bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence, lethality, and post-stroke functional status in different Brazilian macro-regions: The SAMBA study (analysis of stroke in multiple Brazilian areas)
Authors: Santos Emily dos , Wollmann Giulia M. , Nagel Vivian , Ponte Herminia M. S. , Furtado Luis E. T. A. , Martins-Filho Rui K. V. , Weiss Gustavo , Martins Sheila C. O. , Ferreira Leslie E. , França Paulo H. C. de , Cabral Norberto L. 
Published: September 2022

BackgroundStroke is the second leading cause of death in Brazil. The social and financial burden of stroke is remarkable; however, the epidemiological profile remains poorly understood.ObjectiveThe aim of this study was to report the incidence, lethality, and functional status at 30 and 90 days post-stroke in the cities of different Brazilian macro-regions.MethodsThis is an observational, prospective, and population-based study, led in Canoas (South), Joinville (South, reference center), Sertãozinho (Southeast), and Sobral (Northeast) in Brazil. It was developed according to the three-step criteria recommended by the World Health Organization to conduct population-based studies on stroke. Using different sources, all hospitalized and ambulatory patients with stroke were identified and the same criteria were kept in all cities. All first events were included, regardless of sex, age, or type of stroke. Demographic and risk factor data were collected, followed by biochemical, electrocardiographic, and radiological test results. Functional status and lethality were obtained using the mRankin scale through telephonic interview (validated Brazilian version).ResultsIn 1 year, 932 stroke cases were registered (784 ischemic stroke, 105 hemorrhagic stroke, and 43 subarachnoid hemorrhage). The incidence rates per 100,000 inhabitants, adjusted for the world population, were 63 in Canoas, 106 in Joinville, 72 in Sertãozinho, and 96 in Sobral. The majority (70.8%) were followed for 90 days. Kaplan–Meier curves showed that 90-day survival was different among cities. Sobral, which has the lowest socioeconomic indexes, revealed the worst results in terms of lethality and functional status.ConclusionThis study expands the knowledge of stroke epidemiology in Brazil, a middle-income country with enormous socioeconomic and cultural diversity. The discrepancy observed regarding the impact of stroke in patients from Joinville and Sobral highlights the need to improve the strategic allocation of resources to meet the health priorities in each location.
The functional connectivity of the middle frontal cortex predicts ketamine’s outcome in major depressive disorder
Authors: Zhang Fan , Wang Chengyu , Lan Xiaofeng , Li Weicheng , Fu Ling , Ye Yanxiang , Liu Haiyan , Wu Kai , Zhou Yanling , Ning Yuping 
Published: September 2022

BackgroundKetamine, a robust antidepressant, has promising potential in the treatment of major depressive disorder (MDD). However, it does not work for all MDD patients, and the mechanism underlying its anti-depressive effects is unclear. Researchers have explored the mechanisms of ketamine action in MDD patients through MRI, a technique that measures brain activity intuitively. Notably, many MRI results were inconsistent because they selected different brain regions as seeds, particularly with respect to functional connectivity (FC) analysis. To eliminate the influence of prior seeds as much as possible, we used the significantly different results in degree centrality (DC) analysis as seeds to explore the FC changes in MDD patients to identify an imaging biomarker of ketamine’s effect.MethodsForty-four MDD patients and 45 healthy controls (HCs) were included in the study. Patients, aged 18–65, received six intravenous ketamine injections over 12 days. Depressive symptoms were estimated and MRI scans were performed at baseline and the day after the sixth infusion. We estimated FC differences between responders, non-responders and HCs using the region that showed significant differences between responders and non-responders in DC analysis as the seed. The correlation between the MADRS changes and zFC values was performed, and the potential of zFC values to be a neuroimaging biomarker was explored using the receiver operating characteristic curve.ResultCompared with non-responders, responders had significantly decreased DC values in the right middle frontal gyrus (MFG). In the analysis of FC using the region that showed significant differences in DC as a seed, there was a significant difference in the region of the right supplementary motor area (SMA) among responders, non-responders, and HCs. This region also overlapped with the bilateral median cingulate gyrus. In post hoc analysis, responders had higher FC than non-responders and HCs, and non-responders had lower FC than HCs. Importantly, the FC between the MFG and SMA (overlapping bilateral median cingulate gyrus) was correlated with the improvement of symptoms, which was estimated by the Mongomery-Asberg Depression Scale (MADRS). FC has the potential to be an imaging biomarker that can predict the ketamine effect in MDD patients according to the receiver operating characteristic curve analysis.ConclusionOur results revealed that FC between the SMG and SMA and mACC was highly correlated with depressive symptoms and has the potential to be a neuroimaging biomarker to predict the effect of ketamine in MDD.
Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways
Authors: Semlali Abdelhabib , Papadakos Sofia , Contant Camille , Zouaoui Ikram , Rouabhia Mahmoud 
Published: September 2022

Treatment of oral cancer is based exclusively on surgery combined with or without chemotherapy. However, it has several side effects. Targeting a new, more effective therapy has become an urgent matter. The purpose of this study was to evaluate the anti-tumor activity of rapamycin in oral cancer and its mechanism of action. Human gingival carcinoma cells were stimulated with different concentrations of rapamycin to assess proliferation, colony formation, cell migration, as well as apoptosis, and autophagy. The expression of proteins involved in the cell cycle (cyclin D1, p15, p21, p27) and autophagy, as well as that of oncogenes and tumor suppressor genes, were determined by quantitative PCR. The signaling pathways were evaluated by Western blotting. Our results show that rapamycin has a selective effect at a low dose on cancer cell growth/survival. This was confirmed by low colony formation and the inhibition of cell migration, while increasing cell apoptosis by activating caspase-9 and -3. Rapamycin promoted cell autophagy and increased mitochondrial oxidative stress by being involved in DNA damage in the exposed cells. Finally, rapamycin exhibits potent anti-oral cancer properties through inhibition of several cancer-promoting pathways (MAPK, NF-κB, and Wnt/beta-catenin). These results indicate that rapamycin could be a potential agent for the treatment of oral cancer and for a prevention strategy.
Clinical implication of minimal residual disease assessment by next-generation sequencing-based immunoglobulin clonality assay in pediatric B-acute lymphoblastic leukemia
Authors: Lee Jae Wook , Kim Yonggoo , Ahn Ari , Lee Jong Mi , Yoo Jae Won , Kim Seongkoo , Cho Bin , Chung Nack-Gyun , Kim Myungshin 
Published: September 2022

Measuring minimal residual disease (MRD) during treatment is valuable to identify acute lymphoblastic leukemia (ALL) patients who require intensified treatment to avert relapse. We performed the next-generation sequencing (NGS)-based immunoglobulin gene (Ig) clonality assay and evaluated its clinical implication in pediatric B-ALL patients to assess MRD. Fifty-five patients who were diagnosed and treated with de novo (n = 44) or relapsed/refractory B-ALL (n = 11) were enrolled. MRD assessment was performed using the LymphoTrack® Dx IGH and IGK assay panels. The percentage of the clonal sequences per total read count was calculated as MRD (% of B cells). The data were normalized as the proportion of total nucleated cells (TNC) by LymphoQuant™ Internal control or the B-cell proportion in each sample estimated by flow cytometry or immunohistochemistry. Clonal Ig rearrangement was identified in all patients. The normalized MRD value was significantly lower than the unnormalized MRD value (p &lt; 0.001). When categorizing patients, 27 of 50 patients (54%) achieved normalized MRD &lt;0.01%, while 6 of them did not achieve MRD &lt;0.01% when applying the unnormalized value. The normalized post-induction MRD value of 0.01% proved to be a significant threshold value for both 3-year event-free survival (100% for MRD &lt;0.01% vs. 60.9% ± 10.2% for MRD ≥0.01%, p = 0.007) and 3-year overall survival (100% for MRD &lt;0.01% vs. 78.3% ± 8.6% for MRD ≥0.01%, p = 0.011). However, unnormalized MRD was not a significant factor for outcome in this cohort. Our study demonstrated that MRD assessment by NGS-based Ig clonality assay could be applied in most pediatric B-ALL patients. Normalized post-induction MRD &lt;0.01% was a significant prognostic indicator.
Radiation therapy for de novo anorectal cancer in patients with a history of prostate radiation therapy
Authors: Hilal Lara , Wu Abraham J. , Reyngold Marsha , Cuaron John J. , Navilio John , Romesser Paul B. , Dreyfuss Alexandra , Yin Sean , Zhang Zhigang , Bai Xing , Berry Sean L. , Zinovoy Melissa , Nusrat Maliha , Pappou Emmanouil , Zelefsky Michael J. , Crane Christopher H. , Hajj Carla 
Published: September 2022

IntroductionRadiation therapy (RT) for anorectal cancer after prior prostate cancer RT is usually avoided due to concern for complications. Data on this topic is scarce. Our aim was to evaluate tolerability, toxicity, and clinical outcomes associated with a second course of pelvic radiation in men with de novo anorectal cancers previously treated with RT for prostate cancer.Materials/methodsWe conducted a single-institution retrospective study of men treated with RT for rectal or anal cancer after prior prostate RT. Toxicity data were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Cumulative incidence was calculated for local and distant progression. Kaplan-Meier curves were used to estimate overall survival (OS) and progression-free survival (PFS).ResultsWe identified 26 patients who received anorectal RT after prostate cancer RT: 17 for rectal cancer and 9 for anal cancer. None had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR), external beam RT (EBRT), or EBRT + LDR. RT for rectal cancer was delivered most commonly using 50.4Gy/28 fractions (fr) or 1.5 Gy twice-daily to 30-45 Gy. The most used RT dose for anal cancer was 50Gy/25 fr. Median interval between prostate and anorectal RT was 12.3 years (range:0.5 - 25.3). 65% and 89% of rectal and anal cancer patients received concurrent chemotherapy, respectively. There were no reported ≥Grade 4 acute toxicities. Two patients developed fistulae; one was urinary-cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other was recto-vesicular after prostate LDR and 50Gy/25fr for anal cancer. In 11 patients with available dosimetry, coverage for anorectal cancers was adequate. With a median follow up of 84.4 months, 5-yr local progression and OS were 30% and 31% for rectal cancer, and 35% and 49% for anal cancer patients, respectively.ConclusionRT for anorectal cancer after prior prostate cancer RT is feasible but should be delivered with caution since it poses a risk of fistulae and possibly bleeding, especially in patients treated with prior LDR brachytherapy. Further studies, perhaps using proton therapy and/or rectal hydrogel spacers, are needed to further decrease toxicity and improve outcomes.
Autonomic nervous system markers of music-elicited analgesia in people with fibromyalgia: A double-blind randomized pilot study
Authors: Lepping Rebecca J. , McMillan Miranda L. , Chadwick Andrea L. , Mansour Zaid M. , Martin Laura E. , Gustafson Kathleen M. 
Published: September 2022

PurposeTo investigate the feasibility of using music listening by adults with fibromyalgia (FM) as a potential tool for reducing pain sensitivity.Patients and methodsWe report results from a double-blind two-arm parallel randomized pilot study (NCT04059042) in nine participants with FM. Pain tolerance and threshold were measured objectively using quantitative sensory tests; autonomic nervous system (ANS) reactivity was measured with an electrocardiogram. Participants were randomized to listen to instrumental Western Classical music or a nature sound control to test whether music listening elicits greater analgesic effects over simple auditory distraction. Participants also completed separate control testing with no sound that was counterbalanced between participants.ResultsParticipants were randomized 1:1 to music or nature sounds (four Music and five Nature). Although the groups were not different on FM scores, the Music group had marginally worse temporal pain summation (p= 0.06), and the Nature group had higher anxiety scores (p&lt; 0.05). Outcome measures showed a significant difference between groups in the magnitude of change in temporal summation between sessions (p&lt; 0.05), revealing that the Nature group had greater pain reduction during audio compared to silence mode, while the Music group had no difference between the sessions. No significant effects were observed for either mechanical pain tolerance or ANS testing. Within the Music group, there was a trend of vagal response increase from baseline to music listening, but it did not reach statistical significance; this pattern was not observed in the Nature group.ConclusionAuditory listening significantly altered pain responses. There may be a greater vagal response to music vs. nature sounds; however, results could be due to group differences in pain and anxiety. This line of study will help in determining whether music could be prophylactic for people with FM when acute pain is expected.
Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments
Authors: Xu Xiaotong , Li Naping , Wu Yongrong , Yan Ke , Mi Yilin , Yi Nanxing , Tan Xuyi , Kuang Gaoyan , Lu Min 
Published: September 2022

Background: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.Purpose: This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.Study design:In vivo, we established a rabbit KOA model using the modified Videman method. In vitro, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.Results: The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.Conclusion: ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors.
The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients
Authors: Qu Jinlong , Bian Rongrong , Liu Binguo , Chen Jiani , Zhai Jingwen , Teng Fei , Guo Wenyuan , Wei Hua 
Published: September 2022

Objectives: Wuzhi Capsule (WZC) is often administrated with tacrolimus in liver transplant patients to reduce the toxicity of tacrolimus and relieve the financial burden of patients. We aimed to investigate the interaction between Wuzhi Capsule (WZC) and tacrolimus in liver transplant patients.Methods: We applied the LC-MS/MS analytical method previously established to study the pharmacokinetic characteristics of the analytes in 15 liver transplant patients. CYP3A5 genotypes were determined in 15 donors and recipients, and they were categorized into CYP3A5 expressers and non-expressers respectively.Results: The influences of CYP3A5 in donors and recipients on the pharmacokinetics of tacrolimus with or without WZC were also studied. We found that 1) WZC could influence the metabolism of tacrolimus, which shortened the Tmax of tacrolimus and decreased V/F and CL/F. 2) Moreover, our results showed that, in donors, the CL/F of tacrolimus were significantly lower in CYP3A5 (CYP3A5*1) expressers (decreased from 24.421 to 12.864) and non-expressers (decreased from 23.532 to 11.822) when co-administration with WZC. For recipients, the decreased trend of CL/F of tacrolimus was seen when co-administrated with WZC by 15.376 and 12.243 in CYP3A5 expressers and non-expressers, respectively.Conclusion: In this study, the pharmacokinetics effects of WZC on tacrolimus were identified. The co-administration of WZC can increase the tacrolimus blood concentration in Chinese liver transplant patients in clinical practice.
Long-term follow-up results of patients with left bundle branch pacing and exploration for potential factors affecting cardiac function
Authors: Hu Qingyun , Lu Wenzhao , Chen Keping , Dai Yan , Lin Jinxuan , Xu Nan , Lin Jingru , Chen Ruohan , Li Yao , Cheng Chendi , Zhou Yu’an , Zhang Shu 
Published: September 2022

Background: Left bundle branch pacing (LBBP) is an alternative strategy for His bundle pacing (HBP). This study aimed to analyze the long-term performance of LBBP and the potential factors affecting long-term cardiac function.Methods: Patients with LBBP were continuously enrolled from January 2018 to August 2020. Pacing parameters, electrocardiogram (ECG), and echocardiography were collected. The anatomic position of LBBP leads was described by echocardiographic and fluoroscopic parameters.Results: A total of 91 patients with a median follow-up of 18 months were enrolled. Most patients maintained stable pacing parameters during follow-up. The intra-septal position of the 3830 lead also remained stable as the distance from the lead tip to the left surface of the ventricular septum was 0.4 (0, 1.4) mm. The overall level of left ventricular ejection fraction (LVEF) slightly increased. 59 patients had improved LVEF (∆LVEF &gt; 0), while 28 patients had unchanged or reduced LVEF (∆LVEF ≤ 0). The declines of baseline LVEF, ∆ Paced QRSd, and corrected longitudinal distance (longit-dist) of lead-implanted site correlated with LVEF improvement, and these three factors had negative linear correlations with ∆LVEF. Patients with tricuspid valve regurgitation (TVR) deterioration had longer follow-up duration (20.5 vs. 15.0 months, p = 0.01) and shorter Lead-TVA-dist (18.6 vs. 21.6 mm, p = 0.04) than those without TVR deterioration.Conclusion: Patients with LBBP generally remained stable in pacing performance, anatomic lead positions, and cardiac function in long-term follow-up. Baseline LVEF, ∆ Paced QRSd, and corrected longit-dist might be associated with potential LVEF decrease, which required further confirmation.
A case study on the use of Public Narrative as a leadership development approach for Patient Leaders in the English National Health Service
Authors: Aiello Emilia , Perera Kathryn , Ade Mo , Sordé-Martí Teresa 
Published: September 2022

BackgroundIn 2016 the National Health Service (NHS) England embraced the commitment to work for maternity services to become safer, more personalized, kinder, professional and more family-friendly. Achieving this involves including a service users' organizations to co-lead and deliver the services. This article explores how Public Narrative, a framework for leadership development used across geographical and cultural settings worldwide, can enhance the confidence, capability and skills of service-user representatives (or Patient Leaders) in the National Health Service (NHS) in England. Specifically, we analyse a pilot initiative conducted with one cohort of Patient Leaders, the Chairs of local Maternity Voices Partnerships (MVPs), and how they have used Public Narrative to enhance their effectiveness in leading transformation in maternity services as part of the NHS Maternity Transformation Programme.MethodsQualitative two-phase case study of a pilot training and coaching initiative using Public Narrative with a cohort of MVP Chairs. Phase 1 consisted of a 6-month period, during which the standard framework was adapted in co-design with the MVP Chairs. A core MVP Chair Co-Design Group underwent initial training and follow-up coaching in Public Narrative. Phase 2 consisted of qualitative data collection and data analysis.ResultsThe study of this pilot initiative suggests two main ways in which Public Narrative can enhance the effectiveness of Patient Leaders in service improvement in general and maternity services in specific. First, training and coaching in the Public Narrative framework enables Patient Leaders to gain insight into, articulate and then craft their lived experience of healthcare services in a way that connects with and activates the underlying values of others (“shared purpose”), such that those experiences become an emotional resource on which Patient Leaders can draw to influence future service design and decision-making processes. Second, Public Narrative provides a simple and compelling structure through which Patient Leaders can enhance their skills, confidence and capability as “healthcare leaders,” both individually and collectively.ConclusionsThe Public Narrative framework can significantly enhance the confidence, capability and skills of Patient Leaders, both to identify and coalesce around shared purpose and to advance genuine co-production in the design and improvement of healthcare services in general and maternity services in specific.