bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-α may help prevent molecular relapse of chronic myeloid leukemia after the discontinuation of tyrosine kinase inhibitors
Authors: Jun Kong , Ya-zhen Qin , Xiao-su Zhao , Hong-Xia Shi , Yue-Yun Lai , Kai-yan Liu , Xiao-jun Huang , Hao Jiang 
Published: January 2021

Background: Currently, the goal of chronic myeloid leukemia (CML) treatment is normal survival and good quality of life without life-long treatment, namely, “treatment-free remission” (TFR). At present, approximately only 50% of patients with CML with a deep molecular response are able to discontinue tyrosine kinase inhibitor (TKI) without experiencing molecular relapse [MR; loss of major molecular response (MMR)]. In addition, prior interferon (IFN) treatment is associated with a higher rate of TFR. Methods: We aimed to evaluate the feasibility of TKI discontinuation in Chinese patients with CML and determine whether IFN could prevent MR when used after TKI discontinuation in patients with 0.0032% < BCR-ABLIS ⩽0.1%. Therefore, we retrospectively analyzed the data of patients with CML who discontinued TKI treatment at our center. Results: Forty-nine patients who discontinued TKI therapy after achieving MR 4.5 were included in this study, and the median follow-up time from TKI discontinuation was 27 (7, 75) months. Nineteen patients eventually lost MMR, and the TFR rate of the 49 patients was 67% (95% confidence interval 53.6%, 80.3%) at 12 months. The duration of MR 4.5 ⩾54 months and duration of imatinib ⩾85 months were significantly associated with a higher TFR rate. Of the 22 patients with 0.0032% < BCR-ABLIS ⩽0.1%, 12 received IFN-α treatment. The median IFN-α therapy duration was nine (2, 18) months, and three patients eventually lost MMR. Three patients discontinued IFN-α after 2, 2.5, and 10 months, and maintained MMR for 9, 8, and 11 months after IFN discontinuation, respectively. Of the 10 patients not receiving IFN-α treatment, eight eventually lost MMR. The MR-free survival rate was significantly different between the patients treated with and those treated without IFN-α over 24 months (70.7% versus 15.0%, p = 0.002). Conclusion: These results indicate that after TKI discontinuation, IFN-α can be administered to patients with 0.0032% < BCR-ABLIS ⩽0.1%, which may help prevent MR.
Understanding racial differences of COPD patients with an ecological model: two large cohort studies in the US and Korea
Authors: Park Hye Yun , Lee Hyun , Kang Danbee , Choi Hye Sook , Ryu Yeong Ha , Jung Ki-Suck , Sin Don D. , Cho Juhee , Yoo Kwang Ha 
Published: January 2021

Background: There are limited data about the racial difference in the characteristics of chronic obstructive pulmonary disease (COPD) patients who are treated at clinics. We aimed to compare sociodemographic and clinical characteristics between US and Korean COPD patients using large-scale nationwide COPD cohorts. Methods: We used the baseline demographic and clinical data of COPD patients aged 45 years or older with at least a 10 pack-per year smoking history from the Korean COPD Subtype Study (KOCOSS, n = 1686) cohort (2012–2018) and phase I (2008–2011) of the US Genetic Epidemiology of COPD (COPDGene) study ( n = 4477, 3461 were non-Hispanic whites [NHW], and 1016 were African Americans [AA]). Results: Compared to NHW, AA had a significantly lower adjusted prevalence ratio (aPR) of cough >3 months (aPR: 0.67; 95% CI [confidence interval]: 0.60–0.75) and phlegm >3 months (aPR: 0.78, 95% CI: 0.70–0.86), but higher aPR of dyspnea (modified Medical Round Council scale ⩾2) (aPR: 1.22; 95% CI: 1.15–1.29), short six-minute walk distance (<350 m) (aPR: 1.98; 95% CI: 1.81–2.14), and poor quality of life (aPR: 1.10; 95% CI: 1.05–1.15). Compared to NHW, Koreans had a significantly lower aPR of cough >3 months (aPR: 0.53; 95% CI: 0.47–0.59), phlegm >3 months (aPR: 0.75; 95% CI: 0.67–0.82), dyspnea (aPR: 0.72; 95% CI: 0.66–0.79), and moderate-to-severe acute exacerbation in the previous year (aPR: 0.73; 95% CI: 0.65–0.82). NHW had the highest burden related to chronic bronchitis symptoms and cardiovascular diseases related to comorbidities. Conclusion: There are substantial differences in sociodemographic characteristics, clinical presentation, and comorbidities between COPD patients from the KOCOSS and COPDGene, which might be caused by interactions between various intrapersonal, interpersonal, and environmental factors of the ecological model. Thus, a broader and more comprehensive approach would be necessary to understand the racial differences of COPD patients.
Cardiac manifestations of eosinophilic granulomatosis with polyangiitis from a single-center cohort in China: clinical features and associated factors
Authors: Liu Suying , Guo Ling , Zhang Zhaocui , Li Mengtao , Zeng Xiaofeng , Wang Li , Liu Yongtai , Zhang Fengchun 
Published: January 2021

Background: Cardiac manifestations are common and life-threatening in eosinophilic granulomatosis with polyangiitis (EGPA), which remains poorly studied in China. We aim to investigate its clinical features, associated factors, treatment, and outcomes. Methods: We reviewed the clinical records of 110 EGPA patients and examined the independent factors associated with cardiac manifestations using multivariate logistic regression. Receiver operating characteristic curves determined the cut-off values, and survival was calculated via Kaplan–Meier curves. Results: Cardiac involvement was present in 36.4% (40/110) of EGPA patients, which mainly manifested as pericardial effusion (16.4%, 18/110), myocardial involvement (13.6%, 15/110), and heart failure (8.2%, 9/110). The mean age was 42.1 ± 14.23 years with no female/male predominance. Compared with the cardiac-unaffected group, the cardiac-affected group showed a lower rate of biopsy-proved vasculitis (0% versus 20%, p = 0.002). The eosinophil count [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.029–1.267] was independently associated with cardiac manifestations in EGPA, with a cut-off value of 3.66 × 109/L [area under the curve (AUC) = 0.692, p = 0.001]. Regarding treatment, the cardiac-affected group displayed a higher ratio of glucocorticoid pulse combined with intravenous cyclophosphamide (CYC-IV) (40% versus 21.4%, p = 0.037), and intravenous immunoglobulin combined with glucocorticoid plus CYC-IV (17.5% versus 4.3%, p = 0.035) than the control group. Outcomes ( p = 0.131) and survival ( p = 0.1972) were not significantly different between the groups. Conclusion: In this single-center Chinese EGPA cohort, cardiac manifestations are observed in 36.4% of patients, which primarily presents as myocardial involvement, pericardial effusion, and heart failure, independently associated with eosinophil count. Glucocorticoid combined with cyclophosphamide is the treatment cornerstone for EGPA patients with cardiac manifestations.
Insulin resistance in transgender individuals correlates with android fat mass
Authors: Bretherton Ingrid , Spanos Cassandra , Leemaqz Shalem Y. , Premaratne Gehan , Grossmann Mathis , Zajac Jeffrey D. , Cheung Ada S. 
Published: January 2021

Background: Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance. Aims: To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT. Methods: Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported. Results: Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5), p < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3), p < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of −6.9 kg (–10.6, –3.1), p < 0.001, fat mass of +9.8 kg (3.9, 14.5), p = 0.001, lower android:gynoid fat ratio −0.1 (–0.2,–0.0), p < 0.05), and higher insulin resistance 1.6 (1.3–1.9), p < 0.001). Higher HOMA2-IR correlated with higher android ( r2 = 0.712, p < 0.001) and gynoid ( r2 = 0.572, p < 0.001) fat mass in both trans men and trans women. Conclusion: Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.
Integrative analysis of a phase 2 trial combining lenalidomide with CHOP in angioimmunoblastic T-cell lymphoma
Authors: Lemonnier François , Safar Violaine , Beldi-Ferchiou Asma , Cottereau Anne-Ségolène , Bachy Emmanuel , Cartron Guillaume , Fataccioli Virginie , Pelletier Laura , Robe Cyrielle , Letourneau Audrey , Missiaglia Edoardo , Fourati Slim , Moles-Moreau Marie-Pierre , Delmer Alain , Bouabdallah Reda , Voillat Laurent , Becker Stéphanie , Bossard Céline , Parrens Marie , Casasnovas Olivier , Cacheux Victoria , Régny Caroline , Camus Vincent , Delfau-Larue Marie-Hélène , Meignan Michel , de Leval Laurence , Gaulard Philippe , Haioun Corinne 
Published: January 2021

Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is a frequent T-cell lymphoma in the elderly population that has a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Lenalidomide, which has been safely combined with CHOP to treat B-cell lymphoma, has shown efficacy as a single agent in AITL treatment. We performed a multicentric phase 2 trial combining 25 mg lenalidomide daily for 14 days per cycle with 8 cycles of CHOP21 in previously untreated AITL patients aged 60 to 80 years. The primary objective was the complete metabolic response (CMR) rate at the end of treatment. Seventy-eight of the 80 patients enrolled were included in the efficacy and safety analysis. CMR was achieved in 32 (41%; 95% confidence interval [CI], 30%-52.7%) patients, which was below the prespecified CMR rate of 55% defined as success in the study. The 2-year progression-free survival (PFS) was 42.1% (95% CI, 30.9%-52.8%), and the 2-year overall survival was 59.2% (95% CI, 47.3%-69.3%). The most common toxicities were hematologic and led to treatment discontinuation in 15% of patients. This large prospective and uniform series of AITL treatment data was used to perform an integrative analysis of clinical, pathologic, biologic, and molecular data. TET2, RHOA, DNMT3A, and IDH2 mutations were present in 78%, 54%, 32%, and 22% of patients, respectively. IDH2 mutations were associated with distinct pathologic and clinical features and DNMT3A was associated with shorter PFS. In conclusion, the combination of lenalidomide and CHOP did not improve the CMR in AITL patients. This trial clarified the clinical impact of recurrent mutations in AITL. This trial was registered at www.clincialtrials.gov as #NCT01553786.
G-quadruplexes in H1N1 influenza genomes
Authors: Brázda Václav , Porubiaková Otília , Cantara Alessio , Bohálová Natália , Coufal Jan , Bartas Martin , Fojta Miroslav , Mergny Jean-Louis 
Published: January 2021

Abstract
Background
Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment.

Results
PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods.

Conclusions
The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.
High prevalence of Campylobacter jejuni CC21 and CC257 clonal complexes in children with gastroenteritis in Tehran, Iran
Authors: Sarhangi Mahnaz , Bakhshi Bita , Peeraeyeh Shahin Najar 
Published: January 2021

AbstractBackgroundCampylobacter jejuni (C. jejuni) is a leading cause of acute gastroenteritis in human worldwide. The aim of study was to assess the distribution of sialylated lipooligosaccharide (LOS) classes and capsular genotypes inC. jejuniisolated from Iranian children with gastroenteritis. Furthermore, the level ofdnaKgene expression inC. jejunistrains with selected capsular genotypes and LOS classes was intended. Moreover, a comprehensive study ofC. jejuniMLST-genotypes and inclusive comparison with peer sequences worldwide was intended.MethodsTwenty clinicalC. jejunistrains were isolated from fecal specimens of 280 children aged 0–5 years, suspected of bacterial gastroenteritis, which admitted to 3 children hospitals from May to October, 2018. Distribution of sialylated LOS classes and specific capsular genotypes were investigated inC. jejuniof clinical origin. The expression ofdnaKinC. jejunistrains was measured by Real-Time-PCR. MLST-genotyping was performed to investigate the clonal relationship of clinicalC. jejunistrains and comparison with inclusive sequences worldwide.ResultsC. jejuniHS23/36c was the predominant genotype (45%), followed by HS2 (20%), and HS19 and HS4 (each 10%). A total of 80% of isolates were assigned to LOS class B and C. Higher expression level ofdnaKgene was detected in strains with HS23/36c, HS2 and HS4 capsular genotypes and sialylated LOS classes B or C. MLST analysis showed that isolates were highly diverse and represented 6 different sequence types (STs) and 3 clonal complexes (CCs). CC21 and CC257 were the most dominant CCs (75%) among ourC. jejunistrains. No new ST and no common ST with our neighbor countries was detected.ConclusionsTheC. jejuniisolates with LOS class B or C, and capsular genotypes of HS23/36, HS2, HS4 and HS19 were dominant in population under study. The CC21 and CC257 were the largest CCs among our isolates. In overall picture, CC21 and CC353 complexes were the most frequently and widely distributed clonal complexes worldwide, although members of CC353 were not detected in our isolates. This provides a universal picture of movement of dominant Campylobacter strains worldwide.
Restricted TcR β chain CDR3 clonotype is associated with resolved acute hepatitis B subjects
Authors: Xiao Dangsheng , Wang Ju , Chen Zhitao , Jin Xiuyuan , Xie Yirui , Yan Dong , Yang Jiezuan 
Published: January 2021

Abstract
Background
T cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor β-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS).

Methods
The clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq).

Results
The overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20–1/BD1/BJ1–2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180–1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05).

Conclusions
Thus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status.
Light chain deposition disease involving kidney and liver in a patient with IgD myeloma
Authors: Tsushima Takafumi , Suzuki Tomo , Terao Toshiki , Miura Daisuke , Narita Kentaro , Takeuchi Masami , Shimuzu Akira , Matsue Kosei 
Published: January 2021

AbstractBackgroundIgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma.Case presentationA 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Igκlight chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Igκ light chain with more than 95% probability confirm the diagnosis of κ-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Igκ chain along the perisinusoidal space indicating the hepatic involvement of κ-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab.ConclusionsThis report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement.
Clinical impact of creatine phosphokinase and c-reactive protein as predictors of postgastrectomy complications in patients with gastric cancer
Authors: Okubo Keishi , Arigami Takaaki , Matsushita Daisuke , Kijima Takashi , Shimonosono Masataka , Uenosono Yoshikazu , Yanagita Shigehiro , Kurahara Hiroshi , Mori Shinichiro , Ohtsuka Takao , Natsugoe Shoji 
Published: January 2021

Abstract
Background
Postoperative complications have been linked to the morbidity and mortality of several cancers. However, predicting whether complications will occur in the early period after surgery or not is challenging. Hence, this study aimed to examine the diagnostic accuracy of serum creatine phosphokinase (CPK) and c-reactive protein (CRP) in predicting the development of postgastrectomy complications.

Methods
We retrospectively analyzed 188 patients with gastric cancer (GC) who underwent gastrectomy. The diagnostic accuracy of serum CPK and CRP was investigated using the areas under the curves (AUC). The CPK ratio was defined as the CPK on postoperative day (POD) 1 to the CPK on a preoperative day.

Results
Out of 188 patients, 48 (25.5%) developed postoperative complications. The complications group had a greater operative time (p = 0.037), higher CPK ratio on POD1 (p < 0.0001), and a higher serum CRP level on POD3 (p = 0.001). The AUC for the CPK ratio was 0.772, with an optimal cutoff value of 7.05, whereas that for CRP was 0.659, with an optimal cutoff value of 11.4 mg/L. The CPK ratio on POD1 (p < 0.0001) and the CRP on POD3 (p = 0.007) were independent factors for predicting the development of postgastrectomy complications. The CPK ratio on POD1 and the CRP on POD3 predicted postgastrectomy complications in 41 patients (85.4%). According to combined value of both CPK ratio and CRP level, the positive predictive value and the negative predictive value was 0.70 and 0.829. And sensitivity and specificity were 0.438 and 0.936.

Conclusion
The CPK ratio on POD1 and the CRP on POD3 after gastrectomy for GC were predictive factors for complication development and may be employed to prevent the development of such complications and improve the prognosis of patients with GC.
Correlation between improvement in visual acuity and QOL after Ranibizumab treatment for age-related macular degeneration patients: QUATRO study
Authors: Oshima Yuji , Ishibashi Yumi , Umeda Naoyasu , Nagata Tatsuo , Yoshida Shigeo , Uchio Eiichi , Kondo Hiroyuki , Sonoda Koh-hei , Ishibashi Tatsuro 
Published: January 2021

Abstract
Background
To evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD.

Methods
In this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.5 mg ranibizumab as needed after three initial monthly doses. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at every visit. Evaluations with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and patient satisfaction questionnaire were performed at baseline and 3 and 12 months after initial treatment. The primary endpoint was change in BCVA and QOL 3 months after ranibizumab treatment. QOL outcomes were also assessed in the better and poor BVCA subgroups.

Results
The study enrolled 100 patients. The mean logMAR BCVA after treatment improved significantly from 0.43 to 0.30 at 3 months (p< 0.0001), and 0.28 at 12 months (p< 0.0001). The mean NEI-VFQ-25 composite scores improved from 79.48 to 84.13 at 3 months (p< 0.0001), and 86.0 at 12 months (p< 0.0001). The 3 and 12-month changes in NEI-VFQ-25 score and BCVA showed significant correlation. In the poor baseline visual acuity group (decimal BCVA ≤0.5), there was a significant correlation between the changes in the NEI-VFQ-25 score and BCVA (p=0.02) but not in the better baseline visual acuity group (decimal BCVA > 0.6, p=0.1) at 3 months. There were no significant differences in the satisfaction questionnaire score from baseline to at 3 months (p=0.54) and 12 months (p=0.23). The average CMT improved significantly from 340 to 264 μm at 3 months (p< 0.0001) and to 268 μm at 12 months (p< 0.0001).

Conclusions
Intravitreal ranibizumab treatment resulted in improvement in visual acuity, anatomical change, and visual function change in Japanese AMD patients. Significant improvement was seen in patient visual function, and this was correlated with changes in VA, except immediately after loading dose treatment in patients with higher baseline VA. The patients’ satisfaction with the treatment remained unchanged during the study period.

Trial registration
This study is registered at UMIN Clinical Trials Registry (UMIN000012013). Registered October 10, 2013, as prospective study.