bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pear polyphenol oxidase enhances theaflavins in green tea soup through the enzymatic oxidation reaction
Authors: Li Yan , Bai Ruoxue , Wang Jintao , Li Yonglin , Hu Yongdan , Ren Dabing , Dong WenJiang , Yi Lunzhao 
Published: October 2022

AbstractPolyphenol oxidase (PPO) is a necessary medium for converting catechins into theaflavins in tea. This study aimed to provide an efficient and cost‐effective method for the purpose of developing a tea beverage rich in four main theaflavins (TFs) by optimizing the key factors affecting the enzymatic oxidation reaction to produce TFs. Autumn green tea (AT) soup was mixed with pear PPO crude enzyme solution and then reacted for different time at varying reaction temperatures, pH, ratios of tea soup to crude enzyme solution, and ratios of tea to water. The content of TFs in tea beverage was monitored by UPLC‐Q‐Orbitrap‐MS/MS to select the optimal process parameters to produce the maximum TFs. The TFs content after the reaction increased 968.49 times compared with that before the reaction. The results showed that the use of the enzymatic oxidation reaction of pear PPO crude enzyme solution to improve the TFs in AT soup was efficient. This method helped regulate the strong bitter and astringent taste sensation in AT, and it is unnecessary to purify the PPO enzyme source. This method is expected to be a breakthrough to use AT to produce high TFs tea beverages in a cost‐effective way with high value.
Exercise‐induced changes in pulmonary artery wedge pressure in adults post‐Fontan versus heart failure with preserved ejection fraction and non‐cardiac dyspnoea
Authors: Miranda William R. , Borlaug Barry A. , Jain C. Charles , Anderson Jason H. , Hagler Donald J. , Connolly Heidi M. , Egbe Alexander C. 
Published: October 2022

AbstractAimsDespite their universal predisposition, diagnosing diastolic dysfunction in patients post‐Fontan palliation is challenging. Our aim was to compare exercise haemodynamics between adults post‐Fontan and patients with heart failure with preserved ejection fraction (HFpEF) and non‐cardiac dyspnoea (NCD).Methods and resultsTwenty‐four adults (age ≥18 years) post‐Fontan palliation with resting and exercise pulmonary artery wedge pressure (PAWP) measured during supine biking were identified. Forty‐eight patients with HFpEF and 48 with NCD diagnosed at catheterization were selected for comparison. Mean age for Fontan patients was 30.3 ± 7.5 years; median ventricular ejection fraction was 52.5% (45–55.8), being <50% in 37.5%. Resting PAWP among Fontan patients was 10.2 ± 3.5 mmHg (>12 mmHg in 25%); PAWP was lower in Fontan patients than in HFpEF but higher than NCD. During exercise, PAWP was lower in the Fontan group than HFpEF (22.5 mmHg [19.3–28] vs. 28.2 ± 6.3; p = 0.0006) but higher than NCD (11.2 ± 4.2, p ≤ 0.0001). However, there were no differences in ΔPAWP/ΔQs between Fontan and HFpEF patients (4.0 [2.1–7.3] vs. 2.7 [1.6–4.4]; p = 0.10) with the ratio being higher post‐Fontan than in NCD (0.6 [0.2–1.2]; p < 0.0001). ΔPAWP/ΔQs remained similar between HFpEF and Fontan patients even when those with ejection fraction <50% were excluded (2.7 [1.6–4.4] vs. 2.7 [1.0–5.8]; p = 0.97).ConclusionThere were no differences in ΔPAWP/ΔQs ratios between post‐Fontan and HFpEF patients, supporting markedly abnormal single ventricle compliance despite lower resting and exercise PAWP. Therefore, exercise invasive haemodynamics may represent a novel tool for the diagnosis of diastolic dysfunction in Fontan patients.
Effects of empagliflozin on cardiovascular and renal outcomes in heart failure with reduced ejection fraction according to age: a secondary analysis of EMPEROR‐Reduced
Authors: Filippatos Gerasimos , Anker Stefan D. , Butler Javed , Farmakis Dimitrios , Ferreira João Pedro , Gollop Nicholas D. , Brueckmann Martina , Iwata Tomoko , Pocock Stuart , Zannad Faiez , Packer Milton ,   the EMPEROR‐Reduced Trial Committees and Investigators
Published: October 2022

AbstractAimsEmpagliflozin improves cardiovascular and renal outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but its efficacy and safety across patient's age is not well established.Methods and resultsWe assessed the effects of empagliflozin (10 mg daily) versus placebo, on top of standard HF therapy, in symptomatic HFrEF patients with a left ventricular ejection fraction ≤40% and increased natriuretic peptides stratified by age (<65, 65–74, ≥75 years). The primary endpoint was a composite of cardiovascular death or HF hospitalization. Key secondary endpoints included first and recurrent HF hospitalizations and slope of change in estimated glomerular filtration rate (eGFR); the latter was supported by an analysis of a renal composite endpoint (chronic dialysis or renal transplantation or profound and sustained reduction in eGFR). Of 3730 patients, 38% were <65 years, 35% were 65–74 years and 27% were ≥75 years. Compared with placebo, empagliflozin reduced the primary endpoint consistently across the three age groups (hazard ratio 0.71 [95% confidence interval 0.57–0.89] for <65 years, 0.72 [0.57–0.93] for 65–74 years, 0.86 [0.67–1.10] for ≥75 years, interaction p‐trend test = 0.24). The effects of empagliflozin were also consistent across age groups for key secondary endpoints of first and recurrent HF hospitalization (p‐trend = 0.30), the rate of decline in eGFR (p‐trend = 0.78) and the renal composite (p‐trend = 0.94). Adverse events (AEs), serious AEs and AEs leading to drug discontinuation increased with age in both treatment arms, but empagliflozin did not increase their incidence over placebo within each age group.ConclusionThe efficacy and safety of empagliflozin in improving cardiovascular and renal outcomes in HFrEF was consistent across the spectrum of age, including older patients (aged ≥75).
Experimental and Theoretical Evaluation of Four NLO‐Active Divalent Transition‐Metal Complexes Supported by an Enantiomerically Pure Tetradentate Schiff Base Ligand
Authors: Celedón Salvador , Hamon Paul , Artigas Vania , Fuentealba Mauricio , Kahlal Samia , Ledoux‐Rak Isabelle , Carrillo David , Saillard Jean‐Yves , Manzur Carolina , Hamon Jean‐René 
Published: October 2022

AbstractThis paper reports on a series of five chiral Schiff base push‐pull compounds derived from enantiomerically pure (1R,2R)‐(−)‐1,2‐diaminocyclohexane. The NiII, CuII, ZnII and PdII complexes supported by a ferrocene‐containing unsymmetrically‐substituted N2O2 quadridentate Schiff base ligand were prepared via template reactions and isolated in 74–87 % yields. A combination of EA, IR, UV/vis and 1H/13C{1H} NMR spectroscopy, HRMS spectrometry, cyclic voltammetry and single‐crystal X‐ray analysis (for the proligand 2 and its NiII derivative 3), together with computational methods (DFT and TD‐DFT) was used to fully characterize and study the properties of all products. Both 2 and 3 crystallize in the orthorhombic non‐centrosymmetric space group P212121, with two (R,R)‐(−)‐chiral carbon atoms in their structure. Second‐order nonlinear polarizabilities β have been measured by using Harmonic Light Scattering at 1.91 μm, with the Pd(II) species showing the higher NLO response of 460×10−30 esu.
Asymmetric Pd(II)‐Catalyzed C−O, C−N, C−C Bond Formation Using Alkenes as Substrates: Insight into Recent Enantioselective Developments
Authors: Giofrè Sabrina , Molteni Letizia , Beccalli Egle M. 
Published: October 2022

AbstractThis Review summarizes the advances in the catalytic enantioselective mono‐ and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved.
Electrochemical Rearrangement of Indoles to Spirooxindoles in Continuous Flow
Authors: Liu Dingjin , Xu Hai‐Chao 
Published: October 2022

AbstractThe oxidative rearrangement of indoles induced by various chemical oxidants is a frequently employed method for the construction of spirooxindole structures. Herein, we report an electrochemical method for the oxidative rearrangement of indoles to spirooxindoles in continuous flow. The electrochemical reactions require no chemical oxidants and can be scaled up easily without need for re‐optimization of reaction conditions by passing more starting material through parallel reactors.
Decision‐making traps behind low regional absorption of Cohesion Policy funds
Authors: Cunico Giovanni , Aivazidou Eirini , Mollona Edoardo 
Published: October 2022

AbstractWithin European Cohesion Policy, some regions manifest chronic problems with absorbing structural funds, probably due to inadequate administrative capacity. Despite the continuous assistance to improve capacity and the accumulation of learning and experience, poor performances still persist in some territories, rendering the initial explanation partial. By collecting (reports' analysis and field research), consolidating (grounded theory), and mapping (system dynamics) two Italian regions with contrasting absorption performance, this study investigates how regional authorities may be trapped in systemic decision‐making structures that prioritize short‐term outcomes perpetuating low absorption rates. Within a multilevel‐governance context, we suggest that these decision‐making traps stem from the discrepancy between European and local policy‐makers' mental models; although European policies aim to promote timely absorption, sometimes they fail to acknowledge local authorities' actual agenda and may unintentionally prompt regions to overemphasize short term funds' expenditure instead of improving administrative capacity in the long term.
Berechnung der Versagenswahrscheinlichkeit von Böschungen unter Berücksichtigung der Bodenvariabilität
Authors: Buschendorf Phil , Schorr Joshua , Pena Olarte Andres Alfonso 
Published: October 2022

AbstractThe soil is a heterogeneous three‐phase system with varying mechanical properties. It is usually abstracted to a subsurface model with homogeneous layers. The basic data for this model are individual probings/boreholes. Assumptions are made to describe the structure of the unsampled areas and the general scatter of the soil properties within the layers is not taken into account. This results in an approximation of the real conditions, which leads to uncertainties. In order to compensate this, the soil variability can be covered by a number of different parameter combinations. In the field of geotechnical engineering, this approach is called the Random Finite Element Method (RFEM).In terms of a master thesis, the technical implementation of such method has been investigated. It was used for the stability analysis of a theoretical slope and the results were compared with the Limit Equilibrium Method (LEM) and the Strength Reduction Finite Element Method (SRFEM). The last one was also used to identify the relevant failure criteria for the finite element. By using different meshes of the same slope, their effect on the safety factor was observed.
Practical recommendations for machine learning in underground rock engineering – On algorithm development, data balancing, and input variable selection
Authors: Morgenroth Josephine , Unterlaß Paul J. , Sapronova Alla , Khan Usman T. , Perras Matthew A. , Erharter Georg H. , Marcher Thomas 
Published: October 2022

AbstractResearch has demonstrated that machine learning algorithms (MLAs) are a powerful addition to the rock engineering toolbox, and yet they remain a largely untapped resource in engineering practice. The reluctance to adopt MLAs as part of standard practice is often attributed to the ‘opaque’ nature of the algorithms, the complexity in developing them, and the difficulty in determining how the algorithms use the datasets. This article presents tools and processes for developing MLAs, input selection, and data balancing for practical underground rock engineering. MLAs for classification and regression – two main machine learning applications – are presented in terms of developing MLA to extract information from the dataset to obtain the desired output. Engineering verification metrics are selected based on their suitability for specific output. Methods for input selection and data balancing are discussed with a focus on selecting appropriate input data for the problem without introducing bias or excess complexity. Each tool and process for algorithm development, data preparation, and input selection is illustrated with a case study. This article demonstrates that geotechnical practitioners can extract additional value by applying MLAs to rock engineering problems. Once an understanding of the functions of MLAs is reached, the building blocks and open‐source code are available to be adapted to suit the rock mass behaviour of interest.
Prevalence and predictors of Motoric Cognitive Risk syndrome in a community‐dwelling older Scottish population: A longitudinal observational study
Authors: Mullin Donncha S. , Stirland Lucy E. , Welstead Miles , Russ Tom C. , Luciano Michelle , Muniz‐Terrera Graciela 
Published: October 2022

AbstractObjectivesMotoric Cognitive Risk (MCR) is a gait‐based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia.MethodsIn this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.3 [0.8] years; wave 3) of the Lothian Birth Cohort 1936 (LBC1936) into non‐MCR or MCR groups. We examined their baseline (age 69.5 [0.8] years; wave 1) risk factors for MCR at waves 3, 4, and 5 (6, 9, and 12 years later respectively).ResultsMCR prevalence rate ranged from 5.3% to 5.7% across the three waves. The presence of MCR was associated with older baseline age (6 and 9 years later), lower occupational socioeconomic status (6 years later), and worse scores in a range of tests of executive function (6, 9 and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment, and almost everyone in the MCR group had either Prefrailty or Frailty.ConclusionsThe prevalence of MCR in this Scottish cohort is lower than the pooled global average, possibly reflecting the general good health of the LBC cohort. However, it is higher than the prevalence in two neighbouring countries' cohorts, which may reflect the younger average ages of those cohorts. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status.
Role of sentinel lymph node biopsy for oral squamous cell carcinoma: Current evidence and future challenges
Authors: Jang Sophie S. , Davis Morgan E. , Vera David R. , Lai Stephen Y. , Guo Theresa W. 
Published: October 2022

AbstractSentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2–4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative complications, and advancement in preoperative and intraoperative imaging technology can guide the appropriate application to SLNB in OCSCC. The aim of this review is to discuss the current evidence for SLNB in the treatment of early stage OCSCC, imaging technologies that support SLNB procedures, and studies that are currently underway.
Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB‐506 from Phase 1 studies in healthy subjects and those with hepatitis B
Authors: Yuen Man‐Fung , Berliba Elina , Sukeepaisarnjaroen Wattana , Ahn Sang Hoon , Tanwandee Tawesak , Lim Young‐Suk , Kim Yoon Jun , Poovorawan Kittiyod , Tangkijvanich Pisit , Schwabe Christian , Eley Timothy , Brown Joanne , Lee Amy C. H. , Thi Emily P. , Paratala Bhavna , Mani Nagraj , Sofia Michael J. , Picchio Gaston , Sims Karen D. , Gane Edward J. 
Published: October 2022

Abstract
AB‐506 is a potent, pan‐genotypic small molecule capsid inhibitor that inhibits hepatitis B virus (HBV) pregenomic RNA encapsidation. We assessed the safety, pharmacokinetics, and antiviral activity of AB‐506 in two randomized, double‐blinded Phase 1 studies in healthy subjects (HS) and subjects with chronic HBV infection (CHB). Single ascending and multiple doses of AB‐506 or placebo (30–1000 mg or 400 mg daily for 10 days) were assessed in HS. AB‐506 or placebo was assessed at either 160 mg or 400 mg daily for 28 days in subjects with CHB. A second follow‐up study examined AB‐506 or placebo at 400 mg daily for 28 days in 14 Caucasian and 14 East‐Asian HS. Twenty‐eight days of AB‐506 at 160 mg and 400 mg produced mean HBV‐DNA declines from baseline of 2.1 log10 IU/ml and 2.8 log10 IU/ml, respectively. Four subjects with CHB (all Asian) had Grade 4 alanine aminotransferase (ALT) elevations (2 at each dose) as HBV DNA was declining; three events led to treatment discontinuation. In the second follow‐up study, 2 Asian HS had serious transaminitis events leading to treatment and study termination. No subjects had bilirubin elevations or signs of hepatic decompensation. Conclusion: AB‐506 demonstrated mean HBV‐DNA declines of >2 log10; however, transient but severe ALT flares were observed in 4 Asian subjects with CHB. In the follow‐up study in HS, 2 additional Asian HS had Grade 4 flares, suggesting that AB‐506 hepatotoxicity contributed to the ALT elevations. The AB‐506 development program was terminated because of these findings.
Zinc fingers and homeoboxes 2 is required for diethylnitrosamine‐induced liver tumor formation in C57BL/6 mice
Authors: Jiang Jieyun , Turpin Courtney , Qiu Guofang (Shirley) , Xu Mei , Lee Eun , Hinds Terry D. , Peterson Martha L. , Spear Brett T. 
Published: October 2022

Abstract
Liver cancer, comprised primarily of hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide and increasing in Western countries. We previously identified the transcription factor zinc fingers and homeoboxes 2 (Zhx2) as a regulator of hepatic gene expression, and many Zhx2 target genes are dysregulated in HCC. Here, we investigate HCC in Zhx2‐deficient mice using the diethylnitrosamine (DEN)–induced liver tumor model. Our study using whole‐body Zhx2 knockout (Zhx2

KO
) mice revealed the complete absence of liver tumors 9 and 10 months after DEN exposure. Analysis soon after DEN treatment showed no differences in expression of the DEN bioactivating enzyme cytochrome P450 2E1 (CYP2E1) and DNA polymerase delta 2, or in the numbers of phosphorylated histone variant H2AX foci between Zhx2

KO
and wild‐type (Zhx2

wt
) mice. The absence of Zhx2, therefore, did not alter DEN bioactivation or DNA damage. Zhx2

KO
livers showed fewer positive foci for Ki67 staining and reduced interleukin‐6 and AKT serine/threonine kinase 2 expression compared with Zhx2

wt
livers, suggesting that Zhx2 loss reduces liver cell proliferation and may account for reduced tumor formation. Tumors were reduced but not absent in DEN‐treated liver‐specific Zhx2 knockout mice, suggesting that Zhx2 acts in both hepatocytes and nonparenchymal cells to inhibit tumor formation. Analysis of data from the Cancer Genome Atlas and Clinical Proteomic Tumor Consortium indicated that ZHX2 messenger RNA and protein levels were significantly higher in patients with HCC and associated with clinical pathological parameters. Conclusion: In contrast to previous studies in human hepatoma cell lines and other HCC mouse models showing that Zhx2 acts as a tumor suppressor, our data indicate that Zhx2 acts as an oncogene in the DEN‐induced HCC model and is consistent with the higher ZHX2 expression in patients with HCC.
Autologous hematopoietic cell transplantation versus whole‐brain radiotherapy consolidation in primary central nervous system lymphoma: A systematic review and meta‐analysis
Authors: Epperla Narendranath , Reljic Tea , Chowdhury Sayan Mullick , Ferreri Andrés J. M. , Kumar Ambuj , Hamadani Mehdi 
Published: October 2022

AbstractThe management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high‐dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto‐HCT] vs. whole‐brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta‐analysis of all randomized controlled trials that compared auto‐HCT versus WBRT consolidation for patients with PCNSL after first‐line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression‐free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment‐related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single‐arm studies that incorporated auto‐HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95–2.36), PFS (HR = 0.99; 95% CI = 0.44–2.22), ORR (RR = 1.48; 95% CI = 0.90–2.44), CR rate (RR = 1.21; 95% CI = 0.90–1.63), relapse rate (RR = 0.46; 95% CI = 0.05–4.28), and TRM (RR = 5.67; 95% CI = 1.01–31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta‐analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto‐HCT. We found 9 single‐arm phase II studies that reported data on outcomes associated with either auto‐HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto‐HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%–17%) for those receiving auto‐HCT and there was no heterogeneity between studies (I2 = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%–78%) for those receiving WBRT and there was high heterogeneity between studies (I2 = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto‐HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto‐HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co‐morbidities.