ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins.

ASARs are a family of very-long noncoding RNAs that control replication timing on individual human autosomes, and are essential for chromosome stability. The eight known ASAR lncRNAs remain closely associated with their parent chromosomes. Analysis of RNA-protein interaction data (from ENCODE) revealed numerous RBPs with significant interactions with multiple ASAR lncRNAs, with several hnRNPs as abundant interactors. An ~7 kb domain within the ASAR6-141 lncRNA shows a striking density of RBP interaction sites. Genetic deletion and ectopic integration assays indicate that this ~7 kb RNA binding protein domain contains functional sequences for controlling replication timing of entire chromosomes in cis. shRNA-mediated depletion of 10 different RNA binding proteins, including HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1, results in dissociation of ASAR lncRNAs from their chromosome territories, and disrupts the synchronous replication that occurs on all autosome pairs, recapitulating the effect of individual ASAR knockouts on a genome-wide scale. Our results further demonstrate the role that ASARs play during the temporal order of genome-wide replication, and we propose that ASARs function as essential RNA scaffolds for the assembly of hnRNP complexes that help maintain the structural integrity of each mammalian chromosome.

The US FDA's proposed rule on laboratory-developed tests: Impacts on clinical laboratory testing.

Objectives: To solicit quantifiable feedback from clinical laboratorians on the U.S. Food and Drug Administration (FDA) proposed rule to regulate laboratory-developed tests (LDTs) as medical devices. Design and Methods: A ten-item questionnaire was developed and submitted to clinical laboratory customers of ARUP Laboratories, a national nonprofit clinical laboratory of the University of Utah Department of Pathology. Results: Of 503 clinical laboratory respondents, only 41 (8 %) support the FDA's proposed rule. 67 % of respondents work in laboratories that perform LDTs and were therefore asked additional questions regarding the proposed rule. 84 % of these respondents believe that the proposed rule will negatively impact their laboratories, while only 3 % believe that they have the financial resources to pay for FDA user fees. 61 % of respondents anticipate removing tests from their laboratory menus if the proposed rule is enacted, while an additional 33 % indicated that they do not yet know. Only 11 % of respondents believe that they would pursue FDA submissions for all of their existing LDTs if the final rule is enacted. The vast majority of respondents (>80 %) were either 'extremely concerned' or 'very concerned' about the impact of the proposed rule on patient access to essential testing, financial and personnel resources to comply, innovation, the FDA's ability to implement the rule, and send-out costs and test prices. Conclusions: The majority of clinical laboratorians surveyed do not support the FDA's proposed rule on LDTs and report having insufficient resources to comply with the rule if it is enacted.

Collaboration in the midst of chaos: perspectives of inpatient occupational and physical therapists during the COVID-19 pandemic.

The COVID-19 pandemic has affected over 700 million people globally, straining healthcare systems and highlighting the need for interprofessional collaboration. The aim of this study was to describe interprofessional collaborative practice (IPCP) experiences from the perspectives of occupational therapists (OTs) and physical therapists (PTs) who were employed in a medical center both before and during the COVID-19 pandemic. This qualitative study, conducted from July 2020-November 2021, delved into the lived experiences of occupational and physical therapists in an inpatient setting during the pandemic through analysis of semi-structured interviews and journal entries. The pandemic prompted fear, uncertainty, and ethical dilemmas among therapists, affecting patient-centered care. Roles expanded, and teamwork challenges emerged in defining boundaries, while communication dynamics were transformed by virtual technologies. The pandemic affected therapists' values and ethics, and evolving roles brought expanded tasks. The crisis showcased both collaboration potential and the need to address team disparities. This study highlights the significance of values, roles, teams, and communication for occupational and physical therapists during the COVID-19 pandemic providing valuable insights into interprofessional collaboration's effect on healthcare delivery in times of crisis and beyond.

Implementation and Mixed-Methods Assessment of an Early Mobility Interprofessional Education Simulation.

INTRODUCTION: Extended periods of bed rest and mechanical ventilation (MV) have devastating effects on the body. BACKGROUND: Early mobility (EM) for patients in respiratory failure is safe and feasible, and an interprofessional team is recommended. Using simulation to train EM skills improves student confidence. The purpose of this study was to enable health care student collaboration as an interprofessional team in providing safe management and monitoring during an EM simulation for a patient requiring MV. METHODS: Nursing (n = 33), respiratory (n = 7), occupational (n = 24), and physical therapist students (n = 55) participated in an EM interprofessional education (IPE) simulation experience. A mixed-methods analytic approach was used with pre/post quantitative analysis of the Student Perceptions of Interprofessional Clinical Education-Revised, Version 2 instrument and qualitative analysis of students' guided reflection papers. RESULTS: Pre/post surveys completion rate was 39.5% (n = 47). The Student Perceptions of Interprofessional Clinical Education-Revised, Version 2 instrument indicated a significant improvement (P = .037) in students' perceptions of interprofessional collaborative practice. Qualitative data showed a positive response to the EM simulation IPE. Themes reflected all 4 Interprofessional Education Collaborative competencies. DISCUSSION: This study demonstrated improved perception of interprofessional collaborative practice and better understanding of the Interprofessional Education Collaborative competencies. CONCLUSION: Students collaborated in the simulation-based IPE to provide EM for a patient requiring MV and reported perceived benefits of the experience.

Bringing the Genomic Revolution to Comparative Oncology: Human and Dog Cancers.

Dogs are humanity's oldest friend, the first species we domesticated 20,000-40,000 years ago. In this unequaled collaboration, dogs have inadvertently but serendipitously been molded into a potent human cancer model. Unlike many common model species, dogs are raised in the same environment as humans and present with spontaneous tumors with human-like comorbidities, immunocompetency, and heterogeneity. In breast, bladder, blood, and several pediatric cancers, in-depth profiling of dog and human tumors has established the benefits of the dog model. In addition to this clinical and molecular similarity, veterinary studies indicate that domestic dogs have relatively high tumor incidence rates. As a result, there are a plethora of data for analysis, the statistical power of which is bolstered by substantial breed-specific variability. As such, dog tumors provide a unique opportunity to interrogate the molecular factors underpinning cancer and facilitate the modeling of new therapeutic targets. This review discusses the emerging field of comparative oncology, how it complements human and rodent cancer studies, and where challenges remain, given the rapid proliferation of genomic resources. Increasingly, it appears that human's best friend is becoming an irreplaceable component of oncology research.

The Role of Fish Skin Xenografts in Healing Complex Wounds: A Brief Case Report.

Non-healing wounds profoundly impact patient quality of life and present a significant financial burden. The Kerecis™ fish skin xenograft is a decellularized skin matrix that has been introduced to treat complicated wounds. The objective of this presentation is to highlight the use of fish skin xenograft in the treatment of a complex right flank wound with stool contamination, necrotizing soft tissue infection due to perforated colon cancer, and sepsis. This presentation follows the wound healing for 28 days following the operation and demonstrates the efficacy of fish skin xenografts in improved wound healing. A 61-year-old female with a past medical history of colon cancer and recent chemotherapy treatment presented with colon perforation causing right flank cellulitis and sepsis with necrotic abdominal wall tissue extending into the hip joint. She was taken for an emergent exploratory laparotomy, drainage of abdominal and retroperitoneal abscesses, open right hemicolectomy, diverting ileostomy, abdominal washout, intra-abdominal omental patch, placement of Strattice mesh, and debridement of necrotizing soft tissue infection of the right flank. After extensive debridement of her 15x10cmx5cm deep wound and placement of a Kerecis™ fish skin xenograft, the wound had completely healed with excellent granulation tissue, and the patient was scheduled for placement of a skin graft 28 days following the initial procedure. The results after xenograft application were outstanding, supporting the use of polyunsaturated fatty acid (PUFA) based xenografts in wound treatment due to their anti-inflammatory and angiogenic properties. This is definitely an option that needs to be considered in expediting the healing process for complex wounds.

Nature-based virtual reality intervention to manage stress in family caregivers of allogeneic hematopoietic stem cell transplant recipients: a two-phase pilot study protocol.

Millions of family members and/or friends in the U.S. serve as unpaid caregivers for individuals with chronic conditions, such as cancer. Caregiving for someone undergoing an intense allogeneic hematopoietic stem cell transplant (HSCT) is particularly demanding, with accompanying physical and psychological stress. Increased stress and stress-related symptoms could make it difficult for caregivers to fulfill their roles and could negatively impact the health status and quality of life of themselves and the recipients. Virtual reality (VR) is a promising technology increasingly used for treatment and wellness in various medical settings. There is growing evidence that studies have reported the positive effects of the VR intervention in managing and reducing stress among diverse populations in various clinical scenarios; however, no published studies have focused on family caregivers of patients with cancer. The study aims to assess the feasibility and acceptability of a four-week nature-based VR intervention and to examine the effectiveness of the VR intervention on stress in HSCT caregivers. This study comprises two phases. Phase I of the study will be a single-arm pre-post design focused on assessing the feasibility and acceptability of the VR intervention. Phase II of the study will be a prospective randomized controlled group design to examine the effectiveness of the VR intervention on perceived stress. Adults (≥ 18 years) who serve as primary caregivers for a person who will undergo an allogeneic HSCT will be recruited. Fifteen participants will be enrolled for Phase I and 94 participants for Phase II (Active VR arm N=47; Sham VR arm N=47). The nature-based immersive VR program contains 360° high-definition videos of nature scenes along with nature sounds through a head-mounted display (HMD) for 20 minutes every day for four weeks. Primary outcome is perceived stress measured by the Perceived Stress Scale. Secondary/exploratory outcomes are stress-related symptoms (e.g., fatigue, sleep disturbance) and physiological biomarkers (e.g., cortisol, alpha-amylase). The importance and innovativeness of this study consist of using a first-of-its-kind, immersive VR technology to target stress and investigating the health outcomes assessed by validated objective biomarkers as well as self-report measures of the nature-based intervention in the caregiver population. Clinical trial registration: ClinicalTrials.gov, identifier NCT05909202.

Virtual Interprofessional Education: Team Collaboration in Discharge Planning Simulation.

PURPOSE OF STUDY: This study assessed the effectiveness of a virtual interprofessional education (IPE) discharge planning simulation, focusing on collaborative patient education, and recommendations for hospital discharge. PRIMARY PRACTICE SETTING: An acute care hospital. METHODOLOGY AND SAMPLE: The study utilized a virtual IPE discharge planning simulation for health care students from six different programs. The simulation involved prebriefing, icebreaker, team meeting, patient interaction, and debriefing. Assessment included pre- and post-IPE surveys that included the Interprofessional Education Collaborative (IPEC) Competency Self-Assessment Tool, and video analysis using the Modified McMaster-Ottawa Rating Scale. RESULTS: Student participants from diverse health care programs (n =143) included nursing (n = 20), occupational therapy (n = 21), physical therapy (n = 42), physician assistant (n = 38), respiratory therapy (n = 3), and social work (n = 19). All programs except respiratory therapy showed significant improvement in IPEC Competency scores post-IPE, with positive outcomes for understanding other professions' roles. Students' self-reported perceptions of team performance were rated highly in various categories. Video analysis demonstrated strong interrater reliability for team scores. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Effective hospital discharge planning is vital for cost reduction and patient care improvement. IPE emphasizes collaborative learning among health care students. Previous studies highlight positive outcomes from IPE discharge planning, including virtual formats. This virtual IPE discharge planning simulation significantly improved students' understanding and collaboration competencies, evident in increased IPEC scores across five professions.

A Preliminary Investigation into the Frequency Dose Effects of High-Intensity Functional Training on Cardiometabolic Health.

The objective of this study was to explore the effects of three weekly frequency doses of high-intensity functional training (HIFT) on an array of cardiometabolic markers in adults with metabolic syndrome (MetS). Twenty-one men and women, randomized into one (HIFT1), two (HIFT2), or three (HIFT3) days per week of HIFT, completed 3-weeks of familiarization plus a 12-week progressive training program. Pre- and post-intervention, several cardiometabolic, body composition, oxygen consumption, metabolic syndrome severity, and perceptions of fitness measurements were assessed. Additionally, an exercise enjoyment survey was administered post-intervention. A Cohen's d was used to demonstrate within-group change effect size. Although this study was not fully powered, a one-way and two-way ANOVA were used to compare the dose groups to provide provisional insights. No differences were found when frequency dose groups were compared. Many cardiometabolic, body composition, and fitness improvements were seen within each group, with clinically meaningful improvements in the metabolic syndrome severity score (MSSS) (HIFT1: -0.105, d = 0.28; HIFT2: -0.382, d = 1.20; HIFT3: -0.467, d = 1.07), waist circumference (HIFT1: -4.1cm, d = 3.33; HIFT2: -5.4cm, d = 0.89; HIFT3: -0.7cm, d = 0.20), and blood glucose (HIFT1: -9.5mg/dL, d = 0.98; HIFT2: -4.9mg/dL, d = 1.00; HIFT3: -1.7mg/dL, d = 0.23). All three groups similarly reported high exercise enjoyment and likeliness to continue after the intervention. In conclusion, HIFT performed once, twice, or thrice a week elicits improvements in MetS and is considered enjoyable. HIFT, even at a low weekly dose, therefore represents a potential strategy to reduce the global MetS burden.

Optimizing Blood Culture Collection Volumes.

ABSTRACT: Infection in an immunocompromised person can be a life-threatening emergency. Collection of blood culture specimens is an important method for detecting organisms when infection is suspected. One aspect of proper blood culture collection is obtaining an accurate blood volume in the sample in accordance with the blood culture bottle manufacturer's recommendation. Underfilling the culture bottle can lead to false-negative results, while overfilling it can lead to false-positive results. At our institution, the Department of Laboratory Medicine (DLM) routinely monitors blood culture bottle volumes and notifies the nursing department of underfill/overfill events, which the department then reviews. Over several years, the DLM and the nursing department noted an increase in these events. A clinical nurse specialist and three staff nurses in the oncology/critical care services area partnered with the DLM to determine why. Upon investigation, two key issues-imprecise weighing of bottles and staff misunderstanding of the proper blood culture collection technique-were discovered. In response, the nursing standard of practice and guidance on the DLM webpage were updated and nursing education was performed. As a result, underfill/overfill events decreased by 71% in a little over a year.

Equitable machine learning counteracts ancestral bias in precision medicine, improving outcomes for all.

Gold standard genomic datasets severely under-represent non-European populations, leading to inequities and a limited understanding of human disease [1-8]. Therapeutics and outcomes remain hidden because we lack insights that we could gain from analyzing ancestry-unbiased genomic data. To address this significant gap, we present PhyloFrame, the first-ever machine learning method for equitable genomic precision medicine. PhyloFrame corrects for ancestral bias by integrating big data tissue-specific functional interaction networks, global population variation data, and disease-relevant transcriptomic data. Application of PhyloFrame to breast, thyroid, and uterine cancers shows marked improvements in predictive power across all ancestries, less model overfitting, and a higher likelihood of identifying known cancer-related genes. The ability to provide accurate predictions for underrepresented groups, in particular, is substantially increased. These results demonstrate how AI can mitigate ancestral bias in training data and contribute to equitable representation in medical research.

The Impact of COVID-19 on Interprofessional Collaborative Practice Through the Lens of Acute Care Physical Therapists: A Case Series.

This case report describes interprofessional collaborative practice experiences through the viewpoints of 3 acute care physical therapists who worked with patients with coronavirus disease-2019 (COVID-19) during the early months of the pandemic. Methods: The cases presented in this case report were selected from a larger longitudinal qualitative multiple-case study investigating interprofessional collaborative practice experiences of physical therapists employed in inpatient settings prior to and during the pandemic. The cases provide detailed narrative descriptions of interprofessional collaborative practice before and during the pandemic from the perspective of 3 physical therapists working in acute care environments. Results: The 3 physical therapists reported challenges to and opportunities for interprofessional collaborative practices that align with the 4 interprofessional educational competencies (values/ethics, roles/responsibilities, communication, and teams/teamwork). Conclusions: The ability to provide patient-centered care through interprofessional collaborative practices was impacted by the COVID-19 pandemic. The rich narrative descriptions of our participants' experiences as members of interprofessional teams provide additional insight regarding the effect of the COVID-19 pandemic on interprofessional collaborative practice.

Communications and High-Precision Positioning (CHP2): Hardware Architecture, Implementation, and Validation.

Spectral congestion and modern consumer applications motivate radio technologies that efficiently cooperate with nearby users and provide several services simultaneously. We designed and implemented a joint positioning-communications system that simultaneously enables network communications, timing synchronization, and localization to a variety of airborne and ground-based platforms. This Communications and High-Precision Positioning (CHP2) system simultaneously performs communications and precise ranging (<10 cm) with a narrow band waveform (10 MHz) at a carrier frequency of 915 MHz (US ISM) or 783 MHz (EU Licensed). The ranging capability may be extended to estimate the relative position and orientation by leveraging the spatial diversity of the multiple-input, multiple-output (MIMO) platforms. CHP2 also digitally synchronizes distributed platforms with sub-nanosecond precision without support from external systems (GNSS, GPS, etc.). This performance is enabled by leveraging precise time-of-arrival (ToA) estimation techniques, a network synchronization algorithm, and the intrinsic cooperation in the joint processing chain that executes these tasks simultaneously. In this manuscript, we describe the CHP2 system architecture, hardware implementation, and in-lab and over-the-air experimental validation.

Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial.

PURPOSE: Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with IFNs and monocytes. PATIENTS AND METHODS: Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of IFNs α and γ with monocytes. We translated these preclinical findings into a phase I trial of autologous IFN-activated monocytes administered intraperitoneally to platinum-resistant or -refractory ovarian cancer patients. RESULTS: IFN-treated monocytes induced caspase 8-dependent apoptosis by the proapoptotic TRAIL and mediated by the death receptors 4 and 5 (DR4 and DR5, respectively) on cancer cells. Therapy was well tolerated with evidence of clinical activity, as 2 of 9 evaluable patients had a partial response by RECIST criteria, and 1 additional patient had a CA-125 response. Upregulation of monocyte-produced TRAIL and cytokines was confirmed in peripheral blood. Long-term responders had alterations in innate and adaptive immune compartments. CONCLUSIONS: Given the mechanism of cancer cell death, and the acceptable tolerability of the clinical regimen, this platform presents a possibility for future combination therapies to augment anticancer immunity. See related commentary by Chow and Dorigo, p. 299.

Robotic Sigmoidectomy With Natural Orifice Specimen Extraction: A Single-Center Experience.

Background Natural orifice specimen extraction (NOSE) involves the removal of specimens through a naturally occurring orifice, such as the anus, rather than trans-abdominal extraction. NOSE procedures have been shown to significantly reduce postoperative complications and improve healing.  Objective The purpose of this case series is to report the outcomes of 27 patients undergoing sigmoidectomies through natural orifice specimen extraction. Materials and methods We carefully recorded demographic data on age and BMI, as well as operative data on surgical indication, and length of stay. We also collected data on postoperative complications, including infection, hernia, wound dehiscence, urinary tract infections (UTIs), or anastomotic leaks. Results Our patients were majority female (n = 21, 77.8%) with a median age of 53.5 (range: 25-79) and median BMI of 33.2 kg/m2 (range: 16.7 - 48.3 kg/m2). Thirteen patients (48.1%) were obese (BMI > 30.0 kg/m2). The majority of these patients underwent sigmoidectomies for benign conditions such as recurrent diverticulitis (n = 9, 33.3%), rectal prolapse (n = 8, 29.6%), perforated diverticulitis (n = 3, 11.1%), colovesical fistula (n = 3, 11.1%), and abdominal abscess (n = 3, 11.1%) (Table 1). One patient was receiving treatment for sigmoid cancer. The average estimated blood loss was 63.26 mL. The average hospital stay was 3.61 days. Three patients (11.1%) developed a fever postoperatively (temperature >= 100.4 F), which resolved the day after. One patient completed a post-operative hospital stay of 19 days for dialysis and rehab placement. No patients (0.0%) experienced any postoperative complications, including wound infection, hernia, dehiscence, UTIs, or anastomotic leakages. There was no postoperative mortality. Conclusions Our study demonstrates the practicality and safety of NOSE procedures for sigmoidectomies as an alternative to transabdominal approaches to treat benign colon diseases.

Robotic Single-Site Cholecystectomy: A Single-Center Retrospective Study.

Objective Our goal is to describe and report the outcomes of patients undergoing robotic single-site cholecystectomy at a single institution. Background Cholecystectomy is a common procedure performed to remove the gallbladder. Robotic single-site cholecystectomy (RSSC) is rapidly emerging as a safe and feasible alternative to conventional 4-port laparoscopic techniques. Patients who undergo RSSC procedures may also have a decreased need for postoperative analgesics and a lower postoperative pain score. Methods From September 2020 to August 2023, there were 33 cases of RSSC performed by a single surgeon at a single institution. We recorded demographic data including sex, age, and BMI as well as postoperative outcome data including wound dehiscence, postoperative infection, biliary leakage, wound herniation, blood loss, and conversion to open procedure. Results The patient group included 24 females (72.7%) and nine males (27.3%) with a median age of 32 (Range: 9-70) and a median BMI of 24.2 kg/m2 (Range: 18.1-30.7). The majority of these patients were receiving cholecystectomies for benign conditions such as symptomatic cholelithiasis (n = 18, 54.5%), biliary dyskinesia (n = 13, 39.4%), acute cholecystitis (n = 1, 0.03%), and biliary colic (n = 1, 0.03%). The average estimated blood loss was 5.91 mL. Thirty-two patients (96.9%) were discharged home the same day of surgery. One patient was admitted overnight for observation due to severe biliary dyskinesia diagnosed preoperatively. The patient had no complications and was discharged the following day. One patient presented with acute abdominal wall cellulitis and omphalitis with no underlying abscess four weeks after the operation. They were treated with therapeutic antibiotics. No patients underwent conversion to an open procedure. There were no incidences of postoperative wound dehiscence or biliary leakages. One patient was admitted overnight for observation of biliary dyskinesia and another experienced abdominal wall cellulitis four weeks post-operation. Conclusions Although conventional multi-incision laparoscopic cholecystectomy remains the gold standard treatment for benign gallbladder disease, our study demonstrates the practicality and safety of Robotic Single-Site Cholecystectomy procedures.

The Effects of a Single Session of High Intensity Functional Training on Energy Expenditure, VO2, and Blood Lactate.

High intensity functional training (HIFT) provides a potential option to meet public exercise recommendations for both cardiorespiratory and strength outcomes in a time efficient manner. To better understand the potential for HIFT as an exercise approach, energy expenditure (EE) and relative intensity need quantifying. In thirteen sedentary men and women with metabolic syndrome (MetS), we used both indirect calorimetry and blood lactate levels to calculate EE of a single session of HIFT. The HIFT session included four, 6-minute sets of consecutive functional exercises. Examples of the exercises involved were squats, deadlifts, suspension rows, suspension chest press, and planks. Intensity is described relative to individual ventilatory thresholds. The total group EE was 270.3 ± 77.3 kcal with approximately 5% attributed anaerobic energy production. VO2 ranged between 88.8 ± 12.3% and 99 ± 12% of the second ventilatory threshold (VT2), indicating a vigorous effort. After each work interval, peak blood lactate ranged between 7.9 ± 1.9 and 9.3 ± 2.9 mmol, and rate of perceived exertion between 6.9 ± 1.0 and 8.7 ± 0.8 arbitrary units from 1-10. These were achieved in approximately 46 minutes of exercise per participant. In conclusion, HIFT elicits the energy expenditure and effort requisite to result in the adaptive responses to produce the known suite of benefits of exercise for individuals with MetS.

Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability.

ASARs are long noncoding RNA genes that control replication timing of entire human chromosomes in cis. The three known ASAR genes are located on human chromosomes 6 and 15, and are essential for chromosome integrity. To identify ASARs on all human chromosomes we utilize a set of distinctive ASAR characteristics that allow for the identification of hundreds of autosomal loci with epigenetically controlled, allele-restricted behavior in expression and replication timing of coding and noncoding genes, and is distinct from genomic imprinting. Disruption of noncoding RNA genes at five of five tested loci result in chromosome-wide delayed replication and chromosomal instability, validating their ASAR activity. In addition to the three known essential cis-acting chromosomal loci, origins, centromeres, and telomeres, we propose that all mammalian chromosomes also contain "Inactivation/Stability Centers" that display allele-restricted epigenetic regulation of protein coding and noncoding ASAR genes that are essential for replication and stability of each chromosome.