University of North Carolina at Chapel Hill

Background Detection of acute (pre-seroconversion) HIV infection (AHI), the phase of highest transmission risk, requires resource-intensive RNA- or antigen-based detection methods that can be infeasible for routine use. Risk score algorithms can improve the efficiency of AHI detection by identifying persons at highest risk of AHI for prioritized RNA/antigen testing, but prior algorithms have not considered geospatial information, potential differences by sex, or current antibody testing paradigms. Methods We used elastic net models to develop sex-stratified risk score algorithms in a case-control study of persons (136 with AHI, 250 without HIV) attending a sexually transmitted infections (STI) clinic in Lilongwe, Malawi from 2015 to 2019. We designed algorithms for varying clinical contexts according to three levels of data availability: 1) routine demographic and clinical information, 2) behavioral and occupational data obtainable through patient interview, and 3) geospatial variables requiring external datasets or field data collection. We calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to assess model performance and developed a web application to support implementation. Results The highest-performing AHI risk score algorithm for men (AUC=0.74) contained five variables (condom use, body aches, fever, rash, genital sores/ulcers) from the first two levels of data availability. The highest-performing algorithm for women (AUC=0.81) contained fifteen variables from all three levels of data availability. A risk score cut-point of 0.26 had an AHI detection sensitivity of 93% and specificity of 27% for males, and a cut-point of 0.15 had 97% sensitivity and 44% specificity for females. Additional models are available in the web application. Conclusion Risk score algorithms can facilitate efficient AHI detection in STI clinic settings, creating opportunities for HIV transmission prevention interventions during this critical period of elevated transmission risk.

Personalized robotic exoskeleton control is essential in assisting individuals with motor deficits. However, current research still lacks a solution from the end of a practical need of the problem to the end of its successful demonstration in physical environments, namely an end-to-end solution, that enables stable and continuous walking across different tasks. This study addresses this challenge by introducing a hierarchical control framework for the purpose. At the low level, impedance control ensures joint compliance without causing injury to users. At the high level, a reinforcement learning (RL)-based optimal adaptive controller automatically personalizes assistance to both hip extension and flexion (namely, bi-directional) to reach a target range of motion (ROM) under multiple walking conditions. As the first potentially feasible approach to this challenging problem and to meet practical use requirements, we developed a least-square policy iteration-based solution to configure the intrinsic parameters within the well-established finite state machine impedance control (FSM-IC). We successfully tested the control solution on eight young unimpaired participants and one participant post-stroke wearing a hip exoskeleton while walking on an instrumented treadmill. The proposed method can be applied to solving for optimal impedance parameters for individual users and different task scenarios to increase joint ROM. Our next step is to further evaluate this solution framework on additional people with hemiparesis who may benefit from hip joint assistance in therapy or daily activities to restore normative or improve gait patterns.

Background Patients with decompensated cirrhosis have a higher risk of hospitalization, ICU admission, and death from COVID‐19. The impact of demographics on these outcomes remains uncertain. Methods The SECURE‐Liver and COVID‐Hep databases were utilized to evaluate disparities in COVID‐19 outcomes. Patients were stratified by North American and European cohorts. Bivariate and multivariable logistic regression was performed. Results A total of 718 cirrhosis patients with COVID‐19 were evaluated. In the North American cohort, Black patients had more comorbidities (CI: 1.86 vs. 1.83, p < 0.01), higher rates of hospitalization (77% vs. 85%, p < 0.01), ICU admission (27% vs. 40%, p = 0.05), and death (18% vs. 28%, p = 0.07). Hispanic patients had the lowest adverse outcome rates. In the European cohort, White patients had more comorbidities (CI; 1.63 vs. 1.31, p = 0.02), but non‐White patients had higher hospitalization rates (82% vs. 67%, p = 0.01), ICU admissions (15% vs. 18%, p = 0.04), and lower mortality rates (28% vs. 34%, p = 0.01). Conclusion Black patients in North America had higher hospitalization, ICU admission, and death rates. In the European subgroup, White patients had higher death rates than non‐White patients. These disparities became statistically insignificant after adjusting for confounders, suggesting that non‐liver‐related comorbidities might increase the risk of adverse outcomes.

Background Obesity is a chronic, relapsing, progressive disease of excess adiposity that increases the risk of dying from at least 16 types of cancer. The prevalence of obesity has increased more rapidly in cancer survivors compared with the general population. Tailored weight management strategies are needed to improve prognosis and health outcomes in the growing population of cancer survivors. However, certain cancer survivor population subgroups require unique consideration when developing weight management strategies. Methods In a symposium convened by The Obesity Society during ObesityWeek 2023 titled “From Surviving to Thriving: Key Considerations for Weight Control Across Diverse Cancer Survivorship Populations,” experts presented the current state of the science and highlighted existing research gaps. Results Topics included key considerations for weight management in adolescent and young adult cancer survivors, older adult cancer survivors, and understudied cancer survivor subgroups at high risk for poor health outcomes and innovative interventions that can be tested to improve cancer survivorship. Conclusions This report reviews the symposium and offers perspectives from the expert panel about unique opportunities for future research on tailored weight management strategies to equitably improve prognosis and health outcomes in the diverse and growing population of cancer survivors.

We present a novel method for identifying topological features of chromatin domains in live cells using single-particle tracking and topological data analysis (TDA). By applying TDA to particle trajectories, we can effectively detect complex spatial patterns, such as loops, that are often missed by traditional time series analysis. Using simulations of polymer bead–spring chains, we have validated the accuracy of our method and determined its limitations for detecting loops. Our approach offers a promising avenue for exploring the topological complexity of chromatin in living cells using TDA techniques.

Synopsis Kenyan adolescent girls and young women with a history of pregnancy experience poor psychological well‐being, highlighting the need for targeted interventions for this vulnerable demographic.

Hematopoietic cell transplantation (HCT) is a promising treatment for hematologic malignancies, but intensive conditioning leads to immunosuppression and susceptibility to healthcare-associated infections (HAI). Despite standard prevention measures, bloodstream infections (BSI) impact a significant percentage of immunocompromised HCT patients. Incidence of BSI can be mitigated by chlorhexidine gluconate (CHG) bathing—an underutilized infection-prevention strategy. Gaining HCT recipients’ perceptions on CHG bathing can inform strategies to improve adherence and enhance patient outcomes. Purpose This study explored patients’ perceived facilitators, barriers, and education/knowledge related to CHG bathing and thus addresses the gap in implementation for immunocompromised HCT patients. Methods This study used a qualitative description approach to explore patients’ perceived facilitators, barriers, and knowledge of CHG bathing. Fourteen HCT recipients (mean 51 ± 16 years) completed semi-structured interviews. Data were analyzed using a rapid qualitative analysis approach to identify themes. Results Participants identified facilitators to using CHG wipes including ease of use, comfort, and staff assistance, along with barriers including wait time, discomfort, and physical challenges. Patient education themes encompassed patient understanding of CHG purpose, perceived ease in learning/application, inconsistent instruction, and inconsistent procedures. Conclusion CHG bathing is a valuable infection prevention strategy for HCT patients. Participants’ perspectives highlight the importance of addressing practical challenges and improving education to enhance adherence. This study contributes insights from HCT recipients, emphasizing the need for patient-centered interventions to reduce HAI and improve overall patient care.

Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes. Similarly, dual beta-lactam combinations show promise in vitro, but clinical use is sparse. We report here a patient with an uncontrolled Mycobacterium abscessus infection following a bilateral lung transplant and failed antibiotic therapy. Both smooth and rough colony morphotype strains were initially present, but treatment with two phages that kill the rough strain – including epigenetic-modification to overcome restriction – resulted in isolation of only the smooth strain. The rough and smooth strains have similar antibiotic susceptibilities suggesting that the phages specifically eliminated the rough strain. Dual beta-lactam therapy with meropenem and ceftazidime-avibactam provided further clinical improvement, and the phages act synergistically with meropenem in vitro.

Background Leptin, an energy balance regulator secreted by adipocytes, increases metastatic potential of breast cancer cells. The impact on cancer cell metabolism remains unclear given that most studies of leptin and breast cancer cell metabolism utilize supraphysiological glucose concentrations. Methods Using two murine models of metastatic triple-negative breast cancer (TNBC) differing in genetic alterations (4T1: p53 and Pik3ca mutations; metM-Wntlung: increased Wnt signaling) and cultured in physiological (5 mM) glucose media, we tested the hypothesis that leptin increases migration of metastatic breast cancer cells through regulation of glucose metabolism. Results Our results showed that leptin treatment, compared with vehicle, increased cell migration in each cell line, with decreased leptin receptor (Ob-R) mRNA expression in 4T1, but not metM-Wntlung, cells. AMP-activated protein kinase (AMPK) was activated in 4T1 with leptin treatment but decreased in metM-Wntlung. Leptin decreased fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1a (Cpt1a) mRNA expression in 4T1 cells but increased their expression in metM-Wntlung cells. Fatty acid oxidation was not necessary for leptin-induced migration in either cell line. Leptin increased palmitate synthesis from glucose in metM-Wntlung, but not 4T1 cells. Moreover, although leptin increased glucose transporter 1 (Glut1) mRNA expression in both cell lines and inhibition of glycolysis blocked leptin-induced migration in metM-Wntlung, but not 4T1 cells. Conclusion Taken together, these results demonstrate that at physiological glucose concentrations, leptin increases migration of 4T1 and metM-Wntlung cells via shared and distinct effects on energy metabolism, suggesting that the type of TNBC genetic alteration plays a role in differential metabolic regulation of leptin-induced migration.

Administration of fecal microbiota spores, live-brpk [Vowst Oral Spores (VOS)], an oral microbiome therapeutic approved for prevention of recurrent Clostridioides difficile infection in adults, requires antibiotic washout using a laxative prior to administration. Patient acceptability of the prerequisite laxative is important. This study assessed psychometric properties of the Antibiotic Washout Patient Satisfaction Scale (AWPSS) which was minimally modified from a previously validated patient satisfaction scale for bowel preparation prior to colonoscopy. Patients from the ECOSPOR IV trial who received a laxative preparation prior to oral administration of VOS and were administered the AWPSS were included. Reliability and construct validity of the AWPSS were evaluated. AWPSS data were available for 110 patients; all completed all 6 items of the AWPSS, supporting its acceptability. Domain 1 mean/median transformed total scores of 105.9/100 [range (best–worst), 0–300] suggested that patients were satisfied with the laxative preparation; a Cronbach’s alpha of 0.81 showed acceptable reliability. Almost all patients (97.3%) reported they were able to consume the entire laxative solution as instructed and would take it again if needed (95.5%). Higher satisfaction with the laxative preparation predicted higher acceptability of future use if needed (lower score) with mean/median of 101.7/100 and 195.0/200.00 for those who were willing or not willing to accept, respectively (P = 0.008). AWPSS is a valid and reliable 6-item patient-reported outcome measure for use in patients requiring a laxative prior to oral microbiome therapy. AWPSS showed antibiotic washout was well tolerated and predicted that patients would be willing to consume the laxative in the future if needed.

Divorce and remarriage rates have increased dramatically in China, and more children live in stepfamilies. There remain valuable opportunities to understand the various family and school assets that support the well‐being of Chinese youth amid family structural transitions, such as the transition to stepfamily life. Using latent profile analysis, the current study seeks to identify patterns of youth support using seven family‐related variables and two school‐related variables as indicators among a sample of Chinese youth ( N = 269; = 14 years; 129 females and 117 males) residing with a parent and stepparent. Four profiles were identified: low support, academic focus/low support, moderate support, and high support. Results further demonstrated that youth in the moderate support profile had significantly better well‐being outcomes compared to youth in the low support or academic focus/low support profiles; demographic characteristics such as low SES families and parents with lower education backgrounds were associated with the low support profile; and stepfamilies with stepfathers were overrepresented in the moderate support profile, whereas stepfamilies with stepmothers were overrepresented in the low support and academic focus/low support profiles. These findings can inform the development of interventions intended to bolster the well‐being of Chinese adolescents in stepfamilies.

The ethics surrounding the development and deployment of generative artificial intelligence (genAI) is an important topic as institutions of higher education adopt the technology for educational purposes. Concurrently, stakeholders from various organizations have reviewed the literature about the ethics of genAI and proposed frameworks about it. However, there is a dearth of tools available to end users when deciding to adopt a genAI tool. In response, this study’s authors analyzed 30 documents – 10 from industry professionals, 10 from governmental organizations, and 10 from academic scholars – that included frameworks, principles, and guidelines that address the ethics of genAI. Using a content analysis, the authors identified key factors and leveraged them to develop a decision tree that end users can employ for making ethical considerations when choosing to adopt different genAI tools.

Vascular access conduits (fistulas and grafts) are the best options to receive life-sustaining dialysis treatments. Dialysis vascular accesses are prone to malfunction, resulting in numerous problems. Recognition of physical exam and dialysis treatment issues help dialysis staff make recommendations for interventions to fistulas and grafts that are at high risk of thrombosis or other complications. Routine surveillance of the dialysis vascular access helps maintain their functionality and longevity. Screening for access flow via physical exam, ultrasound dilution or dynamic venous pressure monitoring has been used to determine when interventions, including angioplasty, may be indicated.

An access that is difficult to cannulate can prolong dialysis catheter exposure and cause access infiltration, dialysis access vessel injury, pain, and patient discomfort. The success of cannulation depends on a competent cannulator and favorable dialysis access characteristics. The development and optimization of formal training programs for cannulators including quality improvement, regular competency assessments and ultrasound training likely increases successful and safe cannulations. Fistula characteristics including depth, tortuosity, and vein caliber are also important factors. Several surgical and minimally invasive/endovascular techniques have been described to improve those relevant fistula characteristics. In addition, the advent of the endovascular fistula presents a new challenge for the cannulator needing education and in many cases surgical/endovascular interventions to improve the chances of successful cannulation.

Gemtuzumab ozogamicin (GO) is a CD33‐targeting antibody‐drug conjugate approved for the treatment of CD33‐positive de novo and relapsed and refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable‐risk disease. It is unclear whether the addition of GO to cytarabine and anthracycline chemotherapy (7+3) improves clinical outcomes compared with other conventional regimens for AML. We evaluated the real‐world experience with GO added to 7+3 chemotherapy for patients with favorable risk AML. This retrospective analysis included 174 patients with de novo favorable risk AML undergoing induction chemotherapy between 2010 and 2020. The primary outcome was overall survival (OS) and secondary outcomes included rates of remission, measurable residual disease (MRD), and toxicity. Eighteen patients received GO, 37 received a high‐dose (HD) anthracycline, and 119 received an intermediate‐dose anthracycline. Composite complete remission was achieved in 162 patients (93.1%). Among the 54 patients who were assessed for MRD at remission, 66.7% were undetectable. An improvement in OS was seen for patients who received GO and those treated with HD anthracycline, which was better explained by differences in patient performance status and comorbidities. Patients who received GO did not show increased toxicity.

We studied cervicovaginal β-/γ-human papillomavirus (HPV) and their relationship to cervical precancer in women with HIV (WWH); having previously reported strong positive associations of β-/γ-HPV with incident head and neck cancer in the general population. Cases (N=124) had cervical intraepithelial neoplasia (CIN)-3 or CIN-2. Controls (N=247) were individually matched 2:1 to cases. Unexpectedly, multivariate analyses found strong inverse associations between β-/γ-HPV and CIN-2/CIN-3 (OR=0.19; 95% CI 0.04-0.86; P=0.03) with Ptrend<0.01. This is, to our knowledge, the first study of β-/γ-HPV and cervical precancer. If confirmed, a strong inverse (protective) association would be of potential clinical and biologic relevance.