bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tissue-Engineered 3D Microvessel Model Reveals the Dynamics of Mosaic Vessel Formation in Breast Cancer
Authors: Silvestri Vanesa L. , Henriet Elodie , Linville Raleigh M. , Wong Andrew D. , Searson Peter C. , Ewald Andrew J. 
Published: July 2020

Abstract

In solid tumors, vascular structure and function varies from the core to the periphery. This structural heterogeneity has been proposed to influence the mechanisms by which tumor cells enter the circulation. Blood vessels exhibit regional defects in endothelial coverage, which can result in cancer cells directly exposed to flow and potentially promoting intravasation. Consistent with prior reports, we observed in human breast tumors and in a mouse model of breast cancer that approximately 6% of vessels consisted of both endothelial cells and tumor cells, so-called mosaic vessels. Due, in part, to the challenges associated with observing tumor–vessel interactions deep within tumors in real-time, the mechanisms by which mosaic vessels form remain incompletely understood. We developed a tissue-engineered model containing a physiologically realistic microvessel in coculture with mammary tumor organoids. This approach allows real-time and quantitative assessment of tumor–vessel interactions under conditions that recapitulate many in vivo features. Imaging revealed that tumor organoids integrate into the endothelial cell lining, resulting in mosaic vessels with gaps in the basement membrane. While mosaic vessel formation was the most frequently observed interaction, tumor organoids also actively constricted and displaced vessels. Furthermore, intravasation of cancer cell clusters was observed following the formation of a mosaic vessel. Taken together, our data reveal that cancer cells can rapidly reshape, destroy, or integrate into existing blood vessels, thereby affecting oxygenation, perfusion, and systemic dissemination. Our novel assay also enables future studies to identify targetable mechanisms of vascular recruitment and intravasation.

Significance:
A tissue-engineered microdevice that recapitulates the tumor–vascular microenvironment enables real-time imaging of the cellular mechanisms of mosaic vessel formation and vascular defect generation.
Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial
Authors: Uppaluri Ravindra , Campbell Katie M. , Egloff Ann Marie , Zolkind Paul , Skidmore Zachary L. , Nussenbaum Brian , Paniello Randal C. , Rich Jason T. , Jackson Ryan , Pipkorn Patrik , Michel Loren S. , Ley Jessica , Oppelt Peter , Dunn Gavin P. , Barnell Erica K. , Spies Nicholas C. , Lin Tianxiang , Li Tiantian , Mulder David T. , Hanna Youstina , Cirlan Iulia , Pugh Trevor J. , Mudianto Tenny , Riley Rachel , Zhou Liye , Jo Vickie Y. , Stachler Matthew D. , Hanna Glenn J. , Kass Jason , Haddad Robert , Schoenfeld Jonathan D. , Gjini Evisa , Lako Ana , Thorstad Wade , Gay Hiram A. , Daly Mackenzie , Rodig Scott J. , Hagemann Ian S. , Kallogjeri Dorina , Piccirillo Jay F. , Chernock Rebecca D. , Griffith Malachi , Griffith Obi L. , Adkins Douglas R. 
Published: July 2020

Abstract

Purpose:
Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)–unrelated HNSCC.

Patients and Methods:
Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (&lt;10%), pTR-1 (10%–49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684).

Results:
Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3–4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%–41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.

Conclusions:
Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.
HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment
Authors: Johard Helena , Omelyanenko Anna , Fei Gao , Zilberter Misha , Dave Zankruti , Abu-Youssef Randa , Schmidt Linnéa , Harisankar Aditya , Vincent C. Theresa , Walfridsson Julian , Nelander Sven , Harkany Tibor , Blomgren Klas , Andäng Michael 
Published: July 2020

Abstract

Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor–initiating cells, which also express HCN channels, remain proliferative during HCN inhibition.

Implications:
Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.
МЕДИКО-СОЦІАЛЬНІ АСПЕКТИ ПРОБЛЕМИ НАДАННЯ ПАЛІАТИВНОЇ ДОПОМОГИ У РОДИНАХ ТЯЖКОХВОРИХ ТА ІНКУРАБЕЛЬНИХ ПАЦІЄНТІВ
Authors: Smachylo A. I. , Matviyev L. F. , Kachun O. M. , Ivaskevych L. I. 
Published: July 2020

Тернопільський національний медичний університет імені І. Я. Горбачевського МОЗ України
Confessionalization, Symphony, or Democratization?
Authors: Tsvietkova Yulianna V. 
Published: July 2020

Abstract
This article analyzes modern religious life in Ukraine, specifically the relations between religious organizations and government bodies in state and social domains. Particular attention is given to the concrete territorial and historical evolution of state Christian doctrines and church relations in Ukrainian lands. The article also examines the main problems and conflicts regarding the registration and functioning of the largest religious organizations in the country, and relations between them. Special attention is paid to the role that religious organizations play in the democratic processes, and to their effect on the relations between state and church. These relations have unfolded against the background of the political events of the last 15 years in Ukraine and the region: internal social conflicts, the general trend toward pro-European democratization, and the Russian-Ukrainian conflict.
New Indices for Better Understanding ENSO by Incorporating Convection Sensitivity to Sea Surface Temperature
Authors: Xie Ruihuang , Mu Mu , Fang Xianghui 
Published: July 2020

AbstractObserved outgoing longwave radiation (OLR) data indicate that convection is nonlinearly sensitive to sea surface temperature anomalies (SSTA) for background SSTs in the 25.25°–30.25°C high-impact range. In this study, we use that observed convection sensitivity to derive a proxy of the convective responses to SSTA only [referred to as fluctuations of the accumulated convection strength (FACT)]. FACT reproduces the pattern of the observed convection response to ENSO in the central and eastern Pacific, but underestimates the amplitude due to the exclusion of the effect of ENSO-induced atmospheric convergence anomalies on convection. We thus use FACT to define new indices (InFACT) of ENSO diversity that explicitly account for the nonlinear convection–SST sensitivity. The amplitude of InFACT allows us to easily classify El Niño events into weak, moderate, and strong types that markedly differ in terms of SSTA spatial patterns and their convective responses. La Niña events classified by InFACT display much less pattern diversity, and mostly differ through their amplitudes. Finally, our study supports some previous studies that the nonlinear SST–convection relation plays a strong role for the development of extreme El Niño events with the presence of high-impact SSTs and large convection anomalies in the equatorial eastern Pacific.
Influence of Siberian Blocking on Long-Lived Cold Surges over the South China Sea
Authors: Pang Bo , Lu Riyu , Ren Rongcai 
Published: July 2020

AbstractCold surges occur frequently over the South China Sea (SCS) in winter, and most of them last only a few days. However, some cold surge events can persist longer, for instance, more than 5 days. This study focuses on these long-lived cold surge events and investigates the associated extratropical circulation anomalies. The results indicate that long-lived cold surges, characterized as strong northerlies over the SCS, can be triggered by a successive high anomaly center over East Asia. Accompanying this is an anomalously extensive and quasi-stationary anticyclone over Siberia in the midtroposphere, hinting at a more frequent occurrence of Siberian blocking. Further analyses reveal that the blocking frequency is indeed significantly high over 90°–150°E from day −4 to day +2 relative to the onset of long-lived cold surge events. Furthermore, there exist significant correlations between the leading occurrence of Siberian blocking and the sea level pressure (SLP) anomalies over East Asia, which are directly related to long-lived cold surges. The intensification of the high SLP anomaly over East Asia is found to mainly result from cold advection induced by the anomalous northerly winds along the southeastern edge of the Siberian blocking.
Repair Integrity and Retear Pattern After Arthroscopic Medial Knot-Tying After Suture-Bridge Lateral Row Rotator Cuff Repair
Authors: Takeuchi Yasutaka , Sugaya Hiroyuki , Takahashi Norimasa , Matsuki Keisuke , Tokai Morihito , Morioka Takeshi , Ueda Yusuke , Hoshika Shota 
Published: July 2020

Background: Type 2 failure is a big issue after suture-bridge rotator cuff repair, which may be because of stress concentration at the medial row stitches. We have been performing medial knot-tying after suture-bridge lateral row repair to avoid the stress concentration. This study aimed to evaluate clinical and radiological outcomes after arthroscopic rotator cuff repair using this technique. Hypothesis: This technique would yield better radiological outcomes with a reduced type 2 failure rate compared with reported outcomes after conventional suture-bridge repair. Study Design: Case series; Level of evidence, 4. Methods: The inclusion criteria of this study were (1) full-thickness tears, (2) primary surgery, and (3) minimum 2-year follow-up with pre- and postoperative magnetic resonance imaging (MRI). We investigated active ranges of motion (forward elevation and external rotation), as well as the Japanese Orthopaedic Association (JOA) and University of California, Los Angeles (UCLA), scores preoperatively and at the final follow-up. Results: This study included 384 shoulders in 373 patients (205 men and 168 women) with a mean age of 65 years (range, 24-89 years) at the time of surgery. The mean follow-up was 29 months (range, 24-60 months). There were 91 small, 137 medium, 121 large, and 35 massive tears. Postoperative MRI scans demonstrated successful repair in 324 shoulders (84.4%, group S) and retear in 60 shoulders (15.6%). Among 60 retears, 40 shoulders (67%) had type 1 failure (group F1) and 20 shoulders (33%) had type 2 failure (group F2). Forward elevation and external rotation significantly improved after surgery ( P < .001 for both). Postoperative JOA and UCLA scores in group F2 were significantly lower than those in the other groups. Conclusion: The medial knot-tying after suture-bridge lateral row repair demonstrated excellent functional and radiological outcomes after surgery, with a retear rate of 15.6%. The type 2 failure showed significantly inferior functional outcomes; however, the rate of type 2 failure was less relative to previous studies using conventional suture-bridge techniques. Our technique could be a good alternative to conventional suture-bridging rotator cuff repair because it may reduce the rate of postoperative type 2 failure.
New micronutrient biocomponents based on blackcurrant seeds pomace – Bench-scale kinetic studies
Authors: Chojnacka Katarzyna , Samoraj Mateusz , Tuhy Łukasz , Mironiuk Małgorzata , Moustakas Konstantinos , Witek-Krowiak Anna 
Published: July 2020

In the present work new universal bench-scale plant for biosorption, useful in production of new micronutrient biocomponents, was described. The new installation enabling working in a fixed bed or stirred tank batch mode. Reactors may also be used in serial or parallel mode, which gives many application possibilities. Copper ions were selected as a sorbate for kinetic modelling. The results of the adsorption capacities of Cu(II) were 13.9 mg/g for fixed bed and 12.8 mg/g for stirred tank. During biosorption of Cu(II) ions from aqueous solution ion exchange and release of Ca(II), K(I), Mg(II), and Na(I) were observed. For kinetics description of stirred tank process pseudo-1st-and pseudo-2nd order models were used. For fixed bed process the Thomas, Yoon-Nelson, Adams-Bohart and Wolborska models were used. The use of blackcurrant seed residues as biosorbents enables the generation of new products from waste biomass, which can become an alternative to the traditional fertilizers with microelements. The presented technology is an attempt to reduce environmental impact of the conventional micronutrient fertilizers, which contain toxic chelators such as EDTA. Minimization of waste and maximization of product output makes it an efficient tool supporting cleaner production.
Adverse pregnancy outcomes among multi-ethnic systemic lupus erythematosus patients in Malaysia
Authors: Shaharir Syahrul S , Maulana Suhaida A , Shahril Nor S , Mohd Rozita , Mustafar Ruslinda , Said Mohd S Mohamed , Rahman Rahana A 
Published: July 2020

Background Despite the improvement in the live birth rate among patients with systemic lupus erythematosus (SLE), they are still at an increased risk of adverse pregnancy outcomes (APOs). Objective To determine the prevalence and factors associated with APOs in the multi-ethnic SLE populations in Malaysia. Methodology: This was a retrospective review of the consecutive SLE patients who attended the outpatient clinic in two major rheumatology centres from January 2016 until December 2019 with complete pre-pregnancy, antenatal and intra-partum records. APOs include pregnancy loss, prematurity, pre-eclampsia, intra-uterine growth restriction (IUGR) and maternal death. Univariate and multivariable logistic regression with generalised estimating equation (GEE) analyses were performed to determine the factors associated with APOs. Results A total of 153 patients with 240 pregnancies were included and the majority of the patients were Malay (69.9%), followed by Chinese (24.2%) and Indian (5.9%). The prevalence of APOs was 61.7% with the commonest complication being prematurity (28.3%), followed by pregnancy loss (24.6%) and pre-eclampsia (21.8%). Logistic regression model-based GEE analysis revealed that the independent predictors of APOs were active haematological system during pregnancy, pre-pregnancy active disease, Indian patients and positive lupus anticoagulant. Hydroxychloroquine use was associated with lower APOs including pre-eclampsia, prematurity and IUGR in the univariate analyses but it was no longer significant in the GEE analysis. Conclusion The prevalence of APOs was high particularly among the Indian patients. Positive lupus anticoagulant and pre-pregnancy active disease were the factors strongly associated with APOs in our multi-ethnic cohort. Hydroxychloroquine may protect against APOs but further larger studies are needed to confirm this.
Happiness at the End of Life: A Qualitative Study
Authors: O’Callaghan Anne , Bickford Ben , Rea Conor , Fernando Antonio , Malpas Phillipa 
Published: July 2020

Background: Happiness is a core ingredient of health and well-being, yet relatively little is known about what happiness means for individuals near the end of life, and whether perceptions of happiness change as individuals approach the end of their lives. Aim: The aim of this study was to explore, through interviews, how individuals experiencing hospice care understood and conceptualized happiness. Design: Qualitative interviews with hospice patients were analyzed thematically. Setting/Participants: Adult patients (n = 20) in a New Zealand hospice who were receiving palliative care and who could give their informed consent were invited by hospice nurse coordinators to an interview. Results: Four themes emerged from analysis of the transcribed interviews. Participants defined happiness most frequently and in most depth in relation to connection with others. They identified being in the present moment, particularly in relation to nature, and that happiness had become less associated with money, status, or possessions. They had an attitude of determination to focus on what mattered now. Conclusion: Patients receiving palliative care were generally happy with their lives, appreciated the simpler aspects of life away from the material. There was a common exhortation to young people to avoid focusing too much on acquisition and the internet and to prioritize instead social connection and engagement with the natural world.
Anterior-Posterior (AP) Calcaneal Profile View: A Novel Radiographic Image to Assess Varus Malalignment
Authors: Kwon John Y. , Moura Bruno , Gonzalez Tyler , Miller Christopher P. , Briceno Jorge 
Published: July 2020

Background: Assessing and correcting malalignment is important when treating calcaneus fractures. The Harris axial view is commonly utilized to assess varus deformity but may be inherently inaccurate due to its tangential nature. The anterior-posterior (AP) calcaneal profile view is a novel radiographic view that is easily obtained with demonstrated increased accuracy for assessing calcaneal axial alignment. Methods: Five nonpaired ankle cadaveric specimens were used in this investigation. Oblique osteotomies were created in relation to the long axis, and varus deformities were produced by inserting solid radiolucent wedges into the osteotomies to create models of 10, 20, and 30 degrees of angulation of the calcaneal tuberosity. Specimens were imaged using both the Harris axial view and the AP calcaneal profile view. Results: For cadavers with 10 degrees of actual varus angulation, the mean Harris axial view angle and the AP calcaneal profile view angle were 10.9 ± 4.8 (range, 5.5-16.0) degrees and 13.0 ± 5.5 (range, 7.3-20.9) degrees, respectively. For cadavers with 20 degrees of actual varus angulation, the mean Harris view angle and the AP calcaneal profile view angle were 11.5 ± 2 (range, 8.2-13.6) degrees and 18.1 ± 4.8 (range, 11.7-23.5) degrees, respectively ( P = .005). On pairwise comparison with Bonferroni correction, there was a significant difference between the Harris axial view angle and both the AP calcaneal profile view angle ( P = .012) and actual angulation ( P = .011). For cadavers with 30 degrees of actual varus angulation, the mean Harris axial view angle and the AP calcaneal profile view angle were 18.3 ± 4.3 (range, 13.3-23.6) degrees and 28.3 ± 2.9 (range, 24.4-31.1) degrees, respectively ( P < .001). On pairwise comparison with Bonferroni correction, there was a significant difference between the Harris axial view angle and both the AP calcaneal profile view angle ( P = .001) and actual angulation ( P < .001). There was no significant difference between the AP calcaneal profile view angle and actual angulation ( P > .999). Conclusion: The AP calcaneal profile view is a novel radiographic view that is easily obtained with demonstrated increased accuracy for assessing calcaneal axial alignment. While both views demonstrated similar measurement error for lesser degrees of varus malalignment, the AP calcaneal profile view demonstrated more accurate measurement of increasing heel varus compared with the Harris view. Clinical Relevance: The AP calcaneal profile view could be used in addition to other radiographic views when treating displaced, intra-articular calcaneus fractures to help optimize correction of hindfoot alignment.
Evaluation of the potential complications of surgical wound drainage in primary total hip arthroplasty: a prospective controlled double-blind study
Authors: Lychagin Alexey V , Rosenberg Nahum , Gritsyuk Andrey A 
Published: July 2020

Background: The routine use of postoperative wound drainage following total hip arthroplasty (THA) to avoid the creation of excessive haematomas is controversial because of the potential risk of blood loss and wound infection. Methods: In a prospective double-blind controlled study, 2 groups of patients with hip joint osteoarthritis were operated with primary THA, 1 with surgical wound negative pressure drainage (Group 1 – 635 patients) and the other without (Group 2 – 527 patients). Postoperative blood haemoglobin and haematocrit levels, the necessity for blood transfusion, values of the potential infection markers (serum C-reactive protein values and erythrocyte sedimentation rate), postoperative pain level (according to the VAS scale) and functional outcome (according to Harris Hip Score [HHS] and SF-36 scores) at 12 months postoperatively were compared. Results: A significantly higher drop in blood haemoglobin and haematocrit values was observed in the Group 1 patients (mean drop of 2.2 gr/dl ± 0.25 vs. 1.6 gr/dl ± 0.35 and mean drop of 16% ± 4.0 vs. 11% ± 3.0, respectively, p  < 0.01, paired t test). The need for blood transfusion was significantly higher in the Group 1 patients (4.9% vs. 3.9%, p  < 0.05, t test). The severity of pain (VAS scale) on the first day after the operation was significantly lower in the Group 1 patients ( p < 0.05, t test), but overall, in both groups it was of low intensity (VAS <3). A similar postoperative wound infection rate was observed in both groups (0.4%). HHS and SF-36 scores were similar in both groups. Conclusions: The drainage of surgical wounds following primary THA due to hip osteoarthritis has a low added value and might cause an increased requirement for blood transfusion.