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Abstract Long non-coding RNAs (lncRNAs) play fundamental roles in cellular processes and pathologies, regulating gene expression at multiple levels. Despite being highly cell type-specific, their study at single-cell (sc) level is challenging due to their less accurate annotation and low expression compared to protein-coding genes. Here, we systematically benchmark different preprocessing methods and develop a computational framework, named ELATUS, based on the combination of the pseudoaligner Kallisto with selective functional filtering. ELATUS enhances the detection of functional lncRNAs from scRNA-seq data, detecting their expression with higher concordance than standard methods with the ATAC-seq profiles in single-cell multiome data. Interestingly, the better results of ELATUS are due to its advanced performance with an inaccurate reference annotation such as that of lncRNAs. We independently confirm the expression patterns of cell type-specific lncRNAs exclusively detected with ELATUS and unveil biologically important lncRNAs, such as AL121895.1, a previously undocumented cis-repressor lncRNA, whose role in breast cancer progression is unnoticed by traditional methodologies. Our results emphasize the necessity for an alternative scRNA-seq workflow tailored to lncRNAs that sheds light on the multifaceted roles of lncRNAs.

El principio de continuidad es hoy, afortunadamente, uno de los principios que caracterizan un parlamento moderno. Entre nosotros, la Constitución y sus normas de desarrollo han cambiado la tradición histórica de suspensiones y cierres por voluntad de sujetos ajenos a las Cámaras. Se han previsto normativamente unas diputaciones permanentes con capacidad de reacción en períodos de disolución. Se ha garantizado la sucesión automática de legislaturas. Hay amplios períodos anuales ordinarios de trabajo y existe la posibilidad de que las Cámaras celebren sesiones extraordinarias. Y, en desarrollo de las normas, las Cámaras, con numerosos acuerdos, precedentes y usos, algunos poco conocidos, han contribuido decisivamente a ampliar el modelo de continuidad. Las especiales circunstancias que se acaban de vivir en la Legislatura XIV han servido, además, para certificar que hoy se demanda la continuidad parlamentaria incluso en las circunstancias más extraordinarias.

Objetivo: revisar y validar un cuestionario de conocimientos sobre manejo de insulinas inyectables (JH-SEFAC) por pacientes con diabetes para utilización en las farmacias comunitarias (FC). Métodos: diseño del estudio: observacional transversal en FC españolas durante el primer semestre de 2023. Criterios de inclusión: pacientes con diabetes, mayores de edad, en tratamiento con insulina. Diseño del cuestionario: un grupo nominal de FC revisó y pilotó el cuestionario inicial para determinar su viabilidad. Fue aprobado por el CEIC de Aragón (PI22/375). Validación de contenido: por un grupo multidisciplinar de expertos en diabetes, mediante un cuestionario de evaluación ad hoc de 10 preguntas (escala Likert de 1-5). Fiabilidad: mediante el índice de consistencia interna (alfa de Cronbach) y el coeficiente de correlación intraclase (CCI). Reproducibilidad (test/retest): se compararon los resultados del cuestionario administrado dos veces separadas 2-3 semanas al grupo de pacientes. Colaboraron farmacéuticos miembros del Grupo de Trabajo de Diabetes de SEFAC. Muestra: se calculó en 127 sujetos (IC del 95 % y precisión del 10 %). Resultados: 20 FC de 13 CCAA incorporaron 131 pacientes. La valoración de los expertos fue de 4,52 sobre 5 (90,4 %). El test Keiser-Meyer-Olkin fue de 0,626 y la prueba de Bartlett resultó significativa (p

Abstract The colonization of the pelagic realm by the vertebrates represents one of the major transitions in the evolutionary success of the group and in the establishment of modern complex marine ecosystem. It has been traditionally related with the Devonian rise of jawed vertebrates, but new evidences indicate that first active swimmers, invading the water column, occurred within earlier armoured jawless fishes (“ostracoderms”). These “primitive” fishes lacked conventional fish control surfaces and the precise mechanism used to generate lift and stabilizing forces still remains unclear. We show that, because of their shape, the rigid cephalic shield of Pteraspidiformes, a group of Silurian-Devonian “ostracoderms”, generate significant forces for hydrodynamic lift. Particle Image Velocimetry and force measurements in a water channel shows that the flow over real-sized Pteraspidiformes models is similar to that over delta wings, dominated by the formation of leading-edge vortices resulting in enhanced vortex lift forces and delayed stall angles of attack. Additionally, experiments simulating ground effect show that Pteraspidiformes present better hydrodynamic performance under fully pelagic conditions than in a benthic scenario. This suggests that, lacking movable appendages other than the caudal fin, leading-edge vortices were exploited by earliest vertebrates to colonize the water column more than 400 Mya.

Background: Middle ear active implants, such as the Vibrant Soundbridge (VSB), offer an alternative to reconstructive surgery and other implantable hearing aid systems for patients with conductive, mixed, or sensorineural hearing loss. The primary objective of this work is to describe the auditory results obtained with VSB in our patient cohort, measuring the auditory gain in terms of average tonal thresholds and spoken word discrimination at 65 dB. Secondly, auditory gain differences between different types of hearing loss, coupling to the ossicular chain compared to round and oval windows, and the impact of open versus more conservative surgical approaches, were analyzed. Methods: A cross-sectional observational study, with retrospective data collection, was conducted at a tertiary care center. Clinical and audiometric data pre- and post-implantation were included, from patients who underwent VSB device placement surgery between 2001 and 2024. Results: 55 patients with an average age of 62.58 ± 17.83 years and a slight preference in terms of the female gender (52.72%) were included in the study. The average gain in the PTA for all types of hearing loss was 41.56 ± 22.63 dB, while for sensorineural hearing loss (SNHL) the gain was 31.04 ± 8.80 dB. For mixed-conductive hearing loss (C-MHL) a gain of 42.96 ± 17.70 was achieved, notably, in terms of absolute values, at frequencies of 4000 and 6000 Hz, with gains reaching 49.25 ± 20.26 dB at 4 K and 51.16 ± 17.48 dB at 6 K. In terms of spoken word discrimination, for all types of hearing loss, an improvement of 75.20 ± 10.11% was achieved. However, patients with C-MHL exhibited an approximately 13% higher gain compared to those with SNHL (69.32 ± 24.58% vs. 57.79 ± 15.28%). No significant differences in auditory gain were found between open and closed surgical techniques, nor in the proportion of adverse effects, when comparing one technique with the other. Conclusions: The VSB is effective in improving hearing in patients with mixed, conductive, and sensorineural hearing loss, with significant gains at high frequencies, especially through the round window membrane approach. The choice of surgical technique should consider the patient’s anatomical characteristics and specific needs in order to optimize auditory outcomes and minimize postoperative complications.

Background: Audiovestibular disorders in childhood occur with considerable frequency. However, the difficulty of obtaining medical history, the nonspecificity of symptoms, and the lack of cooperation during complementary tests often contribute significantly to diagnostic biases, attributing clinical presentations to psychosomatic disorders. The objectives of this work are, firstly, to characterize, from an auditory and vestibular perspective, the most frequent causes of vertigo in childhood and a possible relationship with emotional symptoms. On the other hand, to propose the usefulness of the MSSQ-Short questionnaire as a predictive variable in the evolution of children diagnosed with recurrent vertigo of childhood (RVC). Methods: An observational cross-sectional study was designed with retrospective data collection at three tertiary hospitals. Results: Among the 117 patients recruited between 2016 and 2024, 32 patients (27.35%) were diagnosed with an anxious-depressive syndrome prior to audiovestibular testing. The mean age was 11.19 ± 5.61 years and the most frequent final diagnoses were vestibular migraine (VM) with 41.03% and RVC with 23.93%. Patients with VM, compared with RVC, are approximately 1.12 times more likely to have psychosomatic pathology (CI 0.39 to 3.25). The most sensitive and frequently altered test was VEMPS (39.32%), with statistical significance in VM and otic capsule dehiscence, while regarding the MSSQ-Short questionnaire, the linear regression of 0.28 indicates an increase in clinical duration with high questionnaire scores. Conclusions: Vestibular disorders causing dizziness and vertigo are challenging to diagnose, often due to lack of cooperation and/or symptom nonspecificity. A thorough medical history and complementary tests, including audiovestibular and imaging studies, are advisable, thus avoiding systematically attributing children’s complaints to other psychosomatic disorders.

BackgroundUntreated hearing loss has an effect on cognition. It is hypothesized that the additional processing required to compensate for the sensory loss affects the cognitive resources available for other tasks and that this could be mitigated by a hearing device.MethodsThe impact on cognition of cochlear implants (CIs) was tested in 100 subjects, ≥60 years old, with bilateral moderately-severe to profound post linguistic deafness using hearing aids. Data was compared pre and 12 and 18 months after cochlear implantation for the speech spatial qualities questionnaire, Mini Mental State Examination (MMSE), Trail making test B (TMTB) and digit symbol coding (DSC) from the Wechsler Adult Intelligence Scale version IV and finally the timed up and go test (TUG). Subjects were divided into young old (60–64), middle old (65–75) and old old (75+) groups. Cognitive test scores and times were standardized according to available normative data.ResultsHearing significantly improved pre- to post-operatively across all age groups. There was no change post-implant in outcomes for TMTB, TUG or MMSE tests. Age-corrected values were within normal expectations for all age groups for the TUG and MMSE. However, DSC scores and TMTB times were worse than normal. There was a significant increase in DSC scores between baseline and 12-months for 60- to 64-year-olds (t[153] = 2.608, p = 0.027), which remained at 18 months (t[153] = 2.663, p = 0.023).DiscussionThe improved attention and processing speed in the youngest age group may be a consequence of reallocation of cognitive resources away from auditory processing due to greatly improved hearing. The oldest age group of participants had cognition scores closest to normal values, suggesting that only the most able older seniors tend to come forward for a CI. Severe to profoundly deaf individuals with hearing aids or cochlear implants were still poorer than age-equivalent normally hearing individuals with respect to cognitive flexibility, attention, working memory, processing speed and visuoperceptual functions. Due to a lack of data for the TUG, TMTB and DSC in the literature for hearing impaired individuals, the results reported here provide an important set of reference data for use in future research.

Sònia Travé-Huarte, James S Wolffsohn Optometry and Vision Science Research Group, College of Health and Life Sciences, Aston University, Birmingham, UKCorrespondence: Sònia Travé-Huarte, School of Optometry, Aston University, Birmingham, UK, Tel +44 1212044400, Email s.trave-huarte@aston.ac.ukPurpose: To assess changes in symptoms and ocular surface signs following a bilateral sutureless treatment of dehydrated amniotic membrane (dAM) under a specialised bandage contact lens (sBCL) in patients with moderate-to-severe dry eye disease (DED).Patients and Methods: In this prospective pre-post interventional study, 35 patients diagnosed with moderate-to-severe DED, with an Ocular Surface Disease Index (OSDI) score > 30 on current treatment, were enrolled. Assessments were conducted at baseline (day − 30), after 30 days run-in with no additional treatment (day 0 – control), and 30 days post sBCL+dAM treatment (day 30 – treatment). Intervention involved two successive bilateral 4-5 day sutureless applications of dAM (17mm diameter, with a 6 mm central aperture, Omnigen® VIEW) under an 18mm sBCL (OmniLenz®). Symptomatology and ocular signs were measured using OSDI, Dry Eye Questionnaire-5 (DEQ-5), Symptom Assessment iN Dry Eye (SANDE), and other ocular surface health indicators including non-invasive breakup time, corneal and conjunctival staining, and lid wiper epitheliopathy length and width (LWE).Results: While symptomatology remained stable during the 30-day no-treatment run-in, 1-month post-dAM treatment, there was a significant reduction in OSDI scores (from 55.8 to 32.3, p< 0.001), DEQ-5 (from 14.6 to 10.0, p< 0.001), SANDE frequency (from 65.2 to 43.6, p< 0.001), and SANDE severity (from 59.8 to 41.1, p< 0.001). Additionally, there was a notable decrease in the width of LWE staining, from grade 2 (50– 75% of the lid wiper) to grade 1 (25– 50% of the lid wiper) (p=0.011).Conclusion: A bilateral 8– 10-day treatment duration with dAM applied with sBCL demonstrated a 31 to 42% improvement in symptomatology and a decrease in ocular surface signs of mechanical stress. This innovative bilateral treatment approach offers a promising treatment modality for patients with refractory moderate-to-severe DED.Keywords: dry eye disease, amniotic membrane, bandage contact lens

Introduction: We present a series of six cases whose clinical presentations exhibited audiovestibular manifestations of a third mobile window mechanism, bearing a reasonable resemblance to Ménière’s disease and otosclerosis. The occurrence of these cases in such a short period has prompted a review of the underlying causes of its development. Understanding the pathophysiology of third mobile window syndrome and considering these entities in the differential diagnosis of conditions presenting with vertigo and hearing loss with slight air-bone gaps is essential for comprehending this group of pathologies. Materials and Methods: A descriptive retrospective cohort study of six cases diagnosed at a tertiary center. All of them went through auditive and vestibular examinations before and after a therapeutic strategy was performed. Results: Out of 84 cases of dehiscences described in our center during the period from 2014 to 2024, 78 belonged to superior semicircular canal dehiscence, while 6 were other otic capsule dehiscences. Among these six patients with a mean age of 47.17 years (range: 18–73), all had some form of otic capsule dehiscence with auditory and/or vestibular repercussions, measured through hearing and vestibular tests, with abnormalities in the results in five out of six patients. Two of them were diagnosed with Ménière’s disease (MD). Another two had cochleo-vestibular hydrops without meeting the diagnostic criteria for MD. In two cases, the otic capsule dehiscence diagnosis resulted from an intraoperative complication due to a gusher phenomenon, while in one case, it was an accidental radiological finding. All responded well to the proposed treatment, whether medical or surgical, if needed. Conclusions: Otic capsule dehiscences are relatively new and unfamiliar entities that should be considered when faced with cases clinically suggestive of Ménière’s disease, with discrepancies in complementary tests or a poor response to treatment. While high-sensitivity and specificity audiovestibular tests exist, completing the study with imaging, especially petrous bone CT scans, is necessary to locate and characterize the otic capsule defect responsible for the clinical presentation.

ABSTRACT Besides the well-characterized protein network involved in the replication stress response, several regulatory RNAs have been shown to play a role in this critical process. However, it has remained elusive whether they act locally at the stressed forks. Here, by investigating the RNAs localizing on chromatin upon replication stress induced by hydroxyurea, we identified a set of lncRNAs upregulated in S-phase and controlled by stress transcription factors. Among them, we demonstrate that the previously uncharacterized lncRNA lncREST (long non-coding RNA REplication STress) is transcriptionally controlled by p53 and localizes at stressed replication forks. LncREST-depleted cells experience sustained replication fork progression and accumulate un-signaled DNA damage. Under replication stress, lncREST interacts with the protein NCL and assists in engaging its interaction with RPA. The loss of lncREST is associated with a reduced NCL-RPA interaction and decreased RPA on chromatin, leading to defective replication stress signaling and accumulation of mitotic defects, resulting in apoptosis and a reduction in tumorigenic potential of cancer cells. These findings uncover the function of a lncRNA in favoring the recruitment of replication proteins to sites of DNA replication.

The rapid emergence of new applications and services, and their increased demand for Quality of Service (QoS), have a significant impact on the development of today’s communication networks. As a result, communication networks are constantly evolving towards new architectures, such as the 6th Generation (6G) of communication systems, currently being studied in academic and research environments. One of the most critical aspects of designing communication networks is meeting the restricted delay and packet loss requirements. In this context, although link failure recovery has been widely addressed in the literature, it remains one of the main causes of packet losses and delays in the network. The failure recovery time in currently deployed technologies is still far from the sub-millisecond delay required in 6G networks. The time required for distributed network architectures to converge to a common network state after a link failure is excessive. In contrast, centralized architectures such as Software-Defined Networking (SDN) solve this problem but still need to notify the failure to a centralized controller, which increases the recovery time. This paper proposes a very Fast Failure Recovery (vFFR) strategy that can recover from link failures in sub-millisecond timescales by reacting directly from the data plane of the network devices while maintaining a synchronized state with the centralized controller. We first analyze current failure recovery strategies and classify them according to the techniques used to optimize failure recovery time. Afterward, we describe the design of a vFFR strategy that combines three data plane recovery algorithms to reduce latency and packet loss under varying network conditions. Our vFFR strategy has been modeled in P4 language and tested on an emulation platform to validate the three data plane recovery algorithms under different conditions. The results show that latency varies according to the alternate path selected in the recovery algorithm, and the packet loss rate remains constant even when the background traffic reaches 90% of the link capacity. In addition, the vFFR strategy has been implemented on Intel Tofino devices, achieving a failure recovery time lower than $500~\mu s$ and a total frame loss rate below 0.005% in all cases, including those with a 35 Gbps load.

Objetivo: analizar los resultados de las campañas de SEFAC de cribado del riesgo de padecer diabetes, realizados en las farmacias comunitarias españolas desde 2014. Métodos: estudio descriptivo acumulativo de los resultados de las campañas del Día Mundial de la Diabetes, en 2014, 2016-2018, 2020 y 2021. Pacientes: usuarios ≥18 años no diagnosticados de diabetes con consentimiento firmado. Variables: puntuación del test de Findrisc, media (m) y desviación estándar (DE) y participantes en intervalos de riesgo, n (%). Variables demográficas (sexo, edad) y antropométricas, índice de masa corporal (IMC) (kg/m2), perímetro de cintura (cm), glucemia capilar m (DE) (mg/dl). Resultados: participaron 1.146 farmacéuticos, 12402 usuarios. 8.799 (70,9 %) tenían IMC ≥25 kg/m2. 7366 (59,4 %) tomaban antihipertensivos. 6047 (48,8 %) con perímetro abdominal excesivo. 5962 (48,0 %) tenían antecedentes familiares de diabetes. El riesgo medio (puntuación Findrisc) fue de 11,3 (4,6), sin diferencias entre sexos (p>0,05). El número de participantes con riesgo alto/muy alto (F≥15) fue 3107 (25,0 %) sin diferencias entre sexos (p>0,05). El riesgo alto/muy alto aumenta con la edad, de 282 (15,1 %) personas de 45-54 años hasta 1695 (40,1 %) personas >64 años. Se derivaron al médico 1762 (14,2 %), sin datos de resultado. Tiempo medio de entrevista: 10,3 (5,3) minutos, sin diferencias entre sexos (p>0,05). Conclusiones: la cuarta parte de los encuestados tenían riesgo alto/muy alto y fueron derivados al médico uno de cada siete. Los factores de riesgo más prevalentes fueron IMC, hipertensión arterial, perímetro abdominal y antecedentes familiares de diabetes. Debe mejorarse la comunicación interprofesional, pues no se obtuvo resultado de las derivaciones al médico.

Background and Objectives: Infrared light is used to image the Meibomian glands through their thermal profile. This study aimed to investigate the effects of a combination of heating and an eyelid massage on Meibomian gland visibility and tear film parameters. Materials and Methods: Twenty-four participants (26 ± 6.9 years) were enrolled in this prospective study, which involved imaging the Meibomian glands of both the lower and upper eyelid and assessing the non-invasive breakup time (NIBUT), tear meniscus height (TMH), and blink rate (using the CA-800, Topcon) at baseline after five minutes of eyelid warming followed by a five-minute eyelid massage. The second session, which was randomised in sequence, repeated the same measurements but without the inclusion of any eyelid warming or massage as the control condition. Results: While there was no change in lower lid Meibomian gland appearance as a result of eyelid heating, eyelid massage, or multiple lid eversion (median 2.0, range 0.0 to 4.0; p = 0.782), there was a change in upper lid appearance 5 min after heating and lid massage (p = 0.025), but again, multiple lid eversion had no effect (p > 0.05). The NIBUT decreased on second lid eversion (p = 0.049), although this was not evident on the third lid eversion (p = 0.090). The effect on NIBUT was also apparent with heating (p = 0.034 immediately after) but was sustained with 5 min of eyelid massage (p = 0.031). The TMH increased with heating (p < 0.001), and this effect was sustained with 5 min of eyelid massage (p = 0.011), but there was no lid eversion effect (p > 0.05). The blink rate was unaffected by heating, eyelid massage, or multiple eversions of the eyelids (median 24 blinks/min, range 8 to 59 blinks/min; p = 0.61). Conclusions: Eyelid warming can increase the visibility of the Meibomian glands, although this effect was only observed with upper lid imaging and the effect dissipated after 5 min of eyelid massage. Warming and massage also disrupt the tear film, as does multiple lid eversion, emphasising the need to use the least invasive tear film assessment techniques first.

Reducing hot cracking is essential for ensuring seamless production of nickel superalloys, which are extensively used in welded structures for aircraft engines. The prevalence of hot cracking in precipitation-strengthened alloy 718 is primarily governed by two factors: firstly, the chemical composition and the coarse microstructure formed during solidification, and secondly, the activation of hot cracking mechanisms, which is particularly critical in mushroom-shaped welding morphologies. In this study, different nickel-based superalloys welded using laser beam welding (LBW), more specifically bead on plate welding (BoP), specimens are compared. The cracking susceptibility of both wrought and two investment casting 718 alloys with tailored chemical compositions is examined through the application of both continuous and pulsed LBW. Additionally, various pre-weld treatments, including with and without Pre-HIP (hot isostatic pressing), are analyzed. The influences of chemical composition, LBW parameters and pre- and post-welding treatments on both internal and external cracks determined by conventional and advanced non-destructive tests are studied. A clear reduction of hot cracking susceptibility and overall welding quality improvement was observed in a tailored 718 alloy with relatively high Ni (55.6% wt) and Co (1.11% wt) contents.

Abstract Background Alterations in progranulin (PGRN) expression are associated with multiple neurodegenerative diseases (NDs), including frontotemporal dementia (FTD), Alzheimer’s disease (AD), Parkinson’s disease (PD), and lysosomal storage disorders (LSDs). Recently, the loss of PGRN was shown to result in endo-lysosomal system dysfunction and an age-dependent increase in the expression of another protein associated with NDs, glycoprotein non-metastatic B (GPNMB). Main body It is unclear what role GPNMB plays in the context of PGRN insufficiency and how they interact and contribute to the development or progression of NDs. This review focuses on the interplay between these two critical proteins within the context of endo-lysosomal health, immune function, and inflammation in their contribution to NDs. Short conclusion PGRN and GPNMB are interrelated proteins that regulate disease-relevant processes and may have value as therapeutic targets to delay disease progression or extend therapeutic windows.

Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice. Resumen: La hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR) es una técnica de diálisis caracterizada por un cartucho de resina con poder adsorbente que combina los mecanismos difusión, convección y adsorción en un solo esquema terapéutico. Después de cerca de 20 años de experiencia clínica con HFR, el presente artículo revisa la evidencia acumulada con esta técnica, planteando si la adición de la adsorción, como tercer mecanismo depurativo, debería ser el siguiente paso en el tratamiento de los pacientes en hemodiálisis. La HFR, a pesar de producir una extensa eliminación de toxinas urémicas, ha demostrado reducir la pérdida de nutrientes y componentes fisiológicos durante la sesión de diálisis frente a la hemodiafiltración on-line, mitigando el estado inflamatorio y el estrés oxidativo en esta población. Además de su facilidad de uso, la técnica también es altamente biocompatible y puede utilizarse en situaciones de un acceso vascular comprometido. En base a estas observaciones, la HFR parece ser una técnica especialmente útil para pacientes con elevada comorbilidad, incluyendo aquellos con fragilidad, desnutrición o enfermedad cardiovascular. En esta revisión, como panel de consenso de nefrólogos con experiencia clínica en HFR, examinamos la literatura existente y resumimos nuestros puntos de vista sobre cómo usar esta técnica, qué perfil de paciente puede ser más adecuado para la HFR, y cómo prescribir y monitorizar de manera práctica esta modalidad de diálisis.

Resumen: La hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR) es una técnica de diálisis caracterizada por un cartucho de resina con poder adsorbente que combina los mecanismos difusión, convección y adsorción en un solo esquema terapéutico. Después de cerca de 20 años de experiencia clínica con HFR, el presente artículo revisa la evidencia acumulada con esta técnica, planteando si la adición de la adsorción, como tercer mecanismo depurativo, debería ser el siguiente paso en el tratamiento de los pacientes en hemodiálisis. La HFR, a pesar de producir una extensa eliminación de toxinas urémicas, ha demostrado reducir la pérdida de nutrientes y componentes fisiológicos durante la sesión de diálisis frente a la hemodiafiltración on-line, mitigando el estado inflamatorio y el estrés oxidativo en esta población. Además de su facilidad de uso, la técnica también es altamente biocompatible y puede utilizarse en situaciones de un acceso vascular comprometido. En base a estas observaciones, la HFR parece ser una técnica especialmente útil para pacientes con elevada comorbilidad, incluyendo aquellos con fragilidad, desnutrición o enfermedad cardiovascular. En esta revisión, como panel de consenso de nefrólogos con experiencia clínica en HFR, examinamos la literatura existente y resumimos nuestros puntos de vista sobre cómo usar esta técnica, qué perfil de paciente puede ser más adecuado para la HFR, y cómo prescribir y monitorizar de manera práctica esta modalidad de diálisis. Abstract: Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice.

Abstract Entomopathogenic fungi such as Beauveria bassiana are the only insect pathogens able to start the infection process by penetrating through the host cuticle. However, some insects try to avoid fungal infection by embedding their cuticle with antifungal compounds. This is the case of the red flour beetle Tribolium castaneum, which generates economical loss of great significance in stored product environments worldwide. In this study, T. castaneum adults were fed during different time periods (from 3 to 72 h) on B. bassiana conidia-covered corn kernels. The progression of fungal infection was monitored using the dual RNA-seq technique to reconstruct the temporal transcriptomic profile and to perform gene enrichment analyses in both interacting organisms. After mapping the total reads with the B. bassiana genome, 904 genes were identified during this process. The more expressed fungal genes were related to carbon catabolite repression, cation binding, peptidase inhibition, redox processes, and stress response. Several immune-related genes from Toll, IMD, and JNK pathways, as well as genes related to chitin modification, were found to be differentially expressed in fungus-exposed T. castaneum. This study represents the first dual transcriptomic approach to help understand the interaction between the entomopathogenic fungus B. bassiana and its tolerant host T. castaneum.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients’ quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central ‘window’) applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.