Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

Pain, Substance Use Disorders, Mental Health, and Buprenorphine Treatment among Patients With and Without HIV.

Treatment of opioid use disorder (OUD) with buprenorphine improves outcomes and mortality among people with HIV (PWH). However, engagement is low and is influenced by comorbidities. We examined the impact of patterns of co-occurring pain, substance use disorders (SUDs), and mental health diagnoses on buprenorphine initiation and retention in PWH.

Concordance of provider chart notation and guideline-based classification of asthma severity.

Objective: To evaluate concordance of asthma severity classification physician chart notation compared with guideline-based criteria in adolescents with diagnosed asthma.

Methods: Of 284 urban primary care and subspecialty clinic patients aged 13-18 years approached through convenience sampling, 203 surveys were completed (RR = 71.5%).

Natural Product Use Among Veterans with Chronic Pain: A Qualitative Study of Attitudes and Communication with Healthcare Providers.

Background: Despite mixed evidence regarding the safety and efficacy of natural products, many are marketed for pain and related symptoms. Use of these products is prevalent among veterans, who have disproportionately high rates of chronic pain. To date, however, there is limited research on veterans' beliefs and attitudes about natural products and their communication with healthcare providers about their natural product use.

FET fusion oncoproteins disrupt physiologic DNA repair networks in cancer.

While oncogenes promote cancer cell growth, unrestrained proliferation represents a significant stressor to cellular homeostasis networks such as the DNA damage response (DDR). To enable oncogene tolerance, many cancers disable tumor suppressive DDR signaling through genetic loss of DDR pathways and downstream effectors (e.g.

Estimated Rates of Incident and Persistent Chronic Pain Among US Adults, 2019-2020.

Importance: Chronic pain risk and prognosis estimates are needed to inform effective interventions.

Objective: To estimate rates of chronic pain and high-impact chronic pain (HICP) incidence and persistence in US adults across demographic groups.

Design, Setting, And Participants: This cohort study examined a nationally representative cohort with 1 year of follow-up (mean [SD], 1.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

Introduction: High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient.

Ras drives malignancy through stem cell crosstalk with the microenvironment.

Squamous cell carcinomas are triggered by marked elevation of RAS-MAPK signalling and progression from benign papilloma to invasive malignancy. At tumour-stromal interfaces, a subset of tumour-initiating progenitors, the cancer stem cells, obtain increased resistance to chemotherapy and immunotherapy along this pathway. The distribution and changes in cancer stem cells during progression from a benign state to invasive squamous cell carcinoma remain unclear.

Divergent regulation of basement membrane trafficking by human macrophages and cancer cells.

Macrophages and cancer cells populations are posited to navigate basement membrane barriers by either mobilizing proteolytic enzymes or deploying mechanical forces. Nevertheless, the relative roles, or identity, of the proteinase -dependent or -independent mechanisms used by macrophages versus cancer cells to transmigrate basement membrane barriers harboring physiologically-relevant covalent crosslinks remains ill-defined. Herein, both macrophages and cancer cells are shown to mobilize membrane-anchored matrix metalloproteinases to proteolytically remodel native basement membranes isolated from murine tissues while infiltrating the underlying interstitial matrix ex vivo.

Physician Office Visits That Included Complementary Health Approaches in U.S. Adults: 2005-2015.

The Institute of Medicine has described the need for comparing models of care delivery involving complementary health approaches and conventional medical practitioners. As a step toward addressing this need, we used a nationally representative 11-year sample of office-based visits to physicians from the National Ambulatory Medical Care Survey (NAMCS), to examine a comprehensive list of factors believed to be associated with visits where complementary health approaches were recommended or provided. NAMCS is a national health care survey designed to collect data on the provision and use of ambulatory medical care services provided by office-based physicians in the United States.

Reasons Office-Based Physicians in the United States Recommend Common Complementary Health Approaches to Patients: An Exploratory Study Using a National Survey.

To examine the reasons why office-based physicians do or do not recommend four selected complementary health approaches to their patients in the context of the Andersen Behavioral Model. Descriptive estimates of physician-level data from the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Induction Interview, a nationally representative survey of office-based physicians ( = 5622, weighted response rate = 59.7%).

Disparities in Local Wellness Policies Implementation Across Maryland Schools.

Background: School-level implementation of district-level local wellness policies (LWPs) is needed to create school environments that promote nutrition and physical activity (PA). Disparities in classroom-specific LWPs implementation were examined.

Methods: An administrator survey (N = 756 schools; 24/24 districts) included 6 classrooms LWP best-practice items (fully/not fully implemented: restricting food celebrations or rewards, incorporating PA breaks or integrating PA in curricula, restricting withholding or using PA as punishment).

Multiple Routes to Animal Consciousness: Constrained Multiple Realizability Rather Than Modest Identity Theory.

The multiple realizability thesis (MRT) is an important philosophical and psychological concept. It says any mental state can be constructed by multiple realizability (MR), meaning in many distinct ways from different physical parts. The goal of our study is to find if the MRT applies to the mental state of consciousness among animals.

HPV Screening Test for the Detection of Precancerous Cervical Lesions and Cervical Cancer in Israeli Women.

Objectives: This work is aimed to summarize the first year of the high-risk human papillomavirus (hrHPV) screening test and compare it to the cytology screening test, regarding positivity rates and premalignant lesions diagnosed in the Israeli population. A specific consideration is for the age group 25-30 that is not considered mandatory for the HPV primary screening testing.

Methods: A retrospective study was performed in women who were screened for prevention of cervical cancer in Maccabi HealthCare HMO from March 2017 to March 2019.

Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study.

Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction.

Correlates of Manual Therapy and Acupuncture Use Among Rural Patients Seeking Conventional Pain Management: A Cross-sectional Study.

Objective: In this cross-sectional study, we examined correlates of manual therapy (spinal manipulation, massage therapy) and/or acupuncture use in a population engaging in conventional pain care in West Virginia.

Methods: Participants were patients (aged 18+ years) from 4 Appalachian pain and rheumatology clinics. Of those eligible (N = 343), 88% completed an anonymous survey including questions regarding health history, pain distress (Short Form Global Pain Scale), prescription medications, and current use of complementary health approaches for pain management.

Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review.

Background: Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines.

Phenomenal Consciousness and Emergence: Eliminating the Explanatory Gap.

The role of emergence in the creation of consciousness has been debated for over a century, but it remains unresolved. In particular there is controversy over the claim that a "strong" or radical form of emergence is required to explain phenomenal consciousness. In this paper we use some ideas of complex system theory to trace the emergent features of life and then of complex brains through three progressive stages or levels: , and , each representing increasing biological and neurobiological complexity and ultimately leading to the emergence of phenomenal consciousness, all in physical systems.

Diet quality of elementary and middle school teachers is associated with healthier nutrition-related classroom practices.

Many schools have implemented policies and programs to address childhood obesity. However, few have evaluated obesity-related health behaviors among teachers, or how these behaviors may be associated with teachers' nutrition-related practices in the classroom setting. This cross-sectional study utilized data from teachers employed in 20 schools representing three public school districts in a mid-Atlantic state from 2017 to 2019 to examine associations between teachers' diet quality and their nutrition-related classroom practices (e.

A review of the use of hormonal contraception in women with non-cardiovascular coexisting medical conditions. A comprehensive review.

Introduction: Previously, the American College of Obstetrics and Gynecology (ACOG) had published an excellent practice bulletin addressing the use of hormone contraception in women with pre-existing medical conditions. This practice bulletin became out of date. The Centers for Disease Control and prevention (CDC) of the USA subsequently developed a point form guideline for the use of oral contraceptives in women with coexisting medical conditions.

A review of the use of hormonal contraception in women with cardiovascular disease complications and risk factors. A systematic review.

Introduction: The Centers for Disease Control and Prevention (CDC) developed a point form guideline for the use of oral contraceptives in women with coexisting medical conditions. Although this acts as a guide, it leaves the clinician without an understanding of why they are doing what they are doing.

Evidence Acquisition: In this article, which is one of two articles addressing coexisting medical condition and oral contraceptive use, an update of the scientific knowledge is provided.

Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases.

Osteoclasts actively remodel both the mineral and proteinaceous components of bone during normal growth and development as well as pathologic states ranging from osteoporosis to bone metastasis. The cysteine proteinase cathepsin K confers osteoclasts with potent type I collagenolytic activity; however, cathepsin K-null mice, as well as cathepsin K-mutant humans, continue to remodel bone and degrade collagen by as-yet-undefined effectors. Here, we identify a cathepsin K-independent collagenolytic system in osteoclasts that is composed of a functionally redundant network of the secreted matrix metalloproteinase MMP9 and the membrane-anchored matrix metalloproteinase MMP14.

Subjectivity "Demystified": Neurobiology, Evolution, and the Explanatory Gap.

While life in general can be explained by the mechanisms of physics, chemistry, and biology, to many scientists and philosophers, it appears that when it comes to explaining consciousness, there is what the philosopher Joseph Levine called an "explanatory gap" between the physical brain and subjective experiences. Here, we deduce the living and neural features behind primary consciousness within a naturalistic biological framework, identify which animal taxa have these features (the vertebrates, arthropods, and cephalopod molluscs), then reconstruct when consciousness first evolved and consider its adaptive value. We theorize that consciousness is based on all the complex system features of life, plus even more complex features of elaborate brains.

Delusional Misidentification of the Mirror Image.

Purpose Of Review: Delusional misidentification syndromes (DMS) include conditions in which a false belief about the identity of a person, place, or object occurs in the context of psychiatric or neurological disorders. One form of DMS involves the delusion that the patient's mirror image is a separate individual. This review of reported cases characterizes the psychiatric, neuropathological, and neuropsychological aspects of DMS for the mirror image.

Eighteen-Year Trends in the Prevalence of, and Health Care Use for, Noncancer Pain in the United States: Data from the Medical Expenditure Panel Survey.

We used data from the nationally representative Medical Expenditure Panel Survey to determine the 18-year trends in the overall rates of noncancer pain prevalence and pain-related interference, as well as in health care use attributable directly to pain management. The proportion of adults reporting painful health condition(s) increased from 32.9% (99.