bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to PM2.5 is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case–control study
Authors: Tahara Masahiro , Fujino Yoshihisa , Yamasaki Kei , Oda Keishi , Kido Takashi , Sakamoto Noriho , Kawanami Toshinori , Kataoka Kensuke , Egashira Ryoko , Hashisako Mikiko , Suzuki Yuzo , Fujisawa Tomoyuki , Mukae Hiroshi , Suda Takafumi , Yatera Kazuhiro 
Published: March 2021

Abstract
Background
Short-term exposure to ozone and nitrogen dioxide is a risk factor for acute exacerbation (AE) of idiopathic pulmonary fibrosis (AE-IPF). The comprehensive roles of exposure to fine particulate matter in AE-IPF remain unclear. We aim to investigate the association of short-term exposure to fine particulate matter with the incidence of AE-IPF and to determine the exposure-risk time window during 3 months before the diagnosis of AE-IPF.

Methods
IPF patients were retrospectively identified from the nationwide registry in Japan. We conducted a case–control study to assess the correlation between AE-IPF incidence and short-term exposure to eight air pollutants, including particulate matter < 2.5 µm (PM2.5). In the time-series data, we compared monthly mean exposure concentrations between months with AE (case months) and those without AE (control months). We used multilevel mixed-effects logistic regression models to consider individual and institutional-level variables, and also adjusted these models for several covariates, including temperature and humidity. An additional analysis with different monthly lag periods was conducted to determine the risk-exposure time window for 3 months before the diagnosis of AE-IPF.

Results
Overall, 152 patients with surgically diagnosed IPF were analyzed. AE-IPF was significantly associated with an increased mean exposure level of nitric oxide (NO) and PM2.5 30 days prior to AE diagnosis. Adjusted odds ratio (OR) with a 10 unit increase in NO was 1.46 [95% confidence interval (CI) 1.11–1.93], and PM2.5 was 2.56 (95% CI 1.27–5.15). Additional analysis revealed that AE-IPF was associated with exposure to NO during the lag periods lag 1, lag 2, lag 1–2, and lag 1–3, and PM2.5 during the lag periods lag 1 and lag 1–2.

Conclusions
Our results show that PM2.5 is a risk factor for AE-IPF, and the risk-exposure time window related to AE-IPF may lie within 1–2 months before the AE diagnosis. Further investigation is needed on the novel findings regarding the exposure to NO and AE-IPF.
Efficient bioconversion of raspberry ketone in Escherichia coli using fatty acids feedstocks
Authors: Chang Chen , Liu Bo , Bao Yihong , Tao Yong , Liu Weifeng 
Published: March 2021

Abstract
Background
Phenylpropanoid including raspberry ketone, is a kind of important natural plant product and widely used in pharmaceuticals, chemicals, cosmetics, and healthcare products. Bioproduction of phenylpropanoid in Escherichia coli and other microbial cell factories is an attractive approach considering the low phenylpropanoid contents in plants. However, it is usually difficult to produce high titer phenylpropanoid production when fermentation using glucose as carbon source. Developing novel bioprocess using alternative sources might provide a solution to this problem. In this study, typical phenylpropanoid raspberry ketone was used as the target product to develop a biosynthesis pathway for phenylpropanoid production from fatty acids, a promising alternative low-cost feedstock.

Results
A raspberry ketone biosynthesis module was developed and optimized by introducing 4-coumarate-CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone reductase (RZS) in Escherichia coli strains CR1–CR4. Then strain CR5 was developed by introducing raspberry ketone biosynthesis module into a fatty acids-utilization chassis FA09 to achieve production of raspberry ketone from fatty acids feedstock. However, the production of raspberry ketone was still limited by the low biomass and unable to substantiate whole-cell bioconversion process. Thus, a process by coordinately using fatty-acids and glycerol was developed. In addition, we systematically screened and optimized fatty acids-response promoters. The optimized promoter Pfrd3 was then successfully used for the efficient expression of key enzymes of raspberry ketone biosynthesis module during bioconversion from fatty acids. The final engineered strain CR8 could efficiently produce raspberry ketone repeatedly using bioconversion from fatty acids feedstock strategy, and was able to produce raspberry ketone to a concentration of 180.94 mg/L from soybean oil in a 1-L fermentation process.

Conclusion
Metabolically engineered Escherichia coli strains were successfully developed for raspberry ketone production from fatty acids using several strategies, including optimization of bioconversion process and fine-tuning key enzyme expression. This study provides an essential reference to establish the low-cost biological manufacture of phenylpropanoids compounds.
Oncological safety of immediate breast reconstruction with skin- or nipple-sparing mastectomy: the value of tumor-to-dermis distance measured by preoperative ultrasonography
Authors: Fujii Takaaki , Nakazawa Yuko , Ogino Misato , Obayashi Sayaka , Yajima Reina , Honda Chikako , Nakamura Hideharu , Makiguchi Takaya , Shirabe Ken 
Published: March 2021

Abstract
Background
Immediate breast reconstruction with skin-sparing (SSM) or nipple-sparing mastectomy (NSM) has become a common procedure. In this study, we evaluated the distance between breast tumor and skin in a series of patients undergoing IBR as it relates to oncologic safety, namely, the incidence of recurrence.

Methods
The distance of the tumor to the dermis, rather than the outer layer of skin, was the key parameter of our preoperative ultrasound measurements. Our data set comprised the cases of 171 patients and 181 breasts with breast cancer that had undergone two-stage breast reconstruction by expander. The median age of the patients was 47 years (25–75 years). The overall median follow-up period was 47.1 months (8.8–125.3 months). Eighty-five breasts underwent IBR with SSM/NSM; the others underwent conventional mastectomy.

Results
Among the total of 181 reconstructed breast mounds, the locoregional recurrence rate was 1.1% (2 breasts) with no cases of skin flap recurrence or skin flap necrosis. The tumor-to-dermis distance of cases with skin preservation (NSM/SSM) was significantly less than that of cases with conventional mastectomy (3.8 ± 2.7 mm vs 5.2 ± 2.4 mm). In cases with invasive carcinoma, all cases whose tumor-to-dermis distance was less than 2 mm underwent resection of the skin immediately overlying the tumor.

Conclusions
Our results suggested that a 2-mm distance between the dermis and tumor on ultrasound evaluation is sufficient for the use of this tissue as a skin flap in SSM/NSM procedures. Our study indicated that immediate breast reconstruction with SSM/NSM can be an oncologically safe surgical option for breast cancer. However, we recommend that resection of the skin overlying the tumor be performed in cases with invasive breast cancer in which the tumor-to-dermis distance is less than 2 mm.

Trial registration
Patients in this study were retrospectively registered. This study design was approved by our Clinical Ethics Committee (No 1297) (http://ciru.dept.showa.gunma-u.ac.jp/guidance/storage-sample/list.html).
ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study
Authors: Matsumoto Hironori , Takeba Jun , Umakoshi Kensuke , Kikuchi Satoshi , Ohshita Muneaki , Annen Suguru , Moriyama Naoki , Nakabayashi Yuki , Sato Norio , Aibiki Mayuki 
Published: March 2021

Abstract
Background
We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients.

Methods
In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%).

Results
Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121–49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327–61.025, p = 0.028).

Conclusions
ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.
Growth and puberty in children with juvenile idiopathic arthritis
Authors: d’Angelo Debora Mariarita , Di Donato Giulia , Breda Luciana , Chiarelli Francesco 
Published: March 2021

AbstractJuvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2–20 cases per 100,000 and a prevalence of 16–150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10–20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient’s bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
Simultaneous quantification of bioactive components in Chinese herbal spirits by ultra-high performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC–QQQ–MS/MS)
Authors: Hu Yan , Wang Zhe , Xia Fangbo , Yang Wen , Liu Yuan-Cai , Wan Jian-Bo 
Published: March 2021

Abstract
Background
The Chinese medicinal wine made from herbal medicines became prevalent among Chinese people. The Chinese herbal spirit is composed of several herbal extracts, and has the certain health functions, such as anti-fatigue and immune regulation. The quality evaluation of Chinese herbal spirit is greatly challenged by the enormous and complex components with great structural diversity and wide range of concentration distribution.

Methods
An ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) with multiple reaction monitoring (MRM) method was developed to simultaneously determine forty-three bioactive components in the Chinese herbal spirits produced by year 2014 and 2018.

Results
Quantitative results showed that 11 components, i.e.., puerarin (5), purpureaside C (7), daidzin (8), echinacoside (9), acteoside (15), epimedin B (22), epimedin C (23), icariin (24), eugenol (27), chikusetsusaponin iva (30) and Z-ligustilide (40), significantly decreased along with the increasing years of storage, while 5 compounds, i.e.., geniposidic acid (1), protocatechuic acid (2), crustecdysone (14), daidzein (18) and icariside I (35), were basically stable in all samples across the years.

Concusion
The established method allowing to simultaneously determined 43 components with wide structural diversity and trace amounts will facilitate the quality control research of Chinese herbal spirits.
First French study relative to preconception genetic testing: 1500 general population participants’ opinion
Authors: Bonneau Valérie , Nizon Mathilde , Latypova Xenia , Gaultier Aurélie , Hoarau Eugénie , Bézieau Stéphane , Minguet Guy , Turrini Mauro , Jourdain Maud , Isidor Bertrand 
Published: March 2021

Abstract
Background
Until very recently, preconception genetic testing was only conducted in particular communities, ethnic groups or families for which an increased risk of genetic disease was identified. To detect in general population a risk for a couple to have a child affected by a rare, recessive or X-linked, genetic disease, carrier screening is proposed in several countries. We aimed to determine the current public opinion relative to this approach in France, using either a printed or web-based questionnaire.

Results
Among the 1568 participants, 91% are favorable to preconception genetic tests and 57% declare to be willing to have the screening if the latter is available. A medical prescription by a family doctor or a gynecologist would be the best way to propose the test for 73%, with a reimbursement from the social security insurance. However, 19% declare not to be willing to use the test because of their ethic or moral convictions, and the fear that the outcome would question the pregnancy. Otherwise, most participants consider that the test is a medical progress despite the risk of an increased medicalization of the pregnancy.

Conclusion
This first study in France highlights a global favorable opinion for the preconception genetic carrier testing under a medical prescription and a reimbursement by social security insurance. Our results emphasize as well the complex concerns underpinned by the use of this screening strategy. Therefore, the ethical issues related to these tests include the risk of eugenic drift mentioned by more than half of the participants.
Haematological findings in 158 cows with acute toxic mastitis with a focus on the leukogram
Authors: Braun Ueli , Gerspach Christian , Riond Barbara , Oschlies Carina , Corti Sabrina , Bleul Ulrich 
Published: March 2021

AbstractBackgroundIn cows with acute toxic mastitis (ATM), the leukogram aids in the assessment of the severity of disease. The goal of our study was to compare the leukogram of 158 cows with ATM (cases) and 168 clinically healthy cows (controls). We hypothesised that the leukograms of surviving and non-surviving cows differ and that there are variables of the leukogram with sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM. The cows were examined clinically and underwent haematological and biochemical examination of blood and bacteriological culture of milk samples.ResultsAll cows with ATM had a poor appetite or anorexia, and 34 cows (21.5%) were recumbent. A single quarter was affected in 119 cows (75.3%), two quarters in 37 cows (23.4%) and three quarters in two cows (1.3%). Bacteriological culture showed Gram-negative pathogens in 100 cows (63.3%), Gram-positive in 15 (9.5%) and yeast in 4 (2.5%). The median total leukocyte count of cases was 4300 cells/µL (interquartile range = 2300–8200/µL), which was significantly lower than 8000 cells/µL (6525–9300/µL) in controls. Except for band neutrophils and metamyelocytes, the counts of all components of the leukogram were lower in cases compared with controls. Significantly more cows with ATM had leukopenia (60.1 vs. 4.1%) or leukocytosis (10.1 vs. 3.0%) than controls. Diseased cows had significantly lower segmented neutrophil counts than controls (860 vs. 2598 cells/µL), and 69.5 and 17.3%, respectively, had counts below the reference interval. Cases had increased band (77.3%) and metamyelocyte (25.0%) counts compared with controls (0.6 and 0%, respectively). In diseased cows, eosinopenia occurred in 66.4% (controls, 1.8%), monocytopenia in 40.6% (4.2%) and lymphopenia in 60.2% (1.8%). Twenty-one diseased cows (16.4%) had a regenerative and 57 (44.5%) had a degenerative left shift. The median neutrophil-to-lymphocyte ratio was 0.97 in diseased cows and 0.63 in controls. Toxic changes in neutrophils including cytoplasmic basophilia and vacuolisation were seen in 101 (91.8%) of 110 blood smears of diseased cows. The leukogram of the surviving and non-surviving cows did not differ significantly, and the hypothesis was rejected.ConclusionsATM results in severe changes in the leukogram particularly leukopenia, lymphopenia, and degenerative left shift. The hypothesis that the leukograms of surviving and non-surviving cows differ was rejected. The leukogram has not sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM.
Study factors associated with the incompletion of clinical trials that include pediatric patients: a retrospective analysis of the European Clinical Trials Database and a lesson from the European region
Authors: Tanemura Nanae , Sasaki Tsuyoshi , Sato Junko , Urushihara Hisashi 
Published: March 2021

AbstractBackgroundIncomplete clinical trials for pediatric drug development result in a lack of adequate scientific evidence for providing appropriate medication to pediatric populations; this is especially true for Japan. Thus, using the European Clinical Trials Database (EudraCT), this study aimed to identify the factors related to the study design and administration that lead to incompletion of clinical trials that included pediatric patients.MethodsWe focused on clinical trials that included patients under the age of 18 registered in the database, named as the European Clinical Trials Database between January 1, 2014, and December 31, 2018. Two groups of trials were identified: “all cases completed” and “not all cases completed,” reflecting whether they were completed in all participating countries/regions or not. To identify the factors of the occurrence of “not all cases completed,” a logistic regression analysis was performed to calculate the odds ratios and 95% confidence intervals. In total, 142 clinical trials (95 “all cases completed” and 47 “not all cases completed”) were analyzed.ResultsThe logistic regression analysis showed the number of countries in which a clinical trial was conducted to be the only significant factor (odds ratio: 1.3; 95% confidence interval: 1.1-1.5); this was identified as the primary factor for the occurrence of “not all cases completed” in the clinical trials that included pediatric patients.ConclusionOur findings suggest that the feasibility of clinical trials that include pediatric patients, such as whether the countries in which the trial is to be conducted are suitable, must be considered prior to the trial.
Clinical research and burnout syndrome in Italy – only a physicians’ affair?
Authors: Cagnazzo Celeste , Filippi Roberto , Zucchetti Giulia , Cenna Rosita , Taverniti Cristiana , Guarrera Agata Sue Ellen , Stabile Stefano , Federici Irene , Monti Manuela , Pirondi Sara , Testoni Sara , Fagioli Franca 
Published: March 2021

AbstractBackgroundThe burnout phenomenon has been extensively investigated among health care professionals, particularly focusing on physicians and nurses. However, literature concerning burnout in clinical research is poor and often neglects the other professional categories involved.MethodsIn March 2019, all members of Italian Group of Clinical Research Coordinator were invited to participate to a web survey, consisting of three sections: general information and workload; Maslach Burnout Inventory (MBI) test; subjective perception of oneself’s work stress and possible causes.ResultsThe majority of respondents felt a form of distress. The main source was contract type (31.2%), followed by workload (20.5%) and lack of skills recognition (17.8%).Results from MBI test confirmed the interviewees’ subjective perception: an intermediate level of emotional exhaustion (19.1 points) and a very high sense of reduced professional achievement (26.8 points) were observed. Both depersonalization and sense of reduced professional achievement showed weak to moderate correlations with emotional exhaustion. Emotional exhaustion was associated with contract type with high significance.ConclusionIt is necessary to act on those qualitative factors that are greatly increasing the level of perceived stress, jeopardizing the quality of clinical research coordinators work and significantly amplifying the phenomenon of migration towards the private sector.