Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System.

In this paper we synthesize an expansive body of literature examining the multifaceted influence of chiropractic care on processes within and modulators of the neuroendocrine-immune (NEI) system, for the purpose of generating an inductive hypothesis regarding the potential impacts of chiropractic care on integrated physiology. Taking a broad, interdisciplinary, and integrative view of two decades of research-documented outcomes of chiropractic care, inclusive of reports ranging from systematic and meta-analysis and randomized and observational trials to case and cohort studies, this review encapsulates a rigorous analysis of research and suggests the appropriateness of a more integrative perspective on the impact of chiropractic care on systemic physiology. A novel perspective on the salutogenic, health-promoting effects of chiropractic adjustment is presented, focused on the improvement of physical indicators of well-being and adaptability such as blood pressure, heart rate variability, and sleep, potential benefits that may be facilitated through multiple neurologically mediated pathways. Our findings support the biological plausibility of complex benefits from chiropractic intervention that is not limited to simple neuromusculoskeletal outcomes and open new avenues for future research, specifically the exploration and mapping of the precise neural pathways and networks influenced by chiropractic adjustment.

User Information Sharing and Hospital Website Privacy Policies.

Importance: Hospital websites frequently use tracking technologies that transfer user information to third parties. It is not known whether hospital websites include privacy policies that disclose relevant details regarding tracking. Objective: To determine whether hospital websites have accessible privacy policies and whether those policies contain key information related to third-party tracking. Design, Setting, and Participants: In this cross-sectional content analysis of website privacy policies of a nationally representative sample of nonfederal acute care hospitals, hospital websites were first measured to determine whether they included tracking technologies that transferred user information to third parties. Hospital website privacy policies were then identified using standardized searches. Policies were assessed for length and readability. Policy content was analyzed using a data abstraction form. Tracking measurement and privacy policy retrieval and analysis took place from November 2023 to January 2024. The prevalence of privacy policy characteristics was analyzed using standard descriptive statistics. Main Outcomes and Measures: The primary study outcome was the availability of a website privacy policy. Secondary outcomes were the length and readability of privacy policies and the inclusion of privacy policy content addressing user information collected by the website, potential uses of user information, third-party recipients of user information, and user rights regarding tracking and information collection. Results: Of 100 hospital websites, 96 (96.0%; 95% CI, 90.1%-98.9%) transferred user information to third parties. Privacy policies were found on 71 websites (71.0%; 95% CI, 61.6%-79.4%). Policies were a mean length of 2527 words (95% CI, 2058-2997 words) and were written at a mean grade level of 13.7 (95% CI, 13.4-14.1). Among 71 privacy policies, 69 (97.2%; 95% CI, 91.4%-99.5%) addressed types of user information automatically collected by the website, 70 (98.6%; 95% CI, 93.8%-99.9%) addressed how collected information would be used, 66 (93.0%; 95% CI, 85.3%-97.5%) addressed categories of third-party recipients of user information, and 40 (56.3%; 95% CI, 44.5%-67.7%) named specific third-party companies or services receiving user information. Conclusions and Relevance: In this cross-sectional study of hospital website privacy policies, a substantial number of hospital websites did not present users with adequate information about the privacy implications of website use, either because they lacked a privacy policy or had a privacy policy that contained limited content about third-party recipients of user information.

Sex-Specific Expression of Histone Lysine Demethylases (KDMs) in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer in women is 3-4-fold higher than in men. To characterize sex-specific molecular alterations in thyroid cancer, we examined the expression of sex-biased genes in normal thyroids and thyroid tumors. METHODS: Ingenuity pathways analysis was used to define sex-biased gene networks using data from the Cancer Genome Atlas (TCGA). Confirmatory studies were performed through the analysis of histone lysine demethylases (KDMs) expression by real-time PCR and immunostaining. RESULTS: In normal thyroids, 44 sex-biased genes were comparatively upregulated in male and 28 in female patients. The expressions of 37/72 (51%) sex-biased genes were affected in cancer tissues compared with normal thyroids. Gene network analyses revealed sex-specific patterns in the expressions of KDM5C, KDM5D, and KDM6A. In confirmatory studies, KDM5D mRNA and protein were detected only in males, whereas KDM5C and KDM6A were detected in samples from male and female patients. Nuclear staining with anti-KDMs was found in normal thyroids, but a loss of nuclear expression with a concomitant gain of cytoplasmic staining was observed in cancer tissues. CONCLUSIONS: Normal thyroids have a sex-specific molecular signature, and the development of thyroid cancer is associated with a differential expression of sex-biased genes. The sex-specific expression of KDMs, coupled with cancer-related alterations in their intracellular localization, may contribute to mechanisms underlying sex differences in thyroid tumorigenesis.

Parallel gene size and isoform expansion of ancient neuronal genes.

How nervous systems evolved is a central question in biology. A diversity of synaptic proteins is thought to play a central role in the formation of specific synapses leading to nervous system complexity. The largest animal genes, often spanning hundreds of thousands of base pairs, are known to be enriched for expression in neurons at synapses and are frequently mutated or misregulated in neurological disorders and diseases. Although many of these genes have been studied independently in the context of nervous system evolution and disease, general principles underlying their parallel evolution remain unknown. To investigate this, we directly compared orthologous gene sizes across eukaryotes. By comparing relative gene sizes within organisms, we identified a distinct class of large genes with origins predating the diversification of animals and, in many cases, the emergence of neurons as dedicated cell types. We traced this class of ancient large genes through evolution and found orthologs of the large synaptic genes potentially driving the immense complexity of metazoan nervous systems, including in humans and cephalopods. Moreover, we found that while these genes are evolving under strong purifying selection, as demonstrated by low dN/dS ratios, they have simultaneously grown larger and gained the most isoforms in animals. This work provides a new lens through which to view this distinctive class of large and multi-isoform genes and demonstrates how intrinsic genomic properties, such as gene length, can provide flexibility in molecular evolution and allow groups of genes and their host organisms to evolve toward complexity.

Addressing Mental Health Disability in Unsheltered Homelessness: Outpatient Conservatorship in Los Angeles.

OBJECTIVE: The authors sought to describe a pilot program for gravely disabled individuals experiencing unsheltered homelessness in Los Angeles County that illustrates a promising public health framework to address mental health-related disability in homeless populations. METHODS: Homeless outreach teams implementing the outpatient conservatorship (OPC) pilot program adopted a population health approach, multisystem care coordination, and prioritization of the least restrictive environments. The program allowed initiation of a Lanterman-Petris-Short (LPS) conservatorship outside of a hospital, with the goal of serving highly vulnerable individuals in the least restrictive settings. Between August 2020 and July 2021, the OPC pilot program served 43 clients, corresponding to 2% of those served by the outreach teams during that period. Using observational program evaluation data, the authors examined the impact of the program on this sample of participants. RESULTS: At 12 months, 81% of OPC clients were no longer experiencing unsheltered homelessness; 65% accessed an LPS conservatorship. Although most OPC clients utilized a psychiatric hospital, 54% left locked settings earlier than would have been possible without the program. One-third of clients referred for LPS conservatorship used unlocked licensed residential facilities in the first year. Negative events, such as remaining in unsheltered homelessness, were more common among clients not referred for LPS conservatorship. CONCLUSIONS: Timely receipt of street-based services and coordination of care before, during, and after referral for LPS conservatorship reduced use of restrictive settings. The OPC program's components constitute a promising triadic framework for addressing mental health disability among unsheltered individuals that warrants further investigation.

Improving a Sanctioned Homeless Encampment for Veterans During COVID-19 Through Multilevel Partnerships.

A veteran-clinician-researcher partnership-the Care, Treatment, and Rehabilitation Service (CTRS)-enabled quality improvement within a U.S. Department of Veterans Affairs-sanctioned homeless encampment created in response to the COVID-19 pandemic. Although the differing concerns of clinicians and operational leaders led to challenges in defining CTRS's goals and quality metrics, partnering with frontline social work and peer staff (N=11) and veterans (N=21 of 381 CTRS participants) and considering their feedback resolved those differences. Multilevel partnerships improved care within the encampment, leading to the development of an encampment medicine team (providing onsite integrated health care) and a veteran engagement committee (providing feedback).

Coping with disruptive patients: Perspectives of primary care employees.

BACKGROUND: The impact of patient aggression on primary health care employees is underexplored, yet imperative to address, given high rates of burnout. OBJECTIVE: We qualitatively explore perceptions of patient aggression among staff in women's health primary care at the Veterans Health Administration (VA). Our objective is to identify coping strategies that staf devised in response to aggressive behavior. METHODS: We conducted semi-structured interviews with 60 VA women's health primary care employees in 2021 and 2022. Informed by the Job Demands-Resources theoretical model, we used rapid qualitative analysis to identify themes related to patient aggression and employee coping strategies. RESULTS: Disruptive behaviors reported by participants included verbal and physical aggression. Staff cited disruptive patient behavior as emotionally draining and perceived a lack of consequences for low-level aggression. Respondents used coping strategies in response to patient aggression at three time points: before, during, and after a negative interaction. At each point, support from team members emerged as a dominant coping mechanism, as well as rapport-building with patients. CONCLUSION: Patient aggression can negatively impact the work experiences of primary care employees. At VA, women's health primary care staff have devised multiple strategies to cope with these interactions. However, the ability to effectively prevent and manage patient aggression is limited by the lack of meaningful repercussions for aggression at the organizational level, which has important implications for employee well-being and retention. Retention of women's health employees in VA is critical given the need for a highly specialized workforce to address the complex health needs of women veterans.

Secondary Analysis of a Dataset to Estimate the Prevalence of Vertebral Subluxation and Its Implications for Health Promotion and Prevention.

Background Vertebral subluxation (VS) is a clinical entity defined as a misalignment of the spine affecting biomechanical and neurological function. The identification and correction of VS is the primary focus of the chiropractic profession. The purpose of this study is to estimate VS prevalence using a sample of individuals presenting for chiropractic care and explore the preventative public health implications of VS through the promotion of overall health and function. Methodology A brief review of the literature was conducted to support an operational definition for VS that incorporated neurologic and kinesiologic exam components. A retrospective, quantitative analysis of a multi-clinic dataset was then performed using this operational definition. Descriptive statistics on patient demographic data included age, gender, and past health history characteristics. In addition to calculating estimates of the overall prevalence of VS, age- and gender-stratified estimates in the different clinics were calculated to allow for potential variations. Results A total of 1,851 patient records from seven chiropractic clinics in four states were obtained. The mean age of patients was 43.48 (SD = 16.8, range = 18-91 years). There were more females (n = 927, 64.6%) than males who presented for chiropractic care. Patients reported various reasons for seeking chiropractic care, including, spinal or extremity pain, numbness, or tingling; headaches; ear, nose, and throat-related issues; or visceral issues. Mental health concerns, neurocognitive issues, and concerns about general health were also noted as reasons for care. The overall prevalence of VS was 78.55% (95% CI = 76.68-80.42). Female and male prevalence of VS was 77.17% and 80.15%, respectively; notably, all per-clinic, age, or gender-stratified prevalences were ≥50%. Conclusions To date, this is the first study of its magnitude and application of an operational definition to estimate the prevalence of VS. Albeit nonrandom, the sample had a broad geographic distribution. The results of this study suggest a high rate of prevalence of VS in a sample of individuals who sought chiropractic care. Concerns about general health and wellness were represented in the sample and suggest chiropractic may serve a primary prevention function in the absence of disease or injury. Further investigation into the epidemiology of VS and its role in health promotion and prevention is recommended.

Understanding the need for digital twins' data in patient advocacy and forecasting oncology.

Digital twins are made of a real-world component where data is measured and a virtual component where those measurements are used to parameterize computational models. There is growing interest in applying digital twins-based approaches to optimize personalized treatment plans and improve health outcomes. The integration of artificial intelligence is critical in this process, as it enables the development of sophisticated disease models that can accurately predict patient response to therapeutic interventions. There is a unique and equally important application of AI to the real-world component of a digital twin when it is applied to medical interventions. The patient can only be treated once, and therefore, we must turn to the experience and outcomes of previously treated patients for validation and optimization of the computational predictions. The physical component of a digital twins instead must utilize a compilation of available data from previously treated cancer patients whose characteristics (genetics, tumor type, lifestyle, etc.) closely parallel those of a newly diagnosed cancer patient for the purpose of predicting outcomes, stratifying treatment options, predicting responses to treatment and/or adverse events. These tasks include the development of robust data collection methods, ensuring data availability, creating precise and dependable models, and establishing ethical guidelines for the use and sharing of data. To successfully implement digital twin technology in clinical care, it is crucial to gather data that accurately reflects the variety of diseases and the diversity of the population.

Unraveling Vulnerabilities in Endocrine Therapy-Resistant HER2+/ER+ Breast Cancer.

Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/estrogen receptor-positive (HER2+/ER+) breast cancer (BCa) are less responsive to ET than HER2-/ER+. However, real-world evidence reveals that a large subset of patients with HER2+/ER+ receive ET as monotherapy, positioning this treatment pattern as a clinical challenge. In the present study, we developed and characterized 2 in vitro models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic vulnerabilities. To mimic ETR to aromatase inhibitors (AIs), we developed 2 long-term estrogen deprivation (LTED) cell lines from BT-474 (BT474) and MDA-MB-361 (MM361). Growth assays, PAM50 subtyping, and genomic and transcriptomic analyses, followed by validation and functional studies, were used to identify targetable differences between ET-responsive parental and ETR-LTED HER2+/ER+ cells. Compared to their parental cells, MM361 LTEDs grew faster, lost ER, and increased HER2 expression, whereas BT474 LTEDs grew slower and maintained ER and HER2 expression. Both LTED variants had reduced responsiveness to fulvestrant. Whole-genome sequencing of aggressive MM361 LTEDs identified mutations in genes encoding transcription factors and chromatin modifiers. Single-cell RNA sequencing demonstrated a shift towards non-luminal phenotypes, and revealed metabolic remodeling of MM361 LTEDs, with upregulated lipid metabolism and ferroptosis-associated antioxidant genes, including GPX4. Combining a GPX4 inhibitor with anti-HER2 agents induced significant cell death in both MM361 and BT474 LTEDs. The BT474 and MM361 AI-resistant models capture distinct phenotypes of HER2+/ER+ BCa and identify altered lipid metabolism and ferroptosis remodeling as vulnerabilities of this type of ETR BCa.

The genetic basis of novel trait gain in walking fish.

A major goal in biology is to understand how organisms evolve novel traits. Multiple studies have identified genes contributing to regressive evolution, the loss of structures that existed in a recent ancestor. However, fewer examples exist for genes underlying constructive evolution, the gain of novel structures and capabilities in lineages that previously lacked them. Sea robins are fish that have evolved enlarged pectoral fins, six mobile locomotory fin rays (legs) and six novel macroscopic lobes in the central nervous system (CNS) that innervate the corresponding legs. Here, we establish successful husbandry and use a combination of transcriptomics, CRISPR-Cas9 editing, and behavioral assays to identify key transcription factors that are required for leg formation and function in sea robins. We also generate hybrids between two sea robin species with distinct leg morphologies and use allele-specific expression analysis and gene editing to explore the genetic basis of species-specific trait diversity, including a novel sensory gain of function. Collectively, our study establishes sea robins as a new model for studying the genetic basis of novel organ formation, and demonstrates a crucial role for the conserved limb gene tbx3a in the evolution of chemosensory legs in walking fish.

Software is Policy: Electronic Health Record Governance and the Implications of Clinical Standardization.

BACKGROUND: Electronic health record (EHR) implementations, whether replacing paper or electronic systems, are major social and organizational transformations. Yet studies of EHR-to-EHR transitions have largely neglected to elucidate accompanying social and organizational changes. One such underexplored change is the standardization of clinical practice in the context of EHR transitions. The Department of Veterans Affairs (VA) has begun a decade-long process of replacing the approximately 130 separate versions of its homegrown EHR with a single commercial EHR system. This provides an opportunity to explore the standardization of clinical practice amidst an EHR transition. OBJECTIVE: To identify, in the context of a large-scale EHR transition, (1) the scope and content of clinical standardization and (2) the anticipated implications of such standardization. DESIGN: Qualitative study. PARTICIPANTS: Twenty-nine members of VA councils established for the EHR transition. APPROACH: We conducted semi-structured interviews, which were professionally transcribed, and analyzed first using rapid analysis methods, followed by coding and content analysis. KEY RESULTS: Clinical standardization across facilities was a central goal of the EHR transition, encompassing computerized recommendations, order sets, professional roles/permissions, and clinical documentation. The anticipated implications of this standardization include (i) potential efficiency gains, with less duplicated effort across facilities; (ii) expanded bureaucracy; and (iii) increased uniformity, reducing both wanted and unwanted variation in care. CONCLUSIONS: EHR systems shape a wide range of clinical processes, particularly in a large organization like VA with a long history of EHR use. This makes standardization of EHR content a powerful mechanism for standardizing clinical practice itself, which can bring dramatic collateral consequences. Organizations undergoing EHR transitions need to recognize the important role that clinical standardization plays by treating EHR transitions as major organizational transformations in the governance of clinical practice.

Unraveling Vulnerabilities in Endocrine Therapy-Resistant HER2+/ER+ Breast Cancer.

Background: Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/ estrogen receptor-positive (HER2+/HR+) breast cancer (BCa) are less responsive to ET than HER2-/ER+. However, real-world evidence reveals that a large subset of HER2+/ER+ patients receive ET as monotherapy, positioning this treatment pattern as a clinical challenge. In the present study, we developed and characterized two distinct in vitro models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic vulnerabilities. Methods: To mimic ETR to aromatase inhibitors (AI), we developed two long-term estrogen-deprived (LTED) cell lines from BT-474 (BT474) and MDA-MB-361 (MM361). Growth assays, PAM50 molecular subtyping, genomic and transcriptomic analyses, followed by validation and functional studies, were used to identify targetable differences between ET-responsive parental and ETR-LTED HER2+/ER+ cells. Results: Compared to their parental cells, MM361 LTEDs grew faster, lost ER, and increased HER2 expression, whereas BT474 LTEDs grew slower and maintained ER and HER2 expression. Both LTED variants had reduced responsiveness to fulvestrant. Whole-genome sequencing of the more aggressive MM361 LTED model system identified exonic mutations in genes encoding transcription factors and chromatin modifiers. Single-cell RNA sequencing demonstrated a shift towards non-luminal phenotypes, and revealed metabolic remodeling of MM361 LTEDs, with upregulated lipid metabolism and antioxidant genes associated with ferroptosis, including GPX4. Combining the GPX4 inhibitor RSL3 with anti-HER2 agents induced significant cell death in both the MM361 and BT474 LTEDs. Conclusions: The BT474 and MM361 AI-resistant models capture distinct phenotypes of HER2+/ER+ BCa and identify altered lipid metabolism and ferroptosis remodeling as vulnerabilities of this type of ETR BCa.

Medical journals and advertiser tracking-Consequences for patients, clinicians, and editors.

Medical journal websites frequently contain tracking code that transfers data about journal readers to third parties. These data give drug, device, and other medical product companies a potentially powerful resource for targeting advertisements and other marketing materials to journal readers based on unique attributes and medical interests that can be inferred from the articles they read. Thus, while editors may strictly regulate the content of advertisements that such companies place in their journals' pages, they simultaneously provide those companies with the means to target readers in other forums, possibly in ways that subvert editorial guidelines. We examine the implications of third-party tracking on medical journal webpages, and recommend actions that publishers, editors, and academic societies can take to curb it.

3D Covalent Organic Framework as a Metastable Intermediate in the Formation of a Double-Stranded Helical Covalent Polymer.

The design and development of intricate artificial architectures have been pursued for decades. Helical covalent polymer (HCP) was recently reported as an unexpected topology that consists of chiral 1D polymers assembled through weak hydrogen bonds from achiral building blocks. However, many questions remained about the formation, driving force, and the single-handedness observed in each crystal. In this work, we reveal a metastable, racemic, fully covalently cross-linked, 3D covalent organic framework (COF) as an intermediate in the early stage of polymerization, which slowly converts into single-handed HCP double helices through partial fragmentation and self-sorting with the aid of a series of hydrogen bonding. Our work provides an intriguing example where weak noncovalent bonds serve as the determining factor of the overall product structure and facilitate the formation of a sophisticated polymeric architecture.

Veterans Finding Community and a "Home" Within an Emergency Housing Environment.

In April 2020, the Department of Veterans Affairs responded to the COVID-19 pandemic and escalating unsheltered homelessness in Los Angeles by sanctioning a tent turned tiny shelter encampment at the West Los Angeles Veterans Affairs medical center. Initially, staff offered linkages to on-campus VA healthcare. However, as many Veterans living in the encampment struggled to avail themselves of these services, our "encampment medicine" team was launched to provide on-site care coordination and healthcare at the tiny shelters. This case study showcases the team's engagement with a Veteran experiencing homelessness struggling with opioid use disorder and depicts how this co-located, comprehensive care team allowed for trusting care relationships formed with, and empowerment of the Veterans living in the encampment. The piece highlights a healthcare model that engages with persons experiencing homelessness on their own terms while building trust and solidarity, focuses on the sense of community that formed in the tiny shelter encampment, and gives recommendations for how homeless services might adapt to use the strengths of this unique community.

Ethical Responsibilities for Companies That Process Personal Data.

It has become increasingly difficult for individuals to exercise meaningful control over the personal data they disclose to companies or to understand and track the ways in which that data is exchanged and used. These developments have led to an emerging consensus that existing privacy and data protection laws offer individuals insufficient protections against harms stemming from current data practices. However, an effective and ethically justified way forward remains elusive. To inform policy in this area, we propose the Ethical Data Practices framework. The framework outlines six principles relevant to the collection and use of personal data-minimizing harm, fairly distributing benefits and burdens, respecting autonomy, transparency, accountability, and inclusion-and translates these principles into action-guiding practical imperatives for companies that process personal data. In addition to informing policy, the practical imperatives can be voluntarily adopted by companies to promote ethical data practices.