bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing Agriculture‐Related Characteristics of Flash and Normal Drought Reveals Heterogeneous Crop Response
Authors: Ho Sarah , Buras Allan , Tuo Ye 
Published: November 2023

AbstractDespite rapid progress in the burgeoning field of flash drought research, few studies directly compare the differences in characteristics between flash drought (commonly understood as quick, rapid‐onset drought) and drought traditionally defined as slow‐moving (henceforth normal drought), particularly over agricultural regions where drought effects may be economically the most disastrous. In this study, flash and normal drought events are identified using reanalysis of soil moisture in the data‐rich agricultural region of the California Central Valley for investigation of characteristics related to agriculture. In particular, we investigate the relative duration of pixels in drought events, the correlation of drought intensity with vegetation condition, the impact of aridity on vegetation response and drought, and the differences in the different characteristics between rainfed and irrigated agriculture. Overall, we found considerable differences between flash and normal drought, particularly in their spatial distributions and behavior in relation to aridity. Flash droughts even indicate a counterintuitive improvement in vegetation condition in the northern, more humid regions, likely due to the release of growth limiting factors (e.g., below‐optimum temperature and radiation) associated with drought. Results also indicate improvements in vegetation conditions during normal drought for irrigated land over rainfed, highlighting the importance of irrigation as a drought protection strategy in agriculture.
Effective Permeability in Fractured Reservoirs: Discrete Fracture Matrix Simulations and Percolation‐Based Effective‐Medium Approximation
Authors: Agbaje Tolulope Q. , Ghanbarian Behzad , Hyman Jeffrey D. 
Published: November 2023

AbstractFractured reservoirs are complex and multi‐scale systems composed of matrix and fractures. Accordingly, modeling flow in such geological media has been a great challenge. In this study, we investigated the effect of scale as well as matrix and fracture network characteristics on the effective permeability (keff) in matrix‐fracture systems under fully saturated conditions. We generated fracture networks, embedded within a matrix of permeability of 10−18 m2, with fracture lengths followed a truncated power‐law distribution with exponent α = 1.5, 2.0, and 2.5. We set fracture permeability equal to 10−16, 10−14, and 10−12 m2 and numerically simulated fluid flow to determine the keff at six fracture densities for 36 fractured reservoirs. Results showed that the effect of α and scale on the keff became more significant as the contrast between matrix and fracture permeabilities increased. We also fit the percolation‐based effective‐medium approximation (P‐EMA) to the simulations and optimized its two parameters critical fracture density and scaling exponent. Results exhibited that both P‐EMA model parameters were scale‐dependent. Through linear regression analysis, we found that the critical fracture density and scaling exponent were highly correlated to other matrix‐fracture system properties and proposed two regression‐based models evaluated using a new six sets of simulations. Comparing the estimated keff values with the simulated ones demonstrated the reliability and predictability of the P‐EMA. The matrix‐fracture systems studied here were finite in size. We also showed that one may extend results to infinitely large reservoirs using the P‐EMA framework.
Efficacy of an app-based multimodal lifestyle intervention on body weight in persons with obesity: results from a randomized controlled trial
Authors: Gemesi Kathrin , Winkler Stefanie , Schmidt-Tesch Susanne , Schederecker Florian , Hauner Hans , Holzapfel Christina 
Published: November 2023

Abstract
Background
Despite an increasing number of smartphone applications (apps) addressing weight management, data on the effect of app-based multimodal obesity treatment approaches on weight loss is limited. This study aimed to examine the effect of a digital multimodal weight loss intervention program delivered by an app on body weight in persons with obesity.

Methods
For this single-centre randomized controlled study, 168 adults with a body mass index (BMI) between 30.0 and 40.0 kg/m2 without severe comorbidities were recruited in the region of Munich and randomized into two intervention groups. The ADHOC group received an app-based multimodal weight loss program from baseline on for 12 weeks plus 12 weeks of follow-up. The EXPECT group received the app-based intervention for 12 weeks after 12 weeks of “waiting” (no intervention). Anthropometric data, data on quality of life (EuroQol, EQ-5D-5L), and app usage data were collected.

Results
64.3% of study participants were women, mean age was 46.8 ± 11.0 years, and mean BMI was 34.2 ± 2.8 kg/m2. The completers analysis resulted in a weight loss of 3.2 ± 3.2 kg (3.2 ± 3.0%) in the ADHOC group and 0.4 ± 2.6 kg (0.3 ± 2.6%) in the EXPECT group after 12 weeks, with a significant difference between the groups (β [95% CI] = −2.9 [−3.8; −1.9], p < 0.001). Completers in the ADHOC group showed weight maintenance after 24 weeks. The time spent on the app was associated with weight reduction (β [95% CI] = −0.10 [−0.18; −0.01], p = 0.03).

Conclusions
Application of a multimodal app-based weight loss program results in moderate weight loss in persons with obesity.

Trial registration
This study was registered in the German Clinical Trials Register (Registration number: DRKS00025291).
Comparison of 18F-based PSMA radiotracers with [68Ga]Ga-PSMA-11 in PET/CT imaging of prostate cancer—a systematic review and meta-analysis
Authors: Huang Siyu , Ong Sean , McKenzie Dean , Mirabelli Adam , Chen David C. , Chengodu Thilakavathi , Murphy Declan G. , Hofman Michael S. , Lawrentschuk Nathan , Perera Marlon 
Published: November 2023

Abstract
Background
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (18F)-labelled PSMA PET/CT is significantly different from Gallium-68 (68Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence.

Methods
A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared 18F-based PSMA radiotracers and [68Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2).

Results
Twenty-four studies were analysed. [18F]DCFPyL and [18F]PSMA-1007 were the two most commonly studied 18F based PSMA tracers. [18F]JK-PSMA-7, [18F]rhPSMA-7, [18F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [18F]DCFPyL was observed to have a similar lesion detection rate to [68Ga]Ga-PSMA-11 with no increase in false positive rates. [18F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [68Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [18F]PSMA-1007 was found to have a significant number of benign bone uptakes.

Conclusions
[18F]DCFPyL was observed to be similar to [68Ga]Ga-PSMA-11. [18F]PSMA-1007 was observed to be less preferrable to [68Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.
TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination
Authors: Ma Qinmei , Yu Jialin , Liu Li , Ma Xiaoyan , Zhang Jiaxue , Zhang Jiamei , Wang Xiaoping , Deng Guangcun , Wu Xiaoling 
Published: November 2023

AbstractTumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Mycobacterium-induced autophagy has not been completely characterized. Herein, the present study showed that TRAF6 interacted with lysosomal key proteins Rab7 through RING domain which caused Rab7 ubiquitination and subsequently ubiquitinated Rab7 binds to STX17 (syntaxin 17, a SNARE protein that is essential for mature autophagosome), and thus promoted the fusion of autophagosomes and lysosomes. Furthermore, TRAF6 enhanced the initiation and formation of autophagosomes in Mycobacterium-induced autophagy in both BMDMs and RAW264.7 cells, as evidenced by autophagic flux, colocalization of LC3 and BCG, autophagy rates, and autophagy-associated protein expression. Noteworthy to mention, TRAF6 deficiency exacerbated lung injury and promoted BCG survival. Taken together, these results identify novel molecular and cellular mechanisms by which TRAF6 positively regulates Mycobacterium-induced autophagy.
Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2
Authors: Pan Xin , Ye Fang , Ning Peiruo , Zhang Zhiyi , Li Xinyu , Zhang Binghao , Wang Qian , Chen Geng , Gao Wei , Qiu Chen , Wu Zhangsong , Li Jiancheng , Zhu Lizhe , Xia Jiang , Gong Kaizheng , Du Yang 
Published: November 2023

AbstractHydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of cardiovascular, neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2–Gi1 complexes with or without agonists, including the drugs niacin (2.69 Å) and acipimox (3.23 Å), the highly subtype-specific agonist MK-6892 (3.25 Å), and apo form (3.28 Å). Combined with molecular dynamics simulation and functional analysis, we have revealed the recognition mechanism of HCAR2 for different agonists and summarized the general pharmacophore features of HCAR2 agonists, which are based on three key residues R1113.36, S17945.52, and Y2847.43. Notably, the MK-6892–HCAR2 structure shows an extended binding pocket relative to other agonist-bound HCAR2 complexes. In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which shed light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects.
Does diet quality matter? A secondary analysis of a randomized clinical trial
Authors: Kahleova Hana , Brennan Haley , Znayenko-Miller Tatiana , Holubkov Richard , Barnard Neal D. 
Published: November 2023

AbstractThis secondary analysis assessed the association of a plant-based index (PDI), healthful (hPDI), and unhealthful (uPDI), with weight loss in overweight adults. Participants (n = 244) were randomly assigned to a vegan (n = 122) or control group (n = 122) for 16 weeks. Three-day dietary records were analyzed and PDI indices were calculated. A repeated measure ANOVA was used for statistical analysis. All three scores increased in the vegan group; the effect sizes were: PDI +10.6 (95% CI +8.6 to +12.6; p < 0.001); hPDI +10.9 (95% CI +8.4 to +13.4; p < 0.001); and uPDI +5.4 (95% CI +3.4 to +7.4; p < 0.001). The change in all three scores significantly correlated with change in body weight: PDI (r = −0.40; p < 0.001); hPDI (r = −0.37; p < 0.001); and uPDI (r = −0.21; p = 0.002). These findings suggest that minimizing the consumption of animal products and oil may be an effective weight loss strategy in overweight adults. ClinicalTrials.gov number, NCT02939638.
Aneuploidy during development in facultative parthenogenetic Drosophila
Authors: Sperling A. L. , Glover D. M. 
Published: November 2023

AbstractFrom concatenated chromosomes to polyploidization, large-scale genome changes are known to occur in parthenogenetic animals. Here, we report mosaic aneuploidy in larval brains of facultatively parthenogenetic Drosophila. We identified a background of aneuploidy in D. mercatorum strains and found increased levels of aneuploidy in the larval brain tissue of animals arising parthenogenetically versus those arising from sexual reproduction. There is also intra-individual variation in germline-derived aneuploidy within the same strain. To determine if this is a general feature of facultative parthenogenesis in drosophilids, we compared sexually reproduced and parthenogenetic offspring from an engineered facultative parthenogenetic strain of D. melanogaster. In addition to germline-derived aneuploidy, this revealed somatic aneuploidy that increased by up to fourfold in parthenogens compared to sexually reproduced offspring. Therefore, the genetic combination identified in D. mercatorum that causes facultative parthenogenesis in D. melanogaster results in aneuploidy, which indicates that the loss of mitotic control resulting in parthenogenesis causes subsequent genome variation within the parthenogenetic offspring. Our findings challenge the assumption that parthenogenetic offspring are near genetic replicas of their mothers.
Electrophysiological population dynamics reveal context dependencies during decision making in human frontal cortex
Authors: Shih Wan-Yu , Yu Hsiang-Yu , Lee Cheng-Chia , Chou Chien-Chen , Chen Chien , Glimcher Paul W. , Wu Shih-Wei 
Published: November 2023

AbstractEvidence from monkeys and humans suggests that the orbitofrontal cortex (OFC) encodes the subjective value of options under consideration during choice. Data from non-human primates suggests that these value signals are context-dependent, representing subjective value in a way influenced by the decision makers’ recent experience. Using electrodes distributed throughout cortical and subcortical structures, human epilepsy patients performed an auction task where they repeatedly reported the subjective values they placed on snack food items. High-gamma activity in many cortical and subcortical sites including the OFC positively correlated with subjective value. Other OFC sites showed signals contextually modulated by the subjective value of previously offered goods—a context dependency predicted by theory but not previously observed in humans. These results suggest that value and value-context signals are simultaneously present but separately represented in human frontal cortical activity.
The two-qubit singlet/triplet measurement is universal for quantum computing given only maximally-mixed initial states
Authors: Rudolph Terry , Virmani Shashank Soyuz 
Published: November 2023

AbstractIn order to delineate which minimalistic physical primitives can enable the full power of universal quantum computing, it has been fruitful to consider various measurement based architectures which reduce or eliminate the use of coherent unitary evolution, and also involve operations that are physically natural. In this context previous works had shown that the triplet-singlet measurement of two qubit angular momentum (or equivalently two qubit exchange symmetry) yields the power of quantum computation given access to a few additional different single qubit states or gates. However, Freedman, Hastings and Shokrian-Zini1 recently proposed a remarkable conjecture, called the ‘STP=BQP’ conjecture, which states that the two-qubit singlet/triplet measurement is quantum computationally universal given only an initial ensemble of maximally mixed single qubits. In this work we prove this conjecture. This provides a method for quantum computing that is fully rotationally symmetric (i.e. reference frame independent), using primitives that are physically very-accessible, naturally resilient to certain forms of error, and provably the simplest possible.
NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease
Authors: Berven Haakon , Kverneng Simon , Sheard Erika , Søgnen Mona , Af Geijerstam Solveig Amdahl , Haugarvoll Kristoffer , Skeie Geir-Olve , Dölle Christian , Tzoulis Charalampos 
Published: November 2023

AbstractNicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404.
Interrogating ligand-receptor interactions using highly sensitive cellular biosensors
Authors: Funk Maximilian A. , Leitner Judith , Gerner Marlene C. , Hammerler Jasmin M. , Salzer Benjamin , Lehner Manfred , Battin Claire , Gumpelmair Simon , Stiasny Karin , Grabmeier-Pfistershammer Katharina , Steinberger Peter 
Published: November 2023

AbstractInteractions of membrane-resident proteins are important targets for therapeutic interventions but most methods to study them are either costly, laborious or fail to reflect the physiologic interaction of membrane resident proteins in trans. Here we describe highly sensitive cellular biosensors as a tool to study receptor-ligand pairs. They consist of fluorescent reporter cells that express chimeric receptors harboring ectodomains of cell surface molecules and intracellular signaling domains. We show that a broad range of molecules can be integrated into this platform and we demonstrate its applicability to highly relevant research areas, including the characterization of immune checkpoints and the probing of cells for the presence of receptors or ligands. The platform is suitable to evaluate the interactions of viral proteins with host receptors and to test for neutralization capability of drugs or biological samples. Our results indicate that cellular biosensors have broad utility as a tool to study protein-interactions.
Unexpected dynamics in femtomolar complexes of binding proteins with peptides
Authors: Cucuzza Stefano , Sitnik Malgorzata , Jurt Simon , Michel Erich , Dai Wenzhao , Müntener Thomas , Ernst Patrick , Häussinger Daniel , Plückthun Andreas , Zerbe Oliver 
Published: November 2023

AbstractUltra-tight binding is usually observed for proteins associating with rigidified molecules. Previously, we demonstrated that femtomolar binders derived from the Armadillo repeat proteins (ArmRPs) can be designed to interact very tightly with fully flexible peptides. Here we show for ArmRPs with four and seven sequence-identical internal repeats that the peptide-ArmRP complexes display conformational dynamics. These dynamics stem from transient breakages of individual protein-residue contacts that are unrelated to overall unbinding. The labile contacts involve electrostatic interactions. We speculate that these dynamics allow attaining very high binding affinities, since they reduce entropic losses. Importantly, only NMR techniques can pick up these local events by directly detecting conformational exchange processes without complications from changes in solvent entropy. Furthermore, we demonstrate that the interaction surface of the repeat protein regularizes upon peptide binding to become more compatible with the peptide geometry. These results provide novel design principles for ultra-tight binders.
Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing
Authors: Chen Ningbo , Xia Xiaoting , Hanif Quratulain , Zhang Fengwei , Dang Ruihua , Huang Bizhi , Lyu Yang , Luo Xiaoyu , Zhang Hucai , Yan Huixuan , Wang Shikang , Wang Fuwen , Chen Jialei , Guan Xiwen , Liu Yangkai , Li Shuang , Jin Liangliang , Wang Pengfei , Sun Luyang , Zhang Jicai , Liu Jianyong , Qu Kaixing , Cao Yanhong , Sun Junli , Liao Yuying , Xiao Zhengzhong , Cai Ming , Mu Lan , Siddiki Amam Zonaed , Asif Muhammad , Mansoor Shahid , Babar Masroor Ellahi , Hussain Tanveer , Silva Gamamada Liyanage Lalanie Pradeepa , Gorkhali Neena Amatya , Terefe Endashaw , Belay Gurja , Tijjani Abdulfatai , Zegeye Tsadkan , Gebre Mebrate Genet , Ma Yun , Wang Yu , Huang Yongzhen , Lan Xianyong , Chen Hong , Migliore Nicola Rambaldi , Colombo Giulia , Semino Ornella , Achilli Alessandro , Sinding Mikkel-Holger S. , Lenstra Johannes A. , Cheng Haijian , Lu Wenfa , Hanotte Olivier , Han Jianlin , Jiang Yu , Lei Chuzhao 
Published: November 2023

AbstractIndicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.