bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant serum gel formulation with a combination of secretome from mesenchymal stem cells and rosemary oil
Authors: Marlina  , Salman  , Filza H , Nur E , Poppy A N
Published: August 2023

Rosemary Oil (Rosmarinus officinalis) contains carnosic acid, carnosol, and rosmarinic acid, which are sources of active antioxidants. The Secretome of MSC has growth factors such as antioxidants that protect HDFs. This study aimed to obtain a gel formulation from secretome combinates with Rosemary Oil and test its effect as an antioxidant. The gel formulation contains Rosemary Oil as an antioxidant, propylene glycol as humectants, Carbomer 940 as a gelling agent, triethanolamine as an alkalizing agent, DMDM Hydantoin as preservative, and aquadest. The evaluation tests of gel preparations include organoleptic tests, homogeneity, viscosity, pH, dispersion, syneresis, and stability. Antioxidant activity test using DPPH method (1.1-Diphenyl-2 Picrylhydrazil). The results show the gel was in the form of a thick gel, cloudy white and yellowish, having a characteristic smell like rosemary plants. It also has ease of use, is homogeneous, has a cooling sensation, and has good solubility during washing. The gel has an average pH value of 6.39; viscosity <30,000 cp; the average dispersion value is 5.71 cm. Rosemary Oil gel preparations provide antioxidant activity, indicated by the IC50 value. Gel preparations with 5% secretome with 2.5% rosemary oil had an antioxidant activity with an IC50 value of 11.4501 μg/ml. Based on these results, it can be concluded that the Secretome with rosemary oil gel formulations were proven to have an antioxidant effect and showed an increase in antioxidant activity in the formula added with Secretome (P <0.05)
Effectiveness of Well Water Treatment Method with Electrocoagulation, Coagulation, and Electrocoagulation-Coagulation Using Alum as Coagulant
Authors: Nugraheni Putranty Widha , Maleiva Lalak Tarbiyatun Nasyin , Ramadhan Finar , Kusumawardhani Eka , Putra Leonardus Sandy Ade
Published: August 2023

All This study compares the effectiveness of well-water treatment with coagulation, electrocoagulation, and electrocoagulation-coagulation methods in Kubu Raya, West Kalimantan, following the quality standards of the Minister of Health Regulation No. 32 of 2017. This study used an alum and was varied by testing the parameters of turbidity, color, TDS, Fe, Mn, and pH. The study results on the mass variation of alum showed an increase in pH, and increases in TDS, color, turbidity, Fe, and Mn. With the electrocoagulation method, the efficiency results of increased pH were 3.88%, 22.22%, 32.77%, and 42.59%; decrease in TDS 46.34%, 54.07%, 86.79%, and 114.75%; color reduction 95.39%; 28.85%; 88.79%; and 80.02%; decreased in turbidity 99.45%; 99.80%; 99.32%; and 99.10%; decreased Fe concentration 96.60%; 98.99; 96.20%; and 96.99%; and decreased concentration of Mn 99.59%; 99.75%; 99.72%; and 99.75%. Processing with the electrocoagulation method with the addition of 0.5 g alum resulted in a decrease in pH of -29.62%; -26.29%; 13.33; and 15.37%; decrease in TDS of 24.92%; 24.23%; 21.356%; and 16.59%; decreased in watercolor 86.09%; 74.27%; 91.24; and 70.02%; decreased in turbidity value 99.44%; 99.31%; 99.54%; and 98.96%; decreased Fe concentration 97.98%; 96.48%; 97.11; and 98.22%, and a decrease in Mn concentration of 99.75%; 99.55%; 99.75%; and 99.75%.
Continuous motion of an electrically actuated water droplet over a PDMS-coated surface
Authors: Upadhyay Supriya , Muralidhar K
Published: August 2023

Electrically actuated linear motion of a water droplet over PDMS-coated single active electrode is analyzed from detailed experiments and modeling. In an experiment, continuous motion of the droplet is achieved when it is located over an active electrode with a horizontal ground wire placed just above in an open-electrowetting-on-dielectric configuration. Using a CCD camera, the instantaneous centroid position of the droplet is determined and its velocity is inferred by numerical differentiation. The edge-detected image is also used to determine the advancing and receding contact angles of the moving drop relative to the substrate. Motion of 2, 6, and 10 µl water droplets for voltages in the range of 170–270 V
DC is examined to investigate the effect of drop volume and voltage on drop deformation and velocity. The motion of the droplet is initiated by Young-Lippmann spreading at the three-phase contact line, followed by a nonuniform electric force field distributed between the active electrode and the ground wire localized at the droplet-air interface. Simulations carried out using COMSOL© Multiphysics with full coupling between the electric field and hydrodynamics are in conformity with experiments. A contact angle model with pinning and friction leads to close agreement between simulations and drop motion over a bare PDMS layer, particularly in terms of the relevant timescales. When contact line friction is neglected, the fully coupled numerical solution shows a good match with experimentally determined drop movement over a silicone oil-coated PDMS layer. Over both surfaces, continuous motion of the water droplet is seen to be achieved in three stages, namely, initial spreading, acceleration, and attainment of constant speed.
Research on the seagull optimization algorithm-based convolutional neural network rolling bearing fault diagnosis method
Authors: Xue Jijun , Liu Xiaodong , Xu Hao , Zhang Di
Published: August 2023

It is crucial to understand the rolling bearing fault diagnosis procedure since rolling bearings are frequently used in rotating machinery and if a failure occurs, it will interfere with the proper operation of the entire piece of machinery or piece of equipment. Deep learning is increasingly being used in mechanical fault diagnosis, with convolutional neural networks(CNN) being the most common type. In recent years, the rapid growth of artificial intelligence has caused fault diagnosis methods to evolve as well. A CNN fault diagnostic approach based on seagull optimization algorithm (SOA) is suggested and applied to the fault diagnosis of rolling bearings in order to address the issues with convolutional neural networks, such as high data requirements, unstable gradients, and optimization challenges. The seagull optimization approach is used to design a deep learning model by selecting the structural hyperparameters in the CNN model as efficiently as possible. The accelerated life experimental dataset for rolling bearings is trained using the optimized CNN model. The training outcomes of the CNN model on the dataset before and after optimization are compared, and the findings demonstrate that the suggested method has a superior optimization effect. As can be seen, the seagull optimization algorithm and CNN can be organically combined and applied to the fault diagnosis method for rolling bearings.
Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients
Authors: Lobo Anandi , Mishra Sourav K , Jha Shilpy , Tiwari Ankit , Kapoor Rahul , Sharma Shivani , Kaushal Seema , Kiranmai N Sri , Das M Rakshitha , Peddinti Kamal P , Sharma Shailendra K , Bhardwaj Nitin , Arora Samriti , Jain Deepika , Jain Ekta , Munjal Gauri , Shinde Sayali , Malik Vipra , Singh Hena , Varshney Juhi , Pradhan Dinesh , Dixit Mallika , Pattnaik Niharika , Sharma Ashish K , Barapatre Yogesh R , Pradhan Manas , Satapathy Kaliprasad , Rath Debadarshi , Jaiswal Sunil , Das Stithi , Khadenga Chiraranjan , Routa Sudhasmita , Baisakh Manas R , Tiwari Romila , Sampat Nakul Y , Chakrabarti Indranil , Parwani Anil V , Mohanty Sambit K
Published: August 2023

Objectives

Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC.

Methods

A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters.

Results

Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)–associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1–positive tumors had a 3.61-times higher chance of being node positive than PD-L1–negative tumors (P = .0009). In addition, PD-L1 high–positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low–positive tumors (P = .004). The PD-L1–positive tumors had a lower overall survival and cancer-specific survival than PD-L1–negative tumors.

Conclusions

Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1–based immunotherapeutics in PC.
Arterial Health After Preeclampsia: Role of Chronic Hypertension in the Early Vascular Aging (EVA) Study
Authors: Paquin Amelie , Werlang Ana , Coutinho Thais
Published: August 2023

BACKGROUND

Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE.

METHODS

We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity.

RESULTS

Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1–7), and time since last pregnancy 2.1 (range 0.5–5.7) years (not different between groups, P > 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P < 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P < 0.05 for each), with smaller effect sizes.

CONCLUSIONS

This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.
Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes
Authors: Ozdag Acarli Ayse Nur , Tuzun Erdem , Sanli Elif , Koral Gizem , Akbayir Ece , Cakar Arman , Sirin Nermin Gorkem , Soysal Aysun , Aysal Fikret , Durmus Hacer , Parman Yesim , Yilmaz Vuslat
Published: August 2023

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot–Marie–Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = –0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.
Design of Experiment-Based Green UPLC-DAD Method for the Simultaneous Determination of Indacaterol, Glycopyrronium and Mometasone in their Combined Dosage Form and Spiked Human Plasma
Authors: Tarek Mohamed , Ghoniem Nermine S , Hegazy Maha A , Wagdy Hebatallah A
Published: August 2023

Indacaterol, is an ultra-long-acting β2 agonist, glycopyrronium is a long-acting muscarinic-antagonist and mometasone is a synthetic corticosteroid. They were used recently in combination for the treatment of severe asthma symptoms and chronic obstructive pulmonary disease. In this work, it was the first time to develop a green and environment friendly ultra-performance liquid chromatographic method using design expert program for the analysis of the three drugs in their combined dosage form. Also, the method was bioanalytically validated for the analysis of the three drugs in spiked human plasma samples. The method was linear in range from 0.50 to 100.0 μg mL−1 for indacaterol and mometasone and from 1.0 to 150.0 μg mL−1 for glycopyrronium. It showed high accuracy where, the % recovery for indacaterol, glycopyrronium and mometasone in plasma were ranged from 94.27 to 97.86%, 96.43 to 98.75% and 96.86 to 98.43%, respectively. Also, it was precise where, the % relative standard deviation for the inter-day precision was ranged from 2.571 to 3.484%, 3.180 to 4.123% and 3.150 to 3.984% and the intra-day precision was ranged from 2.351 to 3.125%, 2.512 to 3.544% and 2.961 to 3.983% for indacaterol, glycopyrronium and mometasone, respectively. The limit of detection and the limit of quantification for indacaterol and mometasone were 0.03 and 0.10 μg mL−1 while for glycopyrronium, they were 0.16 and 0.50 μg mL−1.

Highlights
Simultaneous Estimation of Berberine and Piperine in a Novel Nanoformulation for Epilepsy Control via HPLC
Authors: El-Nahas Amira E , Elbedaiwy Heba M , Helmy Maged W , El-Kamel Amal H
Published: August 2023

Berberine (Brb) and piperine (Pip) are salient examples of bioactive nutraceuticals possessing a promising role in controlling epilepsy. However, during the development of novel nanoformulation that augments their effects, an adequate determination of each one separately was a challenge since they have nearly the same detection wavelength and diverse solubility profiles. Consequently, a tailored high-performance liquid chromatography technique was developed for their simultaneous detection in routine analyses. The chromatographic separation was achieved using a C18 column. The linear gradient flow of acetonitrile: 0.1%v/v aqueous phosphoric acid was altered from 55:45 to 80:20 v/v over 3 min at a 1.2 mL/min flow rate until the end of the run. Brb and Pip were eluted at 1.6 and 3.4 min, respectively. The linearity of the standard curves was found to be ≥0.999, and the mean % recovery for Brb and Pip lay within the accepted limit. Moreover, the percentage coefficient of variation was <2% for intra- and inter-day precision. Consequently, the developed assay was successfully applied for the quantification of both drugs rapidly with high resolution and minimum interference from each other during the different steps conducted during the nanoformulation development.
Prognostic value of myocardial performance index in individuals with type 1 and type 2 diabetes: Thousand&1 and Thousand&2 studies
Authors: Bahrami Hashmat Sayed Zohori , Jørgensen Peter Godsk , Hove Jens Dahlgaard , Dixen Ulrik , Biering-Sørensen Tor , Rossing Peter , Jensen Magnus T
Published: August 2023

Aims

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations.

Methods and results

We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8–6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0–1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1–1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D.

Conclusion

MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction.
ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures
Authors: Schneider Grégoire , Ruggiero Carmen , Renault Lucie , Doghman-Bouguerra Mabrouka , Durand Nelly , Hingrai Guillaume , Dijoud Frédérique , Plotton Ingrid , Lalli Enzo
Published: August 2023

Objective

The essential role of ACTH on the growth and function of the human foetal adrenal (HFA) has long been recognized. In addition, many studies have suggested a role of the pituitary hormone prolactin (PRL) in the regulation of the HFA, but the effects of this hormone on steroidogenesis and gene expression are still unknown. Our objective was to investigate the effect of ACTH and PRL on the steroidogenic capacities of the HFA.

Design

In vitro/ex vivo experimental study.

Methods

We used a hanging drop in vitro organ culture system. First trimester HFA samples were cultured for 14 days in basal conditions or treated with ACTH, PRL, or a combination of the 2 (3 to 11 replicates depending on the experiment). Steroids were measured by liquid chromatography/tandem mass spectrometry or immunoassay, gene expression by RT-qPCR, and protein expression by immunoblot.

Results

ACTH significantly increased corticosterone, cortisol, and cortisone production, both by itself and when used together with PRL. PRL stimulation by itself had no effect. Combined stimulation with ACTH + PRL synergistically and selectively increased adrenal androgen (DHEAS and Δ4-androstenedione) production and CYP17A1 expression in the HFA, while treatment with each single hormone had no significant effect on those steroids.

Conclusions

These results have important implications for our understanding of the hormonal cues regulating adrenal steroidogenesis in the HFA during the first trimester in physiological and pathological conditions and warrant further studies to characterize the molecular mechanisms of converging ACTH and PRL signalling to regulate CYP17A1 expression.
Emery–Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure
Authors: Cannie Douglas E , Syrris Petros , Protonotarios Alexandros , Bakalakos Athanasios , Pruny Jean-François , Ditaranto Raffaello , Martinez-Veira Cristina , Larrañaga-Moreira Jose M , Medo Kristen , Bermúdez-Jiménez Francisco José , Ben Yaou Rabah , Leturcq France , Mezcua Ainhoa Robles , Marini-Bettolo Chiara , Cabrera Eva , Reuter Chloe , Limeres Freire Javier , Rodríguez-Palomares José F , Mestroni Luisa , Taylor Matthew R G , Parikh Victoria N , Ashley Euan A , Barriales-Villa Roberto , Jiménez-Jáimez Juan , Garcia-Pavia Pablo , Charron Philippe , Biagini Elena , García Pinilla José M , Bourke John , Savvatis Konstantinos , Wahbi Karim , Elliott Perry M
Published: August 2023

Background and Aims

Emery–Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants.

Methods

Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC).

Results

Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3–109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2–60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09).

Conclusions

Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.
Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial
Authors: Kronborg Mads Brix , Frausing Maria Hee Jung Park , Malczynski Jerzy , Riahi Sam , Haarbo Jens , Holm Katja Fiedler , Larroudé Charlotte Ellen , Albertsen Andi Eie , Svendstrup Lene , Hintze Ulrik , Pedersen Ole Dyg , Davidsen Ulla , Fischer Thomas , Johansen Jens Brock , Kristensen Jens , Gerdes Christian , Nielsen Jens Cosedis ,   DANPACE II Investigators, Nielsen Jens Cosedis , Kronborg Mads Brix , Hee Maria , Malczynski Jerzy , Riahi Sam , Holm Katja Fiedler , Haarbo Jens , Larroudé Charlotte Ellen , Albertsen Andi Eie , Svendstrup Lene , Hinze Ulrik , Pedersen Ole Dyg , Davidsen Ulla , Fischer Thomas , Johansen Jens Brock , Kristensen Jens , Gerdes Christian
Published: August 2023

Background and Aims

High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation.

Methods

In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope.

Results

The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76–1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13–2.59, P = .01).

Conclusions

Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.
Prevalence and incidence of diastolic dysfunction in atrial fibrillation: clinical implications
Authors: Naser Jwan A , Lee Eunjung , Scott Christopher G , Kennedy Austin M , Pellikka Patricia A , Lin Grace , Pislaru Sorin V , Borlaug Barry A
Published: August 2023

Background and Aims

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR).

Methods

Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (>MDD) by ≥2/4. Annualized changes in DD indices were determined.

Results

New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6–5.8) years, DD progressed two–four-fold more rapidly in those with new-onset AF (P < .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19–3.32) for SDD and 1.73 (1.49–2.02) for ≥MDD].

Conclusions

Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.
The Rise and Fall of the ‘World Economy’ in Weimar Germany
Authors: Müller Philipp
Published: August 2023

Recent studies have emphasized the role of international institutions in the emergence of a transnational culture of economic experts in the interwar period. According to this view, collaboration over the difficulties of international trade in goods and finance was driven by a common language of problem diagnosis and solution finding. This interpretation has pushed the relevance of the domestic context for ‘agents of the international’ into the background. The World Economic Conference in Geneva organized by the League of Nations in 1927 shows that Weimar business representatives saw their participation as an opportunity to improve their position in their national federations and vis-à-vis the Reich government. Therefore, on the one hand, they sought to be appointed by state authorities to participate in the Geneva discussions. On the other hand, they stressed the relevance of the World Economy as well as their competence in solving world economic problems. As a consequence, immediately before and after the meeting in Geneva, the World Economy was a prominent topic among Weimar’s business representatives. However, this strategy counted on the implementation of the conference’s economic policy proposals by national governments. As it became apparent that the Geneva recommendations would not have lasting impact, interest in the World Economy waned and its spokesmen turned to other forms of international cooperation, in particular regional customs alliances and cartel agreements. The rise and fall of the topic of the World Economy among German business representatives cannot be understood independently of its interaction with the domestic context of Weimar Germany.
Self-supervised machine learning using adult inpatient data produces effective models for pediatric clinical prediction tasks
Authors: Lemmon Joshua , Guo Lin Lawrence , Steinberg Ethan , Morse Keith E , Fleming Scott Lanyon , Aftandilian Catherine , Pfohl Stephen R , Posada Jose D , Shah Nigam , Fries Jason , Sung Lillian
Published: August 2023

Objective

Development of electronic health records (EHR)-based machine learning models for pediatric inpatients is challenged by limited training data. Self-supervised learning using adult data may be a promising approach to creating robust pediatric prediction models. The primary objective was to determine whether a self-supervised model trained in adult inpatients was noninferior to logistic regression models trained in pediatric inpatients, for pediatric inpatient clinical prediction tasks.

Materials and Methods

This retrospective cohort study used EHR data and included patients with at least one admission to an inpatient unit. One admission per patient was randomly selected. Adult inpatients were 18 years or older while pediatric inpatients were more than 28 days and less than 18 years. Admissions were temporally split into training (January 1, 2008 to December 31, 2019), validation (January 1, 2020 to December 31, 2020), and test (January 1, 2021 to August 1, 2022) sets. Primary comparison was a self-supervised model trained in adult inpatients versus count-based logistic regression models trained in pediatric inpatients. Primary outcome was mean area-under-the-receiver-operating-characteristic-curve (AUROC) for 11 distinct clinical outcomes. Models were evaluated in pediatric inpatients.

Results

When evaluated in pediatric inpatients, mean AUROC of self-supervised model trained in adult inpatients (0.902) was noninferior to count-based logistic regression models trained in pediatric inpatients (0.868) (mean difference = 0.034, 95% CI=0.014-0.057; P < .001 for noninferiority and P = .006 for superiority).

Conclusions

Self-supervised learning in adult inpatients was noninferior to logistic regression models trained in pediatric inpatients. This finding suggests transferability of self-supervised models trained in adult patients to pediatric patients, without requiring costly model retraining.
The FoxO1-ATGL axis alters milk lipolysis homeostasis through PI3K/AKT signaling pathway in dairy goat mammary epithelial cells
Authors: He Qiuya , Gao Liangjiahui , Zhang Fuhong , Yao Weiwei , Wu Jiao , Song Ning , Luo Jun , Zhang Yong
Published: August 2023

Goat milk is enriched in fatty acids which are beneficial to human health. Previous research has revealed that 98% of milk fat is composed of triglycerides. However, the mechanisms regulating milk fat composition remain unclear. Forkhead box protein O1 (FoxO1) is a crucial regulatory factor involved in lipid metabolism across various cell types. Chromatin immunoprecipitation sequencing (ChIP)—seq data) and RNA sequencing (RNA-seq) data revealed that have indicated a close association between FoxO1 was closely related to lipid metabolism during lactation in dairy goats. The objective of this study was to investigate the mechanisms by which FoxO1 regulates lipid metabolism in goat mammary epithelial cells (GMECs). FoxO1 knockdown significantly downregulated the expression of adipose triglyceride lipase (ATGL) and suppressed the activity of the ATGL promoter. Consistently, the number of lipid droplets decreased significantly in FoxO1-overexpressing cells and increased in ATGL-knockdown cells. To further verify the effect of FoxO1 on ATGL promoter activity, cells were transfected with four promoter fragments of different lengths. We found that the core region of the ATGL promoter was located between −882 bp and −524 bp, encompassing two FoxO1 binding sites (FKH1 and FKH2). Mutations in the FoxO1 binding sites significantly downregulated ATGL promoter activity in GMECs. Luciferase reporter assays demonstrated that FoxO1 overexpression markedly enhanced ATGL promoter activity. Furthermore, site-directed mutation confirmed that FKH1 and FKH2 sites were simultaneously mutated significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activities simultaneous mutation of FKH1 and FKH2 sites significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activity. ChIP assays showed that FoxO1 directly binds to the FKH2 element located in the ATGL promoter in vivo. Finally, immunofluorescence staining revealed that insulin promotes the translocation of FoxO1 from the nucleus to the cytoplasm, thereby attenuating the FoxO1-induced activation of the ATGL promoter. Collectively, these findings uncover a novel pathway where by FoxO1 may regulate lipid metabolism in GMECs specifically by modulating the transcriptional activity of ATGL.
Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: Issues and interpretation of the results
Authors: de Jong Lutea A A , Kloost Tim , Olyslager Erik J H , Böttcher Michael , Wieferink Jan A , Vossenberg Peter , Belgers Maarten , Beurmanjer Harmen , de Haan Hein A
Published: August 2023

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration however require other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points, oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC–MS-MS. At the second time point, 98% of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100% in oral fluid, 98% in exhaled breath). Methadone-related results were 100% positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6%). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices.
From the Silo to the Landscape: The Role of Law in Landscape-scale Restoration of Coastal and Marine Ecosystems
Authors: Bell-James Justine
Published: August 2023

Internationally, we are in the midst of a shift from an environmental legal regime focussed solely on protection to one encompassing restoration. In the coastal wetland context, this move is especially needed due to the significant legacy of past losses. This article welcomes this shift, but advocates for a legal framework that embeds landscape-scale restoration from the outset, moving us from a siloed focus on single ecosystem services and projects. This argument is made by reference to learnings from the high level of fragmentation in the environmental protection space and by reference to the literature on ecological restoration and nature-based solutions. It will also use a recent example from Australia—the Blue Carbon methodology—to illustrate that momentum towards coastal restoration in legal frameworks is occurring, leaving us with a time-limited opportunity to ensure that this landscape-scale focus is embedded into restoration law before a siloed focus becomes entrenched.
‘Enjoying Time Alone’: Exploring Solitude as a Positive Space for Refugee Wellbeing
Authors: Kale Amber
Published: August 2023

In this article, I draw upon a participatory research project to explore how solitude enhanced a sense of place-attachment and wellbeing for former refugees in Aotearoa New Zealand. Solitude is overlooked in refugee resettlement research, which instead prioritizes theories of social participation and integration. However, positive experiences of aloneness enabled participants to freely regulate their emotions, express their identities, restructure their surroundings, and build meaningful place-attachments. Such emotionally transformative experiences are central to feeling well in new places, and I therefore argue that solitude requires researchers and policymakers’ attention as part of a more balanced resettlement approach; where the stressful work of social participation and integration are tempered with the necessary time and space for individuals to rest, reflect, and rejuvenate. In particular, resettling refugees could benefit from more research on the intersectional nuances of solitude and enhanced access to local knowledge, space, and resources to pursue meaningful solitary activities.
Atypical fundal perforation: a case report
Authors: Davoudi Sadaf , De Decker Marjolein , Willemsen Paul
Published: August 2023

Gastric perforations typically occur in the distal stomach, along the greater curvature or the antrum. The vast majority of upper gastrointestinal (GI) perforations are caused by peptic ulcer disease. We present a case of an atypical location of gastric perforation. A 31-year-old patient was experiencing nausea and severe abdominal pain. Explorative laparoscopy revealed a large fundal perforation. The patient underwent an abdominoplasty 5 days before with revisional surgery for hemorrhage. He had recently lost 42 kg after endoscopic sleeve gastroplasty (ESG) 8 months before. ESG is a minimally invasive alternative for bariatric surgery. Since its implementation, several studies have been published indicating the procedure as safe. However, some major adverse events, such as upper GI-bleeding, peri-gastric leak, and pneumoperitoneum, have been described. The atypical location of the perforation might be explained by a combination of events such as surgical stress, revisional surgery, major weight loss, and the history of ESG.
Retrospective comparison of false-positive result frequencies of 3 syphilis serology screening tests in pregnant and nonpregnant patients at an academic medical center in Appalachia
Authors: Yang Jianbo , Tacker Danyel H , Wen Sijin , LaSala P Rocco
Published: August 2023

Objective

This study retrospectively compared false-positive result frequencies of 3 syphilis serology screening tests and assessed whether false positivity was associated with pregnancy and age.

Methods

Results for 3 screening tests were retrieved from the laboratory database, including rapid plasma reagin (RPR) assay between October 2016 and September 2019, BioPlex 2200 Syphilis Total immunoassay between May 2020 and January 2022, and Alinity i Syphilis TP assay between February 2022 and April 2023. The false-positive result frequencies were calculated based on testing algorithm criteria.

Results

False-positive result frequency for BioPlex was 0.61% (90/14,707), significantly higher than 0.29% (50/17,447) for RPR and 0.38% (55/14,631) for Alinity (both P < .01). Patients with false-positive results were significantly older than patients with nonreactive results for RPR (median age: 36 vs 28, P < .001), but not for BioPlex or Alinity. For all 3 tests, the positive predictive values in pregnant women were lower than those in nonpregnant women or men. However, pregnant women did not exhibit a higher false-positive result frequency.

Conclusion

Although false-positive result frequencies were low overall for all 3 syphilis serology tests, there is a significant difference between different tests. Pregnancy was not associated with more false-positive results for all 3 tests.
Using Focused Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry to Depth Profile Nanoparticles in Polymer Nanocomposites
Authors: Zhang Aria C , Maguire Shawn M , Ford Jamie T , Composto Russell J
Published: August 2023

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a versatile surface-sensitive technique for characterizing both hard and soft matter. Its chemical and molecular specificity, high spatial resolution, and superior sensitivity make it an ideal method for depth profiling polymeric systems, including those comprised of both inorganic and organic constituents (i.e., polymer nanocomposites, PNCs). To best utilize ToF-SIMS for characterizing PNCs, experimental conditions must be optimized to minimize challenges such as the matrix effect and charge accumulation. Toward that end, we have successfully used ToF-SIMS with a Xe+ focused ion beam to depth profile silica nanoparticles grafted with poly(methyl methacrylate) (PMMA-NP) in a poly(styrene-ran-acrylonitrile) matrix film by selecting conditions that address charge compensation and the primary incident beam angles. By tracking the sputtered Si+ species and fitting the resultant concentration profile, the diffusion coefficient of PMMA-NP was determined to be D = 2.4 × 10−14 cm2/s. This value of D lies between that measured using Rutherford backscattering spectrometry (6.4 × 10−14 cm2/s) and the value predicted by the Stokes–Einstein model (2.5 × 10−15 cm2/s). With carefully tuned experimental parameters, ToF-SIMS holds great potential for quantitatively characterizing the nanoparticles at the surfaces and interfaces within PNC materials as well as soft matter in general.
A Machine Learning Framework for Quantifying Chemical Segregation and Microstructural Features in Atom Probe Tomography Data
Authors: Saxena Alaukik , Polin Nikita , Kusampudi Navyanth , Katnagallu Shyam , Molina-Luna Leopoldo , Gutfleisch Oliver , Berkels Benjamin , Gault Baptiste , Neugebauer Jörg , Freysoldt Christoph
Published: August 2023

Atom probe tomography (APT) is ideally suited to characterize and understand the interplay of segregation and microstructure in modern multi-component materials. Yet, the quantitative analysis typically relies on human expertise to define regions of interest. We introduce a computationally efficient, multi-stage machine learning strategy to identify compositionally distinct domains in a semi-automated way, and subsequently quantify their geometric and compositional characteristics. In our algorithmic pipeline, we first coarse-grain the APT data into voxels, collect the composition statistics, and decompose it via clustering in composition space. The composition classification then enables the real-space segmentation via a density-based clustering algorithm, thus revealing the microstructure at voxel resolution. Our approach is demonstrated for a Sm–(Co,Fe)–Zr–Cu alloy. The alloy exhibits two precipitate phases with a plate-like, but intertwined morphology. The primary segmentation is further refined to disentangle these geometrically complex precipitates into individual plate-like parts by an unsupervised approach based on principle component analysis, or a U-Net-based semantic segmentation trained on the former. Following the composition and geometric analysis, detailed composition distribution and segregation effects relative to the predominant plate-like geometry can be readily mapped from the point cloud, without resorting to the voxel compositions.
Structural Identification and Observation of Dose Rate–Dependent Beam-Induced Structural Changes of Micro- and Nanoplastic Particles by Pair Distribution Function Analysis in the Transmission Electron Microscope (ePDF)
Authors: Rohner Christian , Pratsch Christoph , Schlögl Robert , Lunkenbein Thomas
Published: August 2023

Micro- and nanoplastics (MNPs) are considered a possible threat to microorganisms in the aquatic environment. Here, we show that total scattering intensity analysis of electron diffraction (ED) data measured by transmission electron microscopy, which yields the electron pair distribution function (ePDF), is a feasible method for the characterization and identification of MNPs down to 100 nm. To demonstrate the applicability, cryo ball–milled powders of the most common polymers [i.e., polyethylene , polypropylene, polyethylene terephthalate, and polyamide] and nano-sized polystyrene and silica spheres were used as model systems. The comparison of the experimentally determined reduced pair density functions (RDFs) with model RDFs derived from crystallographic data of the respective polymers allows the distinction of the different types of polymers. Furthermore, carbon-based polymers are highly beam-sensitive materials. The degradation of the samples under the electron beam was analyzed by conducting time-resolved ED measurements. Changes in the material can be visualized by the RDF analysis of the time-series of ED patterns, and information about the materials in question can be gained by this beam damage analysis. Prospectively, ePDF analytics will help to understand and study more precisely the input of MNPs into the environment.