OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1.

Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres.

Capture of RNA G-quadruplex structures using an l-RNA aptamer.

G-quadruplexes (dG4 and rG4) are nucleic acid secondary structures formed by the self-assembly of certain G-rich sequences, and they have distinctive chemical properties and play crucial roles in fundamental biological processes. Small molecule G4 ligands were shown to be crucial in characterizing G4s and understanding their functions. Nevertheless, concerns regarding the specificity of these synthetic ligands for further investigation of G4s, especially for rG4 isolation purposes, have been raised.

UBE2D3 facilitates NHEJ by orchestrating ATM signalling through multi-level control of RNF168.

Maintenance of genome integrity requires tight control of DNA damage response (DDR) signalling and repair, with phosphorylation and ubiquitination representing key elements. How these events are coordinated to achieve productive DNA repair remains elusive. Here we identify the ubiquitin-conjugating enzyme UBE2D3 as a regulator of ATM kinase-induced DDR that promotes non-homologous end-joining (NHEJ) at telomeres.

Congenital cholesteatoma: what radiologists need to know.

Congenital cholesteatoma is a rare, non-neoplastic lesion that causes conductive hearing loss in children. It is underrecognized and often diagnosed only when there is an established hearing deficit. In the pediatric population, hearing deficiency is particularly detrimental because it can impede speech and language development and, in turn, the social and academic well-being of affected children.

Acute kidney injury in children with haematological malignancy: a territory-wide study.

Background: In onco-nephrology, data on acute kidney injury (AKI) among children with haematological malignancies are scarce.

Methods: A retrospective cohort study of all patients in Hong Kong diagnosed with haematological malignancies from 2019 to 2021 before 18 years of age, was conducted to investigate the epidemiology, risk factors and clinical outcomes of AKI during the first year of treatment. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

Case report: Suspected plasmablastic lymphoma in a dog resembling the clinical presentation in humans.

Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A 7-year-old Mongrel dog was presented for a large oral and neck mass.

A Retrospective Study of the Effect of Metformin on Patients with Metastatic Prostate Cancer.

Introduction: Previous studies demonstrated that metformin could lead to an inhibition of proliferation of cancer cells through a shift from anabolic to catabolic metabolism. In this study, we seek to investigate the effect of metformin in metastatic prostate cancer.

Methods: Patients followed at Northwell Health Zuckerberg Cancer Center during 2014-2018 were included if they were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC), with ⩾6 months follow-up with and without metformin treatment.

Capture-SELEX: Selection Strategy, Aptamer Identification, and Biosensing Application.

Small-molecule contaminants, such as antibiotics, pesticides, and plasticizers, have emerged as one of the substances most detrimental to human health and the environment. Therefore, it is crucial to develop low-cost, user-friendly, and portable biosensors capable of rapidly detecting these contaminants. Antibodies have traditionally been used as biorecognition elements.

How Does Topicality Affect the Choice of Referential Form? Evidence From Mandarin.

Many models of reference production suggest that speakers tend to use a reduced referential form, such as a pronoun, to signal the topicality of a particular referent, that is, the Topichood Hypothesis. However, little is known about the precise nature of the mapping between topichood and referential form and the mechanisms by which topichood affects referential form. The current study aims to address these issues by investigating how topicality influences different kinds of reduced expressions, namely, null and overt pronouns in Mandarin.

The role of grammatical role and thematic role predictability in reference form production in Mandarin Chinese.

Evidence suggests that English speakers use pronouns when referring to the grammatical subject and predictable thematic role. We tested how grammatical role and thematic role predictability affect different types of referential forms, namely, overt pronouns and null pronouns in Mandarin Chinese. We found that both overt and null pronouns were sensitive to grammatical role.

Multimodality imaging of extra-nodal lymphoma in the head and neck.

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck. The head and neck region is the second most frequent anatomical site of extra-nodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type.

Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia.

Background: Hypoxic-ischemic encephalopathy (HIE) occurs when an infant's brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19-30% survived with significant disability.

Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine.

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens.

Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti-Helicobacter pylori IgG Titers.

Background & Aims: A genome-wide significant association between anti-Helicobacter pylori (H pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigated this association in an updated genome-wide association study (GWAS) meta-analysis for populations with low gastric cancer incidence, address potential causes of cohort heterogeneity, and explore functional implications of genetic variation at the TLR1/6/10 locus.

Methods: The dichotomous GWAS (25% individuals exhibiting highest anti-H pylori IgG titers vs remaining 75%) included discovery and replication sampls of, respectively, n = 15,685 and n = 9676, all of European ancestry.

A new Hypoxic Ischemic Encephalopathy model in neonatal rats.

Background: Hypoxic-Ischemic Encephalopathy (HIE) occurs when an infant's brain does not receive adequate blood and oxygen supply, resulting in ischemic and hypoxic brain damage during delivery. Currently, supportive care and hypothermia have been the standard treatment for HIE. However, there are still a 20% mortality and most of the survivors are associated with significant neurodevelopmental disability.

Technical challenges regarding the use of formalin-fixed paraffin embedded (FFPE) tissue specimens for the detection of bacterial alterations in colorectal cancer.

Background: Formalin-fixed paraffin embedded (FFPE) tissues may provide an exciting resource to study microbial associations in human disease, but the use of these low biomass specimens remains challenging. We aimed to reduce unintentional bacterial interference in molecular analysis of FFPE tissues and investigated the feasibility of conducting quantitative polymerase chain reaction (qPCR) and 16S rRNA amplicon sequencing using 14 colorectal cancer, 14 normal adjacent and 13 healthy control tissues.

Results: Bacterial contaminants from the laboratory environment and the co-extraction of human DNA can affect bacterial analysis.

Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage.

Background And Purpose: Signal transducer and activator of transcription 3 (STAT3) may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses. Thus, this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage (SAH).

Methods: The SAH model was established by endovascular perforation in the mouse.

Loss of Function Variants in the Zinc Hook Domain Associated with Higher Risk of Familial Esophageal Squamous Cell Carcinoma.

Unbiased whole-exome sequencing approaches in familial esophageal squamous cell carcinoma (ESCC) initially prioritized as a candidate cancer predisposition gene. The combined study with 3289 Henan individuals from Northern China identified two pathogenic protein truncation variants, p.Q672X and a recurrent p.

Information Rate in Humans during Visuomotor Tracking.

Previous investigations concluded that the human brain's information processing rate remains fundamentally constant, irrespective of task demands. However, their conclusion rested in analyses of simple discrete-choice tasks. The present contribution recasts the question of human information rate within the context of visuomotor tasks, which provides a more ecologically relevant arena, albeit a more complex one.

Hybrid Magnetic Resonance Imaging with Single Photon Emission Computed Tomography/Computed Tomography Bone Scan for Diagnosis Of Avascular Necrosis of Femoral Head.

Magnetic resonance imaging (MRI) is a commonly used imaging modality to detect early avascular necrosis (AVN). When MRI is inconclusive, bone scan is helpful in detecting AVN during early phase of the disease. As newer nuclear medicine equipment, such as single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography, are emerging in medical science, the role of these imaging modalities in AVN of femoral head is re-evaluated.

Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci.

Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (T = 4.

COVID-19 in children across three Asian cosmopolitan regions.

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared.