treatment of patients with PAH. Overall, 71% of patients were female, the median age was 60 years, most had been diagnosed with PAH for around 2 years and were already taking two other medications for their PAH disease. At the beginning of selexipag treatment, 14% of patients were classified as low risk, 31% as intermediate-low risk, 34% as intermediate-high risk and 20% as high risk of mortality within the next year. More high-risk patients were hospitalised compared with the lower risk groups. After 1 year of treatment, more patients in the low (98%) and intermediate-low groups (98%) were alive than those in the intermediate-high (93%) and high risk groups (80%). The same was true after 2 years of treatment with selexipag (98%, 92%, 81% and 67%, respectively). This study confirms that assessing patients' risk levels can indicate how well they will do over time and shows that earlier treatment with selexipag should be considered to potentially prevent worsening of the disease.

A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions.

This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.

Early Mobilization Decision after an Acute Ischemic Stroke: Protocol for an Umbrella Review.

INTRODUCTION: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes. METHODS AND ANALYSIS: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

Quantitative assessment of carotid ultrasound diameter measurements in the operating room: a comparable analysis of long-axis versus rotated and tilted orientation.

Objective. Carotid ultrasound (US) has been studied as a non-invasive alternative for hemodynamic monitoring. A long-axis (LA) view is traditionally employed but is difficult to maintain and operator experience may impact the diameter estimates, making it unsuitable for monitoring. Preliminary results show that a new, i.e. rotated and tilted (RT) view is more robust to motion and less operator-dependent. This study aimed to quantitatively assess common carotid diameter estimates obtained in a clinical setting from an RT view and compare those to corresponding estimates obtained using other views.Approach. Carotid US measurements were performed in 30 adult cardiac-surgery patients (26 males, 4 females) with short-axis (SA), LA, and RT probe orientations, the first being used as a reference for measuring the true vessel diameter. Per 30 s acquisition, the median and spread in diameter values were computed, the latter representing a measure of robustness, and were statistically compared between views.Main results. The median (IQR) over all the patients of the median diameter per 30 s acquisition was 7.15 (1.15) mm for the SA view, 7.03 (1.51) mm for the LA view, and 6.99 (1.72) mm for the RT view. The median spread in diameter values was 0.18 mm for the SA view, 0.16 mm for the LA view, and 0.18 mm for the RT view. There were no statistically significant differences between views in the median diameter values (p= 0.088) or spread (p= 0.122).Significance. The RT view results in comparable and equally robust median carotid diameter values compared to the reference. These findings open the path for future studies investigating the use of the RT view in new applications, such as in wearable ultrasound devices.

Natalizumab extended interval dosing: what about wearing-off effect?

BACKGROUND: Up to two thirds of patients with multiple sclerosis (MS) under natalizumab report a resurgence of symptoms at the end of the natalizumab cycle (wearing-off (WO) effect). At the outbreak of COVID-19, in line with the international recommendations for MS management, our centre switched all clinically stable patients on natalizumab therapy for more than one year from standard interval dosing (SID) to extended interval dosing (EID) with every six weeks infusions. This study aimed to evaluate the impact of EID in WO in MS patients under natalizumab. METHODS: An observational retrospective study in patients with MS under natalizumab on EID was conducted. A questionnaire regarding current (on EID) and past (on SID) experience of WO effect was applied. RESULTS: Seventy-six patients were included. No significant differences were found in the annual relapse rate after the switch to EID (p = 0.083). However, there was a significant increase in the proportion of patients complaining of WO from 38.2% to 56.6% (p = 0.001). Moreover, patients with WO on SID, referred a significant increase in severity (p = 0.019) and duration of WO symptoms (p = 0.029), due to an anticipation of the symptoms relative to the day of natalizumab infusion (p = 0.019), when switching to EID. Symptoms improved with treatment maintenance in 23.3% of patients; instead, a reduction in interval dosing was needed in 54.8% with symptom improvement. CONCLUSION: WO affects a significant proportion of MS patients under natalizumab. Its prevalence, severity, and duration increase on EID, therefore despite clinical effectiveness maintenance of this posology should be individualized.

Real-World Management of Patients with Pulmonary Arterial Hypertension: Insights from EXPOSURE.

INTRODUCTION: Further insights into real-world management and outcomes of patients with pulmonary arterial hypertension (PAH) are needed. This interim analysis of the ongoing, multicentre, prospective EXPOSURE (EUPAS19085) observational study describes characteristics, treatment patterns and outcomes of patients with PAH initiating a new PAH-specific therapy in Europe/Canada. METHODS AND RESULTS: All analyses were descriptive. In total, 1944 patients with follow-up information were included; the majority were female, with World Health Organization functional class II/III symptoms and with idiopathic PAH or connective tissue disease-associated PAH. Most incident patients (N = 1100; diagnosed for ≤ 6 months) initiated treatment as monotherapy (48%) or double therapy (43%). Of those initiating monotherapy, 38% (199/530) escalated to double therapy (median [Q1, Q3] time to escalation 3.4 [1.9, 6.6] months), and of those initiating double therapy, 17% (78/457) escalated to triple therapy (median [Q1, Q3] time to escalation 7.0 [3.4, 12.7] months) during the observation period (median [Q1, Q3]: 17.0 [7.5, 29.9] months). The majority of the 834 prevalent patients (diagnosed > 6 months) entered the study on initiation of combination therapy and most did not change treatment regimen during the observation period (median [Q1, Q3]: 19.6 [10.2, 32.2] months). One-year survival was 88% for incident patients and 90% for prevalent patients. CONCLUSIONS: Results from EXPOSURE suggest a shift towards combination therapy and the alignment of real-world treatment patterns with current guideline recommendations. While survival estimates are encouraging, the extent of monotherapy use at treatment initiation and follow-up highlight an opportunity for further improvements through optimisation of treatment strategies in line with current guidelines. A graphical abstract is also available with this article. TRIAL REGISTRATION NUMBER: EUPAS19085.

Pulmonary arterial hypertension (PAH) is a progressive disease. Clinical guidelines recommend that most patients start treatment with a combination of different PAH medications. While there is no cure for PAH, these medications help to control symptoms and slow disease worsening. To understand treatments currently used in clinical practice, we analysed data from EXPOSURE (EUPAS19085), an ongoing study collecting information from patients starting a new PAH medication in Europe and Canada. Most patients in the study were female, with World Health Organization functional class II/III symptoms, and idiopathic (unknown cause) PAH or PAH associated with connective tissue disorders. Among 1100 patients who were 'recently diagnosed' (diagnosed with PAH in the past 6 months), 88% were alive after 1 year. We found that 48% started treatment with one PAH medication, and 38% of those patients had a second medication prescribed within a median period of 3 months. Among the 457 'recently diagnosed' patients treated with two PAH medications when they entered the study, 17% had a third medication prescribed within a median period of 7 months. Among 834 patients with 'established PAH' (diagnosed more than 6 months ago), 90% were alive after 1 year. Most entered the study when they started a third medication and did not have further changes in treatment. Our findings show that patients with PAH are often treated with one medication in clinical practice as well as a combination of medications. While survival rates are encouraging, the extent to which one PAH medication is used suggests there is room for treatment improvement.

Human responses in adolescents with oncological disease: a scoping review protocol.

INTRODUCTION: The classification of human responses to health conditions or life processes, assuming that human responses are the way that a person responds, referring to the individual's experiences, feelings, perceptions, behaviours and physical reactions, can be an exercise that, although challenging, is central to nursing diagnoses and, consequently, to nursing practice. It is necessary to gather and organise the existing knowledge about the human responses in adolescents with cancer, starting from the moment of diagnosis, due to the specificities inherent to this stage of human development. A scoping review is an appropriate method to use in order to map the existing knowledge on human responses in adolescents with oncological diseases experienced since the diagnosis. INCLUSION CRITERIA: Will encompass all types of studies, including 'grey literature' that centres on human responses related to adolescents aged 10-19 years with oncological diseases. There will be no restrictions based on the type of cancer, disease stage or other contextual factors, whether in home or healthcare settings. METHODS AND ANALYSIS: The review will be conducted following the guidelines outlined by the Joanna Briggs Institute for scoping reviews. The search will encompass the following databases: CINAHL Complete (EBSCOhost), Cochrane Database of Systematic Reviews (EBSCOhost), MEDLINE Complete (EBSCOhost), Nursing and Allied Health Collection: Comprehensive (EBSCOhost), Cochrane Clinical Answers (EBSCOhost Answers), Latin American and Caribbean Literature on Health Sciences (LILACS) and 'grey literature' sources accessible through the Scientific Open Access Repositories of Portugal (RCAAP). A three-step search strategy will be implemented. Titles and abstracts will undergo analysis by two independent reviewers. Articles selected for a full-text review will be organised. The results will be presented in tables and narratively summarised. ETHICS AND DISSEMINATION: Ethics approval and patient consent for publication are not necessary. Findings will be disseminated through publication in scientific journals and through conference presentations. REVIEW REGISTRATION NUMBER: EXUB4. Registration was made in the Open Science Framework (OSF).

Extra-Neural Metastases of Glioblastoma: A Case Series.

Glioblastoma (GBM) is the most common brain tumor and has a median survival of less than two years. The current standard of care consists of surgery followed by concomitant radio and chemotherapy with temozolomide. Although it is an aggressive tumor, distant metastases are extremely rare. The dissemination mechanisms are not fully understood and currently there is no standard of care for its treatment. In this study, the authors present a comprehensive analysis of all the existing cases of extra-neural metastases of GBM in a tertiary care center over the last five years, along with the procedures carried out in each case.

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. Methods: We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. Results: We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Discussion and conclusion: Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Adjuvant Hyperthermic Intravesical Chemotherapy in Intermediate- and High-Risk Non-muscle Invasive Bladder Cancer.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a frequently diagnosed neoplasm, which is typically managed with transurethral resection of bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus Calmette-Guérin (BCG) is used as first-line adjuvant treatment in high- (HR) and intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also be used. Multiple limitations to the use of BCG encouraged the search for therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for NMIBC. The aim of our study was to evaluate the tolerability, compliance, and survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. MATERIAL AND METHODS: This was a single-center retrospective analysis of IR- and HR- NMIBC patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. Levels of risk stratification were defined using the European Association of Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC instillations (induction) followed by six monthly instillations (maintenance). The primary outcomes were to evaluate the tolerability and compliance with the HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and overall survival (OS). For the purpose of statistical analysis, methods of descriptive statistics, survival analysis (Kaplan-Meier estimation), and multivariate analysis (Cox regression, and binary logistic regression) were used. RESULTS: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease recurrence and adverse events (AEs) were the most common reasons to stop the protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six patients (10.5%) died, although only one death was directly attributable to bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC protocol were found to be significant predictive factors of OS but lost their significance on multivariate analysis. However, if we exclude those who experienced recurrence during the maintenance phase protocol, treatment completion had a significant positive impact on OS (HR: 42.8, 95% CI 1.75-1045.072, p= 0.021). CONCLUSIONS: Our study suggests that HIVEC is a secure and well-tolerated treatment with promising efficacy data, making this therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in those who cannot tolerate or have contraindications to BCG therapy, but also as an alternative during BCG shortages.

Eco-Friendly Methods for Extraction and Modification of Cellulose: An Overview.

Cellulose is the most abundant renewable polymer on Earth and can be obtained from several different sources, such as trees, grass, or biomass residues. However, one of the issues is that not all the fractionation processes are eco-friendly and are essentially based on cooking the lignocellulose feedstock in a harsh chemical mixture, such as NaOH + Na2S, and water, to break loose fibers. In the last few years, new sustainable fractionation processes have been developed that enable the obtaining of cellulose fibers in a more eco-friendly way. As a raw material, cellulose's use is widely known and established in many areas. Additionally, its products/derivatives are recognized to have a far better environmental impact than fossil-based materials. Examples are textiles and packaging, where forest-based fibers may contribute to renewable and biodegradable substitutes for common synthetic materials and plastics. In this review, some of the main structural characteristics and properties of cellulose, recent green extraction methods/strategies, chemical modification, and applications of cellulose derivatives are discussed.

Radiogenomics Analysis Linking Multiparametric MRI and Transcriptomics in Prostate Cancer.

Prostate cancer (PCa) is a highly prevalent cancer type with a heterogeneous prognosis. An accurate assessment of tumor aggressiveness can pave the way for tailored treatment strategies, potentially leading to better outcomes. While tumor aggressiveness is typically assessed based on invasive methods (e.g., biopsy), radiogenomics, combining diagnostic imaging with genomic information can help uncover aggressive (imaging) phenotypes, which in turn can provide non-invasive advice on individualized treatment regimens. In this study, we carried out a parallel analysis on both imaging and transcriptomics data in order to identify features associated with clinically significant PCa (defined as an ISUP grade ≥ 3), subsequently evaluating the correlation between them. Textural imaging features were extracted from multi-parametric MRI sequences (T2W, DWI, and DCE) and combined with DCE-derived parametric pharmacokinetic maps obtained using magnetic resonance dispersion imaging (MRDI). A transcriptomic analysis was performed to derive functional features on transcription factors (TFs), and pathway activity from RNA sequencing data, here referred to as transcriptomic features. For both the imaging and transcriptomic features, different machine learning models were separately trained and optimized to classify tumors in either clinically insignificant or significant PCa. These models were validated in an independent cohort and model performance was used to isolate a subset of relevant imaging and transcriptomic features to be further investigated. A final set of 31 imaging features was correlated to 33 transcriptomic features obtained on the same tumors. Five significant correlations (p < 0.05) were found, of which, three had moderate strength (|r| ≥ 0.5). The strongest significant correlations were seen between a perfusion-based imaging feature-MRDI A median-and the activities of the TFs STAT6 (-0.64) and TFAP2A (-0.50). A higher-order T2W textural feature was also significantly correlated to the activity of the TF STAT6 (-0.58). STAT6 plays an important role in controlling cell proliferation and migration. Loss of the AP2alpha protein expression, quantified by TFAP2A, has been strongly associated with aggressiveness and progression in PCa. According to our findings, a combination of texture features extracted from T2W and DCE, as well as perfusion-based pharmacokinetic features, can be considered for the prediction of clinically significant PCa, with the pharmacokinetic MRDI A feature being the most correlated with the underlying transcriptomic information. These results highlight a link between quantitative imaging features and the underlying transcriptomic landscape of prostate tumors.

On Hair Care Physicochemistry: From Structure and Degradation to Novel Biobased Conditioning Agents.

Hair is constantly exposed to various adverse external stimuli, such as mechanical or thermal factors, that may cause damage or cause it to lose its shine and smooth appearance. These undesirable effects can be minimized by using hair conditioners, which repair the hair and restore the smooth effect desired by the consumer. Some of the currently used conditioning agents present low biodegradability and high toxicity to aquatic organisms. Consumers are also becoming more aware of environmental issues and shifting their preferences toward natural-based products. Therefore, developing novel, sustainable, natural-based derivatives that can act as conditioning agents in hair care products and thus compete with the traditional systems obtained from non-renewable sources is highly appealing. This paper presents the key physicochemical aspects of the hair conditioning process, including hair structure and degradation, and reviews some of the new alternative conditioning agents obtained from natural resources.

Influence of dietary pattern on anti-tuberculosis treatment outcomes in persons with dysglycemia: a Peruvian prospective cohort study.

Introduction: Dietary patterns (DPs) are associated with overall nutritional status and may alter the clinical prognosis of tuberculosis. This interaction can be further intricated by dysglycemia (i.e., diabetes or prediabetes). Here, we identified DPs that are more common with tuberculosis-dysglycemia and depicted their association with tuberculosis treatment outcomes. Methods: A prospective cohort study of persons with tuberculosis and their contacts was conducted in Peru. A food frequency questionnaire and a multidimensional systems biology-based analytical approach were employed to identify DPs associated with these clinical groups. Potential independent associations between clinical features and DPs were analyzed. Results: Three major DPs were identified. TB-dysglycemia cases more often had a high intake of carbohydrates (DP1). Furthermore, DP1 was found to be associated with an increased risk of unfavorable TB outcomes independent of other factors, including dysglycemia. Conclusion: Our findings suggest that the evaluation of nutritional status through DPs in comorbidities such as dysglycemia is a fundamental action to predict TB treatment outcomes. The mechanisms underlying the association between high intake of carbohydrates, dysglycemia, and unfavorable tuberculosis treatment outcomes warrant further investigation.

Novel HER-2 Targeted Therapies in Breast Cancer.

Human epidermal growth factor 2 (HER-2)-positive breast cancer represents 15-20% of all breast cancer subtypes and has an aggressive biological behavior with worse prognosis. The development of HER-2-targeted therapies has changed the disease's course, having a direct impact on survival rates and quality of life. Drug development of HER-2-targeting therapies is a prolific field, with numerous new therapeutic strategies showing survival benefits and gaining regulatory approval in recent years. Furthermore, the acknowledgement of the survival impact of HER-2-directed therapies on HER-2-low breast cancer has contributed even more to advances in the field. The present review aims to summarize the newly approved therapeutic strategies for HER-2-positive breast cancer and review the new and exploratory HER-2-targeted therapies currently under development.

Syndrome of subjective doubles as a rare presentation of a first-episode psychosis.

In this paper, we report the case of a man in his 30s with a first-episode psychosis, characterised by a subtype of delusional misidentification syndrome in which the delusion of doubles is exclusively of the patient's own self. This subdivision can be termed 'syndrome of doubles of the self' or 'syndrome of subjective doubles'. Additionally, an examination of the patient's mental state showed paranoid delusions. After being evaluated in the emergency department, the patient was hospitalised, and medicated with antipsychotic drugs. One week later, he was discharged with total remission of psychotic symptoms. This is a rare and curious presentation of a psychotic episode, with very few similar cases described to date.

Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs.

Tuberculosis (TB) is a lethal disease and remains one of the top ten causes of mortality by an infectious disease worldwide. It can also result in significant morbidity related to persistent inflammation and tissue damage. Pulmonary TB treatment depends on the prolonged use of multiple drugs ranging from 6 months for drug-susceptible TB to 6-20 months in cases of multi-drug resistant disease, with limited patient tolerance resulting from side effects. Treatment success rates remain low and thus represent a barrier to TB control. Adjunct host-directed therapy (HDT) is an emerging strategy in TB treatment that aims to target the host immune response to Mycobacterium tuberculosis in addition to antimycobacterial drugs. Combined multi-drug treatment with HDT could potentially result in more effective therapies by shortening treatment duration, improving cure success rates and reducing residual tissue damage. This review explores the rationale and challenges to the development and implementation of HDTs through a succinct report of the medications that have completed or are currently being evaluated in ongoing clinical trials.