bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmentation of macular neovascularization and leakage in fluorescein angiography images in neovascular age-related macular degeneration using deep learning
Authors: Holomcik David , Seeböck Philipp , Gerendas Bianca S. , Mylonas Georgios , Najeeb Bilal Haj , Schmidt-Erfurth Ursula , Deak Gabor 
Published: July 2022

Abstract
Background/objectives
We aim to develop an objective fully automated Artificial intelligence (AI) algorithm for MNV lesion size and leakage area segmentation on fluorescein angiography (FA) in patients with neovascular age-related macular degeneration (nAMD).

Subjects/methods
Two FA image datasets collected form large prospective multicentre trials consisting of 4710 images from 513 patients and 4558 images from 514 patients were used to develop and evaluate a deep learning-based algorithm to detect CNV lesion size and leakage area automatically. Manual segmentation of was performed by certified FA graders of the Vienna Reading Center. Precision, Recall and F1 score between AI predictions and manual annotations were computed. In addition, two masked retina experts conducted a clinical-applicability evaluation, comparing the quality of AI based and manual segmentations.

Results
For CNV lesion size and leakage area segmentation, we obtained F1 scores of 0.73 and 0.65, respectively. Expert review resulted in a slight preference for the automated segmentations in both datasets. The quality of automated segmentations was slightly more often judged as good compared to manual annotations.

Conclusions
CNV lesion size and leakage area can be segmented by our automated model at human-level performance, its output being well-accepted during clinical applicability testing. The results provide proof-of-concept that an automated deep learning approach can improve efficacy of objective biomarker analysis in FA images and will be well-suited for clinical application.
Clinical enrollment assay to detect preexisting neutralizing antibodies to AAV6 with demonstrated transgene expression in gene therapy trials
Authors: Cao Liching , Ledeboer Annemarie , Pan Yonghua , Lu Yanmei , Meyer Kathleen 
Published: July 2022

AbstractRecombinant adeno-associated virus (AAV) vectors are the leading platform for gene delivery for a variety of clinical applications. Patients with preexisting antibodies to AAV are currently excluded from most AAV gene therapy trials to avoid vector neutralization and ensure response to therapy. Anti-AAV neutralizing antibodies (NAbs) are typically assessed by in vitro cell-based transduction inhibition (TI) assays. However, clinical relevance of the determined enrollment cutoff and the inherent variability of a cell-based assay present challenges for use as an enrollment screening test. Here, we describe an enrollment cutoff that was clinically validated and strategies to overcome assay challenges to enable long-term stable performance. A validated anti-AAV6 cell-based TI assay was used to support clinical enrollment across multiple investigational gene therapies and to evaluate AAV6 seroprevalence in healthy and disease populations. The clinical enrollment cutoff was determined statistically using samples collected from healthy donors, applying a 0.1% false error rate with the inclusion of a minimum significant ratio (MSR) metric and in consideration of results from in vivo mouse passive transfer studies. Our strategy for long-term monitoring and control of assay performance employed plate quality control samples flanking the predefined cutoff. An approach using donor samples was implemented to bridge different lots of critical reagents without the need to redefine the cutoff.
Nanoparticle suspensions from carbon-rich fluid make high-grade gold deposits
Authors: Petrella Laura , Thébaud Nicolas , Fougerouse Denis , Tattitch Brian , Martin Laure , Turner Stephen , Suvorova Alexandra , Gain Sarah 
Published: July 2022

AbstractEconomic gold deposits result from a 100- to 10,000-fold enrichment in gold relative to crustal background. In hydrothermal systems, this enrichment is achieved through the transport and accumulation of metals via deeply sourced fluids to a site of deposition. However, the generally low metal solubility of Au in aqueous solutions in orogenic systems requires additional processes in order to explain high-grade gold formation. Reports of Au nanoparticles in high-grade gold veins infer that their formation is linked to mineralisation. However, processes leading to nanoparticle nucleation and deposition remain poorly understood. Here we show that formation of metal nanoparticles (Au, AuAg, Cu, Ag2O) is one of the essential contributors to efficient and focused gold deposition. We report systematic and previously unrecognized metal nanoparticles preserved in amorphous silica and/or carbonic phases in five high-grade deposits. The association of metal, silica and carbonic phases helps to constrain the multiple reactive processes involved in Au, Cu and Ag metallogenesis and formation of high-grade gold mineralisation.
Rapid Eocene diversification of spiny plants in subtropical woodlands of central Tibet
Authors: Zhang Xinwen , Gélin Uriel , Spicer Robert A. , Wu Feixiang , Farnsworth Alexander , Chen Peirong , Del Rio Cédric , Li Shufeng , Liu Jia , Huang Jian , Spicer Teresa E. V. , Tomlinson Kyle W. , Valdes Paul J. , Xu Xiaoting , Zhang Shitao , Deng Tao , Zhou Zhekun , Su Tao 
Published: July 2022

AbstractSpinescence is an important functional trait possessed by many plant species for physical defence against mammalian herbivores. The development of spinescence must have been closely associated with both biotic and abiotic factors in the geological past, but knowledge of spinescence evolution suffers from a dearth of fossil records, with most studies focusing on spatial patterns and spinescence-herbivore interactions in modern ecosystems. Numerous well-preserved Eocene (~39 Ma) plant fossils exhibiting seven different spine morphologies discovered recently in the central Tibetan Plateau, combined with molecular phylogenetic character reconstruction, point not only to the presence of a diversity of spiny plants in Eocene central Tibet but a rapid diversification of spiny plants in Eurasia around that time. These spiny plants occupied an open woodland landscape, indicated by numerous megafossils and grass phytoliths found in the same deposits, as well as numerical climate and vegetation modelling. Our study shows that regional aridification and expansion of herbivorous mammals may have driven the diversification of functional spinescence in central Tibetan woodlands, ~24 million years earlier than similar transformations in Africa.
Manipulating polariton condensates by Rashba-Dresselhaus coupling at room temperature
Authors: Li Yao , Ma Xuekai , Zhai Xiaokun , Gao Meini , Dai Haitao , Schumacher Stefan , Gao Tingge 
Published: July 2022

AbstractSpin-orbit coupling plays an important role in the spin Hall effect and topological insulators. Bose-Einstein condensates with spin-orbit coupling show remarkable quantum phase transition. In this work we control an exciton polariton condensate – a macroscopically coherent state of hybrid light and matter excitations – by virtue of the Rashba-Dresselhaus (RD) spin-orbit coupling. This is achieved in a liquid-crystal filled microcavity where CsPbBr3 perovskite microplates act as the gain material at room temperature. Specifically, we realize an artificial gauge field acting on the CsPbBr3 exciton polariton condensate, splitting the condensate fractions with opposite spins in both momentum and real space. Besides the ground states, higher-order discrete polariton modes can also be split by the RD effect. Our work paves the way to manipulate exciton polariton condensates with a synthetic gauge field based on the RD spin-orbit coupling at room temperature.
Global stocks and capacity of mineral-associated soil organic carbon
Authors: Georgiou Katerina , Jackson Robert B. , Vindušková Olga , Abramoff Rose Z. , Ahlström Anders , Feng Wenting , Harden Jennifer W. , Pellegrini Adam F. A. , Polley H. Wayne , Soong Jennifer L. , Riley William J. , Torn Margaret S. 
Published: July 2022

AbstractSoil is the largest terrestrial reservoir of organic carbon and is central for climate change mitigation and carbon-climate feedbacks. Chemical and physical associations of soil carbon with minerals play a critical role in carbon storage, but the amount and global capacity for storage in this form remain unquantified. Here, we produce spatially-resolved global estimates of mineral-associated organic carbon stocks and carbon-storage capacity by analyzing 1144 globally-distributed soil profiles. We show that current stocks total 899 Pg C to a depth of 1 m in non-permafrost mineral soils. Although this constitutes 66% and 70% of soil carbon in surface and deeper layers, respectively, it is only 42% and 21% of the mineralogical capacity. Regions under agricultural management and deeper soil layers show the largest undersaturation of mineral-associated carbon. Critically, the degree of undersaturation indicates sequestration efficiency over years to decades. We show that, across 103 carbon-accrual measurements spanning management interventions globally, soils furthest from their mineralogical capacity are more effective at accruing carbon; sequestration rates average 3-times higher in soils at one tenth of their capacity compared to soils at one half of their capacity. Our findings provide insights into the world’s soils, their capacity to store carbon, and priority regions and actions for soil carbon management.
Comparing high versus low-altitude populations to test human adaptations for increased ventilation during sustained aerobic activity
Authors: Callison W. Éamon , Kiyamu Melisa , Villafuerte Francisco C. , Brutsaert Tom D. , Lieberman Daniel E. 
Published: July 2022

AbstractDespite aerobic activity requiring up to tenfold increases in air intake, human populations in high-altitude hypoxic environments can sustain high levels of endurance physical activity. While these populations generally have relatively larger chest and lung volumes, how thoracic motions actively increase ventilation is unknown. Here we show that rib movements, in conjunction with chest shape, contribute to ventilation by assessing how adulthood acclimatization, developmental adaptation, and population-level adaptation to high-altitude affect sustained aerobic activity. We measured tidal volume, heart rate, and rib-motion during walking and running in lowland individuals from Boston (~ 35 m) and in Quechua populations born and living at sea-level (~ 150 m) and at high altitude (> 4000 m) in Peru. We found that Quechua participants, regardless of birth or testing altitudes, increase thoracic volume 2.0–2.2 times more than lowland participants (p < 0.05). Further, Quechua individuals from hypoxic environments have deeper chests resulting in 1.3 times greater increases in thoracic ventilation compared to age-matched, sea-level Quechua (p < 0.05). Thus, increased thoracic ventilation derives from a combination of acclimatization, developmental adaptation, and population-level adaptation to aerobic demand in different oxygen environments, demonstrating that ventilatory demand due to environment and activity has helped shape the form and function of the human thorax.
MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome
Authors: Pieper C. C. , Wagenpfeil J. , Henkel A. , Geiger S. , Köster T. , Hoss K. , Luetkens J. A. , Hart C. , Attenberger U. I. , Müller A. 
Published: July 2022

AbstractNoonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.
Low predictive power of clinical features for relapse prediction after antidepressant discontinuation in a naturalistic setting
Authors: Berwian Isabel M. , Wenzel Julia G. , Kuehn Leonie , Schnuerer Inga , Seifritz Erich , Stephan Klaas E. , Walter Henrik , Huys Quentin J. M. 
Published: July 2022

AbstractThe risk of relapse after antidepressant medication (ADM) discontinuation is high. Predictors of relapse could guide clinical decision-making, but are yet to be established. We assessed demographic and clinical variables in a longitudinal observational study before antidepressant discontinuation. State-dependent variables were re-assessed either after discontinuation or before discontinuation after a waiting period. Relapse was assessed during 6 months after discontinuation. We applied logistic general linear models in combination with least absolute shrinkage and selection operator and elastic nets to avoid overfitting in order to identify predictors of relapse and estimated their generalisability using cross-validation. The final sample included 104 patients (age: 34.86 (11.1), 77% female) and 57 healthy controls (age: 34.12 (10.6), 70% female). 36% of the patients experienced a relapse. Treatment by a general practitioner increased the risk of relapse. Although within-sample statistical analyses suggested reasonable sensitivity and specificity, out-of-sample prediction of relapse was at chance level. Residual symptoms increased with discontinuation, but did not relate to relapse. Demographic and standard clinical variables appear to carry little predictive power and therefore are of limited use for patients and clinicians in guiding clinical decision-making.
Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China
Authors: Jia Chun-Hong , Feng Zhou-Shan , Lin Xiao-Jun , Cui Qi-Liang , Han Sha-Sha , Jin Ya , Liu Guo-Sheng , Yang Chuan-Zhong , Ye Xiao-Tong , Dai Yi-Heng , Liang Wei-Yi , Ye Xiu-Zhen , Mo Jing , Ding Lu , Wu Ben-Qing , Chen Hong-Xiang , Li Chi-Wang , Zhang Zhe , Rong Xiao , Huang Wei-Min , Shen Wei , Yang Bing-Yan , Lv Jun-Feng , Huo Le-Ying , Huang Hui-Wen , Rao Hong-Ping , Yan Wen-Kang , Yang Yong , Ren Xue-Jun , Liu Dong , Wang Fang-Fang , Diao Shi-Guang , Liu Xiao-Yan , You Chu-Ming , Meng Qiong , Wang Bin , Zhang Li-Juan , Huang Yu-Ge , Ao Dang , Li Wei-Zhong , Chen Jie-Ling , Chen Yan-Ling , Li Wei , Chen Zhi-Feng , Ding Yue-Qin , Li Xiao-Yu , Huang Yue-Fang , Lin Ni-Yang , Cai Yang-Fan , Wan Zhong-He , Ban Yi , Bai Bo , Li Guang-Hong , Yan Yue-Xiu , Wu Fan 
Published: July 2022

AbstractWith the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008–2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.
The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C
Authors: Tajiri Hitoshi , Suzuki Mitsuyoshi , Bessho Kazuhiko , Ito Yoshinori , Murakami Jun , Hatori Reiko , Takano Tomoko , Miyoshi Yoko , Brooks Stephen 
Published: July 2022

AbstractAt present, noninvasive fibrosis markers are not available for the assessment of liver fibrosis in children with chronic hepatitis C. Sixty-three children with chronic hepatitis C were included. Changes in Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) levels were evaluated in l3 of 27 treatment-naive patients during the natural course of disease (median 4, range 3–6 years). Changes during treatment were evaluated in 27 of 36 patients for 4 (2–9) years of posttreatment follow-up. There were significant differences in the levels of M2BPGi between control group and HCV F0 group (P = 0.002) and between control group and HCV F1 group (P < 0.001). Receiver operating characteristic curve analysis showed that to discriminate stage F1 fibrosis from F0, the cut-off value was 0.95 for M2BPGi with a sensitivity of 52%, specificity of 90%, and area under the curve of 0.687. A substantial decrease in M2BPGi levels by treatment was shown from 0.98 ± 0.57 at pretreatment to 0.42 ± 0.15 at posttreatment (P < 0.001) in the 27 treated patients. Our study shows new findings that M2BPGi may be useful to predict the presence of a mild degree of fibrosis in children with chronic hepatitis C, and such mild fibrosis may be quickly resolved by treatment.
Metabolic modeling-based drug repurposing in Glioblastoma
Authors: Tomi-Andrino Claudio , Pandele Alina , Winzer Klaus , King John , Rahman Ruman , Kim Dong-Hyun 
Published: July 2022

AbstractThe manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a source of potential drug targets. Drug discovery is a long and resource-demanding process aiming at identifying and testing compounds early in the drug development pipeline. While drug repurposing efforts (i.e., inspecting readily available approved drugs) can be supported by a mechanistic rationale, strategies to further reduce and prioritize the list of potential candidates are still needed to facilitate feasible studies. Although a variety of ‘omics’ data are widely gathered, a standard integration method with modeling approaches is lacking. For instance, flux balance analysis is a metabolic modeling technique that mainly relies on the stoichiometry of the metabolic network. However, exploring the network’s topology typically neglects biologically relevant information. Here we introduce Transcriptomics-Informed Stoichiometric Modelling And Network analysis (TISMAN) in a recombinant innovation manner, allowing identification and validation of genes as targets for drug repurposing using glioblastoma as an exemplar.
Impact of deafness on numerical tasks implying visuospatial and verbal processes
Authors: Buyle Margot , Vencato Valentina , Crollen Virginie 
Published: July 2022

AbstractThe literature suggests that deaf individuals lag behind their hearing peers in terms of mathematical abilities. However, it is still unknown how unique sensorimotor experiences, like deafness, might shape number-space interactions. We still do not know either the spatial frame of reference deaf individuals use to map numbers onto space in different numerical tasks. To examine these issues, deaf, hearing signer and hearing control adults were asked to perform a number comparison and a parity judgment task with the hands uncrossed and crossed over the body midline. Deafness appears to selectively affect the performance of the numerical task relying on verbal processes while keeping intact the task relying on visuospatial processes. Indeed, while a classic SNARC effect was found in all groups and in both hand postures of the number comparison task, deaf adults did not show the SNARC effect in both hand postures of the parity judgment task. These results are discussed in light of the spatial component characterizing the counting system used in sign language.
Sp1 induced gene TIMP1 is related to immune cell infiltration in glioblastoma
Authors: Liu Lu , Yang Shuyao , Lin Kefeng , Yu Xiaoman , Meng Jiaqi , Ma Chao , Wu Zheng , Hao Yuchao , Chen Ning , Ge Qi , Gao Wenli , Wang Xiang , Lam Eric W.-F. , Zhang Lin , Li Fangcheng , Jin Bilian , Jin Di 
Published: July 2022

AbstractTumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.