Cancer and COVID-19 Vaccines on Twitter:The Voice and Vaccine Attitude of Cancer Community.

We investigate social media discourses on the relationship between cancer and COVID-19 vaccines focusing on the key textual topics, themes reflecting the voice of cancer community, authors who contribute to the discourse, and valence toward vaccines. We analyzed 6,427 tweets about cancer and COVID-19 vaccines, posted from when vaccines were approved in the U.S. (December 2020) to the February 2022. We mixed quantitative text mining, manual coding and statistical analysis, and inductive qualitative thematic analysis. Nearly 16% of the tweets posted by a cancer community member mentioned about refusal or delay of their vaccination at the state/local level during the initial rollout despite the CDC's recommendation to prioritize adults with high-risk medical conditions. Most tweets posted by cancer patients (pro = 82.4% vs. anti = 5.1%) and caregivers (pro = 89.2% vs. anti = 4.2%) showed positive valence toward vaccines and advocated for vaccine uptake increase among cancer patients and the general population. Vaccine hesitancy, self-reported adverse events, and COVID-19 disruption of cancer treatment also appeared as key themes. The cancer community called for actions to improve vaccination procedures to become safe and accessible especially for elderly cancer patients, develop COVID-19 vaccines suitable for varying type, stage, and treatment of cancer, and advance cancer vaccines. Future research should continue surveilling conversations around continuous impacts of COVID-19 interference with the cancer control continuum, beyond vaccination, focusing on the voice and concern of cancer community.

Emergency Department Pediatric Readiness and Short-term and Long-term Mortality Among Children Receiving Emergency Care.

Importance: Emergency departments (EDs) with high pediatric readiness (coordination, personnel, quality improvement, safety, policies, and equipment) are associated with lower mortality among children with critical illness and those admitted to trauma centers, but the benefit among children with more diverse clinical conditions is unknown. Objective: To evaluate the association between ED pediatric readiness, in-hospital mortality, and 1-year mortality among injured and medically ill children receiving emergency care in 11 states. Design, Setting, and Participants: This is a retrospective cohort study of children receiving emergency care at 983 EDs in 11 states from January 1, 2012, through December 31, 2017, with follow-up for a subset of children through December 31, 2018. Participants included children younger than 18 years admitted, transferred to another hospital, or dying in the ED, stratified by injury vs medical conditions. Data analysis was performed from November 1, 2021, through June 30, 2022. Exposure: ED pediatric readiness of the initial ED, measured through the weighted Pediatric Readiness Score (wPRS; range, 0-100) from the 2013 National Pediatric Readiness Project assessment. Main Outcomes and Measures: The primary outcome was in-hospital mortality, with a secondary outcome of time to death to 1 year among children in 6 states. Results: There were 796 937 children, including 90 963 (11.4%) in the injury cohort (mean [SD] age, 9.3 [5.8] years; median [IQR] age, 10 [4-15] years; 33 516 [36.8%] female; 1820 [2.0%] deaths) and 705 974 (88.6%) in the medical cohort (mean [SD] age, 5.8 [6.1] years; median [IQR] age, 3 [0-12] years; 329 829 [46.7%] female, 7688 [1.1%] deaths). Among the 983 EDs, the median (IQR) wPRS was 73 (59-87). Compared with EDs in the lowest quartile of ED readiness (quartile 1, wPRS of 0-58), initial care in a quartile 4 ED (wPRS of 88-100) was associated with 60% lower in-hospital mortality among injured children (adjusted odds ratio, 0.40; 95% CI, 0.26-0.60) and 76% lower mortality among medical children (adjusted odds ratio, 0.24; 95% CI, 0.17-0.34). Among 545 921 children followed to 1 year, the adjusted hazard ratio of death in quartile 4 EDs was 0.59 (95% CI, 0.42-0.84) for injured children and 0.34 (95% CI, 0.25-0.45) for medical children. If all EDs were in the highest quartile of pediatric readiness, an estimated 288 injury deaths (95% CI, 281-297 injury deaths) and 1154 medical deaths (95% CI, 1150-1159 medical deaths) may have been prevented. Conclusions and Relevance: These findings suggest that children with injuries and medical conditions treated in EDs with high pediatric readiness had lower mortality during hospitalization and to 1 year.

Emergency Department Pediatric Readiness Among US Trauma Centers: A Machine Learning Analysis of Components Associated With Survival.

OBJECTIVE: We used machine learning to identify the highest impact components of emergency department (ED) pediatric readiness for predicting in-hospital survival among children cared for in US trauma centers. BACKGROUND: ED pediatric readiness is associated with improved short-term and long-term survival among injured children and part of the national verification criteria for US trauma centers. However, the components of ED pediatric readiness most predictive of survival are unknown. METHODS: This was a retrospective cohort study of injured children below 18 years treated in 458 trauma centers from January 1, 2012, through December 31, 2017, matched to the 2013 National ED Pediatric Readiness Assessment and the American Hospital Association survey. We used machine learning to analyze 265 potential predictors of survival, including 152 ED readiness variables, 29 patient variables, and 84 ED-level and hospital-level variables. The primary outcome was in-hospital survival. RESULTS: There were 274,756 injured children, including 4585 (1.7%) who died. Nine ED pediatric readiness components were associated with the greatest increase in survival: policy for mental health care (+8.8% change in survival), policy for patient assessment (+7.5%), specific respiratory equipment (+7.2%), policy for reduced-dose radiation imaging (+7.0%), physician competency evaluations (+4.9%), recording weight in kilograms (+3.2%), life support courses for nursing (+1.0%-2.5%), and policy on pediatric triage (+2.5%). There was a 268% improvement in survival when the 5 highest impact components were present. CONCLUSIONS: ED pediatric readiness components related to specific policies, personnel, and equipment were the strongest predictors of pediatric survival and worked synergistically when combined.

Impact of individual components of emergency department pediatric readiness on pediatric mortality in US trauma centers.

BACKGROUND: Injured children initially treated at trauma centers with high emergency department (ED) pediatric readiness have improved survival. Centers with limited resources may not be able to address all pediatric readiness deficiencies, and there currently is no evidence-based guidance for prioritizing different components of readiness. The objective of this study was to identify individual components of ED pediatric readiness associated with better-than-expected survival in US trauma centers to aid in the allocation of resources targeted at improving pediatric readiness. METHODS: This cohort study of US trauma centers used the National Trauma Data Bank (2012-2017) matched to the 2013 National Pediatric Readiness Project assessment. Adult and pediatric centers treating at least 50 injured children (younger than 18 years) and recording at least one death during the 6-year study period were included. Using a standardized risk-adjustment model for trauma, we calculated the observed-to-expected mortality ratio for each trauma center. We used bivariate analyses and multivariable linear regression to assess for associations between individual components of ED pediatric readiness and better-than-expected survival. RESULTS: Among 555 trauma centers, the observed-to-expected mortality ratios ranged from 0.07 to 4.17 (interquartile range, 0.93-1.14). Unadjusted analyses of 23 components of ED pediatric readiness showed that trauma centers with better-than-expected survival were more likely to have a validated pediatric triage tool, comprehensive quality improvement processes, a pediatric-specific disaster plan, and critical airway and resuscitation equipment (all p < 0.03). The multivariable analysis demonstrated that trauma centers with both a physician and a nurse pediatric emergency care coordinator had better-than-expected survival, but this association weakened after accounting for trauma center level. Child maltreatment policies were associated with lower-than-expected survival, particularly in Levels III to V trauma centers. CONCLUSION: Specific components of ED pediatric readiness were associated with pediatric survival among US trauma centers. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Micelle Formation and Phase Separation of Poloxamer 188 and Preservative Molecules in Aqueous Solutions Studied by Small Angle X-ray Scattering.

Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of the preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated.

Cladribine Reduces Trans-Endothelial Migration of Memory T Cells across an In Vitro Blood-Brain Barrier.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory effect on lymphocytes at the blood-brain barrier (BBB) in addition to its lymphocyte-depleting and modulating effects, this has not been properly studied. Here, we aimed to determine if cladribine treatment influences trans-endothelial migration of T cell subsets across an inflamed BBB. Human brain endothelial cells stimulated with pro-inflammatory cytokines were used to mimic the BBB. Peripheral blood mononuclear cells were obtained from healthy controls, untreated and cladribine-treated MS patients. The trans-endothelial migration of CD4+ effector memory T (TEM) and CD8+ central memory T (TCM) cells was reduced in cladribine-treated MS patients. CD28 expression was decreased on both CD4+ TEM and CD8+ TCM cells, suggesting lowered peripheral activation of these cells thereby maintaining the integrity of the BBB. In addition, these cells have likely reconstituted following cladribine treatment, revealing a long-term anti-migratory effect. These results highlight new mechanisms by which cladribine acts to control MS pathogenesis.

Aggregation Kinetics of Polysorbate 80/m-Cresol Solutions: A Small-Angle Neutron Scattering Study.

Polysorbate 80 (PS80), a nonionic surfactant used in pharmaceutical formulation, is known to be incompatible with m-cresol, an antimicrobial agent for multi-dose injectable formulations. This incompatibility results in increased turbidity caused by micelle aggregation progressing over weeks or longer, where storage temperature, ionic strength, and component concentration influence the aggregation kinetics. Small-angle neutron scattering (SANS) analysis of PS80/m-cresol solutions over a pharmaceutically relevant concentration range of each component reveals the cause of aggregation, the coalescence mechanism, and aggregate structure. PS80 solutions containing m-cresol concentrations below ≈2.0 mg/mL and above ≈4.5 mg/mL are kinetically stable and do not aggregate over a 50 h period. At 5 mg/mL of m-cresol, the mixture forms a kinetically stable microemulsion phase, despite being well below the aqueous solubility limit of m-cresol. Solutions containing intermediate m-cresol concentrations (2.0-4.5 mg/mL) are unstable, resulting in aggregation, coalescence, and eventual phase separation. In unstable solutions, two stages of aggregate growth (nucleation and power-law growth) are observed at m-cresol concentrations at or below ≈3.6 mg/mL. At higher m-cresol concentrations, aggregates experience a third stage of exponential growth. A single kinetic model is developed to explain the stages of aggregate growth observed in both kinetic mechanisms. This work establishes the phase diagram of PS80/m-cresol solution stability and identifies component concentrations necessary for producing stable formulations.

The Oxymoron of Financial Illiteracy in a Highly Educated Population: Are We Appropriately Equipping Trainees?

Medical professionals often incur a significant financial burden in pursuit of a medical education. Despite rigorous medical education, financial education appears to be lacking during training. This study intended to explore the financial preparedness and education of 2 cohorts of medical professionals-alumni graduates of a single institution and current plastic surgery residency trainees. METHODS: An electronic survey of the residency alumni at a single institution across all specialties over a 50-year period was conducted. This was conducted concurrent with a survey to current plastic surgery residency trainees across the country. The survey explored several core financially relevant areas, including financial education at various levels of training, fiscal goals, debt profile, spending and saving habits, investment management, financial and family obligations, estate planning, and retirement preparedness. RESULTS: A total of 521 alumni and 84 residents completed the survey from the residency alumni cohort and plastic surgery training programs cohort, respectively. Results from both groups demonstrated that although the large majority considered financial education a priority, this was not prioritized in medical or residency training. Most were introduced to financial education either by a family member or by self-directed learning. Data on investments, savings, finances, and retirement planning are also presented. CONCLUSIONS: As a very literate group, there is an unacceptably high level of "illiteracy" concerning financial education at an early stage. Practicing physicians and current trainees believe that a more directed approach to financial education should be adopted, rather than the current laissez-faire climate during medical education and residency training.

The structure and organisation of home-based postnatal care in public hospitals in Victoria, Australia: A cross-sectional survey.

BACKGROUND: There is limited evidence regarding the provision of home-based postnatal care, resulting in a weak evidence-base for policy formulation and the further development of home-based postnatal care services. AIM: To explore the structure and organisation of public hospital home-based postnatal care in Victoria, Australia. METHODS: An online survey including mostly closed-ended questions was sent to representatives of all public maternity providers in July 2011. FINDINGS: The response rate of 87% (67/77) included rural (70%; n=47), regional (15%; n=10) and metropolitan (15%; n=10) services. The majority (96%, 64/67) provided home-based postnatal care. The median number of visits for primiparous women was two and for multiparous women, one. The main reason for no visit was the woman declining. Two-thirds of services attempted to provide some continuity of carer for home-based postnatal care. Routine maternal and infant observations were broadly consistent across the services, and various systems were in place to protect the safety of staff members during home visits. Few services had a dedicated home-based postnatal care coordinator. DISCUSSION AND CONCLUSION: This study demonstrates that the majority of women receive at least one home-based postnatal visit, and that service provision on the whole is similar across the state. Further work should explore the optimum number and timing of visits, what components of care are most valued by women, and what model best ensures the timely detection and prevention of postpartum complications, be they psychological or physiological.

The safe zone for placement of chin implants.

BACKGROUND: Alloplastic chin augmentation requires the surgeon to predict the location of the mental foramen and the origin of the mentalis muscle to avoid the postoperative sequelae lower lip parasthesia, lower lip incompetence, or chin ptosis. The authors define a safe zone of dissection along the inferior border of the mandible for placement of alloplastic chin implants. METHODS: Fourteen fresh cadaveric hemifaces were dissected with the aid of loupe magnification. Previously described anatomic landmarks were used to identify the origin of the mentalis muscle and the location of the mental foramen along the alveolar ridge of the mandible. Vertical distances were then measured from the mandibular border to the inferior aspect of the mentalis muscle origin and the lower edge of the mental foramen to construct the zone of safe dissection. RESULTS: The mentalis was identified as a fan-shaped muscle originating from the alveolar process below the incisors roots and inserting into the chin just below the labiomental sulcus. The mental foramen was located most commonly below the roots of the first and second premolars or in the space between the roots. The mentalis origin and the mental foramen were 1.8 ± 0.3 cm and 1.5 ± 0.2 cm cephalad to the inferior edge of the mandible, respectively. These distances define the borders of a safe zone above the mandibular border. CONCLUSIONS: A safe zone of dissection for alloplastic chin augmentation is identified. This study is applicable to implant placement through a submental or an intraoral incision. This safe zone is also useful for reconstructive or orthognathic mandible procedures.

Caudal resection of the upper lateral cartilages and its measured effect on tip rotation.

BACKGROUND: Commonly used maneuvers for upward tip rotation include cephalic trim of the lateral alar cartilages, caudal resection of the septum, and shortening of the upper lateral cartilages (ULCs). Few techniques for surgical manipulation of the ULCs are found in the literature, and none accurately describe the measured effect of the caudal resection on tip rotation. The purpose of this study is to predict the change in upward rotation of the nasal tip for a measured incremental resection of the ULCs. METHODS: Ten fresh cadaveric noses were dissected with the aid of loupe magnification via an open rhinoplasty approach. The ULCs were sectioned in 20% increments, and measurements of the nasolabial angle (NLA) were recorded with the use of a goniometer. True lateral photographs were obtained for the photographic analysis of the specimens. RESULTS: The average length of the ULC was 16.8 ± 1.6 mm. Serial reduction of the ULC length by 4 sequential 20% increments resulted in a mean NLA change of 3.6, 2.7, 2.1, and 1.9 degrees, respectively. The average incremental change in NLA for the 4 resections was 2.6 degrees. CONCLUSIONS: Caudal resection of the ULC has a measurable effect on the upward rotation of the nasal tip. A 20% resection correlates with an average change in the NLA of 2.6 degrees. Because caudal resection of the ULC is a powerful tool in the armamentarium of the rhinoplasty surgeon that can cause narrowing of the internal nasal valve and hallowing of the lower nasal sidewalls, it should be used with caution in a selected group of patients when attempting to elevate the "droopy" tip.

Africa has unique and urgent barriers to cleft care: lessons from practitioners at the Pan-African Congress on Cleft Lip and Palate.

BACKGROUND: The goals of this study were to delineate the protocols employed for managing patients with cleft lip and palate deformities, delineate the challenges facing practitioners and patients, and to determine the patient and physician barriers to cleft care delivery in the region. METHODS: Survey questionnaires were administered to practitioners attending the second Pan-African Congress on Cleft Lip and Palate (PACCLIP), which took place in Ibadan, Nigeria, West Africa from February 4-7, 2007. The conference included 225 participants, representing 17 African countries RESULTS: Protocols for repair of cleft lip and palate deformities were varied, with Millard's and von Langenbeck's techniques being the preferred approach for the management of cleft lip and palate deformities, respectively. A large proportion of providers have limited access to core cleft care supporting teams, especially speech language pathologists, orthodontists, and audiologists. Several challenging barriers to cleft care were also identified at both the institutional and individual levels and are reported. CONCLUSION: Geographic separation in Africa presents a similar challenge due to isolationism as it does to surgeons in Europe. Specific to Africa are the increased barriers to care, and economic and financial hardship at various levels. A focus on funding, team building, infrastructural support, and patient education appear to be crucial in improving the care and lives of children with facial clefts in Africa.

Quantitative Interactor Screening with next-generation Sequencing (QIS-Seq) identifies Arabidopsis thaliana MLO2 as a target of the Pseudomonas syringae type III effector HopZ2.

BACKGROUND: Identification of protein-protein interactions is a fundamental aspect of understanding protein function. A commonly used method for identifying protein interactions is the yeast two-hybrid system. RESULTS: Here we describe the application of next-generation sequencing to yeast two-hybrid interaction screens and develop Quantitative Interactor Screen Sequencing (QIS-Seq). QIS-Seq provides a quantitative measurement of enrichment for each interactor relative to its frequency in the library as well as its general stickiness (non-specific binding). The QIS-Seq approach is scalable and can be used with any yeast two-hybrid screen and with any next-generation sequencing platform. The quantitative nature of QIS-Seq data make it amenable to statistical evaluation, and importantly, facilitates the standardization of experimental design, data collection, and data analysis. We applied QIS-Seq to identify the Arabidopsis thaliana MLO2 protein as a target of the Pseudomonas syringae type III secreted effector protein HopZ2. We validate the interaction between HopZ2 and MLO2 in planta and show that the interaction is required for HopZ2-associated virulence. CONCLUSIONS: We demonstrate that QIS-Seq is a high-throughput quantitative interactor screen and validate MLO2 as an interactor and novel virulence target of the P. syringae type III secreted effector HopZ2.

Protein glycosylation in Helicobacter pylori: beyond the flagellins?

Glycosylation of flagellins by pseudaminic acid is required for virulence in Helicobacter pylori. We demonstrate that, in H. pylori, glycosylation extends to proteins other than flagellins and to sugars other than pseudaminic acid. Several candidate glycoproteins distinct from the flagellins were detected via ProQ-emerald staining and DIG- or biotin- hydrazide labeling of the soluble and outer membrane fractions of wild-type H. pylori, suggesting that protein glycosylation is not limited to the flagellins. DIG-hydrazide labeling of proteins from pseudaminic acid biosynthesis pathway mutants showed that the glycosylation of some glycoproteins is not dependent on the pseudaminic acid glycosylation pathway, indicating the existence of a novel glycosylation pathway. Fractions enriched in glycoprotein candidates by ion exchange chromatography were used to extract the sugars by acid hydrolysis. High performance anion exchange chromatography with pulsed amperometric detection revealed characteristic monosaccharide peaks in these extracts. The monosaccharides were then identified by LC-ESI-MS/MS. The spectra are consistent with sugars such as 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Ac7Ac) previously described on flagellins, 5-acetamidino-7-acetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac), bacillosamine derivatives and a potential legionaminic acid derivative (Leg5AmNMe7Ac) which were not previously identified in H. pylori. These data open the way to the study of the mechanism and role of protein glycosylation on protein function and virulence in H. pylori.

Pituitary duplication with nasopharyngeal teratoma and cleft palate.

Pituitary gland duplication is a rare malformation of unknown cause that is often associated with a nasopharyngeal teratoma, among other secondary malformations. This clinical report describes a case of pituitary gland duplication with a nasopharyngeal teratoma, cleft palate, and hypothalamic hamartoma, as well as the surgical management of this patient. This case also raises the question of whether the nasopharyngeal teratoma is the cause of the pituitary duplication above and the cleft palate below or whether it is a result of the primary duplication of the notochordal process. Various theories are presented in an attempt to answer this question, but the exact cause of these malformations remains equivocal. Future research in this topic may elucidate the answer to this question.