bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Cumulative Exposure to Increased Low-Density Lipoprotein Cholesterol and the New Occurrence of Peripheral Artery Disease
Authors: Liu Xinmin , Wang Yu , Wu Jianwei , Wang Anxin , Zhang Xiaoli , Cao Zhentang , Zhao Xingquan 
Published: October 2021

Background and Purpose: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis with increased risk of severe cardiovascular and cerebrovascular events. The relationship between one-time measuring of low-density lipoprotein cholesterol (LDL-C) and PAD is inconsistent. Increasing evidence shows that the predictive value of non-high-density lipoprotein cholesterol (non-HDLC) on atherosclerosis disease is superior to LDL-C. We aimed to investigate the relationship between cumulative exposure to increased LDL-C and the risk of newly developed PAD and compare the predictive value of LDL-C with non-HDLC.Materials and Methods: In the Asymptomatic Polyvascular Abnormalities Community study, we enrolled 2,923 participants with LDL-C and non-HDLC measured every 2 years from 2006 to 2012. Cumulative exposure to increased LDL-C and non-HDLC, defined as LDL-C burden and non-HDLC burden, respectively, was calculated as the weighted sum of the difference between the measured value and the cutoff value. A new occurrence of PAD was identified through ankle brachial index measured in 2010 and 2012. Multivariate models were adopted to analyze the association of LDL-C burden and non-HDLC burden with the newly developed PAD. The receiver operating curve was drawn, and the area under the curve was calculated to compare the predictive performance of LDL-C burden with a single measure of LDL-C in 2006 and non-HDL-C burden adjusted with a model including traditional risk factors.Results: Of the 2,923 participants, 5.4% (158/2,923) were diagnosed as newly developed PAD. In the univariate analysis, the highest quartile of LDL-C burden was significantly associated with new occurrence of PAD [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.13–2.73]. After adjustment for confounding factors, the same result was obtained (OR 1.59, 95%CI 1.01–2.49). The non-HDLC burden failed to show any statistical significance on the newly developed PAD (OR 1.31, 95% CI 0.84–2.04). Though LDL-C burden had a tendency to show better predictive performance than non-HDLC, it did not reach statistical significance (AUCLDL−C = 0.554 vs. AUCnon−HDLC = 0.544, P = 0.655).Conclusions: Cumulative exposure to increased LDL-C is an independent risk factor of newly developed PAD. The predictive value of non-HDLC burden was not revealed.
Detraining Effect on Pulmonary and Cardiovascular Autonomic Function and Functional Outcomes in Patients With Parkinson's Disease After Respiratory Muscle Training: An 18-Month Follow-Up Study
Authors: Huang Chih-Cheng , Lai Yun-Ru , Wu Fu-An , Kuo Nai-Ying , Cheng Ben-Chung , Tsai Nai-Wen , Kung Chia-Te , Chiang Yi-Fang , Lu Cheng-Hsien 
Published: October 2021

Background: The effect of 3-month respiratory muscle training (RMT) on pulmonary and autonomic function and functional outcomes has been demonstrated in patients with Parkinson's disease (PD); however, there is a paucity of information on the durability of the training effect. In this study, we monitored the pulmonary and cardiovascular autonomic function and clinical severity scales until 18 months after the cessation of RMT to elucidate the detraining effect after RMT.Methods: All patients with PD receiving RMT were assessed with clinical severity scales as well as pulmonary and autonomic function tests at four different stages (baseline on enrollment, immediately after 3 months of RMT, and 6 and 18 months after cessation of RMT). A control group of PD patients who did not receive RMT was also recruited for comparison. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP), were assessed. Cardiovascular autonomic function was assessed using measures including heart rate response to deep breathing (HRDB), Valsalva ratio, and baroreflex sensitivity. Clinical severity scores were also measured using the Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS).Results: The results showed significant improvements in MIP, MEP, HRDB, and UPDRS immediately after RMT. Despite some decay, the improvements in pulmonary function (MIP and MEP) and functional outcomes (UPDRS) remained significant until 6 months of detraining (9 months after enrollment). However, the improvement in cardiovascular autonomic function (HRDB) was reversed after 6 months of detraining.Conclusions: Based on these findings, we recommend that RMT may be repeated after at least 6 months after previous session (9 months after enrollment) for patients with PD to maintain optimal therapeutic effects.
Effect of Bilateral Subthalamic Nucleus Deep Brain Stimulation on Pisa Syndrome in Parkinson's Disease
Authors: He Jing , Cui Zhuang , Li Shuhua , Chen Haibo , Su Wen 
Published: October 2021

Objective: To observe the efficacy of bilateral subthalamic nucleus deep brain stimulation on Pisa syndrome in patients with Parkinson's disease.Methods: A total of 52 patients with Parkinson's disease who underwent deep brain stimulation in Beijing Hospital from July 1, 2016 to July 1, 2020 were reviewed. The clinical data were collected for the patients who met the diagnostic criteria of Pisa syndrome on “Medication-Off” state pre-operatively.Results: Two patients met the diagnostic criteria of Pisa syndrome before operation, with a Pisa angle of 10 and 14°, respectively. The lateral trunk flexion of the two patients improved after operation. In stimulation-on/medication-off state, the Pisa angle decreased from 10 to 2° and from 14 to 6°, respectively.Conclusion: Bilateral subthalamic nucleus deep brain stimulation might have beneficial effects on lateral trunk flexion in PD patients, but the predictors of curative effect are not clear.
A Retrospective Study on Statins and Post-stroke Patients: What About Functional Outcome and Follow-Up in a Stroke Rehabilitation Cohort?
Authors: Mele Chiara , Maggioni Giorgio , Giordano Andrea , Lunardon Clara , Balsamo Francesca , Mazzone Alessandra , Pistarini Caterina 
Published: October 2021

Objective: Statins exert pleiotropic effects by influencing several mechanisms, including synaptogenesis, neurogenesis, cerebral flow regulation, and angiogenesis. Results from in vitro and animal models suggest that statins could have beneficial effect on functional recovery and outcome after stroke events. However, results in human studies are still controversial. The aim of our study was to evaluate the role of statin in influencing functional outcome and subsequent clinical follow-up in a large cohort of post-stroke rehabilitation patients.Methods: This retrospective study consecutively enrolled 413 adult patients with stroke event, admitted to the division of Neurorehabilitation of the IRCCS ICS Maugeri, Veruno (Italy), for an individual rehabilitation program between 2015 and 2017. Follow-up lasted 3–5 years after discharge. Demographic data, etiology, classification, and anatomical site of stroke lesion, functional assessment, use and duration of statin therapy, and death during hospitalization were collected at baseline and on discharge. Clinical data on subsequent follow-up were also evaluated, considering these as variables: stroke recurrence, bone fractures, cardiovascular complications, and death.Results: In our cohort, 177 patients (42.9%) were prescribed statin therapy, of whom 50 (28.2%) before the stroke event and 127 (71.8%) at the beginning of the rehabilitation process. The use and type of statin therapy as well as the duration of treatment were not associated with recovery and functional outcome, regardless of confounders including sex, age, etiology, and site of stroke lesion, and initial functional level. For what concern post-discharge clinical follow-up, the use of statin therapy was significantly associated with a lower risk of bone fractures (OR = 0.095, CI 95%: 0.012–0.743, p = 0.01) independently from age, sex, initial and final functional level, and comorbidities.Conclusions: The use of statins does not seem to influence the functional outcome in post-stroke patients. However, they could exert a protective role against bone fractures during post-discharge follow-up, suggesting further evaluation on this topic.
Alexithymia and Autistic Traits: Associations With Social and Emotional Challenges Among College Students
Authors: Vaiouli Potheini , Panayiotou Georgia 
Published: October 2021

Background: Alexithymia is a multifaceted personality construct defined by marked difficulties in identifying and describing feelings and in externally oriented thinking. Given its intrinsic role in social-emotional processing, alexithymia is now recognized as a trans-diagnostic trait in a range of neurodevelopmental disorders, including autism. Research has pinpointed to the co-occurrence of autism with characteristics typical of alexithymic normative samples, such as social-communication difficulties and decreased emotion regulation abilities. Nonetheless, the role of individual facets of alexithymia in predicting challenges in social communication functioning is still understudied.Methods: In total, 275 young adults completed the Toronto Alexithymia Scale, the Autism Spectrum Quotient (short form), the Interpersonal Competence Questionnaire, and the Difficulties in Emotion Regulation Scale self-reported questionnaires for assessing alexithymic and autistic traits, social-communication abilities, and emotion regulation difficulties. We used regression models to establish cross-sectional associations between autism, alexithymia, and social-emotional difficulties. Also, we ran a parallel mediation analysis to determine whether the relationship between autistic traits and emotion regulations challenges are mediated by Alexithymia facets.Results: Analysis showed a significant positive association between autistic traits and alexithymic traits and between autistic traits and emotion regulation difficulties while, as expected, autistic traits were negatively correlated with social skills. A significant relationship was found among the participants’ levels of alexithymia and their interpersonal skills with two of three alexithymic subscales significantly contributing to the model. Similarly, a significant relationship was found among alexithymia subscales and emotion regulation difficulties with all three alexithymia subscales being statistically significant. Finally, analysis on two mediator models indicated a significant effect of autistic traits on social skills mediated by alexithymic traits as well as a significant indirect effect of autistic traits on emotion regulation difficulties mediated by alexithymic traits.Conclusion: The results of this study provide evidence of the influence of different alexithymic facets on the relationship between autistic traits and social-emotional challenges in young adults. Longitudinal studies may explore further alexithymia and its associations with social-emotional difficulties in autism as well as the potential implications of these findings in intervention and treatment programs.
Risk of Pneumonitis Associated With Immune Checkpoint Inhibitors in Melanoma: A Systematic Review and Network Meta-Analysis
Authors: Sun You-Meng , Li Wei , Chen Zhi-Yu , Wang Ying 
Published: October 2021

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta‐analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma.MethodsPhase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all‐grade (grade 1‐5) and high‐grade (grade 3‐5) immune‐related pneumonitis (IRP) were estimated by odds ratios (ORs).ResultsA total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1–5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1–5 IRP. No significant difference in grade 1–5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3‐5 IRP, no statistically significant difference was found among different ICIs-based regimens.ConclusionThese findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.
A New Prognostic Algorithm Predicting HCC Recurrence in Patients With Barcelona Clinic Liver Cancer Stage B Who Received PA-TACE
Authors: Hu Shuyang , Gan Wei , Qiao Liang , Ye Cheng , Wu Demin , Liao Boyi , Yang Xiaoyu , Jiang Xiaoqing 
Published: October 2021

BackgroundPostoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) is effective in preventing the recurrence of hepatocellular carcinoma (HCC) in patients treated with surgery. However, there is a lack of reports studying the risk factors associated with recurrence in HCC patients who received PA-TACE. In this study, we identified the independent risk factors for recurrence of HCC patients who received PA-TACE. We also developed a novel, effective, and valid nomogram to predict the individual probability of recurrence, 1, 3, and 5 years after PA-TACE.MethodsA retrospective study was performed to identify the independent risk factors for recurrence of HCC in a group of 502 patients diagnosed in stage B based on the Barcelona Clinic Liver Cancer (BCLC) evaluation system for HCC that underwent curative resections. Then, subgroup analysis was performed for 184 patients who received PA-TACE, who were included in the training cohort. The other 147 HCC patients were included in a validation cohort. A recurrence-free survival (RFS)-predicting nomogram was constructed, and results were assessed using calibration and decision curves and a time-dependent AUC diagram.ResultsPA-TACE was shown to be a significant independent prognostic value for patients with BCLC stage B [p &lt; 0.001, hazard ratio (HR) = 0.508, 95% CI = 0.375–0.689 for OS, p = 0.002; HR = 0.670, 95%CI = 0.517–0.868 for RFS]. Alpha fetoprotein (AFP), tumor number, tumor size, microvascular invasion (MVI), and differentiation were considered as independent risk factors for RFS in the training cohort, and these were further confirmed in the validation cohort. Next, a nomogram was constructed to predict RFS. The C-index for RFS in the nomogram was 0.721 (95% CI = 0.718–0.724), which was higher than SNACOR, HAP, and CHIP scores (0.587, 0.573, and 0.607, respectively). Calibration and decision curve analyses and a time-dependent AUC diagram were used. Our nomogram showed stronger performance than these other nomograms in both the training and validation cohorts.ConclusionsHCC patients diagnosed as stage B according to BCLC may benefit from PA-TACE after surgery. The RFS nomogram presented here provides an accurate and reliable prognostic model to monitor recurrence. Patients with a high recurrence score based on the nomogram should receive additional high-end imaging exams and shorter timeframes in between follow-up visits.
Radiation Plus Anti-PD-1 Therapy for NSCLC Brain Metastases: A Retrospective Study
Authors: Liao Guixiang , Qian Yuting , Arooj Sumbal , Zhao Zhihong , Yan Maosheng , Li Zihuang , Yang Hongli , Zheng Tao , Li Gang , Li Xianming , Khan Muhammad 
Published: October 2021

BackgroundRadiation therapy (RT) is the mainstay of brain metastases (BMs), and anti-PD-1 blockade has led to intracranial responses in non-small cell lung carcinoma (NSCLC) patients with BMs.ObjectiveThis study aimed to evaluate the efficacy and safety of adding anti-PD-1 blockade to RT in the management of NSCLC patients with BM in terms of survival outcome.Materials and MethodsWe retrospectively reviewed 70 NSCLC patients with BMs who were treated with whole brain radiation therapy (WBRT) between January 2016 and January 2021. Of the 70 patients, 29 additionally received anti-PD-1 therapy within 30 days of WBRT initiation. Baseline characteristics of the patients and efficacy outcomes such as progression-free survival (PFS) and overall survival (OS) were statistically compared using SPSS v26. Results were obtained using the Chi-square test/Fisher exact test, t-test, Kaplan-Meier, and Cox regression survival analyses.ResultsThe median survival for the entire cohort was 24 months (95% CI, 19.5–28.5). The median survival times for WBRT alone and WBRT plus anti-PD-1 therapy cohorts were 20 months (95% CI, 11.6–28.3) and 27 months (95% CI, 19.5–28.5), respectively (p=0.035). There was no statistical difference in PFS for the treatment cohorts (median PFS for WBRT alone: 7 months vs. 12 months for WBRT plus anti-PD-1, p=0.247). In EGFR wild-type subgroup (n=31), both PFS (p=0.037) and OS (p=0.012) were significantly improved. Only the treatment group (WBRT plus anti-PD-1) was a significant predictor of OS on univariate and multivariate analyses (p=0.040). There were no significant differences in adverse events among the treatment groups.ConclusionsNSCLC patients with BM receiving additional anti-PD-1 therapy may derive better OS than WBRT alone without any increase in adverse events. Prospective well-designed studies are warranted to validate and elucidate the additive effects of the two modalities in this group of patients.
PD-L1, Mismatch Repair Protein, and NTRK Immunohistochemical Expression in Cervical Small Cell Neuroendocrine Carcinoma
Authors: Chen Longyun , Yang Fan , Feng Ting , Wu Shafei , Li Kaimi , Pang Junyi , Shi Xiaohua , Liang Zhiyong 
Published: October 2021

BackgroundCervical small cell neuroendocrine carcinoma (SCNC) is a rare and aggressive disease that lacks a standard treatment strategy or effective methods of targeted therapy. PD-L1 inhibitors for DNA mismatch repair system-deficient (dMMR) tumors and neurotrophin receptor tyrosine kinase (NTRK) inhibitors offer potential pan-cancer treatments.MethodsImmunohistochemistry was employed as the main detection method, and any NTRK positive cases, identified by immunohistochemistry, were further submitted for evaluation by fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (RT-PCR) methods.ResultsForty-six patients were enrolled. Positive PD-L1 expression was seen in 22 of the 43 patients (51.16%) with an average combined positive score of 6.82. PD-L1-positive patients were more likely to have a higher proliferation rate in the tumor, and they experienced less recurrence and death (p = 0.048 and 0.033, respectively) compared with the patients with negative PD-L1 expression. However, in the multivariate analysis, none of the clinical parameters was associated with the expression of PD-L1. There was no association between PD-L1 expression and disease recurrence or overall survival in the Kaplan-Meier analysis. All cases were found to be MMR-stable and lacked NTRK gene fusion. However, pan-Trk expressed in 14 (32.56%) of the 43 tested cases, but FISH and RT-PCR failed to confirm any positive fusion signals in IHC-positive cases.ConclusionsPD-L1 may be an effective therapeutic target for cervical SCNC. Cervical SCNC is a MMR-stable tumor and lacks NTRK gene fusion. IHC isn’t a reliable method in the detection of NTRK gene fusion in cervical SCNC.
The Role of Genetic Polymorphisms in High-Dose Methotrexate Toxicity and Response in Hematological Malignancies: A Systematic Review and Meta-Analysis
Authors: Song Zaiwei , Hu Yang , Liu Shuang , Jiang Dan , Yi Zhanmiao , Benjamin Mason M. , Zhao Rongsheng 
Published: October 2021

Objective: High-dose methotrexate (HDMTX) is a mainstay therapeutic agent for the treatment of diverse hematological malignancies, and it plays a significant role in interindividual variability regarding the pharmacokinetics and toxicity. The genetic association of HDMTX has been widely investigated, but the conflicting results have complicated the clinical utility. Therefore, this systematic review aims to determine the role of gene variants within the HDMTX pathway and to fill the gap between knowledge and clinical practice.Methods: Databases including EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and the Clinical Trials.gov were searched from inception to November 2020. We included twelve single-nucleotide polymorphisms (SNPs) within the HDMTX pathway, involving RFC1, SLCO1B1, ABCB1, FPGS, GGH, MTHFR, DHFR, TYMS, and ATIC. Meta-analysis was conducted by using Cochrane Collaboration Review Manager software 5.3. The odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were analyzed to evaluate the associations between SNPs and clinical outcomes. This study was performed according to the PRISMA guideline.Results: In total, 34 studies with 4102 subjects were identified for the association analysis. Nine SNPs involving MTHFR, RFC1, ABCB1, SLCO1B1, TYMS, FPGS, and ATIC genes were investigated, while none of studies reported the polymorphisms of GGH and DHFR yet. Two SNPs were statistically associated with the increased risk of HDMTX toxicity: MTHFR 677C&gt;T and hepatotoxicity (dominant, OR=1.52, 95% CI=1.03-2.23; recessive, OR=1.68, 95% CI=1.10–2.55; allelic, OR=1.41, 95% CI=1.01–1.97), mucositis (dominant, OR=2.11, 95% CI=1.31–3.41; allelic, OR=1.91, 95% CI=1.28–2.85), and renal toxicity (recessive, OR=3.54, 95% CI=1.81–6.90; allelic, OR=1.89, 95% CI=1.18–3.02); ABCB1 3435C&gt;T and hepatotoxicity (dominant, OR=3.80, 95% CI=1.68-8.61), whereas a tendency toward the decreased risk of HDMTX toxicity was present in three SNPs: TYMS 2R&gt;3R and mucositis (dominant, OR=0.66, 95% CI=0.47–0.94); RFC1 80A&gt;G and hepatotoxicity (recessive, OR=0.35, 95% CI=0.16–0.76); and MTHFR 1298A&gt;C and renal toxicity (allelic, OR=0.41, 95% CI=0.18–0.97). Since the data of prognosis outcomes was substantially lacking, current studies were underpowered to investigate the genetic association.Conclusions: We conclude that genotyping of MTHFR and/or ABCB1 polymorphisms prior to treatment, MTHFR 677C&gt;T particularly, is likely to be potentially useful with the aim of tailoring HDMTX therapy and thus reducing toxicity in patients with hematological malignancies.