bluuebunny/crossref_metadata_2025_split huggingface dataset:
High spontaneous integration rates of end-modified linear DNAs upon mammalian cell transfection
Authors: Lim Samuel , Yocum R. Rogers , Silver Pamela A. , Way Jeffrey C. 
Published: April 2023

AbstractIn gene therapy, potential integration of therapeutic transgene into host cell genomes is a serious risk that can lead to insertional mutagenesis and tumorigenesis. Viral vectors are often used as the gene delivery vehicle, but they are prone to undergoing integration events. More recently, non-viral delivery of linear DNAs having modified geometry such as closed-end linear duplex DNA (CELiD) have shown promise as an alternative, due to prolonged transgene expression and less cytotoxicity. However, whether modified-end linear DNAs can also provide a safe, non-integrating gene transfer remains unanswered. Herein, we compare the genomic integration frequency upon transfection of cells with expression vectors in the forms of circular plasmid, unmodified linear DNA, CELiDs with thioester loops, and Streptavidin-conjugated blocked-end linear DNA. All of the forms of linear DNA resulted in a high fraction of the cells being stably transfected—between 10 and 20% of the initially transfected cells. These results indicate that blocking the ends of linear DNA is insufficient to prevent integration.
Effects of liquid surface tension on gas capillaries and capillary forces at superamphiphobic surfaces
Authors: Eriksson Mimmi , Claesson Per M. , Järn Mikael , Wallqvist Viveca , Tuominen Mikko , Kappl Michael , Teisala Hannu , Vollmer Doris , Schoelkopf Joachim , Gane Patrick A. C. , Mäkelä Jyrki M. , Swerin Agne 
Published: April 2023

AbstractThe formation of a bridging gas capillary between superhydrophobic surfaces in water gives rise to strongly attractive interactions ranging up to several micrometers on separation. However, most liquids used in materials research are oil-based or contain surfactants. Superamphiphobic surfaces repel both water and low-surface-tension liquids. To control the interactions between a superamphiphobic surface and a particle, it needs to be resolved whether and how gas capillaries form in non-polar and low-surface-tension liquids. Such insight will aid advanced functional materials development. Here, we combine laser scanning confocal imaging and colloidal probe atomic force microscopy to elucidate the interaction between a superamphiphobic surface and a hydrophobic microparticle in three liquids with different surface tensions: water (73 mN m−1), ethylene glycol (48 mN m−1) and hexadecane (27 mN m−1). We show that bridging gas capillaries are formed in all three liquids. Force-distance curves between the superamphiphobic surface and the particle reveal strong attractive interactions, where the range and magnitude decrease with liquid surface tension. Comparison of free energy calculations based on the capillary menisci shapes and the force measurements suggest that under our dynamic measurements the gas pressure in the capillary is slightly below ambient.
Upregulation of alveolar fluid clearance is not sufficient for Na+,K+-ATPase β subunit-mediated gene therapy of LPS-induced acute lung injury in mice
Authors: Liu Jing , Schiralli-Lester Gillian M. , Norman Rosemary , Dean David A. 
Published: April 2023

AbstractAcute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is characterized by diffuse alveolar damage and significant edema accumulation, which is associated with impaired alveolar fluid clearance (AFC) and alveolar‐capillary barrier disruption, leading to acute respiratory failure. Our previous data showed that electroporation‐mediated gene delivery of the Na+, K+-ATPase β1 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS‐induced ALI in mice. More importantly, our recent publication showed that gene delivery of MRCKα, the downstream effector of β1 subunit-mediated signaling towards upregulation of adhesive junctions and epithelial and endothelial barrier integrity, also provided therapeutic potential for ARDS treatment in vivo but without necessarily accelerating AFC, indicating that for ARDS treatment, improving alveolar capillary barrier function may be of more benefit than improving fluid clearance. In the present study, we investigated the therapeutical potential of β2 and β3 subunits, the other two β isoforms of Na+, K+-ATPase, for LPS‐induced ALI. We found that gene transfer of either the β1, β2, or β3 subunits significantly increased AFC compared to the basal level in naïve animals and each gave similar increased AFC to each other. However, unlike that of the β1 subunit, gene transfer of the β2 or β3 subunit into pre-injured animal lungs failed to show the beneficial effects of attenuated histological damage, neutrophil infiltration, overall lung edema, or increased lung permeability, indicating that β2 or β3 gene delivery could not treat LPS induced lung injury. Further, while β1 gene transfer increased levels of key tight junction proteins in the lungs of injured mice, that of either the β2 or β3 subunit had no effect on levels of tight junction proteins. Taken together, this strongly suggests that restoration of alveolar-capillary barrier function alone may be of equal or even more benefit than improving AFC for ALI/ARDS treatment.
Position-reconfigurable pinning for magnetic domain wall motion
Authors: Lee Taekhyeon , Jeong Seyeop , Kim Sanghoon , Kim Kab-Jin 
Published: April 2023

AbstractPrecise control of magnetic domain wall (DW) motion is crucial for DW-based spintronic devices. To date, artificially designed DW pinning sites, such as notch structures, have been used to precisely control the DW position. However, the existing DW pinning methods are not reconfigurable because they cannot change the position of pinning site after being fabricated. Herein, a novel method for attaining reconfigurable DW pinning is proposed, which relies on the dipolar interactions between two DWs located in different magnetic layers. Repulsion between DWs in both layers was observed, indicating that one of the DWs acts as a pinning barrier for the other. Because the DW is mobile in the wire, the position of pinning can be modulated, thereby resulting in reconfigurable pinning that was experimentally demonstrated for current-driven DW motion. These findings provide additional controllability of DW motion, which may expand the functionality of DW-based devices to broader spintronic applications.
Genotype–phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea
Authors: Kim Ji Hyun , Lim Seon Hee , Song Ji Yeon , Cho Myung Hyun , Hyun HyeSun , Yang Eun Mi , Lee Jung Won , Cho Min Hyun , Park Min Ji , Lee Joo Hoon , Jung Jiwon , Yoo Kee Hwan , Jang Kyung Mi , Pai Ki Soo , Suh Jin-Soon , Namgoong Mee Kyung , Chung Woo Yeong , Kim Su Jin , Cho Eun Young , Kim Kyung Min , Kim Nam Hee , Kim Minsun , Paik Jin Ho , Kang Hee Gyung , Ahn Yo Han , Cheong Hae Il 
Published: April 2023

AbstractThe genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype–phenotype correlation not only in male patients but also in female patients with XLAS.
Screening marker genes of type 2 diabetes mellitus in mouse lacrimal gland by LASSO regression
Authors: Pei Xiaoting , Qi Di , Liu Jiangman , Si Hongli , Huang Shenzhen , Zou Sen , Lu Dingli , Li Zhijie 
Published: April 2023

AbstractType 2 diabetes mellitus (T2DM) is characterized by insulin resistance and a relative deficiency of insulin. This study aims to screen T2DM-related maker genes in the mouse extraorbital lacrimal gland (ELG) by LASSO regression.C57BLKS/J strain with leptin db/db homozygous mice (T2DM, n = 20) and wild-type mice (WT, n = 20) were used to collect data. The ELGs were collected for RNA sequencing. LASSO regression was conducted to screen marker genes with the training set. Five genes were selected from 689 differentially expressed genes by LASSO regression, including Synm, Elovl6, Glcci1, Tnks and Ptprt. Expression of Synm was downregulated in ELGs of T2DM mice. Elovl6, Glcci1, Tnks, and Ptprt were upregulated in T2DM mice. Area under receiver operating curve of the LASSO model was 1.000(1.000–1.000) and 0.980(0.929–1.000) in the training set and the test set, respectively. The C-index and the robust C-index of the LASSO model were 1.000 and 0.999, respectively, in the training set, and 1.000 and 0.978, respectively, in the test set. In the lacrimal gland of db/db mice, Synm, Elovl6, Glcci1, Tnks and Ptprt can be used as marker genes of T2DM. Abnormal expression of marker genes is related to lacrimal gland atrophy and dry eye in mice.
Graphene oxide decorated multi-frequency surface acoustic wave humidity sensor for hygienic applications
Authors: Jung Soon In , Jang Il Ryu , Ryu Chaehyun , Park Jeonhyeong , Padhan Aneeta Manjari , Kim Hoe Joon 
Published: April 2023

AbstractThis work presents the single-chip integration of a multi-frequency surface acoustic wave resonator (SAWR) based humidity sensor. Graphene oxide (GO), a humidity-sensing material, is integrated onto a confined sensing area of SAWR via electrospray deposition (ESD). The ESD method allows ng-resolution deposition of GO, optimizing the amount of sensing material. The proposed sensor consists of SWARs at three different resonant frequencies (180, 200 and 250 MHz) with a shared common sensing region, thus allowing direct analysis of sensor performances at different operating frequencies. Our findings reveal that the resonant frequency of the sensor impacts both measurement sensitivity and stability. A higher operating frequency ensures better sensitivity but suffers from a larger damping effect from absorbed water molecules. The maximum measurement sensitivity of 17.4 ppm/RH% is achieved with low drift. In addition, the developed sensor exhibits improved stability and sensitivity by as much as 150% and 75% in frequency shift and Quality factor (Q), respectively, by carefully selecting the operating frequencies at a given RH% range. Finally, the sensors are used for various hygienic applications, such as non-contact proximity detection and face mask inspection.
First trimester abortion protocols by facility type in Switzerland and potential barriers to accessing the service
Authors: Eckstein Samuel Martin , von Felten Stefanie , Perotto Laura , Brun Romana , Vorburger Denise 
Published: April 2023

AbstractSimplified first-trimester abortion protocols are well established. However, data on the use of medical or surgical abortion protocols across Switzerland is lacking. We report protocol characteristics in abortion care for two different facility types, hospital vs private practices (office-based) in Switzerland. Furthermore, we investigate an association between protocol characteristics and the likelihood of following through with the abortion at the same facility. We also report abortion outcomes of an office-based cohort where doctors use simplified abortion protocols. This study consists of two parts. (i) Between April and July, 2019, we collected data regarding medical and surgical abortion protocols of institutions offering abortions, in a nationwide survey. We assessed whether the proportion of patients who followed through with the abortion (primary outcome) after first appointment was associated with predefined protocol characteristics, considered to complicate access to abortion services, using generalised estimating equations. (ii) We analysed abortion outcomes of six selected office-based facilities from January, 2008, to December, 2018, using simplified abortion protocols in accordance with the Worlds Health Organisation (WHO) guidelines. (i) We included a total of 39 institutions. Hospitals showed more protocol-based barriers to abortion access compared with office-based facilities. The odds of undergoing an abortion after the first appointment were increased using protocols with minimal barriers. Overall, office-based facilities applied higher gestational age limits, required fewer appointments, and administered mifepristone more often after the first visit than did hospitals. (ii) We included a total of 5274 patients with an incidence of complications requiring surgery of 2.5% in line with rates reported in published literature. Only a few hospitals provide abortion care with easy access to medical and surgical abortion, whereas most office-based facilities do. Access to abortion services is generally crucial, and should be provided in a single visit whenever clinically permissible.
AI-assisted prediction of differential response to antidepressant classes using electronic health records
Authors: Sheu Yi-han , Magdamo Colin , Miller Matthew , Das Sudeshna , Blacker Deborah , Smoller Jordan W. 
Published: April 2023

AbstractAntidepressant selection is largely a trial-and-error process. We used electronic health record (EHR) data and artificial intelligence (AI) to predict response to four antidepressants classes (SSRI, SNRI, bupropion, and mirtazapine) 4 to 12 weeks after antidepressant initiation. The final data set comprised 17,556 patients. Predictors were derived from both structured and unstructured EHR data and models accounted for features predictive of treatment selection to minimize confounding by indication. Outcome labels were derived through expert chart review and AI-automated imputation. Regularized generalized linear model (GLM), random forest, gradient boosting machine (GBM), and deep neural network (DNN) models were trained and their performance compared. Predictor importance scores were derived using SHapley Additive exPlanations (SHAP). All models demonstrated similarly good prediction performance (AUROCs ≥ 0.70, AUPRCs ≥ 0.68). The models can estimate differential treatment response probabilities both between patients and between antidepressant classes for the same patient. In addition, patient-specific factors driving response probabilities for each antidepressant class can be generated. We show that antidepressant response can be accurately predicted from real-world EHR data with AI modeling, and our approach could inform further development of clinical decision support systems for more effective treatment selection.
Mechanistic insights into the development of severe fetal growth restriction
Authors: Gumina Diane L. , Su Emily J. 
Published: April 2023

Abstract
Fetal growth restriction (FGR), which most commonly results from suboptimal placental function, substantially increases risks for adverse perinatal and long-term outcomes. The only “treatment” that exists is delivery, which averts stillbirth but does not improve outcomes in survivors. Furthermore, the potential long-term consequences of FGR to the fetus, including cardiometabolic disorders, predispose these individuals to developing FGR in their future pregnancies. This creates a multi-generational cascade of adverse effects stemming from a single dysfunctional placenta, and understanding the mechanisms underlying placental-mediated FGR is critically important if we are to improve outcomes and overall health. The mechanisms behind FGR remain unknown. However, placental insufficiency derived from maldevelopment of the placental vascular systems is the most common etiology. To highlight important mechanistic interactions within the placenta, we focus on placental vascular development in the setting of FGR. We delve into fetoplacental angiogenesis, a robust and ongoing process in normal pregnancies that is impaired in severe FGR. We review cellular models of FGR, with special attention to fetoplacental angiogenesis, and we highlight novel integrin-extracellular matrix interactions that regulate placental angiogenesis in severe FGR. In total, this review focuses on key developmental processes, with specific focus on the human placenta, an underexplored area of research.
Sonographic Fracture Diagnosis in Children and Adolescents
Authors: Moritz Jörg Detlev 
Published: April 2023

Background Clinical examination after trauma, especially in young children, often proves difficult. As a result, the majority of images show unremarkable findings in the imaging workup of trauma by radiography. Sonography represents an imaging technique without the use of X-rays. As the quality of ultrasound equipment has increased over the past 20 years, numerous studies have demonstrated that fractures in children and adolescents can be detected with very high sensitivity and specificity by sonography.Method This paper reviews the results obtained so far in the literature. Based on these findings, the importance of sonographic fracture diagnosis in childhood and adolescence for the most important locations is demonstrated.Results When examining with a high-frequency linear transducer, sensitivities and specificities of more than 90 % can be achieved for the detection of fractures. Dislocations are also reliably detected. In contrast to X-ray examination, sonography allows the diagnosis of cartilage and soft-tissue injuries. Sonography reveals callus formation earlier than radiographs. The examination causes less pain than X-ray examination. If sonographic clarification is limited purely to fracture detection or exclusion, less time is required compared to X-ray diagnosis. The procedure can be learned quickly. If the documentation follows a defined standard examination procedure, the results can also be reproduced by non-examiners.Conclusion So far, sonography has only been an additive procedure in fracture diagnosis. However, there are now initial recommendations for sonographic fracture diagnosis alone, such as in skull, clavicle and non-displaced distal forearm fractures.Key Points:Zitierweise
Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute
Authors: Geng Yuanming , Dong Qian , Cong Zixiang , Zhu Junhao , Li Zhenxing , Du Chaonan , Yuan Feng , Zeng Xinrui , Ali Alleyar , Yang Jin , Tang Chao , Ma Chiyuan 
Published: April 2023

Abstract
Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas.
Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order.
Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level (p = 0.166), basal GH level (p = 0.001), and nadir GH level (p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery.
Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.
Challenges of Integrating APOL1 Genetic Test Results into the Electronic Health Record
Authors: Rasmussen Luke V. , Agrawal Akansha H. , Botsford Paul , Powers Andrew , Schnoebelen Jeffrey , Xinos Stavroula , Harper Gail , Thanner Jane , McCabe Sarah , Moore Stephen , Wicklund Catherine A. , Duquette Debra , Gordon Elisa J. 
Published: April 2023

Abstract
Objectives Integrating genetic test results into the electronic health record (EHR) is essential for integrating genetic testing into clinical practice. This article describes the organizational challenges of integrating discrete apolipoprotein L1 (APOL1) genetic test results into the EHR for a research study on culturally sensitive genetic counseling for living kidney donors.
Methods We convened a multidisciplinary team across three institutions (Northwestern University, Northwestern Memorial HealthCare [NMHC], and OHSU Knight Diagnostic Laboratories [KDL]), including researchers, physicians, clinical information technology, and project management. Through a series of meetings over a year between the team and the genetic testing laboratory, we explored and adjusted our EHR integration plan based on regulatory and budgetary constraints.
Results Our original proposal was to transmit results from KDL to NMHC as structured data sent via Health Level Seven (HL7) v2 message. This was ultimately deemed infeasible given the time and resources required to establish the interface, and the low number of samples to be processed for the study (n = 316). We next explored the use of Epic's Care Everywhere interoperability platform, but learned it was not possible as a laboratory test ordered for a research study; even though our intent was to study the APOL1 genetic test result's clinical use and impact, test results were still considered “research results.” Faced with two remaining options—downloading a PDF from the KDL laboratory portal or scanning a faxed result from KDL—only a PDF of the APOL1 test result could be integrated into the EHR, reinforcing the status quo.
Conclusion Even with early and ongoing stakeholder engagement, dedicated project management, and funding, unanticipated implementation challenges—especially for research projects—can result in drastic design tradeoffs.