bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal perinatal depression and health services utilisation in the first 2 years of life: a cohort study
Authors: Adler Limor , Azuri Joseph
Published: November 2021

Objectives

Maternal perinatal depression is a common phenomenon, influencing infants’ development. Studies have shown an inconsistent association between perinatal depression and healthcare resource utilisation. This study aimed to assess whether perinatal depression in mothers is associated with their infants’ healthcare utilisation, during the first 2 years of life.

Design

A cohort study based on computerised medical records.

Setting

Nationwide primary care clinics in the second largest health maintenance organisation in Israel.

Participants

593 children of women with depression (the exposed group) and 2310 children of women without depression.

Primary and secondary outcome measures

Primary outcome variables included general practitioner/paediatrician (GP/Paed) visits (regular and telehealth), emergency room (ER) visits, hospital admission rates and child-development clinic visits. Secondary outcomes included antibiotic use and anaemia status. The exposure variable, perinatal depression, was based on Edinburgh Postnatal Depression Scale. A score of ≥10 was classified as depression.

Results

Multivariable analysis of the number of regular visits and telehealth to the GP/Paed showed an adjusted incidence rate ratio (aIRR) of 1.08, 95% CI 1.03 to 1.13 and aIRR 0.95, 95% CI 0.82 to 1.10, respectively. Children of mothers with perinatal depression had more hospital admissions (aIRR 1.21, 95% CI 1.01 to 1.46) and more visits to child development clinics (aIRR 1.33, 95% CI 1.04 to 1.70). There was a non-significant increase in ER visits (IRR 1.26, 95% CI 0.66 to 2.42), and non-significant decrease in antibiotics prescriptions (IRR 0.95, 95% CI 0.86 to 1.05) and anaemia status (IRR 0.93, 95% CI 0.72 to 1.20).

Conclusion

This study shows higher health services utilisation among children of mothers with perinatal depression, including regular GP/Paed visits, hospital admission rates, and child-development clinics.
Effectiveness of interventions to address the negative health outcomes of informal caregiving to older adults: protocol for an umbrella review
Authors: Calderón-Larrañaga Amaia , Kirvalidze Mariam , Dahlberg Lena , Sacco Lawrence B , Morin Lucas
Published: November 2021

Introduction

Informal (unpaid) caregivers play an essential role in caring for older people, whose care needs are often not fully met by formal services. While providing informal care may be a positive experience, it can also exert a considerable strain on caregivers’ physical and mental health. How to best support the needs of informal caregivers remains largely debated. This umbrella review (review of systematic reviews) aims to evaluate (1) whether effective interventions can mitigate the negative health outcomes of informal caregiving, (2) whether certain types of interventions are more effective than others, (3) whether effectiveness of interventions depends on caregiver/receiver, context or implementation characteristics and (4) how these interventions are perceived in terms of acceptability, feasibility and added value.

Methods and analysis

We will include systematic reviews of primary studies focusing on the effectiveness of interventions (public or private, unifaceted or multifaceted, delivered by health or social care professionals or volunteers) aimed at reducing the impact of caregiving on caregivers’ physical or mental health. This will also include quantitative and qualitative syntheses of implementation studies. The literature search will include the following databases: Medline, CINAHL, PsycINFO and Web of Science. A key informant-guided search of grey literature will be performed. Quality appraisal will be conducted with the AMSTAR-2 checklist for quantitative reviews and with anad hocchecklist for qualitative syntheses. Narrative and tabular summaries of extracted data will be produced, and framework synthesis will be employed for weaving together evidence from quantitative studies in effectiveness reviews with findings on implementation from qualitative studies.

Ethics and dissemination

This umbrella review will use data from secondary sources and will not involve interactions with study participants; it is thus exempt from ethical approval. Results will be presented at international conferences and will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42021252841.
Determinants of change in the inequality and associated predictors of teenage pregnancy in Uganda for the period 2006–2016: analysis of the Uganda Demographic and Health Surveys
Authors: Wasswa Ronald , Kabagenyi Allen , Kananura Rornald Muhumuza , Jehopio Joseph , Rutaremwa Gideon
Published: November 2021

Objective

Teenage pregnancy has become a public health concern in Uganda because of its negative consequences to both the mother and child. The objective of this study was to examine the determinants of change in the inequality and associated predictors of teenage pregnancy in Uganda for the period 2006–2016.

Study design

A retrospective national cross-sectional study.

Setting

Uganda.

Participants

Uganda Demographic and Health Survey secondary data of only female teenagers aged 15–19 years. The samples selected for analyses were 1936 in 2006; 2048 in 2011 and 4264 in 2016.

Outcome measure

The primary outcome was teenage pregnancy. Analysis was performed using the logistic regression, equiplots, concentration curve, normalised concentration index, decomposition of the concentration index and Oaxaca-type decomposition.

Results

The prevalence of teenage pregnancy has seemingly remained high and almost constant from 2006 to 2016 with the risk worsening to the disadvantage of the poor. Household wealth-index, teenagers’ years of education, early sexual debut and child marriage were the main key predictors and contributors of the large inequality in teenage pregnancy from 2006 to 2016.

Conclusion

Teenage pregnancy is disproportionately prevalent among different subpopulations of adolescent girls in Uganda. We therefore recommend policy actions to sensitise communities and enforcement of child rights and child protection laws to stop child marriages. There is also need to promote girl child education, improving household incomes, and intensifying mass media awareness on the risks of early pregnancies. Further, ensuring that villages have operational adolescent and youth friendly services as well as incorporating sex education and other different adolescent reproductive health programmes in school curriculum will be key measures in reducing the large inequality in teenage pregnancy.
Interventions to improve early cancer diagnosis of symptomatic individuals: a scoping review
Authors: Okoli George N , Lam Otto L T , Reddy Viraj K , Copstein Leslie , Askin Nicole , Prashad Anubha , Stiff Jennifer , Khare Satya Rashi , Leonard Robyn , Zarin Wasifa , Tricco Andrea C , Abou-Setta Ahmed M
Published: November 2021

Objectives

To summarise the current evidence regarding interventions for accurate and timely cancer diagnosis among symptomatic individuals.

Design

A scoping review following the Joanna Briggs Institute’s methodological framework for the conduct of scoping reviews and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist.

Data sources

MEDLINE (Ovid), CINAHL (EBSCOhost) and PsycINFO (Ovid) bibliographic databases, and websites of relevant organisations. Published and unpublished literature (grey literature) of any study type in the English language were searched for from January 2017 to January 2021.

Eligibility and criteria

Study participants were individuals of any age presenting at clinics with symptoms indicative of cancer. Interventions included practice guidelines, care pathways or other initiatives focused on achieving predefined benchmarks or targets for wait times, streamlined or rapid cancer diagnostic services, multidisciplinary teams and patient navigation strategies. Outcomes included accuracy and timeliness of cancer diagnosis.

Data extraction and synthesis

We summarised findings graphically and descriptively.

Results

From 21 298 retrieved citations, 88 unique published articles and 16 unique unpublished documents (on 18 study reports), met the eligibility for inclusion. About half of the published literature and 83% of the unpublished literature were from the UK. Most of the studies were on interventions in patients with lung cancer. Rapid referral pathways and technology for supporting and streamlining the cancer diagnosis process were the most studied interventions. Interventions were mostly complex and organisation-specific. Common themes among the studies that concluded intervention was effective were multidisciplinary collaboration and the use of a nurse navigator.

Conclusions

Multidisciplinary cooperation and involvement of a nurse navigator may be unique features to consider when designing, delivering and evaluating interventions focused on improving accurate and timely cancer diagnosis among symptomatic individuals. Future research should examine the effectiveness of the interventions identified through this review.
Are climate change and mental health correlated?
Authors: Ramadan Abdullah Mohammed Hassan , Ataallah Ahmed G
Published: November 2021

Climate change is one of the biggest challenges of our time and is likely to affect human beings in substantial ways. Recently, researchers started paying more attention to the changes in climate and their subsequent impact on the social, environmental and economic determinants of health, and the role they play in causing or exacerbating mental health problems. The effects of climate change-related events on mental well-being could be classified into direct and indirect effects. The direct effects of climate change mostly occur after acute weather events and include post-traumatic stress disorder, anxiety, substance abuse disorder, depression and even suicidal ideation. The indirect effects include economic losses, displacement and forced migration, competition over scarce resources and collective violence. The risk factors for developing those mental health issues include young age, female gender, low socioeconomic status, loss or injury of a loved one, being a member of immigrant groups or indigenous people, pre-existing mental illness and inadequate social support. However, in some individuals, especially those undisturbed by any directly observable effects of climate change, abstract awareness and acknowledgement of the ongoing climate crisis can induce negative emotions that can be intense enough to cause mental health illness. Coping strategies should be provided to the affected communities to protect their mental health from collapse in the face of climate disasters. Awareness of the mental health impacts of climate change should be raised, especially in the high-risk groups. Social and global attention to the climate crisis and its detrimental effects on mental health are crucial.

This paper was written with the aim of trying to understand the currently, scientifically proven impact of climate change-related disasters on mental health and understanding the different methods of solving the problem at the corporate level, by trying to decrease greenhouse gas emissions to zero, and at the individual level by learning how to cope with the impacts of those disasters.
Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study
Authors: Wang Kunyuan , Xia Ying , Zhu Yun , Yu Wenxuan , Guo Yabing , Liu Li
Published: November 2021

Background

Immune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data demonstrating the impact of ICIs on HBV DNA level in HBV-HCC patients undergoing nucleos(t)ide analog (NA) therapy and of HBV DNA variation on patient survival. In this study, we aimed to investigate this issue in the real world.

Methods

In this single-center retrospective study, we reviewed 182 baseline hepatitis B surface antigen (HBsAg)-positive HBV-HCC patients who were treated with ICIs and pre-emptive NAs. The demographic characteristics, tumor status, treatments, HBV DNA, HBsAg, liver function, antitumor response, and patient survival were investigated. The primary endpoints were the virological breakthrough (VB) rate, HBV reactivation (HBVr) rate, and long-term HBV DNA control; the secondary endpoints were the overall survival (OS) and progression-free survival (PFS).

Results

(1) VB and HBVr occurred in 18.1% (33/182) and 4.4% (8/182) of patients with a median occurrence time of 3.9 months (range, 0.7–16.0) and 8.0 months (range, 3.0–16.0), respectively. The HBV DNA negative rates were 26.1% and 0 at 24 and 48 weeks in the VB group and 12.5% and 0 in the HBVr group, respectively. A baseline HBsAg level ≥200 IU/mL was the only risk factor for VB (OR 9.9, 95% CI 2.2 to 45.2, p=0.003); (2) patients with VB had much shorter median OS and median PFS than those without (12.3 months vs 18.1 months, p=0.035; 4.5 months vs 7.5 months, p=0.011).

Conclusions

There was a high risk of VB and a moderate risk of HBVr in HBsAg-positive HBV-HCC patients (with poor long-term HBV DNA control) undergoing ICI and pre-emptive NA therapies. The only risk factor for VB was the pretreatment HBsAg level. Further, VB might be considered as a clinical biomarker predicting inferior OS and PFS in the patients.
40 Precise spatial multiplexing for immune profiling in non-small cell lung cancer FFPE samples with ChipCytometry
Authors: Campbell Thomas , Christians Arne , Northcutt Adam , Winkeler Crystal , Gamber Kevin
Published: November 2021

Background

Emergent data indicate that highly multiplexed spatial biomarker analysis has the potential to advance precision medicine in immuno-oncology and inform the discovery of novel biomarkers.

Methods

Here we present the analysis of clinical FFPE samples from non-small cell lung cancer patients using ChipCytometry, a novel precise spatial multiplexing technology which combines iterative immuno-fluorescent staining with high-dynamic range imaging to facilitate quantitative phenotyping with single-cell resolution. Standard FCS files are generated from multichannel OME-TIFF images, enabling identification of cellular phenotypes via flow cytometry-like hierarchical gating. In this study, a 27-plex assay was used to identify and quantify more than 30 cellular phenotypes and subtypes in FFPE samples.

Results

The results show precise expression levels for each marker in the assay in each individual cell in the sample, maintaining spatial information about each cell. Spatial analysis of the samples reveals quantifiable heterogeneity of immune cell infiltration within the tumor samples, demonstrating the utility of the ChipCytometry platform for the in-depth immune profiling in clinical samples.

Conclusions

N/A
46 Proximity between cytotoxic antigen-experienced T cells and tumor cells is associated with improved clinical outcomes in early-stage NSCLC
Authors: Luo Qianyun , Parra Edwin , Negrao Marcelo , Akhave Neal , Bayley Erin , Mitchell Kyle , Zhang Jianjun , Heymach John , Sepesi Boris , Wistuba Ignacio , Gibbons Don , Reuben Alexandre
Published: November 2021

Background

While the development of immunotherapies has improved the treatment of non-small cell lung cancer (NSCLC), most patients still fail to respond. Immune cell densities have been utilized to predict clinical responses but have largely failed to do so. However, the spatial distribution and interaction of these cells at the tissue level have been less studied. Here, we performed spatial analysis of the cells within the tumor immune microenvironment in order to evaluate their relationship with clinical outcomes in early-stage NSCLC.

Methods

Multiplex immunofluorescence was performed on 123 early-stage NSCLC patients from the ICON (Immunogenomic profiling of non-small cell lung cancer) cohort including Cytokeratin (CK), CD3, CD8, CD45RO, FoxP3, CD68, CD20, CD57, Granzyme B (GzmB), PD-1, and PD-L1. Area under the curve (AUC) was calculated using Ripley’s L function, which evaluates the degree of spatial proximity of two cell populations, with a high AUC indicating clustering and low AUC indicating scattering. Findings were integrated with clinical parameters.

Results

Adenocarcinomas demonstrated CD3+PD1+ T cells were closer to CK+ tumor cells (n=60, p=0.035), and B cells were closer to cytotoxic T cells (n=43, p=0.03) than in squamous cell carcinoma. Higher AUC was observed between CD3+PD1+ T cells (n=56, p=0.035), with cytotoxic antigen-experienced T cells (CD45RO+GzmB+) closer to tumor cells (n=35, p=0.017) in stage I and II compared to stage III tumors. Untreated patient tumors exhibited higher proximity between CD20+ B cells and CD57+ NK cells (n=59, p=0.012), CD3+ T cells and PD-L1+ tumor cells (n=56, p=0.027), and CD68+ macrophages and PD-L1+ tumor cells (n=52, p=0.016) than neoadjuvant chemotherapy-treated patients. Patients with no recurrence presented higher AUC in antigen-experienced CD45RO+GzmB+ T cells and tumor cells (n=36, p=0.006), while those with improved survival demonstrated greater proximity between CD68+ macrophages and PD-L1+ tumors (n=52, p=0.016), CD20+ B cells and GzmB+ cells (n=49, p=0.03), and antigen-experienced CD45RO+GzmB+ T cells and tumor cells (n=36, p=0.047). Lastly, patients with improved survival also displayed greater proximity between CD3+CD8+ cytotoxic T cells and PD-L1- epithelial cells (n=76, p=0.04) in tumors versus matched adjacent lungs.

Conclusions

Overall, our findings shed light on some of the potential cell interactions at play in the tumor microenvironment of early-stage NSCLC patients and suggest cell distributions could be utilized to predict clinical outcomes in early-stage NSCLC patients.
47 Tertiary lymphoid structures (TLS) in desmoplastic melanomas (DM) differ from non-DM-associated TLS by their intratumoral location and enhanced immune activity
Authors: Mauldin Ileana , Stowman Anne , Hickman Alexandra , Mahmutovic Adela , Gru Alejandro , Lynch Kevin , Young Samuel , Meneveau Max , Wages Nolan , Engelhard Victor , Slingluff Craig
Published: November 2021

Background

Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that are localized near tumors and other sites of inflammation, and are commonly believed to support antitumor immunity. We previously published studies that show that most desmoplastic melanomas contain TLS, and that TLS in cutaneous metastatic melanomas varied widely in maturation state, in proportions of proliferating T and B cells, and in markers of B cell function, including AID and CD21. Thus, we hypothesized that there may be diversity in TLS function, or immunologic activity, among melanomas. To address this hypothesis, we evaluated TLS in primary desmoplastic melanomas (DM), and non-desmoplastic melanomas (non-DM) for markers of cell proliferation which are indicative of early immune activity.

Methods

DM and non-DM tumor specimens, which included primary melanomas (PM), and cutaneous metastatic melanomas (CMM), were evaluated for TLS by multiplex Immunofluorescence histology, by staining for CD20, CD8, PNAd, Ki67, FoxP3, and DAPI. Lymphoid aggregates were identified in 20x spectrally unmixed images by visual inspection and identified as TLS if possessing organized T-cell and B-cell regions in addition to high endothelial venule-like vasculature (PNAd+). TLS were identified in 30 out of 64 screened (48%) CMM, 4/4 non-DM PM, and 8 out of 11 screened (73%) DM. Immune cells localized in TLS were enumerated using Halo software (Indica Labs). Mann-Whitney tests were used for statistical assessments.

Results

DM commonly contain a dense network of fibroblasts and associated stroma, which are not typical for other non-DM (PM and CMM). TLS in DM are located throughout the tumors, intratumorally, in sharp distinction from the peritumoral location of TLS in non-DM. Furthermore, when compared to TLS of non-DM (PM and CMM), TLS of DM contain increased densities of CD20+ B cells (PM p=0.007; CMM p<0.0001) and CD8+ T cells (PM p=0.017; CMM p=0.0006), and a higher proportion of proliferating (Ki67+) CD20+ B cells (PM p=0.04; CMM p=0.009).

Conclusions

Recently published studies have identified tumor-associated fibroblasts as the likely initiating cells for TLS formation in murine melanomas. The intratumoral location of TLS in DM puts them in close proximity to the dense fibroblasts and desmoplastic stroma in these tumors, which may be responsible for their intratumoral location. The increased density of B and T cells, and higher proportion of proliferating (Ki67+) B cells, in DM than in non-DM, suggests that there may be greater immune activation, increased germinal center maturation, or less regulation in TLS of DM.

Ethics Approval

Approval was obtained for these studies under IRB protocol #’s 10598 and 19694.
55 Baseline glycolytic tumor burden predicts response and survival in NSCLC and melanoma patients treated with immune checkpoint inhibitors
Authors: Silva Saulo , Wanderley Carlos Wagner , Marin Jose Flavio , Macedo Mariana De , Nascimento Ellen , Antonacio Fernanda , Cunha Fernando , Castro Gilberto de
Published: November 2021

Background

Tumor metabolic remodeling is considered one of the hallmarks of cancers and has been implicated in immune evasion. Highly glycolytic tumors can lead to immune suppression by both nutrient competition and toxic metabolite accumulation. Immune checkpoint inhibitors (ICIs) are essential in treating melanoma and non-small cell lung cancer (NSCLC) patients, but novel predictive biomarkers can significantly contribute to clinical practice. Herein we analyzed the predictive and prognostic value of baseline metabolic tumor volumes in NSCLC and melanoma patients treated with ICIs.

Methods

This retrospective, single-center study includes patients with metastatic NSCLC or melanoma and a baseline 18F-FDG-PET/CT (PET) performed before ICI. PET studied parameters were SUV (maximum standardized uptake value), wMTV (whole metabolic tumor value), and wTLG (whole total lesion glycolysis). Best response rates were analyzed through RECIST. High or low glycolytic tumor burden (GTB) patients were defined according to SUV, wMTV, and wTLG cut-offs that best discriminate progressive disease. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and curves were compared with log-rank.

Results

Among 151 patients included, 107 had NSCLC and 44 melanoma. Regarding NSCLC patients, there was a significant correlation between GTB and responses among all PET parameters (figure 1). Noteworthily, only one patient with a low wTLG (<146) showed progressive disease after ICIs (figure 2C). In regard to the potential in predicting response to ICIs, the area under the curve (AUC) obtained for each glycolytic parameter was higher than that for PD-L1 expression (figure 2D-H). Furthermore, when patients were categorized according to ICI exposure (1st or ≥ 2nd line), AUC for glycolytic parameters was higher in ≥ 2nd line versus 1st line (figure 3). Lastly, a low GTB was associated with improved PFS (figure 4) and OS (figure 5).Regarding melanoma patients, wMTV and wTLG were significantly associated with response (figure 6), and a low GTB was significantly associated with improved PFS and OS (figure 7).

Abstract 55 Figure 1Abstract 55 Figure 2Abstract 55 Figure 3Abstract 55 Figure 4Abstract 55 Figure 5Abstract 55 Figure 6Abstract 55 Figure 7

Conclusions

GTB accessed through a baseline PET is associated with survival and response to ICIs in NSCLC and melanoma patients, suggesting that the tumor metabolism might impact immune responses and be a promising predictive tool.

Ethics Approval

The study obtained ethics approval by Sírio-Libanês Hospital institutional review board. Study participants were not required to give an informed consent before taking part.
83 Spatially resolved transcriptomic and proteomic investigation of breast cancer and its immune microenvironment
Authors: Chew Jennifer , Uytingco Cedric , Spalinskas Rapolas , Yin Yifeng , Shuga Joe , Veire Benton , Anaparthy Naishitha , Hatori Ryo , Katsor Anna-Maria , Katiraee Layla , Hermes Alexander , Chiang Jun Ding , Roelli Patrick , Williams Stephen , Nitsch William , Weisenfeld Neil , Walkser Dan , Koth Jason , Basu Subham , Howat Will , Ganapathy Karthik , Stoeckius Marlon
Published: November 2021

Background

The tumor microenvironment (TME) is composed of highly heterogeneous extracellular structures and cell types such as endothelial cells, immune cells, and fibroblasts that dynamically influence and communicate with each other. The constant interaction between a tumor and its microenvironment plays a critical role in cancer development and progression and can significantly affect a tumor’s response to therapy and capacity for multi-drug resistance. High resolution analyses of gene and protein expression with spatial context can provide deeper insights into the interactions between tumor cells and surrounding cells within the TME, where a better understanding of the underlying biology can improve treatment efficacy and patient outcomes. Here, we demonstrated the ability to perform streamlined multi-omic tumor analyses by utilizing the 10X Genomics Visium Spatial Gene Expression Solution for FFPE with multiplex protein enablement. This technique simultaneously assesses gene and protein expression to elucidate the immunological profile and microenvironment of different breast cancer samples in conjunction with standard pathological methods.

Methods

Serial (5 µm) sections of FFPE human breast cancer samples were placed on Visium Gene Expression (GEX) slides. The Visium GEX slides incorporate ~5,000 molecularly barcoded, spatially encoded capture spots onto which tissue sections are placed, stained, and imaged. Following incubation with a human whole transcriptome, probe-based RNA panel and an immuno-oncology oligo-tagged antibody panel, developed with Abcam conjugated antibodies, the tissues are permeabilized and the representative probes are captured. Paired GEX and protein libraries are generated for each section and then sequenced on an Illumina NovaSeq at a depth of ~50,000 reads per spot. Resulting reads from both libraries are aligned and overlaid with H&E-stained tissue images, enabling analysis of both mRNA and protein expression. Additional analyses and data visualizations were performed on the Loupe Browser v4.1 desktop software.

Conclusions

Spatial transcriptomics technology complements pathological examination by combining histological assessment with the throughput and deep biological insight of highly-multiplexed protein detection and RNA-seq. Taken together, our work demonstrated that Visium Spatial technology provides a spatially-resolved, multi-analyte view of the tumor microenvironment, where a greater understanding of cellular behavior in and around tumors can help drive discovery of new biomarkers and therapeutic targets.
318 Enforced tumor specific MHC-I heterogeneity in triple negative breast cancer drives immunotherapy resistance
Authors: Taylor Brandie , Balko Justin , Sanders Melinda , Gonzalez-Ericsson Paula , Sanchez Violeta
Published: November 2021

Background

Despite the broad success of immune checkpoint inhibition (ICI e.g. anti-Programmed Death Ligand-1 [PD-L1]) in cancer treatment, tumor-intrinsic factors leading to intrinsic and acquired resistance are poorly understood. Tumor specific MHC-I expression is indispensable for anti-PD-1/L1 response as complete loss of MHC-I via B2M deletion results in inability of CD8+ T cells to recognize tumor-associated antigens. However, MHC-I is heterogeneously downregulated or lost in many tumor types. Tumor cell destruction can also occur through non-synaptic mechanisms, in a so-called ‘field effect’. Therefore, we modeled heterogeneous loss of MHC-I expression in breast cancer and experimentally evaluated how heterogeneous MHC-I loss affects response to anti-PD-L1 therapy.

Methods

We performed quantitative immunofluorescence for MHC-I and Pan-CK on breast cancer tumors (n=410). To determine the functional effect of MHC-I heterogeneity on anti-PD-L1 response, we used an immunocompetent EMT6 orthotopic mammary tumor model which ubiquitously expresses MHC-I at baseline. Using CRISPR/Cas9, we engineered EMT6 cells with B2m loci excision resulting in complete knockout of MHC-I on the cell surface. We then orthotopically implanted B2m-comtetent and B2m-KO cells at varying inoculum ratios (100:0, 90:10, 50:50, 10:90, 0:100) into syngeneic Balb/C mice and assessed immune responsiveness and efficacy of checkpoint inhibition. Additionally, to look at how loss of MHC-I affects the tumor microenvironment we will use the PanCancer Immune NanoString panel (n=770 genes) to evaluate gene expression patterns in tumor cells and infiltrating immune cells.

Results

In patient samples, we identified high diversity in MHC-I expression across all clinical subtypes, with triple negative breast cancer (TNBC) having the highest MHC-I expression. Chemotherapy-treated tumors had higher MHC-I levels than untreated tumors. In mice when 10% of cells were B2m-KO, we observed a 50% reduction in complete eradication of EMT6 tumors with aPD-L1 treatment and reduced disease-stabilization and no complete responses when a 50% mixture of MHC-I deficient cells. An increasing percentage of B2m KO leads to worse outcomes overall and a decrease in infiltrating T cells.

Conclusions

Our work suggests that there is an ICI-responsive phenotype that is driven by heterogeneity in MHC-I expression levels. As little as 10% of tumor specific MHC-I loss can lead to therapeutic resistance and a decrease in complete responders. This represents that early TNBC may be less responsive to single-agent PD-L1 due to specific percentages of MHC-I loss. MHC-I expression can influence therapy outcomes and potentially lead to novel observations of how to overcome lack of, or limited, MHC-I expression.
Long-term effects of snowmelt timing and climate warming on phenology, growth, and reproductive effort of Arctic tundra plant species
Authors: Frei Esther R. , Henry Gregory H.R.
Published: November 2021

Arctic regions are particularly affected by rapidly rising temperatures and altered snow regimes. Snowmelt timing depends on spring temperatures and winter snow accumulation. Scenarios for the Arctic include both decreases and increases in snow accumulation. Predictions of future snowmelt timing are, thus, difficult and experimental evidence for ecological consequences is scarce. In 1995, a long-term factorial experiment was set up in a High Arctic evergreen shrub heath community on Ellesmere Island, Canada. We investigated how snow removal, snow addition, and passive warming affected phenology, growth and reproductive effort of the four common tundra plant species Cassiope tetragona (L.) D. Don, Dryas integrifolia Vahl, Luzula arctica Blytt, and Papaver radicatum Rottb. Timing of flowering and seed maturation as well as flower production were more strongly influenced by the combined effects of snowmelt timing and warming in the two shrub species than in the two herbaceous species. Warming effects persisted over the course of the growing season and resulted in increased shrub growth. Moreover, the long-term trend of increasing growth in two species suggests that ambient warming promotes tundra plant growth. Our results confirm the importance of complex interactions between temperature and snowmelt timing in driving species-specific plant responses to climate change in the Arctic.
Generalized uncertainty principle: from the harmonic oscillator to a QFT toy model
Authors: Bosso Pasquale , Luciano Giuseppe Gaetano
Published: November 2021

Several models of quantum gravity predict the emergence of a minimal length at Planck scale. This is commonly taken into consideration by modifying the Heisenberg uncertainty principle into the generalized uncertainty principle. In this work, we study the implications of a polynomial generalized uncertainty principle on the harmonic oscillator. We revisit both the analytic and algebraic methods, deriving the exact form of the generalized Heisenberg algebra in terms of the new position and momentum operators. We show that the energy spectrum and eigenfunctions are affected in a non-trivial way. Furthermore, a new set of ladder operators is derived which factorize the Hamiltonian exactly. The above formalism is finally exploited to construct a quantum field theoretic toy model based on the generalized uncertainty principle.
Determination of composition of mixed biological samples using laser-induced fluorescence and combined classification/regression models
Authors: Fellner Lea , Kraus Marian , Walter Arne , Duschek Frank , Bocklitz Thomas , Gabbarini Valentina , Rossi Riccardo , Puleio Alessandro , Malizia Andrea , Gaudio Pasquale
Published: November 2021

Laser-induced fluorescence (LIF) provides the ability to distinguish organic materials by a fast and distant in situ analysis. When detecting the substances directly in the environment, e.g., in an aerosol cloud or on surfaces, additional fluorescence signals of other fluorophores occurring in the surrounding are expected to mix with the desired signal. We approached this problem with a simplified experimental design for an evaluation of classification algorithms. An upcoming question for enhanced identification capabilities is the case of mixed samples providing different signals from different fluorophores. For this work, mixtures of up to four common fluorophores (NADH, FAD, tryptophan and tyrosine) were measured by a dual-wavelength setup and spectrally analyzed. Classification and regression are conducted with neural networks and show an excellent performance in predicting the ratios of the selected ingredients.
The role of noise in the tumor dynamics under chemotherapy treatment
Authors: Bashkirtseva Irina , Ryashko Lev , Duarte Jorge , Seoane Jesús M. , Sanjuan Miguel A. F.
Published: November 2021

Dynamical systems modeling tumor growth have been investigated to analyze the dynamics between tumor and healthy cells. Recent theoretical studies indicate that these interactions may lead to different dynamical outcomes under the effect of particular cancer therapies. In the present paper, we derive a system of nonlinear differential equations, in order to investigate solid tumors in vivo, taking into account the impact of chemotherapy on both tumor and healthy cells. We start by studying our model only in terms of deterministic dynamics under the variation of a drug concentration parameter. Later, with the introduction of noise, a stochastic model is used to analyze the impact of the unavoidable random fluctuations. As a result, new insights into noise-induced transitions are provided and illustrated in detail using techniques from dynamical systems and from the theory of stochastic processes.
High-Fidelity 3D Digital Human Head Creation from RGB-D Selfies
Authors: Bao Linchao , Lin Xiangkai , Chen Yajing , Zhang Haoxian , Wang Sheng , Zhe Xuefei , Kang Di , Huang Haozhi , Jiang Xinwei , Wang Jue , Yu Dong , Zhang Zhengyou
Published: November 2021

We present a fully automatic system that can produce high-fidelity, photo-realistic three-dimensional (3D) digital human heads with a consumer RGB-D selfie camera. The system only needs the user to take a short selfie RGB-D video while rotating his/her head and can produce a high-quality head reconstruction in less than 30 s. Our main contribution is a new facial geometry modeling and reflectance synthesis procedure that significantly improves the state of the art. Specifically, given the input video a two-stage frame selection procedure is first employed to select a few high-quality frames for reconstruction. Then a differentiable renderer-based 3D Morphable Model (3DMM) fitting algorithm is applied to recover facial geometries from multiview RGB-D data, which takes advantages of a powerful 3DMM basis constructed with extensive data generation and perturbation. Our 3DMM has much larger expressive capacities than conventional 3DMM, allowing us to recover more accurate facial geometry using merely linear basis. For reflectance synthesis, we present a hybrid approach that combines parametric fitting andConvolutional Neural Networks (CNNs)to synthesize high-resolution albedo/normal maps with realistic hair/pore/wrinkle details. Results show that our system can produce faithful 3D digital human faces with extremely realistic details. The main code and the newly constructed 3DMM basis is publicly available.
TightCap: 3D Human Shape Capture with Clothing Tightness Field
Authors: Chen Xin , Pang Anqi , Yang Wei , Wang Peihao , Xu Lan , Yu Jingyi
Published: November 2021

In this article, we present TightCap, a data-driven scheme to capture both the human shape and dressed garments accurately with only a single three-dimensional (3D) human scan, which enables numerous applications such as virtual try-on, biometrics, and body evaluation. To break the severe variations of the human poses and garments, we propose to model the clothing tightness field—the displacements from the garments to the human shape implicitly in the global UV texturing domain. To this end, we utilize an enhanced statistical human template and an effective multi-stage alignment scheme to map the 3D scan into a hybrid 2D geometry image. Based on this 2D representation, we propose a novel framework to predict clothing tightness field via a novel tightness formulation, as well as an effective optimization scheme to further reconstruct multi-layer human shape and garments under various clothing categories and human postures. We further propose a new clothing tightness dataset of human scans with a large variety of clothing styles, poses, and corresponding ground-truth human shapes to stimulate further research. Extensive experiments demonstrate the effectiveness of our TightCap to achieve the high-quality human shape and dressed garments reconstruction, as well as the further applications for clothing segmentation, retargeting, and animation.
Assessing Interests in the Twenty-First-Century Workforce: Building on a Century of Interest Measurement
Authors: Nye Christopher D.
Published: November 2021

Recent research has re-emphasized the importance of vocational interests for understanding workplace attitudes and behavior. As a result, there is a renewed interest in the assessment of vocational interests in organizations. Numerous interest assessments have been developed over the past century, and they are now administered to millions of people throughout the world. Nevertheless, there is still work to be done, particularly as interest assessments are increasingly being used in organizational settings. This article reviews developments in interest assessments and discusses the implications of their use for both research and practice. It discusses the advantages and disadvantages of examining vocational interests in organizational contexts and proposes future research directions.
Understanding the Effect of Feed Gas Humidity on the Freeze Start Behavior of Polymer Electrolyte Fuel Cells
Authors: Sabharwal Mayank , Charalambous Margarita , Dörenkamp Tim , Nagashima Shinya , Marone Federica , Büchi Felix N. , Eller Jens
Published: November 2021

Understanding the water dynamics during the sub-zero operation of polymer electrolyte fuel cells can help to optimize the materials and operating strategies to achieve successful freeze starts. This study employs sub-second X-ray tomographic microscopy to study the effect of downstream flow conditions on the water distributions during dynamic freeze starts from −30 °C by varying the feed gas humidity. An increase in the feed gas humidity resulted in a decrease in electrochemical performance. To probe the catalyst layer (CL)-micro-porous layer (MPL) interface, a MPL with grooves across it’s entire thickness was used. Imaging results showed that during the initial phase of performance drop due to ice formation, all the water produced was limited to the CL and membrane. The total water observed during the sub-zero operation in the MPL grooves was 1–2 orders of magnitude lower than the theoretical water produced and increased with an increase in the gas RH from 0% to 50% but reduced with further increase to 100% RH due to a lower cell performance. The overall saturation in the GDL was zero during the sub-zero operation and increased to less than 1% above 0 °C indicating minimal effect of the GDL mass transport on the freeze start performance.
An Intelligent Scheduling Access Privacy Protection Model of Electric Vehicle Based on 5G-V2X
Authors: Xu Cheng , Wu Hongjun , Liu Hongzhe , Li Xuewei , Liu Li , Wang Pengfei
Published: November 2021

It is more and more important to optimize electric power system scheduling in the development of the Internet of Vehicles. How to improve the applicability and scientific nature of electric vehicle charging is an urgent problem to be solved. This paper proposes an intelligent scheduling access model for electric vehicles based on blockchain. Firstly, the layout simplification calculation is carried out for the layout of the traditional distributed power grid. Then, a data storage and consensus system is built using blockchain smart contracts to ensure that all historical data are not tampered with and are traceable. Finally, the model forms an electricity price guidance model in the intelligent scheduling and access of electric vehicles, optimizes the multivehicle line congestion in operation, and can dynamically schedule and correct the model. In terms of the experiment, 13 test electric vehicles were dispatched based on 12 real power station nodes and 36 test nodes of Yunnan Power Grid Co. Information Center for verification. The result analysis shows that the model can effectively and quickly solve the blocking and unblocking of the Internet of Vehicles and can develop a scheduling scheme conforming to the safety constraints of electric vehicles in a relatively short time.
Load Frequency Control for Power Systems with Actuator Faults within a Finite-Time Interval
Authors: Qiu Haifeng , Weng Liguo , Yu Bin , Zhang Yanghui
Published: November 2021

This paper is concerned with the issue of finite-time

H

∞

load frequency control for power systems with actuator faults. Concerning various disturbances, the actuator fault is modeled by a homogeneous Markov chain. The aperiodic sampling data controller is designed to alleviate the conservatism of attained results. Based on a new piecewise Lyapunov functional, some novel sufficient criteria are established, and the resulting power system is stochastic finite-time bounded. Finally, a single-area power system is adjusted to verify the effectiveness of the attained results.
Flexural Behavior Performance of Reinforced Concrete Slabs Mixed with Nano- and Microsilica
Authors: Kancharla Rakesh , Maddumala Venkata Rao , Prasanna T. V. N. , Pullagura Lokaiah , Mukiri Ratna Raju , Prakash M. Viju
Published: November 2021

Present technology has been evaluated greatly over the past decades, where new particles are being designed and fabricated to fulfill specific needs. The field of nano- and micromaterials has prospered in many disciplines. It has been recently used in reinforced concrete in the production of high-strength, high-performance concrete. Microsilica (MS) and nanosilica (NS) particles have proven to be highly profitable to the concrete mix. Concrete has become denser with considerable improvement in their mechanical characteristics, particularly compressive strength. This proposed method includes a comparative study of the flexural bending behavior of conventional reinforced concrete (without MS or NS) slabs with other slabs. Each has various mixes of MS and NS particles incorporated into the concrete mix. The material content utilized in the slabs is kept constant by replacing a portion of the cement with an equivalent amount of either NS or MS particles or both. MS particles are altered from 0, 5, and 10% while NS particles are altered from 0, 0.5, and 1.0%. It cracks the widths and has higher final load-bearing capacity.
Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis
Authors: Fu Yan , Shen Jingjing , Li Yinhong , Liu Fanglin , Ning Bangzuo , Zheng Yuejuan , Jiang Xin
Published: November 2021

Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1β and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug.
The Largest Component of Near-Critical Random Intersection Graph with Tunable Clustering
Authors: Huang Shiying , Wang Bin
Published: November 2021

In this paper, we study the largest component of the near-critical random intersection graph

G

n
,
m
,
p

with

n

nodes and

m

elements, where

m
=
Θ

n

which leads to the fact that the clustering is tunable. We prove that with high probability the size of the largest component in the weakly supercritical random intersection graph with tunable clustering on

n

vertices is of order

n
ϵ

n

, and it is of order

ϵ

−
2

n

log

n

ϵ

3

n

in the weakly subcritical one, where

ϵ

n

⟶
0

and

n

1
/
3

ϵ

n

⟶
∞

as

n
⟶
∞

.
Progression of Subclinical Pachychoroid Neovasculopathy to an Active Neovascularization in the Presence of Acquired Vitelliform Lesions
Authors: Soman Manoj , Iqbal Sameer , Sheth Jay U. , Meleth Padmanaban , Nair Unnikrishnan
Published: November 2021

We describe a unique case of bilateral acquired vitelliform lesions in a 67-year-old-female with pachychoroid associated with subretinal fluid in the right eye (OD) and a nonexudative choroidal neovascular membrane (CNVM) in the left eye (OS). Multimodal imaging performed at baseline and over the ensuing two years showed an increase in the OS vitelliform lesions with a concurrent transformation of quiescent CNVM to an exudative form. Further studies are warranted to gain better insight into the etiopathogenesis of these vitelliform lesions in pachychoroid and their potential role in instigating CNVM activation.