bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antidepressant properties of voluntary exercise mediated by gut microbiota
Authors: Watanabe Chihiro , Oyanagi Eri , Aoki Takafumi , Hamada Hiroki , Kawashima Masato , Yamagata Takashi , Kremenik Michel J , Yano Hiromi 
Published: September 2023

ABSTRACT
Although regular exercise has been reported to prevent depression, it has not been clarified whether the gut microbiota is involved in the factors that prevent depression through exercise. We investigated the effects of voluntary exercise on the gut microbiota and the prevention of depression-like behaviors using mice. C57BL/6 J male mice were subjected to 10 weeks of sedentary control or wheel running, then they were subjected to social defeat stress (SDS). Exercise attenuated that sucrose drinking was decreased by SDS treatment. Exercise increased the expression of Bdnf and decreased expression of Zo-1 and Claudin5 in the brain. Fecal Turicibacter, Allobaculum, and Clostridium sensu stricto, and propionate in the cecum were decreased by the exercise. Voluntary exercise-induced antidepressant properties might be partially caused by suppression of serotonin uptake into gut microbiota and increase the permeability of the blood-brain barrier via reduced propionate production.
Pentapeptide IIAEK ameliorates cholesterol metabolism via the suppression of intestinal cholesterol absorption in mice
Authors: Takeuchi Asahi , Ye Yuyang , Takada Keigo , Mori Ryosuke , Nakamura Toma , Oda Natsuki , Mijiti Maihemuti , Banno Arata , Nagaoka Satoshi 
Published: September 2023

ABSTRACT
Dietary protein-derived peptides are effective in improving dyslipidemia and hypercholesterolemia. We previously identified a novel cholesterol-lowering pentapeptide IIAEK from milk beta-lactoglobulin. However, it remains unclear whether IIAEK affects the micellar solubility of cholesterol and the bile acid-binding ability to lower cholesterol. Moreover, there is no direct evidence that IIAEK inhibits intestinal cholesterol absorption and affects hepatic cholesterol and fecal steroid excretion in vivo. Herein, we showed that IIAEK did not affect the micellar solubility of cholesterol and the bile acid-binding ability. However, we found that IIAEK decreased serum and liver cholesterol levels and increased fecal steroid excretion in mice. Interestingly, IIAEK markedly suppressed the intestinal absorption of [3H]-cholesterol in mice. In conclusion, we found that IIAEK ameliorated cholesterol metabolism by suppressing intestinal cholesterol absorption without affecting in vitro micellar solubility of cholesterol and the bile acid-binding ability in mice.
Eriodictyol and thymonin act as GPR35 agonists
Authors: Nakashima Fumie , Qi Loh Wei , Wakabayashi Mayuka , Shimomura Sayako , Hattori Hiroyuki , Kita Masaki , Inoue Asuka , Uchida Koji , Shibata Takahiro 
Published: September 2023

ABSTRACT
Although herbs and spices have been used in traditional medicine for more than a century owing to their health benefits, the associated underlying mechanism is still not clear. Since the G protein-coupled receptor 35 (GPR35) has been linked to exert various antioxidant and anti-inflammatory effects, we screened 19 different herbs and spices for possible GPR35 agonist(s) to understand the GPR35-dependent functions of herbs and spices. Among the screened extracts, the ethyl acetate extract of thyme exhibited a remarkable GPR35 agonistic activity. Activity-guided separations allowed us to identify 2 polyphenolic phytochemicals, eriodictyol and thymonin, acting as GPR35 agonists. Both eriodictyol and thymonin showed a potent and specific agonist activity toward GPR35 with half maximal effective concentration values of 5.48 and 8.41 µm, respectively. These findings indicate that these phytochemicals may have beneficial health effects upon GPR35 activation.
Isolation, structure elucidation, and biological activities of sesquiterpenes and phthalides from two edible mushrooms Pleurotus species
Authors: De Padua Jewel C , Fukushima-Sakuno Emi , Ueno Kotomi , dela Cruz Thomas Edison E , Ishihara Atsushi 
Published: September 2023

ABSTRACT
Antimicrobial compounds were purified from culture filtrates from 2 edible Pleurotus species. Using a bioassay-guided fractionation of the culture filtrate extracts, 3 compounds (1-3) were obtained from Pleurotus ostreatus, and another compound (4) was obtained from Pleurotus pulmonarius. Spectroscopic analysis revealed that 1-3 was identified as 5,7-dimethoxyphthalide, 4,6-dimethoxyphthalide, and cheimonophyllon E, respectively, while 4 were identified as pleuroton A. The minimum inhibitory concentration and minimum bactericidal concentration of these compounds were determined against 6 pathogenic bacterial species, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. Compounds 2 and 4 were inhibitory against all tested bacteria, while 1 and 4 were inhibitory against 3 and 2 species, respectively. In addition, 1-4 inhibited tyrosinase, with IC50 values of 0.10-0.30 mg/mL, and α-glucosidase, with IC50 values of 0.12-0.54 mg/mL. However, their antioxidant capacities were marginal.
Cell type-specific interaction analysis using doublets in scRNA-seq
Authors: Schiebout Courtney , Lust Hannah , Huang Yina , Frost H Robert 
Published: September 2023

Abstract

Summary
Doublets are usually considered an unwanted artifact of single-cell RNA-sequencing (scRNA-seq) and are only identified in datasets for the sake of removal. However, if cells have a juxtacrine interaction with one another in situ and maintain this association through an scRNA-seq processing pipeline that only partially dissociates the tissue, these doublets can provide meaningful biological information regarding the intercellular signals and processes occurring in the analyzed tissue. This is especially true for cases such as the immune compartment of the tumor microenvironment, where the frequency and the type of immune cell juxtacrine interactions can be a prognostic indicator. We developed Cell type-specific Interaction Analysis using Doublets in scRNA-seq (CIcADA) as a pipeline for identifying and analyzing biologically meaningful doublets in scRNA-seq data. CIcADA identifies putative doublets using multi-label cell type scores and characterizes interaction dynamics through a comparison against synthetic doublets of the same cell type composition. In performing CIcADA on several scRNA-seq tumor datasets, we found that the identified doublets were consistently upregulating expression of immune response genes.

Availability and implementation
An R package implementing the CIcADA method is in development and will be released on CRAN, but for now it is available at https://github.com/schiebout/CAMML.
Drivers of large mammal distribution: an overview and modelling approach for palaeoecological reconstructions of extinct ecosystems
Authors: Brooke Christopher F , Marean Curtis W , Wren Colin D , Bergin Sean , Fahey B Patrick , Venter Jan A 
Published: September 2023

AbstractOne of the primary goals of the palaeosciences is to produce robust understandings of palaeoecologies of extinct ecosystems. The time has arrived where such palaeoecologies can be significantly improved—agent-based models (ABMs) that synthesize our modern understandings of animal ecology with past conditions provide a unique opportunity for this. The Palaeo-Agulhas Plain (PAP), a now submerged landscape off the south coast of South Africa, formed a novel ecosystem during the lower sea levels of the Pleistocene. Here we provide a review of the utility of ABMs for understanding herbivores in prehistoric environments using the Paleoscape Model. The Paleoscape Model is fortunate to have features models of climate, geology and vegetation upon which we can understand how herbivores used the PAP environment. To incorporate aspects of herbivore behaviour and habitat suitability into the model requires analogies from extant systems. In addition to reconstructions of the availability of resources and associated risks, data on herbivore behaviour and physiology are imperative to our understanding of these systems. Behaviour, driven by changes in the environment, is interpreted by species, leading to selection of suitable habitats ultimately driving the herbivore’s decisions within ABMs. Finally, we discuss herbivore integration into these models that can be used in numerous other scenarios (past, present and future).
Risk-stratified faecal immunochemical testing (FIT) for urgent colonoscopy in Lynch syndrome during the COVID-19 pandemic
Authors: Lincoln Anne G , Benton Sally C , Piggott Carolyn , Sheikh Shama Riaz , Beggs Andrew D , Buckley Leah , DeSouza Bianca , East James E , Sanders Pete , Lim Michael , Sheehan Donal , Snape Katie , Hanson Helen , Greenaway John R , Burn John , Nylander David , Hawkins Menna , Lalloo Fiona , Green Kate , Lee Thomas J , Walker Julie , Matthews Gillian , Rutherford Terry , Sasieni Peter , Monahan Kevin J 
Published: September 2023

Abstract

Background
Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing (‘FIT’) in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were limited.

Methods
An emergency service protocol was designed to improve colonoscopic surveillance access throughout the COVID-19 pandemic in England for people with Lynch syndrome when services were extremely restricted (1 March 2020 to 31 March 2021) and promoted by the English National Health Service. Requests for faecal immunochemical testing from participating centres were sent to the National Health Service Bowel Cancer Screening South of England Hub and a faecal immunochemical testing kit, faecal immunochemical testing instructions, paper-based survey, and pre-paid return envelope were sent to patients. Reports with faecal haemoglobin results were returned electronically for clinical action. Risk stratification for colonoscopy was as follows: faecal haemoglobin less than 10 µg of haemoglobin/g of faeces (µg/g)—scheduled within 6–12 weeks; and faecal haemoglobin greater than or equal to 10 µg/g—triaged via an urgent suspected cancer clinical pathway. Primary outcomes of interest included the identification of highest-risk Lynch syndrome patients and determining the impact of faecal immunochemical testing in risk-stratified colonoscopic surveillance.

Results
Fifteen centres participated from June 2020 to March 2021. Uptake was 68.8 per cent amongst 558 patients invited. For 339 eligible participants analysed, 279 (82.3 per cent) had faecal haemoglobin less than 10 µg/g and 60 (17.7 per cent) had faecal haemoglobin greater than or equal to 10 µg/g. In the latter group, the diagnostic accuracy of faecal immunochemical testing was 65.9 per cent and escalation to colonoscopy was facilitated (median 49 versus 122 days, χ2 = 0.0003, P &lt; 0.001).

Conclusion
Faecal immunochemical testing demonstrated clinical value for Lynch syndrome patients requiring colorectal cancer surveillance during the pandemic in this descriptive report of an emergency COVID-19 response service. Further longitudinal investigation on faecal immunochemical testing efficacy in Lynch syndrome is warranted and will be examined under the ‘FIT for Lynch’ study (ISRCTN15740250).
Neuromelanin-sensitive MRI as a promising biomarker of catecholamine function
Authors: Trujillo Paula , Aumann Megan A , Claassen Daniel O 
Published: September 2023

Abstract
Disruptions to dopamine and noradrenergic neurotransmission are noted in several neurodegenerative and psychiatric disorders. Neuromelanin-sensitive (NM)-MRI offers a non-invasive approach to visualize and quantify the structural and functional integrity of the substantia nigra and locus coeruleus. This method may aid in the diagnosis and quantification of longitudinal changes of disease and could provide a stratification tool for predicting treatment success of pharmacological interventions targeting the dopaminergic and noradrenergic systems. Given the growing clinical interest in NM-MRI, understanding the contrast mechanisms that generate this signal is crucial for appropriate interpretation of NM-MRI outcomes and for the continued development of quantitative MRI biomarkers that assess disease severity and progression. To date, most studies associate NM-MRI measurements to the content of the neuromelanin pigment and/or density of neuromelanin-containing neurons, while recent studies suggest that the main source of the NM-MRI contrast is not the presence of neuromelanin but the high-water content in the dopaminergic and noradrenergic neurons. In this review, we consider the biological and physical basis for the NM-MRI contrast and discuss a wide range of interpretations of NM-MRI. We describe different acquisition and image processing approaches and discuss how these methods could be improved and standardized to facilitate large-scale multisite studies and translation into clinical use. We review the potential clinical applications in neurological and psychiatric disorders and the promise of NM-MRI as a biomarker of disease, and finally, we discuss the current limitations of NM-MRI that need to be addressed before this technique can be utilized as a biomarker and translated into clinical practice and offer suggestions for future research.
Cellular and molecular mechanisms in vascular repair after traumatic brain injury: a narrative review
Authors: Zhao Zi-Ai , Yan Lingli , Wen Jing , Satyanarayanan Senthil Kumaran , Yu Feng , Lu Jiahong , Liu Yong U , Su Huanxing 
Published: September 2023

Abstract
Traumatic brain injury (TBI) disrupts normal brain function and is associated with high morbidity and fatality rates. TBI is characterized as mild, moderate or severe depending on its severity. The damage may be transient and limited to the dura matter, with only subtle changes in cerebral parenchyma, or life-threatening with obvious focal contusions, hematomas and edema. Blood vessels are often injured in TBI. Even in mild TBI, dysfunctional cerebral vascular repair may result in prolonged symptoms and poor outcomes. Various distinct types of cells participate in vascular repair after TBI. A better understanding of the cellular response and function in vascular repair can facilitate the development of new therapeutic strategies. In this review, we analyzed the mechanism of cerebrovascular impairment and the repercussions following various forms of TBI. We then discussed the role of distinct cell types in the repair of meningeal and parenchyma vasculature following TBI, including endothelial cells, endothelial progenitor cells, pericytes, glial cells (astrocytes and microglia), neurons, myeloid cells (macrophages and monocytes) and meningeal lymphatic endothelial cells. Finally, possible treatment techniques targeting these unique cell types for vascular repair after TBI are discussed.
Suppression of sweetness: evidence for central mechanism for suppression of sweetness from sucrose by citric acid
Authors: Junge Jonas Yde , Andersen Glenn Hjorth , Kidmose Ulla 
Published: September 2023

Abstract
The underlying mechanisms of taste interactions in humans are not well understood, and three mechanisms have been proposed, namely a chemical interaction, a peripheral physiological, and a central mechanism. In the present study, it was investigated which of these mechanisms causes the suppression of sweetness by citric acid. This was investigated using a split-tongue gustometer that can stimulate the two sides of the tongue with different stimuli simultaneously, enabling a comparison of sucrose and citric acid presented either separately on each side of the tongue simultaneously or in a mixture on one side. Two studies were conducted using low (Study 1; n = 50) and high (Study 2: n = 59) concentrations of sucrose (2.5% (w/w) and 10% (w/w), respectively), and citric acid (0.14% (w/w) and 0.18% (w/w), respectively). In neither of the studies was there a significant difference in sweetness intensity ratings between the two conditions where sucrose and citric acid were presented either separately or in a mixture form. However, both showed significantly lower sweetness ratings than without citric acid indicating suppression of the sweetness of sucrose from citric acid. This provides strong evidence for a central mechanism for the suppression of the sweetness of sucrose by citric acid. This mechanism seems to be equal in high and low concentrations of both sucrose and citric acid.
Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study
Authors: Inaguma Daijo , Koiwa Fumihiko , Tokumoto Masanori , Fukagawa Masafumi , Yoneda Shinji , Yasuzawa Hisami , Asano Kenji , Hagita Keiko , Inagaki Yosuke , Honda Daisuke , Akizawa Tadao 
Published: September 2023

ABSTRACT

Background
Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT).

Methods
A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52 weeks; the starting dose was 50 μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300 μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60–240 pg/mL (target achievement rate) at week 18.

Results
A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of &lt;7.5 mg/dL recovered to ≥7.5 mg/dL immediately after the interruption.

Conclusions
In haemodialysis patients with SHPT, upacicalcet doses of 25–300 μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.
Contemporary secondary prevention in survivors of ST-elevation myocardial infarction with and without chronic kidney disease: a retrospective analysis
Authors: Engelbertz Christiane , Feld Jannik , Makowski Lena , Lange Stefan A , Günster Christian , Dröge Patrik , Ruhnke Thomas , Gerß Joachim , Reinecke Holger , Köppe Jeanette 
Published: September 2023

ABSTRACT

Background
Survivors of myocardial infarction have an elevated risk of long-term mortality. We sought to evaluate guideline-directed medical treatment and its impact on long-term mortality in survivors of ST-elevation myocardial infarction (STEMI) according to their chronic kidney disease (CKD) stage.

Methods
Using German health insurance claims data, 157 663 hospitalized survivors of STEMI were identified. Regarding different CKD stages, we retrospectively analysed the filled prescriptions of platelet inhibitors (PAI)/oral anticoagulation, statins, beta-blocker and angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor antagonists (ACE-I/AT1-A) and their association with long-term mortality.

Results
Prescription rates for all four guideline-directed drugs were highest in patients without or with mild CKD and lowest in patients on dialysis. They dropped from 73.4% to 39.2% in patients without CKD and from 47.1% to 29% in patients on dialysis within the 5-year follow-up period. Mortality rates were dramatically increased in patients with CKD compared with patients without CKD (5-year mortality: no CKD, 16.7%; CKD stage 3, 47.1%; CKD stage 5d, 69.7%). Filled prescriptions of at least one drug class [one drug: hazard ratio (HR) 0.70, 95% confidence interval (95% CI) 0.66–0.74; four drugs: HR 0.28, 95% CI 0.27–0.30; P &lt; .001 for both] as well as the distinct drug classes (statins: HR 0.55, 95% CI 0.54–0.56; ACE-I/AT1-A: HR 0.68, 95% CI 0.67–0.70; beta-blocker: HR 0.87, 95% CI 0.85–0.90; PAI/oral anticoagulation: HR 0.97, 95% CI 0.95–1.00; all P &lt; .05) improved long-term mortality.

Conclusions
An improved long-term guideline-recommended drug therapy after STEMI regardless of renal impairment might lead to beneficial effects on long-term mortality.
Long-term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study
Authors: Genovesi Simonetta , Porcu Luca , Rebora Paola , Slaviero Giorgio , Casu Gavino , Bertoli Silvio , Airoldi Flavio , Buskermolen Monique , Gallieni Maurizio , Pieruzzi Federico , Rovaris Giovanni , Montoli Alberto , Piccaluga Emanuela , Molon Giulio , Alberici Federico , Adamo Marianna , Gaspardone Achille , D'Angelo Giuseppe , Merella Pierluigi , Vezzoli Giuseppe , Trezzi Barbara , Mazzone Patrizio 
Published: September 2023

ABSTRACT

Background
The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk.

Methods and Results
The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04–0.96; p = 0.045) and 0.16 (95%CI 0.04–0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16–0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23–1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38–0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34–0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3–3.0] vs 6.7 events per 100 person/years, p &lt; 0.001).

Conclusion
In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.