Critical lessons from a pragmatic randomized trial of home-based COVID-19 testing in rural Native American and Latino communities.

PURPOSE: Native Americans and Latinos have higher COVID-19 infection and mortality rates and may have limited access to diagnostic testing. Home-based testing may improve access to care in rural and underserved populations. This study tests the effect of community health worker (CHW) support on accessibility, feasibility, and completion of COVID-19 home testing among Native American and Latino adults living on the Flathead Reservation in Montana and in Yakima Valley, Washington. METHODS: A two-arm, multisite, pragmatic randomized controlled trial was conducted using block randomization stratified by site and participant age. Active arm participants received CHW assistance with online COVID-19 test kit registration and virtual swabbing support. The passive arm participants received standard-of-care support from the kit vendor. Logistic regression modeled the association between study arm and test completion (primary outcome) and between study arm and test completion with return of valid test results (secondary outcome). Responses to posttest surveys and interviews were summarized using deductive thematic analysis. FINDINGS: Overall, 63% of participants (n = 268) completed COVID-19 tests, and 50% completed tests yielding a valid result. Active arm participants had higher odds of test completion (odds ratio: 1.66, 95% confidence interval [1.01, 2.75]). Differences were most pronounced among adults ≥60 years. Participants cited ease of use and not having to leave home as positive aspects, and transportation and mailing issues as negative aspects of home-based testing. CONCLUSIONS: CHW support led to higher COVID-19 test completion rates, particularly among older adults. Significant testing barriers included language, educational level, rurality, and test kit issues.

Fibre-optic based exploration of lung cancer autofluorescence using spectral fluorescence lifetime.

Fibre-optic based time-resolved fluorescence spectroscopy (TRFS) is an advanced spectroscopy technique that generates sample-specific spectral-temporal signature, characterising variations in fluorescence in real-time. As such, it can be used to interrogate tissue autofluorescence. Recent advancements in TRFS technology, including the development of devices that simultaneously measure high-resolution spectral and temporal fluorescence, paired with novel analysis methods extracting information from these multidimensional measurements effectively, provide additional insight into the underlying autofluorescence features of a sample. This study demonstrates, using both simulated data and endogenous fluorophores measured bench-side, that the shape of the spectral fluorescence lifetime, or fluorescence lifetimes estimated over high-resolution spectral channels across a broad range, is influenced by the relative abundance of underlying fluorophores in mixed systems and their respective environment. This study, furthermore, explores the properties of the spectral fluorescence lifetime in paired lung tissue deemed either abnormal or normal by pathologists. We observe that, on average, the shape of the spectral fluorescence lifetime at multiple locations sampled on 14 abnormal lung tissue, compared to multiple locations sampled on the respective paired normal lung tissue, shows more variability; and, while not statistically significant, the average spectral fluorescence lifetime in abnormal tissue is consistently lower over every wavelength than the normal tissue.

National Disability Insurance Scheme timeframes and functional outcomes for inpatient rehabilitation patients: a 5-year retrospective audit.

Objective The aim of this study was to compare National Disability Insurance Scheme (NDIS) timeframes and functional outcomes for a patient population managed in an inpatient hospital rehabilitation unit. Methods A retrospective hospital audit was undertaken of adult patients admitted to a tertiary-level, regional inpatient rehabilitation unit between January 2017 and December 2021 who were either referred, or not, to the NDIS. A hospital NDIS patient database, Australasian Rehabilitation Outcome Centre episode data, and patient medical records were analysed. The main outcome measures included actual rehabilitation length of stay versus expected length of stay, and Functional Independence Measure (FIM) efficiency for all inpatients, with NDIS timeframes analysed for the NDIS-referred patient subgroup. Results Rehabilitation inpatients referred for NDIS services significantly exceeded expected rehabilitation length of stay compared to those not referred to the NDIS. Furthermore, expected length of stay was significantly exceeded for those patients who required implementation of a NDIS plan to safely transition from hospital. FIM efficiency was significantly lower for patients referred to the NDIS. Recent improvement in timeframes for being accepted as a NDIS participant did not reduce length of stay. Conclusions NDIS timeframes for rehabilitation inpatients incur a significant opportunity cost for the provision of efficient inpatient rehabilitation services that are unaccounted for in current benchmarking performance standards.

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

Implementation of a novel peer review academy by Surgery and the Association of Women Surgeons.

BACKGROUND: A novel Peer Review Academy was developed as a collaborative effort between the Association of Women Surgeons and the journal Surgery to provide formal training in peer review. We aimed to describe the outcomes of this initiative using a mixed methods approach. METHODS: We developed a year-long curriculum with monthly online didactic sessions. Women surgical trainee mentees were paired 1:1 with rotating women surgical faculty mentors for 3 formal peer review opportunities. We analyzed pre-course and post-course surveys to evaluate mentee perceptions of the academy and assessed changes in mentee review quality over time with blinded scoring of unedited reviews. Semi-structured interviews were conducted upon course completion. RESULTS: Ten women surgical faculty mentors and 10 women surgical trainees from across the United States and Canada successfully completed the Peer Review Academy. There were improvements in the mentees' confidence for all domains of peer review evaluated, including overall confidence in peer review, study novelty, study design, analytic approach, and review formatting (all, P ≤ .02). The mean score of peer review quality increased over time (59.2 ± 10.8 vs 76.5 ± 9.4; P = .02). In semi-structured interviews, important elements were emphasized across the Innovation, Implementation Process, and Individuals Domains, including the values of (1) a comprehensive approach to formal peer review education; (2) mentoring relationships between women faculty and resident surgeons; and (3) increasing diversity in the scientific peer review process. CONCLUSION: Our novel Peer Review Academy was feasible on a national scale, resulting in significant qualitative and quantitative improvements in women surgical trainee skillsets, and has the potential to grow and diversify the existing peer review pool.

Tube Thoracostomy Complications in Patients With ARDS Requiring ECMO: Worse in COVID-19 Patients?

INTRODUCTION: The incidence and management outcomes of COVID-19 patients with acute respiratory distress syndrome (ARDS) on veno-venous extracorporeal membrane oxygenation (V-V ECMO) requiring chest tubes are not well-described. This study sought to explore differences in tube thoracostomy rates and subsequent complications between patients with and without COVID-19 ARDS on V-V ECMO. MATERIALS AND METHODS: This study is a single institution, retrospective cohort study of patients with COVID-19 ARDS requiring V-V ECMO. The control cohort consisted of patients who required V-V ECMO for ARDS-related diagnoses from January 2018 to January 2021. The primary outcome was any complication following initial tube thoracostomy placement. Study approval was obtained from the Brooke Army Medical Center Institutional Review Board (C.2017.152d). RESULTS: Twenty-five COVID-19 patients and 38 controls were included. Demographic parameters did not differ between the groups. The incidence of pneumothorax was not significantly different between the two groups (44% COVID-19 vs. 22% control, OR 2.8, 95% CI 0.95-7.9, P = 0.09). Patients with COVID-19 were as likely to receive tube thoracostomy as controls (36% vs. 24%, OR 1.8, 95% CI 0.55-5.7). Complications, however, were more likely to occur in the COVID-19 group (89% vs. 33%, OR 16, 95% CI, 1.6-201, P = 0.0498). CONCLUSIONS: Tube thoracostomy placement in COVID-19 patients with ARDS requiring V-V ECMO is common, as are complications following initial placement. Clinicians should anticipate the need for re-intervention in this patient population. Small-bore (14Fr and smaller) pigtail catheters appeared to be safe and efficacious in this setting, but further study on tube thoracostomy management in ECMO patients is needed.

A Call to Improve Usability, Accuracy, and Equity of Self-Testing for COVID-19 and Other Rapid Diagnostic Tests.

The increasing availability of rapid diagnostic self-tests (RDSTs) for COVID-19 has played an important and increasing role during the pandemic. However, for many underserved communities, RDSTs potential benefits are offset by problems with usability, accuracy, and equity. Given the increased need for and interest in home testing for acute and chronic diseases, including COVID-19, this piece offers ways that regulatory agencies, federal public health agencies, and test developers should engage with diverse communities to ensure equity throughout test development, implementation, and evaluation. Such engagement will ensure maximum personal and public health benefits for current and future RDSTs under real-world conditions.

Factors influencing COVID-19 testing among Native Americans and Latinos in two rural agricultural communities: a qualitative study.

Objective: To examine factors influencing decisions to test for COVID-19 among Native Americans on the Flathead Reservation in Montana and the Latino community in the Yakima Valley of Washington state. Methods: We conducted 30 key informant interviews with community leaders and six focus groups with community members to examine factors impacting decisions to test for COVID-19 during the second year of the COVID-19 pandemic from May 2021 to June 2021. Results: Three major themes that impacted testing for COVID-19 were identified: (1) Social factors, including the influence of families and friends and employment practices; (2) health factors, including testing procedures, home-based testing, and health communication; and (3) contextual factors, including distrust for government and medical communities and the impact on cultural practices and celebrations. Conclusions: Social, health, and contextual factors influence the decision to test for COVID-19. Understanding the community's perception is critical for successful implementation of preventive strategies.

Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis.

BACKGROUND: The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (±granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients. METHODS: Patients with clinically disease-free stage III/IV melanoma were randomized 2:1 initially to TLPLDC versus placebo (n=124) and subsequently TLPO versus TLPLDC (n=63). All patients were randomized and blinded; however, the placebo control arm was replaced in the second randomization scheme with another novel vaccine; some analyses in this paper therefore reflect a combination of the two randomization schemes. Patients receiving the TLPLDC vaccine were further divided by their method of DC harvest (with or without G-CSF pretreatment); this was not randomized. The use of standard of care checkpoint inhibitors was not stratified between groups. Safety was assessed and Kaplan-Meier and log-rank analyses compared disease-free (DFS) and overall survival (OS). RESULTS: After combining the two randomization processes, a total of 187 patients were allocated between treatment arms: placebo (n=41), TLPLDC (n=103), or TLPO (n=43). The allocation among arms created by the addition of patients from the two separate randomization schemes does not reflect concurrent randomization among all treatment arms. TLPLDC was further divided by use of G-CSF in DC harvest: no G-CSF (TLPLDC) (n=47) and with G-CSF (TLPLDC+G) (n=56). Median follow-up was 35.8 months. Only two patients experienced a related adverse event ≥grade 3, one each in the TLPLDC+G and placebo arms. DFS was 27.2% (placebo), 55.4% (TLPLDC), 22.9% (TLPLDC+G), and 60.9% (TLPO) (p<0.001). OS was 62.5% (placebo), 93.6% (TLPLDC), 57.7% (TLPLDC+G), and 94.6% (TLPO) (p=0.002). CONCLUSIONS: The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial. TRIAL REGISTRATION NUMBER: NCT02301611.

A qualitative analysis of patients' experiences with an emergency department diagnosis of gastrointestinal cancer.

OBJECTIVES: Optimally, cancer is diagnosed through periodic screening or detection of early symptoms in primary care settings. However, an estimated 23%-52% of gastrointestinal (GI) cancers are diagnosed in the emergency department (ED). Cancer diagnosed in the ED has been associated with worse clinical and patient-reported outcomes even after adjustment for cancer stage. We sought to explore patients' accounts of patient and health care system factors related to their diagnosis in the ED and their lived experience of receiving a diagnosis in this setting. METHODS: Patients with an ED visit during or within 30 days of their GI cancer diagnosis at an urban academic hospital serving a largely disadvantaged population were recruited. Interviews were coded in NVivo 12 and analyzed using a thematic analysis approach. RESULTS: Patient-reported factors associated with their experiences included denial and avoidance of symptoms, mistrust of the health system, and lack of cancer screening knowledge. Health care system factors included misdiagnosis and delayed access to specialty care or tests. Experiences receiving a cancer diagnosis in the ED were overwhelmingly negative. CONCLUSIONS: This study highlights the unmet needs in identifying and diagnosing patients who ultimately present to the ED for evaluation and eventual diagnosis of cancer. Our results shed light on several modifiable factors, including the need for increased public awareness of the asymptomatic nature of cancer and the importance of cancer screening. Additionally, health care systems modifications beyond the ED are needed to improve access to timely care when symptoms arise.

Mature and Myelinating Oligodendrocytes Are Specifically Vulnerable to Mild Fluid Percussion Injury in Mice.

Myelin loss and oligodendrocyte death are well documented in patients with traumatic brain injury (TBI), as well as in experimental animal models after moderate-to-severe TBI. In comparison, mild TBI (mTBI) does not necessarily result in myelin loss or oligodendrocyte death, but causes structural alterations in the myelin. To gain more insight into the impact of mTBI on oligodendrocyte lineage in the adult brain, we subjected mice to mild lateral fluid percussion injury (mFPI) and characterized the early impact (1 and 3 days post-injury) on oligodendrocytes in the corpus callosum using multiple oligodendrocyte lineage markers (platelet-derived growth factor receptor [PDGFR]-α, glutathione S-transferase [GST]-π, CC1, breast carcinoma-amplified sequence 1 [BCAS1], myelin basic protein [MBP], myelin-associated glycoprotein [MAG], proteolipid protein [PLP], and FluoroMyelin™). Two regions of the corpus callosum in relation to the impact site were analyzed: areas near (focal) and anterior (distal) to the impact site. mFPI did not result in oligodendrocyte death in either the focal or distal corpus callosum, nor impact on oligodendrocyte precursors (PDGFR-α+) and GST-π+ oligodendrocyte numbers. In the focal but not distal corpus callosum, mFPI caused a decrease in CC1+ as well as BCAS1+ actively myelinating oligodendrocytes and reduced FluoroMyelin intensity without altering myelin protein expression (MBP, PLP, and MAG). Disruption in node-paranode organization and loss of Nav1.6+ nodes were observed in both the focal and distal regions, even in areas without obvious axonal damage. Altogether, our study shows regional differences in mature and myelinating oligodendrocyte in response to mFPI. Further, mFPI elicits a widespread impact on node-paranode organization that affects regions both close to and remotely located from the site of injury.

Pathogen and human NDPK-proteins promote AML cell survival via monocyte NLRP3-inflammasome activation.

A history of infection has been linked with increased risk of acute myeloid leukaemia (AML) and related myelodysplastic syndromes (MDS). Furthermore, AML and MDS patients suffer frequent infections because of disease-related impaired immunity. However, the role of infections in the development and progression of AML and MDS remains poorly understood. We and others previously demonstrated that the human nucleoside diphosphate kinase (NDPK) NM23-H1 protein promotes AML blast cell survival by inducing secretion of IL-1ß from accessory cells. NDPKs are an evolutionary highly conserved protein family and pathogenic bacteria secrete NDPKs that regulate virulence and host-pathogen interactions. Here, we demonstrate the presence of IgM antibodies against a broad range of pathogen NDPKs and more selective IgG antibody activity against pathogen NDPKs in the blood of AML patients and normal donors, demonstrating that in vivo exposure to NDPKs likely occurs. We also show that pathogen derived NDPK-proteins faithfully mimic the catalytically independent pro-survival activity of NM23-H1 against primary AML cells. Flow cytometry identified that pathogen and human NDPKs selectively bind to monocytes in peripheral blood. We therefore used vitamin D3 differentiated monocytes from wild type and genetically modified THP1 cells as a model to demonstrate that NDPK-mediated IL-1ß secretion by monocytes is NLRP3-inflammasome and caspase 1 dependent, but independent of TLR4 signaling. Monocyte stimulation by NDPKs also resulted in activation of NF-κB and IRF pathways but did not include the formation of pyroptosomes or result in pyroptotic cell death which are pivotal features of canonical NLRP3 inflammasome activation. In the context of the growing importance of the NLRP3 inflammasome and IL-1ß in AML and MDS, our findings now implicate pathogen NDPKs in the pathogenesis of these diseases.

"Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli".

Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the potential to provide an alternative treatment option for individuals struggling with mental illness. Sustainable and economic production methods are thus needed to facilitate enhanced study of these drug candidates to support future clinical efforts. Here, we expand upon current bacterial psilocybin biosynthesis by incorporating the cytochrome P450 monooxygenase, PsiH, to enable the de novo production of psilocybin as well as the biosynthesis of 13 psilocybin derivatives. The substrate promiscuity of the psilocybin biosynthesis pathway was comprehensively probed by using a library of 49 single-substituted indole derivatives, providing biophysical insights to this understudied metabolic pathway and opening the door to the in vivo biological synthesis of a library of previously unstudied pharmaceutical drug candidates.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

Interactions across the ages: How concerns about warmth and competence impact age-based stereotype threat in the workplace.

Although the disengagement consequences of age-based stereotype threat in the workplace are well-documented, it is less clear what causes employees to experience age-based stereotype threat. Based on socioemotional selectivity theory, the present study examines whether and why daily cross-age interactions in the workplace lead to stereotype threat. Using a diary study design over 2 weeks, 192 employees (86 employees aged 30 and younger; 106 employees aged 50 and older), completed 3570 reports on daily interactions with coworkers. Results showed that both younger and older employees experienced stereotype threat when they engaged in cross-age interactions compared to interactions with people of a similar age. The characteristics of cross-age interactions that led employees to experience stereotype threat differed by age, however. Consistent with socioemotional selectivity theory, cross-age interactions were problematic for younger employees to the degree that they triggered concerns about competence, whereas concerns about warmth led to stereotype threat among older employees. Daily stereotype threat was associated with reduced feelings of workplace belonging for both younger and older employees but, contrary to expectations, stereotype threat was not related to energy and stress. These findings suggest that cross-age interactions can lead to stereotype threat for both younger and older employees, particularly when younger employees worry they are perceived as incompetent or older employees worry they are perceived as less warm. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro.

Introduction: In vitro models of traumatic brain injury (TBI) commonly use neurons isolated from the central nervous system. Limitations with primary cortical cultures, however, can pose challenges to replicating some aspects of neuronal injury associated with closed head TBI. The known mechanisms of axonal degeneration from mechanical injury in TBI are in many ways similar to degenerative disease, ischemia, and spinal cord injury. It is therefore possible that the mechanisms that result in axonal degeneration in isolated cortical axons after in vitro stretch injury are shared with injured axons from different neuronal types. Dorsal root ganglia neurons (DRGN) are another neuronal source that may overcome some current limitations including remaining healthy in culture for long periods of time, ability to be isolated from adult sources, and myelinated in vitro. Methods: The current study sought to characterize the differential responses between cortical and DRGN axons to mechanical stretch injury associated with TBI. Using an in vitro model of traumatic axonal stretch injury, cortical and DRGN neurons were injured at a moderate (40% strain) and severe stretch (60% strain) and acute alterations in axonal morphology and calcium homeostasis were measured. Results: DRGN and cortical axons immediately form undulations in response to severe injury, experience similar elongation and recovery within 20 min after the initial injury, and had a similar pattern of degeneration over the first 24 h after injury. Additionally, both types of axons experienced comparable degrees of calcium influx after both moderate and severe injury that was prevented through pre-treatment with tetrodotoxin in cortical neurons and lidocaine in DRGNs. Similar to cortical axons, stretch injury also causes calcium activated proteolysis of sodium channel in DRGN axons that is prevented by treatment with lidocaine or protease inhibitors. Discussion: These findings suggest that DRGN axons share the early response of cortical neurons to a rapid stretch injury and the associated secondary injury mechanisms. The utility of a DRGN in vitro TBI model may allow future studies to explore TBI injury progression in myelinated and adult neurons.

Simultaneous Spectral Temporal Modelling for a Time-Resolved Fluorescence Emission Spectrum.

Innovations in complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) technology has featured in the development of next-generation instruments for point-based time-resolved fluorescence spectroscopy (TRFS). These instruments provide hundreds of spectral channels, allowing the collection of fluorescence intensity and fluorescence lifetime information over a broad spectral range at a high spectral and temporal resolution. We present Multichannel Fluorescence Lifetime Estimation, MuFLE, an efficient computational approach to exploit the unique multi-channel spectroscopy data with an emphasis on simultaneous estimation of the emission spectra, and the respective spectral fluorescence lifetimes. In addition, we show that this approach can estimate the individual spectral characteristics of fluorophores from a mixed sample.

Tumor infiltrating lymphocytes as an endpoint in cancer vaccine trials.

Checkpoint inhibitors have invigorated cancer immunotherapy research, including cancer vaccination. Classic early phase trial design and endpoints used in developing chemotherapy are not suited for evaluating all forms of cancer treatment. Peripheral T cell response dynamics have demonstrated inconsistency in assessing the efficacy of cancer vaccination. Tumor infiltrating lymphocytes (TILs), reflect the local tumor microenvironment and may prove a superior endpoint in cancer vaccination trials. Cancer vaccines may also promote success in combination immunotherapy treatment of weakly immunogenic tumors. This review explores the impact of TILs as an endpoint for cancer vaccination in multiple malignancies, summarizes the current literature regarding TILs analysis, and discusses the challenges of providing validity and a standardized implementation of this approach.