bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of peri- and intraoperative outcomes of open vs robotic-assisted partial nephrectomy for renal cell carcinoma: a propensity-matched analysis
Authors: Hoeh Benedikt , Wenzel Mike , Eckart Olivia , Fleisgarten Felicia , Garcia Cristina Cano , Köllermann Jens , Würnschimmel Christoph , Larcher Alessandro , Karakiewicz Pierre , Kluth Luis A. , Chun Felix K. H. , Mandel Philipp , Becker Andreas 
Published: June 2023

Abstract
Background
Partial nephrectomy (PN) is the gold standard surgical treatment for resectable renal cell carcinoma (RCC) tumors. However, the decision whether a robotic (RAPN) or open PN (OPN) approach is chosen is often based on the surgeon’s individual experience and preference. To overcome the inherent selection bias when comparing peri- and postoperative outcomes of RAPN vs. OPN, a strict statistical methodology is needed.

Materials and methods
We relied on an institutional tertiary-care database to identify RCC patients treated with RAPN and OPN between January 2003 and January 2021. Study endpoints were estimated blood loss (EBL), length of stay (LOS), rate of intraoperative and postoperative complications, and trifecta. In the first step of analyses, descriptive statistics and multivariable regression models (MVA) were applied. In the second step of analyses, to validate initial findings, MVA were applied after 2:1 propensity-score matching (PSM).

Results
Of 615 RCC patients, 481 (78%) underwent OPN vs 134 (22%) RAPN. RAPN patients were younger and presented with a smaller tumor diameter and lower RENAL-Score sum, respectively. Median EBL was comparable, whereas LOS was shorter in RAPN vs. OPN. Both intraoperative (27 vs 6%) and Clavien-Dindo > 2 complications (11 vs 3%) were higher in OPN (both < 0.05), whereas achievement of trifecta was higher in RAPN (65 vs 54%; p = 0.028). In MVA, RAPN was a significant predictor for shorter LOS, lower rates of intraoperative and postoperative complications as well as higher trifecta rates. After 2:1 PSM with subsequent MVA, RAPN remained a statistical and clinical predictor for lower rates of intraoperative and postoperative complications and higher rates of trifecta achievement but not LOS.

Conclusions
Differences in baseline and outcome characteristics exist between RAPN vs. OPN, probably due to selection bias. However, after applying two sets of statistical analyses, RAPN seems to be associated with more favorable outcomes regarding complications and trifecta rates.
Factors predicting recurrence after left‑sided pancreatectomy for pancreatic ductal adenocarcinoma
Authors: Xia Tao , Xu Peng , Mou Yiping , Zhang Xizhou , Song Shihao , Zhou Yucheng , Lu Chao , Zhu Qicong , Xu Yunyun , Jin Weiwei , Wang Yuanyu 
Published: June 2023

Abstract
Background
Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately.

Methods
Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified.

Results
One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019).

Conclusions
Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.
Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis
Authors: Wu Yongming , Song Wenpeng , Wang Denian , Chang Junke , Wang Yan , Tian Jie , Zhou Sicheng , Dong Yingxian , Zhou Jing , Li Jue , Zhao Ziyi , Che Guowei 
Published: June 2023

Abstract
Background
Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it.

Methods
We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0.

Results
A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42–2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27–1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients.

Conclusions
In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.
Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Authors: Tang Xiaotong , Cao Yueying , Wu Dan , Sun Lizhou , Xu Yetao 
Published: June 2023

Abstract
Background
Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8.

Methods
DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2.

Results
The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification.

Conclusion
Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.
ATXN3 promotes prostate cancer progression by stabilizing YAP
Authors: Wu Longxiang , Ou Zhenyu , Liu Peihua , Zhao Cheng , Tong Shiyu , Wang Ruizhe , Li Yangle , Yuan Junbin , Chen Minfeng , Fan Benyi , Zu Xiongbing , Wang Yongjie , Tang Jianing 
Published: June 2023

Abstract
Background
Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized.

Methods
Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP.

Results
In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression.

Conclusions
In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC.
Pharmacologic inhibition of NLRP3 reduces the levels of α-synuclein and protects dopaminergic neurons in a model of Parkinson’s disease
Authors: Amo-Aparicio Jesus , Daly Jonathan , Højen Jesper Falkesgaard , Dinarello Charles A. 
Published: June 2023

Abstract
Background
Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons, which leads to irreversible loss of peripheral motor functions. Death of dopaminergic neurons induces an inflammatory response in microglial cells, which further exacerbates neuronal loss. Reducing inflammation is expected to ameliorate neuronal loss and arrest motor dysfunctions. Because of the contribution of the NLRP3 inflammasome to the inflammatory response in PD, we targeted NLRP3 using the specific inhibitor OLT1177®.

Methods
We evaluated the effectiveness of OLT1177® in reducing the inflammatory response in an MPTP neurotoxic model of PD. Using a combination of in vitro and in vivo studies, we analyzed the effects of NLRP3 inhibition on pro-inflammatory markers in the brain, α-synuclein aggregation, and dopaminergic neuron survival. We also determined the effects of OLT1177® on locomotor deficits associated with MPTP and brain penetrance.

Results
Treatment with OLT1177® prevented the loss of motor function, reduced the levels of α-synuclein, modulated pro-inflammatory markers in the nigrostriatal areas of the brain, and protected dopaminergic neurons from degeneration in the MPTP model of PD. We also demonstrated that OLT1177® crosses the blood–brain barrier and reaches therapeutic concentrations in the brain.

Conclusions
These data suggest that targeting the NLRP3 inflammasome by OLT1177® may be a safe and novel therapeutic approach to arrest neuroinflammation and protect against neurological deficits of Parkinson’s disease in humans.
The role of implementation organizations in scaling evidence-based psychosocial interventions
Authors: Crane Margaret E. , Kendall Philip C. , Chorpita Bruce F. , Sanders Matthew R. , Miller Allen R. , Webster-Stratton Carolyn , McWilliam Jenna , Beck Judith S. , Ashen Ceth , Embry Dennis D. , Pickering John A. , Daleiden Eric L. 
Published: June 2023

AbstractBackgroundTo bring evidence-based interventions (EBIs) to individuals with behavioral health needs, psychosocial interventions must be delivered at scale. Despite an increasing effort to implement effective treatments in communities, most individuals with mental health and behavioral problems do not receive EBIs. We posit that organizations that commercialize EBIs play an important role in disseminating EBIs, particularly in the USA. The behavioral health and implementation industry is growing, bringing the implementation field to an important inflection point: how to scale interventions to improve access while maintaining EBI effectiveness and minimizing inequities in access to psychosocial intervention.Main bodyWe offer a first-hand examination of five illustrative organizations specializing in EBI implementation: Beck Institute for Cognitive Behavioral Therapy; Incredible Years, Inc.; the PAXIS Institute; PracticeWise, LLC; and Triple P International. We use the Five Stages of Small Business Growth framework to organize themes. We discuss practical structures (e.g., corporate structures, intellectual property agreements, and business models) and considerations that arise when trying to scale EBIs including balancing fidelity and reach of the intervention. Business models consider who will pay for EBI implementation and allow organizations to scale EBIs.ConclusionWe propose research questions to guide scaling: understanding the level of fidelity needed to maintain efficacy, optimizing training outcomes, and researching business models to enable organizations to scale EBIs.
Clinical efficacy of denosumab, teriparatide, and oral bisphosphonates in the prevention of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis
Authors: Yuan Chuanjian , Liang Yanchen , Zhu Kai , Xie Wenpeng 
Published: June 2023

Abstract
Background
Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs.

Methods
We systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models.

Results
We included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61–4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97–3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47–3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs.

Conclusions
Teriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.
RHAMM regulates MMTV-PyMT-induced lung metastasis by connecting STING-dependent DNA damage sensing to interferon/STAT1 pro-apoptosis signaling
Authors: Tolg Cornelia , Milojevic Maja , Qi Freda W. , Pavanel Hailie A. , Locke M. Elizabeth O. , Ma Jenny , Price Mathew , Nelson Andrew C. , McCarthy James B. , Hill Kathleen A. , Turley Eva A. 
Published: June 2023

Abstract
Background
RHAMM is a multifunctional protein that is upregulated in breast tumors, and the presence of strongly RHAMM+ve cancer cell subsets associates with elevated risk of peripheral metastasis. Experimentally, RHAMM impacts cell cycle progression and cell migration. However, the RHAMM functions that contribute to breast cancer metastasis are poorly understood.

Methods
We interrogated the metastatic functions of RHAMM using a loss-of-function approach by crossing the MMTV-PyMT mouse model of breast cancer susceptibility with Rhamm−/− mice. In vitro analyses of known RHAMM functions were performed using primary tumor cell cultures and MMTV-PyMT cell lines. Somatic mutations were identified using a mouse genotyping array. RNA-seq was performed to identify transcriptome changes resulting from Rhamm-loss, and SiRNA and CRISPR/Cas9 gene editing was used to establish cause and effect of survival mechanisms in vitro.

Results
Rhamm-loss does not alter initiation or growth of MMTV-PyMT-induced primary tumors but unexpectedly increases lung metastasis. Increased metastatic propensity with Rhamm-loss is not associated with obvious alterations in proliferation, epithelial plasticity, migration, invasion or genomic stability. SNV analyses identify positive selection of Rhamm−/− primary tumor clones that are enriched in lung metastases. Rhamm−/− tumor clones are characterized by an increased ability to survive with ROS-mediated DNA damage, which associates with blunted expression of interferon pathway and target genes, particularly those implicated in DNA damage-resistance. Mechanistic analyses show that ablating RHAMM expression in breast tumor cells by siRNA knockdown or CRISPR-Cas9 gene editing blunts interferon signaling activation by STING agonists and reduces STING agonist-induced apoptosis. The metastasis-specific effect of RHAMM expression-loss is linked to microenvironmental factors unique to tumor-bearing lung tissue, notably high ROS and TGFB levels. These factors promote STING-induced apoptosis of RHAMM+ve tumor cells to a significantly greater extent than RHAMM−ve comparators. As predicted by these results, colony size of Wildtype lung metastases is inversely related to RHAMM expression.

Conclusion
RHAMM expression-loss blunts STING-IFN signaling, which offers growth advantages under specific microenvironmental conditions of lung tissue. These results provide mechanistic insight into factors controlling clonal survival/expansion of metastatic colonies and has translational potential for RHAMM expression as a marker of sensitivity to interferon therapy.
6D-QSAR for predicting biological activity of human aldose reductase inhibitors using quasar receptor surface modeling
Authors: Sokouti Babak , Hamzeh-Mivehroud Maryam 
Published: June 2023

AbstractThe application of QSAR analysis dates back a half-century ago and is currently continuously employed in any rational drug design. The multi-dimensional QSAR modeling can be a promising tool for researchers to develop reliable predictive QSAR models for designing novel compounds. In the present work, we studied inhibitors of human aldose reductase (AR) to generate multi-dimensional QSAR models using 3D- and 6D-QSAR methods. For this purpose, Pentacle and Quasar’s programs were used to produce the QSAR models using corresponding dissociation constant (Kd) values. By inspecting the performance metrics of the generated models, we achieved similar results with comparable internal validation statistics. However, considering the externally validated values, 6D-QSAR models provide significantly better prediction of endpoint values. The obtained results suggest that the higher the dimension of the QSAR model, the higher the performance of the generated model. However, more studies are required to verify these outcomes.
A tension spline fitted numerical scheme for singularly perturbed reaction-diffusion problem with negative shift
Authors: Ejere Ababi Hailu , Dinka Tekle Gemechu , Woldaregay Mesfin Mekuria , Duressa Gemechis File 
Published: June 2023

Abstract
Objective
The paper is focused on developing and analyzing a uniformly convergent numerical scheme for a singularly perturbed reaction-diffusion problem with a negative shift. The solution of such problem exhibits strong boundary layers at the two ends of the domain due to the influence of the perturbation parameter, and the term with negative shift causes interior layer. The rapidly changing behavior of the solution in the layers brings significant difficulties in solving the problem analytically. We have treated the problem by proposing a numerical scheme using the implicit Euler method in the temporal direction and a fitted tension spline method in the spatial direction with uniform meshes.

Result
Stability and uniform error estimates are investigated for the developed numerical scheme. The theoretical finding is demonstrated by numerical examples. It is obtained that the developed numerical scheme is uniformly convergent of order one in time and order two in space.
Legionella associated rhabdomyolysis: a case report
Authors: Ma Helena , Bavishi Avni , Jain Bijal 
Published: June 2023

AbstractBackgroundInfections have been recognized as an uncommon cause of rhabdomyolysis, with evidence indicating a worse prognosis when compared to rhabdomyolysis caused by other etiologies. Diseases caused byLegionella pneumophilacan present variably, ranging from mild to severe illness, as is sometimes the case with pneumonia. In particular, the triad of Legionnaire’s disease, rhabdomyolysis, and acute kidney injury is associated with a significant increase in the morbidity and mortality, with most patients requiring initiation of renal replacement therapy such as hemodialysis. While the exact mechanism of both the muscle and kidney injury in this setting remains unknown, several hypotheses exist, with some research suggesting multiple yet distinct processes occurring in both target organs.Case presentationIn this case report, we describe a 53-year-old African American man who presented withLegionella pneumophilapneumonia complicated by rhabdomyolysis and acute kidney injury. He was treated with aggressive fluid resuscitation and a 2-week course of azithromycin. His clinical status improved without necessitating renal replacement therapy or mechanical ventilation. We postulate that early recognition and treatment were key to his recovery. He was discharged 10 days later without recurrence of rhabdomyolysis at the time of this report.ConclusionWhile there are several well-established and more common causes of rhabdomyolysis, clinicians should recognizeLegionella sp.as an etiology, given its association with significant morbidity and mortality.