bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterolateral thoracotomy: unique approach to tricuspid valve replacement after right pneumonectomy
Authors: Hingtgen Austin , Siems Chesney , Huddleston Stephen J , John Ranjit 
Published: April 2023

Abstract
A 72-year-old patient presented with severe tricuspid regurgitation and patent foramen ovale (PFO) in the setting of severe mediastinal shifting after remote right pneumonectomy. Surgical approach was challenging given the significant herniation of the heart and left lung into the right hemithorax. This report describes tricuspid valve replacement with PFO closure via a right posterolateral thoracotomy and alternative cardiopulmonary bypass cannulation strategy.
Atp7b deficiency induces zebrafish eye developmental defects
Authors: Wu You , Liu Wenye , Li Lingya , Tai Zhipeng , Gao BaoXiang , Liu Jing-Xia 
Published: April 2023

Abstract
As a copper (Cu) transport ATPase, ATP7B plays an important role in maintaining Cu homeostasis in the body and its dysfunction is associated with retinal disease. How ATP7B dysfunction and the subsequent Cu overload induce retinal damage, however, are unknown. Here, we show that atp7b−/− homozygous zebrafish larvae are insensitive to light stimulation, with a reduction in retinal cells but normal like morphological phenotypes. Additionally, a series of differentially expressed genes are unveiled in atp7b−/− mutated larvae, which enrich in photo-transduction, structural constituent of eye lens, sensory perception of light stimulus, oxidative phosphorylation, and ATPase activity. Moreover, we show the Cu accumulation in retinal cells in atp7b−/− mutated larvae, which results in endoplasmic reticulum (ER) stress and retinal cell apoptosis and subsequent retinal defects. The integral data in this study demonstrate that atp7b mutation leads to Cu accumulation in zebrafish retinal cells and the consequence ER stress and retinal cell death. These data may give some possible hints to explain retinal disease occurred in the Cu dysregulation syndromes Wilson’s disease with ATP7B mutation.
A dual gene-specific mutator system installs all transition mutations at similar frequencies in vivo
Authors: Seo Daeje , Koh Bonghyun , Eom Ga-eul , Kim Hye Won , Kim Seokhee 
Published: April 2023

Abstract
Targeted in vivo hypermutation accelerates directed evolution of proteins through concurrent DNA diversification and selection. Although systems employing a fusion protein of a nucleobase deaminase and T7 RNA polymerase present gene-specific targeting, their mutational spectra have been limited to exclusive or dominant C:G→T:A mutations. Here we describe eMutaT7transition, a new gene-specific hypermutation system, that installs all transition mutations (C:G→T:A and A:T→G:C) at comparable frequencies. By using two mutator proteins in which two efficient deaminases, PmCDA1 and TadA-8e, are separately fused to T7 RNA polymerase, we obtained similar numbers of C:G→T:A and A:T→G:C substitutions at a sufficiently high frequency (∼6.7 substitutions in 1.3 kb gene during 80-h in vivo mutagenesis). Through eMutaT7transition-mediated TEM-1 evolution for antibiotic resistance, we generated many mutations found in clinical isolates. Overall, with a high mutation frequency and wider mutational spectrum, eMutaT7transition is a potential first-line method for gene-specific in vivo hypermutation.
DeepNeo: a webserver for predicting immunogenic neoantigens
Authors: Kim Jeong Yeon , Bang Hyoeun , Noh Seung-Jae , Choi Jung Kyoon 
Published: April 2023

Abstract
Non-self epitopes, whether originated from foreign substances or somatic mutations, trigger immune responses when presented by major histocompatibility complex (MHC) molecules and recognized by T cells. Identification of immunogenically active neoepitopes has significant implications in cancer and virus medicine. However, current methods are mostly limited to predicting physical binding of mutant peptides and MHCs. We previously developed a deep-learning based model, DeepNeo, to identify immunogenic neoepitopes by capturing the structural properties of peptide-MHC pairs with T cell reactivity. Here, we upgraded our DeepNeo model with up-to-date training data. The upgraded model (DeepNeo-v2) was improved in evaluation metrics and showed prediction score distribution that better fits known neoantigen behavior. The immunogenic neoantigen prediction can be conducted at https://deepneo.net.
Differential effects of hypergravity on immune dysfunctions induced by simulated microgravity
Authors: Moser Dominique , Biere Katharina , Liemersdorf Christian , Tuschen Marina , Hemmersbach Ruth , Choukér Alexander 
Published: April 2023

AbstractMicrogravity (μg) is among the major stressors in space causing immune cell dysregulations. These are frequently expressed as increased pro‐inflammatory states of monocytes and reduced activation capacities in T cells. Hypergravity (as artificial gravity) has shown to have beneficial effects on the musculoskeletal and cardiovascular system both as a countermeasure option for μg‐related deconditioning and as “gravitational therapy” on Earth. Since the impact of hypergravity on immune cells is sparsely explored, we investigated if an application of “mild” mechanical loading of 2.8 g is able to avoid or treat μg‐mediated immune dysregulations. For this, T cell and monocyte activation states and cytokine pattern were first analyzed after whole blood antigen incubation in simulated μg (s‐μg) by using the principle of fast clinorotation or in hypergravity. Subsequent hypergravity countermeasure approaches were run at three different sequences: one preconditioning setting, where 2.8 g was applied before s‐μg exposure and two therapeutic approaches in which 2.8 g was set either intermediately or at the end of s‐μg. In single g‐grade exposure experiments, monocyte pro‐inflammatory state was enhanced in s‐μg and reduced in hypergravity, whereas T cells displayed reduced activation when antigen incubation was performed in s‐μg. Hypergravity application in all three sequences did not alleviate the increased pro‐inflammatory potential of monocytes. However, in T cells the preconditioning approach restored antigen‐induced CD69 expression and IFNγ secretion to 1 g control values and beyond. This in vitro study demonstrates a proof of concept that mild hypergravity is a gravitational preconditioning option to avoid adaptive immune cell dysfunctions induced by (s‐)μg and that it may act as a booster of immune cell functions.
Three‐dimensional‐printed MPBI@β‐TCP scaffold promotes bone regeneration and impedes osteosarcoma under near‐infrared laser irradiation
Authors: Lu Liangjie , Wang Huihan , Yang Minjie , Wang Lijun , Gan Kaifeng 
Published: April 2023

AbstractBeta‐tricalcium phosphate (β‐TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2)/polydopamine (PDA)/−bone morphogenetic protein 2 (BMP2)‐insulin‐like growth factor‐1 (IGF‐1) coating on the β‐TCP scaffold and analyzed the outcomes. The MoS2/PDA‐BMP2‐IGF‐1@β‐TCP (MPBI@β‐TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@β‐TCP scaffold was evaluated. It was found that MPBI@β‐TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@β‐TCP. Additionally, MPBI@β‐TCP stimulated endothelial cells to secrete VEGF and promoted capillary‐like tubule formation. We then confirmed the biocompatibility of MPBI@β‐TCP to macrophages and its anti‐inflammatory effects. Furthermore, under near‐infrared (NIR) laser irradiation, MPBI@β‐TCP produced photothermal effect to not only kill MG‐63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D‐printed MPBI@β‐TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.
Student and Teacher Perspectives on Equity in Clinical Feedback: A Qualitative Study Using a Critical Race Theory Lens
Authors: Mason Hyacinth R.C. , Pérez Maria , Colson Eve R. , Jeffe Donna B. , Aagaard Eva M. , Teherani Arianne , Hanson Janice L. 
Published: April 2023

Purpose
The authors aimed to gain a better understanding of students’ and teachers’ perspectives about whether clinical clerkship feedback is provided equitably irrespective of a student’s race/ethnicity.

Method
A secondary analysis of existing interview data was conducted, focusing on racial/ethnic disparities in clinical grading. Data had been acquired from 29 students and 30 teachers at 3 U.S. medical schools. The authors performed secondary coding on all 59 transcripts, writing memos focused on statements related to aspects of feedback equity and developing a template for coding students’ and teachers’ observations and descriptions specific to clinical feedback. Using the template, memos were coded, and thematic categories emerged describing perspectives on clinical feedback.

Results
Forty-eight (22 teachers and 26 students) participants’ transcripts provided narratives about feedback. Both student and teacher narratives described how students who are racially/ethnically underrepresented in medicine may receive less helpful formative clinical feedback needed for professional development. Thematic analysis of narratives yielded 3 themes related to feedback inequities: 1) teachers’ racial/ethnic biases influence the feedback they provide students, 2) teachers have limited skill sets to provide equitable feedback, and 3) racial/ethnic inequities in the clinical learning environment shape clinical and feedback experiences.

Conclusions
Narratives indicated that both students and teachers perceived racial/ethnic inequities in clinical feedback. Teacher- and learning environment-related factors influenced these racial/ethnic inequities. These results can inform medical education’s efforts to mitigate biases in the learning environment and provide equitable feedback to ensure every student has what they need to develop into the competent physician they aspire to be.
Correlation of Computed Tomography, Pathological Findings, and Clinical Outcomes for Appendicoliths in Appendicitis
Authors: Weitzner Zachary N. , Chung Alex , Naini Bita V. , Graham Danielle , Livingston Edward H. 
Published: April 2023

Objectives:
To correlate preoperative imaging of fecaliths with what is seen in surgical specimens.

Background:
Early studies considered radiological findings of appendicoliths as a contraindication for nonoperative treatment of appendicitis. There is no standard definition for what is labeled as an appendicolith radiologically and little is known about the pathological correlates of these lesions.

Methods:
A single center, retrospective study of a consecutive series of adult patients who underwent appendectomy for acute appendicitis from March 2021 to February 2022 was performed. The primary outcome was concordance between preoperative cross-sectional imaging description of appendicolith with postoperative gross pathology description. Images were retrospectively reviewed by an independent radiologist, and the presence and characteristics of appendicoliths and appendices were examined.

Results:
Of 88 cases of appendicitis, 86 were diagnosed preoperatively by computed tomography (CT) imaging. Appendicoliths were seen either on CT or pathology in 45 (51%) patients. Of these 45 patients, a total of 38 (84%) were identified radiographically, and 28 (62%) were identified on pathology. Of the 38 appendicoliths diagnosed on preoperative imaging, only 21 (55%) were confirmed pathologically. Additionally, of the 28 appendicoliths observed on pathology, only 21 (75%) were identified preoperatively on imaging. There was no appendiceal obstruction in 10 of the 40 cases (25%) in which retrospective radiological review identified appendicoliths.

Conclusions:
Discrepancies were observed between CT and pathology findings of appendicoliths. Not all appendicoliths seem to cause appendicitis. Because the presence of appendicolith influences the treatment decisions, there is a need to standardize their radiological diagnosis and better understand their pathophysiology.
Go or no-go for treat-to-target in axial spondyloarthritis?
Authors: Webers Casper , Been Marin , van Tubergen Astrid 
Published: April 2023

Purpose of review
For almost a decade, treat-to-target (T2T) has been advocated as a management strategy for axial spondyloarthritis (axSpA), despite a lack of trial evidence. Recently, the first and only published T2T trial in axSpA did not meet its primary endpoint. The purpose of this review is to discuss whether we should continue with a T2T approach in axSpA and to describe some experiences with T2T in clinical practice.

Recent findings
The trial showed no superiority of T2T compared with usual care; however, several secondary trial outcomes and the health economic analysis actually favoured T2T, and there are conceivable reasons for the negative trial results. Furthermore, several knowledge gaps related to an optimal T2T approach in axSpA were identified. In clinical practice, a T2T approach was applied to only a limited extent, possibly because of several challenges.

Summary
Despite one negative trial, it is too early to abandon T2T in axSpA. Not only more evidence from clinical trials but also research on the optimal target and management of all facets of axSpA, are highly needed. For successful implementation of T2T in clinical practice, it is important that barriers and facilitators to application are identified and subsequently addressed.
Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials
Authors: Milosavljevic Milos N. , Stefanovic Srdjan M. , Pejcic Ana V. 
Published: April 2023

Abstract
An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.
Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites
Authors: Chakraborty Saroj , Lulla Anju , Cheng Xi , Yeo Ji-Youn , Mandal Juthika , Yang Tao , Mei Xue , Saha Piu , Golonka Rachel M. , Yeoh Beng San , Mell Blair , Jia Wei , Putluri Vasanta , Piyarathna Danthasinghe Waduge Badrajee , Putluri Nagireddy , Sreekumar Arun , Meyer Katie , Vijay-Kumar Matam , Joe Bina 
Published: April 2023

Background:
Hypertension is the largest risk factor affecting global mortality. Despite available medications, uncontrolled hypertension is on the rise, whereby there is an urgent need to develop novel and sustainable therapeutics. Because gut microbiota is now recognized as an important entity in blood pressure regulation, one such new avenue is to target the gut-liver axis wherein metabolites are transacted via host-microbiota interactions. Knowledge on which metabolites within the gut-liver axis regulate blood pressure is largely unknown.

Method:
To address this, we analyzed bile acid profiles of both human and hypertensive rat models and report that conjugated bile acids are inversely correlated with blood pressure in humans and rats.

Results:
Notably intervening with taurine rescued bile acid conjugation and reduced blood pressure in hypertensive rats. Subsequently, untargeted metabolomics uncovered lower energy metabolism following conjugation of bile acids as a mechanism alleviating high blood pressure.

Conclusion:
Together this work reveals conjugated bile acids as nutritionally re-programmable anti-hypertensive metabolites.

Graphical abstract:

http://links.lww.com/HJH/C165
Relationship between measures of adiposity, blood pressure and arterial stiffness in adolescents. The MACISTE study
Authors: Pucci Giacomo , Martina Maria R. , Bianchini Elisabetta , D’abbondanza Marco , Curcio Rosa , Battista Francesca , Anastasio Fabio , Crapa Mariano E. , Sanesi Leandro , Gemignani Vincenzo , Vaudo Gaetano 
Published: April 2023

Objective:
Children and adolescents with adiposity excess are at increased risk of future cardiovascular (CV) disease. Fat accumulation promotes the development of elevated blood pressure (BP) and arterial stiffness, two main determinants of CV risk which are strongly inter-related. We aimed at investigating whether the association between overweight and arterial stiffness, taken at different arterial segments, is mediated by increased BP or is BP-independent.

Methods:
Three hundred and twenty-two Italian healthy adolescents (mean age 16.9±1.4 years, 12% with overweight) attending the “G. Donatelli” High School in Terni, Italy, underwent measurement of arterial stiffness by arterial tonometry (aortic stiffness) and semiautomatical detection of pressure–volume ratio of the common carotid (carotid stiffness). The mediator effect of BP was tested for each anthropometric or biochemical measure of fat excess related to arterial stiffness.

Results:
Both carotid and aortic stiffness showed positive correlations with body mass index, waist, hip, and neck circumferences (NC). Only carotid stiffness, but not aortic stiffness, was associated with serum markers of fat accumulation and metabolic impairment such as insulin, homeostatic model of insulin resistance (HOMA-IR), serum gamma-glutamyl transferase (sGGT) and uric acid. The association with NC was stronger for carotid than for aortic stiffness (Fisher z-to-R 2.07, P = 0.04), and independent from BP.

Conclusions:
In healthy adolescents, fat accumulation is associated with arterial stiffness. The degree of this association differs by arterial segments, since carotid stiffness is more strongly associated to adipose tissue excess than aortic stiffness and shows a BP-independent association with NC whereas aortic stiffness does not.
The renal resistive index is associated with microvascular remodeling in patients with severe obesity
Authors: Moriconi Diego , Mengozzi Alessandro , Duranti Emiliano , Cappelli Federica , Taddei Stefano , Nannipieri Monica , Bruno Rosa Maria , Virdis Agostino 
Published: April 2023

Background:
Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity.

Methods:
We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with NG-nitro arginine methyl ester (L-NAME), were measured.

Results:
Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT (P = 0.042). Multivariable analysis showed a relationship between M/L and RRI (P = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation (P
= 0.036, St. β = −0.34). Notably, all these correlations were consistent also after adjustment for confounding factors.

Conclusions:
The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption.