bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors
Authors: Paolini Francesca , Amici Carla , Carosi Mariantonia , Bonomo Claudia , Di Bonito Paola , Venuti Aldo , Accardi Luisa 
Published: January 2021

Abstract
Background
The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells.

Methods
Envisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed.

Results
We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway.

Conclusion
Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.
Association between morphologic grading and implantation rate of Euploid blastocyst
Authors: Lou Hua , Li Na , Guan Yichun , Zhang Yuchao , Hao Dayong , Cui Shihong 
Published: January 2021

Abstract
Background
Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles.

Methods
A total of 271 patients aged 20–40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted.

Results
Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P<0.001). Planned subgroup analyses by age and the day of TE biopsy were conducted. Logistic regression analyses that adjusted for these variables identified higher implantation rates (adjusted odds ratio(aOR) = 4.083, 95% confidence interval (CI):1.836–9.082, P<0.001) for the good-quality blastocysts than for those that underwent poor-quality cycles in women aged < 35 years, but not in women aged ≥35 years (aOR = 6.074, 95% CI: 0.456–80.919, P = 0.172). The implantation rates were higher among women with good-quality blastocysts on both Day 5 and Day 6 of TE biopsy than among those with poor-quality blastocysts (Day 5, aOR = 3.294, 95% CI:1.260–8.616, P = 0.015; Day 6, aOR = 4.179, 95% CI:1.004 ~ 17.399, P = 0.049). Day 5 euploid blastocysts had no significant difference in implantation potential and early spontaneous abortion rate compared with similarly graded Day 6 euploid blastocysts.

Conclusions
Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.
Gender and socioeconomic disparities in reasons for not smoking cigarettes among Danish adolescents
Authors: Kjeld Simone Gad , Glenstrup Stine , Bast Lotus Sofie 
Published: January 2021

Abstract
Objective
To examine gender and socioeconomic differences in adolescents’ reasons for not smoking cigarettes using self-reported data from Danish 14-year-olds (N = 1,559) collected in 2018. χ2-tests were used to assess whether the proportion of students who rated 12 statements as important reasons for not smoking cigarettes differed according to gender and family occupational social class (OSC).

Results
More girls than boys stated that thinking the taste of cigarettes is disgusting, not being allowed to smoke by parents, knowing smoking is dangerous, not being allowed to smoke before the age of 18, not wanting to be addicted to smoking, and that smoking makes you smell bad were important reasons for choosing not to smoke cigarettes. More boys than girls reported exercising a lot and having a partner that does not smoke as important reasons for not smoking cigarettes. More students with a high OSC compared with a low OSC stated exercising a lot and that smoking makes you smell bad were important reasons. In conclusion, reasons for not smoking cigarettes differed substantially across gender and less according to socioeconomic position.
Faecopneumothorax due to missing diaphragmatic hernia: a case report
Authors: Nusretoğlu Resul , Dönder Yunus 
Published: January 2021

Abstract
Background
Diaphragmatic hernias may occur as either congenital or acquired. The most important cause of acquired diaphragmatic hernias is trauma, and the trauma can be due to blunt or penetrating injury. Diaphragmatic hernia may rarely be seen after thoracoabdominal trauma.

Case presentation
A 54-year-old Turkish male patient admitted to the emergency department with abdominal pain and dyspnea ongoing for 2 days. He had general abdominal tenderness in all quadrants. He had a history of a stabbing incident in his left subcostal region 3 months ago without any pathological findings in thoracoabdominal computed tomography scan. New thoracoabdominal computed tomography showed a diaphragmatic hernia and fluid in the hernia sac. Due to respiratory distress and general abdominal tenderness, the decision to perform an emergency laparotomy was made. There was a 6 cm defect in the diaphragm. There were also necrotic fluids and stool in the hernia sac in the thorax colon resection, and an anastomosis was performed. The defect in the diaphragm was sutured. The oral regimen was started, and when it was tolerated, the regimen was gradually increased. The patient was discharged on the postoperative 11th day.

Conclusions
Acquired diaphragmatic hernia may be asymptomatic or may present with complications leading to sepsis. In this report, acquired diaphragmatic hernia and associated colonic perforation of a patient with a history of stab wounds was presented.
Construction and analysis of unified 4-point interpolating nonstationary subdivision surfaces
Authors: Bari Mehwish , Mustafa Ghulam , Ghaffar Abdul , Nisar Kottakkaran Sooppy , Baleanu Dumitru 
Published: January 2021

AbstractSubdivision schemes (SSs) have been the heart of computer-aided geometric design almost from its origin, and several unifications of SSs have been established. SSs are commonly used in computer graphics, and several ways were discovered to connect smooth curves/surfaces generated by SSs to applied geometry. To construct the link between nonstationary SSs and applied geometry, in this paper, we unify the interpolating nonstationary subdivision scheme (INSS) with a tension control parameter, which is considered as a generalization of 4-point binary nonstationary SSs. The proposed scheme produces a limit surface having $C^{1}$

C
1

smoothness. It generates circular images, spirals, or parts of conics, which are important requirements for practical applications in computer graphics and geometric modeling. We also establish the rules for arbitrary topology for extraordinary vertices (valence ≥3). The well-known subdivision Kobbelt scheme (Kobbelt in Comput. Graph. Forum 15(3):409–420, 1996) is a particular case. We can visualize the performance of the unified scheme by taking different values of the tension parameter. It provides an exact reproduction of parametric surfaces and is used in the processing of free-form surfaces in engineering.
Backward-forward linear-quadratic mean-field Stackelberg games
Authors: Si Kehan , Wu Zhen 
Published: January 2021

AbstractThis paper studies a controlled backward-forward linear-quadratic-Gaussian (LQG) large population system in Stackelberg games. The leader agent is ofbackwardstate and follower agents are offorwardstate. The leader agent is dominating as its state enters those of follower agents. On the other hand, the state-average of all follower agents affects the cost functional of the leader agent. In reality, the leader and the followers may represent two typical types of participants involved in market price formation: the supplier and producers. This differs from standard MFG literature and is mainly due to the Stackelberg structure here. By variational analysis, the consistency condition system can be represented by some fully-coupled backward-forward stochastic differential equations (BFSDEs) with high dimensional block structure in an open-loop sense. Next, we discuss the well-posedness of such a BFSDE system by virtue of the contraction mapping method. Consequently, we obtain the decentralized strategies for the leader and follower agents which are proved to satisfy theε-Nash equilibrium property.
Seasonal shifts in the gut microbiome indicate plastic responses to diet in wild geladas
Authors: Baniel Alice , Amato Katherine R. , Beehner Jacinta C. , Bergman Thore J. , Mercer Arianne , Perlman Rachel F. , Petrullo Lauren , Reitsema Laurie , Sams Sierra , Lu Amy , Snyder-Mackler Noah 
Published: January 2021

Abstract
Background
Adaptive shifts in gut microbiome composition are one route by which animals adapt to seasonal changes in food availability and diet. However, outside of dietary shifts, other potential environmental drivers of gut microbial composition have rarely been investigated, particularly in organisms living in their natural environments.

Results
Here, we generated the largest wild nonhuman primate gut microbiome dataset to date to identify the environmental drivers of gut microbial diversity and function in 758 samples collected from wild Ethiopian geladas (Theropithecus gelada). Because geladas live in a cold, high-altitude environment and have a low-quality grass-based diet, they face extreme thermoregulatory and energetic constraints. We tested how proxies of food availability (rainfall) and thermoregulatory stress (temperature) predicted gut microbiome composition of geladas. The gelada gut microbiome composition covaried with rainfall and temperature in a pattern that suggests distinct responses to dietary and thermoregulatory challenges. Microbial changes were driven by differences in the main components of the diet across seasons: in rainier periods, the gut was dominated by cellulolytic/fermentative bacteria that specialized in digesting grass, while during dry periods the gut was dominated by bacteria that break down starches found in underground plant parts. Temperature had a comparatively smaller, but detectable, effect on the gut microbiome. During cold and dry periods, bacterial genes involved in energy, amino acid, and lipid metabolism increased, suggesting a stimulation of fermentation activity in the gut when thermoregulatory and nutritional stress co-occurred, and potentially helping geladas to maintain energy balance during challenging periods.

Conclusion
Together, these results shed light on the extent to which gut microbiota plasticity provides dietary and metabolic flexibility to the host, and might be a key factor to thriving in changing environments. On a longer evolutionary timescale, such metabolic flexibility provided by the gut microbiome may have also allowed members of Theropithecus to adopt a specialized diet, and colonize new high-altitude grassland habitats in East Africa.
Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum
Authors: Höpfinger Alexandra , Berghoff Martin , Karrasch Thomas , Schmid Andreas , Schäffler Andreas 
Published: January 2021

Abstract

Context
Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain.

Objective
This work aimed to quantify RBP4, PEDF, and clusterin in paired serum and CSF samples of patients undergoing neurological evaluation.

Methods
A total of 268 patients (109 male, 159 female) were included. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay in duplicate.

Results
RBP4 was abundant in serum (mean, 31.9 ± 24.2 μg/mL). The serum concentrations were approximately 145 times higher than in CSF (CSF to serum RBP4 ratio, 8.2 ± 4.3 × 10–3). PEDF was detectable in serum (mean, 30.2 ± 11.7 μg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to serum PEDF ratio, 42.3 ± 15.6 × 10–3). Clusterin serum concentrations were abundant with mean levels of 346.0 ± 114.6 μg/mL, which were approximately 40 times higher than CSF levels (CSF to serum clusterin ratio, 29.6 ± 23.4 × 10–3). RBP4 and PEDF serum levels correlated positively with CSF levels, which were increased in overweight/obese patients and in type 2 diabetic patients. The CSF concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF correlated positively with inflammatory parameters. In detail, only RBP4 showed the kinetics and associations that are mandatory for a putative mediator of the fat-brain axis.

Conclusion
RBP4, PEDF, and clusterin are permeable to the BBB and increase with the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis.
Glucose Metabolism After Pancreatectomy: Opposite Extremes Between Pancreaticoduodenectomy and Distal Pancreatectomy
Authors: Niwano Fumimaru , Babaya Naru , Hiromine Yoshihisa , Matsumoto Ippei , Kamei Keiko , Noso Shinsuke , Taketomo Yasunori , Takeyama Yoshifumi , Kawabata Yumiko , Ikegami Hiroshi 
Published: January 2021

AbstractContextThe rate of glucose metabolism changes drastically after partial pancreatectomy.ObjectiveThis work aims to analyze changes in patients’ glucose metabolism and endocrine and exocrine function before and after partial pancreatectomy relative to different resection types (Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy: KIP-MEP study).MethodsA series of 278 consecutive patients with scheduled pancreatectomy were enrolled into our prospective study. Of them, 109 individuals without diabetes, who underwent partial pancreatectomy, were investigated. Data were compared between patients with pancreaticoduodenectomy (PD, n = 73) and those with distal pancreatectomy (DP, n = 36).ResultsBlood glucose levels during the 75-g oral glucose tolerance test (75gOGTT) significantly decreased after pancreatectomy in the PD group (area under the curve [AUC] –9.3%, P &lt; .01), and significantly increased in the DP population (AUC + 16.8%, P &lt; .01). Insulin secretion rate during the 75gOGTT and glucagon stimulation test significantly decreased after pancreatectomy both in the PD and DP groups (P &lt; .001). Both groups showed similar homeostasis model assessment of insulin resistance (HOMA-IR) values after pancreatectomy. Decrease in exocrine function quality after pancreatectomy was more marked in association with PD than DP (P &lt; .01). Multiple regression analysis indicated that resection type and preoperative HOMA-IR independently influenced glucose tolerance-related postoperative outcomes.ConclusionsBlood glucose levels after the OGTT differed markedly between PD and DP populations. The observed differences between PD and DP suggest the importance of individualization in the management of metabolism and nutrition after partial pancreatectomy.
Preoperative Vitamin D Deficiency is a Risk Factor for Postthyroidectomy Hypoparathyroidism: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Vaitsi Konstantina D , Anagnostis Panagiotis , Veneti Stavroula , Papavramidis Theodosios S , Goulis Dimitrios G 
Published: January 2021

Abstract

Context
Whether preoperative vitamin D deficiency (VDD) contributes to postoperative hypoparathyroidism (hypoPT) risk is unknown.

Objective
This work aimed to meta-analyze the best available evidence regarding the association between preoperative vitamin D status and hypoPT risk.

Methods
A comprehensive literature search was conducted in PubMed, CENTRAL, and Scopus databases, up to October 31, 2020. Study selection included patients undergoing thyroidectomy with preoperative vitamin D status and postoperative hypoPT data. Two researchers independently extracted data from eligible studies. Data were expressed as risk ratio (RR) with 95% CI. The I2 index was employed for heterogeneity.

Results
Thirty-nine studies were included in the quantitative analysis (61 915 cases with transient and 5712 with permanent hypoPT). Patients with VDD demonstrated a higher risk for transient hypoPT compared with those with preoperative vitamin D sufficiency (RR 1.92, 95% CI, 1.50-2.45, I2 = 85%). These results remained significant for patients with preoperative 25-hydroxyvitamin D concentrations less than or equal to 20 ng/mL (mild VDD; RR 1.46, 95% CI, 1.10-1.94, I2 = 88%) and less than or equal to 10 ng/mL (severe VDD; RR 1.98, 95% CI 1.42-2.76, I2 = 85%). The risk of permanent hypoPT was increased only in cases with severe VDD (RR 2.45, 95% CI, 1.30-4.63, I2 = 45%). No difference was evident in subgroup analysis according to study design or quality.

Conclusion
Patients with preoperative VDD are at increased risk of transient hypoPT following thyroidectomy. The risk for permanent hypoPT is increased only for those with severe VDD.
Hormonal Therapy for Prostate Cancer
Authors: Desai Kunal , McManus Jeffrey M , Sharifi Nima 
Published: January 2021

Abstract
Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today’s standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today’s standard of care will require an accounting of an individual’s androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.
The Opioid Epidemic and Nonmarital Childbearing in the United States, 2000–2016
Authors: Caudillo Mónica L. , Villarreal Andrés 
Published: January 2021

Abstract
The United States has experienced a dramatic rise in opioid addiction and opioid overdose deaths in recent years. We investigate the effect of the opioid epidemic at the local level on nonmarital fertility using aggregate- and individual-level analyses. Opioid overdose death rates and prescriptions per capita are used as indicators of the intensity of the opioid epidemic. We estimate area fixed-effects models to test the effect of the opioid epidemic on nonmarital birth rates obtained from vital statistics for 2000–2016. We find an increase in nonmarital birth rates in communities that experienced a rise in opioid overdose deaths and higher prescription rates. Our analyses also show that the local effect of the opioid epidemic is not driven by a reduction in marriage rates and that marital birth rates are unaffected. Individual-level data from the ACS 2008–2016 are then used to further assess the potential causal mechanisms and to test heterogeneous effects by education and race/ethnicity. Our findings suggest that the opioid epidemic increased nonmarital birth rates through social disruptions primarily affecting unmarried women but not through changes in their economic condition.
Old Age and Radical History
Authors: Ciafone Amanda , McGeehan Muchmore Devin 
Published: January 2021

AbstractThis essay introduces readers to key themes in critical gerontology and age studies and asserts their centrality to contemporary history and politics. Age scholars and critical gerontologists push back against perspectives that individualize and medicalize old age as a natural or universal stage in a singular life course explained solely by biology, psychology, or personal choices. Instead, they challenge us to see contemporary life stages and even chronological age itself as historically and culturally specific structures. The contributions in this issue demonstrate the power of this approach, exploring histories of later life in the context of slave societies, retirement, social movements, and gendered embodiment. Together, contributors model a radical history of old age that centers power, historical struggle, and linked lives.
Negotiating Care
Authors: Sandler Maya C. 
Published: January 2021

AbstractThis article explores the creation of the Over 60 Health Clinic in Berkeley, California, during the mid-1970s. Developed by a local network of the activist group Gray Panthers, the clinic offered screening and preventive care to elderly clients and was intended to serve as a catalyst for broader health reform. Drawing on the proposals, contracts, and reports that structured the clinic’s early operations, the article traces the clinic’s efforts to imagine new modes of care, even within the constraints of collaboration with bureaucratic public agencies. In so doing, the East Bay Gray Panthers articulated a distinct understanding of “healthy aging” as relational and contingent on the maintenance of existing intergenerational communities.