bluuebunny/crossref_metadata_2025 huggingface dataset:
MITNet: a fusion transformer and convolutional neural network architecture approach for T-cell epitope prediction
Authors: Darmawan Jeremie Theddy , Leu Jenq-Shiou , Avian Cries , Ratnasari Nanda Rizqia Pradana
Published: May 2023

Classifying epitopes is essential since they can be applied in various fields, including therapeutics, diagnostics and peptide-based vaccines. To determine the epitope or peptide against an antibody, epitope mapping with peptides is the most extensively used method. However, this method is more time-consuming and inefficient than using present methods. The ability to retrieve data on protein sequences through laboratory procedures has led to the development of computational models that predict epitope binding based on machine learning and deep learning (DL). It has also evolved to become a crucial part of developing effective cancer immunotherapies. This paper proposes an architecture to generalize this case since various research strives to solve a low-performance classification problem. A proposed DL model is the fusion architecture, which combines two architectures: Transformer architecture and convolutional neural network (CNN), called MITNet and MITNet-Fusion. Combining these two architectures enriches feature space to correlate epitope labels with the binary classification method. The selected epitope–T-cell receptor (TCR) interactions are GILG, GLCT and NLVP, acquired from three databases: IEDB, VDJdb and McPAS-TCR. The previous input data was extracted using amino acid composition, dipeptide composition, spectrum descriptor and the combination of all those features called AADIP composition to encode the input data to DL architecture. For ensuring consistency, fivefold cross-validations were performed using the area under curve metric. Results showed that GILG, GLCT and NLVP received scores of 0.85, 0.87 and 0.86, respectively. Those results were compared to prior architecture and outperformed other similar deep learning models.
PPIntegrator: semantic integrative system for protein–protein interaction and application for host–pathogen datasets
Authors: Martins Yasmmin Côrtes , Ziviani Artur , Cerqueira e Costa Maiana de Oliveira , Cavalcanti Maria Cláudia Reis , Nicolás Marisa Fabiana , de Vasconcelos Ana Tereza Ribeiro
Published: May 2023

Semantic web standards have shown importance in the last 20 years in promoting data formalization and interlinking between the existing knowledge graphs. In this context, several ontologies and data integration initiatives have emerged in recent years for the biological area, such as the broadly used Gene Ontology that contains metadata to annotate gene function and subcellular location. Another important subject in the biological area is protein–protein interactions (PPIs) which have applications like protein function inference. Current PPI databases have heterogeneous exportation methods that challenge their integration and analysis. Presently, several initiatives of ontologies covering some concepts of the PPI domain are available to promote interoperability across datasets. However, the efforts to stimulate guidelines for automatic semantic data integration and analysis for PPIs in these datasets are limited. Here, we present PPIntegrator, a system that semantically describes data related to protein interactions. We also introduce an enrichment pipeline to generate, predict and validate new potential host–pathogen datasets by transitivity analysis. PPIntegrator contains a data preparation module to organize data from three reference databases and a triplification and data fusion module to describe the provenance information and results. This work provides an overview of the PPIntegrator system applied to integrate and compare host–pathogen PPI datasets from four bacterial species using our proposed transitivity analysis pipeline. We also demonstrated some critical queries to analyze this kind of data and highlight the importance and usage of the semantic data generated by our system.

Availability and implementation

https://github.com/YasCoMa/ppintegrator, https://github.com/YasCoMa/ppi_validation_process and https://github.com/YasCoMa/predprin.
Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models
Authors: Kang Da Hee , Kim Min Jae , Mohamed Elsayed A , Kim Da Som , Jeong Jea Sic , Kim So Young , Kang Hyeon-Gu , Lee Geun-Shik , Hong Eui-Ju , Ahn Changhwan , Jung Eui-Man , An Beum-Soo , Kim Seung-Chul
Published: May 2023

The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.
Multiple-statistical genome-wide association analysis and genomic prediction of fruit aroma and agronomic traits in peaches
Authors: Li Xiongwei , Wang Jiabo , Su Mingshen , Zhang Minghao , Hu Yang , Du Jihong , Zhou Huijuan , Yang Xiaofeng , Zhang Xianan , Jia Huijuan , Gao Zhongshan , Ye Zhengwen
Published: May 2023

‘Chinese Cling’ is an important founder in peach breeding history due to the pleasant flavor. Genome-wide association studies (GWAS) combined with genomic selection are promising tools in fruit tree breeding, as there is a considerable time lapse between crossing and release of a cultivar. In this study, 242 peaches from Shanghai germplasm were genotyped with 145 456 single-nucleotide polymorphisms (SNPs). The six agronomic traits of fruit flesh color, fruit shape, fruit hairiness, flower type, pollen sterility, and soluble solids content, along with 14 key volatile odor compounds (VOCs), were recorded for multiple-statistical GWAS. Except the reported candidate genes, six novel genes were identified as associated with these traits. Thirty-nine significant SNPs were associated with eight VOCs. The putative candidate genes were confirmed for VOCs by RNA-seq, including three genes in the biosynthesis pathway found to be associated with linalool, soluble solids content, and cis-3-hexenyl acetate. Multiple-trait genomic prediction enhanced the predictive ability for γ-decalactone to 0.7415 compared with the single-trait model value of 0.1017. One PTS1-SSR marker was designed to predict the linalool content, and the favorable genotype 187/187 was confirmed, mainly existing in the ‘Shanghai Shuimi’ landrace. Overall, our findings will be helpful in determining peach accessions with the ideal phenotype and show the potential of multiple-trait genomic prediction to improve accuracy for highly correlated genetic traits. The diagnostic marker will be valuable for the breeder to bridge the gap between quantitative trait loci and marker-assisted selection for developing strong-aroma cultivars.
Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis
Authors: Wei Feixue , Alberts Catharina J , Albuquerque Andreia , Clifford Gary M
Published: May 2023

Background

We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN).

Methods

We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies).

Results

We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]–negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%–90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%–67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%–91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV).

Conclusions

There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.
Canadian records of Branchinecta serrata Rogers, 2006 and its confusion with B. paludosa (Müller, 1788) (Branchiopoda: Anostraca: Branchinectidae), with a key to the B. paludosa species group
Authors: Rogers D Christopher , Gardiner Ian R
Published: May 2023

Branchinecta serrata Rogers, 2006 was originally thought to be limited to four localities in the central USA. We present new records of this species in prairie pools in central Canada, greatly extending its known distribution. Previous records from Canada were misidentified as the common and widespread B. paludosa (Müller, 1788). We present images emphasizing the differences between the two species, updated geochemical tolerance data, and revise the conservation status of B. serrata. Finally, we present an identification key to the Branchinecta paludosa species group.
Keeping Up with Current Practices in a Rapidly Evolving Field Through Dissemination of “Tips and Tricks” in a Monthly Webinar
Authors: Zimanyi Christina M , Rayaprolu Vamseedhar
Published: May 2023

In the past decade, cryo-electron microscopy (cryoEM) has become a vital tool for structural biologists. Using cryoEM to determine structures of biomolecules at high resolution is a rapidly evolving technique with high barriers to entry for non-microscopists. To help academic researchers remain competitive in their fields, the NIH established a network of centers to broaden access and training in cryoEM. One initiative from this network is the monthly CryoEM Current Practices webinar that provides practical methodological tips and tricks and is openly accessible to anyone interested. Now in its third year, the webinar continues to attract a sizable audience and provides a forum for network building within the structural biology community.
Using Antibodies in Microscopy: A Guide to Immunohistochemistry. Part 2: IHC Staining Protocols
Authors: Guerin Christopher J
Published: May 2023

Immunohistochemistry (IHC) is the use of antibodies as probes to determine the localization of proteins in a cell or tissue sample. In microscopy, the technique has been in use since the 1940s by pathologists and research scientists. At first glance it appears a straightforward procedure. However, in practice, an IHC protocol has a number of steps where problems can occur, resulting in either false positive or false negative data. IHC can be used in both transmitted light and fluorescence microscopy, and it can be used in combinations to identify and mark multiple proteins of interest. While the technique has been published extensively, a certain amount of confusion exists as to how to optimize it. This series of three articles describes the steps involved in IHC, their function, and some variations that occur in specific protocols on differing cell and tissue types. It is hoped that a better understanding of these steps will help to guide users in determining the optimal conditions for carrying through IHC protocols.
Survival of U.S. Military Service Members With Lymphoma
Authors: Ancira Gilbert , Romain Joshua , Pham Kevin , Thornton Jennifer A , DeStefano Christin B
Published: May 2023

Introduction

Cancer is a prominent cause of mortality in today’s active duty service members (ADSMs), killing over 700 ADSMs between 2004 and 2015. Hence, more research is needed to better understand the survival of U.S. service members with cancer. Lymphoma is the most common hematologic malignancy diagnosed in ADSMs, serving as a good cancer type to study.

Materials and Methods

The Department of Defense tumor registry and the Surveillance, Epidemiology, and End Result (SEER) databases were retrospectively accessed to analyze overall survival (OS) of ADSMs with lymphoma and to compare outcomes with matched civilians. ADSMs with Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and indolent lymphoma diagnosed between 1997 and 2017 were included, and SEER comparator patients were matched by age, sex, race, stage, and year of diagnosis using a 4:1 ratio of civilians to ADSMs.

Results

There were 1,170, 443, and 284 ADSMs with HL, DLBCL, and indolent lymphoma, respectively, and all three groups had superior OS when compared to their matched civilian counterparts with 35%, 49%, and 48% reductions in the risk of death, respectively. There were no differences in ADSM survival based on race, sex, or rank, despite disparities being pervasive in the civilian sector.

Conclusions

Service members with lymphoma have superior survival than their matched civilian counterparts, without evident racial or sex disparities. Results of this study are favorable in terms of readiness. Further research on cancer mortality in ADSMs is needed to improve long-term outcomes.
The role of student effort on performance in PISA: revisiting the gender gap in achievement
Authors: Anaya Lina M , Zamarro Gema
Published: May 2023

International assessments are important to benchmark the quality of education internationally. However, ignoring students’ efforts in low-stakes tests can lead to biased interpretations of test performance. We use data from the PISA to analyse the potential role of student effort in explaining gender achievement gaps across countries. We build two effort measures based on students’ response times to test questions (i.e. rapid-guessing rates) and the student effort on the post-test survey (i.e. item non-response rates). We find a strong association between student efforts and test scores. After accounting for differences in effort, the estimated gender achievement gap in mathematics and science could be up to 36% and 40% of an standard deviation wider, respectively, in favour of boys. Altogether, our effort measures on average explain between 51% and 56% of the cross-country variation in test scores.
Sulfopeptide CLEL6 inhibits anthocyanin biosynthesis in Arabidopsis thaliana
Authors: Bühler Eric , Fahrbach Elisa , Schaller Andreas , Stührwohldt Nils
Published: May 2023

Posttranslationally modified peptides are now recognized as important regulators of plant stress responses. Here, we identified the small sulfated CLE-LIKE6 (CLEL6) peptide as a negative regulator of anthocyanin biosynthesis in etiolated and in light-stressed Arabidopsis (Arabidopsis thaliana) seedlings. CLEL6 function depends on proteolytic processing of the CLEL6 precursor by subtilisin-like serine proteinase 6.1 (SBT6.1) and on tyrosine sulfation by tyrosylprotein sulfotransferase (TPST). Loss-of-function mutants of either sbt6.1 or tpst showed significantly higher anthocyanin accumulation than the wild type upon light stress. The anthocyanin overaccumulation phenotype of sbt6.1 and tpst was suppressed by application of mature CLEL6. Overexpression and external application of CLEL6 inhibited the expression of anthocyanin biosynthesis genes in etiolated and light-stressed seedlings, confirming the role of CLEL6 as an inhibitor of anthocyanin biosynthesis. Small posttranslationally modified peptides are perceived by leucine-rich repeat receptor-like kinases. Using a quintuple mutant of ROOT MERISTEM GROWTH FACTOR 1 INSENSITIVE (RGI) receptors, we showed the essential function of the RGI receptor family in CLEL6 signaling. Our data indicate that overexpression or application of CLEL6 inhibits anthocyanin biosynthesis through RGI receptors. We propose that CLEL6 inhibits anthocyanin biosynthesis in etiolated seedlings, and that anthocyanin biosynthesis is derepressed when CLEL6 expression is downregulated upon light exposure. Hyperaccumulation of anthocyanins in light-stressed tpst and sbt6.1 mutant seedlings suggests that CLEL6, or related sulfopeptides, continues to act as negative regulators to limit pigment accumulation in the light.
Fast-forward generation of non-equilibrium steady states of a charged particle under the magnetic field
Authors: Setiawan Iwan , Sugihakim Ryan , Gunara Bobby Eka , Masuda Shumpei , Nakamura Katsuhiro
Published: May 2023

The fast-forward (FF) is one of the ideas to speed up the dynamics of given systems, and reproduces series of events on a shortened time scale, just like rapid projection of movie films on a screen. Considering a charged particle under the electromagnetic field, we present a scheme of FF generation of its non-equilibrium steady state, which realizes with complete fidelity the underlying quantum adiabatic dynamics throughout the FF protocol. We then apply the scheme to Landau states of a clean spin-less electron gas in a 2D x − y plane under the constant magnetic field B in the z direction. We have found how the electric field should be applied in rapid preparation of the quantum-mechanical Hall state as a non-equilibrium steady state. The FF electric field expressed in terms of the time-scaling function is found to be common to both the ground and excited Landau states. The FF driving avoids the decoherence inevitable in slow adiabatic procedures and eliminates the undesired mixing among Landau states with different quantum numbers that usually occurs in fast control.
The classical solutions with k− = 0 in Kaku theory
Authors: Ando Yuji
Published: May 2023

We consider Kaku theory as introduced in M. Kaku, Phys. Lett. B 200, 22 (1988) and investigate classical solutions. In particular, we obtain that the equation of motion with the restriction k− = 0 in the Kaku theory is equivalent to the equation of motion in Witten theory. Because of this property, some solutions including the tachyon vacuum solution in the Witten theory satisfy also the equation of motion in the Kaku theory. In addition, we confirm that the cohomology around the tachyon vacuum solution is trivial also in the Kaku theory.
An “Eye For an Eye” Versus “Turning The Other Cheek”? The Status Consequences of Revenge and Forgiveness in Intergroup Conflict
Authors: Benard Stephen , Doan Long , Nicholson D Adam , Meanwell Emily , Wright Eric L , Lista Peter
Published: May 2023

Conflict between groups plays a powerful role in shaping social interaction within groups. Within groups, social status—respect, prestige, and deference—organizes, motivates, and stratifies social interaction. Yet, studies exploring how conflict between groups shapes social status within groups are relatively rare. We argue that intergroup conflict creates opportunities for individuals to gain or lose status by demonstrating group commitment. We examine two contrasting intergroup behaviors—revenge and forgiveness—and evaluate the idea that these behaviors will be viewed as status-worthy to the extent that they are perceived to signal group motivation. Furthermore, we test the hypothesis that avengers and forgivers gain status by offering group-motivated accounts of their behavior. Pairing an original national probability sample with an experimental survey design, we examine how avengers and forgivers are viewed in everyday conflicts across three widely held identities: national identity, political partisanship, and sports team fandom. We find that Americans perceive intergroup forgiveness as more status-worthy, and a stronger indicator of group motivation, than intergroup revenge. In open-ended survey questions, forgiving ingroup members were described as more status-worthy, competent, and warm, and less dominant than their vengeful counterparts. However, we find little evidence that individuals can directly gain status by claiming that their actions are motivated by concern for the group. Our work speaks to theories of conflict, identity, and social status. More broadly, understanding how Americans value intergroup revenge and forgiveness offers insight into the frequency and intensity of identity-based conflict in contemporary American society.
Best for Whom? Heterogeneous Treatment Effects of Breastfeeding on Child Development
Authors: Su Jessica Houston , Raissian Kerri M , Kim Jiyeon
Published: May 2023

The slogan “Breast is Best” has been popularized by medical organizations and parenting networks to extoll the benefits of breastfeeding, yet the causal effects are widely debated. Our study contributes to the debate by examining whether breastfeeding has differential effects based on the propensity to breastfeed, which is also known as causal effect heterogeneity. Prior studies attempt to isolate the causal effect of breastfeeding by netting out confounding characteristics, but we argue that the effects of breastmilk are unlikely to operate in a vacuum. The social forces that promote or constrain breastfeeding among different populations in American society can also shape its effects. Using rich intergenerational panel data from the NLSY79 Child and Young Adult cohort (n = 7902), we evaluate heterogeneous treatment effects in the relationship between breastfeeding and child development from ages 4 to 14 using stratification-multilevel propensity score models. We find that breastfeeding is associated with small benefits for behavioral development, math scores, and academic ability among those with the highest propensities to breastfeed. By contrast, its small benefits for reading comprehension and vocabulary are concentrated among children with the lowest propensities to breastfeed. Our findings suggest that the social process of selection into breastfeeding cannot be fully disentangled from its estimated effects. The social context not only shapes who breastfeeds in American society, but also who benefits most.
ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes
Authors: Lee Sung Woo , Kim Bokyung , Seong Jung Bae , Park Young-Ho , Lee Hong Jun , Lee Dong-Seok
Published: May 2023

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.
UCHL1 aggravates skin fibrosis through an IGF‐1‐induced Akt/mTOR/HIF‐1α pathway in keloid
Authors: Guo Chipeng , Liang Lizhu , Zheng Jingbin , Xie Yang , Qiu Xiaonan , Tan Guozhen , Huang Jingang , Wang Liangchun
Published: May 2023

Keloid is a heterogeneous disease featured by the excessive production of extracellular matrix. It is a great challenge for both clinicians and patients regarding the exaggerated and uncontrolled outgrowth and the therapeutic resistance of the disease. In this study, we verified that UCHL1 was drastically upregulated in keloid fibroblasts. UCHL1 had no effects on cell proliferation and migration, but instead promoted collagen I and α‐SMA expression that was inhibited by silencing UCHL1 gene and by adding in LDN‐57444, a pharmacological inhibitor for UCHL1 activity as well. The pathological process was mediated by IGF‐1 promoted Akt/mTOR/HIF‐1α signaling pathway because inhibition of any of them could reduce the expression of collagen I and α‐SMA driven by UCHL1 in fibroblasts. Also, we found that UCHL1 expression in keloid fibroblasts was promoted by M2 macrophages via TGF‐β1. These findings extend our understanding of the pathogenesis of keloid and provide potential therapeutic targets for the disease.
Investigation of the effect of subacromial corticosteroid injections on intraocular pressure
Authors: Engin Onur , Durmaz Engin Ceren , Samanci Rumeysa , Teberik Kuddusi , Ataoglu Safinaz
Published: May 2023

Background:

Subacromial corticosteroid injection is one of the most commonly used procedures to treat subacromial impingement syndrome. Despite their significant efficacy, corticosteroids have several serious adverse effects, including increased intraocular pressure (IOP) and visual loss. The purpose of this study is to determine the effect of subacromial corticosteroid injections on IOP.

Materials and Methods:

42 patients with impingement syndrome, who received subacromial corticosteroid injection, were included in the study. Patients received a single dose of betamethasone. IOP was monitored using a tonometer prior to injection, 24 hours after injection, and one week following injection.

Results:

The average age of the patients was 52.1±9.0, and 31 (74%) of them were female. Patients’ mean IOP values were 16.0±2.6 mmHg, 16.4±2.4 mmHg, and 16.1±2.31 mmHg before injection, one day after injection, and one week after injection, respectively. Repeated ANOVA tests revealed no statistically significant difference between the three measurements (P=0.386). Age, gender, history of diabetes, and history of hypertension didn’t have a significant effect on IOP change after corticosteroid injection. Those with a family history of glaucoma had a significantly greater increase in IOP on day 1 post-injection than those without (P=0.05).

Conclusions:

This is the first study to examine the effect of subacromial corticosteroid injections on IOP change. While a single subacromial steroid injection has no statistically significant effect on IOP change, care should be taken, particularly in susceptible individuals and those who need repeated injections.
Impact of Transfused Citrate on Pathophysiology in Massive Transfusion
Authors: Schriner Jacob B. , Van Gent J. Michael , Meledeo M. Adam , Olson Scott D. , Cotton Bryan A. , Cox Charles S. , Gill Brijesh S.
Published: May 2023

OBJECTIVES:

This narrative review article seeks to highlight the effects of citrate on physiology during massive transfusion of the bleeding patient.

DATA SOURCES:

A limited library of curated articles was created using search terms including “citrate intoxication,” “citrate massive transfusion,” “citrate pharmacokinetics,” “hypocalcemia of trauma,” “citrate phosphate dextrose,” and “hypocalcemia in massive transfusion.” Review articles, as well as prospective and retrospective studies were selected based on their relevance for inclusion in this review.

STUDY SELECTION:

Given the limited number of relevant studies, studies were reviewed and included if they were written in English. This is not a systematic review nor a meta-analysis.

DATA EXTRACTION AND SYNTHESIS:

As this is not a meta-analysis, new statistical analyses were not performed. Relevant data were summarized in the body of the text.

CONCLUSIONS:

The physiologic effects of citrate independent of hypocalcemia are poorly understood. While a healthy individual can rapidly clear the citrate in a unit of blood (either through the citric acid cycle or direct excretion in urine), the physiology of hemorrhagic shock can lead to decreased clearance and prolonged circulation of citrate. The so-called “Diamond of Death” of bleeding—coagulopathy, acidemia, hypothermia, and hypocalcemia—has a dynamic interaction with citrate that can lead to a death spiral. Hypothermia and acidemia both decrease citrate clearance while circulating citrate decreases thrombin generation and platelet function, leading to ionized hypocalcemia, coagulopathy, and need for further transfusion resulting in a new citrate load. Whole blood transfusion typically requires lower volumes of transfused product than component therapy alone, resulting in a lower citrate burden. Efforts should be made to limit the amount of citrate infused into a patient in hemorrhagic shock while simultaneously addressing the induced hypocalcemia.
Do the incidence and severity of lower urinary tract symptoms measured by the international consultation on incontinence questionnaires correlate with urodynamic findings in patients with systemic sclerosis?
Authors: Faddan Amr Abou , Hassanien Manal , Talaat Esraa Ahmed , Gadelkareem Rabea Ahmed
Published: May 2023

Background

Systemic sclerosis (SSC) affects the urinary bladder and many other body organs. Systemic sclerosis commonly manifests as lower urinary tract symptoms (LUTS), which are usually reported using validated questionnaires. This study aimed to correlate questionnaire-reported LUTS with urodynamic findings in patients with SSC.

Materials and methods

This cross-sectional study was performed at our center between August 2018 and July 2021. Lower urinary tract symptoms were assessed using the International Consultation on Incontinence Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) and ICIQ Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS) and urodynamic studies. Univariate analyses were then performed on variables affecting detrusor activity.

Results

This study included 22 patients (5 men, 17 women). The mean ± standard deviation age, body mass index, and disease duration were 37.2 ± 11.1 years, 25.5 ± 4.2 kg/m2, and 6.2 ± 5.3 years, respectively. Lower urinary tract symptoms occurred in 19 (86.4%) patients, of whom 18 (94.7%) had mild to moderate symptoms. The ICIQ scores for voiding and filling symptoms were higher than those for incontinence. The most frequent organ involvements included Raynaud’s phenomenon in 22 (100%), skin conditions in 20 (90.9%), gastrointestinal tract maladies in 17 (77.3%), joint disorders in 16 (72.7%), and lung diseases in 14 (63.6%) patients. Abnormal detrusor contractions occurred in only 5 patients (22.7%). Univariate analyses showed that disease duration <5 years (p = 0.010), nonobstructive uroflowmetry findings (p = 0.024), absence of incontinence (p = 0.024) and telangiectasia (p = 0.010), and negative rheumatoid factors (p = 0.043) were significantly associated with normal detrusor contractions.

Conclusions

Mild to moderate severity of ICIQ-measured LUTS affected most patients with SSC but was not correlated with urodynamic findings. Normal detrusor contractions were significantly associated with shorter disease duration, nonobstructive uroflowmetry findings, absence of incontinence and telangiectasia, and negative rheumatoid factors.
The Relationship of Preconception and Early Pregnancy Isoprostanes with Fecundability and Pregnancy Loss
Authors: Nobles Carrie J. , Mendola Pauline , Mumford Sunni L. , Silver Robert M. , Kim Keewan , Perkins Neil J. , Schisterman Enrique F.
Published: May 2023

Background:

Although redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women’s reproductive health outcomes.

Methods:

The Effects of Aspirin in Gestation and Reproduction trial (2007–2011) enrolled 1228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-prostaglandin F2α (8-iso-PGF2α), its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks gestation. We evaluated pregnancy among participants in each menstrual cycle using human chorionic gonadotropin (hCG) and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional hazards models and relative risk of pregnancy loss using adjusted log-binomial models.

Results:

Higher preconception isoprostane levels were associated with lower fecundability [e.g., FOR = 0.89; 95% CI = 0.81, 0.97 per interquartile range (IQR) increase in 8-iso-PGF2α]. Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks gestation (e.g., mean difference = 0.12; 95% CI = 0.10, 0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks gestation were associated with lower risk of pregnancy loss (e.g., RR = 0.79; 95% CI = 0.62, 1.00 per IQR increase in 8-iso-PGF2α).

Conclusions:

Preconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and the associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.
Disparities in Fatal Occupational Injury Rates in North Carolina, 1978–2017: Comparing Nonmanagerial Employees to Managers
Authors: Richardson David B. , Cole Stephen R. , Martin Amelia T. , McClure Elizabeth S. , Nocera Maryalice , Cantrell John , Ranapurwala Shabbar I. , Marshall Stephen W.
Published: May 2023

Background:

We examined fatal occupational injuries among private-sector workers in North Carolina during the 40-year period 1978–2017, comparing the occurrence of fatal injuries among nonmanagerial employees to that experienced by managers.

Methods:

We estimated a standardized fatal occupational injury ratio by inverse probability of exposure weighting, taking nonmanagerial workers as the target population. When this ratio measure takes a value greater than unity it signals settings in which nonmanagerial employees are not provided as safe a work environment as that provided for managers.

Results:

Across all industries, nonmanagerial workers in North Carolina experienced fatal occupational injury rates 8.2 (95% CI = 7.0, 10.0) times the rate experienced by managers. Disparities in fatal injury rates between managers and the employees they supervise were greatest in forestry, rubber and metal manufacturing, wholesale trade, fishing and extractive industries, and construction.

Conclusions:

The results may help focus discussion about workplace safety between labor and management upon equity, with a goal of providing a work environment for nonmanagerial employees as safe as the one provided for managers.
Microbiota transfer following liver surgery involves microbial extracellular vesicle migration that affects liver immunity
Authors: Cohen Shmuel J. , Meyerovich Guy , Blank Simcha , Ovdat Esther , Loewenstein Shelly , Kania-Almog Juliane , Cohen Meir , Lahat Guy , Klausner Joseph M. , Lubezky Nir
Published: May 2023

Background:

Short-term perioperative administration of probiotics was shown to alleviate postoperative complications and promote liver recovery among patients undergoing resection for liver malignancy. The mechanisms by which probiotic bacteria effectively influence the gut microbiome composition during the perioperative time are controversial. Here, we aim to elucidate the short-term direct biological effect of probiotic microbiota–derived vesicles on host liver cells during the perioperative period.

Methods:

Probiotic-derived vesicles (pbMVs) were administered postoperatively. pbMVs were isolated and characterized from probiotics, mainly from the bacteria genus Lactobacillus, Bifidobacterium, and Lactococcus. Mice underwent bile duct ligation, sham laparotomy (SHAM), or 70% partial hepatectomy (70%PH). pbMVs were tracked in vivo, and intrahepatic cellular and molecular aspects were analyzed by flow cytometry and qRT-PCR techniques. Liver sinusoidal endothelial cells (LSECs) analysis for Vascular Cell Adhesion Molecule-1(VCAM-1) expression following pbMV stimulation of cultured liver non-parenchymal cells which had been activated by LPS.

Results:

The administered pbMV rapidly translocated to the liver after surgery. pbMV administrations following surgeries enhanced neutrophil clearance; there was a dramatic decline in the liver neutrophil-to-lymphocyte ratio Ly6G+/CD3+ and an increase in IL6 levels. pbMVs reduced intrahepatic VCAM1 and ICAM2 expression compared with control following SHAM and decrease in IL10 levels following 70%PH. The administration of pbMV improved liver regeneration 72 hours following surgical liver resection with a significant decrease in IL17 expression. pbMVs modulated VCAM-1 on liver sinusoidal endothelial cells in liver cell culture.

Conclusions:

Our study findings provide mechanistic insights into the liver-gut axis following surgery and illustrate how probiotic vesicles can reduce adhesion molecule expression and affect immune cell invasion and liver immunity, resulting in improved liver recovery following hepatic surgery.
Refractive lens exchange – who is getting it, what are they getting, how are they doing?
Authors: Ong Lauren F. , Oh Alyce , Yi Joseph K. , Gu Joshua S. , Marvasti Amir H. , Nguyen Betsy B. , Tran Dan B. , Lee Jimmy K.
Published: May 2023

Purpose of review

The purpose of this article is to provide a review of the literature on refractive lens exchange and present a retrospective analysis of 55 patients who underwent refractive lens exchange at a single practice.

Recent findings

Our study substantiates refractive lens exchange as an important option for presbyopic patients, hyperopic patients or patients with extremely high refractive error who desire spectacle independence.

Our study reveals that the refractive lens exchange population is younger than the average cataract population and their primary motivations are to resolve hyperopic or myopic refractive errors, gain spectacle independence, and address near vision loss. A variety of presbyopia-addressing intraocular lens options are available and we present our experience with multifocal, extended depth-of-focus, light-adjustable, and monofocal lenses.
Recent advances in cell-based regenerative therapies for corneal disease
Authors: Kaufman Ron , Jun Albert S.
Published: May 2023

Purpose of review

With limited access of more than half the world's population to corneal transplantation, regenerative medicine may represent a promising alternative. This review explores the main advancements achieved in cell-based therapies for corneal epithelium, stroma, and endothelium during 2021–2022.

Recent findings

Multiple surgical techniques have been developed for epithelial limbal stem cell replacement. Recent studies aimed to gain greater understanding and characterization of these techniques. Though no clear superiority could be demonstrated, simple limbal epithelial transplantation seems to have the most clinical and cost effectiveness. For stromal disease, autologous adipose-derived stem cells have shown favorable results. For endothelial dysfunction, the validity of intracameral cultivated allogeneic endothelial cell injection and Descemetorrhexis without endothelial keratoplasty, as well as the benefits of adjunctive rho-associated kinase inhibitors, were emphasized.

A plethora of innovative cell-based regenerative therapies for corneal diseases have been developed in past years. While recent literature solidifies our knowledge, most studies are still in preliminary or preclinical stages. Though showing great promise, these approaches will require larger studies with better-defined endpoints to establish their benefits over currently available treatments.
Opportunities to improve high-risk behavior screenings during well-child examinations
Authors: Ederle Hannah M. , Finley Kallie M. , Reisinger Michele E. , Hartman Amanda L.
Published: May 2023

Background:

Nurse practitioners serve an essential role in the completion of age-appropriate adolescent high-risk behavior screenings including tobacco/nicotine, alcohol, illicit drug use, and sexual activity during well-child examinations (WCEs).

Local problem:

Midwestern adolescents demonstrate a suboptimal rate of engaging in annual preventative medical visits in comparison to national data.

Methods:

This mixed-methods quality improvement pilot sought to evaluate health care providers' beliefs, general clinic processes, and the overall quality of WCEs among adolescents aged 11–17 years in two midwestern primary care clinics. Quantitative data were obtained through queried reports and manual electronic health record chart audits. Qualitative data were obtained through focus group interviews.

Interventions:

Interventional strategies included providing education to key stakeholders regarding data analysis findings indicating process deficiencies regarding adolescent WCEs. Project members championed integration of advanced practice nurses as leaders of change within urban, multisite tertiary health care systems.

Results:

Results demonstrate that the lack of standardized assessment during an adolescent WCE can lead to fragmentation of high-risk behavior screenings.

Conclusions:

This quality improvement pilot demonstrates the need for nurse practitioners to be at the forefront of interprofessional committees advancing the implementation of evidence-based guidelines and practice improvement initiatives. Standardization of high-risk behavior screening as part of the WCE in adolescence provides the foundation for health promotion and chronic disease prevention spanning into adulthood.
Nurse practitioner educational preparation and confidence related to managing antipsychotic medications and associated drug-induced movement disorders
Authors: Gallagher Shawn , Bouchard Lindsay
Published: May 2023

Background:

Antipsychotic medications (APMs) have been used to treat multiple psychiatric disorders for decades. The conditions to use these medications have expanded from primarily psychotic disorders to Food and Drug Administration–approved uses as first-line mood stabilizers in bipolar disorder and adjunctive pharmacotherapy in unipolar depression. Antipsychotic medications can have serious side effects, including drug-induced movement disorders (DIMDs). Nurse practitioners (NPs) in non–psychiatric-mental health specialties are increasingly managing psychotropic medication regimes. There is a void in peer-reviewed literature capturing the scope of NPs managing APMs, such as whether they received training to prescribe and manage risks of APM, and if so, what type (e.g., continuing education, attending conferences, consulting), and their confidence assessing and managing DIMDs.

Purpose:

To describe the scope of NP management, knowledge, and confidence related to APMs and associated risks of DIMDs.

Methodology:

Nonexperimental, descriptive, cross-sectional survey. Participants (n = 400) recruited through a professional association membership portal.

Results:

Nearly two-thirds of participants reported managing APMs (64%) and receiving training to prescribe and manage risks of APMs (63%). More than half (54%) reported they received training to do so in their NP education program. Thirty-five percent of participants indicated they were either completely (6%) or fairly (29%) confident, whereas most (65%) endorsed being somewhat (26%), slightly (20%), or not (19%) confident in assessing and managing DIMDs.

Conclusions/Implications:

Opportunities exist to broaden NP education in managing APMs and associated risks of DIMDs.
Betahistine Prescribing Practices in England: An Analysis of Prescribing and National Spending Pre- and Post-BEMED Trial
Authors: Sutton Liam , Ghedia Reshma , Harcourt Jonny
Published: May 2023

Objective

Betahistine has not been proven to be superior to placebo in the BEMED study, a multicenter, double-blind, randomized, placebo controlled trial. Our study aimed to establish the prescribing practices of clinicians in England in relation to betahistine and to assess if there has been any change in prescribing practices since the publication of the BEMED trial.

Study Design

Retrospective study and clinician survey.

Patients

All patients who were prescribed betahistine from primary care.

Main Outcome Measure

Total quantity of betahistine prescribed and total actual cost.

Results

The average total monthly quantity prescribed was 11,143,253 tablets (range, 10,056,516–12,276,423). Prescribing did not decrease from the period before (January 2014–February 2016) to after (February 2016–February 2021) the publication of the BEMED trial, with the average monthly prescribing before publication being 11,294,848 tablets (range, 10,280,942– 12,276,423) and the average monthly prescribing after publication being 11,081,123 tablets (range, 10,056,516–11,915,707). The average actual monthly cost increased from the period before publication to after publication from a sum of £279,264.82 to a sum of £428,846.22. Most (90.5%) of the survey respondents prescribed betahistine for Menière’s disease. Less than half (38.09%) prescribed betahistine for indications other than Menière’s disease. Only 45.24% of the clinicians were aware of the results of the BEMED trial.

Conclusions

Knowledge of the BEMED trial among otology and neurotology subspecialists is lacking. The results of the BEMED have made no difference to prescribing practice, and in fact, the cost of the medication to the health bill has increased.