bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short chain fatty acids prime colorectal cancer cells to activate antitumor immunity
Authors: Mowat Courtney , Dhatt Jasmine , Bhatti Ilsa , Hamie Angela , Baker Kristi 
Published: May 2023

IntroductionColorectal cancer (CRC) is a leading cause of death worldwide and its growth can either be promoted or inhibited by the metabolic activities of intestinal microbiota. Short chain fatty acids (SCFAs) are microbial metabolites with potent immunoregulatory properties yet there is a poor understanding of how they directly regulate immune modulating pathways within the CRC cells.MethodsWe used engineered CRC cell lines, primary organoid cultures, orthotopic in vivo models, and patient CRC samples to investigate how SCFA treatment of CRC cells regulates their ability to activate CD8+ T cells.ResultsCRC cells treated with SCFAs induced much greater activation of CD8+ T cells than untreated CRC cells. CRCs exhibiting microsatellite instability (MSI) due to inactivation of DNA mismatch repair were much more sensitive to SCFAs and induced much greater CD8+ T cell activation than chromosomally instable (CIN) CRCs with intact DNA repair, indicating a subtype-dependent response to SCFAs. This was due to SCFA-induced DNA damage that triggered upregulation of chemokine, MHCI, and antigen processing or presenting genes. This response was further potentiated by a positive feedback loop between the stimulated CRC cells and activated CD8+ T cells in the tumor microenvironment. The initiating mechanism in the CRCs was inhibition of histone deacetylation by the SCFAs that triggered genetic instability and led to an overall upregulation of genes associated with SCFA signaling and chromatin regulation. Similar gene expression patterns were found in human MSI CRC samples and in orthotopically grown MSI CRCs independent of the amount of SCFA producing bacteria in the intestine.DiscussionMSI CRCs are widely known to be more immunogenic than CIN CRCs and have a much better prognosis. Our findings indicate that a greater sensitivity to microbially produced SCFAs contributes to the successful activation of CD8+ T cells by MSI CRCs, thereby identifying a mechanism that could be therapeutically targeted to improve antitumor immunity in CIN CRCs.
The Aspect Hypothesis and L2 Russian
Authors: Whitehead Martelle Wendy , Shirai Yasuhiro 
Published: May 2023

IntroductionNumerous studies have been conducted regarding the second language acquisition of tense-aspect morphology. A prevailing principle in this area is the Aspect Hypothesis, which predicts that learners are influenced by lexical aspect when applying tense- aspect markers (specifically, that learners will associate perfective/past markers with telic verbs and imperfective/past markers with atelic verbs). The Aspect Hypothesis has been widely tested in the acquisition of English, several Romance languages, Japanese, and Chinese. However, few studies have explored the second language acquisition of aspect in Slavic languages, which tend to have morphologically rich and complex tense-aspect systems. Additionally, few studies address the potential impact of task modality (for example, written vs. oral tasks) on the production of aspect.MethodsThe present study addresses these gaps by investigating how second language learners of Russian at varying proficiency levels use aspectual markers in the past tense when producing oral and written narratives. Data from written narratives (N= 42) and oral narratives (N= 42) were analyzed for lexical aspect and tense-aspect marking.ResultsThe results indicate that the Aspect Hypothesis is supported to varying degrees depending on the task: the activity involving lower planning levels (oral narratives) was more supportive of the Aspect Hypothesis, compared to the written narrative task, which involves a higher level of planning. However, the results also show that the aspectual production of beginning-level Russian learners is not consistent with certain predictions of the Aspect Hypothesis.DiscussionThe study concludes by discussing the role of instruction and the L1 as possible explanations for this inconsistency.
Off-label use of rituximab in patients with systemic lupus erythematosus with extrarenal disease activity: a retrospective study and literature review
Authors: Sans-Pola Carla , Danés Immaculada , Bosch Josep Àngel , Marrero-Álvarez Patricia , Cortés Josefina , Agustí Antònia 
Published: May 2023

IntroductionOff-label rituximab is commonly used for patients with systemic lupus erythematosus (SLE) with extrarenal disease activity.MethodsThe outcomes and tolerability of rituximab in adult patients with non-renal SLE treated at our hospital from 2013 to 2020 were described. Patients were followed-up until December 2021. Data were retrieved from electronic medical records. Response was classified into complete, partial or no response according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2 K)-based definitions.ResultsA total of 44 cycles were administered to 33 patients. Median age was 45 years and 97% were female. Median follow-up was 5.9 years (IQR 3.7–7.2). The most frequent symptoms that motivated rituximab use were thrombocytopenia (30.3%), arthritis (30.3%), neurological manifestations (24.2%) and cutaneous lupus (15.2%). After most treatment cycles a partial remission was achieved. The median SLEDAI-2 K score declined from 9 (IQR 5–13) to 1.5 (IQR 0–4) (p &lt; 0.00001). The median number of flares significantly declined after receiving rituximab. Platelet counts significantly improved in patients with thrombocytopenia and patients with skin disorders or neurological manifestations also had a partial or complete response. Only 50% of patients with a predominant joint involvement had either a complete or a partial response. The median time to relapse after the first cycle was 1.6 years (95% CI, 0.6–3.1). Anti-dsDNA levels decreased significantly after rituximab from a median of 64.3 (IQR 12–373.9) to 32.7 (IQR 10–173), p = 0.00338. The most frequent adverse events were infusion-related reactions (18.2%) and infections (57.6%). All patients needed further treatment to maintain remission or to treat new flares.ConclusionA partial or complete response was documented after most rituximab cycles in patients with non-renal SLE. Patients with thrombocytopenia, neurolupus, and cutaneous lupus had better response than those with a predominant joint involvement.
Hepatic encephalopathy increases the risk for mortality and hospital readmission in decompensated cirrhotic patients: a prospective multicenter study
Authors: Riggio Oliviero , Celsa Ciro , Calvaruso Vincenza , Merli Manuela , Caraceni Paolo , Montagnese Sara , Mora Vincenzina , Milana Martina , Saracco Giorgio Maria , Raimondo Giovanni , Benedetti Antonio , Burra Patrizia , Sacco Rodolfo , Persico Marcello , Schepis Filippo , Villa Erica , Colecchia Antonio , Fagiuoli Stefano , Pirisi Mario , Barone Michele , Azzaroli Francesco , Soardo Giorgio , Russello Maurizio , Morisco Filomena , Labanca Sara , Fracanzani Anna Ludovica , Pietrangelo Antonello , Di Maria Gabriele , Nardelli Silvia , Ridola Lorenzo , Gasbarrini Antonio , Cammà Calogero 
Published: May 2023

IntroductionHepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE.MethodsWe prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT).ResultsDuring follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01–1.06), HE (HR 1.67, 95% CI 1.08–2.56), ascites (HR 2.56, 95% CI 1.55–4.23), and sodium levels (HR 0.94, 95% CI 0.90–0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39–18.49) and BMI (HR 0.86, 95% CI 0.75–0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission.ConclusionIn patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.
Effects of different botanical oil meal mixed with cow manure organic fertilizers on soil microbial community and function and tobacco yield and quality
Authors: Chen Yuxuan , Lv Xiaolin , Qin Yanmin , Zhang Deping , Zhang Chaoqun , Song Zhanfeng , Liu Dongyang , Jiang Lianqiang , Huang Bin , Wang Jie 
Published: May 2023

IntroductionThe continuous application of cow manure in soil for many years leads to the accumulation of heavy metals, pathogenic microorganisms, and antibiotic resistance genes. Therefore, in recent years, cow manure has often been mixed with botanical oil meal as organic fertilizer applied to farmland to improve soil and crop quality. However, the effects of various botanical oil meal and cow manure mixed organic fertilizers on soil microbial composition, community structure, and function, tobacco yield, and quality remain unclear.MethodsTherefore, we prepared organic manure via solid fermentation by mixing cow manure with different oil meals (soybean meal, rape meal, peanut bran, sesame meal). Then, we studied its effects on soil microbial community structure and function, physicochemical properties, enzyme activities, tobacco yield and quality; then we analyzed the correlations between these factors.Results and discussionCompared with cow manure alone, the four kinds of mixed botanical oil meal and cow manure improved the yield and quality of flue-cured tobacco to different degrees. Peanut bran, which significantly improved the soil available phosphorus, available potassium, and NO3–-N, was the best addition. Compared with cow manure alone, soil fungal diversity was significantly decreased when rape meal or peanut bran was combined with cow manure, while soil bacterial and fungal abundance was significantly increased when rape meal was added compared with soybean meal or peanut bran. The addition of different botanical oil meals significantly enriched the subgroup_7 and Spingomonas bacteria and Chaetomium and Penicillium fungi in the soil. The relative abundances of functional genes of xenobiotics biodegradation and metabolism, soil endophytic fungi, and wood saprotroph functional groups increased. In addition, alkaline phosphatase had the greatest effect on soil microorganisms, while NO3–-N had the least effect on soil microorganisms. In conclusion, the mixed application of cow manure and botanical oil meal increased the available phosphorus and potassium contents in soil; enriched beneficial microorganisms; promoted the metabolic function of soil microorganisms; increased the yield and quality of tobacco; and improved the soil microecology.
Soil chemistry, metabarcoding, and metabolome analyses reveal that a sugarcane—Dictyophora indusiata intercropping system can enhance soil health by reducing soil nitrogen loss
Authors: Duan Mingzheng , Li Yijie , Zhu Guanghu , Wu Xiaojian , Huang Hairong , Qin Jie , Long Shengfeng , Li Xiang , Feng Bin , Qin Sunqian , Liu Qi-Huai , Li Changning , Wang Lingqiang , Li Qing , He Tieguang , Wang Zeping 
Published: May 2023

IntroductionGreater amounts of fertilizer are applied every year to meet the growing demand for food. Sugarcane is one of the important food sources for human beings.MethodsHere, we evaluated the effects of a sugarcane—Dictyophora indusiata (DI) intercropping system on soil health by conducting an experiment with three different treatments: (1) bagasse application (BAS process), (2) bagasse + DI (DIS process), and (3) the control (CK). We then analyzed soil chemistry, the diversity of soil bacteria and fungi, and the composition of metabolites to clarify the mechanism underlying the effects of this intercropping system on soil properties.Results and discussionSoil chemistry analyses revealed that the content of several soil nutrients such as nitrogen (N) and phosphorus (P) was higher in the BAS process than in the CK. In the DIS process, a large amount of soil P was consumed by DI. At the same time, the urease activity was inhibited, thus slowing down the loss of soil in the DI process, while the activity of other enzymes such as β-glucosidase and laccase was increased. It was also noticed that the content of lanthanum and calcium was higher in the BAS process than in the other treatments, and DI did not significantly alter the concentrations of these soil metal ions. Bacterial diversity was higher in the BAS process than in the other treatments, and fungal diversity was lower in the DIS process than in the other treatments. The soil metabolome analysis revealed that the abundance of carbohydrate metabolites was significantly lower in the BAS process than in the CK and the DIS process. The abundance of D(+)-talose was correlated with the content of soil nutrients. Path analysis revealed that the content of soil nutrients in the DIS process was mainly affected by fungi, bacteria, the soil metabolome, and soil enzyme activity. Our findings indicate that the sugarcane–DIS intercropping system can enhance soil health.
The balance between fitness advantages and costs drives adaptation of bacteriophage Qβ to changes in host density at different temperatures
Authors: Laguna-Castro Mara , Rodríguez-Moreno Alicia , Llorente Elena , Lázaro Ester 
Published: May 2023

IntroductionHost density is one of the main factors affecting the infective capacity of viruses. When host density is low, it is more difficult for the virus to find a susceptible cell, which increases its probability of being damaged by the physicochemical agents of the environment. Nevertheless, viruses can adapt to variations in host density through different strategies that depend on the particular characteristics of the life cycle of each virus. In a previous work, using the bacteriophage Qβ as an experimental model, we found that when bacterial density was lower than optimal the virus increased its capacity to penetrate into the bacteria through a mutation in the minor capsid protein (A1) that is not described to interact with the cell receptor.ResultsHere we show that the adaptive pathway followed by Qβ in the face of similar variations in host density depends on environmental temperature. When the value for this parameter is lower than optimal (30°C), the mutation selected is the same as at the optimal temperature (37°C). However, when temperature increases to 43°C, the mutation selected is located in a different protein (A2), which is involved both in the interaction with the cell receptor and in the process of viral progeny release. The new mutation increases the entry of the phage into the bacteria at the three temperatures assayed. However, it also considerably increases the latent period at 30 and 37°C, which is probably the reason why it is not selected at these temperatures.ConclusionThe conclusion is that the adaptive strategies followed by bacteriophage Qβ, and probably other viruses, in the face of variations in host density depend not only on their advantages at this selective pressure, but also on the fitness costs that particular mutations may present in function of the rest of environmental parameters that influence viral replication and stability.
Insight into the phylogeny and metabolic divergence of Monascus species (M. pilosus, M. ruber, and M. purpureus) at the genome level
Authors: Zhang Zhiyu , Cui Mengfei , Chen Panting , Li Juxing , Mao Zhitao , Mao Yufeng , Li Zhenjing , Guo Qingbin , Wang Changlu , Liao Xiaoping , Liu Huanhuan 
Published: May 2023

BackgroundSpecies of the genus Monascus are economically important and widely used in the production of food colorants and monacolin K. However, they have also been known to produce the mycotoxin citrinin. Currently, taxonomic knowledge of this species at the genome level is insufficient.MethodsThis study presents genomic similarity analyses through the analysis of the average nucleic acid identity of the genomic sequence and the whole genome alignment. Subsequently, the study constructed a pangenome of Monascus by reannotating all the genomes and identifying a total of 9,539 orthologous gene families. Two phylogenetic trees were constructed based on 4,589 single copy orthologous protein sequences and all the 5,565 orthologous proteins, respectively. In addition, carbohydrate active enzymes, secretome, allergic proteins, as well as secondary metabolite gene clusters were compared among the included 15 Monascus strains.ResultsThe results clearly revealed a high homology between M. pilosus and M. ruber, and their distant relationship with M. purpureus. Accordingly, all the included 15 Monascus strains should be classified into two distinctly evolutionary clades, namely the M. purpureus clade and the M. pilosus-M. ruber clade. Moreover, gene ontology enrichment showed that the M. pilosus-M. ruber clade had more orthologous genes involved with environmental adaptation than the M. purpureus clade. Compared to Aspergillus oryzae, all the Monascus species had a substantial gene loss of carbohydrate active enzymes. Potential allergenic and fungal virulence factor proteins were also found in the secretome of Monascus. Furthermore, this study identified the pigment synthesis gene clusters present in all included genomes, but with multiple nonessential genes inserted in the gene cluster of M. pilosus and M. ruber compared to M. purpureus. The citrinin gene cluster was found to be intact and highly conserved only among M. purpureus genomes. The monacolin K gene cluster was found only in the genomes of M. pilosus and M. ruber, but the sequence was more conserved in M. ruber.ConclusionThis study provides a paradigm for phylogenetic analysis of the genus Monascus, and it is believed that this report will lead to a better understanding of these food microorganisms in terms of classification, metabolic differentiation, and safety.
Contralaterally EMG-triggered functional electrical stimulation during serious gaming for upper limb stroke rehabilitation: a feasibility study
Authors: Höhler Chiara , Wild Laura , de Crignis Alexandra , Jahn Klaus , Krewer Carmen 
Published: May 2023

IntroductionVirtual Reality/serious games (SG) and functional electrical stimulation (FES) therapies are used in upper limb stroke rehabilitation. A combination of both approaches seems to be beneficial for therapy success. The feasibility of a combination of SG and contralaterally EMG-triggered FES (SG+FES) was investigated as well as the characteristics of responders to such a therapy.Materials and methodsIn a randomized crossover trial, patients performed two gaming conditions: SG alone and SG+FES. Feasibility of the therapy system was assessed using the Intrinsic Motivation Inventory (IMI), the Nasa Task Load Index, and the System Usability Scale (SUS). Gaming parameters, fatigue level and a technical documentation was implemented for further information.ResultsIn total, 18 patients after stroke (62.1 ± 14.1 years) with a unilateral paresis of the upper limb (MRC ≤4) were analyzed in this study. Both conditions were perceived as feasible. Comparing the IMI scores between conditions, perceived competence was significantly increased (z = −2.88, p = 0.004) and pressure/tension during training (z = −2.13, p = 0.034) was decreased during SG+FES. Furthermore, the task load was rated significantly lower for the SG+FES condition (z = −3.14, p = 0.002), especially the physical demand (z = −3.08, p = 0.002), while the performance was rated better (z = −2.59, p = 0.010). Responses to the SUS and the perceived level of fatigue did not differ between conditions (SUS: z = −0.79, p = 0.431; fatigue: z = 1.57, p = 0.115). For patients with mild to moderate impairments (MRC 3–4) the combined therapy provided no or little gaming benefit. The additional use of contralaterally controlled FES (ccFES), however, enabled severely impaired patients (MRC 0–1) to play the SG.DiscussionThe combination of SG with ccFES is feasible and well-accepted among patients after stroke. It seems that the additional use of ccFES may be more beneficial for severely impaired patients as it enables the execution of the serious game. These findings provide valuable implications for the development of rehabilitation systems by combining different therapeutic interventions to increase patients' benefit and proposes system modifications for home use.Clinical trial registrationhttps://drks.de/search/en, DRKS00025761.
Physical therapy for sleep apnea: a smartphone application for home-based physical therapy for patients with obstructive sleep apnea
Authors: Bui-Diem Khue , Hung Ching-Hsia , Zhu Guan-Cheng , Tho Nguyen Van , Nguyen-Binh Thu , Vu-Tran-Thien Quan , To-Truong Duy , Ngo-Thanh Hoan , Duong-Quy Sy 
Published: May 2023

PurposeIn this study, we described “PT for Sleep Apnea”, a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA).MethodsThe application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training.ResultsThe application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea.ConclusionIn the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.