bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital
Authors: Prado-Mel Elena , Suárez-Casillas Paloma , Rodríguez-de Francisco Lupe , Estévez-García Purificación , Jiménez-Galán Rocío 
Published: May 2024

Background Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. Objectives To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. Materials and Methods This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76–43.23), and median PFS was 8 months (95% CI: 2.48–13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1–2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. Conclusion This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.
Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn’s disease: a Korean nationwide population-based study
Authors: Jun Yu Kyung , Ji Eunjeong , Yang Hye Ran , Choi Yonghoon , Shin Cheol Min , Park Young Soo , Kim Nayoung , Lee Dong Ho , Yoon Hyuk 
Published: May 2024

Background: Although immunomodulators are widely prescribed in patients with Crohn’s disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045–1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673–0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047–1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134–1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.
Reliability of continuous vital sign monitoring in post-operative patients employing consumer-grade fitness trackers: A randomised pilot trial
Authors: Helmer Philipp , Hottenrott Sebastian , Wienböker Kathrin , Pryss Rüdiger , Drosos Vasileios , Seitz Anna Katharina , Röder Daniel , Jovanovic Aleksandar , Brugger Jürgen , Kranke Peter , Meybohm Patrick , Winkler Bernd E , Sammeth Michael 
Published: May 2024

Introduction Fitness trackers can provide continuous monitoring of vital signs and thus have the potential to become a complementary, mobile and effective tool for early detection of patient deterioration and post-operative complications. Methods To evaluate potential implementations in acute care setting, we included 36 patients after moderate to major surgery in a recent randomised pilot trial to compare the performance of vital sign monitoring by three different fitness trackers (Apple Watch 7, Garmin Fenix 6pro and Withings ScanWatch) with established standard clinical monitors in post-anaesthesia care units and monitoring wards. Results During a cumulative period of 56 days, a total of 53,197 heart rate (HR) measurements, as well as 12,219 measurements of the peripheral blood oxygen saturation (SpO2) and 28,954 respiratory rate (RR) measurements were collected by fitness trackers. Under real-world conditions, HR monitoring was accurate and reliable across all benchmarked devices (r = [0.95;0.98], p < 0.001; Bias = [−0.74 bpm;−0.01 bpm]; MAPE∼2%). However, the performance of SpO2 (r = [0.21;0.68]; p < 0.001; Bias = [−0.46%;−2.29%]; root-mean-square error = [2.82%;4.1%]) monitoring was substantially inferior. RR measurements could not be obtained for two of the devices, therefore exclusively the accuracy of the Garmin tracker could be evaluated (r = 0.28, p < 0.001; Bias = −1.46/min). Moreover, the time resolution of the vital sign measurements highly depends on the tracking device, ranging from 0.7 to 117.94 data points per hour. Conclusion According to the results of the present study, tracker devices are generally reliable and accurate for HR monitoring, whereas SpO2 and RR measurements should be interpreted carefully, considering the clinical context of the respective patients.
Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16
Authors: Mollee Peter , Reynolds John , Janowski Wojt , Quach Hang , Campbell Philip , Gibbs Simon , Lee Sophie , Lee Edwin , Taylor Kerry , Cochrane Tara , Wallington-Gates Craig , Kwok Fiona , Weber Nicholas , Kerridge Ian , Weston Helen , Ho P. Joy , Leahy Michael Francis , Horvath Noemi , Spencer Andrew 
Published: May 2024

Abstract
In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care regimens. In a randomized trial, we tested whether similar improvements would be observed when daratumumab was added to the bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen. Transplant-ineligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). A total of 121 patients were randomized: 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the 2 arms. The median progression-free survival (PFS) was 16.8 months (95% confidence interval [CI], 15.3-21.7) and 25.8 months (95% CI, 19.9-33.5) in the VCD and VCDD arms, respectively (hazard ratio, 0.67; log-rank test P = .066). In a preplanned analysis, it was demonstrated that the daratumumab-containing arm showed a significant improvement in PFS from 18 months onward, based on estimates at fixed time points after randomization. The proportions of patients who were progression-free at the following time points were: 18 months, 48% vs 68% (P = .0002); 24 months, 36% vs 52% (P = .0001); and 30 months, 27% vs 41% (P &lt; .0001) in the VCD and VCDD arms, respectively. The best overall response and very good partial response rate were significantly higher in the daratumumab arm compared with the VCD and VCDD arms, respectively (65% vs 86%, P = .007; and 28% vs 52%, P = .009). Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of transplant-ineligible patients with myeloma. This trial was registered at the Australian New Zealand Clinical Trials Registry (ACTRN12617000202369).
Impact of coating and microstructure on wear resistance of tool steels for wood cutting: a novel approach to quantification and analysis of wear-related damages
Authors: Mbakop Nanshie Vanella , Aidibe Ali , Heidari Majid , Jahazi Mohammad 
Published: May 2024

AbstractSquaring, a wood transformation process, is an operation which consists of introducing the logs into a squaring machine which then uses sharp tools to cut the wood into pieces with high surface quality. Tool steels used in this process experience significant wear, damaging the wood surface and hence leading to substantial scrape rate. This study investigates the wear resistance of three tool steels specifically designed for wood cutting applications: modified AISI A8, modified steels with 0% and 1% tungsten, and powder metallurgy prepared W360 steel. Furthermore, the influence of a PVD coating on the wear resistance of the three alloys was investigated. ASTM G65 abrasive wear tests were conducted using the dry sand/rubber wheel abrasion test. A methodology using a non-contact 3D measurement system and specialized software was developed, allowing for a thorough quantitative assessment of the wear of these steels. The results revealed that the coated A8mod + 1%W steel exhibits the best resistance among the coated steels. Despite the excellent intrinsic resistance of W360 steel, the coating did not provide a significant improvement for this steel, showing only a 10% reduction in wear. Microstructural analysis revealed that the predominant wear mechanisms were abrasion and impact. The relative performance of each steel was quantified and is reported. Field trials conducted under actual cutting conditions, indicate the superiority of W360 steel in terms of resilience to wear and impacts compared to other tested alloys, while confirming the effectiveness of surface treatments in mitigating material wear. However, A8 steel modified with 1% tungsten exhibits increased wear under coating.
Psychological and physiological effects of sole contact with oil-finished wood
Authors: Ikei Harumi , Jo Hyunju , Miyazaki Yoshifumi 
Published: May 2024

AbstractIn Japanese households, it is customary to walk barefoot on wooden floors. Previous reports on the psychological and physiological relaxing effects of feet contact with uncoated solid wood have already been published. However, there are no studies on the effects of feet contact with coated wood, which is commonly used for residential floors. This study aimed to validate the psychological and physiological relaxing effects of sole contact with oil-finished wood. In total, 27 women university students (mean age: 21.9 ± 1.9 years) participated in this study. Psychological indices such as the modified semantic differential method and the Profile of Mood States Second Edition were used. The oxyhemoglobin (oxy-Hb) concentrations in the prefrontal cortex were determined using near-infrared time-resolved spectroscopy. The sympathetic nervous activity and the parasympathetic nervous activity were measured using heart rate variability. The flat plate for tactile stimulation was oil-finished wood, and uncoated wood and marble were used for comparison. The sole of the feet of each participant touched each material for 90 s. Feet contact with oil-finished and uncoated wood had relaxing effects on psychological and physiological responses compared with marble. The relaxing effects of oil-finished wood and uncoated wood were similar. That is, they significantly increased subjective feelings of comfort and relaxation, improved mood states, and decreased oxy-Hb concentration in the left prefrontal cortex compared with marble. However, there were no statistically significant differences in terms of right prefrontal cortex and sympathetic nervous activities between oil-finished wood and marble. Oil-finished wood had a slightly weaker physiological relaxation effect than uncoated wood.
Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function
Authors: Wei Jing , Guo Fangzheng , Song Yamin , Feng Tong , Wang Ying , Xu Kun , Song Jianhan , Kaysar Eldana , Abdukayyum Reyima , Lin Feiyang , Li Kangsheng , Li Baiqing , Qian Zhongqing , Wang Xiaojing , Wang Hongtao , Xu Tao 
Published: May 2024

AbstractBackgroundMycobacterium tuberculosisheat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant ofMycobacterium tuberculosis(Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown.MethodsMtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed inEscherichia coliby genetic engineering technology using pET-28a as a plasmid and purified by Ni–NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantifyMycobacteriumviability by counting CFUs.ResultsIn this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in byEscherichia coligenetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αβ T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb.ConclusionActivated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.
N6-methyladenosine modification of KLF2 may contribute to endothelial-to-mesenchymal transition in pulmonary hypertension
Authors: Kang Kang , Xiang Jingjing , Zhang Xingshi , Xie Yuting , Zhou Mengting , Zeng Le , Zhuang Junhao , Kuang Jiahao , Lin Yuanyuan , Hu Bozhe , Xiong Qianmin , Yin Qing , Su Qiang , Liao Xiaoyun , Wang Jun , Niu Yanqin , Liu Cuilian , Tian Jinglin , Gou Deming 
Published: May 2024

Abstract
Background
Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling. Increasing evidence indicates that endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) is a pivotal trigger initiating this remodeling. However, the regulatory mechanisms underlying EndMT in PH are still not fully understood.

Methods
Cytokine-induced hPAECs were assessed using RNA methylation quantification, qRT-PCR, and western blotting to determine the involvement of N6-methyladenosine (m6A) methylation in EndMT. Lentivirus-mediated silencing, overexpression, tube formation, and wound healing assays were utilized to investigate the function of METTL3 in EndMT. Endothelial-specific gene knockout, hemodynamic measurement, and immunostaining were performed to explore the roles of METTL3 in pulmonary vascular remodeling and PH. RNA-seq, RNA Immunoprecipitation-based qPCR, mRNA stability assay, m6A mutation, and dual-luciferase assays were employed to elucidate the mechanisms of RNA methylation in EndMT.

Results
The global levels of m6A and METTL3 expression were found to decrease in TNF-α- and TGF-β1-induced EndMT in human PAECs (hPAECs). METTL3 inhibition led to reduced endothelial markers (CD31 and VE-cadherin) and increased mesenchymal markers (SM22 and N-cadherin) as well as EndMT-related transcription factors (Snail, Zeb1, Zeb2, and Slug). The endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH (HPH) in mice. Mechanistically, METTL3-mediated m6A modification of kruppel-like factor 2 (KLF2) plays a crucial role in the EndMT process. KLF2 overexpression increased CD31 and VE-cadherin levels while decreasing SM22, N-cadherin, and EndMT-related transcription factors, thereby mitigating EndMT in PH. Mutations in the m6A site of KLF2 mRNA compromise KLF2 expression, subsequently diminishing its protective effect against EndMT. Furthermore, KLF2 modulates SM22 expression through direct binding to its promoter.

Conclusions
Our findings unveil a novel METTL3/KLF2 pathway critical for protecting hPAECs against EndMT, highlighting a promising avenue for therapeutic investigation in PH.
Frailty and depressive symptoms in older kidney transplant recipients: opportunities for collaboration between transplant nephrologists and geriatricians
Authors: Vankova Hana , Schmalz Michal , Andel Ross , Rajnochova Bloudickova Silvie 
Published: May 2024

Abstract
Background
Frailty is one of the key syndromes in geriatric medicine and an important factor for post-transplant outcomes. We aimed to describe the prevalence of frailty and examine the correlates of frailty and depressive symptoms in older kidney transplant recipients (KTRs).

Methods
This cross-sectional study involved 112 kidney transplant recipients (KTRs) aged 70 and above. Frailty syndrome was assessed using the Fried frailty criteria, and patients were categorized as frail, pre-frail, or non-frail based on five frailty components: muscle weakness, slow walking speed, low physical activity, self-reported exhaustion, and unintentional weight loss. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS). The relationship between frailty and depressive symptoms was evaluated using multinomial logistic regression, with the three frailty categories as the dependent variable and the severity of depressive symptoms as the independent variable, while controlling for age, gender, renal graft function, and time since transplant surgery.

Results
The participants had a mean age of 73.3 ± 3.3 years, and 49% were female. The prevalence of frailty syndrome was 25% (n = 28), pre-frailty was 46% (n = 52), and 29% (n = 32) of the KTRs were non-frail. The mean score for depressive symptoms was 3.1 ± 2.4 points, with 18% scoring above the clinical depression cutoff. Depressive symptoms were positively correlated with frailty (r = .46, p < .001). Among the frailty components, self-reported exhaustion (r = .43, p < .001), slow walking speed (r = .26, p < .01), and low physical activity (r = .44, p < .001) were significantly positively correlated with depressive symptoms, while muscle strength (p = .068) and unintentional weight loss (p = .050) were not. A multinomial logistic regression adjusted for covariates indicated that, compared to being non-frail, each additional point on the GDS increased the odds of being pre-frail by 39% (odds ratio [OR] = 1.39, 95% confidence interval [CI] 1.01–1.96) and roughly doubled the odds of being frail (OR = 2.01, 95% CI 1.39–2.89).

Conclusion
There is a strong association between frailty and depression in KTRs aged 70 years and older. Targeted detection has opened up a new avenue for collaboration between geriatricians and transplant nephrologists.
Prognostic impact of chronic lymphocytic leukemia comorbidity index in a young population: a real-world evidence study of a national gulf region cohort
Authors: Alshemmari Salem H. , AlSarraf Ahmad , Kaempf Andy , Danilov Alexey V. 
Published: May 2024

AbstractIn chronic lymphocytic leukaemia (CLL), comorbidities assessed by the CLL comorbidity index (CLL-CI) have been associated with outcomes in Western cohorts. We conducted a retrospective analysis of an unselected Middle Eastern cohort of newly diagnosed CLL patients seen at the Kuwait Cancer Control Center (n = 300). Compared to Western studies, these Middle Eastern patients were diagnosed at a younger age (median of 59) and had a higher comorbidity burden (69% non-low risk CLL-CI). A higher CLL-CI score was independently associated with significantly shorter event-free survival and greater risk of death. Our analysis demonstrates that CLL-CI is a valuable tool for comorbidity assessment and prognostic influence in (relatively young) Middle Eastern CLL patients.