Evolutionary origins and functional diversification of Auxin Response Factors.

The Auxin Response Factors (ARFs) family of transcription factors are the central mediators of auxin-triggered transcriptional regulation. Functionally different classes of extant ARFs operate as antagonistic auxin-dependent and -independent regulators. While part of the evolutionary trajectory to the present auxin response functions has been reconstructed, it is unclear how ARFs emerged, and how early diversification led to functionally different proteins.

Can blood-flow restriction resistance training enhance remote strength transfer? A systematic review with meta-analysis.

Objectives: This systematic review with meta-analysis aimed to examine the effect of blood flow restriction resistance training (BFR-RT) on strength gains in untrained limbs (remote strength transfer [RST]).

Literature Survey: A search for studies was performed using six databases (PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, SPORTDiscus, and ScienceDirect) up to February 2024.

Methodology: Studies that assessed the RST phenomenon following BFR-RT and measured muscle strength were included.

Impact of pharmacist-led interventions in identifying and resolving drug related problems and potentially inappropriate prescriptions among rural patients: A pilot study.

Background: Drug-related problems are a major problem that can lead to increased morbidity, mortality, and healthcare costs due to heightened medical visits, hospital readmissions, or emergency room visits. In rural areas, new tools for clinical pharmacy services, such as medication review, could decrease this problem.

Objective: To analyze the prevalence of clinically relevant drug-related problems (DRPs) and potentially inappropriate prescriptions (PIPs) identified by new medication review software (Revisem®) in rural pharmacies.

The dose-response of the Copenhagen adduction exercise on adductor strength in high-level youth hockey players: A three-arm randomised controlled trial.

The aim of this cluster-randomised controlled trial was to investigate the training and detraining effects of two different-volume Copenhagen Adduction Exercise (CAE) protocols on adductor squeeze strength. Thirty high-level rink hockey players (14 y.o.

Oxygen control in bioreactor drives high yield production of functional hiPSC-like hepatocytes for advanced liver disease modelling.

Hepatocytes-like cells (HLC) derived from human induced pluripotent stem cells show great promise for cell-based liver therapies and disease modelling. However, their application is currently hindered by the low production yields of existing protocols. We aim to develop a bioprocess able to generate high numbers of HLC.

Acidity suppresses CD8 + T-cell function by perturbing IL-2, mTORC1, and c-Myc signaling.

CD8 + T cells have critical roles in tumor control, but a range of factors in their microenvironment such as low pH can suppress their function. Here, we demonstrate that acidity restricts T-cell expansion mainly through impairing IL-2 responsiveness, lowers cytokine secretion upon re-activation, and reduces the cytolytic capacity of CD8 + T cells expressing low-affinity TCR. We further find decreased mTORC1 signaling activity and c-Myc levels at low pH.

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.

Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8 cells that preferentially infiltrated tumors post-ACT.

Design and development of a new pictorial tool to facilitate communication around advance care planning.

Background: Advance care planning (ACP) aims to ensure that people with chronic or advanced disease receive medical care that is consistent with their values and preferences. However, professionals may find it challenging to engage these patients in conversations about the end of life. We sought to develop a pictorial tool to facilitate communication around ACP.

The Wish to Hasten Death in Patients With Life-Limiting Conditions. A Systematic Overview.

Context: A systematic review of the wish to hasten death among people with life-limiting conditions was published in 2011. Since then, other reviews and primary studies have been published that have added to knowledge regarding the conceptual definition, aetiology and assessment of the wish to hasten death.

Objectives: To provide an updated synthesis of the literature on the wish to hasten death in people with life-limiting conditions.

PGE inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

Expansion of antigen-experienced CD8 T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer. Interleukin-2 (IL-2) acts as a key regulator of CD8 cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses.

Correction: Crespo et al. Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway. 2017, , 288.

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Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8 T-myeloid cell networks in melanoma.

Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell-intrinsic immunogenicity and mutational burden.

Definition and validation of the nursing diagnosis label "wish to die": a research protocol.

Background: Euthanasia has been incorporated into the health services of seven countries. The legalisation of these practices has important repercussions for the competences of nurses, and it raises questions about their role. When a patient with advanced disease expresses a wish to die, what is expected of nurses? What are the needs of these patients, and what kind of care plan do they require? What level of autonomy might nurses have when caring for these patients? The degree of autonomy that nurses might or should have when it comes to addressing such a wish and caring for these patients has yet to be defined.

Activation of the transcription factor NFAT5 in the tumor microenvironment enforces CD8 T cell exhaustion.

Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8 T cells in the context of chronic infections and tumors but was selectively required in tumor-induced CD8 T cell exhaustion.

Development of a Guide to Multidimensional Needs Assessment in the Palliative Care Initial Encounter (MAP).

Context: Ensuring patient-centered palliative care requires a comprehensive assessment of needs beginning in the initial encounter. However, there is no generally accepted guide for carrying out this multidimensional needs assessment as a first step in palliative intervention.

Objectives: To develop an expert panel-endorsed interview guide that would enable proactive and systematic Multidimensional needs Assessment in the Palliative care initial encounter (MAP).

Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior.

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of in the nervous system ( ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by mice disappeared in mice in the open field and rota-rod tests.

Fully automatic tracking of native glenohumeral kinematics from stereo-radiography.

The current work introduces a system for fully automatic tracking of native glenohumeral kinematics in stereo-radiography sequences. The proposed method first applies convolutional neural networks to obtain segmentation and semantic key point predictions in biplanar radiograph frames. Preliminary bone pose estimates are computed by solving a non-convex optimization problem with semidefinite relaxations to register digitized bone landmarks to semantic key points.

Experiences of Isolation among Patients Hospitalized during an Infectious Disease Outbreak: A Systematic Review and Meta-Ethnography.

Hospital isolation is common for people during infectious disease outbreaks. Anxiety, stress, depression and other psychosocial outcomes have been reported due to these measures. However, there is scarce evidence about the experience of being isolated and about best practices for empathic clinical care in these circumstances.

Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8 T cells.

To date, no immunotherapy approaches have managed to fully overcome T-cell exhaustion, which remains a mandatory fate for chronically activated effector cells and a major therapeutic challenge. Understanding how to reprogram CD8 tumor-infiltrating lymphocytes away from exhausted effector states remains an elusive goal. Our work provides evidence that orthogonal gene engineering of T cells to secrete an interleukin (IL)-2 variant binding the IL-2Rβγ receptor and the alarmin IL-33 reprogrammed adoptively transferred T cells to acquire a novel, synthetic effector state, which deviated from canonical exhaustion and displayed superior effector functions.

Injury characteristics of young elite inline speed skaters: A one season retrospective study.

Objectives: Determining the rate of injuries related to a certain sport is accepted as the primary step toward designing, implementing and evaluating injury prevention programs. This observational and retrospective study was to examine the injuries sustained by elite young Spanish inline speed skaters during a season.

Methods: Athletes participating in the national championship ( = 80) were surveyed via an anonymous online questionnaire to screen for injury characteristics: incidence, location, and tissue affected; plus training information and demographics.

A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53.

Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (Rco) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology.