Joint TITE-CRM: A Design for Dose Finding Studies for Therapies with Late-Onset Safety and Activity Outcomes.

In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and shows sufficient activity that maximizes some optimality criterion based on safety and activity. In cancer, treatment is typically given over several cycles, complicating the identification of the OBD as both toxicity and activity outcomes may occur at any point throughout the follow up of multiple cycles. In this work we present and assess the Joint TITE-CRM, a model-based design for late onset toxicities and activity based on the well-known TITE-CRM.

Comparison of dark-field chest radiography and CT for the assessment of COVID-19 pneumonia.

Background: Dark-field chest radiography allows the assessment of the structural integrity of the alveoli by exploiting the wave properties of x-rays.

Purpose: To compare the qualitative and quantitative features of dark-field chest radiography in patients with COVID-19 pneumonia with conventional CT imaging.

Materials And Methods: In this prospective study conducted from May 2020 to December 2020, patients aged at least 18 years who underwent chest CT for clinically suspected COVID-19 infection were screened for participation.

Case report: Dirofilarial infection of the face.

An 18-year-old male patient from Ukraine, living in Germany for 2 years, presented with a painless subcutaneous swelling on the left cheek that had been present for several months. Finally, the diagnosis of subcutaneous dirofilariasis caused by was confirmed by 12S rRNA gene PCR and sequencing from tissue by nematode-specific PCRs followed by sequencing after surgical resection of the lesion. Microfilaremia was ruled out and no further treatment was required.

Advances in gastrointestinal vascular bleeding disorders: Successful sirolimus treatment in colonic angioectasia.

Background: Gastrointestinal (GI) vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment responses. Despite advancements in diagnostic and therapeutic techniques, optimal management strategies remain elusive, necessitating further research.

Aim: To assess research trends and clinical advancements in GI vascular bleeding disorders, highlighting key themes and therapeutic progress.

Heart Failure in Atrial Fibrillation Subtypes in Women and Men in the Tromsø Study.

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and impact morbidity and mortality. There is limited knowledge on the association of AF subtypes with HF according to sex.

Objectives: The purpose of this study was to explore sex-specific associations between AF subtypes and subsequent HF, identifying HF risk factors in participants with AF, and exploring the combined impact on mortality.

Elevated Plasma CXCL8 Concentrations in Significant Fibrosis but Not in Subclinical Rejection After Adult Liver Transplantation.

Background: The noninvasive detection of subclinical graft injury including subclinical T cell-mediated rejection (subTCMR) is one of the unresolved challenges after liver transplantation. Recently, serum C-X-C motif chemokine ligand 8 (CXCL8) was proposed as a highly accurate marker of subTCMR in pediatric liver transplant recipients. We aimed to evaluate the accuracy of the quantification of this chemokine for predicting subTCMR in adult liver transplant recipients, as well as its capacity to classify patients who could benefit from immunosuppression reduction.

Reactivity of Wet scCO toward Reservoir and Caprock Formations under Elevated Pressure and Temperature Conditions: Implications for CCS and CO-Based Geothermal Energy Extraction.

Carbon capture and storage (CCS) and CO-based geothermal energy are promising technologies for reducing CO emissions and mitigating climate change. Safe implementation of these technologies requires an understanding of how CO interacts with fluids and rocks at depth, particularly under elevated pressure and temperature. While CO-bearing aqueous solutions in geological reservoirs have been extensively studied, the chemical behavior of water-bearing supercritical CO remains largely overlooked by academics and practitioners alike.

Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword.

Gliomas are the most common lethal tumors of the brain associated with a poor prognosis and increased resistance to chemo-radiotherapy. Circular RNAs (circRNAs), newly identified noncoding RNAs, have appeared as critical regulators of therapeutic resistance among multiple cancers and gliomas. Since circRNAs are aberrantly expressed in glioma and may act as promoters or inhibitors of therapeutic resistance, we categorized alterations of these specific RNAs expression in therapy resistant-glioma in three different classes, including chemoresistance, radioresistance, and glioma stem cell (GSC)-regulation.

Physiological arterial pressure improves renal performance during normothermic machine perfusion in a porcine kidney DCD model.

Background: Normothermic machine perfusion (NMP) provides a platform for kidney quality assessment. Donation after circulatory death (DCD) donor kidneys are associated with great ischemic injury and high intrarenal resistance (IRR). This experimental study aims to investigate the impact of different perfusion pressures on marginal kidney function and injury during NMP.

A framework to evaluate public green spaces with an emphasis on recreational values for sustainable urban and rural areas: A systematic review and content analysis.

Though numerous studies acknowledge the critical role played by green spaces (GS) in bolstering sustainability in various dimensions, a majority of these investigations primarily center on the ecological aspect and urban environments. Due to the multifaceted benefits of GSs, different categories and expectations of these spaces can be identified across disciplines. Hence, no single method exists for evaluating the success of GSs in promoting sustainability due to the multifaceted benefits and variety of expectations.

The impact of preoperative venous thromboembolism on patients undergoing TURBT: Perioperative outcomes and healthcare costs from US insurance claims data.

Objectives: To assess the impact of a positive history of venous thromboembolism (VTE) on perioperative outcomes, including length of in-hospital stay, readmission rates, 90-day postoperative complications, and healthcare costs in bladder cancer (BCa) patients undergoing transurethral resection of bladder tumour (TURBT) in the United States.

Patients And Methods: Patients aged ≥18 years with a BCa diagnosis undergoing TURBT were identified in the Merative® Marketscan® Research de-identified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between diagnosis of VTE before TURBT and 90-day complication rates, new postoperative VTE events, re-hospitalization, and total hospital expenditures (2021 US dollars).

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

The design space of E(3)-equivariant atom-centred interatomic potentials.

Molecular dynamics simulation is an important tool in computational materials science and chemistry, and in the past decade it has been revolutionized by machine learning. This rapid progress in machine learning interatomic potentials has produced a number of new architectures in just the past few years. Particularly notable among these are the atomic cluster expansion, which unified many of the earlier ideas around atom-density-based descriptors, and Neural Equivariant Interatomic Potentials (NequIP), a message-passing neural network with equivariant features that exhibited state-of-the-art accuracy at the time.

Unraveling the Role of Water in Isothermal Methanol Partial Oxidation to Methyl Formate on Gold: A Combined Experimental and Computational Study.

Since water is both a product and a common reactant impurity in the (partial) methanol oxidation to methyl formate (MeFo) on gold, its effect on the isothermal selectivity to methyl formate was investigated under well-defined single-collision conditions employing pulsed molecular beam experiments and in situ IRAS measurements. Both a flat Au(111) and a stepped Au(332) surface were used as model catalysts to elucidate how water affects the reactivity of low-coordinated step sites as compared to (111) terrace sites employing a range of reaction conditions. The interactions of water with methanol/methoxy as well as with oxygen species are addressed.

Evaluating the Mechanical Axis for Detection of Posterior Tibial Slope Malalignment in ACL-Deficient Knees on Lateral Radiographs.

Background: Distal tibial deformities are not assessed using the proximal anatomical axis (PAA) to determine the posterior tibial slope (PTS). Therefore, it seems advantageous to measure PTS on full-length lateral tibial radiographs using the mechanical axis (MA).

Purposes: To (1) compare the PTS measurements using the MA and the PAA and (2) determine whether using the PAA fails to detect a certain number of significantly elevated PTS values compared with using the MA.

Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Experience from the RADAR study.

Arterial spin labelling (ASL) enables non-invasive quantification of regional brain perfusion using MRI. ASL was used in the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) multi-centre trial to pilot the assessment of the effects of the anti-hypertension drug losartan on cerebral blood flow (CBF). In the multi-centre setting, disparities in ASL implementation on scanners from different manufacturers lead to inherent differences in measured CBF and its associated parameters (e.

C-reactive protein and association with disease severity in hospitalized adult patients with Lassa fever in Nigeria.

Objectives: Lassa fever (LF) poses a significant health burden in West Africa. The pathophysiology of LF and determinants of clinical spectrum of disease remain poorly understood. We performed a study to understand the correlation of blood inflammatory marker C-reactive protein (CRP), with LF disease severity.

MLL-AF4 upregulates 5-lipoxygenase expression in t(4;11) leukemia cells via the ALOX5 core promoter.

5-Lipoxygenase (5-LO), encoded by the gene , is implicated in several pathologies. As key enzyme in leukotriene biosynthesis, 5-LO plays a central role in inflammatory diseases, but the 5-LO pathway has also been linked to development of certain hematological and solid tumor malignancies. Of note, previous studies have shown that the leukemogenic fusion protein MLL-AF4 strongly increases gene promoter activity.

Pitfalls in Early Bioprocess Development Using Shake Flask Cultivations.

For about 100 years, the shake flask has been established for biotechnological cultivations as one of the most important cultivation systems in early process development. Its appeal lies in its simple handling and highly versatile application for a wide range of cell types-from bacteria to mammalian cells. In recent decades, extensive research has been conducted on the shake flask, to not perform processes blindly but to gain a deeper understanding of the various process parameters, phenomena, and their impact on the process.

Comparison of immune responses to SARS-CoV-2 spike following Omicron infection or Omicron BA.4/5 vaccination in kidney transplant recipients.

Background: The emergence of novel SARS-CoV-2 variants challenges immunity, particularly among immunocompromised kidney transplant recipients (KTRs). To address this, vaccines have been adjusted to circulating variants. Despite intensive vaccination efforts, SARS-CoV-2 infections surged among KTRs during the Omicron wave, enabling a direct comparison of variant-specific immunity following-vaccination against Omicron BA.

Iron improves the antiviral activity of NK cells.

Natural killer (NK) cells are innate immune cells that play a crucial role as a first line of defense against viral infections and tumor development. Iron is an essential nutrient for immune cells, but it can also pose biochemical risks such as the production of reactive oxygen species. The importance of iron for the NK cell function has gained increasing recognition.

Terminal complement complex deposition on chondrocytes promotes premature senescence in age- and trauma-related osteoarthritis.

Background: The complement system is locally activated after joint injuries and leads to the deposition of the terminal complement complex (TCC). Sublytic TCC deposition is associated with phenotypical alterations of human articular chondrocytes (hAC) and enhanced release of inflammatory cytokines. Chronic inflammation is a known driver of chondrosenescence in osteoarthritis (OA).

Short-term survivors with brain metastases have modest benefits from focal and systemic therapies and remain frequent despite improving treatment landscape.

Purpose: Therapeutic options for patients with brain metastases (BM) increase. While these lead to considerable survival effects in subgroups, there is limited knowledge about characteristics, prognosticators and treatment effects in patients with BM and short survival.

Methods: Patients with a survival time of ≤ 6 months (short-term survivors, STS), diagnosed with BM between 2009-2021 at a large tertiary cancer center were analysed.