bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health economic evaluation of blended collaborative care for older multimorbid heart failure patients: study protocol
Authors: Derendorf Lisa , Stock Stephanie , Simic Dusan , Shukri Arim , Zelenak Christine , Nagel Jonas , Friede Tim , Herbeck Belnap Birgit , Herrmann-Lingen Christoph , Pedersen Susanne S. , Sørensen Jan , Müller and on behalf of the ESCAPE Dirk 
Published: April 2024

Abstract
Background
Integrated care, in particular the ‘Blended Collaborative Care (BCC)’ strategy, may have the potential to improve health-related quality of life (HRQoL) in multimorbid patients with heart failure (HF) and psychosocial burden at no or low additional cost. The ESCAPE trial is a randomised controlled trial for the evaluation of a BCC approach in five European countries. For the economic evaluation of alongside this trial, the four main objectives were: (i) to document the costs of delivering the intervention, (ii) to assess the running costs across study sites, (iii) to evaluate short-term cost-effectiveness and cost-utility compared to providers’ usual care, and (iv) to examine the budgetary implications.

Methods
The trial-based economic analyses will include cross-country cost-effectiveness and cost-utility assessments from a payer perspective. The cost-utility analysis will calculate quality-adjusted life years (QALYs) using the EQ-5D-5L and national value sets. Cost-effectiveness will include the cost per hospital admission avoided and the cost per depression-free days (DFD). Resource use will be measured from different sources, including electronic medical health records, standardised questionnaires, patient receipts and a care manager survey. Uncertainty will be addressed using bootstrapping.

Discussion
The various methods and approaches used for data acquisition should provide insights into the potential benefits and cost-effectiveness of a BCC intervention. Providing the economic evaluation of ESCAPE will contribute to a country-based structural and organisational planning of BCC (e.g., the number of patients that may benefit, how many care managers are needed). Improved care is expected to enhance health-related quality of life at little or no extra cost.

Trial registration
The study follows CHEERS2022 and is registered at the German Clinical Trials Register (DRKS00025120).
MiR-98-5p plays suppressive effects on IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting CASP3
Authors: Lv Hang , Liu Peiran , Hu Hai , Li Xiaodong , Li Pengfei 
Published: April 2024

Abstract
Background
This study aims to explore how miR-98-5p affects osteoarthritis, focusing on its role in chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation.

Methods
Quantitative real-time PCR was used to measure miR-98-5p and CASP3 mRNA levels in OA cartilage tissues and IL-1β-treated CHON-001 cells. We predicted miR-98-5p and CASP3 binding sites using TargetScan and confirmed them via luciferase reporter assays. Chondrocyte viability was analyzed using CCK-8 assays, while pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified via ELISA. Caspase-3 activity was examined to assess apoptosis, and Western blotting was conducted for protein marker quantification.

Results
Our results showed lower miR-98-5p levels in both OA cartilage and IL-1β-stimulated cells. Increasing miR-98-5p resulted in reduced pro-inflammatory cytokines, decreased caspase-3 activity, and improved cell viability. Furthermore, miR-98-5p overexpression hindered IL-1β-induced ECM degradation, evident from the decline in MMP-13 and β-catenin levels, and an increase in COL2A1 expression. MiR-98-5p's impact on CASP3 mRNA directly influenced its expression. Mimicking miR-98-5p's effects, CASP3 knockdown also inhibited IL-1β-induced inflammation, apoptosis, and ECM degradation. In contrast, CASP3 overexpression negated the suppressive effects of miR-98-5p.

Conclusions
In conclusion, our data collectively suggest that miR-98-5p plays a protective role against IL-1β-induced damage in chondrocytes by targeting CASP3, highlighting its potential as a therapeutic target for OA.
A combined subsegmentectomy of right S9 + 10b with single direction thoracoscopic surgery
Authors: Shen Cheng , Liu Chengwu 
Published: April 2024

AbstractSegmentectomy is widely used to treat pulmonary nodules and more functional lungs can be preserved in patients. For pulmonary nodules deep near the intersegmental border, only one single segmentectomy may not achieve adequate surgical margins, and combined subsegmental resection becomes the most suitable treatment option. Thoracoscopic combined anatomical resections involving both of right S9 and S10b are one of the most challenging cases, especially in the right chest. We previously reported a case of combined subsegmental resection of the left complex basal segment (LS9b + 10b). To our knowledge, there has been no report of combined subsegmental resection of the right S9 and S10b. Here, we aim to introduce a different technique named as “open-gate”, which means that the intersegmental border between S7 and S10 was cut open along the intersegmental septa, to deal with complex combined basal subsegmental resections.
A retrospective study of morbidity and mortality of chronic acid sphingomyelinase deficiency in Germany
Authors: Mengel Eugen , Muschol Nicole , Weinhold Natalie , Ziagaki Athanasia , Neugebauer Julia , Antoni Benno , Langer Laura , Gasparic Maja , Guillonneau Sophie , Fournier Marie , Laredo Fernando , Pulikottil-Jacob Ruth 
Published: April 2024

Abstract
Background
Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, potentially fatal lysosomal storage disease that exhibits a broad spectrum of clinical phenotypes. There is a need to expand the knowledge of disease mortality and morbidity in Germany because of limited information on survival analysis in patients with chronic ASMD (type B or type A/B).

Methods
This observational, multicentre, retrospective cohort study was conducted using medical records of patients with the first symptom onset/diagnosis of ASMD type B or type A/B between 1st January 1990 and 31st July 2021 from four German medical centres. Eligible medical records were abstracted to collect data on demographic characteristics, medical history, hospitalisation, mortality, and causes of death from disease onset to the last follow-up/death. Survival outcomes were estimated using the Kaplan–Meier analysis. Standardised mortality ratio (SMR) was also explored.

Results
This study included 33 chart records of patients with ASMD type B (n = 24) and type A/B (n = 9), with a median (interquartile range [IQR]) age of 8.0 [3.0–20.0] years and 1.0 [1.0–2.0] years, respectively, at diagnosis. The commonly reported manifestations were related to spleen (100.0%), liver (93.9%), and respiratory (77.4%) abnormalities. Nine deaths were reported at a median [IQR] age of 17.0 [5.0–25.0] years, with 66.7% of overall patients deceased at less than 18 years of age; the median [IQR] age at death for patients with ASMD type B (n = 4) and type A/B (n = 5) was 31.0 [11.0–55.0] and 9.0 [4.0–18.0] years, respectively. All deaths were ASMD-related and primarily caused by liver or respiratory failures or severe progressive neurodegeneration (two patients with ASMD type A/B). The median (95% confidence interval [CI]) overall survival age since birth was 45.4 (17.5–65.0) years. Additionally, an SMR [95% CI] analysis (21.6 [9.8–38.0]) showed that age-specific deaths in the ASMD population were 21.6 times more frequent than that in the general German population.

Conclusions
This study highlights considerable morbidity and mortality associated with ASMD type B and type A/B in Germany. It further emphasises the importance of effective therapy for chronic ASMD to reduce disease complications.
Augmented ERO1α upon mTORC1 activation induces ferroptosis resistance and tumor progression via upregulation of SLC7A11
Authors: Wang Zixi , Zong Huaiyuan , Liu Weiwei , Lin Wei , Sun Anjiang , Ding Zhao , Chen Xu , Wan Xiaofeng , Liu Yanyan , Hu Zhongdong , Zhang Hongbing , Li Hongwu , Liu Yehai , Li Dapeng , Zhang Sumei , Zha Xiaojun 
Published: April 2024

Abstract
Background
The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood.

Methods
Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models.

Results
ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors.

Conclusions
The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.
Prefrontal intra-individual ERP variability and its asymmetry: exploring its biomarker potential in mild cognitive impairment
Authors: Eyamu Joel , Kim Wuon-Shik , Kim Kahye , Lee Kun Ho , Kim Jaeuk U. 
Published: April 2024

Abstract
Background
The worldwide trend of demographic aging highlights the progress made in healthcare, albeit with health challenges like Alzheimer’s Disease (AD), prevalent in individuals aged 65 and above. Its early detection at the mild cognitive impairment (MCI) stage is crucial. Event-related potentials (ERPs) obtained by averaging EEG segments responded to repeated events are vital for cognitive impairment research. Consequently, examining intra-trial ERP variability is vital for comprehending fluctuations within psychophysiological processes of interest. This study aimed to investigate cognitive deficiencies and instability in MCI using ERP variability and its asymmetry from a prefrontal two-channel EEG device.

Methods
In this study, ERP variability for both target and non-target responses was examined using the response variance curve (RVC) in a sample comprising 481 participants with MCI and 1,043 age-matched healthy individuals. The participants engaged in auditory selective attention tasks. Cognitive decline was assessed using the Seoul Neuropsychological Screening Battery (SNSB) and the Mini-Mental State Examination (MMSE). The research employed various statistical methods, including independent t-tests, and univariate and multiple logistic regression analyses. These analyses were conducted to investigate group differences and explore the relationships between neuropsychological test results, ERP variability and its asymmetry measures, and the prevalence of MCI.

Results
Our results showed that patients with MCI exhibited unstable cognitive processing, characterized by increased ERP variability compared to cognitively normal (CN) adults. Multiple logistic regression analyses confirmed the association between ERP variability in the target and non-target responses with MCI prevalence, independent of demographic and neuropsychological factors.

Discussion
The unstable cognitive processing in the MCI group compared to the CN individuals implies abnormal neurological changes and reduced and (or) unstable attentional maintenance during cognitive processing. Consequently, utilizing ERP variability measures from a portable EEG device could serve as a valuable addition to the conventional ERP measures of latency and amplitude. This approach holds significant promise for identifying mild cognitive deficits and neural alterations in individuals with MCI.
Periprosthetic bacterial and fugal infection after total knee arthroplasty with one-stage debridement: a case report
Authors: Liu Yujiang , Lin Junxin 
Published: April 2024

Abstract
Background
Periprosthetic infection is a serious complication after arthroplasty and is characterized by a long duration, recurrence, and a low cure rate. Although fungal infections are infrequent, they are often catastrophic, with an insidious onset, a long duration, atypical clinical symptoms, and imaging features in the early stage. They are easily misdiagnosed, or the diagnosis is missed, resulting in wrong treatment approaches.

Case presentation
This paper reports a case involving a 62-year-old female patient of Korean ethnicity with a periprosthetic infection after knee arthroplasty who underwent joint debridement. A preoperative metagenomic next-generation sequencing of joint aspirate revealed Staphylococcus epidermidis. However, postsurgical tissue cultures confirmed the fungal infection. The patient received oral voriconazole and intra-articular injection of voriconazole for antifungal treatment. Since bacterial infection could not be ruled out, we also prescribed levofloxacin. No infection recurrence was observed after more than 22 months of follow-up. In the treatment of this patient, successful short-term follow-up was achieved, but long-term efficacy still cannot be determined.

Conclusions
In addition to the case study, we provide an analysis of the diagnosis and treatment of fungal infection after arthroplasty, especially the efficacy of debridement, antibiotics, and implant retention for a short-term outcome.
The effect of physical therapy and mechanical stimulation on dysfunction of lower extremities after total pelvic exenteration in cervical carcinoma patient with rectovesicovaginal fistula induced by radiotherapy: a case report
Authors: Lin Wujian , Yao Bing , He Jiahui , Lin Shuangyan , Wang Yafei , Chen Fangting , Zhang Weichao , Yang Jiashu , Ye Zhihong , Qiu Jianguang , Wang Yuling 
Published: April 2024

Abstract
Background
Total pelvic exenteration is the ultimate solution for rectovesicovaginal fistula caused by radiation therapy, yet total pelvic exenteration frequently causes intraoperative complications and postoperative complications. These complications are responsible for the dysfunction of lower extremities, impaired quality of life, and even the high long-term morbidity rate, thus multidisciplinary cooperation and early intervention for prevention of complications are necessary. Physical therapy was found to reduce the postoperative complications and promote rehabilitation, yet the effect on how physiotherapy prevents and treats complications after total pelvic exenteration and pelvic lymphadenectomy remains unclear.

Case presentation
A 50-year-old Chinese woman gradually developed perianal and pelvic floor pain and discomfort, right lower limb numbness, and involuntary vaginal discharge owing to recurrence and metastasis of cervical cancer more than half a year ago. Diagnosed as rectovesicovaginal fistula caused by radiation, she received total pelvic exenteration and subsequently developed severe lower limb edema, swelling pain, obturator nerve injury, and motor dysfunction. The patient was referred to a physiotherapist who performed rehabilitation evaluation and found edema in both lower extremities, right inguinal region pain (numeric pain rate scale 5/10), decreased temperature sensation and light touch in the medial thigh of the right lower limb, decreased right hip adductor muscle strength (manual muscle test 1/5) and right hip flexor muscle strength (manual muscle test 1/5), inability actively to adduct and flex the right hip with knee extension, low de Morton mobility Index score (0/100), and low Modified Barthel Index score (35/100). Routine physiotherapy was performed in 2 weeks, including therapeutic exercises, mechanical stimulation and electrical stimulation as well as manual therapy. The outcomes showed that physiotherapy significantly reduced lower limb pain and swelling, and improved hip range of motion, motor function, and activities of daily living, but still did not prevent thrombosis.

Conclusion
Standardized physical therapy demonstrates the effect on postoperative complications after total pelvic exenteration and pelvic lymphadenectomy. This supports the necessity of multidisciplinary cooperation and early physiotherapy intervention. Further research is needed to determine the causes of thrombosis after standardized intervention, and more randomized controlled trials are needed to investigate the efficacy of physical therapy after total pelvic exenteration.
Community structure of endophytic bacteria of Sargassum thubergii in the intertidal zone of Qingdao in China
Authors: Li Yang , Wang Jing , Sun Tao , Yu Xinlong , Yang Zhibo , Zhao Yayun , Tang Xuexi , Xiao Hui 
Published: April 2024

AbstractEndophytic bacteria are one of the symbiotic microbial groups closely related to host algae. However, less research on the endophytic bacteria of marine algae. In this study, the endophytic bacterial community of Sargassum thunbergii was investigated using the culture method and high-throughput sequencing. Thirty-nine endophytic bacterial strains, belonging to two phyla, five genera and sixteen species, were isolated, and Firmicutes, Bacillus and Metabacillus indicus were the dominant taxa at the phylum, genus and species level, respectively. High-throughput sequencing revealed 39 phyla and 574 genera of endophytic bacteria, and the dominant phylum was Proteobacteria, while the dominant genus was Ralstonia. The results also indicated that the endophytic bacteria of S. thunbergii included various groups with nitrogen fixation, salt tolerance, pollutant degradation, and antibacterial properties but also contained some pathogenic bacteria. Additionally, the endophytic bacterial community shared a large number of groups with the epiphytic bacteria and bacteria in the surrounding seawater, but the three groups of samples could be clustered separately. In conclusion, there are a variety of functional endophytic bacteria living in S. thunbergii, and the internal condition of algae is a selective factor for the formation of endophytic bacterial communities. This study enriched the database of endophytic bacteria in marine macroalgae, paving the way for further understanding of the interrelationships between endophytic bacteria, macroalgae, and the environment.
Identification of hub genes and establishment of a diagnostic model in tuberculosis infection
Authors: Liu Chunli , Li Xing 
Published: April 2024

AbstractTuberculosis (TB) poses significant challenges due to its high transmissibility within populations and intrinsic resistance to treatment, rendering it a formidable respiratory disease with a substantial susceptibility burden. This study was designed to identify new potential therapeutic targets for TB and establish a diagnostic model. mRNA expression data for TB were from GEO database, followed by conducting differential expression analysis. The top 50 genes with differential expression were subjected to GO and KEGG enrichment analyses. To establish a PPI network, the STRING database was utilized, and hub genes were identified utilizing five algorithms (EPC, MCC, MNC, Radiality, and Stress) within the cytoHubba plugin of Cytoscape software. Furthermore, a hub gene co-expression network was constructed using the GeneMANIA database. Consistency clustering was performed on hub genes, and ssGSEA was utilized to analyze the extent of immune infiltration in different subgroups. LASSO analysis was employed to construct a diagnostic model, and ROC curves were used for validation. Through the analysis of GEO data, a total of 159 genes were identified as differentially expressed. Further, GO and KEGG enrichment analyses revealed that these genes were mainly enriched in viral defense, symbiotic defense, and innate immune response-related pathways. Hub genes, including DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15, were identified using cytoHubba analysis of the PPI network. The GeneMANIA analysis unmasked that the co-expression rate of hub genes was 81.55%, and the physical interaction rate was 12.27%. Consistency clustering divided TB patients into two subgroups, and ssGSEA revealed different degrees of immune infiltration in different subgroups. LASSO analysis identified IFIT1, IFIT2, IFIT3, IFIH1, RSAD2, OAS1, OAS2, and STAT1 as eight immune-related key genes, and a diagnostic model was constructed. The ROC curve demonstrated that the model exhibited excellent diagnostic performance. DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15 were hub genes in TB, and the diagnostic model based on eight immune-related key genes exhibited good diagnostic performance.
Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review
Authors: Shen Yating , Thng Dexter Kai Hao , Wong Andrea Li Ann , Toh Tan Boon 
Published: April 2024

AbstractGlioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks. These studies have revealed that multiple oncogenic pathways are dysregulated, which contributes to the aggressiveness and resistance of GBM. Such findings have shed light on the molecular vulnerability of GBM and have shifted the disease management paradigm from chemotherapy to targeted therapies. Targeted drugs have been developed to inhibit oncogenic targets in GBM, including receptors involved in the angiogenic axis, the signal transducer and activator of transcription 3 (STAT3), the PI3K/AKT/mTOR signalling pathway, the ubiquitination-proteasome pathway, as well as IDH1/2 pathway. While certain targeted drugs showed promising results in vivo, the translatability of such preclinical achievements in GBM remains a barrier. We also discuss the recent developments and clinical assessments of targeted drugs, as well as the prospects of cell-based therapies and combinatorial therapy as novel ways to target GBM. Targeted treatments have demonstrated preclinical efficacy over chemotherapy as an alternative or adjuvant to the current standard of care for GBM, but their clinical efficacy remains hindered by challenges such as blood-brain barrier penetrance of the drugs. The development of combinatorial targeted therapies is expected to improve therapeutic efficacy and overcome drug resistance.