bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pelvic floor therapy program for the treatment of female urinary incontinence in Belize: a pilot study
Authors: Rapp David E. , Zillioux Jacqueline , Sun Fionna , Jones Marieke , Little Michelle , Mitchell Jeanice 
Published: February 2024

IntroductionUrinary incontinence (UI) is highly prevalent in low- and middle-income countries (LMIC). Concurrently, the availability of surgical or conservative UI treatments in LMIC is limited.MethodsWe conducted a prospective feasibility study of Belize women with UI treated with pelvic floor physical therapy (PFPT) and education (PFE). Patients received individual PFPT/PFE over 2 days, consisting of biofeedback-enhanced PFMT in addition to behavioral, dietary, and general pelvic education. Patient completed a daily 6-month home regimen including 7 PFMT exercises (total 70 repetitions) comprising both endurance and quick flick exercises. Patients also performed comprehensive dietary and behavioral modification activities. Outcomes were assessed at baseline and 6-months, including validated symptom (ICIQ-FLUTS) and QOL (IIQ-7) questionnaires, and strength testing (PERFECT score, perineometry).ResultsTwenty-eight patients underwent baseline assessment. Four patients were lost to in-person 6-month follow-up, with two of these patients completing subjective assessment only by telephone. The mean (±SD) patient age, BMI, and parity were 50.0 (±10.0) years, 33.2 (±5.8), and 2.8 (±1.5). Provider assessment demonstrated patient comprehension of basic, endurance, and quick flick pelvic floor contractions in 28 (100%), 24 (86%), and 24 (86%) patients, respectively. At 6-month follow-up, significant improvements were seen across multiple validated questionnaire and strength measurement assessments. Median patient-reported improvement level was 7.0 on a 10-point Likert scale.DiscussionStudy patients demonstrated good understanding of PFMT/PFE and program completion was associated with significant improvements across a variety of subjective incontinence and quality of life outcomes, as well as objective strength testing.
Identification and validation of immune and cuproptosis - related genes for diabetic nephropathy by WGCNA and machine learning
Authors: Chen Yubing , Liao Lijuan , Wang Baoju , Wu Zhan 
Published: February 2024

BackgroundAs the leading cause of chronic kidney disease, diabetic kidney disease (DKD) is an enormous burden for all healthcare systems around the world. However, its early diagnosis has no effective methods.MethodsFirst, gene expression data in GEO database were extracted, and the differential genes of diabetic tubulopathy were obtained. Immune-related genesets were generated by WGCNA and immune cell infiltration analyses. Then, differentially expressed immune-related cuproptosis genes (DEICGs) were derived by the intersection of differential genes and genes related to cuproptosis and immune. To investigate the functions of DEICGs, volcano plots and GO term enrichment analysis was performed. Machine learning and protein-protein interaction (PPI) network analysis helped to finally screen out hub genes. The diagnostic efficacy of them was evaluated by GSEA analysis, receiver operating characteristic (ROC) curve, single-cell RNA sequencing and the Nephroseq website. The expression of hub genes at the animal level by STZ -induced and db/db DKD mouse models was further verified.ResultsFinally, three hub genes, including FSTL1, CX3CR1 and AGR2 that were up-regulated in both the test set GSE30122 and the validation set GSE30529, were screened. The areas under the curve (AUCs) of ROC curves of hub genes were 0.911, 0.935 and 0.922, respectively, and 0.946 when taking as a whole. Correlation analysis showed that the expression level of three hub genes demonstrated their negative relationship with GFR, while those of FSTL1 displayed a positive correlation with the level of serum creatinine. GSEA was enriched in inflammatory and immune-related pathways. Single-nucleus RNA sequencing indicated the main distribution of FSTL1 in podocyte and mesangial cells, the high expression of CX3CR1 in leukocytes and the main localization of AGR2 in the loop of Henle. In mouse models, all three hub genes were increased in both STZ-induced and db/db DKD models.ConclusionMachine learning was combined with WGCNA, immune cell infiltration and PPI analyses to identify three hub genes associated with cuproptosis, immunity and diabetic nephropathy, which all have great potential as diagnostic markers for DKD and even predict disease progression.
Effect of IV ferric carboxy maltose for moderate/severe anemia: a systematic review and meta-analysis
Authors: Khatib Mahalaqua Nazli , Sinha Anju Pradhan , Gaidhane Shilpa , Upadhyay Shilpa , Waghmare Nikita , Anil Abhishek , Saxena Deepak , Sawleshwarkar Shailendra , Simkhada Padam Prasad , Gaidhane Abhay , Quazi Zahiruddin Syed 
Published: February 2024

IntroductionAnemia remains a prevalent global health issue with varying severity. Intravenous iron supplementation, particularly with ferric carboxymaltose (FCM), has appeared as a possible therapeutic intervention for individuals with moderate to severe anemia. The study aimed to assess the efficacy and safety of ferric carboxymaltose (FCM) in reducing anemia.MethodsWe searched electronic databases, registries, websites, e-libraries, reference lists of reviews, citations, etc. We included randomized control trials (RCTs), non-RCTs, and single-arm studies, while observational studies, case series, and case studies were excluded. Two reviewers independently screened the studies and extracted the data. We included studies of moderate-to-severely anemic Indians and excluded Indians with other comorbidities. We assessed the risk of bias and the overall quality of evidence (QoE) using GRADE GDT.ResultWe identified 255 studies and included 14 studies (11 RCT, one non-RCT, and two single-arm studies) with 1,972 participants for qualitative analysis and 10 studies in the meta-analysis. All the included studies detailed the use of FCM for anemia. The primary outcomes assessed in the included studies were anemia, hemoglobin, and adverse events. The outcomes assessed ranged from 2 weeks to 12 weeks. The risk of bias varied across different studies with different outcomes. FCM is consistent with a fewer number of adverse events as compared to other interventions and provides “moderate” to “very low” QoE.ConclusionA slow single infusion of 1 gram of FCM is well-tolerated, safe, and effective in treating iron deficiency anemia (IDA) and surpasses other interventions (Iron Sucrose Complex (ISC), Iron sucrose, and ferrous ascorbate) in elevating hemoglobin levels and replenishing iron stores.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459363, CRD42023459363.
Chemical and microbiological insights into two littoral Antarctic demosponge species: Haliclona (Rhizoniera) dancoi (Topsent 1901) and Haliclona (Rhizoniera) scotti (Kirkpatrick 1907)
Authors: Papale Maria , Giannarelli Stefania , Azzaro di Rosamarina Maurizio , Ghezzi Lisa , Lo Giudice Angelina , Rizzo Carmen 
Published: February 2024

IntroductionAntarctic Porifera have gained increasing interest as hosts of diversified associated microbial communities that could provide interesting insights on the holobiome system and its relation with environmental parameters.MethodsThe Antarctic demosponge species Haliclona dancoi and Haliclona scotti were targeted for the determination of persistent organic pollutant (i. e., polychlorobiphenyls, PCBs, and polycyclic aromatic hydrocarbons, PAHs) and trace metal concentrations, along with the characterization of the associated prokaryotic communities by the 16S rRNA next generation sequencing, to evaluate possible relationships between pollutant accumulation (e.g., as a stress factor) and prokaryotic community composition in Antarctic sponges. To the best of our knowledge, this approach has been never applied before.ResultsNotably, both chemical and microbiological data on H. scotti (a quite rare species in the Ross Sea) are here reported for the first time, as well as the determination of PAHs in Antarctic Porifera. Both sponge species generally contained higher amounts of pollutants than the surrounding sediment and seawater, thus demonstrating their accumulation capability. The structure of the associated prokaryotic communities, even if differing at order and genus levels between the two sponge species, was dominated by Proteobacteria and Bacteroidota (with Archaea abundances that were negligible) and appeared in sharp contrast to communities inhabiting the bulk environment.DiscussionsResults suggested that some bacterial groups associated with H. dancoi and H. scotti were significantly (positively or negatively) correlated to the occurrence of certain contaminants.
Screening of native Saccharomyces cerevisiae strains from Chile for beer production
Authors: Moreira-Ramos Sandra , Saavedra-Torrico Jorge , G-Poblete Camila , Godoy Olivares Liliana , Sangorrin Marcela , Ganga María Angélica 
Published: February 2024

IntroductionBeer is one of the most consumed alcoholic drinks in the world, and this industry is a growing market that demands different properties to satisfy new consumers. The yeasts are used in different fermented beverages to contribute to new flavors. However, yeast strains used in the beer industry are limited so far, thus the diversity of flavors is very restricted. Therefore, the use of native yeast strains has been taking more importance with the purpose of conferring differentiated organoleptic properties to the product. Based on this observation the potentiality of native Saccharomyces cerevisiae strains obtained from different localities in Chile was researched.MethodsIn this work was selected those strains that produced the highest ethanol concentration (nearly 6% v/v), consumed the highest amounts of sugars, and produced the lowest amounts of organic acids in the resulting beers. Finally, we did a beer tasting to select those strains that added different flavors to the final beer compared with a commercial strain used.Results and discussionIn this study, two native strains that produced fruity descriptors are described, which could be used in the future in brewing, craft or industrial production.
A novel rapid bioluminescence-based antimicrobial susceptibility testing method based on adenosine triphosphate consumption
Authors: Sever Elif Arik , Aybakan Esma , Beşli Yeşim , Karatuna Onur , Kocagoz Tanil 
Published: February 2024

IntroductionStandard, phenotypic antimicrobial susceptibility testing (AST) methods require 16–20 h of incubation and are considered as the bottleneck in providing timely input for appropriate antimicrobial treatment. In this study, a novel adenosine triphosphate (ATP)-bioluminescence-based method which allows rapid AST within 3 h was described.MethodsStandard AST was performed for 56 Enterobacterales isolates using EUCAST disk diffusion (DD) methodology. For the bioluminescence-based rapid AST, suspensions of bacteria were prepared using Mueller–Hinton broth to obtain a turbidity of 0.5 McFarland. The suspensions were distributed into 96-well microtiter plates. ATP (20 mM) and fixed concentrations of different antibiotics were added. Following incubation at 37°C for 1 h, a luminescent reaction mixture, including the substrate luciferin and luciferase enzyme solutions, was added. The chemiluminescence was monitored using an imaging system. Light production demonstrated the presence of ATP, indicating that the isolate was susceptible to the antibiotic in the well. Absence or decrease of light intensity, compared with the growth control well, indicated the use of ATP as an indirect measure of bacterial growth, and therefore resistance to the antibiotic in the well.ResultsThe novel AST method was tested using a total of 348 test wells. Concordance was achieved for 290 (83.3%) of the tests, whereas 52 (14.9%) and 6 (1.7%) tests caused minor and major errors, respectively.DiscussionIn this study, a bioluminescence-based rapid AST was developed based on the consumption of ATP by bacteria. Our method’s uniqueness relies on determining ATP consumption by microorganisms in the presence or absence of an antibiotic. The novel AST method described in this study lays the groundwork for obtaining rapid results, which should be considered as a proof of concept. With further optimization studies, this novel method can provide higher accuracy and be introduced into clinical practice as a routine AST method.
Causality of unsaturated fatty acids and psoriasis a Mendelian randomization study
Authors: Li Junchen , Shen Qian , Guo Chenqi , Wang Yingdong , Ma Yuxiao , Zhang Yu 
Published: February 2024

BackgroundMany observational studies have identified a link between unsaturated fatty acids and psoriasis. However, they contain reverse causality and confounding factors, and there is no definite causal study between unsaturated fatty acids and psoriasis.ObjectivesAnalysis of causality between unsaturated fatty acids and psoriasis by Mendelian randomization.MethodsWe used IEU Open GWAS Project, omega-3 PUFA and omega-6 PUFA data from 114,999 subjects, MUFA data from 13,535 subjects, and psoriasis data from 4,510 cases and 212,242 controls were included. We employed the inverse-variance weighted (IVW) method as the primary analytical approach and four additional MR methods. Moreover, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane’s Q and MR-Egger intercept tests, respectively. Finally, we performed sensitivity analyses to enhance our findings’ precision and veracity.ResultsIVW results showed no causal effect of omega-3 PUFA on psoriasis (p = 0.334; OR, 0.909; 95% CI, 0.748–1.104), omega-6 PUFA cause psoriasis (p = 0.046; OR, 1.174; 95% CI, 1.003–1.374), MUFA cause psoriasis (p = 0.032; OR, 1.218; 95% CI, 1.018–1.457), no causal effect of omega-3 PUFA in psoriasis (p = 0.695; OR, 0.989; 95% CI, 0.937–1.044), no causal effect of omega-6 PUFA in psoriasis (p = 0.643; OR, 1.013; 95% CI, 0.960–1.068), psoriasis is not causal to MUFA (p = 0.986; OR, 1.000; 95% CI, 0.949–1.055). Heterogeneity, horizontal pleiotropy, and sensitivity analyses showed reliable results.ConclusionWe found that circulating omega-6 PUFA and MUFA cause psoriasis, while omega-3 PUFA do not. Treatments that lower circulating omega-6 PUFA and MUFA are effective in psoriasis. After a better understanding of fatty acid intake and circulation, the population can be advised to regulate their diet.
Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial
Authors: Germani Marco Maria , Vetere Guglielmo , Giordano Mirella , Ciracì Paolo , Capone Iolanda , Tamborini Elena , Conca Elena , Busico Adele , Pietrantonio Filippo , Piva Vittoria Matilde , Boccaccino Alessandra , Simionato Francesca , Bortolot Martina , Manca Paolo , Lonardi Sara , Conca Veronica , Borelli Beatrice , Carullo Martina , Del Re Marzia , Fontanini Gabriella , Rossini Daniele , Cremolini Chiara 
Published: February 2024

BackgroundRetreatment with anti-EGFR monoclonal antibodies is a promising strategy in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who achieved benefit from previous anti-EGFR exposure upon exclusion of mutations in RAS/BRAF genes according to circulating tumor DNA (ctDNA) analysis by means of liquid biopsy (LB). This treatment approach is now being investigated in the randomized phase II trial PARERE (NCT04787341). We here present preliminary findings of molecular screening.MethodsPatients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. The next-generation sequencing (NGS) panel Oncomine™ was employed for ctDNA testing.ResultsA total of 218 patients underwent LB, and ctDNA sequencing was successful in 201 of them (92%). RAS/BRAFV600E mutations were found in 68 (34%) patients and were mainly subclonal (median variant allele fraction [VAF] for KRAS, NRAS, and BRAF mutant clones: 0.52%, 0.62%, and 0.12%, respectively; p = 0.01), with KRASQ61H being the most frequently detected (31%). Anti-EGFR-free intervals did not predict ctDNA molecular status (p = 0.12). Among the 133 patients with RAS/BRAFV600E wt tumors according to LB, 40 (30%) harbored a mutation in at least another gene potentially implied in anti-EGFR resistance, mainly with subclonal expression (median VAF, 0.56%). In detail, alterations in PIK3CA, FBXW7, GNAS, MAP2K, ERBB2, BRAF (class I and II non-BRAFV600E), SMAD, EGFR, AKT1, and CTNNB1 occurred in 13%, 8%, 7%, 3%, 2%, 2%, 1%, 1%, 1%, and 1% cases, respectively. Co-mutations were detected in 13 (33%) out of 40 patients.ConclusionsThis is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.
Frailty worsens long-term survival in patients with colorectal cancer: a systematic review and meta-analysis
Authors: Han Jiangxue , Zhang Qin , Lan Jiarong , Yu Fang , Liu Jie 
Published: February 2024

BackgroundColorectal cancer (CRC) is the 3rd most common cancer in men and 2nd most common malignancy in females across the globe leading to high mortality rates. Frailty is an age-related syndrome that has been associated with high morbidity and mortality. This systematic review aimed to examine if frailty can predict long-term (&gt;1 year) outcomes of patients with CRC.MethodsThis PROSPERO registered review examined the databases of PubMed, Embase, and Web of Science till 4th September 2023 for cohort studies assessing the association between frailty and long-term outcomes of CRC.Results15 studies with 45288 patients were included. 6573 patients (14.5%) were frail. Meta-analysis demonstrated that frailty was associated with statistically significant poor overall survival (OS) (HR: 2.11 95% CI: 1.44, 3.08 I2 = 94%) (14 studies), cancer-specific survival (CSS) (HR: 4.59 95% CI: 2.75, 7.67 I2 = 38%) (2 studies), and disease-free survival (DFS) (HR: 1.46 95% CI: 1.28, 1.66 I2 = 0%) (5 studies) after CRC. Subgroup analysis for OS based on study type, location, sample size, stage of cancer, percentage with frailty, treatment, adjustment for CRC stage and comorbidities, and follow-up did not change the results. These results were not altered in significance on sensitivity analysis.ConclusionOur results show that frail CRC patients have poor OS and DFS as compared to non-frail patients. Variations in frailty measurement tools and high inter-study heterogeneity are major limitations of the review.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO, CRD42023450586
The role of adjuvant chemotherapy in rectal cancer patients with ypT0-2N0 after neoadjuvant chemoradiotherapy
Authors: Yang Jianguo , Deng Qican , Chen Zhenzhou , Chen Yajun , Fu Zhongxue 
Published: February 2024

BackgroundNeoadjuvant chemoradiotherapy has emerged as the established treatment for locally advanced rectal cancer. Nevertheless, there remains a debate regarding the necessity of adjuvant chemotherapy for patients with locally advanced rectal cancer who exhibit a favorable tumor response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery. Thus, the objective of this study is to investigate the impact of adjuvant chemotherapy on the oncological prognosis of rectal cancer patients who have a good response to neoadjuvant chemoradiotherapy.Materials and methodsThe study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles were searched in the Web of Science, PubMed, and Cochrane Library databases. The primary outcomes assessed were 5-year overall survival, disease-free survival, cancer-specific survival, recurrence-free survival, local recurrence, and distant metastasis. The data was summarized using a random effects model.ResultsA meta-analysis was conducted using 18 retrospective studies published between 2009 and 2023. The studies included 9 from China and 5 from Korea, involving a total of 6566 patients with ypT0-2N0 rectal cancer after neoadjuvant chemoradiotherapy. The pooled data revealed that adjuvant chemotherapy significantly improved 5-year overall survival (OR=1.75, 95% CI: 1.15-2.65, P=0.008), recurrence-free survival (OR=1.73, 95% CI: 1.20-2.48, P=0.003), and reduced distant metastasis (OR=0.68, 95% CI: 0.51-0.92, P=0.011). However, adjuvant chemotherapy did not have a significant effect on disease-free survival, cancer-specific survival, and local recurrence in ypT0-2N0 rectal cancer. Subgroup analysis indicated that adjuvant chemotherapy was beneficial in improving overall survival for ypT1-2N0 rectal cancer (OR=1.89, 95% CI: 1.13-3.19, P=0.003).ConclusionThe findings of the meta-analysis suggest that adjuvant chemotherapy may provide benefits in terms of oncological outcomes for rectal cancer patients with ypT0-2N0 after neoadjuvant chemoradiotherapy and radical surgery. However, further prospective clinical studies are needed to confirm these findings.
Astragalus polysaccharides ameliorate epileptogenesis, cognitive impairment, and neuroinflammation in a pentylenetetrazole-induced kindling mouse model
Authors: Lu Yuling , Lin Minglin , Ou Sijie , Sun Lanfeng , Qian Kai , Kuang Huimin , Wu Yuan 
Published: February 2024

Background: Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that Astragalus polysaccharides (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism.Methods: Initially, we employed pentylenetetrazol-induced seizure mice to validate APS’ effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action.Results: APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model.Conclusion: The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.