bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant Therapy Remodels the Pancreatic Cancer Microenvironment via Depletion of Protumorigenic Immune Cells
Authors: Mota Reyes Carmen , Teller Steffen , Muckenhuber Alexander , Konukiewitz Björn , Safak Okan , Weichert Wilko , Friess Helmut , Ceyhan Güralp O. , Demir Ihsan Ekin 
Published: October 2019

Abstract

Purpose:
Neoadjuvant therapy (neoTx) has dramatically improved the prognosis of patients with locally advanced and borderline resectable pancreatic ductal adenocarcinoma, yet its mechanisms of action on tumor cells and the tumor microenvironment are still unknown. Here, we aimed to characterize the multiple facets of neoTx-induced alterations in the pancreatic cancer microenvironment.

Experimental Design:
We performed the currently most comprehensive histopathologic analysis of desmoplasia, angiogenesis, neural invasion, and immune cell infiltration at the tumor–host interface of pancreatic cancer after neoTx (n = 37) versus after primary resection (n = 37) through quantitative IHC and double immunofluorescence using automated and software-based quantification algorithms.

Results:
We demonstrate that, independently of the applied pretreatment, neoadjuvant regimes are able to reverse the immunosuppressive behavior of malignant cells on pancreatic cancer microenvironment. Here, neoTx-driven selective depletion of regulatory T cells and myeloid-derived suppressor cells was associated with enrichment of antitumor immune cells in the peritumoral niche, decreased stromal activation, and less neural invasion. Importantly, the degree of this antitumor immune remodeling correlates to the degree of histopathologic response to neoTx. Survival analysis revealed that the tumor proliferation rate together with the activation of the stroma and the intratumoral infiltration with CD4+ T cells and natural killer cells constitute as independent prognostic factors for neoadjuvantly treated pancreatic cancer.

Conclusions:
NeoTx is not only cytotoxic but has pleiotropic, beneficial effects on all cellular and noncellular components of pancreatic cancer. Combinational approaches including immunotherapy may unleash long-term and more effective antitumor responses and improve prognosis of pancreatic cancer.
Facts and New Hopes on Selective FGFR Inhibitors in Solid Tumors
Authors: Facchinetti Francesco , Hollebecque Antoine , Bahleda Rastislav , Loriot Yohann , Olaussen Ken A. , Massard Christophe , Friboulet Luc 
Published: October 2019

Abstract
Precision oncology relies on the identification of molecular alterations, responsible for tumor initiation and growth, which are suitable targets of specific inhibitors. The development of FGFR inhibitors represents an edifying example of the rapid evolution in the field of targeted oncology, with 10 different FGFR tyrosine kinase inhibitors actually under clinical investigation. In parallel, the discovery of FGFR activating molecular alterations (mainly FGFR3 mutations and FGFR2 fusions) across many tumor types, especially urothelial carcinomas and intrahepatic cholangiocarcinomas, widens the selection of patients that might benefit from selective FGFR inhibitors. The ongoing concomitant clinical evaluation of selective FGFR inhibitors in molecularly selected solid tumors brings new hopes for patients with metastatic cancer, for tumors so far excluded from molecularly guided treatments. Matching molecularly selected tumors with selective FGFR inhibitors has indeed led to promising results in phase I and II trials, justifying their registration to be expected in a near future, such as the recent accelerated approval of erdafitinib granted by the FDA for urothelial cancer. Widening our knowledge of the activity, efficacy, and toxicities relative to the selective FGFR tyrosine kinase inhibitors under clinical investigation, according to the exact FGFR molecular alteration, will be crucial to determine the optimal therapeutic strategy for patients suffering from FGFR-driven tumors. Similarly, identifying with appropriate molecular diagnostic, every single tumor harboring targetable FGFR alterations will be of utmost importance to attain the best outcomes for patients with FGFR-driven cancer.
Impact of Body Mass Index on the Outcomes of Catheter Ablation of Atrial Fibrillation: A European Observational Multicenter Study
Authors: Providência Rui , Adragão Pedro , de Asmundis Carlo , Chun Julian , Chierchia Gianbattista , Defaye Pascal , Anselme Frédéric , Creta Antonio , Lambiase Pier D. , Schmidt Boris , Chen Shaojie , Cavaco Diogo , Hunter Ross J. , Carmo João , Combes Stephane , Honarbakhsh Shohreh , Combes Nicolas , Sousa Maria João , Jebberi Zeynab , Albenque Jean‐Paul , Boveda Serge 
Published: October 2019

Background

Outcomes of catheter ablation of atrial fibrillation (
AF
) are variable and the predictors of success require further elucidation since the identification of correctable risk factors could help to optimize therapy. We aimed to assess the impact of body mass index (
BMI
) in the overall safety and efficacy of catheter ablation of
AF
, with emphasis on the use of cryoballoon ablation and novel oral anticoagulants.

Methods and Results

There were 2497 consecutive patients undergoing catheter ablation of
AF
in 7 European high volume centers were stratified according to
BMI
(normal weight <25 kg/m
2
, pre‐obese 25–30 kg/m
2
, obesity 30–35 kg/m
2
, and morbid obesity ≥35 kg/m
2
) and comparisons of procedural outcomes evaluated. Pre‐obese and obese patients presented more comorbidities (hypertension, diabetes mellitus, and sleep apnea), and had higher rates of non‐paroxysmal
AF
ablation procedures. The rate of atrial 12‐month arrhythmia relapse increased alongside with
BMI
(35.2%, 35.7%, 43.6%, and 48.0%
P
<0.001). During a median follow‐up of 18.8 months (interquartile range 11–28), after adjusting for all baseline differences,
BMI
was an independent predictor of relapse (hazard ratio=1.01 per kg/m
2
; 95% CI 1.01–1.02;
P
=0.002), adding incremental predictive value to obstructive sleep apnea.
BMI
was not a predictor for any of the reported complications. Using novel oral anticoagulants and cryoballoon ablation was safe and efficacy was comparable with vitamin‐K antagonists and radiofrequency ablation.

Conclusions

Obese patients present with a more adverse comorbidity profile, more advanced forms of
AF
, and have lower chances of being free from
AF
relapse after ablation. Use of novel oral anticoagulants and cryoballoon ablation may be an option in this patient group.
Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus
Authors: Hahad Omar , Wild Philipp S. , Prochaska Jürgen H. , Schulz Andreas , Hermanns Iris , Lackner Karl J. , Pfeiffer Norbert , Schmidtmann Irene , Beutel Manfred , Gori Tommaso , Deanfield John E. , Münzel Thomas 
Published: October 2019

Background
Endothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development.

Methods and Results

In a population‐based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35–74 years at enrollment in 2007–2012), we identified 1610 cases of incident pre–diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A
1c
(HbA
1c
) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow‐mediated dilation and digital volume plethysmography–derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate β coefficients of HbA
1c
levels at follow‐up and relative risks of incident (pre–)diabetes mellitus. Reactive hyperemia index was independently associated with HbA
1c
after multivariable adjustment for baseline HbA
1c
, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack‐years of smoking, non–high‐density lipoprotein/high‐density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C‐reactive protein (β=−0.020;
P
=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02–1.15;
P
=0.012) for incident pre–diabetes mellitus and 1.16 (95% CI, 1.01–1.34;
P
=0.041) for incident type 2 diabetes mellitus. Flow‐mediated dilation independently increased the relative risk for developing pre–diabetes mellitus by 8% (95% CI, 1.02–1.14;
P
=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86–1.19;
P
=0.92) and with HbA
1c
(β=−0.003;
P
=0.59).

Conclusions
Endothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre–)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.
The Play’s the Thing: Toys in Ancient Jewish Society—Visualizing through the Words of the Rabbis
Authors: Schwartz Joshua 
Published: October 2019

Abstract
Everyone plays and that, of course, includes children. In an ideal world, there would be literary traditions, archaeological remains and artistic renditions, which would enable the reconstruction of toys. Unfortunately, the situation does not exist for ancient Jewish society. For the most part, there are depictions in rabbinic literature and it is those toy traditions which I examine.
The study begins with those toys explicitly connected to halakhic issues, firstly with those traditions in which the toy is essential to the law and afterwards to those in which the toy is tangential to the law. The study then deals with those toys mentioned in a nonlegal rabbinic framework. Finally, I discuss toys that were popular in the Greco-Roman world but not mentioned in rabbinic literature. I seek to determine whether descriptions of toys in rabbinic literature and set within the broader Greco-Roman world are sufficient for visualization.
Unpacking Robert Spaemann’s Philosophical Contribution to the Brain Death Debate
Authors: Gardner Elinor 
Published: October 2019

Questions of life and death are primarily philosophical questions, as philosopher Robert Spaemann argues. Spaemann argues that “brain death” is philosophically unsatisfactory as a definition of death, and as the exclusive criterion for determining death, for two main reasons: first, because it attempts to annul the basic perceptions of the ordinary person in regard to death. Second, because the cause of life and unity in a living being cannot be reduced to the brain. This essay is an explication of Spaemann’s contribution to the “brain death” question, which consists in illuminating the philosophical issues at stake. Summary: This article presents Robert Spaemann’s philosophical case that “brain death” suffices neither as a definition of death nor as the sole criterion of death.
Implication and Management of Incidental Oropharyngeal Papillomas—A Retrospective Case Series Review
Authors: Kim Daniel , Siegel Justin , Chouake Robert J. , Geliebter Jan , Zalvan Craig H. 
Published: October 2019

Introduction: Incidental papillomas of the pharynx can be found while examining the nasopharynx, oropharynx, and hypopharynx for other disorders of the head and neck. Purpose of the study is to explore the location, biopsy protocol, and decision to perform office-based versus operative management via potassium titanyl phosphate (KTP) laser when an oropharyngeal papilloma is discovered incidentally. Methods: A retrospective review of the senior author’s patient population was performed using Current Procedural Terminology and/or International Classification of Diseases codes to identify patients who had KTP laser removal of incidental oropharyngeal papillomas. Patients were included based on the incidental nature of the papilloma and confirmed pathology report of squamous papilloma. Demographics, presenting complaint, lesion location, pathological analysis, type of intervention, and outcomes were recorded. When available, human papillomavirus (HPV) subtype was noted. Results: A total of 26 cases were identified, 13 females and 13 males. The median age at time of surgery was 58 years (range: 21-77). The most common presenting symptoms were difficulty swallowing and throat pain. The most common locations were the base of tongue, uvula, tonsils, and the soft palate. Of the 26 patients, 23 patients received KTP laser ablation therapy as an office-based procedure, while the remaining 3 were performed under general anesthesia in the operating room. Only 5 patients had a recorded recurrence that required reoperation. There were no operative or postoperative complications. There were 16 biopsy samples tested for HPV, where 12 were negative for HPV and 4 were positive for HPV. Conclusion: Oropharyngeal papillomas, when present, can be found incidentally during examination of the oropharynx for other symptoms. Office-based biopsy and KTP laser is a safe and efficient means of identifying and removing most oropharyngeal papillomas.
Overstay and Readmission in Ear, Nose, and Throat Day Surgery—Factors Affecting Postanesthesia Course
Authors: Tolvi Morag , Lehtonen Lasse , Tuominen-Salo Hanna , Paavola Mika , Mattila Kimmo , Aaltonen Leena-Maija 
Published: October 2019

Aims: Many procedures in ear, nose, and throat (ENT) day surgery are carried out under local anesthesia in Finland, whereas many other countries use general anesthesia. We investigated overstay and readmission rates in local and general anesthesia at Helsinki University Hospital. Material and Methods: We conducted a retrospective study on ENT (n = 1011) day surgery patients within a 3-month period using the hospital’s surgery database to collect data pertaining to anesthesia, overstays, readmissions, and contacts within 30 days of surgery. Objectives: We examined the effect of American Society of Anesthesiologists (ASA) class, age, sex, type of procedure, and anesthesia type on overstay, contact, and readmission rates. Results: A multivariable logistic regression model included ASA class, age, sex, type of procedure, and anesthesia (local vs general). Sex, age, and type of procedure had an effect on the outcomes of overstay, readmission, or contact. With general anesthesia, 3.2% (n = 23) had an overstay or readmission compared to 1.4% (n = 4) after local anesthesia. This was mainly explained by the number of study outcomes in tonsillar surgery that was performed only in general anesthesia. Conclusions: Day surgery could be done safely using local anesthesia, as the number of study outcomes was no greater than in general anesthesia. Sex, type of procedure, and age affected the rate of study outcomes, but ASA class and anesthesia form did not. Our overstay, contact, and readmission rates are on the same level, or lower, than in international studies.
The Role of the Parotid-Mastoid Fascia in Identification of the Facial Nerve Trunk During Parotidectomy
Authors: Micucci Steven B. , Cheng Siri Sunderi , Song Tara , Rasgon Barry 
Published: October 2019

Objective: We aim to describe the parotid fascia as a landmark that can help identify the immediately underlying facial nerve trunk. Methods: Dissection of the parotid fascia and identification of the facial nerve trunk were carried out on 8 fresh cadaveric parotid glands. The attachments and arrangement of the parotid gland and its fascia were evaluated and histologically assessed, with special attention to the fascia overlying the facial nerve trunk. Results: The parotid fascia envelops the posterior aspect of the parotid gland in an open-book fashion. Posteriorly, it connects to the anterior and medial aspect of the mastoid tip. Posterosuperiorly, it attaches to the inferior aspect of the tragal pointer. Directly medial to the fascia lies the facial nerve trunk. Conclusion: The parotid fascia, particularly the parotid–mastoid segment overlying the facial nerve trunk, can be utilized as an additional landmark of depth to help identify the facial nerve trunk during a parotidectomy in conjunction with other commonly used standard anatomic landmarks. The parotid fascia sling spans from the mastoid and tragal pointer to the parotid gland and can be easily palpated intraoperatively. Once the fascia is removed, the facial nerve trunk is identified.
Morphometric evaluation of aortic coarctation and collateral circulation using computed tomography in the adult population
Authors: Krupiński Maciej , Irzyk Małgorzata , Moczulski Zbigniew , Banyś Robert , Urbańczyk-Zawadzka Małgorzata 
Published: October 2019

Background Analysis of morphometric details of aortic coarctation and collateral circulation using computed tomography (CT) and its impact on clinical symptoms is a perspective which is missing in the published literature. Purpose To perform CT-based qualitative and quantitative evaluation of aortic coarctation and collateral circulation with reference to clinical symptoms. Material and Methods The study comprised 2022 patients who underwent CT angiography. If aortic coarctation was seen, the patients underwent evaluation of its anatomy and associated clinical symptoms. Results Aortic coarctation was found in 33 patients. Follow-up (median 2476 days; range 1692–3543) was performed in 31 (94%) individuals. In this group (median age 42 years; range 30–52.5 years), median stenosis at the site of coarctation was 70% (range 58–85%) of the lumen area, with 17 (55%) patients presenting with significant (≥70%) stenosis. Patients with significant stenosis had a greater right and left internal mammary artery diameter ( P = 0.0070 and P = 0.0114, respectively) than those with mild stenosis. Patients with significant coarctation stenosis revealed hypertension and headache more commonly than those with mild stenosis (17 vs. 9, P = 0.01 and 10 vs. 2, P = 0.02), respectively. In patients who underwent intervention, a decrease in prevalence of hypertension (19 vs. 0, P = 0.008) and headache (12 vs. 3, P = 0.010) were observed in the follow-up. Conclusion CT enables quantitative and qualitative evaluation of aortic coarctation anatomy, including stenosis at the site of coarctation, and collateral circulation. In adult patients with aortic coarctation, the prevalence of hypertension and headache is related to the degree of stenosis at the site of coarctation and decreases after intervention.
Lifestyle and occupational factors associated with participation in breast mammography screening among Western Australian women
Authors: Carey Renee N , El-Zaemey Sonia 
Published: October 2019

Objectives Various lifestyle and occupational factors have been associated with an increased risk of breast cancer, but there is limited research investigating the relationship between these factors and participation in breast cancer screening. This study explores the associations between lifestyle and occupational factors and participation in breast mammography screening among women living in Western Australia. Methods This study involved 1705 women aged 40 and older who participated as controls in the Breast Cancer Environment and Employment Study conducted in Western Australia. Self-reported questionnaire data were collected on participation in mammography screening, demographic factors, and lifestyle and occupational variables (smoking, physical activity, alcohol consumption, body mass index, use of contraceptive pill and hormone replacement therapy, breastfeeding, occupation, and participation in shift work). Multivariate modified Poisson regression was used to identify variables associated with ever participation in breast mammography screening. Results Just over 88% of women reported having ever had a mammogram. Likelihood of having ever had a mammogram was higher among women who had ever used hormone replacement therapy (adjusted prevalence ratio (aPR) = 1.05, 95% CI 1.02–1.07). Women who worked in clerical occupations (aPR = 1.06, 95% CI 1.01–1.11) or home duties (aPR = 1.05, 95% CI 1.00–1.11) were also more likely to report having ever had a mammogram compared with those in professional or technical occupations. Conclusions Participation in mammography screening was found to differ by lifestyle and occupational factors. These results have important implications for public health strategies on improving screening participation.
Being ‘alone’ striving for belonging and adaption in a new reality – The experiences of spouse carers of persons with dementia
Authors: Hammar Lena Marmstål , Williams Christine L. , Meranius Martina Summer , McKee Kevin 
Published: October 2019

Background and aim Spouse carers of a person with dementia report feeling lonely and trapped in their role, lacking support and having no time to take care of their own health. In Sweden, the support available for family carers is not specialised to meet the needs of spouse carers of people with dementia. The aim of the study described in this paper was to explore spouse carers’ experiences of caring for a partner with dementia, their everyday life as a couple and their support needs. Methods Nine spouse carers of a partner with dementia living at home were recruited through a memory clinic and a dementia organisation. Semi-structured interviews were conducted with the participants, focusing on their experiences of providing care, their support needs in relation to their caring situation, their personal well-being and their marital relationship. The interviews were transcribed and underwent qualitative content analysis. Results The analysis resulted in one overall theme Being ‘alone’ striving for belonging and adaption in a new reality, synthesized from four sub-themes: (1) Being in an unknown country; (2) Longing for a place for me and us; (3) Being a carer first and a person second; and (4) Being alone in a relationship. Conclusions The training of care professionals regarding the unique needs of spouse carers of people with dementia needs improvement, with education, in particular, focusing on their need to be considered as a person separate from being a carer and on the significance of the couple’s relationship for their mutual well-being.