Profiling the Roles and Responsibilities of Professionals and Non-Professionals Providing Speech Language Services for Individuals with CLP in Resource-Limited Regions.

Fourteen Speech and Language Therapists/Pathologists (SLT/Ps) from 13 countries across 5 continents made up the International Confederation of Cleft Lip and Palate and Related Craniofacial Anomalies (ICCPCA) CLEFT 2022 Speech Taskforce. Following a group consensus activity led by an external facilitator using Lightning Design Thinking principles, "task-shifting" was identified as the topic for this Taskforce. Absence and scarcity of SLT/Ps in many parts of the world have led to non-SLT/Ps delivering speech and language therapy services to individuals with cleft lip +/- palate.

Online survey of consumer awareness and perceptions of a Massachusetts law for 12-month supply of contraception.

Objectives: This study aimed to characterize awareness of a 2017 Massachusetts (MA) law that ensures access to a 12-month supply of short-acting contraceptive methods (e.g., pill, patch, and vaginal ring) among short-acting contraceptive users in MA and to identify perceived benefits and concerns of a 12-month supply.

Examining the effects of physician burnout on pain management for patients with advanced lung cancer.

Purpose: Physician burnout is generally associated with worse clinical outcomes. The purpose of this study is to examine the effects of physician burnout on the quality of physicians' pain assessment and opioid prescribing for patients with advanced lung cancer. Moreover, we test whether these relationships are moderated by patient-level factors, such as patient race and activation level, that have a demonstrated impact on clinical encounters.

Global partnerships to create communication resources addressing Sustainable Development Goals 3, 4, 8, 10, and 17.

Purpose: This commentary describes the development of global partnerships, capacity-building, and the basis for the creation of a website (Leadersproject.org) used throughout the world that contains free educational resources for the assessment and treatment of people with communication disabilities (PWCD). This website contains speech-language assessment and treatment materials, online skill-building courses, over 200 instructional videos, train-the-trainer course materials, and syntheses of important research and trainings in over 30 languages.

The role of social networks in prognostic understanding of older adults with advanced cancer.

Objectives: Explore how older patients utilize their social networks to inform prognostic understanding.

Methods: In a pilot study of adults (≥65 years old) with advanced cancer, 16 patients completed surveys, social network maps, and semi-structured interviews exploring with whom they preferred to communicate about their illness. Interviews were analyzed using open-coding, and codes were categorized into emergent themes.

Patient activation reduces effects of implicit bias on doctor-patient interactions.

Disparities between Black and White Americans persist in medical treatment and health outcomes. One reason is that physicians sometimes hold implicit racial biases that favor White (over Black) patients. Thus, disrupting the effects of physicians' implicit bias is one route to promoting equitable health outcomes.

Polypharmacy, Potentially Inappropriate Medications, and Drug-Drug Interactions in Vulnerable Older Adults With Advanced Cancer Initiating Cancer Treatment.

Purpose: Polypharmacy is prevalent in older adults starting cancer treatment and associated with potentially inappropriate medications (PIM), potential drug-drug interactions (DDI), and drug-cancer treatment interactions (DCI). For a large cohort of vulnerable older adults with advanced cancer starting treatment, we describe patterns of prescription and nonprescription medication usage, the prevalence of PIM, and the prevalence, severity, and type of DDI/DCI.

Methods: This secondary analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment (University of Rochester Cancer Center [URCC] 13059; PI: Mohile).

SARS-CoV-2 in Quarantined Domestic Cats from COVID-19 Households or Close Contacts, Hong Kong, China.

We tested 50 cats from coronavirus disease households or close contacts in Hong Kong, China, for severe acute respiratory syndrome coronavirus 2 RNA in respiratory and fecal samples. We found 6 cases of apparent human-to-feline transmission involving healthy cats. Virus genomes sequenced from 1 cat and its owner were identical.

Infection of dogs with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19). In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2.

The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability.

The Cdc28 protein kinase subunits, Cks1 and Cks2, play dual roles in Cdk-substrate specificity and Cdk-independent protein degradation, in concert with the E3 ubiquitin ligase complexes SCF and APC. Notable targets controlled by Cks include p27 and Cyclin A. Here, we demonstrate that Cks1 and Cks2 proteins interact with both the Mll and Mll subunits of Mll1 (Mixed-lineage leukaemia 1), and together, the Cks proteins define Mll1 levels throughout the cell cycle.

Deficiency of Cks1 Leads to Learning and Long-Term Memory Defects and p27 Dependent Formation of Neuronal Cofilin Aggregates.

In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in post-mitotic neurons of the adult hippocampus. Interestingly, Cks1 knockout (Cks1-/-) mice exhibited poor long-term memory, and diminished maintenance of long-term potentiation in the hippocampal circuits.

Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival.

Inhibition of the vascular endothelial growth factor (VEGF) pathway has failed to improve overall survival of patients with glioblastoma (GBM). We previously showed that angiopoietin-2 (Ang-2) overexpression compromised the benefit from anti-VEGF therapy in a preclinical GBM model. Here we investigated whether dual Ang-2/VEGF inhibition could overcome resistance to anti-VEGF treatment.

Deficiency of the cyclin-dependent kinase inhibitor, CDKN1B, results in overgrowth and neurodevelopmental delay.

Germline mutations in the cyclin-dependent kinase inhibitor, CDKN1B, have been described in patients with multiple endocrine neoplasia (MEN), a cancer predisposition syndrome with adult onset neoplasia and no additional phenotypes. Here, we describe the first human case of CDKN1B deficiency, which recapitulates features of the murine CDKN1B knockout mouse model, including gigantism and neurodevelopmental defects. Decreased mRNA and protein expression of CDKN1B were confirmed in the proband's peripheral blood, which is not seen in MEN syndrome patients.

The CDK subunit CKS2 counteracts CKS1 to control cyclin A/CDK2 activity in maintaining replicative fidelity and neurodevelopment.

CKS proteins are evolutionarily conserved cyclin-dependent kinase (CDK) subunits whose functions are incompletely understood. Mammals have two CKS proteins. CKS1 acts as a cofactor to the ubiquitin ligase complex SCF(SKP2) to promote degradation of CDK inhibitors, such as p27.

Dia2 controls transcription by mediating assembly of the RSC complex.

Background: Dia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF.

Cks1, Cdk1, and the 19S proteasome collaborate to regulate gene induction-dependent nucleosome eviction in yeast.

Cks1, Cdk1 (Cdc28), and the proteasome are required for efficient transcriptional induction of GAL1 and other genes in Saccharomyces cerevisiae. We show here that one function of these proteins is to reduce nucleosome density on chromatin in a gene induction-specific manner. The transcriptional requirement for Cks1 can be bypassed if nucleosome density is reduced by an alternative pathway, indicating that this is the primary function of Cks1 in the context of gene induction.

Cks1 activates transcription by binding to the ubiquitylated proteasome.

Cyclin-dependent kinase-associated protein 1 (Cks1) is involved in the control of the transcription of a subset of genes in addition to its role in controlling the cell cycle in the budding yeast Saccharomyces cerevisiae. By directly ligating Cks1 onto a GAL1 promoter-driven reporter, we demonstrated that Cks1 acts as a transcription activator. Using this method, we dissected the downstream events from Cks1 recruitment at the promoter.

CKS proteins protect mitochondrial genome integrity by interacting with mitochondrial single-stranded DNA-binding protein.

Cyclin-dependent kinase subunit (CKS) proteins interact with cyclin-dependent kinases (CDKs) with high affinity. Mammalian CKS1 and CKS2 bind CDK1 and CDK2 and partake in the control of cell cycle progression. We identified CKS-interacting proteins by affinity purification followed by mass spectrometry in the human lymphocytic cell line Ramos.

Unusual presentation of Lynch Syndrome.

Lynch Syndrome/HNPCC is a syndrome of cancer predisposition linked to inherited mutations of genes participating in post-replicative DNA mismatch repair (MMR). The spectrum of cancer associated with Lynch Syndrome includes tumours of the colorectum, endometrium, ovary, upper gastrointestinal tract and the urothelium although other cancers are rarely described. We describe a family of Lynch Syndrome with an hMLH1 mutation, that harbours an unusual tumour spectrum and its diagnostic and management challenges.

Epigenetics: an emerging technology in the diagnosis and treatment of cancer.

Transcriptional silencing resulting from changes in epigenetic regulation of gene expression is the most frequent mechanism by which tumor suppressor genes are inactivated in human cancer. Genes participating in numerous functional groups and pathways leading to malignancy are subject to aberrant CpG methylation, with associated downregulation of expression, in human carcinogenesis. Methylation profiling can identify distinct subtypes of common human cancers and may have utility in predicting clinical phenotypes in individual patients, including sensitivity to chemotherapeutic agents.

A kinase-independent function of Cks1 and Cdk1 in regulation of transcription.

We describe a function in transcription for the Saccharomyces cerevisiae cell cycle regulatory cyclin-dependent kinase Cdc28 (Cdk1) and its interacting protein, Cks1. The Cks1/Cdc28 complex is recruited to multiple coding regions in the genome and is necessary for efficient expression of a significant subset of genes. This transcriptional role is mediated through a requirement of Cdc28/Cks1 for recruiting proteasomes to coding regions.

Cks1 is dispensable for survival in Saccharomyces cerevisiae.

Cks1 is a small, evolutionarily conserved protein that was identified due to its genetic interaction with the Cdc28 cyclin-dependent kinase. In S. cerevisieae, Cks1 has long been regarded as a protein essential for cell survival.