bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of prostate cancer in older patients
Authors: Narita Shintaro , Hatakeyama Shingo , Sakamoto Shinichi , Kato Takuma , Inokuchi Juichi , Matsui Yoshiyuki , Kitamura Hiroshi , Nishiyama Hiroyuki , Habuchi Tomonori 
Published: February 2022

Abstract
The incidence of prostate cancer among older men has increased in many countries, including Asian countries. However, older patients are ineligible for inclusion in large randomized trials, and the existing guidelines for the management of patients with prostate cancer do not provide specific treatment recommendations for older men. Therefore, generation of evidence for older patients with prostate cancer is a key imperative. The International Society of Geriatric Oncology has produced and updated several guidelines for management of prostate cancer in older men since 2010. Regarding localized prostate cancer, both surgery and radiotherapy are considered as feasible treatment options for intermediate- and high-risk prostate cancer even in older men, whereas watchful waiting and active surveillance are useful options for a proportion of these patients. With regard to advanced disease, androgen-receptor axis targets and taxane chemotherapy are standard treatment modalities, although dose modification and prevention of adverse events need to be considered. Management strategy for older patients with prostate cancer should take cognizance of not only the chronological age but also psychological and physical condition, socio-economic status and patient preferences. Geriatric assessment and patient-reported health-related quality of life are important tools for assessing health status of older patients with prostate cancer; however, there is a paucity of evidence of the impact of these tools on the clinical outcomes. Personalized management according to the patient’s health status and tumour characteristics as well as socio-economic condition may be necessary for treatment of older patients with prostate cancer.
Empirical Asset Pricing with Functional Factors
Authors: Nadler Philip , Sancetta Alessio 
Published: February 2022

Abstract
We propose a methodology to use functional factors in empirical asset pricing models. We establish conditions under which it is possible to recover linear beta pricing. The proposed estimation approach allows us to use high-dimensional functional curves, such as the term structure of interest rates or the implied volatility smile, as factors. This framework enables the estimation of functional factor loadings as well as risk premium parameters of factor models. We derive estimation algorithms and establish the asymptotic consistency and normality of the parameter estimates. In an empirical application, we show that the implied variance smile of the S&P500 is a potential pricing factor for momentum-sorted portfolios. In particular, a positive risk premium is earned by the convexity of the implied variance curve.
Genetics as a key to improving crop photosynthesis
Authors: Theeuwen Tom P J M , Logie Louise L , Harbinson Jeremy , Aarts Mark G M 
Published: February 2022

Abstract
Since the basic biochemical mechanisms of photosynthesis are remarkably conserved among plant species, genetic modification approaches have so far been the main route to improve the photosynthetic performance of crops. Yet, phenotypic variation observed in wild species and between varieties of crop species implies there is standing natural genetic variation for photosynthesis, offering a largely unexplored resource to use for breeding crops with improved photosynthesis and higher yields. The reason this has not yet been explored is that the variation probably involves thousands of genes, each contributing only a little to photosynthesis, making them hard to identify without proper phenotyping and genetic tools. This is changing, though, and increasingly studies report on quantitative trait loci for photosynthetic phenotypes. So far, hardly any of these quantitative trait loci have been used in marker assisted breeding or genomic selection approaches to improve crop photosynthesis and yield, and hardly ever have the underlying causal genes been identified. We propose to take the genetics of photosynthesis to a higher level, and identify the genes and alleles nature has used for millions of years to tune photosynthesis to be in line with local environmental conditions. We will need to determine the physiological function of the genes and alleles, and design novel strategies to use this knowledge to improve crop photosynthesis through conventional plant breeding, based on readily available crop plant germplasm. In this work, we present and discuss the genetic methods needed to reveal natural genetic variation, and elaborate on how to apply this to improve crop photosynthesis.
The muted voices of the ringworm patients and their families worldwide
Authors: Hoffer Liat 
Published: February 2022

Abstract
The main objective of this chapter is to provide a platform for the muted voices of former ringworm patients around the world to be heard. Most of the patients quoted in this chapter describe their treatment as harsh and traumatic, triggering a sense of fear, helplessness, and sadness. They recall feelings of embarrassment and shame, and painful memories of ridicule and rejection by peers and even by their immediate family. Sometimes their plight was accompanied by feelings of disappointment, shame, and anger regarding their caregivers. Their shared sense of distress is reflected in their comments contrasting the condition of their hair before and after treatment, and their feelings about their current lives as a result. Besides these sources of distress, there is also the shared worry about the health ramifications of the treatment. These feelings are strikingly similar between patients and their family members despite the geographic distances and cultural differences that divide them.
Acrosomal alkalinization occurs during human sperm capacitation
Authors: Carrasquel Martínez Gabriela , Aldana Andrés , Carneiro Jorge , Treviño Claudia Lydia , Darszon Alberto 
Published: February 2022

Abstract
Mammalian sperm capacitation is a prerequisite for successful fertilization. Capacitation involves biochemical and physiological modifications of sperm as they travel through the female reproductive tract. These modifications prepare the sperm to undergo the acrosome reaction (AR), an acrosome vesicle exocytosis that is necessary for gamete fusion. Capacitation requires an increase in both intracellular calcium ([Ca2+]i) and pH (pHi). Mouse sperm capacitation is accompanied by acrosomal alkalinization and artificial elevation of the acrosome pH (pHa) is sufficient to trigger the AR in mouse and human sperm, but it is unknown if pHa increases naturally during human sperm capacitation. We used single-cell imaging and image-based flow cytometry to evaluate pHa during capacitation and its regulation. We found that pHa progressively increases during capacitation. The V-ATPase, which immunolocalized to the acrosome and equatorial segment, is mainly responsible for the acidity of the acrosome. It is likely that the regulation of V-ATPase is at least in part responsible for the progressive increase in pHa during capacitation. Acrosome alkalinization was dependent on extracellular HCO3− and Ca2+. Inhibition of the HCO3−-dependent adenylyl cyclase and protein kinase A induced significant pHa changes. Overall, alkalinization of the acrosome may be a key step in the path toward the AR.
Nesfatin-1 treatment preserves antioxidant status and attenuates renal fibrosis in rats with unilateral ureteral obstruction
Authors: Tezcan Neslihan , Özdemir-Kumral Zarife Nigâr , Özkan Yenal Naziye , Çilingir-Kaya Özlem T , Virlan Aysin Tulunay , Özbeyli Dilek , Çetinel Şule , Yeğen Berrak Ç , Koç Mehmet 
Published: February 2022

ABSTRACT

Background
Nesfatin-1 (NES-1), an anorexigenic peptide, was reported to have anti-inflammatory and anti-apoptotic actions in several inflammation models.

Methods
To elucidate potential renoprotective effects of NES-1, unilateral ureteral obstruction (UUO) was induced in male Sprague Dawley rats by ligating left ureters. The rats were injected intraperitoneally with either saline (SL) or NES-1 (10 µg/kg/day) for 7 or 14 days (n = 8 in each group). On the 7th or 14th day, obstructed kidneys were removed for the isolation of leucocytes for flow-cytometric analysis and the assessments of biochemical and histopathological changes.

Results
Opposite to glutathione levels, renal myeloperoxidase activity in the SL-treated UUO group was significantly increased compared with the sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in the SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated tumour necrosis factor-alpha (TNF-α) levels in SL-treated UUO group were decreased with NES-1. Although total degeneration scores were similarly increased in all UUO groups, tubular dilatation scores were significantly increased in UUO groups and lowered by NES-1 only in the 7-day treated group. Elevated interstitial fibrosis scores in the SL-treated groups were decreased in both 7- and 14-day NES-1 treated groups, while alpha-smooth muscle actin (α-SMA) and apoptosis scores were depressed in both NES-1 treated groups.

Conclusion
The present data demonstrate that UUO-induced renal fibrosis is ameliorated by NES-1, which appears to involve the inhibition of neutrophil infiltration and thereby amelioration of oxidative stress and inflammation. These data suggest that NES-1 may have a regulatory role in protecting the kidneys against obstruction-induced renal injury.
A preclinical model of patient-derived cerebrospinal fluid circulating tumor cells for experimental therapeutics in leptomeningeal disease from melanoma
Authors: Law Vincent , Chen Zhihua , Vena Francesca , Smalley Inna , Macaulay Robert , Evernden Brittany R , Tran Nam , Pina Yolanda , Puskas John , Caceres Gisela , Bayle Simon , Johnson Joseph , Liu James K C , Etame Arnold , Vogelbaum Michael , Rodriguez Paulo , Duckett Derek , Czerniecki Brian , Chen Ann , Smalley Keiran S M , Forsyth Peter A 
Published: February 2022

Abstract

Background
Leptomeningeal disease (LMD) occurs as a late complication of several human cancers and has no rationally designed treatment options. A major barrier to developing effective therapies for LMD is the lack of cell-based or preclinical models that recapitulate human disease. Here, we describe the development of in vitro and in vivo cultures of patient-derived cerebrospinal fluid circulating tumor cells (PD-CSF-CTCs) from patients with melanoma as a preclinical model to identify exploitable vulnerabilities in melanoma LMD.

Methods
CSF-CTCs were collected from melanoma patients with melanoma-derived LMD and cultured ex vivo using human meningeal cell-conditioned media. Using immunoassays and RNA-sequencing analyses of PD-CSF-CTCs, molecular signaling pathways were examined and new therapeutic targets were tested for efficacy in PD-CSF-CTCs preclinical models.

Results
PD-CSF-CTCs were successfully established both in vitro and in vivo. Global RNA analyses of PD-CSF-CTCs revealed several therapeutically tractable targets. These studies complimented our prior proteomic studies highlighting IGF1 signaling as a potential target in LMD. As a proof of concept, combining treatment of ceritinib and trametinib in vitro and in vivo demonstrated synergistic antitumor activity in PD-CSF-CTCs and BRAF inhibitor-resistant melanoma cells.

Conclusions
This study demonstrates that CSF-CTCs can be grown in vitro and in vivo from some melanoma patients with LMD and used as preclinical models. These models retained melanoma expression patterns and had signaling pathways that are therapeutically targetable. These novel models/reagents may be useful in developing rationally designed treatments for LMD.
T lymphocytes as dynamic regulators of glioma pathobiology
Authors: Cordell Elizabeth C , Alghamri Mahmoud S , Castro Maria G , Gutmann David H 
Published: February 2022

Abstract
The brain tumor microenvironment contains numerous distinct types of nonneoplastic cells, which each serve a diverse set of roles relevant to the formation, maintenance, and progression of these central nervous system cancers. While varying in frequencies, monocytes (macrophages, microglia, and myeloid-derived suppressor cells), dendritic cells, natural killer cells, and T lymphocytes represent the most common nonneoplastic cellular constituents in low- and high-grade gliomas (astrocytomas). Although T cells are conventionally thought to target and eliminate neoplastic cells, T cells also exist in other states, characterized by tolerance, ignorance, anergy, and exhaustion. In addition, T cells can function as drivers of brain cancer growth, especially in low-grade gliomas. Since T cells originate in the blood and bone marrow sinuses, their capacity to function as both positive and negative regulators of glioma growth has ignited renewed interest in their deployment as immunotherapeutic agents. In this review, we discuss the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Pattern of treatment failures in patients with central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A pooled analysis of clinical trials
Authors: Fonseca Adriana , Faure-Conter Cecile , Murray Matthew J , Fangusaro Jason , Bailey Shivani , Goldman Stewart , Khatua Soumen , Frappaz Didier , Calaminus Gabriele , Dhall Girish , Nicholson James C , Bouffet Eric , Bartels Ute 
Published: February 2022

Abstract

Background
Central Nervous System Non-Germinomatous Germ Cell Tumors (CNS-NGGCT) are rare but curable tumors. Due to their rarity, patients with treatment failures remain a poorly characterized group with unfavorable outcomes. In this study, we sought to characterize patients with treatment failures in a large, prospectively treated cohort.

Methods
European and North American clinical trials for patients with CNS-NGGCT (SIOP-GCT-96, SFOP-TGM-TC 90/92, COG-ACNS0122, and COG-ACNS1123) were pooled for analysis. Additionally, patients included and treated in the UK and France national registries under strict protocol guidelines were included as an independent, non-overlapping cohort.

Results
A total of 118 patients experienced a treatment failure. Twenty-four patients had progressive disease during therapy, and additional 11 patients were diagnosed with growing teratoma syndrome (GTS). Patients with GTS are significantly younger and present with local failures and negative tumor markers. Eighty-three individuals experienced disease relapses after treatment ended. Patients’ metastatic relapses presented significantly earlier than local relapses and were associated with tumor marker elevation (OR: 4.39; P = .026). In our analysis, focal or whole-ventricular radiation therapy was not associated with an increased risk of metastatic relapses.

Conclusions
Herein, we present the largest pooled dataset of prospectively treated patients with relapsed CNS-NGGCT. Our study identified younger age and negative tumor markers to be characteristic of GTS. Additionally, we elucidated that metastatic relapses occur earlier than local relapses are associated with elevated tumor markers and are not associated with the field of radiation therapy. These findings are of utmost importance for the planning of future clinical trials and the implementation of surveillance strategies in these patients.
ADXS31142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study
Authors: Stein Mark N , Fong Lawrence , Tutrone Ronald , Mega Anthony , Lam Elaine T , Parsi Megan , Vangala Surya , Gutierrez Andres A , Haas Naomi B 
Published: February 2022

AbstractBackgroundADXS31-142 is an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), being evaluated as monotherapy and combined with pembrolizumab for metastatic castration-resistant prostate cancer (mCRPC).Patients and MethodsThe 2-part phase I/II KEYNOTE-046 study enrolled men with mCRPC who have progressed after 2 or fewer prior systemic treatment regimens in the metastatic setting. In Part A, intravenous ADXS31-142 monotherapy was given every 3 weeks (q3w) to 3 dose-escalation cohorts. In Part B, ADXS31-142 (1 × 109 colony-forming units) plus pembrolizumab (200 mg) was administered intravenously q3w for 3 doses with a fourth pembrolizumab dose 3 weeks later (12-week cycles) for up to 24 months or until progression/toxicity. Endpoints included safety, overall response rate, progression-free survival (PFS), overall survival (OS), and immunogenicity.ResultsFifty patients received ADXS31-142 alone (n = 13) or with pembrolizumab (n = 37). Among the 37 RECIST-evaluable patients (n = 8 Part A; n = 29 Part B), there were no objective responses. Median PFS was 2.2 months (95% CI: 0.8-7.4) with monotherapy and 5.4 months (95% CI: 2.3-7.9) with the combination; median OS was 7.8 months (95% CI: 4.4-18.5) and 33.7 months (95% CI: 15.4–not evaluable), respectively. Promising OS benefit was observed in combination-treated patients who had received prior docetaxel (16.0 months, 95% CI: 6.4-34.6; n = 20) and those with visceral metastasis (16.4 months, 95% CI 4.0-not evaluable; n = 11). All patients had ≥1 treatment-related adverse event, mostly grade 1/2 manageable events. No additive toxicity was observed with combination treatment.ConclusionsCombining ADXS31-142 with pembrolizumab was safe and well tolerated. The observed OS in mCRPC warrants further testing of this combination.Clinical Trial registrationNCT02325557.
Temporal factors and distance to human settlement affect nest survival of the endangered Yellow-headed Parrot in Belize, Central America
Authors: Tarazona-Tubens Fabio L , Britt Charles R , Abadi Fitsum , Muschamp Mario , Desmond Martha J 
Published: February 2022

AbstractThe endangered Yellow-headed Parrot (Amazona oratrix) has experienced a considerable reduction in abundance and distribution. Identifying natural and anthropogenic causes of nest failure is a critical step towards developing conservation actions that increase nest survival. In this study, we examined daily nest survival in relation to temporal, habitat, and anthropogenic factors, as well as nest site properties. We monitored nests (n = 124) across 6 study sites in Belize during 2017 and 2018 and independently modeled the effects of predation, abandonment and poaching on daily nest survival rates. Overall, the estimated cumulative nest survival probability was 0.18 (95% CI: 0.12–0.25). Predation was the main cause of nest failure, followed by abandonment, and poaching. Our results showed that nest predation and abandonment usually occurred early in the nesting cycle. Day within the nesting season negatively influenced daily survival for abandoned nests and had a quadratic effect on survival for poached nests. Poaching events occurred at a specific date range later in the season, with nests farther from the nearest human settlement having higher daily survival. Findings from this study highlight the additive mortality effect that nest poaching is having on Yellow-headed Parrot populations in Belize and show that managers can anticipate the timing and location of nests most vulnerable to poaching.
Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components
Authors: Dahhan Dana A , Reynolds Gregory D , Cárdenas Jessica J , Eeckhout Dominique , Johnson Alexander , Yperman Klaas , Kaufmann Walter A , Vang Nou , Yan Xu , Hwang Inhwan , Heese Antje , De Jaeger Geert , Friml Jiří , Van Damme Daniël , Pan Jianwei , Bednarek Sebastian Y 
Published: February 2022

AbstractIn eukaryotes, clathrin-coated vesicles (CCVs) facilitate the internalization of material from the cell surface as well as the movement of cargo in post-Golgi trafficking pathways. This diversity of functions is partially provided by multiple monomeric and multimeric clathrin adaptor complexes that provide compartment and cargo selectivity. The adaptor-protein assembly polypeptide-1 (AP-1) complex operates as part of the secretory pathway at the trans-Golgi network (TGN), while the AP-2 complex and the TPLATE complex jointly operate at the plasma membrane to execute clathrin-mediated endocytosis. Key to our further understanding of clathrin-mediated trafficking in plants will be the comprehensive identification and characterization of the network of evolutionarily conserved and plant-specific core and accessory machinery involved in the formation and targeting of CCVs. To facilitate these studies, we have analyzed the proteome of enriched TGN/early endosome-derived and endocytic CCVs isolated from dividing and expanding suspension-cultured Arabidopsis (Arabidopsis thaliana) cells. Tandem mass spectrometry analysis results were validated by differential chemical labeling experiments to identify proteins co-enriching with CCVs. Proteins enriched in CCVs included previously characterized CCV components and cargos such as the vacuolar sorting receptors in addition to conserved and plant-specific components whose function in clathrin-mediated trafficking has not been previously defined. Notably, in addition to AP-1 and AP-2, all subunits of the AP-4 complex, but not AP-3 or AP-5, were found to be in high abundance in the CCV proteome. The association of AP-4 with suspension-cultured Arabidopsis CCVs is further supported via additional biochemical data.
The Counteracting Nature of Contextual Influences: Peer Effects and Offsetting Mechanisms in Schools
Authors: Borgen Nicolai T , Borgen Solveig T , Birkelund Gunn Elisabeth 
Published: February 2022

Abstract
There is currently a mismatch between the theoretical expectations of peer effects held by many scholars and the quantitative empirical literature. This paper contributes to the understanding of peer effects by highlighting the oft-overlooked conceptual distinction between social influences and a well-defined causal effect; peers may influence one another via several potentially contradicting mechanisms that result in small overall causal peer effects on educational outcomes. We exploit the idiosyncratic variation in gender composition across cohorts within schools to study offsetting mechanisms. Using population-wide Norwegian register and survey data, we find two distinct ways in which the share of girls in lower secondary schools (grades 8–10) affects academic outcomes. First, more girl peers improve the learning environment at school. Simultaneously, however, more girl peers reduce the students’ motivation for schoolwork. Such results suggest that peer effects stem from a complex process where various mechanisms are at odds with one another, and where the influence of peers on academic outcomes is a composite of different mechanisms. Overall, we find that more girl peers lower students’ school grades and reduce students’ likelihood of attending an academic track in upper secondary school (which qualifies for higher education). Supplementary analyses suggest that the achievement level of girls is the main reason for the gender peer effects found in our study.