bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in tryptophan metabolism and de novo NAD+ biosynthesis within the microbiota-gut-brain axis in chronic intestinal inflammation
Authors: Devereaux Jeannie , Robinson Ainsley M. , Stavely Rhian , Davidson Majid , Dargahi Narges , Ephraim Ramya , Kiatos Dimitros , Apostolopoulos Vasso , Nurgali Kulmira 
Published: July 2024

BackgroundInflammatory bowel disease is an incurable and idiopathic disease characterized by recurrent gastrointestinal tract inflammation. Tryptophan metabolism in mammalian cells and some gut microbes comprise intricate chemical networks facilitated by catalytic enzymes that affect the downstream metabolic pathways of de novo nicotinamide adenine dinucleotide (NAD+) synthesis. It is hypothesized that a correlation exists between tryptophan de novo NAD+ synthesis and chronic intestinal inflammation.MethodsTranscriptome analysis was performed using high-throughput sequencing of mRNA extracted from the distal colon and brain tissue of Winnie mice with spontaneous chronic colitis and C57BL/6 littermates. Metabolites were assessed using ultra-fast liquid chromatography to determine differences in concentrations of tryptophan metabolites. To evaluate the relative abundance of gut microbial genera involved in tryptophan and nicotinamide metabolism, we performed 16S rRNA gene amplicon sequencing of fecal samples from C57BL/6 and Winnie mice.ResultsTryptophan and nicotinamide metabolism-associated gene expression was altered in distal colons and brains of Winnie mice with chronic intestinal inflammation. Changes in these metabolic pathways were reflected by increases in colon tryptophan metabolites and decreases in brain tryptophan metabolites in Winnie mice. Furthermore, dysbiosis of gut microbiota involved in tryptophan and nicotinamide metabolism was evident in fecal samples from Winnie mice. Our findings shed light on the physiological alterations in tryptophan metabolism, specifically, its diversion from the serotonergic pathway toward the kynurenine pathway and consequential effects on de novo NAD+ synthesis in chronic intestinal inflammation.ConclusionThe results of this study reveal differential expression of tryptophan and nicotinamide metabolism-associated genes in the distal colon and brain in Winnie mice with chronic intestinal inflammation. These data provide evidence supporting the role of tryptophan metabolism and de novo NAD+ synthesis in IBD pathophysiology.
Metabolomics reveals altered metabolites in cirrhotic patients with severe portal hypertension in Tibetan population
Authors: Ye Yanting , Xia Chao , Hu Hong , Tang Shihang , Huan Hui 
Published: July 2024

BackgroundPortal hypertension (PHT) presents a challenging issue of liver cirrhosis. This study aims to identify novel biomarkers for severe PHT (SPHT) and explore the pathophysiological mechanisms underlying PHT progression.MethodsTwenty-three Tibetan cirrhotic patients who underwent hepatic venous pressure gradient (HVPG) measurement were included. Eleven patients had an HVPG between 5 mmHg and 15 mmHg (MPHT), while 12 had an HVPG ≥16 mmHg (SPHT). Peripheral sera were analyzed using liquid chromatograph-mass spectrometer for metabolomic assessment. An additional 14 patients were recruited for validation of metabolites.ResultsSeven hundred forty-five metabolites were detected and significant differences in metabolomics between MPHT and SPHT patients were observed. Employing a threshold of p &lt; 0.05 and a variable importance in projection score &gt;1, 153 differential metabolites were identified. A significant number of these metabolites were lipids and lipid-like molecules. Pisumionoside and N-decanoylglycine (N-DG) exhibited the highest area under the curve (AUC) values (0.947 and 0.9091, respectively). Additional differential metabolites with AUC &gt;0.8 included 6-(4-ethyl-2-methoxyphenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid, sphinganine 1-phosphate, 4-hydroxytriazolam, 4,5-dihydroorotic acid, 6-hydroxy-1H-indole-3-acetamide, 7alpha-(thiomethyl)spironolactone, 6-deoxohomodolichosterone, glutaminylisoleucine, taurocholic acid 3-sulfate, and Phe Ser. Enzyme-linked immunosorbent assay further confirmed elevated levels of sphinganine 1-phosphate, N-DG, and serotonin in SPHT patients. Significant disruptions in linoleic acid, amino acid, sphingolipid metabolisms, and the citrate cycle were observed in SPHT patients.ConclusionPisumionoside and N-DG are identified as promising biomarkers for SPHT. The progression of PHT may be associated with disturbances in lipid, linoleic acid, and amino acid metabolisms, as well as alterations in the citrate cycle.
Anatomical-related factors and outcome of percutaneous short-term spinal cord stimulation electrode shift in patients with disorders of consciousness: a retrospective study
Authors: He Qiheng , Yang Chaozhi , Xu Yangxi , Niu Hongchuan , Wu Haitao , Huang Haitao , Chai Xiaoke , Cao Tianqing , Wang Nan , Wong Peiling , He Jianghong , Yang Yi , Zhao Jizong 
Published: July 2024

BackgroundDisorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes.MethodsThis retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure.ResultsOur findings revealed that in patients with better outcome, there are significant less patient with electrode shift (p = 0.019). Further, a linear correlation was found between the length of electrode shift and patients’ outcome (Rho = 0.583, p = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode (p = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS (p = 0.033).ConclusionThese results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients’ outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention.
Knowledge graph construction for heart failure using large language models with prompt engineering
Authors: Xu Tianhan , Gu Yixun , Xue Mantian , Gu Renjie , Li Bin , Gu Xiang 
Published: July 2024

IntroductionConstructing an accurate and comprehensive knowledge graph of specific diseases is critical for practical clinical disease diagnosis and treatment, reasoning and decision support, rehabilitation, and health management. For knowledge graph construction tasks (such as named entity recognition, relation extraction), classical BERT-based methods require a large amount of training data to ensure model performance. However, real-world medical annotation data, especially disease-specific annotation samples, are very limited. In addition, existing models do not perform well in recognizing out-of-distribution entities and relations that are not seen in the training phase.MethodIn this study, we present a novel and practical pipeline for constructing a heart failure knowledge graph using large language models and medical expert refinement. We apply prompt engineering to the three phases of schema design: schema design, information extraction, and knowledge completion. The best performance is achieved by designing task-specific prompt templates combined with the TwoStepChat approach.ResultsExperiments on two datasets show that the TwoStepChat method outperforms the Vanillia prompt and outperforms the fine-tuned BERT-based baselines. Moreover, our method saves 65% of the time compared to manual annotation and is better suited to extract the out-of-distribution information in the real world.
The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss
Authors: do Amaral Jônatas Bussador , Peron Kelly Abdo , Soeiro Tracy Lima Tavares , Scott Marina Cançado Passarelli , Hortense Flávia Tatiana Pedrolo , da Silva Michelly Damasceno , França Carolina Nunes , Nali Luiz Henrique da Silva , Bachi André Luis Lacerda , de Oliveira Penido Norma 
Published: July 2024

IntroductionSudden sensorineural hearing loss (SSNHL) is a common emergency symptom in otolaryngology that requires immediate diagnosis and treatment. SSNHL has a multifactorial etiology, and its pathophysiologic mechanisms may be associated with inflammatory and metabolic changes that may affect the cochlear microenvironment or its nervous component, thus triggering the process or hindering hearing recovery. Therefore, the aim of this study was to assess metabolic and inflammatory changes to identify systemic parameters that could serve as prognostic factors for hearing recovery in patients with SSNHL.Materials and methodsThirty patients with a sudden hearing loss of at least 30 dB in three contiguous frequencies were enrolled in this study. Patients were followed up for 4 months and peripheral blood samples were collected at 7 days (V1), 30 days (V2) and 120 days (V3). Interleukins (IL)-1F7, IL-2, IL-4, IL-5, IL-6, IL-10, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and adiponectin were quantified in serum. In addition, lipid and glycemic profiles as well as concentration of creatinine, uric acid, fructosamine, peroxide, total proteins and albumin were analyzed. Patients underwent weekly ear-specific hearing tests with standard pure tone thresholds for frequencies of 250–8,000 Hz, speech recognition threshold and word recognition score.ResultsPatients with SSNHL were divided into a group of patients who did not achieve hearing recovery (n = 14) and another group who achieved complete and significant recovery (n = 16). Most serologic parameters showed no significant changes or values indicating clinical changes. However, IFN-γ levels decreased by 36.3% between V1 and V2. The cytokine TNF-α showed a statistically significant decrease from V1 to V3 (from 22.91 to 10.34 pg./mL). Adiponectin showed a decrease from 553.7 ng/mL in V1 to 454.4 ng/mL in V3.DiscussionOur results show that serologic cytokine levels change in the acute phase of manifestation of SSNHL and establish a parallel between systemic changes and improvements in hearing, especially TNF-α, which showed differences in hearing recovery. The use of IFN-γ, TNF-α and adiponectin may elucidate the clinical improvement in these patients.
Network analysis of negative emotions in patients with episodic migraine: need for a multidisciplinary perspective
Authors: Guerra Federica , Di Giacomo Dina , Ranieri Jessica , Saporito Gennaro , Sucapane Patrizia , Totaro Rocco , Pistoia Francesca 
Published: July 2024

BackgroundEpisodic migraine (EM) is the second most prevalent neurological disorder worldwide and is responsible for more disability than all other neurological disorders combined. Triggers for the development of migraine include, stress, emotional burden, low blood sugar levels, tobacco, skipped meals, anxious and depressive feelings. Migraine affects both children and adults, occurring three times more frequently in women than in men.ObjectiveThe aim of this study was to evaluate the psychological profile of EM patients and the relationship among negative emotions in EM patients, analyzing self-efficacy measures in pain management.DesignWe performed an observational study in 60 outpatients aged 18–55 years (mean age 33.8; SD ±10.4) with EM.MethodsAll patients have been enrolled at the Headache Center of the San Salvatore Hospital of L’Aquila. The assessment comprised five standardized psychological self-assessments investigating relevant emotional dimensions and pain self-efficacy, along with two questionnaires assessing migraine-related disability. A network analysis of negative emotions was performed to evaluate which emotional traits and relationships play a crucial role in pain coping and management.ResultsOur findings indicate that migraine significantly impairs the quality of life of patients in their daily lives. Over half of the patients reported experiencing severe disability, with negative emotions significantly influencing their ability to cope with pain and maintain productivity during migraine attacks. Dysphoric variables (irritability, interpersonal resentment, and surrender) were correlated with difficulties in emotion regulation ability and with the capacity of engaging in goal-directed behaviors despite experiencing pain. The ability to regulate one’s emotions and manage dysphoria were positively correlated with pain self-efficacy, whereas positive mental health was associated with individuals’ confidence in performing activities despite experiencing pain.ConclusionNegative emotions had a negative correlation with positive mental health and were linked to a lower capacity to carry out daily activities despite experiencing migraine pain. This suggests that psychological interventions could improve mental health and potentially surpassing the effects of pharmacological interventions alone in migraine management. An integrated, patient-centered approach may represent an effective paradigm to address and reduce the burden of migraine, leading to a reduction in healthcare costs.
Comparison of the diagnostic efficacy of systemic inflammatory indicators in the early diagnosis of ovarian cancer
Authors: Song Liyun , Wu Qi , Bai Suning , Zhao Jing , Qi Jie , Zhang Junmei 
Published: July 2024

BackgroundThis study aimed to determine the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the combination of the six inflammatory-nutritional markers for ovarian cancer (OC) to identify the best diagnostic indicator for OC early diagnosis. An extensive study was performed to establish the connection between these indicators and the pathological aspects of OC.MethodsA total of 170 individuals were included in this study, with 87 diagnosed with OC and 83 with benign ovarian tumors (BOTs). The diagnostic abilities of the variables were evaluated by calculating sensitivity, specificity, and area under the ROC curves. Through the use of DCA, we evaluated the variables’ clinical value in the discrimination of ovarian masses.ResultsAll markers showed significant diagnostic power for OC. CA125, HE4, SII, FAR, and MLR levels significantly increased from the BOTs group to the early-stage OC group. The advanced-stage OC group had significantly lower PNI values compared to the early-stage OC group but significantly higher levels of CA125, HE4, SII, NLR, and FAR. Moreover, the OC group with lymph node metastasis exhibited significantly higher levels of CA125, HE4, SII, NLR, PLR, and FAR, in contrast to the non-metastatic group, while PNI levels were significantly lower. Categorical factors, such as histological grade and pathological classification, showed noticeable discrepancies in CA125 and HE4 levels. NLR was significantly different among the pathological type groups. Among the six inflammatory-nutritional markers, the FAR displayed the greatest diagnostic value. In the analysis of logistic regression, it was observed that a combination marker containing all six inflammatory-nutritional markers exhibited a notably higher AUC value (0.881; 95% CI, 0.823 - 0.926) than any of the individual marker.ConclusionPNI, NLR, PLR, MLR, SII, and FAR showed excellent diagnostic performance for OC. The combination of these markers demonstrated a superior diagnostic capability compared to each individual one. The systemic inflammatory indicators may be helpful to diagnose OC.
Pure red cell aplasia among ABO mismatched hematopoietic stem cell transplant recipients: a 13-years retrospective study and literature review
Authors: Metafuni Elisabetta , Busnego Barreto Maria Teresa , Valentini Caterina Giovanna , Giammarco Sabrina , Limongiello Maria Assunta , Sorà Federica , Bianchi Maria , Massini Giuseppina , Piccirillo Nicola , Putzulu Rossana , Frioni Filippo , Bacigalupo Andrea , Teofili Luciana , Chiusolo Patrizia , Sica Simona 
Published: July 2024

BackgroundPure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload.MethodsWe performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected.ResultsThe literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p&lt;0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p&lt;0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders.ConclusionsStandardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.
The diagnostic value of CT-based radiomics nomogram for solitary indeterminate smoothly marginated solid pulmonary nodules
Authors: Zhang Chengzhou , Zhou Huihui , Li Mengfei , Yang Xinyu , Liu Jinling , Dai Zhengjun , Ma Heng , Wang Ping 
Published: July 2024

ObjectivesThis study aimed to explore the value of radiomics nomogram based on computed tomography (CT) on the diagnosis of benign and malignant solitary indeterminate smoothly marginated solid pulmonary nodules (SMSPNs).MethodsThis study retrospectively reviewed 205 cases with solitary indeterminate SMSPNs on CT, including 112 cases of benign nodules and 93 cases of malignant nodules. They were divided into training (n=143) and validation (n=62) cohorts based on different CT scanners. Radiomics features of the nodules were extracted from the lung window CT images. The variance threshold method, SelectKBest, and least absolute shrinkage and selection operator were used to select the key radiomics features to construct the rad-score. Through multivariate logistic regression analysis, a nomogram was built by combining rad-score, clinical factors, and CT features. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC).ResultsA total of 19 radiomics features were selected to construct the rad-score, and the nomogram was constructed by the rad-score, one clinical factor (history of malignant tumor), and three CT features (including calcification, pleural retraction, and lobulation). The nomogram performed better than the radiomics model, clinical model, and experienced radiologists who specialized in thoracic radiology for nodule diagnosis. The AUC values of the nomogram were 0.942 in the training cohort and 0.933 in the validation cohort. The calibration curve and decision curve showed that the nomogram demonstrated good consistency and clinical applicability.ConclusionThe CT-based radiomics nomogram achieved high efficiency in the preoperative diagnosis of solitary indeterminate SMSPNs, and it is of great significance in guiding clinical decision-making.
Mapping of flumioxazin tolerance in a snap bean diversity panel leads to the discovery of a master genomic region controlling multiple stress resistance genes
Authors: Saballos Ana I. , Brooks Matthew D. , Tranel Patrick J. , Williams Martin M. 
Published: July 2024

IntroductionEffective weed management tools are crucial for maintaining the profitable production of snap bean (Phaseolus vulgaris L.). Preemergence herbicides help the crop to gain a size advantage over the weeds, but the few preemergence herbicides registered in snap bean have poor waterhemp (Amaranthus tuberculatus) control, a major pest in snap bean production. Waterhemp and other difficult-to-control weeds can be managed by flumioxazin, an herbicide that inhibits protoporphyrinogen oxidase (PPO). However, there is limited knowledge about crop tolerance to this herbicide. We aimed to quantify the degree of snap bean tolerance to flumioxazin and explore the underlying mechanisms.MethodsWe investigated the genetic basis of herbicide tolerance using genome-wide association mapping approach utilizing field-collected data from a snap bean diversity panel, combined with gene expression data of cultivars with contrasting response. The response to a preemergence application of flumioxazin was measured by assessing plant population density and shoot biomass variables.ResultsSnap bean tolerance to flumioxazin is associated with a single genomic location in chromosome 02. Tolerance is influenced by several factors, including those that are indirectly affected by seed size/weight and those that directly impact the herbicide's metabolism and protect the cell from reactive oxygen species-induced damage. Transcriptional profiling and co-expression network analysis identified biological pathways likely involved in flumioxazin tolerance, including oxidoreductase processes and programmed cell death. Transcriptional regulation of genes involved in those processes is possibly orchestrated by a transcription factor located in the region identified in the GWAS analysis. Several entries belonging to the Romano class, including Bush Romano 350, Roma II, and Romano Purpiat presented high levels of tolerance in this study. The alleles identified in the diversity panel that condition snap bean tolerance to flumioxazin shed light on a novel mechanism of herbicide tolerance and can be used in crop improvement.