Attention Analysis in Robotic-Assistive Therapy for Children With Autism.

Children with Autism Spectrum Disorder (ASD) show severe attention deficits, hindering their capacity to acquire new skills. The automatic assessment of their attention response would provide the therapists with an important biomarker to better quantify their behaviour and monitor their progress during therapy. This work aims to develop a quantitative model, to evaluate the attention response of children with ASD, during robotic-assistive therapeutic sessions. Previous attempts to quantify the attention response of autistic subjects during human-robot interaction tasks were limited to restrained child movements. Instead, we developed an accurate quantitative system to assess the attention of ASD children in unconstrained scenarios. Our approach combines gaze extraction (Gaze360 model) with the definition of angular Areas-of-Interest, to characterise periods of attention towards elements of interest in the therapy environment during the session. The methodology was tested with 12 ASD children, achieving a mean test accuracy of 79.5 %. Finally, the proposed attention index was consistent with the therapists' evaluation of patients, allowing a meaningful interpretation of the automatic evaluation. This encourages the future clinical use of the proposed system.

Exercise in cancer patients: assistance levels and referral pathways-a position statement from the Spanish Society of Medical Oncology.

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients.

Scorpion envenomation in Brazil and its relationship with the social determinants of health: A population-based ecological study.

This study comprehensively analyzed cases of scorpion envenomation in Brazil, exploring the temporal trends and geographic patterns of such incidents between January 1, 2012, and December 31, 2022. Simultaneously, we assessed the correlation between scorpion envenomation and social determinants of health and social vulnerability. We conducted a population-based ecological study, gathering information on the number of scorpion envenomation cases in Brazil, as well as socioeconomic data and social vulnerability indicators across the 5,570 Brazilian municipalities. The season-trend model, based on the classical additive decomposition method, informed estimations of scorpion envenomation variations over time. The spatial correlation of scorpion envenomation with socioeconomic and vulnerability indicators was assessed using the Bivariate Moran's I. A total of 1,343,224 cases of scorpion envenomation were recorded in Brazil from Jan 2012 to Dec 2022. A single increasing time trend was observed for the entire country for this period (APC 8.94, P < 0.001). The seasonal analysis was significant for Brazil as a whole and all regions (p < 0.001), with peaks evident between October and November. The spatial distribution of cases was heterogeneous, with spatial clusters concentrated in the high-risk Southeast and Northeast regions. There was a high incidence of scorpion envenomation in municipalities facing social vulnerability, and, paradoxically, in those with better sanitation and waste collection. Our study revealed a heterogeneous geographical distribution of scorpion accidents in Brazil. Municipalities with higher social vulnerability exhibited a high incidence of scorpion envenomation.

Respiratory activity during seizures induced by pentylenetetrazole.

This study investigated the respiratory activity in adult Wistar rats across different behavioral seizure severity induced by pentylenetetrazole (PTZ). Animals underwent surgery for electrodes implantation, allowing simultaneous EEG and diaphragm EMG (DIAEMG) recordings and the respiratory frequency and DIAEMG amplitude were measured. Seizures were acutely induced through PTZ injection and classified based on a pre-established score, with absence-like seizures (spike wave discharge (SWD) events on EEG) representing the lowest score. The respiratory activity was grouped into the different seizure severities. During absence-like and myoclonic jerk seizures, the breathing frequency decreased significantly (∼50% decrease) compared to pre- and post-ictal periods. Pronounced changes occurred with more severe seizures (clonic and tonic) with periods of apnea, especially during tonic seizures. Apnea duration was significantly higher in tonic compared to clonic seizures. Notably, during PTZ-induced tonic seizures the apnea events were marked by tonic DIAEMG contraction (tonic-phase apnea). In the majority of animals (5 out of 7) this was a fatal event in which the seizure-induced respiratory arrest preceded the asystole. In conclusion, we provide an assessment of the respiratory activity in the PTZ-induced acute seizures and showed that breathing dysfunction is more pronounced in seizures with higher severity.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study.

This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

siRNA lipid nanoparticles for CXCL12 silencing modulate brain immune response during Zika infection.

CXCL12 is a key chemokine implicated in neuroinflammation, particularly during Zika virus (ZIKV) infection. Specifically, CXCL12 is upregulated in circulating cells of ZIKV infected patients. Here, we developed a lipid nanoparticle (LNP) to deliver siRNA in vivo to assess the impact of CXCL12 silencing in the context of ZIKV infection. The biodistribution of the LNP was assessed in vivo after intravenous injection using fluorescently tagged siRNA. Next, we investigated the ability of the developed LNP to silence CXCL12 in vivo and assessed the resulting effects in a murine model of ZIKV infection. The LNP encapsulating siRNA significantly inhibited CXCL12 levels in the spleen and induced microglial activation in the brain during ZIKV infection. This activation was evidenced by the enhanced expression of iNOS, TNF-α, and CD206 within microglial cells. Moreover, T cell subsets exhibited reduced secretion of IFN-É£ and IL-17 following LNP treatment. Despite no observable alteration in viral load, CXCL12 silencing led to a significant reduction in type-I interferon production compared to both ZIKV-infected and uninfected groups. Furthermore, we found grip strength deficits in the group treated with siRNA-LNP compared to the other groups. Our data suggest a correlation between the upregulated pro-inflammatory cytokines and the observed decrease in strength. Collectively, our results provide evidence that CXCL12 silencing exerts a regulatory influence on the immune response in the brain during ZIKV infection. In addition, the modulation of T-cell activation following CXCL12 silencing provides valuable insights into potential protective mechanisms against ZIKV, offering novel perspectives for combating this infection.

Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide.

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

Differential effects of intrinsic properties of natural scenes and interference mechanisms on recognition processes in long-term visual memory.

Humans display remarkable long-term visual memory (LTVM) processes. Even though images may be intrinsically memorable, the fidelity of their visual representations, and consequently the likelihood of successfully retrieving them, hinges on their similarity when concurrently held in LTVM. In this debate, it is still unclear whether intrinsic features of images (perceptual and semantic) may be mediated by mechanisms of interference generated at encoding, or during retrieval, and how these factors impinge on recognition processes. In the current study, participants (32) studied a stream of 120 natural scenes from 8 semantic categories, which varied in frequencies (4, 8, 16 or 32 exemplars per category) to generate different levels of category interference, in preparation for a recognition test. Then they were asked to indicate which of two images, presented side by side (i.e. two-alternative forced-choice), they remembered. The two images belonged to the same semantic category but varied in their perceptual similarity (similar or dissimilar). Participants also expressed their confidence (sure/not sure) about their recognition response, enabling us to tap into their metacognitive efficacy (meta-d'). Additionally, we extracted the activation of perceptual and semantic features in images (i.e. their informational richness) through deep neural network modelling and examined their impact on recognition processes. Corroborating previous literature, we found that category interference and perceptual similarity negatively impact recognition processes, as well as response times and metacognitive efficacy. Moreover, images semantically rich were less likely remembered, an effect that trumped a positive memorability boost coming from perceptual information. Critically, we did not observe any significant interaction between intrinsic features of images and interference generated either at encoding or during retrieval. All in all, our study calls for a more integrative understanding of the representational dynamics during encoding and recognition enabling us to form, maintain and access visual information.

Iron and aluminum ore mining pollution induce oxidative and tissue damage on fruit-eating bats from the Atlantic Forest.

Mining, a vital industry for economic growth, poses significant environmental pollution challenges. Failures in tailings dam containment have caused environmental contamination and raised concerns about preserving the globally significant biodiversity in the Atlantic Forest, which is under severe threat. Fruit-eating bats are key for forest regeneration as essential seed dispersers and pollinators. This study focuses on two keystone species, Artibeus lituratus and Sturnira lilium, exploring the effects of iron ore mining area (FEOA) and aluminum ore mining area (ALOA) on these bats, respectively, and comparing to individuals from a preserved Atlantic Forest fragment (FFA). Bats from FEOA showed higher Aluminum (Al), Calcium (Ca), Iron (Fe) and Barium (Ba) liver accumulation, as well as Ca and Fe muscle accumulation. These animals also showed higher liver and kidney oxidative damage associated with liver fibrosis and kidney inflammation. Brain and muscle also showed oxidative stress. Bats from ALOA showed higher Ca and Ba liver accumulation and Ca, Zinc (Zn), and Ba muscle accumulation, along with higher brain oxidative stress, liver fibrosis, and kidney inflammation. Our findings indicate that iron and aluminum ore mining activities cause adverse effects on bat tissues, posing a potential threat to biodiversity maintenance in the Atlantic Forest.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study / Fatores associados ao atraso no diagnóstico da hanseníase em área endêmica no Nordeste do Brasil: um estudo transversal / Factores asociados con el diagnóstico tardío de la lepra en un área endémica del Nordeste de Brasil: un estudio transversal

Abstract: This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

Resumo: Neste estudo objetivou-se investigar os fatores relacionados ao indivíduo e ao sistema de saúde que contribuem para o atraso no diagnóstico da hanseníase em uma área endêmica no Nordeste do Brasil. Trata-se de um estudo transversal que incluiu 120 pacientes com hanseníase. Foram obtidos dados demográficos, clínicos e informações sobre fatores relacionados ao indivíduo e ao sistema de saúde que contribuem para o atraso no diagnóstico da hanseníase. O atraso do diagnóstico em meses foi estimado para cada participante por meio de entrevistas. Foi realizada uma análise multivariada por regressão de Poisson entre o resultado e as variáveis independentes. A mediana de atraso no diagnóstico da hanseníase foi de 10,5 (4,0-24,0) meses. Aproximadamente 12,6% dos participantes apresentavam grau de incapacidade física 2 (GIF 2) no momento do diagnóstico. Na análise multivariada por regressão de Poisson, homens, idosos, baixa escolaridade, residir em área urbana, hanseníase multibacilar, hanseníase tuberculóide, não procurar atendimento imediatamente após perceber os primeiros sintomas, suspeita de hanseníase, encaminhamentos excessivos e três ou mais consultas necessárias para confirmação diagnóstica associaram-se ao maior atraso diagnóstico. Este estudo encontrou um atraso significativo no diagnóstico da hanseníase em Arapiraca, Nordeste do Brasil, o que pode explicar a taxa continuamente alta de GIF 2 entre os casos novos. Fatores relacionados ao indivíduo e ao sistema de saúde foram associados ao maior atraso no diagnóstico. Intervenções para aumentar a conscientização sobre a doença entre a população geral e fortalecer a atenção primária à saúde são urgentemente necessárias.

Resumen: El objetivo de este estudio fue investigar los factores relacionados con el individuo y el sistema de salud que contribuyen al diagnóstico tardío de la lepra en un área endémica del Nordeste de Brasil. Se trata de un estudio transversal que incluyó a 120 pacientes con lepra. Se obtuvieron datos demográficos, clínicos e informaciones sobre los factores relacionados con el individuo y el sistema de salud que contribuyen al diagnóstico tardío de la lepra. Se estimó el retraso del diagnóstico en meses para cada participante a través de entrevistas. Se realizó un análisis multivariante por regresión de Poisson entre el resultado y las variables independientes. La mediana de retraso en el diagnóstico de lepra fue de 10,5 (4,0-24,0) meses. Aproximadamente el 12,6% de los participantes tenían grado de discapacidad física 2 (GIF 2) en el momento del diagnóstico. En el análisis multivariante por regresión de Poisson se encontró que los hombres, ancianos, la baja escolaridad, vivir en área urbana, la lepra multibacilar, la lepra tuberculoide, no buscar atención médica inmediatamente tras notar los primeros síntomas, la sospecha de lepra, las derivaciones excesivas y la necesidad de tres o más consultas para confirmar el diagnóstico se asociaron con un mayor retraso del diagnóstico. Este estudio encontró un retraso significativo en el diagnóstico de la lepra en Arapiraca, Nordeste de Brasil, lo que puede explicar la tasa continuamente alta de GIF 2 entre los nuevos casos. Factores relacionados con el individuo y el sistema de salud se asociaron con el mayor retraso del diagnóstico. Intervenciones para aumentar la concienciación sobre la enfermedad entre la población general y fortalecer la atención primaria de salud son urgentemente necesarias.

Sensor Integration in a Forestry Machine.

This paper presents the integration of multimodal sensor systems for an autonomous forestry machine. The utilized technology is housed in a single enclosure which consolidates a set of components responsible for executing machine control actions and comprehending its behavior in various scenarios. This sensor box, named Sentry, will subsequently be connected to a forestry machine from MDB, model LV600 PRO. The article outlines previous work in this field and then details the integration and operation of the equipment, integrated into the forest machine, providing descriptions of the adopted architecture at both the hardware and software levels. The gathered data enables the assessment of the forestry machine's orientation and position based on the information collected by the sensors. Finally, practical experiments are presented to demonstrate the system's behavior and to analyze the methods to be employed for autonomous navigation, thereby assessing the performance of the established architecture. The novel aspects of this work include the physical and digital integration of a multimodal sensor system on a forestry machine, its use in a real case scenario, namely, forest vegetation removal, and the strategies adopted to improve the machine localization and navigation performance on unstructured environments.

Buffered 2% articaine in buccal infiltration of mandibular molars: a randomized triple-blind clinical trial.

This crossover study aimed to compare the anesthetic effects of buffered 2% articaine with 1:200,000 epinephrine with that of non-buffered 4% articaine with 1:200,000 epinephrine. Forty-seven volunteers were administered two doses of anesthesia in the buccal region of the second mandibular molars in two sessions using 1.8 mL of different local anesthetic solutions. The onset time and duration of pulp anesthesia, soft tissue pressure pain threshold, and the score of pain on puncture and burning during injection were evaluated. The operator, volunteers, and statistician were blinded. There were no significant differences in the parameters: onset of soft tissue anesthesia (p = 0.80), duration of soft tissue anesthesia (p = 0.10), onset of pulpal anesthesia in the second (p = 0.28) and first molars (p = 0.45), duration of pulp anesthesia of the second (p = 0.60) and first molars (p = 0.30), pain during puncture (p = 0.82) and injection (p = 0.80). No significant adverse events were observed. Buffered 2% articaine with 1:200,000 epinephrine did not differ from non-buffered 4% articaine with 1:200,000 epinephrine considering anesthetic success, safety, onset, duration of anesthesia, and pain on injection.

Effects of the probiotic Bacillus cereus GM on experimental schistosomiasis mansoni.

Probiotics contribute to the integrity of the intestinal mucosa and preventing dysbiosis caused by opportunistic pathogens, such as intestinal helminths. Bacillus cereus GM obtained from Biovicerin® was cultured to obtain spores for in vivo evaluation on experimental schistosomiasis. The assay was performed for 90 days, where all animals were infected with 50 cercariae of Schistosoma mansoni on the 15th day. Three experimental groups were formed, as follows: G1-saline solution from the 1st until the 90th day; G2-B. cereus GM (105 spores in 300 µL of sterile saline) from the 1st until the 90th day; and G3-B. cereus GM 35th day (onset of oviposition) until the 90th day. G2 showed a significant reduction of 43.4% of total worms, 48.8% of female worms and 42.5% of eggs in the liver tissue. In G3, the reduction was 25.2%, 29.1%, and 44% of the total number of worms, female worms, and eggs in the liver tissue, respectively. G2 and G3 showed a 25% (p < 0.001) and 22% (p < 0.001) reduction in AST levels, respectively, but ALT levels did not change. ALP levels were reduced by 23% (p < 0.001) in the G2 group, but not in the G3. The average volume of granulomas reduced (p < 0.0001) 65.2% and 46.3% in the liver tissue and 83.0% and 53.2% in the intestine, respectively, in groups G2 and G3. Th1 profile cytokine (IFN-γ, TNF-α, and IL-6) and IL-17 were significantly increased (p < 0.001) stimulated with B. cereus GM in groups G2 and G3. IL-4 showed significant values when the stimulus was mediated by ConA. By modulating the immune response, B. cereus GM reduced the burden of worms, improved some markers of liver function, and reduced the granulomatous inflammatory reaction in mice infected with S. mansoni, especially when administered before infection.

A collective autoethnography of coproduction in mental health research by academic researchers and young people in Brazil.

INTRODUCTION: Coproduction of mental health research and interventions involving researchers and young people is increasingly common. However, this model raises challenges, related, for instance, to communication, power and control. This paper narrates-from a collective first-person perspective-the lived experience of coproduction of a digital intervention by institutional researchers and young citizen researchers in Brazil. METHOD: This study employed a collaborative autoethnographic methodology, utilising autobiographical data such as meeting recordings, individual notes and collective guided reflections on the coproduction process. Our analysis focused on challenges and solutions that arose during the process. RESULTS: Throughout the project, we created formal and informal mechanisms for accountability, transparency and fair inclusion of multiple voices. We engaged in mutual capacity-building, invested in building interpersonal knowledge, and implemented practices to reduce overload and promote equitable participation. Through ongoing reflection and readjustment in response to challenges, we progressively embraced more democratic and egalitarian values. The collective care invested in the process fostered synergy, trust, and intergroup friendship. CONCLUSION: Our experience points to the value of creating a space for multiple research identities: the citizen young person and the institutional researcher, both of whom critically reflect on their roles in the research process. Our focus on coproduced care calls into question participation metaphors that represent the process via a single axis-young people-who linearly progress from minimal participation to full autonomy. Instead, our analysis highlights the importance of a social and caring bond that supports the radical co-production of innovative health solutions in contexts of vulnerability.

Prevalence of sleep disorders in children with Congenital Zika Syndrome.

Studies have reported that children with Congenital Zika Syndrome (CZS) experience changes in their sleep patterns, which can result in mood disturbances, behavioral issues and delays in growth and development. This systematic review synthesized the available evidence on the prevalence of sleep disorders in children with CZS. Eligible studies were those with an observational design that reported sleep disorders in children with CZS using validated questionnaires, polysomnography/electroencephalographic recording or parent/caregiver reports. Searches were conducted in PubMed, Web of Science, SCOPUS and Embase, as well as a gray literature search using Google Scholar. The Freeman-Tukey double-arcsine transformation with a random-effects model was used to estimate the pooled prevalence of sleep disorders with a 95% confidence interval (CI). Five studies were included and data from 340 Brazilian children with CZS were analyzed. The overall prevalence of sleep disorders was 27.4% (95% CI 16.7-39.4), without differences among studies using validated questionnaires (29.4%, 95% CI 21.4-37.8) or report from parents and caregivers (27.4%, 95% CI 11.5-47.0). Sleep disorders are prevalent in children with CZS, impacting their development and quality of life. It is critical to examine the quality of sleep in these children to develop appropriate interventions that can mitigate these issues.

The article discusses a systematic review of studies that have explored the prevalence of sleep disorders in children with Congenital Zika Syndrome (CZS), a condition caused by the Zika virus. The study found that children with CZS often experience changes in their sleep patterns, which can lead to mood disturbances, behavioral issues and delays in growth and development. The review included five studies with a total of 340 Brazilian children with CZS, and the overall prevalence of sleep disorders was found to be 27.4%. This indicates that sleep disorders are prevalent in children with CZS and can significantly impact their development and quality of life. The authors suggest that further research is needed to develop appropriate interventions to mitigate these issues.

PD-1/PD-L1 Inhibitors Response in Triple-Negative Breast Cancer: Can Long Noncoding RNAs Be Associated?

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.