bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex PCR amplicon sequencing revealed community transmission of SARS-CoV-2 lineages on the campus of Sichuan University during the outbreak of infection in Chinese Mainland at the end of 2022
Authors: Tang Langjun , Guo Zhenyu , Lu Xiaoyi , Zhao Junqiao , Li Yonghong , Yang Kun 
Published: May 2023

AbstractDuring the pandemic of COVID-19, wastewater-based epidemiology has become a powerful epidemic surveillance tool widely used around the world. However, the development and application of this technology in Chinese Mainland are relatively lagging. Herein, we report the first case of community circulation of SARS-CoV-2 lineages monitored by WBE in Chinese Mainland during the infection outbreak at the end of 2022 after the comprehensive relaxation of epidemic prevention policies. During the peak period of infection, six precious sewage samples were collected from the manhole in the student dormitory area of Wangjiang Campus of Sichuan University. According to the results RT-qPCR, the six sewage samples were all positive for SARS-CoV-2 RNA. Based on multiplex PCR amplicon sequencing, the local transmission of SARS-CoV-2 variants at that time was analyzed. The results show that the main virus lineages in sewage have clear evolutionary genetic correlations. Furthermore, the sampling time is very consistent with the timeline of concern for these virus lineages and consistent with the timeline for uploading the nucleic acid sequences of the corresponding lineages in Sichuan to the database. These results demonstrate the reliability of the sequencing results of SARS-CoV-2 nucleic acid in wastewater. Multiplex PCR amplicon sequencing is by far the most powerful analytical tool of WBE, enabling quantitative monitoring of virus lineage prevalence at the community level.HighlightsSix sewage samples were collected on Wangjiang Campus of Sichuan university at the end of 2022.SARS-CoV-2 nucleic acid was detected in all six sewage samples via qPCR.Multiplex PCR amplicon sequencing reveals the local transmission of SARS-CoV-2 lineages.Multiplex PCR amplicon sequencing is to date the most powerful WBE tool.GRAPHICAL ABSTRACT
Left Bundle Branch Pacing Facilitated by Novel Surface Electrocardiography in Comparison with Electrophysiology Recording System
Authors: Su Lan , Zhu Ling , Wang Songjie , Wu Shengjie , Chen Xiao , Huang Zhouqing , Wang Liangping , Xu Lei , Zhou Xiaohong , Huang Weijian 
Published: May 2023

AbstractBackgroundLeft bundle branch pacing (LBBP) had been proven to be feasible and safe in patients with a pacemaker indication. In this study, we assessed the feasibility and safety of LBBP procedure using simplified ECG monitoring and LBBP criteria in comparison with that by using the conventional EP system and currently adopted LBBP criteria.MethodsThe single-center study included 143 consecutive patients from March 2021 to January 2022. The operator was single-blind to the electrophysiology recording system (EP system), and only observed the electrophysiological characteristics of the four-lead ECG monitor and the pacing system analyzer (PSA) by naked eye. Other researchers kept synchronized records of the EP system, and analyzed whether the data were correct and consistent after the operation. Intraoperative data were collected and the safety of 3-month follow-up after operation were evaluated.ResultsOf 143 patients enrolled, 139 successfully performed LBBP, with a success rate of 97.2%, and the judgement concordance with EP system was 99.3%. The total operation time was 78.9±26.5min, the total fluoroscopy time was 9.5±6.1min, the fluoroscopy time of left bundle branch (LBB) lead deployment 3.0±2.6min, which had no significant difference with previous studies. Ventricular septal perforation occurred in 2 patients during the operation. Pacing parameters were stable and heart function improved during follow-up.ConclusionsThe simplified LBBP implantation method without an EP system and only relying on a simplified ECG combined with an analyzer is clinically feasible and safe and can be promoted in clinical practice.
The influence of APOE status on cognitive decline
Authors: Morrison Cassandra , Oliver Michael D. , Berry Virginia , Kamal Farooq , Dadar Mahsa 
Published: May 2023

AbstractINTRODUCTIONApolipoprotein (APOE) ε4 and subjective cognitive decline (SCD) increase risk of Alzheimer’s disease. However, few studies have examined the relationship between SCD and APOE, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD.METHODSLinear mixed effects models examined the relationship between APOE status and cognitive change in older adults with SCD (SCD), normal controls (NC), and people with mild cognitive impairment (MCI).RESULTSThe presence of at least one ε2 allele in SCD and MCI results in cognitive change rates similar to a NC with the ε3ε3 genotype. Older SCD-ε4 individuals exhibited increased cognitive decline compared to all groups, including NC-ε4 and MCI-ε4.DISCUSSIONPeople with SCD with at least one ε4 allele will experience increased cognitive decline compared to cognitively healthy older adults and people with MCI. These findings have important implications for treatments and interventions.
Association of Mental Health Treatment on Outcomes in Patients with Heart Failure and Ischemic Heart Disease
Authors: Carmin Cheryl N. , Ownby Raymond L. , Fontanella Cynthia , Steelesmith Danielle , Binkley Philip F. 
Published: May 2023

AbstractBackgroundPrevious studies have not found an impact of mental health treatment on outcomes in patients with heat disease. The aim of this study was to examine whether individuals who received mental health treatment for anxiety or depression after being hospitalized for ischemic disorders or heart failure had a reduced frequency of re-hospitalizations, emergency department (ED) visits or mortality compared to those who did not receive treatment.MethodsA population based, retrospective, cohort design was used to examine the association between psychotherapy or antidepressant medication prescription and health service utilization and mortality in patients with coronary artery disease and comorbid anxiety and/or depression. Those receiving versus not receiving mental health treatment were compared based on the frequency of re-hospitalization, emergency department visits, and mortality.ResultsThe study sample included 1,563 subjects who had a mean age of 50.1 years. Individuals who received both forms of mental health treatment were 87% less likely to be re-hospitalized, 73% less likely to have an emergency department visit, and 65% less likely to die from any cause.ConclusionsMental health treatment has a significant impact on outcomes in patients with cardiovascular disease consisting of reduced hospitalizations, emergency department visits and in some conditions improved survival.
Amyloid Screening and Treatment Drop Off in Patients with Left Ventricular Hypertrophy: Associations with Patient Socio-demographic Characteristics
Authors: Walenczyk Kristie M. , Singh Avinainder , Tong Kimhouy , Burg Matthew M. , Miller Edward J. 
Published: May 2023

AbstractBackgroundCompared to estimated population prevalence rates, relatively few patients at risk are ultimately diagnosed with and treated for transthyretin cardiac amyloidosis (ATTR-CA). Where along the clinical imaging and treatment pathway patient drop off occurs, and the association of drop off at each step with patient socio-demographic characteristics remains unknown.MethodsUsing data from a healthcare system-wide cardiovascular imaging repository and specialty pharmacy we characterized the multi-level clinical pathway from screening for left ventricular hypertrophy (LVH) with transthoracic echocardiograms (TTE), diagnosis with technetium-99m pyrophosphate scintigraphy (PYP), and tafamidis prescription, initiation, and adherence. Standardized differences (d≥0.20 indicating a small effect size or larger) were used to compare socio-demographics (age, sex, race, national and state Area Deprivation Index) among patients with TTE-identified LVH by PYP referral status, patients with PYP-identified ATTR-CA by tafamidis prescription status, and patients prescribed tafamidis by initiation status.ResultsA total of 8575 patients had LVH on TTE, with 1.6% referred for PYP. Of 97 patients with PYP-identified ATTR-CA, 58.8% were prescribed tafamidis, with 80.7% of those initiating therapy. Referral from LVH on TTE to PYP was higher among men, older patients, and those of Black/African American or American Indian/Alaskan Native race (alld’s≥0.20). Patients with PYP-identified ATTR-CA prescribed tafamidis were younger than those not prescribed tafamidis (d=-0.30). Utilization of a specialty pharmacy resulted in enrichment of treatment in subgroups traditionally undertreated in cardiovascular medicine, with higher rates of tafamidis initiation among women (100% initiation), patients of Black/African American race (d=0.40), and those living in more economically disadvantaged areas (d’s≥0.30).ConclusionThese findings highlight the tremendous opportunity for more robust imaging and clinical ATTR-CA screening programs, including potential patient subgroups that should be targeted to reduce disparities. Among patients diagnosed with ATTR-CA, utilization of a specialty pharmacy process appears to ensure the equitable provision of tafamidis therapy.
Penalised neural network with weight correlation descent for predicting polygenic risk score
Authors: Kim Sun bin , Kang Joon Ho , Cheon MyeongJae , Kim Dong Jun , Lee Byung-Chul 
Published: May 2023

AbstractIn this study, we developed a deep neural network (DNN) model with weight correlation descent (WCD) regularization to improve polygenic risk score predictions for complex diseases, specifically gender-specific cancers, using the UK Biobank dataset. Our DNN model with WCD outperformed both conventional PRS models and DNN models without WCD, demonstrating the importance of regularization techniques in enhancing model performance and capturing non-linear effects and interactions in genomic data. These findings contribute to a better understanding of genetic architecture, facilitating personalized interventions based on individual genetic profiles and ultimately benefiting patient care and health outcomes.
Prospective Cohort Study of Surgical Site Infections Following Single Dose Antibiotic Prophylaxis in Caesarean Section at a Tertiary Care Teaching Hospital in Medchal, India
Authors: Basany Kalpana , Chaudhuri Sirshendu , Shailaja Lakshmi , Agiwal Varun , Angaali Neelima , Nirupama AY , Shailendra D , Haggerty Catherine , Reddy PS 
Published: May 2023

AbstractBackgroundCaesarean section (CS) is a considered to be a life-saving operative intervention for women and new-borns in certain antepartum and intrapartum conditions. Caesarean delivery may be accompanied by several complications including surgical site infections (SSI). However, there is a significant lack of uniformity in the administration of antibiotics for preventing surgical site infections (SSI) following Caesarean deliveries. The present study was conducted to determine the incidence of post CS SSI following the adoption of single-dose antibiotic prophylaxis as recommended by WHO at a tertiary care teaching hospital in Medchal, India. Also, to identify the risk factors of SSI and reported the bacteriological profiles and the antimicrobial sensitivity and resistance pattern of the culture positive isolatesMain objectivesTo estimate the incidence of surgical site infections (SSIs) according to CDC criteria following WHO-recommended single-dose antibiotic prophylaxis for Caesarean section at a tertiary care teaching hospital in Medchal, India.MethodsA prospective hospital-based study was conducted between June 2017 and December 2019, in which women who underwent Caesarean delivery were followed up for 30 days post-delivery. Clinical details were collected using a structured questionnaire, and participants were followed up weekly after discharge to document any signs and symptoms of SSI. Symptomatic patients were requested to come to the hospital for further investigation and treatment. Standard microbiological tests were conducted to detect microorganisms and their antibiotic sensitivity.ResultsThe study included 2,015 participants with a mean age of 24.1 years. The majority were multigravida (n=1,274, 63.2%) and underwent emergency Caesarean delivery (n=1,226, 60.8%). Of these, 92 participants (4.6%, 95% CI: 3.7% to 5.6%) developed surgical site infections, with 91 (98.9%) having superficial and 1 (1.1%) having a deep infection. Among those who developed an SSI, 84 (91.3%) did so during their hospital stay, while 8 (8.7%) developed an SSI at home. The adjusted relative risk (aRR) for developing an SSI was 2.5 (95% CI: 1.4 to 4.6; Power 99.9%) among obese women and 2.3 (95% CI: 1.1 to 4.7; Power 100%) among women aged 25 years or younger. Microbial growth was observed in 75.8% (n=50/66) samples. The most common organisms identified wereStaphylococcus aureus(n=23, 46.0%),Klebsiella sp. (n=13, 26.0%), andEscherichia coli(n=12, 24.0%).ConclusionGiven the low rate of SSI following Caesarean deliveries subjected to single-dose antibiotic prophylaxis and the increased risk noted with obesity, it is rationale to practice the latest recommendations of WHO including higher dose for obese patients, unless there is compelling evidence to do otherwise in any context.
Glyoxal Acid-Free (GAF) histological fixative is a suitable alternative to formalin – results from an open label comparative non-inferiority study
Authors: Ryska Ales , Sapino Anna , Landolfi Stefania , Valero Irene Sansano , Cajal Santiago Ramon y , Oliveira Pedro , Detillo Paolo , Lianas Luca , Frexia Francesca , Nicolosi Pier Andrea , Monti Tommaso , Bussolati Benedetta , Marchiò Caterina , Bussolati Gianni 
Published: May 2023

AbstractFormalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field.In the present study, we tested an innovative fixative, Glyoxal Acid-Free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard Phosphate Buffered Formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local centre reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ±0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ±0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organ tested. The present clinical performance study, performed following the international standard for performance evaluation ofin vitrodiagnostic medical devices, highlights the capability of GAF to ensure both, structural preservation and diagnostic value of the preparations.
Optimal Non-Pharmaceutical Interventions Considering Limited Healthcare System Capacity and Economic Costs in the Republic of Korea
Authors: Lim Yuna , Ko Youngsuk , Mendoza Renier , Mendoza Victoria May P. , Lee Jongmin , Jung Eunok 
Published: May 2023

AbstractDue to the relatively low severity and fatality rates of the omicron variant of COVID-19, strict non-pharmaceutical interventions (NPIs) with high economic costs may not be necessary. We develop a mathematical model of the COVID-19 outbreak in Korea that considers NPIs, variants, medical capacity, and economic costs. Using optimal control theory, we propose an optimal strategy for the omicron period. To suggest a realistic strategy, we consider limited hospital beds for severe cases and incorporate it as a penalty term in the objective functional using a logistic function. This transforms the constrained problem into an unconstrained one. Given that the solution to the optimal control problem is continuous, we propose the adoption of a sub-optimal control as a more practically implementable alternative. Our study demonstrates how to strategically balance the tradeoff between minimizing the economic cost for NPIs and ensuring that the number of severe cases in hospitals is manageable.
Neural Network Models for Sequence-Based TCR and HLA Association Prediction
Authors: Liu Si , Bradley Philip , Sun Wei 
Published: May 2023

AbstractT cells rely on their T cell receptors (TCRs) to recognize foreign antigens presented by human leukocyte antigen (HLA) proteins. TCRs contain a record of an individual’s past immune activities, and some TCRs are observed only in individuals with certain HLA alleles. As a result, characterising TCRs requires a thorough understanding of TCR-HLA associations. To this end, we propose a neural network method named Deep learning Prediction of TCR-HLA association (DePTH) to predict TCR-HLA associations based on their amino acid sequences. We show that the DePTH can be used to quantify the functional similarities of HLA alleles, and that these HLA similarities are associated with the survival outcomes of cancer patients who received immune checkpoint blockade treatment.
Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes
Authors: Rigby Charlotte , Sabsay Kimberly , Bisht Karishma , Eggink Dirk , Jalal Hamid , te Velthuis Aartjan J.W. 
Published: May 2023

AbstractRNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays andin silicosequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the IBV genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
Single cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction
Authors: Bae Seo-Gyeong , Yin Guo Nan , Ock Jiyeon , Suh Jun-Kyu , Ryu Ji-Kan , Park Jihwan 
Published: May 2023

AbstractErectile dysfunction (ED) affects a significant proportion of men aged 40–70 and is caused by cavernous tissue dysfunction. Presently, the most common treatment for ED is phosphodiesterase 5 inhibitors; however, this is less effective in patients with severe vascular disease such as diabetic ED. Therefore, there is a need for development of new treatment, which requires a better understanding of the cavernous microenvironment and cell-cell communications under diabetic condition. Pericytes are vital in penile erection; however, their dysfunction due to diabetes remains unclear. In this study, we performed single-cell RNA sequencing to understand the cellular landscape of cavernous tissues and cell type-specific transcriptional changes in diabetic ED. We found a decreased expression of genes associated with collagen or extracellular matrix organization and angiogenesis in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes. Moreover, the newly identified pericyte-specific marker, Limb-bud and Heart (Lbh), in mouse and human cavernous tissues, clearly distinguishing pericytes from smooth muscle cells. Cell–cell interaction analysis revealed that pericytes are involved in angiogenesis, adhesion, and migration by communicating with other cell types in the corpus cavernosum; however, these interactions were highly reduced under diabetic conditions. Lbh expression is low in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration. Furthermore, the LBH-interacting proteins (Crystallin Alpha B and Vimentin) were identified in mouse cavernous pericytes through LC-MS/MS analysis, indicating that their interactions were critical for maintaining pericyte function. Thus, our study reveals novel targets and insights into the pathogenesis of ED in patients with diabetes.Impact statement:Single-cell RNA sequencing analysis of diabetic mouse cavernous tissue revealed that LBH as a novel pericyte marker and may interact with Crystallin Alpha B and Vimentin to promote neurovascular regeneration.
Stoichiometric expression of messenger polycistrons by eukaryotic ribosomes (SEMPER) for compact, ratio-tunable multi-gene expression from single mRNAs
Authors: Duan Mengtong , Dev Ishaan , Lu Andrew , You Mei Yi , Shapiro Mikhail G. 
Published: May 2023

ABSTRACTApplications of mammalian synthetic biology increasingly require the ability to express multiple proteins at user-determined stoichiometries from single, compactly encoded transcripts. Here we present an approach for expressing multiple open reading frames (ORFs) from a single transcript, taking advantage of the leaky scanning model of translation initiation. In this method, adjacent ORFs are translated from a single messenger RNA at tunable ratios determined by their order in the sequence and the strength of their translation initiation sites. We call this approach Stoichiometric Expression of Messenger Polycistrons by Eukaryotic Ribosomes (SEMPER). We demonstrate the principles of this approach by expressing up to three fluorescent proteins from one plasmid in two different cell lines. We then use it to encode a stoichiometrically tuned polycistronic construct encoding gas vesicle acoustic reporter genes, showing that enforcing the optimal ratio in every cell enables efficient formation of the multi-protein complex while minimizing cellular toxicity. Finally, we demonstrate the polycistronic expression of two fluorescent proteins from single mRNAs made throughin vitrotranscription and delivered to cells. SEMPER will enable a broad range of applications requiring tunable expression from compact eukaryotic constructs.