bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027
Authors: Minegishi Yuji , Yamaguchi Ou , Sugawara Shunichi , Kuyama Shoichi , Watanabe Satoshi , Usui Kazuhiro , Mori Masahide , Hataji Osamu , Nukiwa Toshihiro , Morita Satoshi , Kobayashi Kunihiko , Gemma Akihiko 
Published: March 2021

Abstract
Background
Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC).

Methods
This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review.

Results
In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75–91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5–19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2–not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.

Conclusion
Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS.

Trial registration
The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).
Factors associated with awareness, treatment and control of hypertension among 3579 hypertensive adults in China: data from the China Health and Nutrition Survey
Authors: Wei Junxiang , Mi Yang , Li Yan , Xin Bo , Wang Youfa 
Published: March 2021

Abstract
Background
The prevalence of hypertension is high and rising in China, but most people with hypertension do not have their blood pressure under control. This study investigated hypertension awareness, treatment, and control and their associated factors among Chinese adults.

Methods
Data collected from the 2011 China Health and Nutrition Survey (CHNS) from 12,991 Chinese adults were used. Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, self-reported prior diagnosed hypertension, or taking antihypertensive medications. Hypertension awareness, treatment, and control were defined as a self-reported diagnosis of hypertension, current use of antihypertensive medication, and blood pressure < 140/90 mmHg, respectively. Multivariate logistic regression was performed to examine factors associated with hypertension awareness, treatment, and control.

Results
Overall, 3579 (27.6%) of the CHNS adult participants had hypertension, of whom 55.7% were aware of their diagnosis, 46.5% were treated with antihypertensive medications, but only 20.3% had their blood pressure under control. Higher hypertension treatment was associated with older age (OR = 2.57; 95%CI, 1.65–4.02), urban residency (1.50; 1.14–1.97), living in the Eastern region (1.52; 1.14–2.01), and being overweight/obese (1.99; 1.39–2.84). Hypertension awareness was associated with similar factors as hypertension treatment but was also associated with being female (1.37, 1.12–1.66). Poor hypertension control was associated with being overweight/obese (0.56; 0.42–0.76) and minority ethnicity (0.52; 0.31–0.86).

Conclusion
Hypertension is a major public health challenge in China. The prevalence of hypertension awareness, treatment, and control are still low despite existing public health policies and programs to reduce the burden of hypertension. More intensive hypertension screening and treatment programs are warranted in China.
Long-term prognostic factors of clinical success after interventional bronchoscopy in patients with scarring central airway stenosis
Authors: Sun Kunyan , Zhang Hong , Zhang Wei , Cheng Yuan , Wang Guangfa 
Published: March 2021

AbstractBackgroundScarring central airway stenosis (SCAS) is a potentially life-threatening condition with debilitating symptoms. Interventional bronchoscopy is increasingly used to relieve symptoms in patients with SCAS, but recurrent stenosis is frequently observed. Little data exist on the long-term prognosis of interventional bronchoscopy for SCAS. We aimed to assess the prognostic factors of bronchoscopic interventions in patients with SCAS to optimize treatment.MethodsThis was a retrospective study that enrolled 119 consecutive patients with SCAS from January 2010 to April 2019 at our institution. Long-term clinical success was defined as airway stenosis < 50%, no limitation of physical activity, and a stable condition for > 12 months after the last interventional procedure. We compared patients’ demographics, airway stenosis characteristics, and interventional procedures between the successful and unsuccessful groups, and identified significant predictors of long-term outcome with univariate and multivariate logistic regression.ResultsA total of 119 patients with 577 therapeutic bronchoscopies were included. Seventy-five (63%) patients were considered to have long-term clinical success. Older age, male gender, smoking, elevated C-reactive protein level, subglottic stenosis, stent or T-tube implantation, previous interventional treatment, and multiple procedures per year were potentially associated with unsuccessful long-term outcomes in the univariate analysis. Current smoker status (odds ratio [OR] 5.70, 95% confidence interval [CI] 1.35–24.17,P = 0.018), subglottic stenosis (OR 4.35, 95% CI 1.31–14.46,P = 0.017), and stent implantation (OR 4.96, 95% CI 1.33–18.48,P = 0.017) were associated with decreased odds of long-term success in the multivariate logistic regression analysis. Of note, there was no significant difference in odds of success between former smokers and nonsmokers.ConclusionsCurrent smoker status, subglottic stenosis, and stent implantation are independent factors associated with reduced long-term efficacy of interventional bronchoscopy for SCAS. Smoking cessation should be encouraged to improve the outcome of therapeutic bronchoscopy.
Is open bone graft always necessary when treating aseptic subtrochanteric nonunion with a reamed intramedullary nail?
Authors: Shin Won Chul , Jang Jae Hoon , Moon Nam Hoon , Jun Se Bin 
Published: March 2021

AbstractBackgroundThis study aimed to compare the radiological results between closed nailing without bone graft (BG) and open nailing with BG for aseptic subtrochanteric nonunion and to determine when an open procedure with BG should be considered.MethodsIn this retrospective study, we investigated patients who underwent surgical intervention for subtrochanteric nonunion between January 2008 and March 2018 in two institutions. Patients with infection, large bone defect, pathologic fracture, open fracture, previous surgery using plate, and follow-up of less than 1 year were excluded. We compared the demographic details and radiological results between patients who underwent the open procedure with BG (BG group) and the closed procedure without BG (non-BG group) as a historical control, and risk factors for the failure of revision surgery were evaluated.ResultsThirty-seven patients met the criteria and were divided into the following two groups: the BG group (n=19) who underwent open nailing with BG and the non-BG group (n=18) who underwent closed reamed nailing without BG. The mean degrees of correction of varus and flexion deformity were significantly different (p=0.001, respectively), 6.2° and 2.9° in the BG group and 4.1° and 0.6° in the non-BG group, respectively. Bony union was observed in 17 cases (89.5%) in an average of 7.4 months in the BG group and in 16 cases (88.9%) in 7.6 months in the non-BG group, with no significant differences. The factors that were significantly associated with failure of revision were atypical fracture, two or more previous surgeries, and varus and sagittal anterior angulation.ConclusionsThe radiological results of closed reamed nailing without BG for subtrochanteric nonunion were satisfactory. In the effort of percutaneous realignment, gap reduction, and intramedullary reaming, the radiological results of closed nailing without BG were not different from those of open nailing with BG; therefore, closed procedure without BG may be an acceptable option in appropriately selected patients.
Characterization of the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds by SR-FTIR
Authors: Shi Qiang , Chen Can , Li Muzhi , Chen Yang , Xu Yan , Hu Jianzhong , Liu Jun , Lu Hongbin 
Published: March 2021

Abstract
Background
Bone-tendon interface (enthesis) plays a pivotal role in relaxing load transfer between otherwise structurally and functionally distinct tissue types. Currently, decellularized extracellular matrix (DEM) from enthesis provide a natural three-dimensional scaffold with tissue-specific orientations of extracellular matrix molecules for enthesis regeneration, however, the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds from rabbit rotator cuff by SR-FTIR have not been reported.

Methods
Native enthesis tissues (NET) harvested from rabbit rotator cuff were sectioned into cuboid (about 30 mm × 1.2 mm × 10 mm) for decalcification. The decellularized book-shaped enthesis scaffolds and intrinsic ultrastructure were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds from rabbit rotator cuff were also measured innovatively by SR-FTIR.

Results
The decellularized book-shaped enthesis scaffolds from rabbit rotator cuff were successfully obtained. Histomorphology and SEM evaluated the effect of decellularization and the structure of extracellular matrix during decellularization. After mechanical testing, the failure load in the NET group showed significantly higher than that in the DEM group (P < 0.05). Meanwhile, the stiffness of the DEM group was significantly lower than the NET group. Furthermore, the distributions of collagen and PGs content in the decellularized book-shaped enthesis scaffolds were decreased obviously after decellularization by SR-FTIR quantitative analysis.

Conclusion
SR-FTIR was applied innovatively to characterize the histological morphology of native enthesis tissues from rabbit rotator cuff. Moreover, this technology can be applied for quantitative mapping of the distribution of collagen and PGs content in the decellularized book-shaped enthesis scaffolds.
Biochemical characterization of specific Alanine Decarboxylase (AlaDC) and its ancestral enzyme Serine Decarboxylase (SDC) in tea plants (Camellia sinensis)
Authors: Bai Peixian , Wang Liyuan , Wei Kang , Ruan Li , Wu Liyun , He Mengdi , Ni Dejiang , Cheng Hao 
Published: March 2021

Abstract
Background
Alanine decarboxylase (AlaDC), specifically present in tea plants, is crucial for theanine biosynthesis. Serine decarboxylase (SDC), found in many plants, is a protein most closely related to AlaDC. To investigate whether the new gene AlaDC originate from gene SDC and to determine the biochemical properties of the two proteins from Camellia sinensis, the sequences of CsAlaDC and CsSDC were analyzed and the two proteins were over-expressed, purified, and characterized.

Results
The results showed that exon-intron structures of AlaDC and SDC were quite similar and the protein sequences, encoded by the two genes, shared a high similarity of 85.1%, revealing that new gene AlaDC originated from SDC by gene duplication. CsAlaDC and CsSDC catalyzed the decarboxylation of alanine and serine, respectively. CsAlaDC and CsSDC exhibited the optimal activities at 45 °C (pH 8.0) and 40 °C (pH 7.0), respectively. CsAlaDC was stable under 30 °C (pH 7.0) and CsSDC was stable under 40 °C (pH 6.0–8.0). The activities of the two enzymes were greatly enhanced by the presence of pyridoxal-5′-phosphate. The specific activity of CsSDC (30,488 IU/mg) was 8.8-fold higher than that of CsAlaDC (3467 IU/mg).

Conclusions
Comparing to CsAlaDC, its ancestral enzyme CsSDC exhibited a higher specific activity and a better thermal and pH stability, indicating that CsSDC acquired the optimized function after a longer evolutionary period. The biochemical properties of CsAlaDC might offer reference for theanine industrial production.
Analysis of the etiologies of female infertility in Yunnan minority areas
Authors: Zhang Fen , Feng Qing , Yang Linna , Liu Xuelian , Su Lingyun , Wang Chunyan , Yao Huimei , Sun Dawei , Feng Yun 
Published: March 2021

Abstract
Background
The present study aims to provide a comparative analysis of the etiologies of female infertility between Dehong, on the Yunnan Frontier, and Kunming.

Methods
A retrospective study, which included 941 infertile females in Kunming who were treated in the First People’s Hospital of Yunnan Province and infertile females who were treated in the local hospital in Dehong from January 2016 to November 2018, was conducted. A comparative analysis of the etiologies of infertility in the two regions was then carried out.

Results
In patients with primary infertility, ovulation disorder (15.03%) was the main cause of infertility in Kunming, and pelvic inflammatory disease (25.59%) was the main cause in Dehong. With regard to secondary infertility, although pelvic inflammatory disease was the main cause of infertility in both regions, the incidence of intrauterine adhesions in Kunming was significantly higher than in Dehong.

Conclusions
The etiology of infertility showed different epidemiological characteristics depending on the region, hence individualized treatment should be given accordingly
Protective role of Clitoria ternatea L. flower extract on methylglyoxal-induced protein glycation and oxidative damage to DNA
Authors: Chayaratanasin Poramin , Adisakwattana Sirichai , Thilavech Thavaree 
Published: March 2021

Abstract
Background
Methylglyoxal (MG) is a highly reactive dicarbonyl precursor for the formation of advanced glycation end products (AGEs) associated with age-related diseases, including diabetes and its complications. Clitoria ternatea L. flower has been reported to possess antioxidant and antiglycating properties. Evidence indicates that the extract of Clitoria ternatea L. flower inhibits fructose-induced protein glycation and oxidative damage to bovine serum albumin (BSA). However, there is no evidence to support the inhibitory effect of CTE against MG-mediated protein glycation and oxidative damage to protein and DNA. Therefore, the aim of the present study was to investigate whether C. ternatea flower extract (CTE) prevents MG-induced protein glycation and oxidative DNA damage.

Methods
The formation of fluorescent AGEs in BSA was evaluated using spectrofluorometer. The protein carbonyl and thiol group content were used for detecting protein oxidation. DNA strand breakage in a glycation model comprising of MG, lysine and Cu2+ or a free radical generator 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH) systems was investigated using gel electrophoresis. Generation of superoxide anions and hydroxyl radicals in the MG/lysine system was assessed by the cytochrome c reduction assay and thiobarbituric acid reactive substances assay, respectively. High performance liquid chromatography (HPLC) was used to measure the MG-trapping ability.

Results
In the BSA/MG system, CTE (0.25–1 mg/mL) significantly inhibited the formation of fluorescent AGEs and protein oxidation by reducing protein carbonyl content as well as preventing the protein thiol depletion. The concentration of CTE at 0.125–1 mg/mL prevented oxidative DNA cleavage in MG/lysine and AAPH systems associated with the inhibition of superoxide anion and hydroxyl radical formation. It also directly trapped MG in a concentration-dependent manner, ranging from 15 to 43%.

Conclusions
The study findings suggest that the direct carbonyl trapping ability and the free radical scavenging activity of CTE are the underlying mechanisms responsible for the prevention of protein glycation and oxidative DNA damage.
Brexit and European doctors’ decisions to leave the United Kingdom: a qualitative analysis of free-text questionnaire comments
Authors: Milner Adrienne , Nielsen Rebecca , Norris Emma 
Published: March 2021

Abstract
Background
Quantitative evidence suggests that Brexit has had a severe and negative impact on European doctors, with many medical staff leaving the UK. This study provides a detailed examination of European doctors’ feelings towards Brexit, their intentions to leave the UK, and factors that may contribute to their potential decisions to migrate.

Methods
An online questionnaire which included three optional free-text questions explored self-identifying UK-based, European doctors’ views of Brexit. The three questions prompted responses on how Brexit has impacted their personal lives, their professional lives, and their future migration decisions. Fifty-nine doctors participated in the questionnaire with 52 (88.1%) providing one or more responses to the three free-text questions. Twenty-seven doctors provided answers to all three free-text questions (51.9% of included sample). Thematic analysis was used to analyse this qualitative data.

Results
Brexit was reported by the majority of participants to have a profound impact, although some respondents felt it was too soon to assess the potential consequences. Five themes emerged including: feeling unwelcome in the UK, Brexit as racism, uncertainty on legal ability to work, strain on relationships, and in contrast, a current lack of concern about Brexit.

Conclusions
To mitigate the adverse personal and professional impact of Brexit, healthcare providers should provide financial and legal support to doctors applying for settlement in the UK, ensure they are addressing issues of racial and ethnic inequality in hiring, promotion, and pay, and work towards making clinical work environments inclusive for all staff and patients.
A serological survey of brucellosis in wildlife in four major National Parks of Uganda
Authors: Aruho Robert , MacLeod Ewan T. , Manirakiza Leonard , Rwego Innocent B. 
Published: March 2021

Abstract
Background
Brucellosis is a contagious zoonotic disease of great public health and economic significance especially in developing countries. The disease affects humans and several species of livestock and wildlife. Studies on Brucellosis in wildlife in Uganda have been limited to single populations particularly in Queen Elizabeth National Park. This study aimed at estimating the percentage of positive samples of Brucella spp. in wildlife in four major national parks of Uganda. This was a retrospective survey which utilized archived samples collected from wildlife during the annual disease surveillance activities between 2013 and 2017.

Results
A total of 241 samples from seven species namely African buffalo (Syncerus caffer, n = 109), African elephant (Loxodonta africana, n = 22), giraffe (Giraffa camelopardalis rothschildi, n = 41), Uganda kob (Kobus kob thomasi, n = 36), lion (Panthera leo, n = 6), plain zebra (Equus quagga, n = 25), and bushbuck (Tragelaphus scriptus, n = 2), were tested for antibodies using the Rose Bengal Plate Test. The overall percentage of positive samples in the four national parks was 31.1% (75/241; 95% CI: 25.6–37.2). Kidepo Valley National Park had a significantly higher percentage of positive samples of 55.9% (19/34; 95% CI: 39.5–71.1) compared to other sampled national parks (p < 0.05). Lions had significantly higher percentage of positive samples at 66.7% (4/6) than African buffalo at 48.6% (53/109, p < 0.0001). There were no antibodies for Brucella spp. detected in African elephant and bushbuck.

Conclusion
This study shows variations in percentage of positive samples with Brucella spp. between species and across national parks and notably a high percentage with Brucella spp. in wildlife in Uganda than that recorded elsewhere in sub-Saharan region of Africa. Potential for transmission to other wildlife and spill over to livestock is high especially in national parks with high livestock-wildlife interaction.
Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention
Authors: Koedoot Esmee , van Steijn Eline , Vermeer Marjolein , González-Prieto Román , Vertegaal Alfred C. O. , Martens John W. M. , Le Dévédec Sylvia E. , van de Water Bob 
Published: March 2021

AbstractBackgroundTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic opportunities. Recently, splicing factors have gained attention as potential targets for cancer treatment. Here we systematically evaluated the role of RNA splicing factors in TNBC cell proliferation.MethodsIn this study, we performed an RNAi screen targeting 244 individual splicing factors to systematically evaluate their role in TNBC cell proliferation. For top candidates, mechanistic insight was gained using amongst others western blot, PCR, FACS, molecular imaging and cloning. Pulldown followed by mass spectrometry were used to determine protein-protein interactions and patient-derived RNA sequencing data was used relate splicing factor expression levels to proliferation markers.ResultsWe identified nine splicing factors, including SNRPD2, SNRPD3 and NHP2L1, of which depletion inhibited proliferation in two TNBC cell lines by deregulation of sister chromatid cohesion (SCC) via increased sororin intron 1 retention and down-regulation of SMC1, MAU2 and ESPL1. Protein-protein interaction analysis of SNRPD2, SNRPD3 and NHP2L1 identified that seven out of the nine identified splicing factors belong to the same spliceosome complex including novel component SUN2 that was also critical for efficient sororin splicing. Finally, sororin transcript levels are highly correlated to various proliferation markers in BC patients.ConclusionWe systematically determined splicing factors that control proliferation of breast cancer cells through a mechanism that involves effective sororin splicing and thereby appropriate sister chromatid cohesion. Moreover, we identified SUN2 as an important new spliceosome complex interacting protein that is critical in this process. We anticipate that deregulating sororin levels through targeting of the relevant splicing factors might be a potential strategy to treat TNBC.