bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationships between bariatric surgery and sexual function: current evidence based medicine
Authors: Liu Shengzhuo , Cao Dehong , Ren Zhengju , Li Jinze , Peng Lei , Zhang Qin , Cheng Bo , Cheng Zheyu , Ai Jianzhong , Zheng Xiaonan , Liu Liangren , Wei Qiang 
Published: October 2020

Abstract
Background
Controversy remains despite several studies have discussed the role of bariatric surgery in improving male’s sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male’s erectile function.

Methods
PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome.

Results
Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12–6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19–3.94; orgasmic function: MD = 0.50, 95%CI 0.60–0.94; overall satisfaction: MD = 1.67, 95% CI 0.78–2.56; sexual desire: MD = 1.27, 95% CI 0.61–1.93; total erectile function: MD = 7.21, 95% CI 4.33–10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39–2.67; ejaculation: MD = 1.40, 95% CI 1.28–1.51; desire: MD =1.40, 95% CI 1.32–1.49; problem assessment: MD = 2.20, 95% CI 2.06–2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60–0.76) in obese individuals after bariatric surgery.

Conclusions
This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males’s sexual function for obese individuals.
Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime
Authors: Palacios Santiago , Colli Enrico , Regidor Pedro-Antonio 
Published: October 2020

Abstract
Background
A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks.

Methods
Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated.

Results
No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed.

Conclusions
The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors.

Trial registration
EudraCT registration numbers: 2010–021787-15 & 2011–002396-42. Clincaltrials.gov: NCT02269241.
“The whole package deal”: experiences of overweight/obese women living with polycystic ovary syndrome
Authors: Ee Carolyn , Smith Caroline , Moran Lisa , MacMillan Freya , Costello Michael , Baylock Brandi , Teede Helena 
Published: October 2020

Abstract
Background
Polycystic Ovary Syndrome (PCOS) is a common female reproductive disorder with multiple manifestations. There are relatively few qualitative studies exploring the nature of living with PCOS despite its high prevalence. Qualitative research can enhance clinical practice via the provision of patient insights into the experience of living with their condition.

Methods
We conducted two focus groups and three semi-structured interviews of Australian overweight/obese women with PCOS aged 18–46 years between March and April 2017 who were recruited through social media advertising. Interviews and focus groups were audio recorded and transcribed verbatim. Thematic analysis was applied to the data, using the method of constant comparison.

Results
Ten women contributed data from two focus groups and two semi-structured interviews. Five themes emerged from the data: complexity of the condition with its multiple manifestations, difficulties with delayed diagnosis and lack of information provided after diagnosis, negative experiences on social media and online forums and the need for support, frustration over lack of a “cure”; and the impact of symptoms and concern about long-term sequelae.

Conclusions
Living with PCOS appears to generate a significant degree of anxiety about the future, dissatisfaction with current treatment models, and loss of feminine identity. Gaps in timely diagnosis, information and support provision need to be addressed. This includes supporting weight management as a fundamental concern for women with PCOS.
Prediction of incident myocardial infarction using machine learning applied to harmonized electronic health record data
Authors: Mandair Divneet , Tiwari Premanand , Simon Steven , Colborn Kathryn L. , Rosenberg Michael A. 
Published: October 2020

Abstract
Background
With cardiovascular disease increasing, substantial research has focused on the development of prediction tools. We compare deep learning and machine learning models to a baseline logistic regression using only ‘known’ risk factors in predicting incident myocardial infarction (MI) from harmonized EHR data.

Methods
Large-scale case-control study with outcome of 6-month incident MI, conducted using the top 800, from an initial 52 k procedures, diagnoses, and medications within the UCHealth system, harmonized to the Observational Medical Outcomes Partnership common data model, performed on 2.27 million patients. We compared several over- and under- sampling techniques to address the imbalance in the dataset. We compared regularized logistics regression, random forest, boosted gradient machines, and shallow and deep neural networks. A baseline model for comparison was a logistic regression using a limited set of ‘known’ risk factors for MI. Hyper-parameters were identified using 10-fold cross-validation.

Results
Twenty thousand Five hundred and ninety-one patients were diagnosed with MI compared with 2.25 million who did not. A deep neural network with random undersampling provided superior classification compared with other methods. However, the benefit of the deep neural network was only moderate, showing an F1 Score of 0.092 and AUC of 0.835, compared to a logistic regression model using only ‘known’ risk factors. Calibration for all models was poor despite adequate discrimination, due to overfitting from low frequency of the event of interest.

Conclusions
Our study suggests that DNN may not offer substantial benefit when trained on harmonized data, compared to traditional methods using established risk factors for MI.
Using machine learning methods to predict in-hospital mortality of sepsis patients in the ICU
Authors: Kong Guilan , Lin Ke , Hu Yonghua 
Published: October 2020

Abstract
Background
Early and accurate identification of sepsis patients with high risk of in-hospital death can help physicians in intensive care units (ICUs) make optimal clinical decisions. This study aimed to develop machine learning-based tools to predict the risk of hospital death of patients with sepsis in ICUs.

Methods
The source database used for model development and validation is the medical information mart for intensive care (MIMIC) III. We identified adult sepsis patients using the new sepsis definition Sepsis-3. A total of 86 predictor variables consisting of demographics, laboratory tests and comorbidities were used. We employed the least absolute shrinkage and selection operator (LASSO), random forest (RF), gradient boosting machine (GBM) and the traditional logistic regression (LR) method to develop prediction models. In addition, the prediction performance of the four developed models was evaluated and compared with that of an existent scoring tool – simplified acute physiology score (SAPS) II – using five different performance measures: the area under the receiver operating characteristic curve (AUROC), Brier score, sensitivity, specificity and calibration plot.

Results
The records of 16,688 sepsis patients in MIMIC III were used for model training and test. Amongst them, 2949 (17.7%) patients had in-hospital death. The average AUROCs of the LASSO, RF, GBM, LR and SAPS II models were 0.829, 0.829, 0.845, 0.833 and 0.77, respectively. The Brier scores of the LASSO, RF, GBM, LR and SAPS II models were 0.108, 0.109, 0.104, 0.107 and 0.146, respectively. The calibration plots showed that the GBM, LASSO and LR models had good calibration; the RF model underestimated high-risk patients; and SAPS II had the poorest calibration.

Conclusion
The machine learning-based models developed in this study had good prediction performance. Amongst them, the GBM model showed the best performance in predicting the risk of in-hospital death. It has the potential to assist physicians in the ICU to perform appropriate clinical interventions for critically ill sepsis patients and thus may help improve the prognoses of sepsis patients in the ICU.
Breast cancer pathology services in sub-Saharan Africa: a survey within population-based cancer registries
Authors: Ziegenhorn Hannes-Viktor , Frie Kirstin Grosse , Ekanem Ima-Obong , Ebughe Godwin , Kamate Bakarou , Traore Cheick , Dzamalala Charles , Ogunbiyi Olufemi , Igbinoba Festus , Liu Biying , Bauer Marcus , Thomssen Christoph , Parkin Donald Maxwell , Wickenhauser Claudia , Kantelhardt Eva Johanna 
Published: October 2020

Abstract
Background
Pathologists face major challenges in breast cancer diagnostics in sub-Saharan Africa (SSA). The major problems identified as impairing the quality of pathology reports are shortcomings of equipment, organization and insufficiently qualified personnel. In addition, in the context of breast cancer, immunohistochemistry (IHC) needs to be available for the evaluation of biomarkers. In the study presented, we aim to describe the current state of breast cancer pathology in order to highlight the unmet needs.

Methods
We obtained information on breast cancer pathology services within population-based cancer registries in SSA. A survey of 20 participating pathology centres was carried out. These centres represent large, rather well-equipped pathologies. The data obtained were related to the known population and breast cancer incidence of the registry areas.

Results
The responding pathologists served populations of between 30,000 and 1.8 million and the centres surveyed dealt with 10–386 breast cancer cases per year. Time to fixation and formalin fixation time varied from overnight to more than 72 h. Only five centres processed core needle biopsies as a daily routine. Technical problems were common, with 14 centres reporting temporary power outages and 18 centres claiming to own faulty equipment with no access to technical support. Only half of the centres carried out IHC in their own laboratory. For three centres, IHC was only accessible outside of the country and one centre could not obtain any IHC results. A tumour board was established in 13 centres.

Conclusions
We conclude that breast cancer pathology services ensuring state-of-the-art therapy are only available in a small fraction of centres in SSA. To overcome these limitations, many of the centres require larger numbers of experienced pathologists and technical staff. Furthermore, equipment maintenance, standardization of processing guidelines and establishment of an IHC service are needed to comply with international standards of breast cancer pathology.
Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study
Authors: Adank Maria C. , Benschop Laura , Kors Alet W. , Peterbroers Kelly R. , Smak Gregoor Anna M. , Mulder Monique T. , Schalekamp-Timmermans Sarah , Roeters Van Lennep Jeanine E. , Steegers Eric A. P. 
Published: October 2020

AbstractBackgroundLipids such as cholesterol and triglycerides play an important role in both maternal and foetal energy metabolism. Little is known about maternal lipid levels in pregnancy and their effect on foetal growth. The aim of this study was to assess maternal lipid levels, foetal growth and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA).MethodsWe included 5702 women from the Generation R Study, a prospective population-based cohort. Maternal lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]) were measured in early pregnancy (median 13.4 weeks, 90% range [10.5 to 17.2]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Foetal growth was measured repeatedly by ultrasound. Information on birth anthropometrics was retrieved from medical records. A birth weight below the 10th percentile was defined as SGA and above the 90th percentile as LGA.ResultsMaternal triglyceride and remnant cholesterol levels were associated with increased foetal head circumference and abdominal circumference growth rates. Triglycerides and remnant cholesterol were positively associated with the risk of LGA (odds ratio [OR] 1.11, 95% confidence interval [CI] [1.01 to 1.22] and OR 1.11, 95% CI [1.01 to 1.23], respectively). These associations were independent of maternal pre-pregnancy body mass index, but not maternal glucose levels. We observed no association between maternal lipids in early pregnancy and SGA.ConclusionsOur study suggests a novel association of early pregnancy triglyceride and remnant cholesterol levels with foetal growth, patterns of foetal growth and the risk of LGA. Future studies are warranted to explore clinical implication possibilities.
Highly multiplexed quantifications of 299 somatic mutations in colorectal cancer patients by automated MALDI-TOF mass spectrometry
Authors: Xu Chang , Peng Danli , Li Jialu , Chen Meihua , Hu Yujie , Hou Mingliang , Shang Qingjuan , Liang Qi , Li Jie , Li Wenfeng , Wu Xiaoli , Liu Changbao , Hu Wanle , Cai Mao , Zhang Huxiang , Chen Guorong , Yu Lingling , Zheng Xiaoqun , Jiang Feizhao , Luan Ju , Jin Shengnan , Ding Chunming 
Published: October 2020

Abstract
Background
Detection of somatic mutations in tumor tissues helps to understand tumor biology and guide treatment selection. Methods such as quantitative PCR can analyze a few mutations with high efficiency, while next generation sequencing (NGS) based methods can analyze hundreds to thousands of mutations. However, there is a lack of cost-effective method for quantitatively analyzing tens to a few hundred mutations of potential biological and clinical significance.

Methods
Through a comprehensive database and literature review we selected 299 mutations associated with colorectal cancer. We then designed a highly multiplexed assay panel (8-wells covering 299 mutations in 109 genes) based on an automated MADLI-TOF mass spectrometry (MS) platform. The multiplex panel was tested with a total of 319 freshly frozen tissues and 92 FFPE samples from 229 colorectal cancer patients, with 13 samples also analyzed by a targeted NGS method covering 532 genes.

Results
Multiplex somatic mutation panel based on MALDI-TOF MS detected and quantified at least one somatic mutation in 142 patients, with KRAS, TP53 and APC being the most frequently mutated genes. Extensive validation by both capillary sequencing and targeted NGS demonstrated high accuracy of the multiplex MS assay. Out of 35 mutations tested with plasmid constructs, sensitivities of 5 and 10% mutant allele frequency were achieved for 19 and 16 mutations, respectively.

Conclusions
Automated MALDI-TOF MS offers an efficient and cost-effective platform for highly multiplexed quantitation of 299 somatic mutations, which may be useful in studying the biological and clinical significance of somatic mutations with large numbers of cancer tissues.
Everolimus-eluting bioresorbable scaffolds and metallic stents in diabetic patients: a patient-level pooled analysis of the prospective ABSORB DM Benelux Study, TWENTE and DUTCH PEERS
Authors: Hommels T. M. , Hermanides R. S. , Berta B. , Fabris E. , De Luca G. , Ploumen E. H. , von Birgelen C. , Kedhi E. 
Published: October 2020

Abstract
Background
Several studies compared everolimus-eluting bioresorbable scaffolds (EE-BRS) with everolimus-eluting stents (EES), but only few assessed these devices in patients with diabetes mellitus.

Aim
To evaluate the safety and efficacy outcomes of all-comer patients with diabetes mellitus up to 2 years after treatment with EE-BRS or EES.

Methods
We performed a post hoc pooled analysis of patient-level data in diabetic patients who were treated with EE-BRS or EES in 3 prospective clinical trials: The ABSORB DM Benelux Study (NTR5447), TWENTE (NTR1256/NCT01066650) and DUTCH PEERS (NTR2413/NCT01331707). Primary endpoint of the analysis was target lesion failure (TLF): a composite of cardiac death, target vessel myocardial infarction or clinically driven target lesion revascularization. Secondary endpoints included major adverse cardiac events (MACE): a composite of all-cause death, any myocardial infarction or clinically driven target vessel revascularization, as well as definite or probable device thrombosis (ST).

Results
A total of 499 diabetic patients were assessed, of whom 150 received EE-BRS and 249 received EES. Total available follow-up was 222.6 patient years (PY) in the EE-BRS and 464.9 PY in the EES group. The adverse events rates were similar in both treatment groups for TLF (7.2 vs. 5.2 events per 100 PY, p = 0.39; adjusted hazard ratio (HR) = 1.48 (95% confidence interval (CI): 0.77–2.87), p = 0.24), MACE (9.1 vs. 8.3 per 100 PY, p = 0.83; adjusted HR = 1.23 (95% CI: 0.70–2.17), p = 0.47), and ST (0.9 vs. 0.6 per 100 PY, p > 0.99).

Conclusion
In this patient-level pooled analysis of patients with diabetes mellitus from 3 clinical trials, EE-BRS showed clinical outcomes that were quite similar to EES.
Whole-genome and enzymatic analyses of an androstenedione-producing Mycobacterium strain with residual phytosterol-degrading pathways
Authors: Wang Hongwei , Song Shikui , Peng Fei , Yang Fei , Chen Tian , Li Xin , Cheng Xiyao , He Yijun , Huang Yongqi , Su Zhengding 
Published: October 2020

AbstractMycobacterium neoaurum strains can transform phytosterols to 4-androstene-3,17-dione (4-AD), a key intermediate for the synthesis of advanced steroidal medicines. In this work, we presented the complete genome sequence of the M. neoaurum strain HGMS2, which transforms β-sitosterol to 4-AD. Through genome annotation, a phytosterol-degrading pathway in HGMS2 was predicted and further shown to form a 9,10-secosteroid intermediate by five groups of enzymes. These five groups of enzymes included three cholesterol oxidases (ChoM; group 1: ChoM1, ChoM2 and Hsd), two monooxygenases (Mon; group 2: Mon164 and Mon197), a set of enzymes for side-chain degradation (group 3), one 3-ketosteroid-1,2-dehydrogenase (KstD; group 4: KstD211) and three 3-ketosteroid-9a-hydroxylases (Ksh; group 5: KshA226, KshA395 and KshB122). A gene cluster encoding Mon164, KstD211, KshA226, KshB122 and fatty acid β-oxidoreductases constituted one integrated metabolic pathway, while genes encoding other key enzymes were sporadically distributed. All key enzymes except those from group 3 were prepared as recombinant proteins and their activities were evaluated, and the proteins exhibited distinct activities compared with enzymes identified from other bacterial species. Importantly, we found that the KstD211 and KshA395 enzymes in the HGMS2 strain retained weak activities and caused the occurrence of two major impurities, i.e., 1,4-androstene-3,17-dione (ADD) and 9-hydroxyl-4-androstene-3,17-dione (9OH-AD) during β-sitosterol fermentation. The concurrence of these two 4-AD analogs not only lowered 4-AD production yield but also hampered 4-AD purification. HGMS2 has the least number of genes encoding KstD and Ksh enzymes compared with current industrial strains. Therefore, HGMS2 could be a potent strain by which the 4-AD production yield could be enhanced by disabling the KstD211 and KshA395 enzymes. Our work also provides new insight into the engineering of the HGMS2 strain to produce ADD and 9OH-AD for industrial application.
Catabolism of l-rhamnose in A. nidulans proceeds via the non-phosphorylated pathway and is glucose repressed by a CreA-independent mechanism
Authors: MacCabe Andrew P. , Ninou Elpinickie I. , Pardo Ester , Orejas Margarita 
Published: October 2020

Abstractl-rhamnose (6-deoxy-mannose) occurs in nature mainly as a component of certain plant structural polysaccharides and bioactive metabolites but has also been found in some microorganisms and animals. The release of l-rhamnose from these substrates is catalysed by extracellular enzymes including α-l-rhamnosidases, the production of which is induced in its presence. The free sugar enters cells via specific uptake systems where it can be metabolized. Of two l-rhamnose catabolic pathways currently known in microorganisms a non-phosphorylated pathway has been identified in fungi and some bacteria but little is known of the regulatory mechanisms governing it in fungi. In this study two genes (lraA and lraB) are predicted to be involved in the catabolism of l-rhamnose, along with lraC, in the filamentous fungus Aspergillus nidulans. Transcription of all three is co-regulated with that of the genes encoding α-l-rhamnosidases, i.e. induction mediated by the l-rhamnose-responsive transcription factor RhaR and repression of induction in the presence of glucose via a CreA-independent mechanism. The participation of lraA/AN4186 (encoding l-rhamnose dehydrogenase) in l-rhamnose catabolism was revealed by the phenotypes of knock-out mutants and their complemented strains. lraA deletion negatively affects both growth on l-rhamnose and the synthesis of α-l-rhamnosidases, indicating not only the indispensability of this pathway for l-rhamnose utilization but also that a metabolite derived from this sugar is the true physiological inducer.