Asymmetric BODIPY Dyes Enabling Triplet-Triplet Annihilation Upconversion.

The construction of triplet-triplet annihilation upconversion (TTA-UC) systems with upconversion (UC) emission efficiency at low power densities is still under continuing exploration. From an environmental point of view, the utilization of purely organic pairs is more beneficial than the involvement of transition-metal complexes. In this context, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes, which can be found in a wide range of applications, have been previously used as suitable sensitizers in TTA-UC systems. The versatility of these scaffolds makes them magnificent objectives for designing and synthesizing potential entities with different target abilities. Herein, we prepared several asymmetric BODIPY dyes with excellent optical properties to be applied to a bimolecular TTA-UC system. In the presence of 2,5,8,11-tetra-tert-butylperylene (TBPe) as a suitable annihilator, a green-to-blue light conversion was clearly observed by means of detailed spectroscopic investigations. The results revealed a high UC emission efficiency (ηUC) of ∼8%, together with a low threshold intensity (I th) of ∼40-50 mW/cm2. All data indicated that these asymmetric BODIPY dyes were ideal sensitizers for TTA-UC, providing a particular design for further investigations.

Microclimatic effects of tree shelters on the early establishment and resilience of seeded acorns vs. outplanted seedlings.

Little is known about the effects of tree shelters on the early response of oak seedlings produced by acorn seeding. In this paper, we explore the effects on holm oak (Quercus ilex L. subsp. ballota (Desf.) Samp.) seedlings of the microenvironment created by the tree shelters and the restoration method (seeding vs. outplanting) in terms of emergence, survival, growth, and resilience after harvesting. For this purpose, seedling height [H], root collar diameter [RCD], number of leaves, and aerial biomass were monitored. We made two sowings of acorns in February 2017 and February 2018, together with a seedling outplanting in February 2018 in a common garden site in semiarid SE Spain. In total, 600 acorns were randomly sowed and 300 nursery-grown seedlings were outplanted and studied until 2022. Mother tree and initial acorn mass were also monitored as additional variables in the analyses. Tree shelters consisted of closed plastic Tubes, Mixed tubes, Cork shelters, Tiles, and a Control with no shelter. Emergence rate was positively influenced by the Tube shelter (86%) as compared to the Control (64%), and especially by the initial acorn mass. By contrast, mother tree or year of sowing seemed to have no effect. The survival rate for the emerged acorns (88%) was statistically similar to that of outplanted seedlings (91%), and was unaffected by mother tree, tree shelter, or acorn mass. In terms of growth, the slenderness ratio (H:RCD) was considerably higher in seedlings from directly seeded acorns than for those that were outplanted. With the exception of Tile, all the shelters showed a higher slenderness ratio than the Control, especially the Tube shelter, which also showed a lower number of leaves and a lower aboveground dry biomass than the Control, Cork, and Tile shelters. Virtually no interactions were observed between the mother tree and the tree shelter. At harvesting, all the growth-related parameters were still strongly dependent on the acorn mass and the initial seedling features recorded after the first growing season. Resprouting rate and growth were also highly dependent on the acorn mass and the plant features at the beginning of the experiment and at harvesting. In summary, we did not find evidence to support tree shelters to improve the microclimate of holm oak seedlings both seeded or outplanted. Direct acorn seeding can be as successful as outplanting of nursery-grown seedlings. Selection of heavy acorns from mothers with a high germination and emergence rate is highly advisable.

A national evaluation of a multi-modal, blended, digital intervention integrated within Australian youth mental health services.

BACKGROUND: Youth mental health (YMH) services have been established internationally to provide timely, age-appropriate, mental health treatment and improve long-term outcomes. However, YMH services face challenges including long waiting times, limited continuity of care, and time-bound support. To bridge this gap, MOST was developed as a scalable, blended, multi-modal digital platform integrating real-time and asynchronous clinician-delivered counselling; interactive psychotherapeutic content; vocational support; peer support, and a youth-focused online community. The implementation of MOST within Australian YMH services has been publicly funded. OBJECTIVE: The primary aim of this study was to evaluate the real-world engagement, outcomes, and experience of MOST during the first 32 months of implementation. METHOD: Young people from participating YMH services were referred into MOST. Engagement metrics were derived from platform usage. Symptom and satisfaction measures were collected at baseline, 6, and 12 (primary endpoint) weeks. Effect sizes were calculated for the primary outcomes of depression and anxiety and secondary outcomes of psychological distress and wellbeing. RESULTS: Five thousand seven hundred and two young people from 262 clinics signed up and used MOST at least once. Young people had an average of 19 login sessions totalling 129 min over the first 12 weeks of use, with 71.7% using MOST for at least 14 days, 40.1% for 12 weeks, and 18.8% for 24 weeks. There was a statistically significant, moderate improvement in depression and anxiety at 12 weeks as measured by the PHQ4 across all users irrespective of treatment stage (d = 0.41, 95% CI 0.35-0.46). Satisfaction levels were high, with 93% recommending MOST to a friend. One thousand one hundred and eighteen young people provided written feedback, of which 68% was positive and 31% suggested improvement. CONCLUSIONS: MOST is a highly promising blended digital intervention with potential to address the limitations and enhance the impact of YMH services.

Interneurons in the CA1 stratum oriens expressing αTTP may play a role in the delayed-ageing Pol µ mouse model.

Neurodegeneration associated with ageing is closely linked to oxidative stress (OS) and disrupted calcium homeostasis. Some areas of the brain, like the hippocampus - particularly the CA1 region - have shown a high susceptibility to age-related changes, displaying early signs of pathology and neuronal loss. Antioxidants such as α-tocopherol (αT) have been effective in mitigating the impact of OS during ageing. αT homeostasis is primarily regulated by the α-tocopherol transfer protein (αTTP), which is widely distributed throughout the brain - where it plays a crucial role in maintaining αT levels within neuronal cells. This study investigates the distribution of αTTP in the hippocampus of 4- and 24-month-old Pol µ knockout mice (Pol µ-/-), a delayed-ageing model, and the wild type (Pol µ+/+). We also examine the colocalisation in the stratum oriens (st.or) of CA1 region with the primary interneuron populations expressing calcium-binding proteins (CBPs) (calbindin (CB), parvalbumin (PV), and calretinin (CR)). Our findings reveal that αTTP immunoreactivity (-IR) in the st.or of Pol µ mice is significantly reduced. The density of PV-expressing interneurons (INs) increased in aged mice in both Pol µ genotypes (Pol µ-/- and Pol µ+/+), although the density of PV-positive INs was lower in the aged Pol µ-/- mice compared to wild-type mice. By contrast, CR- and CB-positive INs in Pol µ mice remained unchanged during ageing. Furthermore, double immunohistochemistry reveals the colocalisation of αTTP with CBPs in INs of the CA1 st.or. Our study also shows that the PV/αTTP-positive IN population remains unchanged in all groups. A significant decrease of CB/αTTP-positive INs in young Pol µ-/- mice has been detected, as well as a significant increase in CR/αTTP-IR in older Pol µ-/- animals. These results suggest that the differential expression of αTTP and CBPs could have a crucial effect in aiding the survival and maintenance of the different IN populations in the CA1 st.or, and their coexpression could contribute to the enhancement of their resistance to OS-related damage and neurodegeneration associated with ageing.

[Epilepsy and inborn errors of metabolism]. / Epilepsia y errores congénitos del metabolismo.

INTRODUCTION: Epilepsy is a common manifestation in inborn errors of metabolism, with varying degrees of severity and response to treatment. OBJECTIVE: To determine its incidence and characteristics in metabolic diseases. MATERIAL AND METHODS: A retrospective review of neuropaediatric and metabolic databases was performed. Data on the type of epilepsy, age of onset and refractoriness were collected. RESULTS: Two cases out of three (66%) with molybdenum cofactor deficiency and neonatal epileptic encephalopathy; three with vitamin-sensitive epilepsies: pyridoxamine sulphate oxidase deficiency, antichitin and biotinidase deficiency, early onset and good seizure control with biotin; one with homocystinuria, with late onset and polytherapy; one with Menkes disease difficult to control; two with GLUT-1 deficiencies with absent and generalized discharges in the electroencephalogram; five (33%) peroxisomes in monotherapy, except for a suspected peroxisome biogenesis deficiency; 13 (34%) lysosomal deficiencies; a glycosylation disorder, with infantile and refractory spasms; seven (8.5%) organic aminoacidopathies and acidurias, one with infantile spasms (propionic acidemia), three with nonketotic hyperglycinemia with neonatal epileptic encephalopathy, one with monotherapy (leukinosis) and two (3.3%) with unscreened hyperphenylalaninemia; and five (20%) mitochondrial, most of which had oxidative phosphorylation deficiencies. CONCLUSIONS: The diagnosis of metabolic epilepsy requires a high level of suspicion in unscreened diseases. The semiology of the seizures and the electrocardiogram data are not characteristic, but some clinical data may provide guidance, such as early onset and refractoriness, neuroimaging and some biochemical markers. Although genetic studies are increasingly cost-effective in epilepsy, we must continue to search for earlier biomarkers and test targeted therapeutic trials.

TITLE: Epilepsia y errores congénitos del metabolismo.Introducción. La epilepsia es una manifestación común en los errores congénitos del metabolismo, con gravedad y respuesta al tratamiento variables. Objetivo. Determinar su incidencia y características en enfermedades metabólicas. Material y métodos. Se trata de una revisión retrospectiva de bases de datos de neuropediatría y metabolismo. Los datos recogidos son tipo de crisis, edad de inicio y refractariedad. Resultados. Dos casos de tres (66%) con defecto del cofactor del molibdeno y encefalopatía epiléptica neonatal; tres epilepsias sensibles a las vitaminas: déficit de piridoxamina sulfato oxidasa, déficit de antiquitina y de biotinidasa, de comienzo precoz y buen control de crisis con biotina; una homocistinuria, con inicio tardío y politerapia; una enfermedad de Menkes de difícil control; dos déficits de GLUT-1 con ausencias y descargas generalizadas en el electroencefalograma; cinco (33%) peroxisomales en monoterapia, salvo una sospecha de déficit de biogenia de peroxisomas; 13 (34%) lisosomales; un trastorno de la glucosilación, con espasmos infantiles y refractario; siete (8,5%) aminoacidopatías/acidurias orgánicas, uno con espasmos infantiles (acidemia propiónica), tres con hiperglicinemias no cetósicas con encefalopatía epiléptica neonatal, uno con monoterapia (leucinosis) y dos (3,3%) con hiperfenilalaninemias no cribadas; y cinco (20%) mitocondriales, la mayoría con déficit de la fosforilación oxidativa. Conclusiones. El diagnóstico de epilepsia metabólica precisa un alto índice de sospecha en enfermedades no cribadas. La semiología de las crisis y los datos en el electroencefalograma no son característicos, pero algunos datos clínicos, como el inicio precoz y la refractariedad, de neuroimagen y ciertos marcadores bioquímicos pueden orientar. Aunque los estudios genéticos son cada vez más rentables en la epilepsia, debemos seguir buscando biomarcadores más precoces y probar ensayos terapéuticos dirigidos.

Atypical fundoscopic manifestation with good visual prognosis in familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

PURPOSE: Pathogenic variants in the CLDN19 gene are responsible for Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) with ocular pathology (MIM *248190). Our objective was to delineate the ophthalmological and genetic manifestations of a patient with FHHNC and a pathogenic variant in CLDN19. CASE REPORT: A 25-year-old woman presented with renal involvement and a best-corrected visual acuity of 20/25 in the right eye and finger-counting ability in the left eye. The patient exhibited high myopia, convergent strabismus, and chorioretinal atrophic plaques in the perifoveal and peripapillary areas. We conducted a comprehensive ophthalmological examination, including refraction, fundoscopy, color and autofluorescence retinography, optical coherence tomography, and electrophysiology tests. Additionally, next-generation sequencing was performed using Illumina NextSeq500. We identified a homozygous missense variant, c.59G>A p.Gly20Asp, in the CLDN19 gene as the cause of renal and ocular manifestations. CONCLUSION: FHHNC is associated with various ocular alterations. The unique retinal disorders described in this article suggest a more favorable visual prognosis compared to those previously reported in the literature. Determining the phenotypic diversity of this disease may aid in the diagnosis and management of future cases.

In-vitro study on type I collagen synthesis in low-level laser therapy on the early ligament fibroblasts' healing process.

BACKGROUND: Low-level Laser Therapy (LLLT) has demonstrated its potential in promoting fiber matrix maturation, collagen synthesis, and fibroblast proliferation, contributing to tissue regeneration. Our study aimed to investigate the impact of LLLT on collagen type I synthesis, cell proliferation, and viability in human ligament fibroblasts derived from the Anterior Cruciate Ligament (ACL). METHODS: Tissue samples were obtained from individuals undergoing arthroscopic ACL reconstruction surgery. Primary human fibroblasts were isolated, and immunohistochemical assays confirmed their characteristics. LLLT at 850 nm was administered in three groups: Low dose (1.0 J/cm²), High dose (5.0 J/cm²), and Control (0.0 J/cm²). Cell viability was calculated using a membrane integrity assay, proliferation was determined by automated counting, and collagen type I concentration in cell culture was measured using an immunoassay. RESULTS: Fibroblasts showed decreased viability after low and high doses of LLLT, increased proliferation at the low dose, and increased collagen synthesis at the high dose on day 10 for both sexes after treatment. CONCLUSION: Our study demonstrated that LLLT may improve the early ligament healing process by increasing cell proliferation at the low dose and enhancing collagen type I synthesis at the high dose in human ligament fibroblasts.

A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies.

BACKGROUND: LHC165 is a Toll-like receptor (TLR)-7 agonist that generates an effective tumor antigen-specific T-cell adaptive immune response as well as durable antitumor responses. We aimed to evaluate the safety, tolerability, efficacy, dose-limiting toxicities, and pharmacokinetics (PK) of LHC165 single agent (SA) ± spartalizumab [PDR001; anti-programmed cell death protein 1 (PD-1)] in adult patients with advanced solid tumors. MATERIALS AND METHODS: In this phase I/Ib, open-label, dose-escalation/expansion study, patients received LHC165 SA 100-600 µg biweekly through intratumoral (IT) injection and LHC165 600 µg biweekly + spartalizumab 400 mg Q4W through intravenous (IV) infusion. RESULTS: Forty-five patients were enrolled: 21 patients received LHC165 SA, and 24 patients received LHC165 + spartalizumab. The median duration of exposure was 8 weeks (range 2-129 weeks). No maximum tolerated dose was reached. Recommended dose expansion was established as LHC165 600 µg biweekly as SA and in combination with spartalizumab 400 mg Q4W. The most common drug-related adverse events (AEs) were pyrexia (22.2%), pruritus (13.3%), chills (11.1%), and asthenia (4.4%). The only serious AE (SAE) suspected to be related to the study drug was grade 3 pancreatitis (n = 1). Across all tumor types, overall response rate and disease control were 6.7% and 17.8%, respectively. Overall median progression-free survival (PFS) and immune-related PFS was 1.7 months. LHC165 serum PK demonstrated an initial rapid release followed by a slower release due to continued release of LHC165 from the injection site. CONCLUSIONS: LHC165 demonstrated acceptable safety and tolerability both as SA and in combination with spartalizumab, and evidence of limited antitumor activity was seen in adult patients with relapsed/refractory or metastatic solid tumors.

Andean Crops Germination: Changes in the Nutritional Profile, Physical and Sensory Characteristics. A Review.

Andean crops such as quinoa, amaranth, cañihua, beans, maize, and tarwi have gained interest in recent years for being gluten-free and their high nutritional values; they have high protein content with a well-balanced essential amino acids profile, minerals, vitamins, dietary fiber, and antioxidant compounds. During the germination bioprocess, the seed metabolism is reactivated resulting in the catabolism and degradation of macronutrients and some anti-nutritional compounds. Therefore, germination is frequently used to improve nutritional quality, protein digestibility, and availability of certain minerals and vitamins; furthermore, in specific cases, biosynthesis of new bioactive compounds could occur through the activation of secondary metabolic pathways. These changes could alter the technological and sensory properties, such as the hardness, consistency and viscosity of the formulations prepared with them. In addition, the flavor profile may undergo improvement or alteration, a critical factor to consider when integrating sprouted grains into food formulations. This review summarizes recent research on the nutritional, technological, functional, and sensory changes occur during the germination of Andean grains and analyze their potential applications in various food products.

Stability of Cesium-Based Lead Halide Perovskites under UV Radiation.

Lead halide perovskites have been extensively studied for their potential applications, including photodetectors, solar cells, and high-energy radiation detection. These applications are possible because of their unique optoelectronic properties, such as tunable band gap, high optical absorption coefficient, and unique defect self-healing properties, which result in high defect tolerance. Despite these advantages, the long-term stability remains a critical issue that could hinder commercial applications of these materials. Reports on the stability of lead halide perovskites for optoelectronic applications have normally focused on methylammonium (MA)/formamidinium (FA), with very limited information for other systems, in particular, Cs-containing perovskites. In this paper, we report the stability of thick CsPbBr3-x Cl x polycrystalline thin films (∼8 µm) with several halide Br-Cl ratios after exposure to deep UV radiation. The chemical, crystal structure, optical, and electrical properties are analyzed, and the results are used to propose a degradation mechanism. The chemical analysis on the surface and bulk of the films indicates the formation of cesium oxide after UV exposure, with no significant change in the crystalline structure. The proposed mechanism explains the formation of cesium oxides during UV exposure. The I-V characteristics of diode structures also showed significant degradation after UV exposure, primarily at lower diode rectification ratios. The mechanism proposed in this paper can contribute to developing strategies to enhance the long-term stability of inorganic lead halide perovskites under UV exposure.

Substitution of soybean meal for yellow mealworm meal in the diet of slow-growing chickens provides comparable carcass traits and meat quality.

1. This study investigated the effects of incorporating yellow mealworm (Tenebrio molitor) larval meal as a partial and/or complete substitute for soybean meal on carcass and meat quality in slow-growing chickens.2. A total of 256 one-day-old male broilers were randomly allocated to 1 of 32 experimental units distributed among four treatments (n = 8): the control treatment (C), where soybean (SB) meal was the protein source, and three experimental treatments, in which SB meal was replaced by Tenebrio molitor (TM) larval meal at levels of 50% (T1), 75% (T2) and 100% (T3), respectively. Three different feed phases (1-29; 29-57 and 57-92 d of age) were used for each treatment. All chickens were slaughtered at 92 d of age, with eight animals per treatment randomly selected to assess carcass and meat quality. Near-infrared reflectance spectroscopy (NIR) was used to classify meat quality.3. Carcass traits were not significantly different between treatments, except for head and thigh weight, which were higher in the control group (p < 0.01). In terms of physicochemical characteristics, treatment T2 showed less yellowness (p < 0.05), while water and cooking losses were lower in treatments T1 and T2 (p < 0.01). Meat from both T1 and T2 groups had lower shear forces (p < 0.01), higher moisture content (p < 0.01) and less protein (p < 0.05) compared to treatments C andT3. Birds fed T3 had the highest meat ash content (p < 0.01). Chickens consuming TM had higher monounsaturated fatty acid (MUFA) levels and lower polyunsaturated fatty acid (PUFA) and n-6 acidsPUFA (p < 0.01).4. Substitution of SB with TM is a protein alternative for slow-growing chickens that supports carcass and meat quality comparable to those fed a conventional diet.

Robotic sacrocolpopexy for the treatment of pelvic organ prolapse in elderly women: comparative analysis of safety and efficacy versus younger women.

INTRODUCTION: Pelvic organ prolapse is a condition with high prevalence in elderly women. With increasing life expectancy and a desire for improved quality of life, a rise in the frequency of surgical treatments for these women is anticipated. The aim is to compare complication, success, and satisfaction rates among elderly patients (aged >70 years) in comparison to younger women undergoing robotic sacrocolpopexy, thereby assessing the safety and efficacy of this surgery in this group of patients. METHOD: A prospective observational comparative study of 123 robotic sacrocolpopexies conducted between December 2016 and June 2022. Patients were stratified by age (cutoff point: 70 years). Baseline characteristics, type, and grade of prolapse, intra and postoperative data, complications, functional and anatomical outcomes, and satisfaction levels were collected. RESULTS: Among the 123 patients, 62.6% were under 70 years old, while 37.4% were 70 years or older, exhibiting similar baseline characteristics, prolapse grade, and type. The percentages of intraoperative (6.5%) and postoperative complications (4.4-9%) were comparable in both age groups. Furthermore, success and satisfaction rates exceeded 90%, with no significant differences between women under and over 70 years during a two-year follow-up. CONCLUSION: Robotic sacrocolpopexy is at least as effective and safe in women aged 70 years or older as in younger individuals, with no higher rates of intra and postoperative complications and similar rates of anatomical and subjective success.

Unlocking Photocatalytic Activity of Acridinium Salts by Anion-Binding Co-Catalysis.

The in situ generation of active photoredox organic catalysts upon anion-binding co-catalysis by making use of the ionic nature of common photosensitizers is reported. Hence, the merge of anion-binding and photocatalysis permitted the modulation of the photocatalytic activity of simple acridinium halide salts, building an effective anion-binding - photoredox ion pair complex able to promote a variety of visible light driven transformations, such as anti-Markovnikov addition to olefins, Diels-Alder and the desilylative C-C bond forming reactions. Anion-binding studies, together with steady-state and time-resolved spectroscopy analysis, supported the postulated ion pair formation between the thiourea hydrogen-bond donor organocatalyst and the acridinium salt, which proved essential for unlocking the photocatalytic activity of the photosensitizer.

In-Flow Heterogeneous Triplet-Triplet Annihilation Upconversion.

Photon upconversion based on triplet-triplet annihilation (TTA-UC) is an attractive wavelength conversion with increasing use in organic synthesis in the homogeneous phase; however, this technology has not performed with canonical solid catalysts yet. Herein, a BOPHY dye covalently anchored on silica is successfully used as a sensitizer in a TTA system that efficiently catalyzes Mizoroki-Heck coupling reactions. This procedure has enabled the implementation of in-flow reaction conditions for the synthesis of a variety of aromatic compounds, and mechanistic proof has been obtained by means of transient absorption spectroscopy.

Linfoma extranodal de epiglotis en un paciente con recaída de leucemia linfoide aguda de células T. Presentación de un caso / Extranodal lymphoma of the epiglottis in a patient with relapsed T-cell acute lymphoid leukemia. Case report

Los linfomas localizados en la laringe representan un porcentaje muy bajo dentro de los comprendidos en los tumores de cabeza y cuello en la edad pediátrica. El linfoma no Hodgkin es el subtipo más comúnmente reportado en la literatura, el cual dependiendo de su etiología y extensión determinará el pronóstico del paciente. La certeza del diagnóstico, que suele ser muy difícil de alcanzar, se confirma generalmente mediante una biopsia de tejido. En la actualidad, no hay reportes de la literatura acerca de linfomas leucemoides diseminados a laringe. Se presenta el caso de un paciente masculino adolescente de 17 años con diagnóstico de una leucemia linfoide aguda con recaída extra-nodal en la laringe por falla en el esquema quimioterapéutico instaurado.

Lymphomas located at the level of the larynx represent a very low percentage of head and neck tumors in the pediatric age group. Non-Hodgkin's lymphoma is the most reported subtype in the literature, which depending on its etiology and extension will determine the patient's prognosis. Diagnostic certainty, which is often very difficult to achieve, is usually confirmed by tissue biopsy. At present, there are no reports in the literature about leukemoid lymphomas disseminated to the larynx. We present the case of a 17-year-old adolescent male patient diagnosed with acute lymphoid leukemia with extranodal relapse in the larynx due to failure of the chemotherapeutic regimen.

The effect of the alliance on social recovery outcomes and usage in a moderated online social therapy for first-episode psychosis.

OBJECTIVES: We investigated the effect of the therapeutic alliance on both change in social recovery outcomes and usage of a moderated online social therapy platform for first-episode psychosis (FEP), Horyzons. DESIGN: Secondary analysis of a single group pilot trial. METHODS: Clients completed an alliance measure adapted for guided digital interventions at mid-treatment. A series of multi-level models evaluated change in outcomes by mid- and post-treatment assessments (relative to baseline) as a function of the overall alliance. Quasi-Poisson models evaluated the effect of the overall alliance on aggregated counts of platform usage. Exploratory analyses repeated these models in terms of the bond (human-human) or the task/goal (human-program) alliance. RESULTS: Stronger overall alliance at mid-treatment predicted lower loneliness at mid-treatment and lower social anxiety at mid- and post-treatment. It was also associated with higher completion of therapy activities and authoring of comments and reactions. A strong bond with an online therapist was associated with lower loneliness and higher perceived social support at mid-treatment, lower social anxiety at post-treatment as well as a higher number of reactions made on the social network. Stronger alliance with the platform's tasks and goals facilitated lower social anxiety at both follow-up assessments and was further associated with higher completion of therapy activities and reactions in the social network. CONCLUSIONS: The alliance may impact aspects of social recovery and usage in digital interventions for FEP. Specific aspects of the alliance (human-human and human-program relationships) should be considered in future research.