Successful Therapy over 12 Months of People with Cystic Fibrosis with Rare Non-phe508del Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations with Elexacaftor/Tezacaftor/Ivacaftor (ETI).

Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the European Union (EU) for pwCF with non-phe508del mutations is lacking, because data on treatment response in this subgroup are scarce. This retrospective observational study evaluated six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy.

Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system.

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy Tumor Reactive T cell (TRT) Process has been developed.

Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy.

Chimeric antigen receptor (CAR)-T-cell therapy has emerged as a powerful weapon in the fight against cancer. However, its efficacy is often hindered by challenges such as limited tumor penetration, antigen escape, and immune suppression within the tumor microenvironment. This review explores the potential of armored CAR-T cells, or 'micropharmacies', in overcoming these obstacles and enhancing the therapeutic outcomes of adoptive T-cell (ATC) therapy.

Exploring the Effects of Prefrontal Transcranial Direct Current Stimulation on Brain Metabolites: A Concurrent tDCS-MRS Study.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique used to modulates cortical brain activity. However, its effects on brain metabolites within the dorsolateral prefrontal cortex (DLPFC), a crucial area targeted for brain stimulation in mental disorders, remain unclear. This study aimed to investigate whether prefrontal tDCS over the left and right DLPFC modulates levels of key metabolites, including gamma-aminobutyric acid (GABA), glutamate (Glu), glutamine/glutamate (Glx), N-acetylaspartate (NAA), near to the target region and to explore potential sex-specific effects on these metabolite concentrations.

SLAM-seq reveals independent contributions of RNA processing and stability to gene expression in African trypanosomes.

Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control.

The Use of the Facial Sinus Wall as Bone Shell Onlay Graft for Maxillary Posterior Ridge Reconstruction: A Retrospective Case Series.

Purpose: To evaluate the performance and clinical outcome of vertical and horizontal bone augmentation (VHBA) in posterior maxillary regions combining lateral window sinus floor elevation (LWSFE) with a horizontal bone shell technique applying the maxillary facial sinus wall as a bone plate.

Materials And Methods: In 18 patients, LWSFE was combined with a horizontal bone shield augmentation procedure utilizing the maxillary facial sinus bone wall as a lateral bone plate. Both the sinus cavity and the lateral bone box created were grafted with a mixture of autogenous bone/venous blood and bovine bone mineral.

The impact of a ketogenic diet on weight loss, metabolism, body composition and quality of life.

A ketogenic diet (KD) is increasingly debated as a countermeasure against nutrition-related modern diseases. While being immunologically beneficial, KD is still suspected of having severe metabolic side effects and negatively impacting general well-being, which prevents its widespread clinical use. We conducted a prospective pre-post interventional study investigating the effects of an eucaloric KD on metabolism, weight loss, body composition, diet adherence, and quality of life.

STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease.

Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied.

Methods: We present the first evaluation of XBB.

Entrainment of neural oscillations during language processing in Early-Stage schizophrenia.

Background: Impairments in language processing in schizophrenia (ScZ) are a central aspect of the disorder but the underlying pathophysiology mechanisms are unclear. In the current study, we tested the hypothesis that neural oscillations are impaired during speech tracking in early-stage ScZ and in participants at clinical high-risk for psychosis (CHR-P).

Method: Magnetoencephalography (MEG) was used in combination with source reconstructed time-series to examine delta and theta-band entrainment during continuous speech.

Tau-network mapping of domain-specific cognitive impairment in Alzheimer's disease.

Fibrillar tau gradually progresses in the brain during the course of Alzheimer's disease (AD). However, the contribution of tau accumulation in a given brain region to decline in different cognitive domains and thus phenotypic heterogeneity in AD remains unclear. Here, we leveraged the functional connectome to link the locality of tau accumulation to domain-specific cognitive impairment.

Surgical site infections after sarcoma resections in the peripelvic region: do we need perioperative antibiotic prophylaxis?

Introduction: Surgical site infections (SSI) are one of the most common complications after extensive sarcoma resections and represent a daily challenge. SSI occur in up to 50% of cases particularly in the peripelvic area. One possible approach to reduce infection rate is perioperative antibiotic prophylaxis.

Spirometric reference equations and lung function testing in adults from Southwestern Tanzania.

Background: The increasing relevance of lung function testing in diagnosing and treating pulmonary diseases globally requires adequate spirometric reference equations. However, locally derived reference standards from African countries are widely missing.

Methods: This cross-sectional study was conducted in Southwestern Tanzania.

Translating efficacy of liver transplantation in liver-limited metastatic colorectal cancer into clinical practice: the TransMet trial.

Pioneer studies suggested that liver transplantation (LT) has the potential to provide long-term survival in patients with liver-limited metastatic colorectal cancer (mCRC) not amenable for surgery of metastases. Evidence, however, was limited to single-arm studies with few patients enrolled and suboptimal selection criteria, with concerns over access to organ availability overcoming the potential efficacy of LT in this setting. Recently, 5-year survival rates with chemotherapy followed by LT (73%) compared with chemotherapy alone (9%) have been demonstrated by the randomized TransMet trial, enrolling 94 definitively unresectable strictly selected liver-limited mCRC patients.

Extracellular vesicle-mediated trafficking of molecular cues during human brain development.

Cellular crosstalk is an essential process influenced by numerous factors, including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neurodegenerative disorders, but whether EVs display cell-type-specific features for cellular crosstalk during neurodevelopment is unknown. Here, using human-induced pluripotent stem cell-derived cerebral organoids, neural progenitors, neurons, and astrocytes, we identify heterogeneity in EV protein content and dynamics in a cell-type-specific and time-dependent manner.

Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics: a state-of-the-art clinical review.

Introduction: People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes.

Areas Covered: We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics.

Clinical and pathological characterization of tebentafusp-associated skin toxicity: A cohort study with 33 patients.

Background: Tebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects.

Objectives: The aim of this study was to better characterize these heterogenous cutaneous side effects.

Methods: This prospective cohort study evaluated all patients from a tertiary hospital center who were treated with tebentafusp between January 2019 and June 2023 clinically and assessed skin biopsies histologically.

Characterization of the neuropathic pain component contributing to myalgia in patients with myotonic dystrophy type 1 and 2.

Introduction: Chronic muscle pain is common in myotonic dystrophies (DM). Little is known about its pathophysiology. We aimed to investigate the characteristics of the neuropathic pain component contributing contributes to the pathogenesis of chronic pain in DM.

Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators.

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia.

Factors influencing timely diagnosis in neurolymphomatosis.

Background: Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in neurolymphomatosis and factors delaying diagnosis have not been evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort.

Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors.

Chimeric antigen receptor T cell therapy has been established in the treatment of various B cell malignancies. However, translating this therapeutic effect to treat solid tumors has been challenging because of their inter-tumoral as well as intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such as surgery, radiotherapy, local ablation, and locoregional drug delivery, can enhance chimeric antigen receptor T cell therapy in solid tumors by improving tumor infiltration and reducing systemic toxicities.