bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection
Authors: Wettstein Lukas , Weil Tatjana , Conzelmann Carina , Müller Janis A. , Groß Rüdiger , Hirschenberger Maximilian , Seidel Alina , Klute Susanne , Zech Fabian , Prelli Bozzo Caterina , Preising Nico , Fois Giorgio , Lochbaum Robin , Knaff Philip Maximilian , Mailänder Volker , Ständker Ludger , Thal Dietmar Rudolf , Schumann Christian , Stenger Steffen , Kleger Alexander , Lochnit Günter , Mayer Benjamin , Ruiz-Blanco Yasser B. , Hoffmann Markus , Sparrer Konstantin M. J. , Pöhlmann Stefan , Sanchez-Garcia Elsa , Kirchhoff Frank , Frick Manfred , Münch Jan 
Published: March 2021

AbstractSARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.
Photonic resonator interferometric scattering microscopy
Authors: Li Nantao , Canady Taylor D. , Huang Qinglan , Wang Xing , Fried Glenn A. , Cunningham Brian T. 
Published: March 2021

AbstractInterferometric scattering microscopy is increasingly employed in biomedical research owing to its extraordinary capability of detecting nano-objects individually through their intrinsic elastic scattering. To significantly improve the signal-to-noise ratio without increasing illumination intensity, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a dielectric photonic crystal (PC) resonator is utilized as the sample substrate. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create a large intensity contrast. Importantly, the scattered photons assume the wavevectors delineated by PC’s photonic band structure, resulting in the ability to utilize a non-immersion objective without significant loss at illumination density as low as 25 W cm−2. An analytical model of the scattering process is discussed, followed by demonstration of virus and protein detection. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies.
Epigenetic mechanisms in breast cancer therapy and resistance
Authors: Garcia-Martinez Liliana , Zhang Yusheng , Nakata Yuichiro , Chan Ho Lam , Morey Lluis 
Published: March 2021

AbstractThe majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent the main treatment modality. Endocrine therapy has proven successful in the treatment of hormone-responsive breast cancer since its early adoption in the 1940s as an ablative therapy. Unfortunately, therapeutic resistance arises, leading to disease recurrence and relapse. Recent studies increased our understanding in how changes to the chromatin landscape and deregulation of epigenetic factors orchestrate the resistant phenotype. Here, we will discuss how the epigenome is an integral determinant in hormone therapy response and why epigenetic factors are promising targets for overcoming clinical resistance.
Prediction of stimulus-independent and task-unrelated thought from functional brain networks
Authors: Kucyi Aaron , Esterman Michael , Capella James , Green Allison , Uchida Mai , Biederman Joseph , Gabrieli John D. E. , Valera Eve M. , Whitfield-Gabrieli Susan 
Published: March 2021

AbstractNeural substrates of “mind wandering” have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering—stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling—dominated by default-frontoparietal control subnetwork interactions—that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of adults with attention-deficit/hyperactivity disorder (ADHD). In three additional resting-state fMRI studies (total n = 1115), including healthy individuals and individuals with ADHD, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales and contexts.
Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases
Authors: Alhalabi Omar , Soomro Zaid , Sun Ryan , Hasanov Elshad , Albittar Aya , Tripathy Debu , Valero Vicente , Ibrahim Nuhad K. 
Published: March 2021

AbstractThe development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.
Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression
Authors: Mwesigwa Savannah , Williams Lesedi , Retshabile Gaone , Katagirya Eric , Mboowa Gerald , Mlotshwa Busisiwe , Kyobe Samuel , Kateete David P. , Wampande Eddie Mujjwiga , Wayengera Misaki , Mpoloka Sununguko Wata , Mirembe Angella N. , Kasvosve Ishmael , Morapedi Koketso , Kisitu Grace P. , Kekitiinwa Adeodata R. , Anabwani Gabriel , Joloba Moses L. , Matovu Enock , Mulindwa Julius , Noyes Harry , Botha Gerrit ,   Collaborative African Genomics Network (CAfGEN), Tsimako-Johnstone Masego , Katabazi Fred. A. , Kigozi Edgar , Mathuba Keofentse ,   TrypanoGEN Research Group, Brown Chester W. , Mardon Graeme , Matshaba Mogomotsi , Hanchard Neil A. 
Published: March 2021

AbstractHuman immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%;p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), withAnelloviridaeshowing strong association with LTNP status (p = 3 × 10−4;q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02;q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of theAnelloviridaereads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.
Impact of bronchiolitis guidelines publication on primary care prescriptions in the Italian pediatric population
Authors: Barbieri Elisa , Cantarutti Anna , Cavagnis Sara , Cantarutti Luigi , Baraldi Eugenio , Giaquinto Carlo , Donà Daniele 
Published: March 2021

AbstractIn Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0–24 months before (December 2012–December 2014), in between (December 2014–December 2015) and after (December 2015–December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, β2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p < 0.001) after the publication of the second guideline; the highest reduction was in younger patients (from 57% to 44%, p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications.
Crystalline symmetry-protected non-trivial topology in prototype compound BaAl4
Authors: Wang Kefeng , Mori Ryo , Wang Zhijun , Wang Limin , Ma Jonathan Han Son , Latzke Drew W. , Graf David E. , Denlinger Jonathan D. , Campbell Daniel , Bernevig B. Andrei , Lanzara Alessandra , Paglione Johnpierre 
Published: March 2021

AbstractThe BaAl4 prototype crystal structure is the most populous of all structure types, and is the building block for a diverse set of sub-structures including the famous ThCr2Si2 family that hosts high-temperature superconductivity and numerous magnetic and strongly correlated electron systems. The MA4 family of materials (M = Sr, Ba, Eu; A = Al, Ga, In) themselves present an intriguing set of ground states including charge and spin orders, but have largely been considered as uninteresting metals. We predict the exemplary compound BaAl4 to harbor a three-dimensional Dirac spectrum with non-trivial topology and possible nodal lines crossing the Brillouin zone, wherein one pair of semi-Dirac points with linear dispersion along the kz direction and quadratic dispersion along the kx/ky direction resides on the rotational axis with C4v point group symmetry. An extremely large, unsaturating positive magnetoresistance in BaAl4 despite an uncompensated band structure is revealed, and quantum oscillations and angle-resolved photoemission spectroscopy measurements confirm the predicted multiband semimetal structure with pockets of Dirac holes and a Van Hove singularity (VHS) remarkably consistent with the theoretical prediction. We thus present BaAl4 as a topological semimetal, casting its prototype status into a role as a building block for a vast array of topological materials.
Charge density waves in cuprate superconductors beyond the critical doping
Authors: Miao H. , Fabbris G. , Koch R. J. , Mazzone D. G. , Nelson C. S. , Acevedo-Esteves R. , Gu G. D. , Li Y. , Yilimaz T. , Kaznatcheev K. , Vescovo E. , Oda M. , Kurosawa T. , Momono N. , Assefa T. , Robinson I. K. , Bozin E. S. , Tranquada J. M. , Johnson P. D. , Dean M. P. M. 
Published: March 2021

AbstractThe unconventional normal-state properties of the cuprates are often discussed in terms of emergent electronic order that onsets below a putative critical doping of xc ≈ 0.19. Charge density wave (CDW) correlations represent one such order; however, experimental evidence for such order generally spans a limited range of doping that falls short of the critical value xc, leading to questions regarding its essential relevance. Here, we use X-ray diffraction to demonstrate that CDW correlations in La2−xSrxCuO4 persist up to a doping of at least x = 0.21. The correlations show strong changes through the superconducting transition, but no obvious discontinuity through xc ≈ 0.19, despite changes in Fermi surface topology and electronic transport at this doping. These results demonstrate the interaction between CDWs and superconductivity even in overdoped cuprates and prompt a reconsideration of the role of CDW correlations in the high-temperature cuprate phase diagram.
Vitrification of particulated articular cartilage via calculated protocols
Authors: Wu Kezhou , Shardt Nadia , Laouar Leila , Elliott Janet A. W. , Jomha Nadr M. 
Published: March 2021

AbstractPreserving viable articular cartilage is a promising approach to address the shortage of graft tissue and enable the clinical repair of articular cartilage defects in articulating joints, such as the knee, ankle, and hip. In this study, we developed two 2-step, dual-temperature, multicryoprotectant loading protocols to cryopreserve particulated articular cartilage (cubes ~1 mm3 in size) using a mathematical approach, and we experimentally measured chondrocyte viability, metabolic activity, cell migration, and matrix productivity after implementing the designed loading protocols, vitrification, and warming. We demonstrated that porcine and human articular cartilage cubes can be successfully vitrified and rewarmed, maintaining high cell viability and excellent cellular function. The vitrified particulated articular cartilage was stored for a period of 6 months with no significant deterioration in chondrocyte viability and functionality. Our approach enables high-quality long-term storage of viable articular cartilage that can alleviate the shortage of grafts for use in clinically repairing articular cartilage defects.
Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
Authors: van der Lubbe Joan E. M. , Rosendahl Huber Sietske K. , Vijayan Aneesh , Dekking Liesbeth , van Huizen Ella , Vreugdenhil Jessica , Choi Ying , Baert Miranda R. M. , Feddes-de Boer Karin , Izquierdo Gil Ana , van Heerden Marjolein , Dalebout Tim J. , Myeni Sebenzile K. , Kikkert Marjolein , Snijder Eric J. , de Waal Leon , Stittelaar Koert J. , Tolboom Jeroen T. B. M. , Serroyen Jan , Muchene Leacky , van der Fits Leslie , Rutten Lucy , Langedijk Johannes P. M. , Barouch Dan H. , Schuitemaker Hanneke , Zahn Roland C. , Wegmann Frank 
Published: March 2021

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
Quorum quenching, biological characteristics, and microbial community dynamics as key factors for combating fouling of membrane bioreactors
Authors: Shah Syed Salman Ali , De Simone Luigi , Bruno Giuseppe , Park Hyeona , Lee Kibaek , Fabbricino Massimiliano , Angelidaki Irini , Choo Kwang-Ho 
Published: March 2021

AbstractMembrane fouling is a major challenge in membrane bioreactors (MBRs) for wastewater treatment. This study investigates the effects of disturbance and solid retention time (SRT) on quorum-quenching (QQ) MBRs relative to antifouling efficacy and microbial community change. The fouling rate increases with the applied disturbance at a short SRT, counteracting the antifouling effect of QQ; however, it decreases with QQ at a long SRT. The microbial community appears to be responsible for such MBR behaviors. Several bacterial species belonging to the biofilm-forming group are dominant after disturbance, resulting in substantive membrane fouling. However, the balance between the bacterial species plays a key role in MBR fouling propensity when stabilized. Koflera flava becomes dominant with QQ, leading to reduced membrane fouling. QQ makes the MBR microbial community more diverse, while lowering its richness. QQ with long SRT would be a favorable operational strategy for effective MBR fouling control.
Cloud icing by mineral dust and impacts to aviation safety
Authors: Nickovic Slobodan , Cvetkovic Bojan , Petković Slavko , Amiridis Vassilis , Pejanović Goran , Solomos Stavros , Marinou Eleni , Nikolic Jugoslav 
Published: March 2021

AbstractIce particles in high-altitude cold clouds can obstruct aircraft functioning. Over the last 20 years, there have been more than 150 recorded cases with engine power-loss and damage caused by tiny cloud ice crystals, which are difficult to detect with aircraft radars. Herein, we examine two aircraft accidents for which icing linked to convective weather conditions has been officially reported as the most likely reason for catastrophic consequences. We analyze whether desert mineral dust, known to be very efficient ice nuclei and present along both aircraft routes, could further augment the icing process. Using numerical simulations performed by a coupled atmosphere-dust model with an included parameterization for ice nucleation triggered by dust aerosols, we show that the predicted ice particle number sharply increases at approximate locations and times of accidents where desert dust was brought by convective circulation to the upper troposphere. We propose a new icing parameter which, unlike existing icing indices, for the first time includes in its calculation the predicted dust concentration. This study opens up the opportunity to use integrated atmospheric-dust forecasts as warnings for ice formation enhanced by mineral dust presence.
Compatibility between an overnight fasting and random cholesterol tests in Asians
Authors: Phoon Ian Kwong Yun , Koh Yi Ling Eileen , Guo Xiaoxuan , Usha Sankari , Tan Ngiap Chuan 
Published: March 2021

AbstractRecent Western guidelines recommend non-fasting lipid profiles to manage dyslipidaemia. We explored its applicability to an Asian population. We determined the differences between an overnight fasting and non-fasting cholesterol profiles of patients with type-2 diabetes mellitus (T2DM) in Singapore. We studied 470 multi-ethnic Asian adult patients with T2DM and dyslipidaemia from 2 primary care clinics in Singapore. Non-fasting blood specimens were collected within 6 h after their last meal and within 14 days of a fasting specimen. The intraclass correlation coefficient (ICC) was used to compare the intraindividual lipid profiles. An ICC value > 0.75 implies good correlation. The mean age and T2DM duration of the study population were 62.5 years and 9.8 years respectively. Their mean non-fasting period was 2.46 h. The mean differences between non-fasting and fasting total cholesterol (TC), high-density lipoprotein (HDL-C), triglyceride (TG), low-density lipoprotein (LDL-C), and non HDL-C were + 0.04 mmol/l, − 0.001 mmol/l, + 0.48 mmol/l, − 0.15 mmol/l, and − 0.05 mmol/l respectively. The ICC (95% CI) for TC, HDL-C, TG, LDL-C and non-HDL-C were 0.820 (0.788–0.847), 0.873 (0.850–0.893), 0.579 (0.516–0.636), 0.764 (0.723–0.799), and 0.825 (0.794–0.852) respectively. The fasting and non-fasting lipid profiles were similar in our local Asian patients with T2DM taking statin. Their non-fasting lipid profile can be used to assess their cholesterol treatment status.
Pretreatment PSA levels affects the completion rate of Ra-223 treatment
Authors: Utsumi Nobuko , Kurosaki Hiromasa , Miura Kosei , Kitoh Hiroki , Akakura Koichiro 
Published: March 2021

AbstractThe aim of this study was to review our initial experience of using radium 223 (Ra-223) for metastatic castration-resistant prostate cancer (CRPC) and to evaluate whether pretreatment PSA levels correlate with completion of Ra-223 treatment. In addition, we examined change ratios of PSA, ALP and BAP after the third administration to evaluate the correlation of these change ratios with completion of the subsequent Ra-223 treatment. Forty patients were enrolled in this retrospective study. Ra-223 treatment was considered completed in patients who received five or six administrations. Patient backgrounds and changes in biomarkers were compared between patient groups (complete vs. incomplete Ra-223 treatment). PSA levels before treatment were significantly lower in the complete compared with the incomplete group (cutoff value; 21.7). ALP and BAP levels had decreased after the third administration in the complete group, compared with baseline levels, while levels in the incomplete group had increased. Significant difference was seen in ALP levels, while was not seen in BAP levels between the two groups. Ra-223 treatment should be considered for CRPC with low PSA levels. Changes in PSA and ALP during Ra-223 treatment might provide markers to identify patients likely to complete Ra-223 treatment, with implications for prognosis.