Citations

Abstract Introduction The COVID-19 pandemic impacted many higher education institutions. Understanding the personal protective beliefs and behaviors surrounding public health measures such as facemasking, social distancing, and handwashing helps to inform public health outreach measures. Objective This study evaluates the beliefs and occurrences of facemasking, social distancing, and handwashing behaviors among people at a multi-campus, public university in Pennsylvania. Methods From October 5 - November 30, 2021, a 10-minute REDCap survey was available to students, faculty, and staff 18 years of age and older at the Pennsylvania State University (PSU). Recruitment included targeted email, social media, digital advertisements, and university newspapers. 4,231 responses were received. Simple percentage associations between the selected factors and facemasking behaviors as well as beliefs on the origin of the COVID-19 virus were made with IBM SPSS Statistics, version 29.0.2.0 (20). Multivariable logistic regression analyses were performed using R statistical software to identify factors associated with facemasking, social distancing, and handwashing behaviors. Results Of 3,662 completed surveys, 65.2% of respondents were positive that facemasks prevented the transmission of airborne disease, 49.9% of the respondents stated that they wore facemasks always (27.9%), almost always (26.9%), or often (11.1%). 65.3% believed social distancing prevented transmission of COVID-19, 57.5% reported social distancing while on-campus or out in public (always: 18.8%, almost always: 20.3%, often: 18.4%). The response rate for some level of conscientiously washing hands for the 20 second duration was 87.5% (always: 26.0%, almost always: 31.9%, sometimes: 19.9%, only after being out in public: 4.9%, and only when convenient: 4.8%). Belief in effectiveness of personal protective measures was the strongest predictor of masking and social distancing behaviors. Faculty were more likely than students to report consistent masking, while other behaviors lacked this role-based significance. Social distancing was strongly associated with age and political views, and handwashing was strongly associated with gender. Conclusions Beliefs in public health and safety measures during the COVID-19 pandemic did not always match the behaviors of individuals surveyed. Understanding barriers to performing behaviors or public health safety may help inform future areas for targeted intervention. Adherence to personal protective behaviors varied across age, gender, institutional role, and political leaning, further emphasizing the importance of targeted public health education.

Abstract Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4 + and CD8 + T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors’ production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment.

PURPOSE Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care. METHODS SIERRA (ClinicalTrials.gov identifier: NCT02665065 ) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population. RESULTS The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively. CONCLUSION The 131 I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.

AbstractObjectiveThe aim of this study was to evaluate the feasibility and plan quality of spot‐scanning proton arc therapy (SPArc) using a synchrotron‐accelerator‐based proton therapy system compared to intensity‐modulated proton therapy (IMPT).ApproachFive representative disease sites, including head and neck, lung, liver, brain chordoma, and prostate cancers, were retrospectively selected. Both IMPT and SPArc plans are generated with the HITACHI ProBEAT PBS system's minimum MU constraints and physics beam model. The SPArc plans are generated with 2.5° sampling frequency. The static delivery time was simulated based on the previously published synchrotron delivery sequence model, and the dynamic delivery time was simulated using a proton arc gantry mechanical model integrated with the synchrotron delivery sequence. Both dosimetric plan quality and delivery efficiency are evaluated.Main resultsA superior plan quality is reached compared with the IMPT plans generated for the same disease site. However, a relatively prolonged static and dynamic delivery time post new challenge, as static time increased by 49.22% and dynamic time 59.10% on average.SignificanceThis study presents the first simulation results of delivering the SPArc plans using a synchrotron‐accelerated proton therapy system. The result shows its feasibility and limitations, which could guide future development.

This cross-sectional study examines the frequency of increased intracranial pressure and its association with myelin oligodendrocyte glycoprotein antibody-associated disease in patients of various ages.

Abstract Background: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive, and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited. Methods: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case–control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium. Results: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had &gt;20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (&lt;20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population. Conclusions: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification. Impact: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts.

Context.— Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare, and lesions may resemble conventional bowel polyps. Objective.— To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture. Design.— The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin–stained slides. Results.— The patients were 13 men and 2 women aged 26–80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, rectosigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2–2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically, the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass. Conclusions.— Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.