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Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n?=?35) and high-risk (n?=?12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n?=?2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

To be viable therapeutics, antibodies must be tolerated by the human immune system. Rational approaches to reduce the risk of unwanted immunogenicity involve maximizing the ‘humanness’ of the candidate drug. However, despite the emergence of new discovery technologies, many of which start from entirely human gene fragments, most antibody therapeutics continue to be derived from non-human sources with concomitant humanization to increase their human compatibility. Early experimental humanization strategies that focus on CDR loop grafting onto human frameworks have been critical to the dominance of this discovery route but do not consider the context of each antibody sequence, impacting their success rate. Other challenges include the simultaneous optimization of other drug-like properties alongside humanness and the humanization of fundamentally non-human modalities such as nanobodies. Significant efforts have been made to develop in silico methodologies able to address these issues, most recently incorporating machine learning techniques. Here, we outline these recent advancements in antibody and nanobody humanization, focusing on computational strategies that make use of the increasing volume of sequence and structural data available and the validation of these tools. We highlight that structural distinctions between antibodies and nanobodies make the application of antibody-focused in silico tools to nanobody humanization non-trivial. Furthermore, we discuss the effects of humanizing mutations on other essential drug-like properties such as binding affinity and developability, and methods that aim to tackle this multi-parameter optimization problem.

Introduction Human papillomavirus (HPV) vaccination rates are lower than other recommended adolescent vaccines. Cancer survivor narratives are used to promote cancer prevention and control, but little is known about their impact on adolescent HPV vaccination. Objective This pilot study explored the feasibility and effects of a video education intervention using a cancer survivor narrative to improve parents’ attitudes toward and intentions to get the HPV vaccine. Methods This study utilized a one-group design; participants completed a pre-intervention survey, watched the video before attending their sons’ wellness visits, and completed a post-intervention survey within one week of their appointment. Using the narrative persuasion framework, we developed a 4-minute video of a local HPV-related cancer survivor to promote the HPV vaccine as cancer prevention. We recruited 37 participants between June and October 2020. Participants were parents of males ages 9-17 who had not yet initiated HPV vaccination. Results After the video, more parents agreed that HPV vaccination is safe (pre: 66% vs. post: 82%; P = .045) and that their child’s chances of getting HPV-related cancer in the future are high (pre: 24% vs. post: 46%; P = .014). Overall, 91% of parents felt the cancer survivor story helped them understand the risks of HPV cancers, and 52% said the story influenced their decision to start HPV vaccination for their child. Conclusions Our findings suggest that cancer survivor narratives influence parents’ vaccine opinions and understanding of their child’s risk of HPV infection, leading to increased parental intent to get the HPV vaccine for their adolescent males.

Background: We demonstrate a case series of 8 pediatric patients, all under 30 kg, who had leadless pacemaker implants via the internal jugular vein. Methods: A retrospective review of pediatric leadless pacing placement via the internal jugular vein at the University of Minnesota Masonic Children's Hospital and UC Davis Medical Center from 2018 through 2021 was performed. Rationales for pacing, demographics of patients, pacing thresholds, and longevity of devices were recorded. Results: Eight internal jugular pacemaker insertions were performed successfully in patients weighing between 10.9 kg and 29 kg. Five patients had Micra implantation via the right internal jugular vein, whereas 3 patients had insertion via the left internal jugular vein. No surgical cut-downs were performed. No venous complications occurred. Up to 3 years of follow-up were noted. Conclusion: Leadless pacemaker implantation, via left or right internal jugular veins, is feasible without surgical cutdown in patients

Abstract Background The decision to initiate pharmacotherapy is integral in the care for pregnant women with gestational diabetes mellitus (GDM). We sought to compare pregnancy outcomes between two threshold percentages of elevated glucose values prior to initiation of pharmacotherapy for GDM. We hypothesized that a lower threshold at pharmacotherapy initiation will be associated with lower rates of adverse perinatal outcomes. Methods This was a retrospective cohort study of women with GDM delivering in a single tertiary care center. Pregnancy outcomes were compared using bivariable and multivariable analyses between women who started pharmacotherapy (insulin or oral hypoglycemic agent) after a failed trial of dietary modifications at two different ranges of elevated capillary blood glucose (CBG) values: Group 1 when 20–39% CBG values were above goal; Group 2 when ≥40% CBG values were above goal. The primary outcome was a composite GDM-associated neonatal adverse outcome that included: macrosomia, large for gestational age (LGA), shoulder dystocia, hypoglycemia, hyperbilirubinemia requiring phototherapy, respiratory distress syndrome, stillbirth, and neonatal demise. Secondary outcomes included cesarean delivery, preterm birth (

Objectives: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. Patients and methods: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. Results: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. Conclusion: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

We sought to characterize parents who look for second medical opinions to get human papillomavirus (HPV) vaccine for their children and whether second opinions influenced acceptance of HPV vaccine. Between July and August 2019, we conducted an online survey with a national sample of 906 parents of adolescents ages 11–17. We used multivariable logistic regression to assess correlates of looking for second opinions on HPV vaccination. For those who looked for second opinions, the survey assessed their HPV vaccine information needs and whether their child ultimately received the vaccine. Overall, 15% of parents reported looking for second opinions. Parents were more likely to look for second opinions if their self-reported knowledge about HPV vaccine was the same (Odds ratio [OR] = 1.94; 95% confidence interval [CI]:1.13, 3.30) or more (OR = 3.97; 95% CI:2.35, 6.73) than their child’s provider, or if they reported seeing HPV vaccine information on social media (OR = 2.50; 95% CI:1.69, 3.69). Parents were also more likely to look for second opinions if they were male, reported low vaccine confidence, disagreed with social norms favoring HPV vaccination, or had a young child (all p

Objective: We sought to identify patients at risk of incomplete transvaginal oocyte retrieval, develop a risk assessment formula to identify patients who would benefit from a transabdominal approach, and compare complication and pregnancy rates between these two approaches. Materials and Methods: In this retrospective case control study in a private in vitro fertilization center, 95 cases of women undergoing transabdominal follicular aspiration for oocyte retrieval (15 transabdominal only and 80 transabdominal and vaginal combined) were compared with 278 controls of women undergoing the transvaginal aspiration only. Transabdominal oocyte retrieval was performed when one or more ovaries could not be retrieved via the transvaginal approach. Main study outcomes included need for transabdominal retrieval, pregnancy rates, and complications. Results: A risk assessment scoring system was developed as follows: difficulty seeing ovaries on ultrasound (+4), history of pelvic surgery (+3), and body mass index of 30 kg/m2 or greater (+2). With a cutoff score of 4 or greater, the overall sensitivity is 75%, specificity is 80%, positive predictive value is 57%, and negative predictive value is 90%. No statistically significant differences were found for pregnancy rates or complications. Conclusion: The transabdominal approach is an alternative option that would increase the total number of oocytes retrieved with no statistical difference in complication or pregnancy rates. We also developed a scoring system that can serve as a useful screening tool for identifying women at increased risk of transabdominal oocyte retrieval.