bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D–VDR Signaling Inhibits Wnt/β-Catenin–Mediated Melanoma Progression and Promotes Antitumor Immunity
Authors: Muralidhar Sathya , Filia Anastasia , Nsengimana Jérémie , Poźniak Joanna , O'Shea Sally J. , Diaz Joey M. , Harland Mark , Randerson-Moor Juliette A. , Reichrath Jörg , Laye Jonathan P. , van der Weyden Louise , Adams David J. , Bishop D.T. , Newton-Bishop Julia 
Published: November 2019

Abstract

1α,25-Dihydroxyvitamin D3 signals via the vitamin D receptor (VDR). Higher serum vitamin D is associated with thinner primary melanoma and better outcome, although a causal mechanism has not been established. As patients with melanoma commonly avoid sun exposure, and consequent vitamin D deficiency might worsen outcomes, we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D–VDR signaling and replicated the findings in The Cancer Genome Atlas metastases. VDR expression was independently protective for melanoma-related death in both primary and metastatic disease. High tumor VDR expression was associated with upregulation of pathways mediating antitumor immunity and corresponding with higher imputed immune cell scores and histologically detected tumor-infiltrating lymphocytes. High VDR–expressing tumors had downregulation of proliferative pathways, notably Wnt/β-catenin signaling. Deleterious low VDR levels resulted from promoter methylation and gene deletion in metastases. Vitamin D deficiency (&lt;25 nmol/L ∼ 10 ng/mL) shortened survival in primary melanoma in a VDR-dependent manner. In vitro functional validation studies showed that elevated vitamin D–VDR signaling inhibited Wnt/β-catenin signaling genes. Murine melanoma cells overexpressing VDR produced fewer pulmonary metastases than controls in tail-vein metastasis assays. In summary, vitamin D–VDR signaling contributes to controlling pro-proliferative/immunosuppressive Wnt/β-catenin signaling in melanoma and this is associated with less metastatic disease and stronger host immune responses. This is evidence of a causal relationship between vitamin D–VDR signaling and melanoma survival, which should be explored as a therapeutic target in primary resistance to checkpoint blockade.

Significance:
VDR expression could potentially be used as a biomarker to stratify patients with melanoma that may respond better to immunotherapy.
Capping Protein Regulator and Myosin 1 Linker 3 Is Required for Tumor Metastasis
Authors: Wang Huan , Wang Chao , Peng Guang , Yu Doudou , Cui Xin-Gang , Sun Ying-Hao , Ma Xiaojing 
Published: November 2019

Abstract

Metastasis accounts for 90% of deaths caused by solid tumors, but the multitude of mechanisms underlying tumor metastasis remains poorly understood. CARMIL1 and 2 proteins are capping protein (CP) interactants and multidomain regulators of actin-based mobility. However, CARMIL3′s function has not been explored. Through bioinformatic metadata analysis, we find that high CARMIL3 expression correlates with poor survival of patients with breast and prostate cancer. Functional studies in murine and xenograft tumor models by targeted diminution of CARMIL3 expression or forced expression demonstrate that CARMIL3 is vitally important for tumor metastasis, especially for metastatic colonization. Consistent with a predominantly cell-intrinsic mode of action, CARMIL3 is also crucial for tumor cell migration and invasion in vitro. Coimmunoprecipitation coupled with mass spectrometric analyses identifies a group of CARMIL3-interacting proteins, including capping protein, that are involved in actin cytoskeletal organization, which is required for cell polarization and focal adhesion formation. Moreover, molecular pathway enrichment analysis reveals that lack of CARMIL3 leads to loss of cell adhesions and low CARMIL3 expression in breast cancer patient specimens is implicated in epithelial–mesenchymal transition. We also find that CARMIL3 sustains adherens junction between tumor cells. This is accomplished by CARMIL3 maintaining E-cadherin transcription downstream of HDACs through inhibiting ZEB2 protein level, also via protecting β-catenin from ubiquitination-mediated degradation initiated by the destruction complex.

Implications:
This study uncovers CARMIL3 as a novel and critical regulator of metastatic progression of cancers and suggests therapeutic potentials to target CARMIL3.
Імплементація протоколів ERAS у хірургічному лікуванні кіст підшлункової залози
Authors: Ioffe O. Yu. , Stetsenko O. P. , Cura Yu. P. , Kryvopustov M. S. 
Published: November 2019

Мета роботи: імплементація програми швидкого відновлення (ERAS) у хірургічному лікуванні кіст підшлункової залози.
Матеріали і методи. Проведено аналіз хірургічного лікування 12 хворих із кістою підшлункової залози, яким було виконано лапароскопічну цистоєюностомію за Ру з приводу псевдокіст підшлункової залози, що сформувалась після перенесеного гострого деструктивного панкреатиту. У всіх пацієнтів використано періопераційну програму ERAS.
Результати досліджень та їх обговорення. Внаслідок використання програми ERAS тривалість операції в середньому склала (172,23 ± 53,30) хв, обʼєм крововтрати до 100 – 150 мл, середній ліжко-день – (3,92±0,92) доби, дренаж видаляли після контрольного УЗД дослідження на першу післяопераційну добу у всіх пацієнтів. У 8 пацієнтів перше випорожнення спостерігали протягом першої післяопераційної доби, у 4-х – протягом 2-ї після використання одноразово послаблюючої клізми. Ускладнень, пов’язаних з неспроможністю анастомозів, не спостерігали. Інтенсивність больового синдрому в першу і другу післяопераційну добу за допомогою ВАШ склало 5,25 і 3,5 бала, відповідно. У всіх оперованих пацієнтів були задовільні показники діастази. Нудоту в першу післяопераційну добу спостерігали в 3 пацієнтів, що одразу ефективно купірувалась введенням медикаментів. Блювання не спостерігали у жодного пацієнта. Протягом 1-го року всі пацієнти знаходились під наглядом з УЗД-контролем. Жодних віддалених післяопераційних ускладнень не виявлено.
Порівняльна оцінка різних методів закриття ранових дефектів у пацієнтів із синдромом стопи діабетика
Authors: Dzyubanovsky I. Ya. , Antoshchuk R. M. , Prodan A. M. 
Published: November 2019

Мета роботи: покращити результати хірургічного лікування хворих із синдромом стопи діабетика (CCД) шляхом використання сучасних методів закриття ранових дефектів.
Матеріали і методи. Проведено аналіз результатів комплексного обстеження й лікування 67 хворих із ССД. Пацієнтів поділені на групу порівняння – 31 (46,27 %) хворий, яким виконано “класичну” автодермопластику, та основну групу – 36 (53,73 %) хворих. Серед них у 17 (47,22 %) хворих проведено закриття ранового дефекту за допомогою еквіваленту дерми, а у 19 (52,78 %) хворих використано PRP методику. Відповідно до клінічних форм ССД виділено невропатичну форму стопи діабетика у 30 (44,78 %) хворих та нейроішемічну форму стопи діабетика у 37 (55,22 %) хворих. На підставі отриманих результатів використання різних способів закриття дефектів обчислювали площу та швидкість загоєння ран.
Результати досліджень та їх обговорення. За результатами аналізу застосування еквіваленту дерми встановлено наступне: на 20-ту добу лікування площа рани у 1,76 раза менша від площі рани в пацієнтів без використання еквіваленту дерми; швидкість загоєння рани вища в 1,41 раза. При застосуванні PRP мембрани встановлено, що на 20-ту добу лікування площа рани у 2,25 раза менша від площі рани в пацієнтів без використання PRP мембрани, а швидкість загоєння рани вища в 1,45 раза. Використання клітинно-тканинних технологій та збагаченою тромбоцитами та факторами росту мембрани у місцевому лікуванні ранового дефекту дозволяє досягти загоєння й поліпшує результати лікування за рахунок прискорення строків епітелізації порівняно із традиційною терапією.
Prosthetic Valve Endocarditis After TAVR and SAVR
Authors: Summers Matthew R. , Leon Martin B. , Smith Craig R. , Kodali Susheel K. , Thourani Vinod H. , Herrmann Howard C. , Makkar Raj R. , Pibarot Philippe , Webb John G. , Leipsic Jonathon , Alu Maria C. , Crowley Aaron , Hahn Rebecca T. , Kapadia Samir R. , Tuzcu E. Murat , Svensson Lars , Cremer Paul C. , Jaber Wael A. 
Published: November 2019

Background:
Prosthetic valve endocarditis (PVE) is a rare but critical mechanism of valve failure and death after transcatheter and surgical aortic valve replacement (TAVR, SAVR) warranting further analysis in modern aortic valve replacement experience. We characterize the incidence, risk factors, microbiological profile and outcomes of PVE from the PARTNER trials and registries (Placement of Aortic Transcatheter Valve).

Methods:
We analyzed a pooled cohort of all patients in PARTNER 1 and PARTNER 2 trials and registries. Patients had severe aortic stenosis, were treated with TAVR or SAVR, and were analyzed with respect to development of PVE. PVE adjudication by a clinical events committee was based on modified Duke Criteria. The incidence, infection timing, organism, and association between PVE and all-cause mortality were analyzed.

Results:

8530 patients were included. PVE occurred in 107 cases (5.06 PVE events per 1000 person-years over a mean follow-up of 2.69±1.55 years [95% CI, 4.19–6.12]). The incidence of TAVR-PVE (5.21 PVE per 1000 person-years [95% CI, 4.26–6.38]) was not significantly different from SAVR-PVE (4.10 per 1000 person-years [95% CI, 2.33–7.22]; incident rate ratio, 1.27 [95% CI, 0.70–2.32];
P
=0.44). Temporal risk of PVE was similar for TAVR and SAVR, even after adjusting for competing risk of death (hazard ratio, 1.15 [95% CI, 0.58–2.28];
P
=0.69). Through multivariable analysis, PVE was associated with baseline cirrhosis (incident rate ratio, 2.86 [95% CI, 1.33–6.16];
P
=0.007), pulmonary disease (incident rate ratio, 1.70 [95% CI, 1.16–2.48];
P
=0.006), and renal insufficiency (incident rate ratio, 1.71 [95% CI, 1.03–2.83];
P
=0.04). Timing of PVE was similar between TAVR and SAVR (<30 days: 4.2% vs 8.3%; 31 days to 1 year: 52.6% vs 66.7%; >1 year: 43.2% vs 25.0%;
P
=0.28). Staphylococcus occurred more commonly after SAVR (58.3% vs 28.4% in TAVR;
P
=0.04). PVE was strongly associated with all-cause mortality after endocarditis diagnosis (hazard ratio, 4.4 [95% CI, 3.42–5.72];
P
<0.0001).

Conclusions:
The widespread adoption of TAVR and application to lower-risk patients makes understanding mechanisms of valve failure increasingly important. PVE is an established mechanism of prosthetic valve failure post-SAVR and TAVR with unclear differences between approaches. We herein demonstrate in the largest trials and registries of TAVR that PVE remains rare, but often fatal, in modern AVR experience and that there is no difference in incidence, predictors, or risk of PVE between TAVR and SAVR.

Clinical Trial Registration:

https://www.clinicaltrials.gov
. Unique identifiers: NCT00530894 (PARTNER 1), NCT01314313 (PARTNER 1IA), NCT02184442 (PARTNER 1IB), NCT03222141 (PII S3HR), NCT03222128 (PII S3i).
Diabetes Mellitus Is Associated With Increased Risk of Ischemic Stroke in Patients With and Without Coronary Artery Disease
Authors: Olesen Kevin K.W. , Madsen Morten , Gyldenkerne Christine , Thrane Pernille G. , Würtz Morten , Thim Troels , Jensen Lisette O. , Eikelboom John , Bøtker Hans Erik , Sørensen Henrik T. , Maeng Michael 
Published: November 2019

Background and Purpose—
Diabetes mellitus (DM) and non-DM patients without coronary artery disease (CAD) have a similar low risk of myocardial infarction after coronary angiography. The risk of ischemic stroke in DM patients dependent on CAD status is less explored. We examined whether DM patients without CAD have a risk of ischemic stroke similar to that in patients with neither DM nor CAD.

Methods—
We conducted a cohort study of patients who underwent coronary angiography between 2004 and 2012 in Western Denmark. Patients diagnosed with previous ischemic stroke or transient ischemic attack were excluded. Patients were stratified according to the presence of DM and CAD. Follow-up started 30 days after coronary angiography. We computed event rates and adjusted incidence rate ratios using patients without DM or CAD as reference. We examined the trend between CAD extent and ischemic stroke in patients with DM.

Results—

A total of 81 909 patients were included. Median follow-up was 3.8 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.32 events per 100 person-years; adjusted incidence rate ratio, 2.00 [95% CI, 1.72–2.32]). Patients with CAD alone (0.77 events per 100 person-years; adjusted incidence rate ratio, 1.27 [95% CI, 1.12–1.44]) or DM alone (0.95 events per 100 person-years; adjusted incidence rate ratio, 1.74 [95% CI, 1.42–2.15]) were at intermediate risk, whereas patients with neither DM nor CAD (0.52 events per 100 person-years) were at the lowest risk. Among patients with DM, extent of CAD was further predictive of risk (
P
trend
<0.001).

Conclusions—
Not only CAD but also DM are associated with the risk of ischemic stroke after coronary angiography. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.
Time Metrics to Endovascular Thrombectomy in 3 Triage Concepts
Authors: Seker Fatih , Fiehler Jens , Möhlenbruch Markus A. , Heimann Friederike , Flottmann Fabian , Ringleb Peter A. , Thomalla Götz , Steiner Thorsten , Kraemer Christoffer , Brekenfeld Caspar , Bendszus Martin 
Published: November 2019

Background and Purpose—
NEUROSQUAD (Stroke Treatment: Quality and Efficacy in Different Referral Systems) is a prospective, observational, bi-center study comparing 3 triage pathways in endovascular stroke treatment: mothership (MS), drip and ship (DS) and transferring a neurointerventionalist to a remote hospital for thrombectomy (drive the doctor [DD]).

Methods—
Between February and October 2018, all stroke patients undergoing thrombectomy at 2 university hospitals and 2 associated remote hospitals were included. Primary outcome measures were time from onset to groin puncture and time from imaging to groin puncture. Secondary outcome measures were time from onset to imaging and time from onset to thrombolysis.

Results—

In total, 440 patients were included (mothership 32.3%, DS 55.9%, DD 11.8%). Median time from onset to groin puncture (168 minutes) and time from imaging to groin puncture (51 minutes) were the shortest in the mothership group. Time from onset to groin puncture (DD median 225 versus DS median 300 minutes;
P
=0.001) and time from imaging to groin puncture (DD median 118 versus DS median 172 minutes;
P
<0.001) were shorter in the DD group compared with DS. Time from onset to imaging was similar among mothership, DS, and DD (
P
=0.363). In patients receiving thrombolysis, time from onset to needle was similar among the groups (
P
=0.620).

Conclusions—
The NEUROSQUAD study adds evidence that DD may be a feasible alternative to DS, leading to shorter delay between symptom onset and groin puncture. Both are time-wise inferior compared with mothership, though.
ʿAnāq bt. Ādam, the Islamic Story of the Very First Witch
Authors: Coulon Jean-Charles 
Published: November 2019

Abstract
Some Islamic traditions mention an enigmatic daughter of Adam named ʿAnāq. Little is known about her; for example, the corresponding entry in the Encyclopaedia of Islam simply states that ʿAnāq is the “name given by the Arabs to the daughter of Adam, the twin sister of Seth, wife of Cain and mother of ʿŪd̲j̲.” ʿAnāq is always mentioned in relation to her son, the giant ʿŪj, who was supposed to be the only creature outside the Ark to have survived the Flood in the time of Noah, and who was assumed to have been killed by Moses. We gather here the information and traditions about the Islamic ʿAnāq in order to draw a more coherent and historically contextualized portrait of this legendary first witch.
The Right to Voluntary Termination of Pregnancy in Italy: Taking Stock Forty Years after the Enactment of Law no. 194/1978. Comparative Law-based Remarks
Authors: Montanari Vergallo Gianluca 
Published: November 2019

Abstract
Forty years after the enactment of Law no. 194/78 that governs voluntary interruption of pregnancy, Italy has been experiencing difficulties guaranteeing that patients gain access to abortion procedures in a timely fashion. Conscientious objection detracts considerably from the very effectiveness of the law, as pointed out by major European institutions as well. Hence, the network of family planning and counselling centres needs to be expanded and supported; such institutions, in fact, may go a long way in ensuring that women make the best, informed decisions. The author has set out to deal with those issues by means of a comparative analysis. He believes that Italian lawmakers ought to follow in the footsteps of other European countries in order to balance the rights of objecting gynaecologists against those of women who choose to have an abortion, despite the relatively small number of doctors willing to carry out the procedure.
Urbanizing Forest: Archaeological Evidence from Southern Bénin
Authors: Merkyte Inga , Albek Søren , Randsborg Klavs 
Published: November 2019

Abstract
Until recently archaeological evidence predating the historically known Kingdom of Dahomey in southern Bénin has been next to non-existent. The situation changed when deep and long drainage channels were dug into the fertile soils at the modern town of Bohicon. In the sides of these channels, rich cultural remains appeared, confirming the assumption that high rates of soil accumulation have caused low archaeological visibility in the forest/former forest belt of West Africa. Geophysical mapping and extensive excavations have revealed two large settlements of 500-600 hectares each, partly overlapping but separated by 2000 years. This paper presents both sites – Sodohomé 1, the earliest site encountered so far in southern Bénin, and Sodohomé 2 (or Sodohomé-Bohicon) which dates to AD 900-1150/1220. Although the first has produced some remarkable results, for instance, an iron spearhead that is the oldest securely dated non-meteoritic iron object in Africa known so far, the focus is on the latter site where evidence demonstrates the existence of a true town with craft specialisation, industrial-scale iron production, long-distance trade and wide communication networks.
Two-Layer Dynamic Recycling Model (2L-DRM): Learning from Moisture Tracking Models of Different Complexity
Authors: Dominguez F. , Hu H. , Martinez J. A. 
Published: November 2019

AbstractAtmospheric moisture tracking models are used to identify and quantify sources and sinks of water in the atmospheric branch of the hydrologic cycle. These models are primarily used to investigate the origin of moisture resulting in precipitation for particular regions around the globe. Moisture tracking models vary widely in their level of complexity, depending on the number of physical processes represented. Complex models are comprehensive in their physical representation, but computationally much more expensive than simple models, which only focus on specific physical processes and use simplifying assumptions. We present the mathematical derivation of the new two-layer dynamical recycling model (2L-DRM), a simple analytical moisture tracking model that relaxes the vertically integrated formulation of the original one-layer DRM. By comparing the simple DRM to a very complex moisture tracking model that uses water vapor tracers embedded within the Weather Research and Forecasting regional climate model (WRF-WVT) for the North American monsoon region, we pinpoint the absence of vertical wind shear as the main deficiency in the simple DRM. When comparing both simple models (DRM and 2L-DRM) to the WRF-WVT (which we treat as “truth”), the 2L-DRM better captures the spatial extent, the net amount, and the temporal variability of precipitation that originates from oceanic and local terrestrial sources. The 2L-DRM is well suited to study the large-scale climatological sources of moisture, and for these applications, performs on par with the much more complex and computationally demanding WRF-WVT model.
“In-Office Balloon Sinus Ostial Dilation with Concurrent Antiplatelet and Anticoagulant Therapy for Chronic Rhinosinusitis without Nasal Polyps”
Authors: Higgins Thomas S. , Öcal Bülent , Adams Ridwan , Wu Arthur W. 
Published: November 2019

Objective: Functional endoscopic sinus surgery (FESS) and balloon sinus ostial dilation (BSD) are well-recognized minimally invasive surgical treatments for chronic rhinosinusitis without nasal polyps (CRSsNP) refractory symptoms to medical therapy. Patients on antiplatelet and anticoagulant therapies (AAT) usually are recommended to discontinue their medications around the period of endoscopic sinus surgery. The goal of this study is to assess the clinical experience of BSD in CRSsNP patients with concurrent anticoagulant or antiplatelet therapy. Methods: A review of prospectively-collected clinical data from October 2012 to March 2017 were used to perform a cohort study of subjects with CRSsNP who met criteria for surgical intervention while on antiplatelet and anticoagulant therapy. Data were collected on demographics, details of the procedures, type of AAT used, pre- and postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores, and complications. Results: Thirty-five patients underwent in-office BSD while on antiplatelet and/or anticoagulant therapy. The mean difference in pre- and postoperative SNOT-22 scores of 9.9 (SD 14.4, P < .001) was both statistically significant and exceeded the minimal clinically important difference of 8.9. Absorbable nasal packing was used for persistent bleeding immediately post-procedure in two patients. Intraoperative bleeding was associated with aspirin 325 mg and warfarin. FESS was required for further management of chronic sinusitis in four patients after anticoagulant/antiplatelet therapy could be discontinued. There were no systemic complications. None of the patients experienced significant bleeding events postoperatively after leaving the office. Conclusion: In-office BSD appears to be a safe alternative to endoscopic sinus surgery in select patients who cannot discontinue antiplatelet and anticoagulant therapy. Levels of Evidence: IV
What gets in the way? Men’s perspectives of barriers to mental health services
Authors: Seidler Zac E , Rice Simon M , Kealy David , Oliffe John L , Ogrodniczuk John S 
Published: November 2019

Background: This study describes barriers to accessing mental health services among men currently experiencing a mental health concern. Methods: Mental health help-seeking survey data from 778 male respondents who self-reported experiencing a mental health concern were analyzed. Results: Of these men, 65% ( n = 513) wanted treatment and 35% ( n = 265) did not want treatment. The most frequently endorsed barriers to mental health treatment were believing that a lot of people feel sad and down (80%; n = 620), not knowing what to look for in a psychotherapist (counselor; 80%; n = 618) and needing to solve one’s own problems (73%; n = 569). Compared with men who wanted help for their mental health concern, those men who did not want help were significantly more likely to be unsure if psychotherapy (counseling) really works or is effective, not tell their physician if they were feeling down or depressed and prefer to solve their own problems. Conclusions: The high endorsement of both structural (e.g., cost) and attitudinal (e.g., beliefs) barriers by respondents suggests that service delivery must adapt to better respond to dominant masculine ideals while also improving men’s ease of access into a transparent treatment process.