bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying different cognitive phenotypes and their relationship with disability in neuromyelitis optica spectrum disorder
Authors: Kong Lingyao , Lang Yanlin , Wang Xiaofei , Wang Jiancheng , Chen Hongxi , Shi Ziyan , Zhou Hongyu 
Published: September 2022

BackgroundThe existence, frequency, and features of cognitive impairment (CI) in patients with neuromyelitis optica spectrum disorder (NMOSD) are still debated. A precise classification and characterization of cognitive phenotypes in patients with NMOSD are lacking.MethodsA total of 66 patients with NMOSD and 22 healthy controls (HCs) underwent a neuropsychological assessment. Latent profile analysis (LPA) on cognitive test z scores was used to identify cognitive phenotypes, and ANOVA was used to define the clinical features of each phenotype. Univariate and multivariate analyses were used to explore the predictors of severe CI, and a corresponding nomogram was created to visualize the predictive model.ResultsLPA results suggested four distinct meaningful cognitive phenotypes in NMOSD: preserved cognition (n = 20, 30.3%), mild-attention (n = 21, 31.8%), mild-multidomain (n = 18, 27.3%), and severe-multidomain (n = 7, 10.6%). Patients with the last three phenotypes were perceived to have CI, which accounts for 67.6% of patients with NMOSD. Patients with NMOSD and worse cognitive function were older (p &lt; 0.001) and had lower educational levels (p &lt; 0.001), later clinical onset (p = 0.01), worse Expanded Disability Status Scale scores (p = 0.001), and poorer lower-limb motor function (Timed 25-Foot Walk, p = 0.029; 12-item Multiple Sclerosis Walking Scale [MSWS-12], p &lt; 0.001). Deterioration of Nine-Hole Peg Test (odds ratio, OR: 1.115 [1, 1.243], p = 0.05) and MSWS-12 (OR: 1.069 [1.003, 1.139], p = 0.04) were the independent risk factors for severe cognitive dysfunction. Finally, a nomogram was built based on the entire cohort and the above factors to serve as a useful tool for clinicians to evaluate the risk of severe cognitive dysfunction.ConclusionsWe introduced a classification scheme for CI and highlighted that the deterioration of upper- and lower-limb motor disability potentially predicts cognitive phenotypes in NMOSD.
Speed up discharge planning at the acute stroke unit: A development and external validation study for the early prediction of discharge home
Authors: Veerbeek Janne Marieke , Ottiger Beatrice , Cazzoli Dario , Vanbellingen Tim , Nyffeler Thomas 
Published: September 2022

BackgroundTo reduce healthcare costs, it has become increasingly important to shorten the length of stay in acute stroke units. The goal of this study was to develop and externally validate a decision tree model applicable &lt; 48 h poststroke for discharge home from an acute stroke unit with a short length of stay, and to assess the inappropriate home discharge rate.MethodsA prospective study including two samples of stroke patients admitted to an acute stroke unit. The outcome was discharge home (yes/no). A classification and regression tree analysis was performed in Sample 1. The model's performance was tested in Sample 2.ResultsIn total, 953 patients were included. The final decision tree included the patients' activities of daily living (ADL) performance &lt;48 h poststroke, including motor function, cognition, and communication, and had an area under the curve (AUC) of 0.84 (95% confidence interval 0.76, 0.91). External validation resulted in an AUC of 0.74 (95% confidence interval 0.72, 0.77). None of the patients discharged home were re-admitted &lt; 2 months after discharge to a hospital or admitted to a rehabilitation center for symptoms that had needed inpatient neurorehabilitation.ConclusionsThe developed decision tree shows acceptable external validity in predicting discharge home in a heterogeneous sample of stroke patients, only based on the patient's actual ADL performance &lt;48 h poststroke. Importantly, discharge was safe, i.e., no re-hospitalization was registered. The tree's application to speed up discharge planning should now be further evaluated.
A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: Results of an exploratory study (RESCU 004)
Authors: Pilankar Aishwarya , Singhavi Hitesh , Raghuram Gorantla V. , Siddiqui Sophiya , Khare Naveen Kumar , Jadhav Vishalkumar , Tandel Harshali , Pal Kavita , Bhattacharjee Atanu , Chaturvedi Pankaj , Mittra Indraneel 
Published: September 2022

BackgroundOur earlier studies have shown that cell-free chromatin particles (cfChPs) that are released from dying cancer cells are readily internalised by bystander cells leading to activation of two hallmarks of cancer viz. genome instability and inflammation. These hallmarks could be down-regulated by deactivating cfChPs via medium of oxygen radicals generated upon admixing small quantities of the nutraceuticals resveratrol (R) and copper (Cu). In this exploratory study, we investigated whether oral administration of R and Cu (R-Cu) would down-regulate the hallmarks of cancer and immune checkpoints in advanced squamous cell carcinoma of oral cavity (OSCC).Patients and methodsThe study comprised of 25 patients divided into 5 equal groups. Five patients acted as controls; the remaining 20 were given R-Cu in four escalating doses. The lowest dose of R-Cu was 5.6mg and 560ng respectively, and the highest dose was 500mg and 5mg respectively. An initial biopsy was taken from patients at first presentation, and a second biopsy was taken 2 weeks later on the operating table. R-Cu was administered orally twice daily in the intervening period. Confocal microscopy was performed on tumour sections after fluorescent immuno-staining with anti-DNA and anti-histone antibodies to detect presence of cfChPs in the tumour micro-environment (TME). Immunofluorescence analysis was performed for 23 biomarkers representing the 10 Hallmarks of cancer, including 5 immune checkpoints, defined by Hanahan and Weinberg.ResultsConfocal microscopy detected copious presence of cfChPs in TME of OSCC, which were eradicated/deactivated following two-week treatment with R-Cu. Eradication of cfChPs from TME was associated with marked down-regulation of 21/23 biomarkers, including the five immune checkpoints. The lower two doses of R-Cu were more effective than the higher doses. No adverse effects attributable to R-Cu were observed.ConclusionThese results suggest that cfChPs released into TME from dying cancer cells are global instigators for cancer hallmarks and immune checkpoints in surviving cancer cells. The ability of R-Cu to deactivate cfChPs raises the prospect of a novel and non-toxic form of cancer treatment which sans killing of cancer cells, and instead induces healing by down-regulating cancer hallmarks and immune check-points.Clinical Trial Registrationhttp://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19801&amp;EncHid=&amp;userName=CTRI/2018/03/012459.
Propensity score-matched comparison of robotic- and video-assisted thoracoscopic surgery, and open lobectomy for non-small cell lung cancer patients aged 75 years or older
Authors: Pan Hanbo , Gu Zenan , Tian Yu , Jiang Long , Zhu Hongda , Ning Junwei , Huang Jia , Luo Qingquan 
Published: September 2022

IntroductionAlthough robot-assisted thoracoscopic surgery (RATS) has been widely applied in treating non-small cell lung cancer (NSCLC), its advantages remain unclear for very old patients. The present study compared the perioperative outcomes and survival profiles among RATS, video-assisted thoracoscopic surgery (VATS), and open lobectomy (OL), aiming to access the superiority of RATS for NSCLC patients aged ≥75 years.MethodsPathological IA-IIIB NSCLC patients aged ≥75 years who underwent RATS, VATS, or OL between June 2015 and June 2021 in Shanghai Chest Hospital were included. Propensity score matching (PSM, 1:1:1 RATS versus VATS versus OL) was based on 10 key prognostic factors. The primary endpoints were perioperative outcomes, and the secondary endpoints were disease-free (DFS), overall (OS), and cancer-specific survival (CS).ResultsA total of 504 cases (126 RATS, 200 VATS, and 178 OL) were enrolled, and PSM led to 97 cases in each group. The results showed that RATS led to: 1) the best surgical-related outcomes including the shortest operation duration (p &lt;0.001) and the least blood loss (p &lt;0.001); 2) the fastest postoperative recoveries including the shortest ICU stay (p = 0.004), chest tube drainage duration (p &lt;0.001), and postoperative stay (p &lt;0.001), and the most overall costs (p &lt;0.001); 3) the lowest incidence of postoperative complications (p = 0.002), especially pneumonia (p &lt;0.001). There was no difference in the resection margins, reoperation rates, intraoperative blood transfusion, and volume of chest tube drainage among the three groups. Moreover, RATS assessed more N1 (p = 0.009) and total (p = 0.007) lymph nodes (LNs) than VATS, while the three surgical approaches dissected similar numbers of N1, N2, and total LN stations and led to a comparable incidence of postoperative nodal upstaging. Finally, the three groups possessed comparable DFS, OS, and CS rates. Further subgroup analysis found no difference in DFS or OS among the three groups, and multivariable analysis showed that the surgical approach was not independently correlated with survival profiles.ConclusionRATS possessed the superiority in achieving better perioperative outcomes over VATS and OL in very old NSCLC patients, though the three surgical approaches achieved comparable survival outcomes.
Long response duration to pembrolizumab in metastatic, castration-resistant prostate cancer with microsatellite instability-high and neuroendocrine differentiation: A case report
Authors: Yoshida Tsukasa , Yaegashi Hiroshi , Toriumi Ren , Kadomoto Suguru , Iwamoto Hiroaki , Izumi Kouji , Kadono Yoshifumi , Ikeda Hiroko , Mizokami Atsushi 
Published: September 2022

BackgroundThe detection of microsatellite instability in urologic cancers is rare, especially in metastatic, castration-resistant prostate cancer with neuroendocrine differentiation.Case presentationThis is a case of a 66-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. Despite combined androgen deprivation therapy, his prostate-specific antigen (PSA) progressively increased, and prostate re-biopsy revealed small cell carcinoma. He was treated with platinum-based systemic chemotherapy, and his tumor markers, including PSA, remained negative; however, his local symptoms worsened. Subsequently, microsatellite instability-high was detected, and pembrolizumab was administered resulting in complete remission with the resolution of symptoms and continued therapeutic effect for more than 14 months.ConclusionMicrosatellite instability testing should be considered, despite its low detection rate, because the response to pembrolizumab in metastatic, castration-resistant prostate cancer with detectable microsatellite instability is associated with a prolonged duration of response.
Performance of the IOTA ADNEX model combined with HE4 for identifying early-stage ovarian cancer
Authors: Yang Suying , Tang Jing , Rong Yue , Wang Min , Long Jun , Chen Cheng , Wang Cong 
Published: September 2022

ObjectiveThis work was designed to investigate the performance of the International Ovarian Tumor Analysis (IOTA) ADNEX (Assessment of Different NEoplasias in the adneXa) model combined with human epithelial protein 4 (HE4) for early ovarian cancer (OC) detection.MethodsA total of 376 women who were hospitalized and operated on in Women and Children’s Hospital of Chongqing Medical University were selected. Ultrasonographic images, cancer antigen-125 (CA 125) levels, and HE4 levels were obtained. All cases were analyzed and the histopathological diagnosis serves as the reference standard. Based on the IOTA ADNEX model post-processing software, the risk prediction value was calculated. We analyzed receiver operating characteristic curves to determine whether the IOTA ADNEX model alone or combined with HE4 provided better diagnostic accuracy.ResultsThe area under the curve (AUC) of the ADNEX model alone or combined with HE4 in predicting benign and malignant ovarian tumors was 0.914 (95% CI, 0.881–0.941) and 0.916 (95% CI, 0.883–0.942), respectively. With the cutoff risk of 10%, the ADNEX model had a sensitivity of 0.93 (95% CI, 0.87–0.97) and a specificity of 0.73 (95% CI, 0.67–0.78), while combined with HE4, it had a sensitivity of 0.90 (95% CI, 0.84–0.95) and a specificity of 0.81 (95% CI, 0.76–0.86). The IOTA ADNEX model combined with HE4 was better at improving the accuracy of the differential diagnosis between different OCs than the IOTA ADNEX model alone. A significant difference was found in separating borderline masses from Stage II–IV OC (p = 0.0257).ConclusionsA combination of the IOTA ADNEX model and HE4 can improve the specificity of diagnosis of ovarian benign and malignant tumors and increase the sensitivity and effectiveness of the differential diagnosis of Stage II–IV OC and borderline tumors.
Prolonged neoadjuvant chemotherapy without radiation versus total neoadjuvant therapy for locally advanced rectal cancer: A propensity score matched study
Authors: Zhao Xuan , Han Peiyi , Zhang Luyang , Ma Junjun , Dong Feng , Zang Lu , He Zirui , Zheng Minhua 
Published: September 2022

BackgroundAlthough neoadjvuant chemoradiotherapy (CRT) improves the local control rate of locally advanced rectal cancer (LARC), it fails to significantly improve disease-free survival (DFS) and overall survival (OS). We explored the efficacy of prolonged neoadjuvant chemotherapy (pNCT) without radiation and compared this schema with total neoadjuvant therapy (TNT).Material and methodsPatients diagnosed with LARC and received TNT (4 cycles of induction CapeOX/FOLFOX followed with CRT) or pNCT (6~8 cycles of CapeOX/FOLFOX) between June 2016 and October 2021 were retrospective analyzed. All patients underwent total mesorectal excision (TME). A 1:1 propensity score match was performed to adjust baseline potential confounders. The tumor response, toxicity, recurrence-free survival (RFS) and OS were observed.ResultsA total of 184 patients with 92 patients in each group were finally enrolled. The median follow-up time was 35 months. TNT showed better pathological complete response (pCR) rate (25.0% vs 16.3%) and objective regression rate (73.9% vs 59.8%) than pNCT. TNT and pNCT produce similar 3-year RFS and OS rates in patients with mid-to-upper rectal cancer. TNT was associated with improved tumor responsiveness in all patients and improved 3-year RFS rates in those with low rectal cancer.ConclusionpNCT is an option for patients with mid-to-upper rectal cancer, but radiation is still necessary for low rectal cancer. To determine optimal schema for neoadjuvant therapy and patient selection, additional randomized controlled studies are needed.
First-line treatment of camrelizumab combined with chemotherapy in advanced gastroenteropancreatic neuroendocrine carcinoma: Study protocol for a prospective, multicenter, phase II study
Authors: Li Xiaofen , Ma Qing , Chang Chen , Li Hao , Cao Dan 
Published: September 2022

BackgroundGastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a group of rare but highly aggressive malignancies. The standard chemotherapy regimens composed of etoposide and cisplatin/carboplatin (EP/EC) are of limited efficacy. This prospective, multicenter, phase II study is conducted to explore the effectiveness and safety of first-line anti-PD-1 antibody (camrelizumab) combined with chemotherapy in advanced GEP-NEC patients.MethodsPatients with unresectable or metastatic GEP-NEC will receive camrelizumab combined with standard first-line chemotherapy every 3 weeks (camrelizumab 200 mg, administered intravenously on day 1; etoposide 100 mg/m2, administered intravenously on days 1–3; cisplatin 75 mg/m2, administered intravenously on day 1 or carboplatin area under the curve 5 mg/ml per min, administered intravenously on day 1). All patients were naïve to systemic therapy in the advanced setting. The primary endpoint is a 6-month progression-free survival (PFS) rate. The secondary endpoints are objective response rate, PFS, overall survival and adverse reactions.DiscussionThis is the first study to investigate the therapeutic potential of camrelizumab plus chemotherapy for advanced GEP-NEC. It is expected that this trial will propose a new and effective treatment strategy for GEP-NEC in the first-line setting.Clinical Trial RegistrationThis trial is registered at the Chinese Clinical Trial Registry http://www.chictr.org.cn, identifier ChiCTR2100047314.Date of RegistrationJune 12, 2021.
Pien-Tze-Huang alleviates CCl4-induced liver fibrosis through the inhibition of HSC autophagy and the TGF-β1/Smad2 pathway
Authors: Zhang Yuqin , Hua Liping , Lin Chunfeng , Yuan Mingzhou , Xu Wei , Raj D. Anand , Venkidasamy Baskar , Cespedes-Acuna Carlos L. , Nile Shivraj Hariram , Yan Guohong , Zheng Haiyin 
Published: September 2022

Ethnopharmacological relevance: Pien-Tze-Huang (PZH)—a traditional Chinese medicine (TCM) compound—has been employed to treat various liver inflammation and tumors for over 10 decades. Interestingly, most of the pharmacological effects had been validated and explored toward liver ailment along with pro-inflammatory conditions and cancer at the cellular and molecular level to date.Aim of the study: The present study aimed to investigate the therapeutic effect of PZH on autophagy and TGF-β1 signaling pathways in rats with liver fibrosis and hepatic stellate cell line (HSC).Materials and methods: Male SD rats with carbon tetrachloride (CCl4)-induced liver fibrosis were used as the animal model. Next, PZH treatment was given for 8 weeks. Afterward, the therapeutic effects of PZH were analyzed through a hepatic tissue structure by hematoxylin-eosin (H&amp;E), Van Gieson (VG) staining, and transmission electron microscopy (TEM), activity of ALT and AST by enzyme-associated immunosorbent assay as well. Subsequently, mRNA and protein expression were examined by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC). Then, the cell vitality of PZH-treated HSC and the expression of key molecules prevailing to autophagy were studied in vitro. Meanwhile, SM16 (a novel small molecular inhibitor which inhibits TGFβ-induced Smad2 phosphorylation) was employed to confirm PZH’s effects on the proliferation and autophagy of HSC.Results: PZH pharmacologically exerted anti-hepatic fibrosis effects as demonstrated by protecting hepatocytes and improving hepatic function. The results revealed the reduced production of extracellular collagen by adjusting the balance of matrix metalloproteinase (MMP) 2, MMP9, and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) in PZH-treated CCl4-induced liver fibrosis. Interestingly, PZH inhibited the activation of HSC by down-regulating TGF-β1 and phosphorylating Smad2. Furthermore, PZH down-regulated yeast Atg6 (Beclin-1) and microtubule-associated protein light chain 3 (LC3) toward suppressing HSC autophagy, and PZH exhibited similar effects to that of SM16.Conclusion: To conclude, PZH alleviated CCl4-induced liver fibrosis to reduce the production of extracellular collagen and inhibiting the activation of HSC. In addition, their pharmacological mechanisms related to autophagy and TGF-β1/Smad2 signaling pathways were revealed for the first time.
Influence of launch beam distribution on power flow and angular division multiplexing in seven-core silica optical fibers
Authors: Savović Svetislav , Dai Wenjing , Djordjevich Alexandar , Aidinis Konstantinos , Li Zheng , Min Rui 
Published: September 2022

We analyze the effect of launch beam distribution on space-division multiplexing (SDM) performance in multimode multicore silica optical fibers (MM MC SOF) with seven cores. The time-independent power flow equation (TI PFE) is used to explore the effect of the width of the distribution of the Gaussian launch beam on power flow in each of the seven cores. We show that the optical fiber length at which the equilibrium mode distribution (EMD) and steady-state distribution (SSD) are obtained is greatly influenced by the width of the Gaussian launch beam distribution. We further show that when the width of the Gaussian launch beam distribution widens, the optical fiber length at which angular division multiplexing (ADM) in each of the seven cores can be realized with minimal crosstalk between neighboring angular optical channels decreases. We demonstrate that, for increasing the capacity of an optical fiber transmission system, an SDM system with two- and three-channel ADM and multicore optical fiber multiplexing can be implemented with the proposed seven-core MM MC SOF at optical fiber lengths up to ≈1 km (2 ADM channels × 7 cores) and ≈200 m (3 ADM channels × 7 cores), respectively. Such characterization of MM MC SOFs under various launch conditions is important for building a multicore optical fiber SDM transmission system.
Suppression of estrogen receptor beta classical genomic activity enhances systemic and adipose-specific response to chronic beta-3 adrenergic receptor (β3AR) stimulation
Authors: Queathem Eric D. , Fitzgerald Maggie , Welly Rebecca , Rowles Candace C. , Schaller Kylie , Bukhary Shahad , Baines Christopher P. , Rector R. Scott , Padilla Jaume , Manrique-Acevedo Camila , Lubahn Dennis B. , Vieira-Potter Victoria J. 
Published: September 2022

White adipose tissue (WAT) dysfunction independently predicts cardiometabolic disease, yet there is a lack of effective adipocyte-targeting therapeutics. B3AR agonists enhance adipocyte mitochondrial function and hold potential in this regard. Based on enhanced sensitivity to B3AR-mediated browning in estrogen receptor (ER)alpha-null mice, we hypothesized that ERβ may enhance the WAT response to the B3AR ligand, CL316,243 (CL).Methods: Male and female wild-type (WT) and ERβ DNA binding domain knock-out (ERβDBDKO) mice fed high-fat diet (HFD) to induce obesity were administered CL (1 mg/kg) daily for 2 weeks. Systemic physiological assessments of body composition (EchoMRI), bioenergetics (metabolic chambers), adipocyte mitochondrial respiration (oroboros) and glucose tolerance were performed, alongside perigonadal (PGAT), subcutaneous (SQAT) and brown adipose tissue (BAT) protein expression assessment (Western blot). Mechanisms were tested in vitro using primary adipocytes isolated from WT mice, and from Esr2-floxed mice in which ERβ was knocked down. Statistical analyses were performed using 2 × 2 analysis of variance (ANOVA) for main effects of genotype (G) and treatment (T), as well as GxT interactions; t-tests were used to determine differences between in vitro treatment conditions (SPSS V24).Results: There were no genotype differences in HFD-induced obesity or systemic rescue effects of CL, yet ERβDBDKO females were more sensitive to CL-induced increases in energy expenditure and WAT UCP1 induction (GxT, p &lt; 0.05), which coincided with greater WAT B3AR protein content among the KO (G, p &lt; 0.05). Among males, who were more insulin resistant to begin with (no genotype differences before treatment), tended to be more sensitive to CL-mediated reduction in insulin resistance. With sexes combined, basal WAT mitochondrial respiration trended toward being lower in the ERβDBDKO mice, but this was completely rescued by CL (p &lt; 0.05). Confirming prior work, CL increased adipose tissue ERβ protein (T, p &lt; 0.05, all), an effect that was enhanced in WAT and BAT the female KO (GxT, p &lt; 0.01). In vitro experiments indicated that an inhibitor of ERβ genomic function (PHTPP) synergized with CL to further increase UCP1 mRNA (p = 0.043), whereas full ERβ protein was required for UCP1 expression (p = 0.042).Conclusion: Full ERβ activity appears requisite and stimulatory for UCP1 expression via a mechanism involving non-classical ERβ signaling. This novel discovery about the role of ERβ in adipocyte metabolism may have important clinical applications.