STEPS (Study To Examine Parent, Patient/Dental Provider Systems) to Prevent Human Papillomavirus (HPV)-Related Cancers: A Piloted Dental Patient and Provider Evaluation of Current and Future HPV Education.

Oropharyngeal human papillomavirus (HPV) cancers are prevalent, but HPV education in dental clinics is uncommon. The purpose of this study was to evaluate dental provider and patient knowledge from, attitudes towards, and preferences for HPV education, then assess perceptions of existing HPV educational materials for use at dental visits. Appalachian Ohio dental patients (n = 13) and general/pediatric dental providers (n = 10) completed an initial, close-ended survey on current HPV knowledge and HPV educational attitudes, participation, and resource preferences. Select individuals reviewed existing HPV educational videos and toolkits via virtual focus groups (n = 9) or independent review surveys (n = 6). Using a discussion guide, participants responded to overall, visual, auditory, and content satisfaction statements, orally (focus groups) or with Likert scales (independent reviews). Surveys were summarized with frequencies/percentages; transcripts were qualitatively coded to identify potential material modifications. Dental providers and patients were more comfortable with HPV and oral cancer education (87% and 96%, respectively) and screening (96%) than with HPV vaccine education (74%) and referrals (61%) during dental visits. Providers were neither sharing HPV educational materials (80%) nor initiating educational conversations with dental patients (100%). The American Cancer Society videos and the "Team Maureen" toolkit were the most liked resources (i.e., fewer negative/disagree statements) by all participant groups. Findings indicate that future dental HPV educational efforts should be informed by currently available materials. Additional interventions are needed to promote dental provider discussions and sharing of educational materials with patients to increase education and promotion of the HPV vaccine and reduce oropharyngeal cancers.

Habitat and movement selection processes of American lobster/jakej within a restricted bay in the Bras d'Or Lake/Pitu'paq, Nova Scotia, Canada.

American lobster inhabit the unique, brackish Bras d'Or Lake system, although densities are low compared to areas with similar habitats in the Atlantic Ocean. Nevertheless, lobsters are an important part of local First Nation (Mi'kmaq) food and culture. We used acoustic telemetry and habitat mapping, combined with local Mi'kmaw knowledge, to document the movements and habitat use of adult lobsters within a section of the Lake. Movement patterns of acoustically tagged individual lobsters were analyzed with both resource selection functions and integrated step selection functions using data obtained from a high-resolution VEMCO Positioning System within a restricted bay in the Bras d'Or Lake. The resource selection function suggested stronger selections of substrates that contained a combination of soft and hard sediments. While the integrated step selection functions found substantial individual variability in habitat selections, there was a trend for lobsters to exhibit more resident behaviour on the combined soft/hard substrates despite the fact these sediments provided little in the way of obvious shelters for the animals. Adult lobsters at this site have very little risk of predation, which presumably allows them to freely exhibit exploratory behaviours and reduce their association with substrates that provide shelters.

A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer".

What is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that uses a patient's own immune system to treat endometrial cancer. Dostarlimab is a type of medicine called an immunotherapy. Immunotherapies help the immune system find and attack cancer cells. Dostarlimab stops cancer cells from being able to hide from the immune system, which allows the patient to have a boosted immune response against their cancer.The RUBY study is a phase 3 clinical study of primary advanced (cancer that has spread outside the uterus) or recurrent (cancer that has come back) endometrial cancer. A phase 3 clinical study looks at how well a new treatment works compared to the standard, or usual, treatment in a large patient population. The RUBY study is testing how well dostarlimab given with chemotherapy, followed by dostarlimab alone, works at delaying primary advanced or recurrent endometrial cancer from getting worse and preventing patients from dying, compared to chemotherapy given alone (the current standard treatment for primary advanced or recurrent endometrial cancer).What were the results? When dostarlimab was given with chemotherapy, this combination was found to delay primary advanced or recurrent endometrial cancer from getting worse and to prevent patients from dying, compared with chemotherapy given alone (without dostarlimab). Patients in the study who received dostarlimab with chemotherapy had a 36% lower risk of dying or having their cancer get worse.What do the results mean? The results from this study contributed to the approval of dostarlimab with chemotherapy as a new treatment option for patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer. As of the publication of this plain language summary of publication (PLSP), this combination of dostarlimab with chemotherapy has been approved in the United States of America, the United Kingdom, the European Union and Hong Kong.Clinical Trial Registration: NCT03981796 (RUBY).

Exploration of helpful elements contributing to engage in physical activity in patients with cancer.

PURPOSE: Although there are many reported benefits of physical activity for patients with cancer (e.g., improving quality of life), many patients with cancer do not meet the recommendations of physical activity guidelines. The amount of physical activity declines after diagnosis of cancer. This study aimed to clarify the elements that contribute engagement in regular moderate-or-higher-level intensity of physical activity (MHPA), based on the Health Action Process Approach (HAPA), among patients with cancer. METHODS: Two web surveys were conducted among cancer outpatients, asking them to respond to a questionnaire. Participants provided information regarding their demographics, physical activity, purpose, advantages, disadvantages, barriers, triggers, and need for support for regular MHPA. RESULTS: Categories were obtained for purposes, advantages, disadvantages, barriers, triggers, and support needs for regular MHPA. For example, the support they considered necessary to regularly engage in MHPA were developed 9 categories, such as Improving the environment, Support for the implementation of PA (interpersonal), and Reducing the burden. Women and younger patients provided more statements about reducing their burden; younger patients also mentioned on improving the environment more among those who did not engage in MHPA. Additionally, patients with cancer who provided statements about interpersonal support reported higher barriers to physical activity. CONCLUSIONS: These findings will contribute to the development of a scale to measure the components of the HAPA on physical activity in patients with cancer. In addition, it will help develop a support system that promotes engagement in regular MHPA.

Performance and failure of right ventricle to pulmonary artery conduit in congenital heart disease.

INTRODUCTION: Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery but with limited durability leading to re-intervention. Current single-center, retrospective, cohort study is reporting results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. METHODS: Patients with CHD referred for RV-PA conduits surgical implantation (October 1997 and January 2022) have been included. Primary outcome was conduit failure defined as peak gradient above 64mmHg/severe regurgitation/need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effect linear regression analysis. RESULTS: Two-hundred and fifty-two patients were initially included. One hundred and forty-nine patients were elegible for follow-up data collection. After a median follow-up time of 49 months the primary study endpoint occurred in 44 (29%) patients. Multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft as protective factors (HR 0.11, 95% CI 0.02-0.47 and HR 0.34, 95% CI 0.16-0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (OR 4.29, 95% CI 1.41-13.01). Longterm use of oral anticoagulant was independently associated with slower progression of peak echocardiographic gradient across conduits (mixed effect linear regression p-value 0.027). CONCLUSION: In patients with CHD, surgically implanted RV-PA conduit failure is faster in children and after non-homograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Longterm anticoagulation seems to exert a protective effect.

Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data.

BACKGROUND: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. METHODS: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. RESULTS: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF. CONCLUSIONS: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles.

Using GPS-defined venue-based affiliation networks among Black sexually minoritized men and transgender women to identify locations for HIV prevention interventions.

PURPOSE: HIV biomedical intervention uptake is suboptimal among Black sexually minoritized men (SMM) and transgender women (TW). Venues where people meet and interact shape HIV-related risk and prevention behaviors. We aimed to construct GPS-defined venue-based affiliation networks and identify the unique set of venues that could maximize reach of HIV biomedical interventions among Black SMM and TW. METHODS: We used baseline survey and GPS data from 272 Black SMM and TW in the Neighborhoods and Networks (N2) Cohort Study in Chicago, Illinois (2018-2019). We mapped participants' GPS data to the nearest pre-identified SMM- and TW-friendly venue (n = 222) to construct affiliation networks. Network analyses were performed to identify influential venues that can yield high reach to intervention candidates. RESULTS: Participants were affiliated with 75.5 % of all pre-identified venues based on GPS data. Two influential venues were identified in the non-PrEP use network, which when combined, could reach 52.5 % of participants not taking PrEP. Participants that could be reached through these two influential venues reported more non-main sex partners than participants not affiliated with either venue (p = 0.049). CONCLUSION: We demonstrate a potential for GPS-defined venue-based affiliation networks to identify unique combinations of venues that could maximize the impact of HIV prevention interventions.

Confined Crystallization Polyether-Based Flexible Phase Change Film for Thermal Management.

Phase change materials (PCMs) possess the potential to regulate temperature by utilizing their thermal properties to absorb and release heat. Nevertheless, the application of PCMs in thermal management is constrained by issues such as liquid leakage and limited flexibility. In this study, we propose a novel approach to address these challenges by incorporating a pore structure within nanofibers to confine the crystallization of phase change molecules, thereby enhancing the flexibility of the composite material. Additionally, inspired by the adaptive mechanisms observed in plants, we have developed a form stable PCM based on polyether, which effectively mitigates the issue of liquid leakage at higher temperatures. Despite being a solid-liquid PCM at its core, this material exhibits molecular-scale flow and macroscopic shape stability as a result of intermolecular forces. The composite film material possesses remarkable flexibility, efficient thermal management capabilities, adjustable phase transition temperature, and the ability to undergo repeated processing and utilization. Consequently, it holds promising potential for applications in personal thermal energy management.

Management of traumatic incomplete lacerating rectus muscle injuries using multimodal imaging approach (ASOCT and CT/MRI).

Purpose: To describe the pathophysiology, importance of multimodal imaging approach, and the clinical outcomes of incomplete lacerating rectus muscle injuries. Methods: A retrospective review was conducted to identify patients with ocular deviation secondary to rectus muscle injuries. Between 2019 and 2022, a total of 30 patients were identified, amongst whom eleven patients had incompletely lacerated rectus muscles (secondary to penetrating adnexal trauma and sino-orbital surgeries). Patients' demography, nature of injury, computed tomography/magnetic resonance imaging, anterior segment optical coherence tomography features, intra-operative findings, and post-operative outcomes were reviewed. Results: The mean age of 11 patients was 31.36 ± 14.38 years. All patients had external trauma which severed the muscle in its anterior portion. Five patients had isolated inferior rectus muscle injury (45.45%), three had inferior and medial rectus muscle injuries together (27.27%), two had isolated lateral rectus muscle injury (18.18%), and one remaining patient had isolated medial rectus muscle injury (9.05%). In ten patients (90.90%) CT/MRI revealed features suggestive of muscle injury, however details with respect to muscle insertion and scleral course were lacking. In this difficult scenario, ASOCT filled these lacunae in nearly 90% of the patients by providing surgically useful details. Moreover, when CT/MRI-ASOCT imaging features were combined, the management and outcomes were even more predictable. Conclusions: Penetrating rectus muscle injuries can be better identified as incompletely lacerated muscle using multimodal imaging approach. This simple image correlation process customizes the treatment approach and hence the clinical outcomes.

Household- and community-level factors of zero vegetable or fruit consumption among children aged 6-23 months in East Africa.

Introduction: The World Health Organization recommends that children aged 6-23 months should consume a diversified diet, including fruits and vegetables, during each meal. However, low consumption of fruits and vegetables contributes to 2.8% of child deaths globally. The literature review indicates limited research on factors that affect zero vegetable or fruit consumption among children aged 6-23 months in East Africa. Therefore, this study aimed to investigate the household- and community-level factors determining zero vegetable or fruit consumption among children aged 6-23 months in East Africa. Method: The study analyzed cross-sectional secondary data from the recent rounds of demographic and health surveys conducted in East Africa from 2015 to 2023. The weighted sample comprised 113,279 children aged 6-23 months. A multilevel mixed-effect analysis was used, measuring the random variation between the clusters based on the intra-cluster correction coefficient, median odds ratio, and proportional change variance. Adjusted odds ratio with a 95% confidence interval was reported while considering variables having a p < 0.05 as statistically significant. Results: The overall prevalence of zero vegetable or fruit consumption among children aged 6-23 months in East Africa was 52.3%, with Ethiopia showing the highest prevalence (85.9%). The factors associated with zero vegetable or fruit consumption were maternal educational level, number of household members, short birth interval, multiple births, sex of the household head, household wealth index, community-level maternal literacy, community-level wealth index, and countries. Conclusion: Considering the high overall prevalence of zero vegetable or fruit consumption among children aged 6-23 months in East Africa, overlooking this nutritional gap among children is a serious oversight. Therefore, efforts should be geared toward improving individual- and community-level maternal literacy. In particular, nutrition and public health organizations should support low-income communities to achieve vegetable or fruit consumption for infants and young children.

Association of dietary vitamin C consumption with severe headache or migraine among adults: a cross-sectional study of NHANES 1999-2004.

Background: An antioxidant-rich diet has been shown to protect against migraines in previous research. However, little has been discovered regarding the association between migraines and vitamin C (an essential dietary antioxidant). This study assessed the dietary vitamin C intake among adult migraineurs in the United States to determine if there is a correlation between migraine incidence and vitamin C consumption in adults. Methods: This cross-sectional research encompassed adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, providing detailed information on their dietary vitamin C intake as well as their history of severe headaches or migraines. The study used weighted multivariable and logistic regression analyses to find an independent connection between vitamin C consumption and severe headache or migraine. Tests of interactions and subgroup analysis were conducted. Results: Among the 13,445 individuals in the sample, 20.42% had a severe headache or migraine. In fully adjusted models, dietary vitamin C consumption was substantially linked negatively with severe headache or migraine (odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.91-0.98, p = 0.0007). Compared to quartile 1, quartile 4 had 22% fewer odds of having a severe headache or migraine (OR = 0.78, 95% CI = 0.69-0.89, p = 0.0002). Subgroup analyses showed a significant difference between vitamin C intake and severe headaches or migraines by gender (p for interaction < 0.01). Conclusion: Reduced risk of severe headaches or migraines may be associated with increased consumption of vitamin C.

Schwannoma in the Rectum: A Case Report.

A woman in her 60s with a past medical history of recurrent Helicobacter pylori (H. pylori) presented for surgical consultation after a colonoscopy revealed a mass in the rectum. Preoperative biopsy revealed mucosal excrescence with no dysplasia or malignant changes. The final pathology showed a solid, submucosal rectal mass that was positive for SOX10 and S100 on immunohistochemistry, supporting our diagnosis of Schwannoma. This case emphasizes the importance of considering schwannomas in the differential diagnosis of patients presenting with a rectal mass no matter how rare it may be.

Impact of therapeutic inhibition of oncogenic cell signaling tyrosine kinase on cell metabolism: in vivo-detectable metabolic biomarkers of inhibition.

BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

Using community-based participatory research methods to build the foundation for an equitable integrated health data system within a Canadian urban context.

Health inequalities amplified by the COVID-19 pandemic have disproportionately affected racialized and equity-deserving communities across Canada. In the Municipality of Peel, existing data, while limited, illustrates that individuals from racialized and equity-deserving communities continue to suffer, receive delayed care, and die prematurely. In response to these troubling statistics, grassroots community advocacy has called on health systems leaders in Peel to work with community and non-profit organizations to address the critical data and infrastructure gaps that hinder addressing the social determinants of health in the region. To support these advocacy efforts, we used a community-based participatory research approach to understand how we might build a data collection ecosystem across sectors, alongside community residents and service providers, to accurately capture the data about the social determinants of health. This approach involved developing a community engagement council, defining the problem with the community, mapping what data is actively collected and what is excluded, and understanding experiences of sociodemographic data collection from community members and service providers. Guided by community voices, our study focused on sociodemographic data collection in the primary care context and identified which service providers use and collect these data, how data are used in their work, the facilitators and barriers to data use and collection. Additionally, we gained insight into how sociodemographic data collection could be respectful, safe, and properly governed from the perspectives of community members. From this study, we identify a set of eight recommendations for sociodemographic data collection and highlight limitations. This foundational community-based work will inform future research in establishing data governance in partnership with diverse and equity-deserving communities.

Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Vesico-ureteral reflux diagnosis after initial kidney abscess: Results from a Paediatric Tertiary Hospital.

AIMS: Guidelines regarding voiding cystourethrogram (VCUG) indications following a paediatric kidney abscess are lacking. This study evaluates vesicoureteral reflux (VUR) prevalence and outcome after a first kidney abscess. METHODS: This retrospective study included all children presenting to a tertiary paediatric reference centre with de-novo kidney abscesses from 2011 to 2022, diagnosed through imaging (ultrasonography or computed tomography). VCUG's clinical utility was assessed by exploring outcomes related to interventions. RESULTS: Among the 17 patients (median age 9 months, IQR; 6 months-6 years), VCUG identified VUR in 7 (41%; 95% CI: 18-65%), including two with grade IV-V. Median abscess size was 19 mm (IQR; 14-27). 7/8 (88%) children with DMSA scan presented scars, including 4 with hypofunctioning (20%-44%), and one with a non-functioning kidney. Scarring on the DMSA scan was similar regardless of identified VUR. Six children had subsequent pyelonephritis. Three of the remaining 11 had grade I-III and two IV-V VUR. Surgery was required in four children overall: three for recurrent pyelonephritis and one for high-grade VUR and scars. CONCLUSION: Among initial kidney abscess cases, 41% had VUR, similar to children experiencing their first uncomplicated pyelonephritis. VCUG results guided antibiotic prophylaxis but not surgical decisions. We suggest considering VCUG following recurrent pyelonephritis/kidney abscess and/or kidney scarring.

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

The prognostic role of albumin levels in lung cancer patients receiving third-line or advanced immunotherapy: a retrospective study.

Background: Immunotherapy functions by leveraging immunoregulation drugs to bolster the immune system's capacity to identify and eliminate cancerous cells. In contrast to radiotherapy and chemotherapy, immunotherapy exhibits diminished side effects, heightened efficacy, and prolonged survival rates. Nevertheless, meticulous exploration into the determinants governing the advantageous effects of immunotherapy among patients who have previously undergone multiple prior therapies has yet to be conducted. Albumin (ALB) as a nutritional indicator has not been thoroughly studied for its prognostic effect on efficacy or survival. This study aims to identify factors that influence treatment outcomes among patients undergoing third-line or later immunological therapies. Methods: A cohort of 250 lung cancer patients undergoing toripalimab or tislelizumab immunotherapy was the focal point of data collection. The determination of the median value facilitated the establishment of a cut-off point, enabling the categorization of continuous variables. After data collection, a series of statistical analyses of various clinical factors at baseline were performed, including nonparametric tests, logistic regression, and Cox proportional risk modeling. The last follow-up was in May 2022. The primary study endpoint was overall survival (OS). Results: A total of 250 patients were enrolled in the study, of which 129 patients received first- or second-line immunotherapy and 121 patients received third-line or subsequent immunotherapy. According to Cox multifactor regression analysis, in patients receiving either first- or second-line therapy, the ALB level exhibited negligible prognostic relevance (P>0.05). However, in patients subjected to immunotherapy beyond the second line, the ALB level manifested significant prognostic importance (P=0.039). Notably, patients demonstrating elevated ALB levels achieved a higher disease control rate (DCR) (70.0% vs. 52.5%, P=0.05) and displayed a tendency towards a heightened objective response rate (ORR) (20.0% vs. 16.4%, P=0.61) in comparison to those with lower ALB levels. Conclusions: Among patients undergoing immunotherapy in the third line or subsequent treatment phases, elevated ALB levels in baseline correlated with DCR and OS. Thus, the pre-immunotherapy ALB level emerges as an autonomous predictor of OS in patients subjected to third- or later line immunotherapy interventions.

Transient response to high-dose niacin therapy in a patient with NAXE deficiency.

Background: NAXE-encephalopathy or early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL-1) and NAXD-encephalopathy (PEBEL-2) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures with the onset being usually within the first three years of life. It usually leads to rapid disease progression and death in early childhood. Anecdotal reports suggest that niacin, through its role in nicotinamide adenine dinucleotinde (NAD) de novo synthesis, corrects biochemical derangement, and slows down disease progression. Reports so far have supported this observation. Methods: We describe a patient with a confirmed PEBEL-1 diagnosis and report his clinical response to niacin therapy. Moreover, we systematically searched the literature for PEBEL-1 and PEBEL-2 patients treated with niacin and details about response to treatment and clinical data were reviewed. Furthermore, we are describing off-label use of a COX2 inhibitor to treat niacin-related urticaria in NAXE-encephalopathy. Results: So far, seven patients with PEBEL-1 and PEBEL-2 treated with niacin were reported, and all patients showed a good response for therapy or stabilization of symptoms. We report a patient exhibiting PEBEL-1 with an unfavorable outcome despite showing initial stabilization and receiving the highest dose of niacin reported to date. Niacin therapy failed to halt disease progression or attain stabilization of the disease in this patient. Conclusion: Despite previous positive results for niacin supplementation in patients with PEBEL-1 and PEBEL-2, this is the first report of a patient with PEBEL-1 who deteriorated to fatal outcome despite being started on the highest dose of niacin therapy reported to date.

Optimal vaccination strategies for imperfect vaccines and variable host susceptibility.

I present a method to allocate a given number of vaccines to members of a population who differ in their susceptibility to the disease so that the final size of the epidemic is minimised. I consider an arbitrary distribution of protection that the vaccine confers, including the extreme cases of leaky and all-or-none vaccines. The optimal vaccination policy depends on the distribution of protection. While for low values of the basic reproduction number R0 the optimal policy prioritises the most susceptible hosts, I show that for almost any distribution there is a threshold value of R0 above which the order of priority reverses and the least susceptible hosts should be vaccinated. The exception where this does not happen is the all-or-none vaccine. However, even a small deviation from the ideal all-or-none distribution can imply that the limited number of vaccines should be given to less susceptible hosts already at realistic values of R0.