bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologous recombination deficiency test validation in patients with high-grade advanced ovarian cancer
Authors: Nogueira Rodrigues Angelica , Souto Andreza Karine de Barros Almeida , de Andrade Diocésio Alves Pinto , Gomes Larissa Müller , Koide Sandra Satie , e Silva Renata de Godoy , de Souza Bruno Batista , Massaro Juliana Doblas , de Melo Andréia Cristina , Borges Andrea Morais , Giro Camila , de Andrade Carlos Augusto Vasconcelos , da Costa Cesar Martins , Gimenes Daniel Luiz , de Mello Eduardo Caminha Bandeira , de Oliveira Fernanda Cesar , Lima Frederico Müller de Toledo , Lopes Gabriel Lima , Bretas Gustavo de Oliveira , Jacob Gustavo Guerra , Silva Herika Lucia da Costa , Notaro Juliana Ferrari , Alves Lara Ladislau , Moitinho Marcos Veloso , da Silva Mirian Cristina , Abramoff Roberto , Rauber Thais Amaral da Cunha , Dienstmann Rodrigo , Koyama Fernanda Christtanini 
Published: February 2025

BackgroundAlong with BRCA mutation status, homologous recombination deficiency (HRD) testing is a prognostic and predictive biomarker for poly-ADP-ribose polymerase (PARP) inhibitor therapy indication in high-grade epithelial ovarian, fallopian tube, or peritoneal cancer. Approximately 50% of high-grade serous ovarian cancers exhibit HRD, even in the absence of germline or somatic BRCA1/2 loss-of-function mutations. In this scenario, access to a validated diagnostic HRD test can optimize treatment selection and increase the effectiveness of the intervention.ObjectiveTo technically validate an in-house next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx® Plus HRD (Myriad Genetics), which is used in routine care.MethodsThis is a prospective cohort study conducted at the Oncoclínicas Precision Medicine (OCPM) laboratory using samples from patients with advanced or relapsed platinum-sensitive ovarian cancer eligible for HRD testing in a diagnostic clinical setting at Oncoclínicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen’s kappa statistic to measure agreement with the gold standard assay (MyChoice® HRD Plus CDx) in HRD status classification, along with other accuracy metrics.ResultsIn total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice® HRD Plus CDx assay). The GS Focus HRD test demonstrated high concordance for HRD status with the reference test (kappa: 0.8 and 95% CI: 0.60–0.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had BRCA1/2 mutations identified by the MyChoice® HRD Plus CDx, all of which were detected by the GS Focus HRD test.ConclusionIn summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice® HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.
Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review
Authors: Ishaq Shahid , Shah Iqbal Ali , Lee Shin-Da , Wu Bor-Tsang 
Published: February 2025

BackgroundThe excitatory imbalance of glutamatergic neurons, caused by insufficient input from dopaminergic neurons, contributes the pathogenesis of Parkinson’s disease (PD). Exercise training is one of the non-pharmacological, non-invasive therapeutic approaches.ObjectiveThis systematic review is the first to summarize the effects of exercise training on the regulation of protein and gene expressions within the nigrostriatal glutamatergic pathway and its receptor interactions in animal models of Parkinson’s disease (PD).MethodologyThe PubMed, Web of Science, and Embase electronic databases were searched, and 9 out of 96 studies that met the PRISMA guidelines were included. These studies received a CAMARADES score ranging from 4 to 6 out of 10. The included studies utilized pharmacologically induced PD models in mice or rats with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA). The majority of studies (89%) employed treadmill training, while 11% used voluntary wheel running, with training protocols consisting of 5 days per week for 4 weeks.ResultsExercise training reduced extracellular glutamate (Glu) and increased the expression of GLT-1, GS, Gln, and mGluR2/3 while down-regulating VGULT1 in the presynaptic terminal of the glutamatergic neurons within the nigrostriatal pathway in PD animal models. It also downregulated mGluR5 and modulated the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits: GluA1 was downregulated, inhibiting long-term potentiation, while GluA2 and GluA3 were upregulated in the nigrostriatal pathway in PD animal models. In addition, the exercise training downregulated the N-methyl-D-aspartate (NMDA) receptors, Arc, Cav1.3, CaMKII, and p-CaMKII in the nigrostriatal pathway in PD animal models.ConclusionExercise training exerted a neuroprotective effect on the glutamatergic pathway in Parkinson’s disease (PD) animal models by limiting excess glutamate in the synaptic cleft. Exercise training modulated the ionotropic receptors and limited the glutamatergic excitatory imbalance within the nigrostriatal pathway in PD animal models. It also improved motor function, including balance, coordination, and gait parameters.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024564127
Time trends in mechanical thrombectomy (2017–2021): do real-world data reflect advances in evidence?
Authors: Riegler Christoph , Rücker Viktoria , von Rennenberg Regina , Bollweg Kerstin , Cheng Bastian , Alegiani Anna C. , Flottmann Fabian , Schnieder Marlena , Ernst Marielle , Pfeilschifter Waltraud , Kraemer Christoffer , Mühl-Benninghaus Ruben , Tiedt Steffen , Kellert Lars , Zimmermann Hanna , Bode Felix J. , Petzold Gabor C. , Dorn Franziska , Berrouschot Jörg , Bormann Albrecht , Bernkopf Kathleen , Wunderlich Silke , Boeckh-Behrens Tobias , Petersen Martina , Krause Lars Udo , Lowens Stephan , Audebert Heinrich J. , Siebert Eberhard , Heuschmann Peter U. , Nolte Christian H. 
Published: February 2025

BackgroundIn recent years, we have witnessed a continuous, evidence-based expansion of indications for endovascular therapy (EVT) in the treatment of ischaemic stroke, driven by advancements in extended time windows and target vessel occlusion. Our study aimed to evaluate the temporal changes in patients’ characteristics, treatment, and outcomes in clinical practice.MethodsWe used data from the German Stroke Registry, a large national multicentre prospective registry, which includes all patients receiving EVT for ischaemic stroke at its participating centers. We analysed baseline factors, treatment details, and clinical outcomes [Modified Rankin Scale (mRS) at 3 months] over a 5-year period (2017–2021).ResultsWe included 6,251 patients from eight centres. Over time, the characteristics of patients undergoing EVT changed in several aspects (2017 vs. 2021). Patients became older (median age from 76 [IQR: 65–82] to 77 [65–84 years]; ptrend = 0.02), and less severely affected (NIHSS from 15 [11–19] to 13 [8–18]; ptrend &lt;0.001). There was an increase in patients treated more than 6 h after last seen well (22.0% to 28.3%; ptrend&lt;0.001), and more patients were treated for medium vessel occlusion (16.1% to 28.1%; ptrend&lt;0.001). The use of intravenous thrombolysis decreased (52.4% to 40.4%; ptrend&lt;0.01). Good functional outcome declined (percentage of patients with mRS ≤ 2 from 36.0 to 34.9%; aOR 0.94 per year [0.89–0.99]), while mortality at 3 months increased from 25.3% in 2017 to 34.7% in 2021; aOR 1.13 per year [1.07–1.19].ConclusionBetween 2017 and 2021, there were significant shifts in the demographic and clinical profiles of patients undergoing EVT, along with an expansion in EVT indications. Despite these patients presenting with less severe stroke symptoms, improvements in functional outcomes were not observed, and mortality rates increased. These trends may reflect willingness to treat patients with more severe underlying health conditions.
Affective touch enhances low gamma activity during hand proprioceptive perception in children with different neurodevelopmental conditions
Authors: Sabater-Gárriz Álvaro , Mingorance José Antonio , Mestre-Sansó Francesc , Canals Vicent , Bleyenheuft Yannick , Montoya Pedro , Riquelme Inmaculada 
Published: February 2025

BackgroundGamma wave activity in the sensorimotor cortex is a critical neural mechanism associated with proprioceptive processing, which is essential for motor coordination, balance, and spatial orientation. The modulation of gamma oscillations by different types of tactile stimuli, including affective touch, is not well understood, particularly in children with neurodevelopmental disorders such as cerebral palsy and autism spectrum disorder.AimsThis study aims to explore how affective touch influences gamma oscillatory activity and proprioceptive performance in children with typical development, cerebral palsy and autism spectrum disorders.Methods and proceduresEEG data were recorded from participants during passive wrist mobilizations under three conditions: following an affective touch stimulus, after a non-affective touch stimulus, and with no tactile stimulation. Time-frequency analysis of low gamma activity (30–45 Hz) on the left somatosensory cortex was conducted for each condition. Proprioceptive performance was assessed through participants’ accuracy in identifying wrist positions. Proprioception and pleasantness of affective and non-affective touch were also assessed.ResultsAffective touch increased proprioceptive gamma power density. Children with cerebral palsy had poorer proprioception and higher brain gamma power density for processing movement than children with typical development or autism, and their proprioception worsened with non-affective touch.Conclusion and implicationsThese findings highlight the potential of affective touch to modulate gamma oscillatory activity and enhance proprioceptive function, particularly in children with cerebral palsy. The results underscore the importance of incorporating emotionally meaningful sensory inputs in therapeutic interventions to support proprioceptive and motor function in children with neurodevelopmental disorders.
Impact of nutritional screening on mortality and intensive care unit length of stay
Authors: Díaz Chavarro Blanca Cecilia , Romero-Saldaña Manuel , Assis Reveiz Jorge Karim , Molina-Recio Guillermo 
Published: February 2025

BackgroundNutritional assessment is a fundamental part of the treatment of patients hospitalized in the ICU, allowing the implementation of interventions appropriate to the identified requirements. Since the risk of malnutrition is a modifiable factor, its correct management can positively influence hospital evolution. This study aims to test the impact of the incorporation of nutritional screening and assessment on mortality and length of stay in patients hospitalized in an Intensive Care Unit in Cali, Colombia, during the years 2019 and 2021–2022.MethodsThis is a historical cohort epidemiological study where one cohort consisted of 114 patients who received a standard nutritional screening (interpretation of body mass index and its clinical impression). The other cohort of 630 patients was those exposed to screening with the Malnutrition Universal Screening Tool (MUST) scale. Hematological, clinical, and nutritional variables were considered and their relationship with adverse events, length of hospital stay, and discharge status.ResultsThere were significant differences between the two cohorts (p &lt; 0.001), with increased mortality and length of hospital stay in patients who received standard nutritional screening without MUST. Furthermore, there was a greater presence of enteral support, diarrhea, anemia, leukocytosis, and lymphopenia in this cohort.ConclusionImplementing the MUST screening method and specific nutritional interventions resulted in a significant improvement in patient mortality figures. In addition, the predictive mortality model revealed that emesis and leukopenia increased the probability of death.
Comparison of efficacy and safety of thrombus prevention strategies after abdominal and pelvic cancer surgery: Bayesian network based meta-analysis
Authors: Qin Shiran , Guo Sitong , Yao Yucheng , He Ying , Xu Dandan , Su Henghai , Chen Xiaoyu , Meng Haoru 
Published: February 2025

BackgroundThe occurrence of venous thromboembolism (VTE) after abdominal and pelvic cancer surgery increases the risk of mortality and disability. However, there is insufficient evidence supporting the choice of anticoagulation strategies.MethodsWe searched PubMed, The Cochrane Library, Embase, and Web of Science for randomized controlled trials from inception to January 2024. Studies concerning thrombosis prevention after abdominal and pelvic surgery were included. Network meta-analysis(NMA) and direct meta-analysis (DMA) methods were employed to evaluate the efficacy and safety of various prophylactic strategies.ResultsTwenty clinical trials involving a total of 4923 patients were included. The DMA results showed that low molecular weight heparin (LMWH) was more effective in preventing VTE compared to no treatment (OR = 1.96; 95% CI: 1.21 to 3.19), and LMWH plus physiotherapy was more effective than LMWH (OR = 10.95; 95% CI: 1.33 to 90.40). The NMA results indicated that DOACs (OR = 0.34; 95% CI: 0.11 to 0.76) and LMWH (OR = 0.51; 95% CI: 0.32 to 0.77) were significantly effective in preventing venous thrombosis compared with no treatment. The cumulative ranking probability curve (SUCRA) showed that direct oral anticoagulants (DOACs) were the best intervention. In terms of major bleeding, unfractionated heparin (UFH) had a higher risk than LMWH, physiotherapy, and no treatment, with statistically significant differences. The SUCRA analysis indicated that physiotherapy was the best intervention for major bleeding.ConclusionExisting evidence suggests that DOACs can provide better thromboprophylaxis efficacy for patients after abdominal and pelvic cancer surgery, achieving an optimal balance between efficacy and safety. LMWH has become an intervention with efficacy second only to DOACs, with similar safety.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024513090.
Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis
Authors: Tang Kai , Deng Wei , Huang Zhiying , Chen Simin , Zhu Zilin , Lin Shukun , Zhong Lubin , Zheng Quanxin , Zhao Wenhua , Zhang Zhida , Mo Ling 
Published: February 2025

BackgroundOsteoporosis (OP), as the prevalent systemic metabolic bone disease worldwide, progresses insidiously and slowly. The clinical discomfort and complications associated with OP impose a significant burden on patients. Therefore, finding more effective treatments for OP remains an urgent challenge.MethodWe first conducted in vitro experiments to determine whether Neoandrographolide (NEO) exhibits cytotoxic or proliferative effects on bone marrow macrophages (BMMs) and to explore the specific timeframe during which NEO exerts its inhibitory action on osteoclast (OC) differentiation. Through Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot analysis, we examined the relative expression levels of genes and proteins associated with OC differentiation like CTSK,c-Fos,MMP9,NFATc1, and verified the underlying mechanisms. Finally, we performed in vivo experiments to further investigate the inflammation.ResultsNEO exhibits no significant cytotoxic effects on BMMs at concentrations less than or equal to 30 μM while exerting inhibitory effects on OC differentiation during its early and middle stages. RT-PCR and Western blot results reveal that NEO suppresses the expression of genes and proteins including CTSK,c-Fos,MMP9,NFATc1. Western blot findings also indicate that NEO inhibits the phosphorylation of ERK, P38, JNK, and P65 but does not reverse the degradation of IκB-α. Additionally, NEO affects the phosphorylation of proteins in the PI3K/AKT, GSK3β, and PPARγ signaling pathways, demonstrating that NEO can inhibit OC formation through multiple pathways and targets. In vivo experiments further validated the in vitro findings by constructing an OP model, showing that NEO can mitigate bone loss induced by OC differentiation.ConclusionNEO has the potential to serve as a therapeutic agent for OP by targeting multiple sites and inhibiting the formation of mature OC through various signaling pathways.
FBR2 modulates ferroptosis via the SIRT3/p53 pathway to ameliorate pulmonary fibrosis
Authors: Cheng Yu , Jiao Yang , Wei Wan , Kou Mengjia , Cai Yaodong , Li Yang , Li Hao , Liu Tonghua 
Published: February 2025

BackgroundIdiopathic Pulmonary Fibrosis (IPF), an interstitial lung disease of unknown etiology, remains incurable with current therapies, which fail to halt disease progression or restore lung function. However, Feibi Recipe No. 2 (FBR2), a clinically validated traditional Chinese medicine formula, exhibits potential as an IPF treatment.ObjectiveThis study aimed to investigate the regulatory effect of FBR2 on ferroptosis through the SIRT3/p53 pathway and its therapeutic potential in improving IPF.MethodsPulmonary fibrosis was induced in C57BL/6J mice by intratracheal instillation of Bleomycin (BLM), followed by FBR2 treatment via gavage. Assessments encompassed histopathology, ELISA for cytokine detection, IHC and Western blot for protein expression analysis, and qRT-PCR for gene expression quantification. Transmission electron microscopy (TEM) was used to observe mitochondrial morphology. The roles of Erastin and the SIRT3 inhibitor 3-TYP were also explored to elucidate FBR2’s mechanisms of action.ResultsFBR2 treatment significantly mitigated BLM-induced lung injury in mice, as evidenced by improved body weight and survival rates, and reduced levels of inflammatory cytokines, including IL-6 and TNF-α. FBR2 decreased collagen deposition in lung tissue, as shown by Masson’s staining and IHC detection of Col-I and α-SMA, confirming its anti-fibrotic effects. It also reduced iron and MDA levels in lung tissue, increased GSH-Px activity, improved mitochondrial morphology, and enhanced the expression of GPX4 and SLC7A11, indicating its ferroptosis-inhibitory capacity. Furthermore, FBR2 increased SIRT3 levels and suppressed p53 and its acetylated forms, promoting the translocation of p53 from the nucleus to the cytoplasm where it co-localized with SIRT3. The protective effects of FBR2 were reversed by Erastin, confirming the central role of ferroptosis in pulmonary fibrosis treatment. The use of 3-TYP further confirmed FBR2’s intervention in ferroptosis and cellular senescence through the SIRT3/p53 pathway.ConclusionFBR2 shows therapeutic potential in a BLM-induced pulmonary fibrosis mouse model, with its effects mediated through modulation of the ferroptosis pathway via the SIRT3/p53 mechanism. This study provides novel evidence for the targeted treatment of IPF and offers further insights into its pathogenesis.
Exploring information technology utilization and needs in community pharmacies: a cross-sectional survey in Shanghai, China
Authors: Li Qin , Jin Zhao , Liao Yun , Dai Huihua , Meng Jie , Li Ling 
Published: February 2025

BackgroundCommunity pharmacists are critical in managing medication therapy and ensuring patient safety. However, in many countries, including China, challenges such as limited access to real-time patient data, fragmented communication systems, and underdeveloped clinical decision-support tools hinder the effectiveness of pharmacy services. Integrating information technology (IT) into community pharmacies can improve medication management by providing timely access to patient information, enhancing medication safety, and facilitating communication with healthcare providers.ObjectiveThis study aimed to explore the medication management practices of community pharmacists, the existing IT support available, and their specific requirements for IT-assisted medication management in community pharmacies in Shanghai, China.MethodsAn online self-assessment survey was conducted to evaluate the utilization and needs of IT-based medication management among community pharmacists in Shanghai. Demographic data and information on pharmaceutical care practices were collected and analyzed to examine correlations between these factors and the need for IT support.Results963 out of 2,178 surveys were completed over 6 months. Nearly all respondents (99.3%) provided at least one type of pharmaceutical care, but only 0.93% offered all types. Regarding current utilization and needs for IT systems, community pharmacists rated access to patient/medication information and digital standardized documentation flow as poor satisfaction with the highest level of needs. Multivariate regression analysis showed that IT needs were significantly associated with time spent in clinical pharmacy practice, time dedicated exclusively to clinical pharmacy, and the number of prescriptions dispensed weekly.ConclusionWhile community pharmacists are key in providing pharmaceutical care, IT support remains inadequate. There is a pressing need for an integrated IT system that offers real-time access to patient medical information, a standardized documentation system, improved clinical decision support software, and enhanced communication with other healthcare providers.
The effects of acute and chronic exercise on immune markers of TH1/TH2 cells in older adults: a systematic review
Authors: Teodoro Thiago Henrique , Costa Katerine Palharini Manfrin , Prestes Jonato , Campanholi José , Navalta James , Pereira Guilherme Borges 
Published: February 2025

PurposeImbalance between Th1 and Th2 cells correlated with increased disease incidence, is well-documented in the older adult. Both acute and chronic exercise induce a transient shift in organic homeostasis, modulating the immune system and impacting the balance between Th1 and Th2 cells. This review investigates the impact of acute and chronic exercise on immune markers of Th1 and Th2 cells in the older adults.MethodsThis study was conducted as a systematic review, following PRISMA guidelines, databases including PubMed, Web of Science, Embase, Science Direct, and Scopus were searched until March 2024, identifying randomized controlled trials and prospective observational studies that examined the effects of acute and chronic exercise on intracellular and surface markers, cytokines, and immunoglobulins in older adults. Studies involving animal subjects, isolated cells, diseased patients, or exposure to medications and drugs were excluded. The quality of the selected studies was assessed using the Cochrane risk of bias tool (ROB2), with data organized and presented in tables and figures.ResultsFourteen studies with 525 participants were included in the analysis. An acute session significantly increased serum IL-4, IL-6, and IL-10 levels immediately afterward, returning to baseline within 1 hour at moderate to high intensities. Chronic exercise at moderate to high intensities reduced serum TNF-α, IL-6, and the CD4/CD8 ratio, while increasing IL-10 levels after 24 weeks. Intracellular, other surface markers and cytokines, and immunoglobulins were not analyzed.ConclusionChronic exercise decreases serum TNF-α and IL-6 levels, lowers the CD4/CD8 ratio, and increases IL-10 after 24 weeks, aiding Th1 and Th2 balance. Acute exercise temporarily increases serum IL-4, IL-6, and IL-10 levels, returning to baseline within an hour, indicating short-term immune modulation of Th1/Th2 balance.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244426, Identifier CRD42021244426.