Longitudinal outcomes of iStent inject with cataract surgery compared to cataract surgery alone: real-world data from the Fight Glaucoma Blindness registry.

Purpose: To compare combined phacoemulsification and iStent inject to phacoemulsification alone.

Setting: Fight Glaucoma Blindness (FGB) registry - Australia.

Design: Prospective observational registry study.

Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.

Chromosome Region Maintenance 1 (CRM1), also known as Exportin 1 (XPO1), is a protein that is critical for transport of proteins and RNA to the cytoplasm through the nuclear pore complex. CRM1 inhibition with small molecule inhibitors is currently being studied in many cancers, including leukemias, solid organ malignancies and brain tumors. We review the structure of CRM1, its role in nuclear export, the current availability of CRM1 inhibitors, and the role of CRM1 in a number of distinct cellular processes.

Prototypical innate immune mechanism hijacked by leukemia-initiating mutant stem cells for selective advantage and immune evasion in Ptpn11-associated juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML), a clonal hematologic malignancy, originates from mutated hematopoietic stem cells (HSCs). The mechanism sustaining the persistence of mutant stem cells, leading to leukemia development, remains elusive. In this study, we conducted comprehensive examination of gene expression profiles, transcriptional factor regulons, and cell compositions/interactions throughout various stages of tumor cell development in Ptpn11 mutation-associated JMML.

Outcomes and Baseline Predictors of Failure in Primary Standalone Xen45 Gel Stent versus Trabeculectomy for Glaucoma.

Purpose: To compare safety, effectiveness, and baseline predictors of failure in standalone primary Xen45 gel stent (Xen) versus trabeculectomy (Trab) in glaucoma.

Design: Retrospective study.

Subjects: Subjects that underwent primary Xen or Trab augmented by mitomycin-C with at least 12 months follow-up.

Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed -rearranged acute lymphoblastic leukemia: Children's Oncology Group trial AALL15P1.

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of failure to achieve remission, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies.

Outcomes of iStent inject combined with cataract surgery in Asian eyes: Australian data from the Fight Glaucoma Blindness international registry.

Purpose: To analyse real-world outcomes in Asian eyes of iStent inject, a second-generation trabecular micro-bypass stent, combined with phacoemulsification.

Methods: This is a multi-centre, observational study of glaucomatous Asian eyes that have undergone iStent inject implantation combined with cataract surgery. Patient data were extracted from the Fight Glaucoma Blindness! Registry.

Mechanistic interactions as the origin of modularity in biological networks.

Biological networks are often modular. Explanations for this peculiarity either assume an adaptive advantage of a modular design such as higher robustness, or attribute it to neutral factors such as constraints underlying network assembly. Interestingly, most insights on the origin of modularity stem from models in which interactions are either determined by highly simplistic mechanisms, or have no mechanistic basis at all.

Comparing findings from the random-intercept cross-lagged panel model and the monozygotic twin difference cross-lagged panel model: Maladaptive parenting and offspring emotional and behavioural problems.

Background: In this study we compare results obtained when applying the monozygotic twin difference cross-lagged panel model (MZD-CLPM) and a random intercept cross-lagged panel model (RI-CLPM) to the same data. Each of these models is designed to strengthen researchers' ability to draw causal inference from cross-lagged associations. We explore differences and similarities in how each model does this, and in the results each model produces.

Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia.

Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets.

Assessing aetiological overlap between child and adult attention-deficit hyperactivity disorder symptoms in an extended family design.

Background: Several longitudinal studies have cast doubt on the aetiological overlap between child and adult attention-deficit hyperactivity disorder (ADHD). However, a lack of genetically sensitive data following children across adulthood precludes direct evaluation of aetiological overlap between child and adult ADHD.

Aims: We circumvent the existing gap in longitudinal data by exploring genetic overlap between maternal (adult) and offspring (child) ADHD and comorbid symptoms in an extended family cohort.

Socioeconomic status and risk for child psychopathology: exploring gene-environment interaction in the presence of gene-environment correlation using extended families in the Norwegian Mother, Father and Child Birth Cohort Study.

Background: Low socioeconomic status (SES) is associated with increased risk for emotional and behavioural problems among children. Evidence from twin studies has shown that family SES moderates genetic and environmental influences on child mental health. However, it is also known that SES is itself under genetic influence and previous gene-environment interaction (G×E) studies have not incorporated the potential genetic overlap between child mental health and family SES into G×E analyses.

Evaluation for Bleeding Disorders in Suspected Child Abuse.

Bruising or bleeding in a child can raise the concern for child abuse. Assessing whether the findings are the result of trauma and/or whether the child has a bleeding disorder is critical. Many bleeding disorders are rare, and not every child with bruising/bleeding that may raise a concern for abuse requires an evaluation for bleeding disorders.

Comprehensive Genomic Profiling of High-Risk Pediatric Cancer Patients Has a Measurable Impact on Clinical Care.

Purpose: Profiling of pediatric cancers through deep sequencing of large gene panels and whole exomes is rapidly being adopted in many clinical settings. However, the most impactful approach to genomic profiling of pediatric cancers remains to be defined.

Methods: We conducted a prospective precision medicine trial, using whole-exome sequencing of tumor and germline tissue and whole-transcriptome sequencing (RNA Seq) of tumor tissue to characterize the mutational landscape of 127 tumors from 126 unique patients across the spectrum of pediatric brain tumors, hematologic malignancies, and extracranial solid tumors.

Production of Putrescine and Cadaverine by .

Lactic acid bacteria (LAB) play a key role in many food fermentations. However, some LAB species can also cause food spoilage, e.g.

Cheating in Mutualisms Promotes Diversity and Complexity.

AbstractMutualisms such as those between flowering plants and their pollinators are common in nature. Yet understanding their persistence in the face of cheaters and identifying the mechanisms behind their stunning diversity provide formidable challenges for evolutionary biologists. To shed light onto these questions, we introduce an individual-based model of two coevolving species in which individuals of one species use a Boolean circuit to discriminate between cooperators and cheaters in the other species.

High-throughput qPCR and 16S rRNA gene amplicon sequencing as complementary methods for the investigation of the cheese microbiota.

Background: Next-generation sequencing (NGS) methods and especially 16S rRNA gene amplicon sequencing have become indispensable tools in microbial ecology. While they have opened up new possibilities for studying microbial communities, they also have one drawback, namely providing only relative abundances and thus compositional data. Quantitative PCR (qPCR) has been used for years for the quantification of bacteria.

Multicenter Analysis of Genomically Targeted Single Patient Use Requests for Pediatric Neoplasms.

Purpose: The US Food and Drug Administration-expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer.

Wet-Chemically Prepared Porphyrin Layers on Rutile TiO(110).

Porphyrins are large organic molecules that are interesting for different applications, such as photovoltaic cells, gas sensors, or in catalysis. For many of these applications, the interactions between adsorbed molecules and surfaces play a crucial role. Studies of porphyrins on surfaces typically fall into one of two groups: (1) evaporation onto well-defined single-crystal surfaces under well-controlled ultrahigh vacuum conditions or (2) more application-oriented wet chemical deposition onto less well-defined high surface area surfaces under ambient conditions.

Five-Year Outcomes of Trabeculectomy and Phacotrabeculectomy.

Purpose The purpose of this study is to examine five-year outcomes of trabeculectomy and compare the stand-alone procedure when combined with phacoemulsification. Patients and methods This study included 123 eyes of 109 patients, with 79 patients in the trabeculectomy group and 44 patients in the phacotrabeculectomy group. Non-randomized comparative cohort study with data collected retrospectively from an existing database compiled by a single surgeon operating in Sydney, Australia from 2007 to 2019.