bluuebunny/crossref_metadata_2025_split huggingface dataset:
Literacy is power: structural drivers of child malnutrition in rural Liberia
Authors: Kumeh Odell W , Fallah Mosoka P , Desai Ishaan K , Gilbert Hannah N , Silverstein Jason B , Beste Sara , Beste Jason , Mukherjee Joia S , Richardson Eugene T 
Published: December 2020

BackgroundIn Liberia, an estimated 32% of children under 5 are stunted. Malnutrition and hunger worsened during the country’s civil war and were further exacerbated by the 2014–2016 outbreak of Ebola virus disease. Studies examining adherence to recommended infant and young child feeding practices frequently do so with an emphasis on the knowledge, attitudes and beliefs of mothers and caregivers. Often overlooked are the structural factors that enable or constrain their agency to practise evidence-based recommendations.MethodsBetween July and December 2017, we surveyed 100 Liberian mothers to assess the sociodemographic factors associated with the risk of severe acute malnutrition in children in Maryland County, Liberia. We also conducted 50 in-depth interviews at two government health facilities to qualitatively explore mothers’ experiences, as well as health workers’ understandings of the determinants of malnutrition in the region. We applied logistic regression to analyse quantitative data and inductive content analysis to thematically interpret qualitative data.ResultsMothers were less likely to have a child with severe acute malnutrition if they had an income greater than US$50 per month (adjusted OR (aOR)=0.14, p<0.001), were literate (aOR=0.21, p=0.009) or exclusively breast fed during the first 6 months of life (aOR=0.18, p=0.049); they were more likely to have a child with severe acute malnutrition if they were married or in domestic partnerships (aOR=8.41, p<0.001). In-depth interviews elucidated several social, economic and programmatic factors that shaped suboptimal feeding practices, as well as decisions for and against seeking formal care for malnutrition.DiscussionThe lived experiences of Liberian mothers and health workers illustrate that child malnutrition is a direct consequence of abject poverty, food insecurity, illiteracy, the precarious nature of formal and informal work, and the lack of robust social protection. Behaviour change and health education interventions that do not seek to alleviate structural barriers to compliance are unlikely to be effective.
Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity
Authors: Douglass Stephen M. , Fane Mitchell E. , Sanseviero Emilio , Ecker Brett L. , Kugel Curtis H. , Behera Reeti , Kumar Vinit , Tcyganov Evgenii N. , Yin Xiangfan , Liu Qin , Chhabra Yash , Alicea Gretchen M. , Kuruvilla Rejji , Gabrilovich Dmitry I. , Weeraratna Ashani T. 
Published: December 2020

AbstractMetastatic dissemination remains a significant barrier to successful therapy for melanoma. Wnt5A is a potent driver of invasion in melanoma and is believed to be secreted from the tumor microenvironment (TME). Our data suggest that myeloid-derived suppressor cells (MDSC) in the TME are a major source of Wnt5A and are reliant upon Wnt5A for multiple actions. Knockdown of Wnt5A specifically in the myeloid cells demonstrated a clear decrease in Wnt5A expression within the TME in vivo as well as a decrease in intratumoral MDSC and regulatory T cell (Treg). Wnt5A knockdown also decreased the immunosuppressive nature of MDSC and decreased expression of TGFβ1 and arginase 1. In the presence of Wnt5A-depleted MDSC, tumor-infiltrating lymphocytes expressed decreased PD-1 and LAG3, suggesting a less exhausted phenotype. Myeloid-specific Wnt5A knockdown also led to decreased lung metastasis. Tumor-infiltrating MDSC from control animals showed a strong positive correlation with Treg, which was completely ablated in animals with Wnt5A-negative MDSC. Overall, our data suggest that while MDSC contribute to an immunosuppressive and less immunogenic environment, they exhibit an additional function as the major source of Wnt5A in the TME.Significance:These findings demonstrate that myeloid cells provide a major source of Wnt5A to facilitate metastatic potential in melanoma cells and rely on Wnt5A for their immunosuppressive function.
Composition, Spatial Characteristics, and Prognostic Significance of Myeloid Cell Infiltration in Pancreatic Cancer
Authors: Väyrynen Sara A. , Zhang Jinming , Yuan Chen , Väyrynen Juha P. , Dias Costa Andressa , Williams Hannah , Morales-Oyarvide Vicente , Lau Mai Chan , Rubinson Douglas A. , Dunne Richard F. , Kozak Margaret M. , Wang Wenjia , Agostini-Vulaj Diana , Drage Michael G. , Brais Lauren , Reilly Emma , Rahma Osama , Clancy Thomas , Wang Jiping , Linehan David C. , Aguirre Andrew J. , Fuchs Charles S. , Coussens Lisa M. , Chang Daniel T. , Koong Albert C. , Hezel Aram F. , Ogino Shuji , Nowak Jonathan A. , Wolpin Brian M. 
Published: December 2020

AbstractPurpose:Although abundant myeloid cell populations in the pancreatic ductal adenocarcinoma (PDAC) microenvironment have been postulated to suppress antitumor immunity, the composition of these populations, their spatial locations, and how they relate to patient outcomes are poorly understood.Experimental Design:To generate spatially resolved tumor and immune cell data at single-cell resolution, we developed two quantitative multiplex immunofluorescence assays to interrogate myeloid cells (CD15, CD14, ARG1, CD33, HLA-DR) and macrophages [CD68, CD163, CD86, IFN regulatory factor 5, MRC1 (CD206)] in the PDAC tumor microenvironment. Spatial point pattern analyses were conducted to assess the degree of colocalization between tumor cells and immune cells. Multivariable-adjusted Cox proportional hazards regression was used to assess associations with patient outcomes.Results:In a multi-institutional cohort of 305 primary PDAC resection specimens, myeloid cells were abundant, enriched within stromal regions, highly heterogeneous across tumors, and differed by somatic genotype. High densities of CD15+ARG1+ immunosuppressive granulocytic cells and M2-polarized macrophages were associated with worse patient survival. Moreover, beyond cell density, closer proximity of M2-polarized macrophages to tumor cells was strongly associated with disease-free survival, revealing the clinical significance and biologic importance of immune cell localization within tumor areas.Conclusions:A diverse set of myeloid cells are present within the PDAC tumor microenvironment and are distributed heterogeneously across patient tumors. Not only the densities but also the spatial locations of myeloid immune cells are associated with patient outcomes, highlighting the potential role of spatially resolved myeloid cell subtypes as quantitative biomarkers for PDAC prognosis and therapy.
Preclinical Characterization of HPN536, a Trispecific, T-Cell–Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors
Authors: Molloy Mary Ellen , Austin Richard J. , Lemon Bryan D. , Aaron Wade H. , Ganti Vaishnavi , Jones Adrie , Jones Susan D. , Strobel Kathryn L. , Patnaik Purbasa , Sexton Kenneth , Tatalick Laurie , Yu Timothy Z. , Baeuerle Patrick A. , Law Che-Leung , Wesche Holger 
Published: December 2020

Abstract

Purpose:
Mesothelin (MSLN) is a glycophosphatidylinositol-linked tumor antigen overexpressed in a variety of malignancies, including ovarian, pancreatic, lung, and triple-negative breast cancer. Early signs of clinical efficacy with MSLN-targeting agents have validated MSLN as a promising target for therapeutic intervention, but therapies with improved efficacy are still needed to address the significant unmet medical need posed by MSLN-expressing cancers.

Experimental Design:
We designed HPN536, a 53-kDa, trispecific, T-cell–activating protein-based construct, which binds to MSLN-expressing tumor cells, CD3ϵ on T cells, and to serum albumin. Experiments were conducted to assess the potency, activity, and half-life of HPN536 in in vitro assays, rodent models, and in nonhuman primates (NHP).

Results:
HPN536 binds to MSLN-expressing tumor cells and to CD3ϵ on T cells, leading to T-cell activation and potent redirected target cell lysis. A third domain of HPN536 binds to serum albumin for extension of plasma half-life. In cynomolgus monkeys, HPN536 at doses ranging from 0.1 to 10 mg/kg demonstrated MSLN-dependent pharmacologic activity, was well tolerated, and showed pharmacokinetics in support of weekly dosing in humans.

Conclusions:
HPN536 is potent, is well tolerated, and exhibits extended half-life in NHPs. It is currently in phase I clinical testing in patients with MSLN-expressing malignancies (NCT03872206).
MTrack: Improved Center Fix of Tropical Cyclones from SMAP Wind Observations
Authors: Mayers David , Ruf Christopher 
Published: December 2020

AbstractMTrack is an automated algorithm that determines the center location (latitude and longitude) of a tropical cyclone from a scalar wind field derived from satellite observations. Accurate storm centers are useful for operational forecasting of tropical cyclones and for their reanalysis (e.g., research on storm surge modeling). Currently, storm center fixes have significantly larger errors for weak, disorganized storms. The MTrack algorithm presented here improves storm centers in some of those cases. It is also automated and, therefore, less subjective than manual fixes made by forecasters. The MTrack algorithm, which was originally designed to work with CYGNSS wind speed measurements, is applied to SMAP winds for the first time. The average difference between MTrack and Best Track storm center locations is 21, 36, and 46 km for major hurricanes, category 1–2 hurricanes, and tropical storms, respectively. MTrack is shown to operate successfully when a storm is only partially sampled by the observing satellite and when the eye of the storm is not resolved.
The Amazon Water Cycle: Perspectives from Water Budget Closure and Ocean Salinity
Authors: Reeves Eyre J. E. Jack , Zeng Xubin 
Published: December 2020

AbstractGlobal and regional water cycle includes precipitation, water vapor divergence, and change of column water vapor in the atmosphere, and land surface evapotranspiration, terrestrial water storage change, and river discharge, which is linked to ocean salinity near the river mouth. The water cycle is a crucial component of the Earth system, and numerous studies have addressed its individual components (e.g., precipitation). Here we assess, for the first time, if remote sensing and reanalysis datasets can accurately and self-consistently portray the Amazon water cycle. This is further assisted with satellite ocean salinity measurements near the mouth of the Amazon River. The widely used practice of taking the mean of an ensemble of datasets to represent water cycle components (e.g., precipitation) can produce large biases in water cycle closure. Closure is achieved with only a small subset of data combinations (e.g., ERA5 precipitation and evapotranspiration plus GRACE satellite terrestrial water storage), which rules out the lower precipitation and higher evapotranspiration estimates, providing valuable constraints on assessments of precipitation, evapotranspiration, and their ratio. The common approach of using the Óbidos stream gauge (located hundreds of kilometers from the river mouth) multiplied by a constant (1.25) to represent the entire Amazon discharge is found to misrepresent the seasonal cycle, and this can affect the apparent influence of Amazon discharge on tropical Atlantic salinity.
Neoliberalism: Unpacking Limited Employment Success for Persons with SMI
Authors: Gruhl Karen Lynn Rebeiro 
Published: December 2020

Background. A mixed-methods case study exploring access to competitive employment for persons with serious mental illness (SMI) revealed limited access to work and low employment success across two northern communities. Purpose. To explore possible explanations for why low employment rates persist despite existing employment services and supports. Methods. A total of 46 individual or group interviews were conducted with persons with SMI, vocational providers, and decision-makers regarding access to competitive employment in the case communities. Data were systematically analysed for dominant ideas, interests and institutions using a neo-institutional framework. Findings. Participants described access to employment to be constrained by provider competition, limited supports, and a lack of consideration of difference—ideas and interests associated with neoliberal influences within provincial employment supports policy. Implications. Enabling participation in meaningful employment for people with SMI will require occupational therapists to appreciate and contest the oppressive nature of neoliberal policies on local programs and services.
Prognostic Significance of HPV Status in Laryngeal Squamous Cell Carcinoma: A Large‐Population Database Study
Authors: Panuganti Bharat A. , Finegersh Andrey , Flagg Mitchell , Tu Xin , Orosco Ryan , Weissbrod Philip A. , Califano Joseph 
Published: December 2020

ObjectiveTo explore the survival implications of human papillomavirus (HPV) positivity and subtype in larynx cancer through a national cancer database. To investigate staging discrepancies in larynx cancer associated with HPV status.Study DesignRetrospective observational cohort study.SettingNational Cancer Database.MethodsData were extracted concerning adults with known HPV status who were treated between 2010 and 2016 for laryngeal squamous cell carcinoma. Patients without known HPV subtype were excluded. Cox multivariable regression models were fit to evaluate the survival impact of HPV status, characterized as a binary variable (HPV+ vs HPV–) and by subtype. Two‐ and 5‐year survival rates were calculated via the Kaplan‐Meier method and compared by stage between the HPV+ and HPV– cohorts per the log‐rank test.ResultsPatients with HPV+ larynx cancer were younger (60.5 vs 64.3 years, P <. 001), more likely to have private insurance (37.2% vs 31.2%, P <. 001), more commonly White (84.6% vs 82.4%, P =. 013), and more likely to present with nodal disease (42.6% vs 33.0%, P <. 001). HPV positivity and HPV subtype 16 were associated with improved overall survival. One‐stage discrepancies in 5‐year survival were observed between the HPV+ and HPV– cohorts: stage II HPV+ (69.45%) vs stage I HPV– (65.77%); stage IV HPV+ (47.67%) vs stage III HPV– (46.80%).ConclusionsHPV positivity and infection with HPV subtype 16 are correlated with improved overall survival in patients with laryngeal squamous cell carcinoma, manifesting with a 1‐stage incremental survival advantage. Future prospective studies are indicated to corroborate the findings from this large‐population database retrospective study.
Selecting Bolt-on Dimensions for the EQ-5D: Testing the Impact of Hearing, Sleep, Cognition, Energy, and Relationships on Preferences Using Pairwise Choices
Authors: Finch Aureliano Paolo , Brazier John , Mukuria Clara 
Published: December 2020

Background Generic preference-based measures (GPBMs) such as the EQ-5D are valid across many conditions, but in some cases, “bolting on” additional dimensions may improve validity. The selection of “bolt-ons” has been based on the psychometric impact of individual dimensions, but preferences provide another important way to select them. This study aims to test the potential of using pairwise choices to inform the selection of bolt-ons for the EQ-5D-5L. Methods General population preferences were collected using an online survey of 1040 UK residents. Three EQ-5D-5L health state pairs were selected based on pairs that had a 50:50 split in respondent preferences from a previous pairwise survey. Participants were presented with pairwise choices of EQ-5D-5L health states without and with bolt-ons of hearing, sleep, cognition, energy, and relationships, each added individually. Logistic models were used to assess the impact of bolt-ons, as well as bolt-ons at different severity levels, on the log odds of responders choosing between health states. Results Preferences varied according to the bolt-ons and their severity level (only levels 1, 3, and 5 were used). Additions of bolt-ons at level 1 generally resulted in nonstatistically significant differences while additions of bolt-ons at level 3 and level 5 produced a negative and statistically significant impact on preferences for the health state with the bolt-on. At level 5, hearing had the largest impact, followed by cognition, relationships, energy, and sleep. At level 3, cognition produced the largest impact, followed by hearing and sleep with similar impacts, energy, and relationships. This ordering offers information for bolt-on selection, with hearing and cognition appearing as the most important. The weight placed on the different health problems is not constant across severity levels between bolt-ons. Conclusions Pairwise choices provide a cost-effective approach of generating information on preferences to support bolt-on selection.
Venovenous ECMO treatment, outcomes, and complications in adults according to large case series: A systematic review
Authors: Kim Jun Hyun , Pieri Marina , Landoni Giovanni , Scandroglio Anna Mara , Calabrò Maria Grazia , Fominskiy Evgeny , Lembo Rosalba , Heo Min Hee , Zangrillo Alberto 
Published: December 2020

Background: Venovenous extracorporeal membrane oxygenation (VV ECMO) has gained popularity for the treatment of refractory respiratory failure during and after the 2009 influenza pandemic, and still represents a precious therapeutic resource for severe novel coronavirus 2019 infection. However, most of the published studies are small case series, and only two randomized trials exist in literature. Aim: Aim of this systematic review is to describe trends in VV ECMO treatment outcomes according to large studies only. Methods: We searched and included studies with more than 100 VV ECMO cases dated up to August 1st, 2019. Results: Thirty-three studies published in the period 2011–2019 met inclusion criteria, for a total of 12,860 patients (age 46.3 ± 17.4 years). ARDS was mainly by pneumonia, in 3126 (37%) cases; further 401(7%) patients had H1N1 Influenza A infection. Cannulation-related complications occurred in 502 (7%) cases. Weighted mean (95% confidence interval) of VV ECMO duration was 8.9 (8.7–9.1) days, and ICU stay was 23.6 (22.4–24.8) days. Mortality at the longest follow up available was 40%. Data collection in 70% of the studies had a duration of >5 years. Conclusion: This study reveals the characteristics of large case VV ECMO studies.
Indian Fertility Transition
Authors: Radkar Anjali 
Published: December 2020

Fighting to curb the population growth, India’s reduction in fertility rate (58%) in 35 years is evident; total fertility rate (TFR) declined from 5.2 to 2.2 meaning three children less. According to the National Family Health Survey (NFHS-4), 2015–2016, TFR has dropped to 2.18 from 3.39 in 1992 (NFHS-1). Proximate determinants indicate that over a period, index of marriage and contraception contribute lesser towards fertility, and postpartum amenorrhoea shows marginal variation. When total fecundity remains constant, share of abortion does not remain one but contribute towards fertility reduction. Benefits of fertility decline include lowering population growth and its positive effects on overall development. As fertility declines, maternal mortality declines; maternal mortality ratio (MRR) declined by 67 per cent in past 13 years. Sharp decline in fertility gives rise to demographic dividend. India is passing through it. Fertility drop is not without consequences. Fertility decline makes pregnancies precious; giving rise to upswing to C-section deliveries and hysterectomy even for a minor cause or is it a response to cancer threat? Preference for sons is universal here. With fertility reduction, it surfaces with unruly consequences of missing girls. Drop in fertility has changed the shape of the population pyramid. Share of elderly is reaching 10 per cent, of which share of women and more so share of oldest women is more. In the absence of social security and low rates of workforce participation, women are getting more dependent on the required care, increasing their vulnerability. Fertility reduction has achieved with moderate level of development. Now the right response to effects of fertility decline is the biggest social challenge.
Evaluation of topical morphine for treatment of oral mucositis in cancer patients
Authors: Nielsen Bettina Nygaard , Friis Susanne Molin , Schmiegelow Kjeld , Henneberg Steen , Rømsing Janne 
Published: December 2020

Introduction: Oral mucositis is a painful side effect to chemotherapy. Orally applied opioids may offer analgesia with fewer side effects than systemic opioids. Methods: A randomized trial comparing the analgesic effect of a morphine oromucosal solution (OM) to placebo and a positive control group receiving intravenous (IV) morphine as an add-on treatment to morphine patient-controlled analgesia (PCA) in a mixed population of paediatric and adult haematology patients. All patients in the study were equipped with a morphine PCA pump and the participating patients were instructed to use this pump as an escape. Primary outcome was morphine consumption (mg/kg/hour) on the PCA pump. Secondary outcomes included pain intensity difference at rest and when performing oral hygiene, time to first PCA bolus, nutrition intake and adverse events. Findings: A total of 60 patients (38 children <18 years) were randomized. Thirty patients were allocated to morphine OM/placebo IV (group MO), 15 patients to placebo OM/morphine IV (group MI) and 15 patients to placebo OM/placebo IV (group P). The median morphine consumption in the MO group (22.7 mcg/kg/hour 95% confidence interval (CI) 19.4–29.4 mcg/kg/hour, p = 0.38) was not significantly different from the placebo group (24.6 mcg/kg/hour 95% CI 16.8–34.4 mcg/kg/hour, p = 0.44) or the MI group (13.7 mcg/kg/hour 95% CI 9.7–37.8 mcg/kg/hour). For the secondary outcomes, the analysis of summed pain intensity difference after the first, third and fourth administrations of study medication indicated a reduction in pain for the MI group compared to the P and MO groups. No serious adverse events were reported. Conclusion: The findings indicate that the analgesic effect of peripherally applied morphine is not significantly different from placebo, and parenteral opioids should continue to be the standard of care.