bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoplasmic Autoinhibition in HCN Channels is Regulated by the Transmembrane Region
Authors: Page Dana A. , Magee Kaylee E. A. , Li Jessica , Jung Matthew , Young Edgar C. 
Published: March 2020

AbstractHyperpolarization-activated cation-nonselective (HCN) channels regulate electrical activity in the brain and heart in a cAMP-dependent manner. The voltage-gating of these channels is mediated by a transmembrane (TM) region but is additionally regulated by direct binding of cAMP to a cyclic nucleotide-binding (CNB) fold in the cytoplasmic C-terminal region. Cyclic AMP potentiation has been explained by an autoinhibition model which views the unliganded CNB fold as an inhibitory module whose influence is disrupted by cAMP binding. However, the HCN2 subtype uses two other CNB fold-mediated mechanisms called open-state trapping and Quick-Activation to respectively slow the deactivation kinetics and speed the activation kinetics, against predictions of an autoinhibition model. To test how these multiple mechanisms are influenced by the TM region, we replaced the TM region of HCN2 with that of HCN4. This HCN4 TM-replacement preserved cAMP potentiation but augmented the magnitude of autoinhibition by the unliganded CNB fold; it moreover disrupted open-state trapping and Quick-Activation so that autoinhibition became the dominant mechanism contributed by the C-terminal region to determine kinetics. Truncation within the CNB fold partially relieved this augmented autoinhibition. This argues against the C-terminal region acting like a portable module with consistent effects on TM regions of different subtypes. Our findings provide evidence that functional interactions between the HCN2 TM region and C-terminal region govern multiple CNB fold-mediated mechanisms, implying that the molecular mechanisms of autoinhibition, open-state trapping, and Quick-Activation include participation of TM region structures.
Flow Dynamics of Bilateral Superior Cavopulomonary Shunts Influence Outcomes After Fontan Completion
Authors: Ono Masamichi , Burri Melchior , Mayr Benedikt , Anderl Lisa , Cleuziou Julie , Strbad Martina , Hager Alfred , Hörer Jürgen , Lange Rüdiger 
Published: March 2020

AbstractBilateral superior vena cava (SVC), which occurs following bilateral bidirectional cavopulmonary shunt (BCPS), is an anomaly marked by unique hemodynamics. This study aimed to determine its effects on outcomes after Fontan completion. Among 405 patients who underwent BCPS and total cavopulmonary connection (TCPC) between 1997 and 2017, 40 required a bilateral-BCPS. The dominant SVC prior to TCPC was identified according to the direction of blood flow in the central pulmonary artery, and its relationship to the inferior vena cava (IVC) was classified as a concordant or discordant relationship. Preoperative factors were analyzed to identify the risk factors for specific adverse outcomes. The length of intensive care unit (ICU) stay after TCPC was longer in the 40 patients who underwent bilateral-BCPS than in those who underwent unilateral BCPS (p = 0.024), and the survival rate was lower in the former group than in the latter group (p = 0.004). In the patients who underwent bilateral-BCPS, the dominant SVC was concordant with the IVC in 30 patients and discordant in 10 patients. With regard to whether certain morphological, hemodynamic, and flow dynamics-related variables were risk factors for adverse outcomes following TCPC, a discordant relationship between dominant SVC and IVC was identified as an independent risk factor for both a longer ICU stay (p = 0.037, HR 2.370) and worse survival (p = 0.019, HR 13.880). Therefore, in patients with a bilateral SVC who have previously undergone bilateral-BCPS, a discordant relationship between dominant SVC and IVC might contribute to worse outcomes following TCPC.
Adenosine-producing regulatory B cells in head and neck cancer
Authors: Jeske Sandra S. , Brand Matthias , Ziebart Andreas , Laban Simon , Doescher Johannes , Greve Jens , Jackson Edwin K. , Hoffmann Thomas K. , Brunner Cornelia , Schuler Patrick J. 
Published: March 2020

Abstract
Background
Multiple mechanisms of immunosuppression have been identified in the tumor microenvironment including regulatory B cells (Breg). Recently, we have shown that Breg suppress T cell function by production of adenosine (ADO). However, the autocrine effect of ADO on B cells and the role of Breg in head and neck cancer remains unclear.

Methods
Blood (n = 42) and tumor tissue (n = 39) of head and neck cancer patients and healthy donors (n = 60) were analyzed by FACS. The effect of ADO on phenotype, intracellular signaling pathways, Ca2+ influx and ADO production was analyzed in Breg and effector B cells (Beff) by FACS, luminescence and mass spectrometry. The blockage of the ADO receptor A2A was analyzed in a murine head and neck cancer model.

Results
ADO-producing Breg were found in tumor tissue and peripheral blood. ADO inhibited the intracellular Bruton’s tyrosine kinase (BTK) and Ca2+ influx only in Beff. The inhibition of BTK by ibrutinib mimicked the effect of ADO, and ibrutinib reduced the production of ADO by downregulation of CD39 in vitro. The inhibition of ADO receptor A2A significantly reduced tumor mass and increased B cell infiltration, in vivo.

Conclusion
Our data demonstrate the presence of a novel ADO-producing Breg population within the tumor microenvironment in mice and humans. A new model is proposed on how ADO-producing Breg can influence the function of Beff cells in healthy donors and cancer patients. Thus, the modulation of the ADO pathway in B cells may serve as a therapeutic approach for cancer patients.
Applicability of shear wave elastography for the evaluation of skin strain in systemic sclerosis
Authors: Sobolewski Piotr , Maślińska Maria , Zakrzewski Jakub , Paluch Łukasz , Szymańska Elżbieta , Walecka Irena 
Published: March 2020

AbstractThe assessment of skin fibrosis is vital for the diagnosis and monitoring of treatment in the systemic sclerosis (SSc)—a severe autoimmune disease. The elastography is a technique of skin fibrosis assessment through the evaluation of skin strain. We compared the efficacy of the shear wave elastography (SWE) and commonly used modified Rodnan skin score (RSS) in skin fibrosis assessment in SSc. The study included 40 SSc patients and 28 healthy individuals, with the exclusion of individuals with other skin/autoimmune diseases. Skin thickness using RSS and skin strain using SWE were assessed in the same 20 body localizations. Subjects’ informed consent and the bioethics committee approval were obtained. Elastographic skin strain correlated positively with both partial and overall RSS values, with strong positive correlation (r ≥ 0.75) for hands and fingers localizations in particular. In SSc patients with normal RSS values, the elastographic strain was significantly higher than in healthy controls. Elastographic strain of fingers’ skin evaluated in SWE is highly accurate for distinguishing SSc patients (sensitivity 0.897–0.923, specificity 0.929–0.964, positive predictive value 0.946–0.973, negative predictive value 0.867–0.900). ESW results are substantially more reproducible than those of RSS examination (intraclass correlation coefficients: 0.987 vs. 0.941). The shear wave elastography is more reproducible and has higher sensitivity than RSS in the evaluation of skin condition in SSc, especially in case of changes non-detectable on physical evaluation, indicating it might become a useful tool in SSc diagnosis.
Forests and foragers: exploitation of wood resources by Mesolithic and para-Neolithic societies in north-eastern Poland
Authors: Wacnik Agnieszka , Gumiński Witold , Cywa Katarzyna , Bugajska Karolina 
Published: March 2020

AbstractNewly acquired palaeobotanical data, including pollen, charred and uncharred wood, provided an exhaustive overview of the temporal changes in woodlands, which changes are due to the cumulative effect of natural processes and the long-term impact of pre-agrarian societies. We used the unique advantage of the peat bog archaeological site at Szczepanki located on an island in the former Lake Staświn (Masurian Lake District) to get an overview of wood exploitation throughout the Stone Age. Special attention was paid to the period of the most intense settlement, the period of the para-Neolithic Zedmar culture. This culture is interesting due to its economy having not been fully recognized so far, especially with respect to the use of plant resources. The evidence from Szczepanki confirmed the use of 16 arboreal taxa, accessible in local woodlands, as a source of timber by foragers. The majority of both unworked wood and fragments bearing traces of processing has been discovered in layers corresponding to the Zedmar period. An important role in the economy was played by wood with medium or low mechanical properties that was however fissile and amenable to woodworking. In addition, other useful properties such as flexibility, lightness, water resistance, strength and ease of splitting were favoured in the selection. The temporal distribution of wood remains in cultural layers at Szczepanki was convergent with a pollen record documenting the course of postglacial migration and local growth of particular taxa, as well as with the archaeologically documented changes in the intensity and time frame of the settlement.
A low-cost, practical acquisition and rendering pipeline for real-time free-viewpoint video communication
Authors: Rasmuson Sverker , Sintorn Erik , Assarsson Ulf 
Published: March 2020

AbstractWe present a semiautomatic real-time pipeline for capturing and rendering free-viewpoint video using passive stereo matching. The pipeline is simple and achieves agreeable quality in real time on a system of commodity web cameras and a single desktop computer. We suggest an automatic algorithm to compute a constrained search space for an efficient and robust hierarchical stereo reconstruction algorithm. Due to our fast reconstruction times, we can eliminate the need for an expensive global surface reconstruction with a combination of high coverage and aggressive filtering. Finally, we employ a novel color weighting scheme that generates credible new viewpoints without noticeable seams, while keeping the computational complexity low. The simplicity and low cost of the system make it an accessible and more practical alternative for many applications compared to previous methods.
Radial flow velocity profiles of a yield stress fluid between smooth parallel disks
Authors: Shamu Tafadzwa John , Zou Liangchao , Kotzé Reinhardt , Wiklund Johan , Håkansson Ulf 
Published: March 2020

AbstractIn rock grouting, idealized 2D-radial laminar flow of yield stress fluids (YSF) is a fundamental flow configuration that is used for cement grout spread estimation. A limited amount of works have presented analytical and numerical solutions on the radial velocity profiles between parallel disks. However, to the best of our knowledge, there has been no experimental work that has presented measured velocity profiles for this geometry. In this paper, we present velocity profiles of Carbopol (a simple YSF), measured by pulsed ultrasound velocimetry within a radial flow model. We describe the design of the physical model and then present the measured velocity profiles while highlighting the plug-flow region and slip effects observed for three different apertures and volumetric flow rates. Although the measured velocity profiles exhibited wall slip, there was a reasonably good agreement with the analytical solution. We then discuss the major implications of our work on radial flow.
Diagnostic power of scleral spur length in primary open-angle glaucoma
Authors: Li Mu , Luo Zhaoxia , Yan Xiaoqin , Zhang Hong 
Published: March 2020

Abstract
Purpose
To investigate the diagnostic capability of scleral spur length in discriminating eyes with primary open-angle glaucoma (POAG) from healthy eyes.

Methods
Seventy-eight eyes of 78 patients with POAG and 93 eyes of 93 age-, sex- and axial length-matched healthy subjects were included. The scleral spur length was measured using swept-source optical coherence tomography. Receiver operating characteristic (ROC) curves were derived based on the measurements.

Results
The scleral spur length was significantly shorter in POAG eyes compared with healthy eyes (Method I, 164.91 ± 23.36 vs. 197.60 ± 25.32 μm; Method II, 145.15 ± 16.59 vs. 166.95 ± 19.31 μm; Method III, 162.33 ± 22.83 vs. 185.12 ± 23.58 μm, respectively; all p < 0.001). The areas under ROC curves were 0.841 (Method I), 0.810 (Method II), and 0.753 (Method III) for the scleral spur length. Moreover, Schlemm’s canal area was significantly associated with the scleral spur length (Method I) in both POAG (β = 0.027; p < 0.001) and healthy (β = 0.016; p = 0.009) groups.

Conclusions
The scleral spur length had a good discriminating capability between POAG and healthy eyes, and it could be a novel biomarker for POAG evaluation clinically.
Albrecht von Graefe in the present, the past, and the future
Authors: Rohrbach Jens Martin 
Published: March 2020

AbstractAlbrecht von Graefe (1828–1870) is the founder of this archive (1854) and the founder of modern ophthalmology. In 2020, the anniversary of his death will be observed for the 150th time. The “German Ophthalmological Society” (DOG), also a Graefe foundation (1857), has therefore proclaimed a “Graefe year.” In Berlin, his hometown, several Graefe-monuments exist. Ophthalmology owes Albrecht von Graefe numerous first discoveries such as excavation of the optic disc in glaucoma (1855), iridectomy in glaucoma (1857), or central artery occlusion (1859). But his after-effects are not only based on his clinical and scientific merits but also on his extraordinary, fascinating personality, which can be characterized by his spirit of internationality, friendship, self-criticism, love of truth, and modesty. Graefe became a myth not only because of his early death but also because he had apart from great successes, to accept human misfortunes at the same time. Albrecht von Graefe can be regarded as the conscience of ophthalmology in Germany.
Does basic information concerning nutrition improve the information needs of breast cancer patients? An evaluation
Authors: Groß Sophie E. , Weidner Doreen , Cecon Natalia , Pfaff Holger , Strauch Carmen , Scholten Nadine 
Published: March 2020

Abstract
Purpose
International and national studies have shown unmet information needs regarding nutrition in breast cancer patients. An intervention study has examined the question of the extent to which a fact sheet on the topic of nutrition is suitable to cover the need for information of breast cancer patients.

Method
The fact sheet with basic information on nutrition was distributed in 21 intervention breast care centres in 2017. The use of the fact sheets was evaluated in a quasi-experimental design as part of the annual breast cancer patients’ survey of the University of Cologne. The breast cancer patients considered were being treated with primary breast carcinoma in a hospital in North Rhine-Westphalia. A multilevel analysis was carried out in order to quantify the effect of the intervention.

Results
Unmet information needs are experienced more by younger and non-native German-speaking patients. With regard to education, patients without a graduation and a high grade of education express more unmet information needs. The multilevel analysis showed that patients who were treated at an intervention site and therefore possibly received the fact sheet have a significantly higher chance of their information needs being met (OR = 1.45; p ≤ 0.05).

Conclusion
The intervention study showed that a fact sheet with basic information on nutrition is a possible instrument to satisfy the information needs of breast cancer patients and therefore reduce unmet information needs regarding nutrition. This intervention study is a pragmatic example on how to reduce unmet information needs among breast cancer patients in Germany.
Long-term excess mortality after chronic subdural hematoma
Authors: Rauhala Minna , Helén Pauli , Seppä Karri , Huhtala Heini , Iverson Grant L. , Niskakangas Tero , Öhman Juha , Luoto Teemu M. 
Published: March 2020

Abstract
Objective
To assess possible long-term excess mortality and causes of death of patients with chronic subdural hematoma (CSDH).

Methods
A retrospective study (1990–2015) of adult patients (n = 1133, median age = 76 years old, men = 65%) with CSDH identified by ICD-codes and verified by medical records. All patients were followed until death or the end of 2017. Cumulative relative survival ratios and relative excess risks of death (RER) were estimated by comparing patients’ mortality with that in the entire regional matched population. The causes of death were compared with a separate reference group formed by randomly choosing sex, age, and calendar time matched controls (4 controls per each CSDH patient).

Results
The median follow-up time was 4.8 years (range = 0–27 years), and 710 (63%) of the patients died (median age at death = 84 years old). The cumulative excess mortality was 1 year = 9%, 5 years = 18%, 10 years = 27%, 15 years = 37%, and 20 years = 48%. A subgroup of CSDH patients (n = 206) with no comorbidity had no excess mortality. Excess mortality was related to poor modified Rankin score at admission (RER = 4.93) and at discharge (RER = 8.31), alcohol abuse (RER = 4.47), warfarin (RER = 2.94), age ≥ 80 years old (RER = 1.83), non-operative treatment (RER = 1.56), and non-traumatic etiology (RER = 1.69). Hematoma characteristics or recurrence were unrelated to excess mortality. Dementia was the most common cause of death among the CSDH patients (21%) and the third most common cause in the reference group (15%, p < 0.001).

Conclusions
Patients with CSDH have continuous excess mortality up to 20 years after diagnosis. Patient-related characteristics have a strong association with excess mortality, whereas specific CSDH-related findings do not. CSDH patients have an increased risk for dementia-related mortality.
The decreased expression of IKBKE in systemic lupus erythematosus
Authors: Zhu Tingting , Hong Jiaqi , Shuai Zongwen , Xu Shengqian , Qian Danfeng , Hong Xiaojie , Liu Yaoguang , Chen Min , Meng Ziyuan , Zheng Lijun , Zheng Danlin , Zhang Xuejun , Liu Lu 
Published: March 2020

Abstract
Objective
The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE.

Methods
We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms.

Results
The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients.

Conclusion
In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals.

Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.
Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS)
Authors: Yamamoto Ryohei , Imai Enyu , Maruyama Shoichi , Yokoyama Hitoshi , Sugiyama Hitoshi , Nitta Kosaku , Tsukamoto Tatsuo , Uchida Shunya , Takeda Asami , Sato Toshinobu , Wada Takashi , Hayashi Hiroki , Akai Yasuhiro , Fukunaga Megumu , Tsuruya Kazuhiko , Masutani Kosuke , Konta Tsuneo , Shoji Tatsuya , Hiramatsu Takeyuki , Goto Shunsuke , Tamai Hirofumi , Nishio Saori , Shirasaki Arimasa , Nagai Kojiro , Yamagata Kunihiro , Hasegawa Hajime , Yasuda Hideo , Ichida Shizunori , Naruse Tomohiko , Nishino Tomoya , Sobajima Hiroshi , Tanaka Satoshi , Akahori Toshiyuki , Ito Takafumi , Terada Yoshio , Katafuchi Ritsuko , Fujimoto Shouichi , Okada Hirokazu , Ishimura Eiji , Kazama Junichiro J. , Hiromura Keiju , Mimura Tetsushi , Suzuki Satoshi , Saka Yosuke , Sofue Tadashi , Suzuki Yusuke , Shibagaki Yugo , Kitagawa Kiyoki , Morozumi Kunio , Fujita Yoshiro , Mizutani Makoto , Shigematsu Takashi , Kashihara Naoki , Sato Hiroshi , Matsuo Seiichi , Narita Ichiei , Isaka Yoshitaka 
Published: March 2020

Abstract
Background
Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan.

Methods
A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model.

Results
Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN.

Conclusions
Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.