bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antioxidative Characteristics and Sensory Acceptability of Bread Substituted with Purple Yam (Dioscorea alata L.)
Authors: Tamaroh Siti , Sudrajat Ajat 
Published: July 2021

In this study, plain bread was made by substituting wheat flour with purple yam flour (Dioscorea alata, L). The addition of 0, 10, 15, 20, and 30% purple yam flour aims to increase the functional value of plain bread as a source of natural antioxidants. The bread produced with two baking temperatures (170°C and 180°C) was tested for anthocyanin levels, total phenol, antioxidant activity (DPPH free radical scavenging), volume expansion, color, and preference test. The results showed that the temperatures of the bread baking did not affect anthocyanin levels, total phenol, antioxidant activity, volume expansion, and bread color (

p
>
0.05

). The substitution of purple yam flour had a significant effect on anthocyanin levels, total phenol, antioxidant activity, volume, and bread color (

p
<
0.05

). The levels of anthocyanins, total phenol, antioxidant activity, and darker color increased with the addition of purple yam flower whereas the rate of expansion reduced. However, the addition of purple yam flour did not affect the level of preference for the bread produced. Purple yam flour can be added to the manufacture of bread made from wheat flour as much as 30% with a baking temperature of 180°C. The resulting bread contained total anthocyanins 54.62 mg/100 g db, total phenol 391.14 mg EAG/100 g db, antioxidant activity 48.53% and volume expansion 64.85%, color

L

∗

=
53.06

,

a

∗

=
6.52

,

b

∗

=
13.32

,

C
=
14.87

,

H
=
64.06

, and

sensory

score
=
3.24

(preferred).
Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Authors: Chua Khi Pin , Teng Yvonne H.F. , Tan Aaron C. , Takano Angela , Alvarez Jacob J.S. , Nahar Rahul , Rohatgi Neha , Lai Gillianne G.Y. , Aung Zaw Win , Yeong Joe P.S. , Lim Kiat Hon , Naeini Marjan Mojtabavi , Kassam Irfahan , Jain Amit , Tan Wan Ling , Gogna Apoorva , Too Chow Wei , Kanesvaran Ravindran , Ng Quan Sing , Ang Mei Kim , Rajasekaran Tanujaa , Anantham Devanand , Phua Ghee Chee , Tan Bien Soo , Lee Yin Yeng , Wang Lanying , Teo Audrey S.M. , Khng Alexis Jiaying , Lim Ming Jie , Suteja Lisda , Toh Chee Keong , Lim Wan-Teck , Iyer N. Gopalakrishna , Tam Wai Leong , Tan Eng-Huat , Zhai Weiwei , Hillmer Axel M. , Skanderup Anders J. , Tan Daniel S.W. 
Published: July 2021

Abstract

Purpose:
Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFRT790M-negative resistance.

Experimental Design:
We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M−) disease.

Results:
Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M− tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M− tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M− and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients.

Conclusions:
Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.
MRN Complex and Cancer Risk: Old Bottles, New Wine
Authors: Elkholi Islam E. , Foulkes William D. , Rivera Barbara 
Published: July 2021

Abstract
The MRN complex, composed of MRE11A, RAD50, and NBN, mediates vital molecular functions to maintain genomic stability and hence protect against related disorders. Germline mutations in the MRN genes predispose to three different syndromes: ataxia-telangiectasia-like disorder (MRE11A deficiency), Nijmegen breakage syndrome (NBS; NBN deficiency), and NBS-like disorder (RAD50 deficiency). The potential cancer component of these syndromes in addition to the close physical and functional proximity of the MRN complex to BRCA1 has promoted the MRN genes as candidate risk genes for developing breast cancer. This notion has been challenged by independent large-scale population-based studies. Despite having their two-decade old candidacy as breast cancer genes close to being refuted, it has recently been reported that the MRN genes rise to have potential new roles in clonal hematopoiesis. In this article, we discuss the history and current status of MRN genes' clinical utility in breast cancer and then focus on their recently uncovered and less understood roles in clonal hematopoiesis that likely predispose to health-related disorders such as hematologic malignancies and/or cardiovascular morbid events.
Efficacy, Safety, and Biomarker Analysis of Combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal Mesothelioma
Authors: Raghav Kanwal , Liu Suyu , Overman Michael J. , Willett Anneleis F. , Knafl Mark , Fu Szu-Chin , Malpica Anais , Prasad Seema , Royal Richard E. , Scally Christopher P. , Mansfield Paul F. , Wistuba Ignacio I. , Futreal Andrew P. , Maru Dipen M. , Solis Soto Luisa M. , Parra Cuentas Edwin R. , Chen Honglei , Villalobos Pamela , Verma Anuj , Mahvash Armeen , Hwu Patrick , Cortazar Patricia , McKenna Edward , Yun Cindy , Dervin Shannon , Schulze Katja , Darbonne Walter C. , Morani Ajaykumar C. , Kopetz Scott , Fournier Keith F. , Woodman Scott E. , Yao James C. , Varadhachary Gauri R. , Halperin Daniel M. 
Published: July 2021

Abstract

Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum–pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTv1.1 by independent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1–64.0] with median response duration of 12.8 months. Six (75%) responses lasted for &gt;10 months. Progression-free and overall survival at one year were 61% (95% CI, 35–80) and 85% (95% CI, 60–95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial–mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease.

Significance:
Efficacy of atezolizumab and bevacizumab vis-à-vis response rates and survival in advanced peritoneal mesothelioma previously treated with chemotherapy surpassed outcomes expected with conventional therapies. Biomarker analyses uncovered epithelial–mesenchymal transition phenotype as an important resistance mechanism and showcase the value and feasibility of performing translationally driven clinical trials in rare tumors.
See related commentary by Aldea et al., p. 2674.
This article is highlighted in the In This Issue feature, p. 2659
Modulation of Sirt1 and FoxO1 on Hypothalamic Leptin‐Mediated Sympathetic Activation and Inflammation in Diet‐Induced Obese Rats
Authors: Liu Xuefei , Zheng Hong 
Published: July 2021

Background
Hypothalamic leptin‐mediated signaling contributes to the exaggerated sympatho‐excitation and increased blood pressure in obesity‐associated hypertension. The aim of the study was to investigate the roles of energy‐sensing enzyme sirtuin1 (Sirt1) and forkhead box protein O1 (FoxO1) on the hypothalamic leptin‐mediated high sympathetic nerve activity and inflammation in obesity.

Methods and Results
Sprague Dawley rats were fed with high‐fat diet (HFD) for 12 weeks. In vivo, the potential of Srit1 and FoxO1 in the sympathetic effects of leptin was investigated via siRNA injection to knockdown Sirt1 or FoxO1 gene in the arcuate nucleus (ARCN) of hypothalamus in rats. In vitro, the effects of Sirt1 or FoxO1 on leptin‐mediated inflammation were observed in proopiomelanocortin (POMC) and microglial cells. Knockdown Sirt1 by siRNA significantly reduced the renal sympathetic nerve activity (RSNA) and blood pressure responses to leptin injection in the ARCN in the HFD rats. Conversely, knockdown FoxO1 significantly enhanced the RSNA and blood pressure responses to leptin injection in the HFD rats. Knockdown Sirt1 reduced the levels of pro‐inflammatory cytokines interleukin 6 (IL‐6), tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), C1q/TNF‐related protein‐1 (CTRP1), and immune cell infiltration in the ARCN in the HFD rats. Knockdown FoxO1 significantly increased the level of IL‐6 in the ARCN of HFD rats. In cultured hypothalamic POMC and microglial cells, knockdown Sirt1 significantly reduced leptin‐induced IL‐6 expression, affected the levels of AMP‐activated protein kinase (AMPK) and serine/threonine‐specific protein kinase (Akt). Knockdown FoxO1 significantly increased leptin‐induced IL‐6 in both POMC cells and microglial cells.

Conclusions
These data suggest that both Sirt1 and FoxO1 are the key modulators of leptin signaling in the hypothalamus contributed to the over sympathetic activation and inflammation in obesity.
Predictors of Permanent Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement ‐ A Systematic Review and Meta‐Analysis
Authors: Ullah Waqas , Zahid Salman , Zaidi Syeda Ramsha , Sarvepalli Deepika , Haq Shujaul , Roomi Sohaib , Mukhtar Maryam , Khan Muhammad Atif , Gowda Smitha Narayana , Ruggiero Nicholas , Vishnevsky Alec , Fischman David L. 
Published: July 2021

Background
As transcatheter aortic valve replacement (TAVR) technology expands to healthy and lower‐risk populations, the burden and predictors of procedure‐related complications including the need for permanent pacemaker (PPM) implantation needs to be identified.

Methods and Results
Digital databases were systematically searched to identify studies reporting the incidence of PPM implantation after TAVR. A random‐ and fixed‐effects model was used to calculate unadjusted odds ratios (OR) for all predictors. A total of 78 studies, recruiting 31 261 patients were included in the final analysis. Overall, 6212 patients required a PPM, with a mean of 18.9% PPM per study and net rate ranging from 0.16% to 51%. The pooled estimates on a random‐effects model indicated significantly higher odds of post‐TAVR PPM implantation for men (OR, 1.16; 95% CI, 1.04–1.28); for patients with baseline mobitz type‐1 second‐degree atrioventricular block (OR, 3.13; 95% CI, 1.64–5.93), left anterior hemiblock (OR, 1.43; 95% CI, 1.09–1.86), bifascicular block (OR, 2.59; 95% CI, 1.52–4.42), right bundle‐branch block (OR, 2.48; 95% CI, 2.17–2.83), and for periprocedural atriorventricular block (OR, 4.17; 95% CI, 2.69–6.46). The mechanically expandable valves had 1.44 (95% CI, 1.18–1.76), while self‐expandable valves had 1.93 (95% CI, 1.42–2.63) fold higher odds of PPM requirement compared with self‐expandable and balloon‐expandable valves, respectively.

Conclusions
Male sex, baseline atrioventricular conduction delays, intraprocedural atrioventricular block, and use of mechanically expandable and self‐expanding prosthesis served as positive predictors of PPM implantation in patients undergoing TAVR.
Risk of Physical Injury for Dispatched Citizen Responders to Out‐of‐Hospital Cardiac Arrest
Authors: Andelius Linn , Malta Hansen Carolina , Tofte Gregers Mads C. , Kragh Astrid M. Rolin , Køber Lars , Gislason Gunnar H. , Kjær Ersbøll Annette , Torp‐Pedersen Christian , Folke Fredrik 
Published: July 2021

Background
Citizen responder programs are implemented worldwide to dispatch volunteer citizens to participate in out‐of‐hospital cardiac arrest resuscitation. However, the risk of injuries in relation to activation is largely unknown. We aimed to assess the risk of physical injury for dispatched citizen responders.

Methods and Results
Since September 2017, citizen responders have been activated through a smartphone application when located close to a suspected cardiac arrest in the Capital Region of Denmark. A survey was sent to all activated citizen responders, including a specific question about risk of acquiring an injury during activation. We included all surveys from September 1, 2017, to May 15, 2020. From May 15, 2019, to May 15, 2020, we followed up on all survey nonresponders by phone call, e‐mail, or text messages to examine if nonresponders were at higher risk of severe or fatal injuries. In 1665 suspected out‐of‐hospital cardiac arrests, 9574 citizen responders were dispatched and 76.6% (7334) answered the question regarding physical injury. No injury was reported by 99.3% (7281) of the responders. Being at risk of physical injury was reported by 0.3% (24), whereas 0.4% (26) reported an injury (25 minor injuries and 1 severe injury [ankle fracture]). When following up on nonresponders (2472), we reached 99.1% (2449). No one reported acquired injuries, and only 1 reported being at risk of injury.

Conclusions
We found low risk of physical injury reported by volunteer citizen responders dispatched to out‐of‐hospital cardiac arrest. Risk of injury should be considered and monitored as a safety measure in citizen responder programs.
The Two-Margin Problem in Insurance Markets
Authors: Geruso Michael , Layton Timothy J. , McCormack Grace , Shepard Mark 
Published: July 2021

AbstractInsurance markets often feature consumer sorting along both an extensive margin (whether to buy) and an intensive margin (which plan to buy). We present a new graphical theoretical framework that extends a workhorse model to incorporate both selection margins simultaneously. A key insight from our framework is that policies aimed at addressing one margin of selection often involve an economically meaningful trade-off on the other margin in terms of prices, enrollment, and welfare. Using data from Massachusetts, we illustrate these trade-offs in an empirical sufficient statistics approach that is tightly linked to the graphical framework we develop.
The Four-Equation New Keynesian Model
Authors: Sims Eric , Wu Jing Cynthia , Zhang Ji 
Published: July 2021

Abstract
This paper develops a New Keynesian model featuring financial intermediation, short- and long-term bonds, credit shocks, and scope for unconventional monetary policy. The log-linearized model reduces to four equations: Phillips and IS curves, as well as policy rules for the short-term interest rate and the central bank's long-bond portfolio (QE). Credit shocks and QE appear in both the IS and Phillips curves. In equilibrium, optimal monetary policy entails adjusting the short-term interest rate to offset natural rate shocks but using QE to offset credit market disruptions. Use of QE significantly mitigates the costs of a binding zero lower bound.
The Problem of Diagnosing Jet Waveguidability in the Presence of Large-Amplitude Eddies
Authors: Wirth Volkmar , Polster Christopher 
Published: July 2021

AbstractThe waveguidability of an upper-tropospheric zonal jet quantifies its propensity to duct Rossby waves in the zonal direction. This property has played a central role in previous attempts to explain large wave amplitudes and the subsequent occurrence of extreme weather. In these studies, waveguidability was diagnosed with the help of ray tracing arguments using the zonal average of the observed flow as the relevant background state. Here, it is argued that this method is problematic both conceptually and mathematically. The issue is investigated in the framework of the nondivergent barotropic model. This model allows the straightforward computation of an alternative “zonalized” background state, which is obtained through conservative symmetrization of potential vorticity contours and that is argued to be superior to the zonal average. Using an idealized prototypical flow configuration with large-amplitude eddies, it is shown that the two different choices for the background state yield very different results; in particular, the zonal-mean background state diagnoses a zonal waveguide, while the zonalized background state does not. This result suggests that the existence of a waveguide in the zonal-mean background state is a consequence of, rather than a precondition for, large wave amplitudes, and it would mean that the direction of causality is opposite to the usual argument. The analysis is applied to two heatwave episodes from summer 2003 and 2010, yielding essentially the same result. It is concluded that previous arguments about the role of waveguidability for extreme weather need to be carefully reevaluated to prevent misinterpretation in the future.
Early Peak of Latent Heat Fluxes Regulates Diurnal Temperature Range in Montane Cloud Forests
Authors: Gu Rong-Yu , Lo Min-Hui , Liao Chi-Ya , Jang Yi-Shin , Juang Jehn-Yih , Huang Cho-Ying , Chang Shih-Chieh , Hsieh Cheng-I , Chen Yi-Ying , Chu Housen , Chang Kuang-Yu 
Published: July 2021

AbstractHydro-climate in the montane cloud forest (MCF) regions is unique for its frequent fog occurrence and abundant water interception by tree canopies. Latent heat (LH) flux, the energy flux associated with evapotranspiration (ET), plays an essential role in modulating energy and hydrological cycles. However, how LH flux is partitioned between transpiration (stomatal evaporation) and evaporation (non-stomatal evaporation), and how it impacts local hydro-climate remain unclear. In this study, we investigate how fog modulates the energy and hydrological cycles of MCF by using a combination of in-situ observations and model simulations. We compare LH flux and associated micrometeorological conditions at two eddy-covariance sites—Chi-Lan (CL), a MCF, and Lien-Hua-Chih (LHC), a non-cloud forest in Taiwan. The comparison between the two sites reveals an asymmetric LH flux with an early peak at 9:00 in CL as opposed to LHC, where LH flux peaks at noon. The early peak of LH flux and its evaporative cooling dampen the increase in near-surface temperature during the morning hours in CL. The relatively small diurnal temperature range, abundant moisture brought by the valley wind, and local ET result in frequent afternoon fog formation. Fog water is then intercepted by the canopy, sustaining moist conditions throughout the night. To further illustrate this hydrological feedback, we used a land surface model to simulate how varying canopy water interception can affect surface energy and moisture budgets. Our study highlights the unique hydro-climatological cycle in MCF and, specifically, the inseparable relationship between the canopy and near-surface meteorology during the diurnal cycle.
Relationship of Convection Initiation and Subsequent Storm Strength to Ensemble Simulated Environmental Conditions during IOP3b of VORTEX Southeast 2017
Authors: Trier Stanley B. , Romine Glen S. , Ahijevych David A. , Sobash Ryan A. , Chasteen Manda B. 
Published: July 2021

AbstractA 50-member convection-allowing ensemble was used to examine environmental factors influencing afternoon convection initiation (CI) and subsequent severe weather on 5 April 2017 during intensive observing period (IOP) 3b of the Verification of the Origins of Rotation in Tornadoes Experiment in the Southeast (VORTEX-SE). This case produced several weak tornadoes (rated EF1 or less), and numerous reports of significant hail (diameter ≥ 2 in.; ≥~5 cm), ahead of an eastward-moving surface cold front over eastern Alabama and southern Tennessee. Both observed and simulated CI was facilitated by mesoscale lower-tropospheric ascent maximized several tens of kilometers ahead of the cold-frontal position, and the simulated mesoscale ascent was linked to surface frontogenesis in the ensemble mean. Simulated maximum 2–5 km AGL updraft helicity (UHmax) was used as a proxy for severe-weather-producing mesocyclones, and considerable variability in UHmax occurred among the ensemble members. Ensemble members with UHmax > 100 m2 s−2 had stronger mesoscale ascent than in members with UHmax < 75 m2 s−2, which facilitated timelier CI by producing greater adiabatic cooling and moisture increases above the PBL. After CI, storms in the larger UHmax members moved northeastward toward a mesoscale region with larger convective available potential energy (CAPE) than in smaller UHmax members. The CAPE differences among members were influenced by differences in the location of an antecedent mesoscale convective system, which had a thermodynamically stabilizing influence on the environment toward which storms were moving. Despite providing good overall guidance, the model ensemble overpredicted severe weather likelihoods in northeastern Alabama, where comparisons with VORTEX-SE soundings revealed a positive CAPE bias.
Farmers’ perception, adaptation to groundwater salinity, and climate change vulnerability: insights from North India
Authors: Mitra Susmita , Mehta Pradeep K. , Mishra Sudipta Kumar 
Published: July 2021

AbstractGroundwater salinity, caused by over-extraction and aggravated by climate change, negatively affects crop productivity and threatens global food security. Poor farmers are vulnerable due to low adaptive capacity. A better understanding of their perceptions and adaptation is important to inform policies for successful adaptation. This paper represents an important study by exploring the same in Mewat, a salinity-affected socioeconomically backward district of northern India. The study uses a mixed-method approach with both secondary data and a primary survey of 250 farmers. A large number of farmers perceived negative impacts on water, crop, income, and assets; and adapt in various ways like water management, crop, and land management, livelihood diversification, and shift towards surface water irrigation. Perceived impacts differed between richer and poorer farmers, whereas adaptation measures varied across the educational, social, and economic backgrounds of farmers. Lack of awareness, education, skill development, and livelihood-opportunities are found to be hindrances, whereas institutional and infrastructural support as facilitators of adaptation. Comparing the findings with global experiences we argued that developed countries intervene more in the policy level and infrastructure, whereas in developing countries, adaptation strategies are local, context-specific, and low-cost. The insights from our study will be useful for intervention in Mewat and similar areas across the developing world. We further argue that farmers take adaptation decisions based on perceived impacts and cost-benefit analysis. Therefore, future research work on quantifying the negative impacts and cost-benefit analysis of various adaptation measures will be useful to ensure successful adaptation in the region and beyond.