bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroids and Olfactory Training for Postviral Olfactory Dysfunction: A Systematic Review
Authors: Yuan Fan , Huang Tianhao , Wei Yongxiang , Wu Dawei 
Published: August 2021

Background:Postviral olfactory dysfunction (PVOD) is a clinical challenge due to limited therapeutic options and poor prognosis. Both steroids and olfactory training have been proved to be effective for olfactory dysfunction with varied etiologies. We sought to perform a systematic review to summarize the evidence of steroids or olfactory training for patients with PVOD.Methods:A systematic literature review using PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify studies assessing olfactory change in patients with PVOD receiving steroid or olfactory training.Results:Of the initial 273 abstracts reviewed, 20 articles with data from 2,415 patients with PVOD were included. Treatments including topical steroids, systemic steroids, classical olfactory training (COT), modified olfactory training (MOT), and olfactory training with steroid were analyzed. Both psychophysical olfactory testing and subjective symptom scores were utilized to assess the olfactory function. The routine use of nasal steroid spray alone during the management of PVOD seems to have no positive effect on olfactory dysfunction. Direct injection of steroid or nasal steroid spray into the olfactory cleft significantly improved the olfactory function in patients with PVOD. Olfactory improvement is greater than that of the natural course of the disease with short-term COT. Patients with PVOD would benefit more from long-term COT (&gt;12 weeks). Treatment duration, various odorants, olfactory training devices, changing the types of odors periodically, different molecular odorants, and different concentrations of odorants tended to increase the efficiency of MOT. Clinically significant improvement after olfactory training was defined as an increase of threshold, discrimination, and identification (TDI) score ≥6. From week 24 to week 36, both COT and MOT groups reached the maximum therapeutic effect regarding the number of participants achieving clinically significant improvement. A combination of local or oral steroids with olfactory training is more efficient than COT only.Conclusion:Olfactory function in patients with PVOD was effectively improved through direct steroid administration in the olfactory cleft, COT, or modification of COT. The addition of topical steroids to COT therapy showed a tendency for greater olfactory improvement in patients with PVOD.
The Induction of Alpha-1 Antitrypsin by Vitamin D in Human T Cells Is TGF-β Dependent: A Proposed Anti-inflammatory Role in Airway Disease
Authors: Chen Yin-Huai , Cheadle Charlotte E. , Rice Louise V. , Pfeffer Paul E. , Dimeloe Sarah , Gupta Atul , Bush Andrew , Gooptu Bibek , Hawrylowicz Catherine M. 
Published: August 2021

Background: Vitamin D upregulates anti-inflammatory and antimicrobial pathways that promote respiratory health. Vitamin D synthesis is initiated following skin exposure to sunlight, however nutritional supplementation can be required to address deficiency, for example during the winter months or due to cultural constraints. We recently reported that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment induced alpha-1 antitrypsin (AAT) expression in CD4+, but not CD8+ T cells, with evidence supporting an immunoregulatory role.Research Question: To understand the relationship between vitamin D, lung AAT levels and T lymphocytes further we investigated whether TGF-β is required as a co-factor for 1,25(OH)2D3-induced upregulation of AAT by vitamin D in CD8+ T cells in vitro and correlated circulating vitamin D levels with lung AAT levels in vivo.Results: 1,25(OH)2D3 in combination with TGF-β1 increased AAT expression by CD8+ T cells, as well as VDR and RXRα gene expression, which may partly explain the requirement for TGF-β. CD4+ T cells may also require autocrine stimulation with TGF-β as a co-factor since 1,25(OH)2D3 was associated with increased TGF-β bioactivity and neutralisation of TGF-β partially abrogated 1,25(OH)2D3-induced SERPINA1 gene expression. Neither CD4+ nor CD8+ T cells responded to the circulating vitamin D precursor, 25-hydroxyvitamin D3 for induction of SERPINA1, suggesting that local generation of 1,25(OH)2D3 is required. Transcriptional gene profiling studies previously demonstrated that human bronchial epithelial cells rapidly increased TGF-β2 gene expression in response to 1,25(OH)2D3. Here, human epithelial cells responded to precursor 25(OH)D3 to increase bioactive TGF-β synthesis. CD8+ T cells responded comparably to TGF-β1 and TGF-β2 to increase 1,25(OH)2D3-induced AAT. However, CD8+ T cells from adults with AAT-deficiency, homozygous for the Z allele of SERPINA1, were unable to mount this response. AAT levels in the airways of children with asthma and controls correlated with circulating 25(OH)D3.Conclusions: Vitamin D increases AAT expression in human T cells and this response is impaired in T cells from individuals homozygous for the Z allele of SERPINA1 in a clinic population. Furthermore, a correlation between circulating vitamin D and airway AAT is reported. We propose that vitamin D-induced AAT contributes to local immunomodulation and airway health effects previously attributed to vitamin D.
Breast-Conserving Therapy Has Better Prognosis for Tumors in the Central and Nipple Portion of Breast Cancer Compared with Mastectomy: A SEER Data-Based Study
Authors: Wang Jing , Wang Xiaoyu , Zhong Zhenyu , Li Xue , Sun Jiazheng , Li Jie , Huang Jiefeng , Li Yunhai , Ren Guosheng , Li Hongzhong 
Published: August 2021

Background and ObjectivesCurrently, the location of primary tumor was an independent prognostic factor of breast cancer. Tumors in the central and nipple portion (TCNP) had poor prognosis compared to other peripheral quadrants. The breast-conserving therapy (BCT) is becoming increasingly common worldwide in breast cancer operations. However, whether the availability of BCT was performed for TCNP remained a matter of debate. We sought to investigate whether BCT was suitable for TCNP with respect to survival outcomes, compared with mastectomy therapy.MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained TCNP breast cancer patients diagnosed during the period of 2010–2015. One-to-one (1:1) propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of BCT and mastectomy groups. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS). Survival analysis was performed with the Kaplan–Meier method.ResultsIn the overall cohort, a total of 9,900 patients were enrolled. We found that patients with BCT showed significantly better BCSS (log-rank, p &lt; 0.001) and OS (log-rank, p &lt; 0.001) than the mastectomy group before PSM. The same finding was also shown in 5,820 patients after PSM. Additionally, none of the subgroups, including age, sex, race, histological grade, AJCC stage, and molecular subtype undergoing mastectomy therapy, had better BCSS than BCT.ConclusionsOur study was the first research to show that BCT exhibited superior prognosis in the cohort of TCNP from SEER databases than mastectomy therapy. This finding could provide a cue for treatment strategies for suitable TCNP patients, especially those with a strong willingness to conserve their breasts.
Diagnostic Potential of Plasma IgG N-glycans in Discriminating Thyroid Cancer from Benign Thyroid Nodules and Healthy Controls
Authors: Zhang Zejian , Wu Jianqiang , Liu Peng , Kang Lin , Xu Xiequn 
Published: August 2021

BackgroundNovel biomarkers are urgently needed to distinguish between benign and malignant thyroid nodules and detect thyroid cancer in the early stage. The associations between serum IgG N-glycosylation and thyroid cancer risk have been revealed. We aimed to explore the potential of IgG N-glycan traits as biomarkers in the differential diagnosis of thyroid cancer.MethodsPlasma IgG N-glycome analysis was applied to a discovery cohort followed by independent validation. IgG N-glycan profiles were obtained using a robust quantitative strategy based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. IgG N-glycans were relatively quantified, and classification performance was evaluated based on directly detected and derived glycan traits.ResultsFour directly detected glycans were significantly changed in thyroid cancer patients compared to that in non-cancer controls. Derived glycan traits and a classification glycol-panel were generated based on the directly detected glycan traits. In the discovery cohort, derived trait BN (bisecting type neutral N-glycans) and the glyco-panel showed potential in distinguishing between thyroid cancer and non-cancer controls with AUCs of 0.920 and 0.917, respectively. The diagnostic potential was further validated. Derived trait BN and the glycol-panel displayed “accurate” performance (AUC&gt;0.8) in discriminating thyroid cancer from benign thyroid nodules and healthy controls in the validation cohort. Meanwhile, derived trait BN and the glycol-panel also showed diagnostic potential in detecting early-stage thyroid cancer.ConclusionsIgG N-glycome analysis revealed N-glycomic differences that allow classification of thyroid cancer from non-cancer controls. Our results suggested that derived trait BN and the classification glyco-panel rather than single N-glycans may serve as candidate biomarkers for further validation.
Vascular Normalization: A New Window Opened for Cancer Therapies
Authors: Yang Ting , Xiao Hongqi , Liu Xiaoxia , Wang Zhihui , Zhang Qingbai , Wei Nianjin , Guo Xinggang 
Published: August 2021

Preclinical and clinical antiangiogenic approaches, with multiple side effects such as resistance, have not been proved to be very successful in treating tumor blood vessels which are important targets for tumor therapy. Meanwhile, restoring aberrant tumor blood vessels, known as tumor vascular normalization, has been shown not only capable of reducing tumor invasion and metastasis but also of enhancing the effectiveness of chemotherapy, radiation therapy, and immunotherapy. In addition to the introduction of such methods of promoting tumor vascular normalization such as maintaining the balance between proangiogenic and antiangiogenic factors and targeting endothelial cell metabolism, microRNAs, and the extracellular matrix, the latest molecular mechanisms and the potential connections between them were primarily explored. In particular, the immunotherapy-induced normalization of blood vessels further promotes infiltration of immune effector cells, which in turn improves immunotherapy, thus forming an enhanced loop. Thus, immunotherapy in combination with antiangiogenic agents is recommended. Finally, we introduce the imaging technologies and serum markers, which can be used to determine the window for tumor vascular normalization.
Beyond Average: Providers' Assessments of Indices for Measuring Pain Intensity in Patients With Chronic Pain
Authors: Goldman Roberta E. , Broderick Joan E. , Junghaenel Doerte U. , Bolton Alicia , May Marcella , Schneider Stefan , Stone Arthur A. 
Published: August 2021

Introduction: Effective clinical care for chronic pain requires accurate, comprehensive, meaningful pain assessment. This study investigated healthcare providers' perspectives on seven pain measurement indices for capturing pain intensity.Methods: Semi-structured telephone interviews were conducted with a purposeful sample from four US regions of 20 healthcare providers who treat patients with chronic pain. The qualitative interview guide included open-ended questions to address perspectives on pain measurement, and included quantitative ratings of the importance of seven indices [average pain, worst pain, least pain, time in no/low pain, time in high pain, fluctuating pain, unpredictable pain]. Qualitative interview data were read, coded and analyzed for themes and final interpretation. Standard quantitative methods were used to analyze index importance ratings.Results: Despite concerns regarding 10-point visual analog and numeric rating scales, almost all providers used them. Providers most commonly asked about average pain, although they expressed misgivings about patient reporting and the index's informational value. Some supplemented average with worst and least pain, and most believed pain intensity is best understood within the context of patient functioning. Worst pain received the highest mean importance rating (7.60), average pain the second lowest rating (5.65), and unpredictable pain the lowest rating (5.20).Discussion: Assessing average pain intensity obviates obtaining clinical insight into daily contextual factors relating to pain and functioning. Pain index use, together with timing, functionality and disability, may be most effective for understanding the meaning to patients of high pain, how pain affects their life, how life affects their pain, and how pain changes and responds to treatment.
Association Between Secondary Hyperparathyroidism and Body Composition in Pediatric Patients With Moderate and Advanced Chronic Kidney Disease
Authors: Karava Vasiliki , Kondou Antonia , Dotis John , Christoforidis Athanasios , Taparkou Anna , Tsioni Konstantina , Farmaki Evangelia , Kollios Konstantinos , Siomou Ekaterini , Liakopoulos Vassilios , Printza Nikoleta 
Published: August 2021

Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4–5) chronic kidney disease (CKD).Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score &lt; −1.65 SD and high adiposity as FTI z-score &gt; 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated.Results: In moderate CKD (31 patients), high iPTH (&gt;90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = −0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002–1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150–45.384, p = 0.035).Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.
Safety and Efficacy of Anti-PD-1/PD-L1 Inhibitors Compared With Docetaxel for NSCLC: A Systematic Review and Meta-Analysis
Authors: Ma Long , Jin Gang , Yao Keying , Yang Yi , Chang Ruitong , Wang Wenhao , Liu Jiawei , Zhu Zijiang 
Published: August 2021

Objective: To evaluate the efficacy and safety of anti-PD-1/PD-L1 Inhibitors versus docetaxel for non-small cell lung cancer by meta-analysis.Methods: Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 Inhibitors versus docetaxel on the treatment of NSCLC were searched in CNKI, WF, VIP, PubMed, EMBASE, Cochrane Library, and Web of Science databases. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies. Meta-analysis was performed by RevMan5.3 software.Results: Compared with the use of docetaxel chemotherapy for NSCLC, the overall survival and progression-free survival of the anti-PD-1/PD-L1 Inhibitors regimen are better [overall survival: (HR= 0.73, 95%CI:0.69∼0.77, P&lt;0.00001], progression-free survival: (HR= 0.89, 95%CI:0.83∼0.94, P&lt;0.00001]), and lower incidence of treatment-related grade 3 or higher adverse events ([OR=0.20, 95% CI: 0.13∼0.31, P&lt;0.00001]).Conclusion: Compared with the docetaxel chemotherapy regimen, the anti-PD-1/PD-L1 Inhibitors has certain advantages in terms of efficacy and safety. The results still need to be confirmed by a multi-center, large sample, and high-quality research.
Efficacy of Thalidomide Treatment in Children With Transfusion Dependent β-Thalassemia: A Retrospective Clinical Study
Authors: Li Xinyu , Hu Shuting , Liu Yong , Huang Junjiu , Hong Weicong , Xu Luhong , Xu Honggui , Fang Jianpei 
Published: August 2021

Background: Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with β-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent β-thalassemia (TDT) is scarce.Methods: Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg·kg-1·d-1. Blood volume for maintenance of hemoglobin above 90 g·L-1 compared with pre-treatment volume is the evaluation index for response.Results: After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g·L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients. Age, sex, genotype category, dosage, and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbF at the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden’s index algorithm in the ROC curve, 47.298 g·L-1 was the optimal cut-off value of the HbF at the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5% and specificity of 93.3%.Conclusions: The dose of thalidomide between 2.5 mg·kg-1·d-1 and 3.6 mg·kg-1·d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g·L-1 at the third month is recommended as the predictor for further major responders.
Nine Forward–Backward Translations of the Hopkins Symptom Checklist-25 With Cultural Checks
Authors: Nabbe Patrice , Le Reste Jean Yves , Guillou-Landreat Morgane , Assenova Radost , Kasuba Lazic Djurdjica , Czachowski Slawomir , Stojanović-Špehar Stanislava , Hasanagic Melida , Lingner Heidrun , Clavería Ana , Rodríguez-Barragán María , Sowinska Agnieszka , Argyriadou Stella , Lygidakis Charileos , Le Floch Bernard , Montier Tristan , Van Marwijk Harm , Van Royen Paul 
Published: August 2021

Introduction: The Hopkins Symptom Checklist-25 (HSCL-25) is an effective, reliable, and ergonomic tool that can be used for depression diagnosis and monitoring in daily practice. To allow its broad use by family practice physicians (FPs), it was translated from English into nine European languages (Greek, Polish, Bulgarian, Croatian, Catalan, Galician, Spanish, Italian, and French) and the translation homogeneity was confirmed. This study describes this process.Methods: First, two translators (an academic translator and an FP researcher) were recruited for the forward translation (FT). A panel of English-speaking FPs that included at least 15 experts (researchers, teachers, and practitioners) was organized in each country to finalize the FT using a Delphi procedure.Results: One or two Delphi procedure rounds were sufficient for each translation. Then, a different translator, who did not know the original version of the HSCL-25, performed a backward translation in English. An expert panel of linguists compared the two English versions. Differences were listed and a multicultural consensus group determined whether they were due to linguistic problems or to cultural differences. All versions underwent cultural check.Conclusion: All nine translations were finalized without altering the original meaning.
Reddit Users' Experiences of Suicidal Thoughts During the COVID-19 Pandemic: A Qualitative Analysis of r/Covid19_support Posts
Authors: Slemon Allie , McAuliffe Corey , Goodyear Trevor , McGuinness Liza , Shaffer Elizabeth , Jenkins Emily K. 
Published: August 2021

Background: The COVID-19 pandemic is having considerable impacts on population-level mental health, with research illustrating an increased prevalence in suicidal thoughts due to pandemic stressors. While the drivers of suicidal thoughts amid the pandemic are poorly understood, qualitative research holds great potential for expanding upon projections from pre-pandemic work and nuancing emerging epidemiological data. Despite calls for qualitative inquiry, there is a paucity of qualitative research examining experiences of suicidality related to COVID-19. The use of publicly available data from social media offers timely and pertinent information into ongoing pandemic-related mental health, including individual experiences of suicidal thoughts.Objective: To examine how Reddit users within the r/COVID19_support community describe their experiences of suicidal thoughts amid the COVID-19 pandemic.Methods: This study draws on online posts from within r/COVID19_support that describe users' suicidal thoughts during and related to the COVID-19 pandemic. Data were collected from creation of this subreddit on February 12, 2020 until December 31, 2020. A qualitative thematic analysis was conducted to generate themes reflecting users' experiences of suicidal thoughts.Results: A total of 83 posts from 57 users were included in the analysis. Posts described a range of users' lived and living experiences of suicidal thoughts related to the pandemic, including deterioration in mental health and complex emotions associated with suicidal thinking. Reddit users situated their experiences of suicidal thoughts within various pandemic stressors: social isolation, employment and finances, virus exposure and COVID-19 illness, uncertain timeline of the pandemic, news and social media, pre-existing mental health conditions, and lack of access to mental health resources. Some users described individual coping strategies and supports used in attempt to manage suicidal thoughts, however these were recognized as insufficient for addressing the multilevel stressors of the pandemic.Conclusions: Multiple and intersecting stressors have contributed to individuals' experiences of suicidal thoughts amid the COVID-19 pandemic, requiring thoughtful and complex public health responses. While ongoing challenges exist with self-disclosure of mental health challenges on social media, Reddit and other online platforms may offer a space for users to share suicidal thoughts and discuss potential coping strategies.