bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of taste-active pyroglutamyl peptide ethyl esters in sake by rice koji peptidases
Authors: Ito Toshihiko , Taguchi Yuki , Oue Haruka , Amano Naomi , Nagae Yusuke , Noge Koji , Hashizume Katsumi 
Published: March 2021

ABSTRACT
Formation of taste-active pyroglutamyl (pGlu) peptide ethyl esters in sake was investigated: 2 enzymes (A and B) responsible for the esterification were purified from a rice koji extract. MADLI-TOF/TOF analysis after deglycosylation identified enzyme (A) as peptidase S28 (GenBank accession number OOO13707.1) and enzyme (B) as serine-type carboxypeptidase (accession number AO090010000534). Both enzymes hydrolyzed pGlu peptides and formed ethyl esters under sake mash conditions: acidic pH (3-4) and in ethanol (5%-20% v/v) aqueous solutions. Enzyme (A) formed pGlu penta-peptide ethyl esters from pGlu undeca-peptides by a prolyl endo-type reaction. Enzyme (B) formed (pGlu) deca-peptide and its ethyl esters from pGlu undeca-peptides in an exo-type reaction. We are the first to report the enzymatic ethyl esterification reaction in the formation of pGlu peptides by rice koji peptidases.
Concise enantioselective synthesis of wine lactone via intramolecular Diels–Alder reaction
Authors: Ohkubo Yasutaka , Masuda Yui , Ogura Yusuke , Takikawa Hirosato , Watanabe Hidenori 
Published: March 2021

ABSTRACT
An enantioselective synthesis of (3S,3aS,7aR)-wine lactone, a major aroma component of white wine and citrus juices, was achieved starting from (S)-2-methyl-3-butenoic acid. An intramolecular Diels–Alder reaction was employed as a key step.
Atypical neural topographies underpin dysfunctional pattern separation in temporal lobe epilepsy
Authors: Li Qiongling , Tavakol Shahin , Royer Jessica , Larivière Sara , Vos De Wael Reinder , Park Bo-yong , Paquola Casey , Zeng Debin , Caldairou Benoitu , Bassett Danielle S , Bernasconi Andrea , Bernasconi Neda , Frauscher Birgit , Smallwood Jonathan , Caciagli Lorenzo , Li Shuyu , Bernhardt Boris C 
Published: March 2021

AbstractEpisodic memory is the ability to remember events from our past accurately. The process of pattern separation is hypothesized to underpin this ability and is defined as the capacity to orthogonalize memory traces, to maximize the features that make them unique. Contemporary cognitive neuroscience suggests that pattern separation entails complex interactions between the hippocampus and neocortex, where specific hippocampal subregions shape neural reinstatement in the neocortex. To test this hypothesis, the current work studied both healthy controls and patients with temporal lobe epilepsy who presented with hippocampal structural anomalies. We measured neural activity in all participants using functional MRI while they retrieved memorized items or lure items, which shared features with the target. Behaviourally, patients with temporal lobe epilepsy were less able to exclude lures than controls and showed a reduction in pattern separation. To assess the hypothesized relationship between neural patterns in the hippocampus and neocortex, we identified the topographic gradients of intrinsic connectivity along neocortical and hippocampal subfield surfaces and determined the topographic profile of the neural activity accompanying pattern separation. In healthy controls, pattern separation followed a graded topography of neural activity, both along the hippocampal long axis (and peaked in anterior segments that are more heavily engaged in transmodal processing) and along the neocortical hierarchy running from unimodal to transmodal regions (peaking in transmodal default mode regions). In patients with temporal lobe epilepsy, however, this concordance between task-based functional activations and topographic gradients was markedly reduced. Furthermore, person-specific measures of concordance between task-related activity and connectivity gradients in patients and controls were related to inter-individual differences in behavioural measures of pattern separation and episodic memory, highlighting the functional relevance of the observed topographic motifs. Our work is consistent with an emerging understanding that successful discrimination between memories with similar features entails a shift in the locus of neural activity away from sensory systems, a pattern that is mirrored along the hippocampal long axis and with respect to neocortical hierarchies. More broadly, our study establishes topographic profiling using intrinsic connectivity gradients, capturing the functional underpinnings of episodic memory processes in a manner that is sensitive to their reorganization in pathology.
The Brain Circuits and Dynamics of Curiosity-Driven Behavior in Naturally Curious Marmosets
Authors: Tian Xiaoguang , Silva Afonso C , Liu Cirong 
Published: March 2021

Abstract
Curiosity is a fundamental nature of animals for adapting to changing environments, but its underlying brain circuits and mechanisms remain poorly understood. One main barrier is that existing studies use rewards to train animals and motivate their engagement in behavioral tasks. As such, the rewards become significant confounders in interpreting curiosity. Here, we overcame this problem by studying research-naïve and naturally curious marmosets that can proactively and persistently participate in a visual choice task without external rewards. When performing the task, the marmosets manifested a strong innate preference towards acquiring new information, associated with faster behavioral responses. Longitudinally functional magnetic resonance imaging revealed behavior-relevant brain states that reflected choice preferences and engaged several brain regions, including the cerebellum, the hippocampus, and cortical areas 19DI, 25, and 46D, with the cerebellum being the most prominent. These results unveil the essential brain circuits and dynamics underlying curiosity-driven activity.
Insular Cortex Mediates Attentional Capture by Behaviorally Relevant Stimuli after Damage to the Right Temporoparietal Junction
Authors: Ptak Radek , Pedrazzini Elena 
Published: March 2021

AbstractThe right temporoparietal junction (rTPJ) and insula both play a key role for the processing of relevant stimuli. However, while both have been conceived as neural “switches” that detect salient events and redirect the focus of attention, it remains unclear how these brain regions interact to achieve this behavioral goal. Here, we tested human participants with focal left-hemispheric or right-hemispheric lesions in a spatial cuing task that requires participants to react to lateralized stimuli preceded by a distracter that shares or does not share a relevant feature with the target. Using machine learning to identify significant lesion–behavior relationships, we found that rTPJ damage produces distinctive, pathologically increased attentional capture, but only by relevant distracters. Functional connectivity analyses revealed that the degree of capture is positively associated with a functional connection between insula and rTPJ, together with functional isolation of the rTPJ from right dorsal prefrontal cortex (dPFC). These findings suggest a mechanistic model where the insula–rTPJ connection constitutes a crucial functional unit that breaks attentional focus upon detection of behaviorally relevant events, while the dPFC appears to attune this activity.
A Distinct Population of L6 Neurons in Mouse V1 Mediate Cross-Callosal Communication
Authors: Liang Yajie , Fan Jiang Lan , Sun Wenzhi , Lu Rongwen , Chen Ming , Ji Na 
Published: March 2021

Abstract
Through the corpus callosum, interhemispheric communication is mediated by callosal projection (CP) neurons. Using retrograde labeling, we identified a population of layer 6 (L6) excitatory neurons as the main conveyer of transcallosal information in the monocular zone of the mouse primary visual cortex (V1). Distinct from L6 corticothalamic (CT) population, V1 L6 CP neurons contribute to an extensive reciprocal network across multiple sensory cortices over two hemispheres. Receiving both local and long-range cortical inputs, they encode orientation, direction, and receptive field information, while are also highly spontaneous active. The spontaneous activity of L6 CP neurons exhibits complex relationships with brain states and stimulus presentation, distinct from the spontaneous activity patterns of the CT population. The anatomical and functional properties of these L6 CP neurons enable them to broadcast visual and nonvisual information across two hemispheres, and thus may play a role in regulating and coordinating brain-wide activity events.
Novelty Detection in Memory for Common and Uncommon Odors over Short Delays
Authors: Wenzel Elizabeth S , Cameron E Leslie , Møller Per , Köster Egon P 
Published: March 2021

AbstractOdor memory is commonly believed to be very strong and long-lasting. The present study examined factors that impact odor recognition memory over short delay intervals (immediately or 30 s after target presentation) with emphasis on memory task (forced-choice vs “monadic”/single stimulus yes/no), odor category, and target/foil relationship. We explored trial-by-trial confidence as well as the effect of target familiarity, pleasantness, and intensity ratings, and odor nameability on memory for odors. Overall odor recognition memory in terms of proportion correct and sensitivity measures did not decline significantly during the 30-s delay interval in either task. However, hit rates were lower at 30 s and correct rejection rates for common odors remained consistently high. Recognition memory was better on trials in which the odor pairs were highly dissimilar, as well as on trials in which the target was an uncommon odor, particularly if it could be named. Familiarity, pleasantness, and intensity had no systematic effect on recognition memory. Whereas the results provide evidence of a fading memory trace, indicated by the decreased hit rates after a 30-s delay, the constant rates of correct rejections and high confidence ratings on those trials, even after delay, suggests that novelty detection (i.e., recognition that an odor is not one that has been encountered previously in that context) may play an important role in the memory for odors over short delays. Whether there is a separate short-term odor memory store is also addressed.
A case report of takotsubo syndrome complicated by ischaemic stroke: the clinical dilemma of anticoagulation
Authors: Iuliano Giuseppe , Napoletano Rosa , Vecchione Carmine , Citro Rodolfo 
Published: March 2021

Abstract

Background
Takotsubo syndrome (TTS) is an acute and transient heart failure syndrome due to reversible myocardial dysfunction characterized by a wide spectrum of possible clinical scenarios. About one-fifth of TTS patients experience adverse in-hospital events. Thromboembolic complications, especially stroke, have been reported, albeit in a minority of patients.

Case summary
A 69-year-old woman presented to our emergency department for dyspnoea after a family quarrel. Electrocardiogram revealed ST-segment elevation in anterolateral leads and laboratory exams showed a slight elevation of high-sensitivity cardiac troponin. The patient was treated according to current guidelines on ST-elevation myocardial infarction and referred to the cath lab. Urgent coronary angiography revealed normal coronary arteries. Based on the patient profile and instrumental findings, a diagnosis of TTS was hypothesized. After 6 days, the patient developed dysarthria and right hemiparesis under therapy with aspirin, whilst low molecular weight heparin had been previously withdrawn. Transthoracic echocardiography (TTE) revealed persisting apical akinesia and a subtle intraventricular thrombus. Head computed tomography and magnetic resonance imaging detected focal areas of ischaemic necrosis resembling diffuse cardioembolic lesions. Anticoagulation therapy was started and regular TTE showed complete recovery of myocardial systolic function and absence of ventricular thrombi at 1-month follow-up. The patient fully recovered speech after 5 months.

Discussion
This challenging case reinforces current recommendations to administer antithrombotic therapy in TTS patients with extensive apical dysfunction up to complete or near-complete recovery of myocardial contractility, regardless of the presence of atrial fibrillation, and highlights the importance of close TTE monitoring during the acute phase.
Efficacy and safety of direct oral anticoagulant in morbidly obese patients with atrial fibrillation: systematic review and meta-analysis
Authors: Thangjui Sittinun , Kewcharoen Jakrin , Yodsuwan Ratdanai , Trongtorsak Angkawipa , Thyagaturu Harshith , Shrestha Bishesh , Winans Amanda R M , Bischof Edward 
Published: March 2021

Abstract

Aims
We conducted a systematic review and meta-analysis on three outcomes. We assessed the efficacy and safety of direct oral anticoagulants (DOAC) compared to vitamin K antagonists (VKA) in morbidly obese patients with atrial fibrillation (AF). We compared the efficacy and safety of DOAC in obese patients and non-obese patients with AF. Finally, we updated the current knowledge of outcomes of AF patients with obesity compared with normal-weight patients regardless of anticoagulation type.

Methods and results
Using PubMed and Embase, we searched for literature published from inception to August 2020 for studies conducted in morbidly obese patients with AF who used DOACs and/or VKA for stroke or systemic embolism (stroke/SE) prevention that report efficacy and/or safety data. GRADE assessment was performed to determine the quality of the meta-analysis results. Direct oral anticoagulant was not statistically different from VKA in reducing stroke/SE with relative risk (RR) of 0.85 [95% confidence interval (CI): 0.56–1.29; very low certainty evidence]. Major bleeding risk was lower in the DOAC groups with RR of 0.62 (95% CI: 0.48–0.80; low certainty evidence). Obese patients with AF who used DOACs had lower risk of stroke/SE and similar major bleeding risk compared to non-obese patients with RR of 0.77 (95% CI: 0.70–0.84; low certainty evidence) and 1.02 (95% CI: 0.94–1.09; low certainty evidence), respectively. Obese patients with AF who used any type of anticoagulant had lower risk of stroke/SE compared to normal-weight patients with RR of 0.62 (95% CI: 0.57–0.69; low certainty evidence).

Conclusion
The use of DOACs in morbidly obese patients may be reasonable if needed, and more dedicated studies are needed to make a more robust recommendation.
Gut microbiome composition predicts summer core range size in two divergent ungulates
Authors: Wolf Jesse F , Kriss Krystal D , MacAulay Kara M , Munro Keith , Patterson Brent R , Shafer Aaron B A 
Published: March 2021

ABSTRACT
The gut microbiome of animals vary by age, diet, and habitat, and directly influences an individual's health. Similarly, variation in home ranges is linked to feeding strategies and fitness. Ungulates (hooved mammals) exhibit species-specific microbiomes and habitat use patterns. We combined gut microbiome and movement data to assess relationships between space use and the gut microbiome in a specialist and a generalist ungulate. We GPS radiocollared 24 mountain goats (Oreamnos americanus) and 34 white-tailed deer (Odocoileus virginianus), collected fecal samples, and conducted high-throughput sequencing of the 16S rRNA gene. We generated gut diversity metrics and key bacterial ratios. Our research question centred around the idea that larger Firmicutes to Bacteroidetes ratios confer body size or fat advantages that allow for larger home ranges, and relationships of disproportionate habitat use are stronger in the habitat specialist mountain goat. Firmicutes to Bacteroidetes ratios were positively correlated with core range area in both species. Mountain goats exhibited a negative relationship between gut diversity and proportional use of treed areas and escape terrain, and no relationships were detected in the habitat generalist white-tailed deer. This is the first study to relate range size to the gut microbiome in wild ungulates and is an important proof of concept that advances the information that can be gleaned from non-invasive sampling.
The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients
Authors: Xu Wen-Xiong , Li Yang-Mei , Li Jian-Guo , Mei Yong-Yu , Chen You-Ming , Li Xue-Jun , Lin Chao-Shuang , Deng Hong , Zhao Zhi-Xin , Xie Dong-Ying , Gao Zhi-Liang , Peng Liang 
Published: March 2021

Abstract

Background
Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs.

Methods
This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed.

Results
After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse.

Conclusions
There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.
Adaptive Metabolic and Inflammatory Responses Identified Using Accelerated Aging Metrics Are Linked to Adverse Outcomes in Severe SARS-CoV-2 Infection
Authors: Márquez-Salinas Alejandro , Fermín-Martínez Carlos A , Antonio-Villa Neftalí Eduardo , Vargas-Vázquez Arsenio , Guerra Enrique C , Campos-Muñoz Alejandro , Zavala-Romero Lilian , Mehta Roopa , Bahena-López Jessica Paola , Ortiz-Brizuela Edgar , González-Lara María Fernanda , Roman-Montes Carla M , Martinez-Guerra Bernardo A , Ponce de Leon Alfredo , Sifuentes-Osornio José , Gutiérrez-Robledo Luis Miguel , Aguilar-Salinas Carlos A , Bello-Chavolla Omar Yaxmehen 
Published: March 2021

Abstract

Background
Chronological age (CA) is a predictor of adverse coronavirus disease 2019 (COVID-19) outcomes; however, CA alone does not capture individual responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components.

Method
In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (intensive care unit admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components.

Results
We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel &gt;0 had higher risk of death and critical illness compared to those with lower values (log-rank p &lt; .001). Using unsupervised clustering, we identified 4 adaptive responses to SARS-CoV-2 infection: (i) inflammaging associated with CA, (ii) metabolic dysfunction associated with cardiometabolic comorbidities, (iii) unfavorable hematological response, and (iv) response associated with favorable outcomes.

Conclusions
Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.
ALS/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ
Authors: Rayner Stephanie L , Cheng Flora , Hogan Alison L , Grima Natalie , Yang Shu , Ke Yazi D , Au Carol G , Morsch Marco , De Luca Alana , Davidson Jennilee M , Molloy Mark P , Shi Bingyang , Ittner Lars M , Blair Ian , Chung Roger S , Lee Albert 
Published: March 2021

AbstractPreviously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD. CCNF encodes for the protein cyclin F, a substrate recognition component of an E3 ubiquitin ligase. We have previously shown that ALS/FTD-linked mutations in CCNF cause disruptions to overall protein homeostasis that leads to a build-up of K48-linked ubiquitylated proteins as well as defects in autophagic machinery. To investigate further processes that may be affected by cyclin F, we used a protein-proximity ligation method, known as Biotin Identification (BioID), standard immunoprecipitations and mass spectrometry to identify novel interaction partners of cyclin F and infer further process that may be affected by the ALS/FTD-causing mutation. Results demonstrate that cyclin F closely associates with proteins involved with RNA metabolism as well as a number of RNA-binding proteins previously linked to ALS/FTD, including SFPQ. Notably, the overexpression of cyclin F(S621G) led to the aggregation and altered subcellular distribution of SFPQ in human embryonic kidney (HEK293) cells, while leading to altered degradation in primary neurons. Overall, our data links ALS/FTD-causing mutations in CCNF to converging pathological features of ALS/FTD and provides a link between defective protein degradation systems and the pathological accumulation of a protein involved in RNA processing and metabolism.