bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous multifunctional transcriptome engineering by CRISPR RNA scaffold
Authors: Liu Zukai , Jillette Nathaniel , Robson Paul , Cheng Albert Wu
Published: July 2023

RNA processing and metabolism are subjected to precise regulation in the cell to ensure integrity and functions of RNA. Though targeted RNA engineering has become feasible with the discovery and engineering of the CRISPR-Cas13 system, simultaneous modulation of different RNA processing steps remains unavailable. In addition, off-target events resulting from effectors fused with dCas13 limit its application. Here we developed a novel platform, Combinatorial RNA Engineering via Scaffold Tagged gRNA (CREST), which can simultaneously execute multiple RNA modulation functions on different RNA targets. In CREST, RNA scaffolds are appended to the 3’ end of Cas13 gRNA and their cognate RNA binding proteins are fused with enzymatic domains for manipulation. Taking RNA alternative splicing, A-to-G and C-to-U base editing as examples, we developed bifunctional and tri-functional CREST systems for simultaneously RNA manipulation. Furthermore, by fusing two split fragments of the deaminase domain of ADAR2 to dCas13 and/or PUFc respectively, we reconstituted its enzyme activity at target sites. This split design can reduce nearly 99% of off-target events otherwise induced by a full-length effector. The flexibility of the CREST framework will enrich the transcriptome engineering toolbox for the study of RNA biology.
PEPseq quantifies transcriptome-wide changes in protein occupancy and reveals selective translational repression after translational stress
Authors: Trendel Jakob , Boileau Etienne , Jochem Marco , Dieterich Christoph , Krijgsveld Jeroen
Published: July 2023

Post-transcriptional gene regulation is accomplished by the interplay of the transcriptome with RNA-binding proteins, which occurs in a dynamic manner in response to altered cellular conditions. Recording the combined occupancy of all proteins binding to the transcriptome offers the opportunity to interrogate if a particular treatment leads to any interaction changes, pointing to sites in RNA that undergo post-transcriptional regulation. Here, we establish a method to monitor protein occupancy in a transcriptome-wide fashion by RNA sequencing. To this end, peptide-enhanced pull-down for RNA sequencing (or PEPseq) uses metabolic RNA labelling with 4-thiouridine (4SU) for light-induced protein–RNA crosslinking, and N-hydroxysuccinimide (NHS) chemistry to isolate protein-crosslinked RNA fragments across all long RNA biotypes. We use PEPseq to investigate changes in protein occupancy during the onset of arsenite-induced translational stress in human cells and reveal an increase of protein interactions in the coding region of a distinct set of mRNAs, including mRNAs coding for the majority of cytosolic ribosomal proteins. We use quantitative proteomics to demonstrate that translation of these mRNAs remains repressed during the initial hours of recovery after arsenite stress. Thus, we present PEPseq as a discovery platform for the unbiased investigation of post-transcriptional regulation.
Establishing artificial gene connections through RNA displacement–assembly-controlled CRISPR/Cas9 function
Authors: Wang Wei-Jia , Lin Jiao , Wu Chao-Qun , Luo Ai-Ling , Xing Xiwen , Xu Liang
Published: July 2023

Construction of synthetic circuits that can reprogram genetic networks and signal pathways is a long-term goal for manipulation of biosystems. However, it is still highly challenging to build artificial genetic communications among endogenous RNA species due to their sequence independence and structural diversities. Here we report an RNA-based synthetic circuit that can establish regulatory linkages between expression of endogenous genes in both Escherichiacoli and mammalian cells. This design employs a displacement–assembly approach to modulate the activity of guide RNA for function control of CRISPR/Cas9. Our experiments demonstrate the great effectiveness of this RNA circuit for building artificial connections between expression of originally unrelated genes. Both exogenous and naturally occurring RNAs, including small/microRNAs and long mRNAs, are capable of controlling expression of another endogenous gene through this approach. Moreover, an artificial signal pathway inside mammalian cells is also successfully established to control cell apoptosis through our designed synthetic circuit. This study provides a general strategy for constructing synthetic RNA circuits, which can introduce artificial connections into the genetic networks of mammalian cells and alter the cellular phenotypes.
A clickable melphalan for monitoring DNA interstrand crosslink accumulation and detecting ICL repair defects in Fanconi anemia patient cells
Authors: Berrada Sara , Martínez-Balsalobre Elena , Larcher Lise , Azzoni Violette , Vasquez Nadia , Da Costa Mélanie , Abel Sébastien , Audoly Gilles , Lee Lara , Montersino Camille , Castellano Rémy , Combes Sébastien , Gelot Camille , Ceccaldi Raphaël , Guervilly Jean-Hugues , Soulier Jean , Lachaud Christophe
Published: July 2023

Fanconi anemia (FA) is a genetic disorder associated with developmental defects, bone marrow failure and cancer. The FA pathway is crucial for the repair of DNA interstrand crosslinks (ICLs). In this study, we have developed and characterized a new tool to investigate ICL repair: a clickable version of the crosslinking agent melphalan which we name click-melphalan. Our results demonstrate that click-melphalan is as effective as its unmodified counterpart in generating ICLs and associated toxicity. The lesions induced by click-melphalan can be detected in cells by post-labelling with a fluorescent reporter and quantified using flow cytometry. Since click-melphalan induces both ICLs and monoadducts, we generated click-mono-melphalan, which only induces monoadducts, in order to distinguish between the two types of DNA repair. By using both molecules, we show that FANCD2 knock-out cells are deficient in removing click-melphalan-induced lesions. We also found that these cells display a delay in repairing click-mono-melphalan-induced monoadducts. Our data further revealed that the presence of unrepaired ICLs inhibits monoadduct repair. Finally, our study demonstrates that these clickable molecules can differentiate intrinsic DNA repair deficiencies in primary FA patient cells from those in primary xeroderma pigmentosum patient cells. As such, these molecules may have potential for developing diagnostic tests.
Ribosomal proteins can hold a more accurate record of bacterial thermal adaptation compared to rRNA
Authors: van den Elzen Antonia , Helena-Bueno Karla , Brown Charlotte R , Chan Lewis I , Melnikov Sergey V
Published: July 2023

Ribosomal genes are widely used as ‘molecular clocks’ to infer evolutionary relationships between species. However, their utility as ‘molecular thermometers’ for estimating optimal growth temperature of microorganisms remains uncertain. Previously, some estimations were made using the nucleotide composition of ribosomal RNA (rRNA), but the universal application of this approach was hindered by numerous outliers. In this study, we aimed to address this problem by identifying additional indicators of thermal adaptation within the sequences of ribosomal proteins. By comparing sequences from 2021 bacteria with known optimal growth temperature, we identified novel indicators among the metal-binding residues of ribosomal proteins. We found that these residues serve as conserved adaptive features for bacteria thriving above 40°C, but not at lower temperatures. Furthermore, the presence of these metal-binding residues exhibited a stronger correlation with the optimal growth temperature of bacteria compared to the commonly used correlation with the 16S rRNA GC content. And an even more accurate correlation was observed between the optimal growth temperature and the YVIWREL amino acid content within ribosomal proteins. Overall, our work suggests that ribosomal proteins contain a more accurate record of bacterial thermal adaptation compared to rRNA. This finding may simplify the analysis of unculturable and extinct species.
Duty-related trauma and PTSD symptoms in US urban firefighters
Authors: Pao C , Arbona C , Fan W , Tran J
Published: July 2023

Background

Little is known about the multi-dimensional nature of traumatic duty-related events encountered by firefighters in relation to their post-traumatic stress disorder (PTSD) risk.

Aims

To describe the types of duty-related events encountered by career firefighters and explore if years in the fire service or total event load moderated the association of trauma exposure to PTSD symptoms.

Methods

Participants included 755 career, male firefighters (19% of the department’s firefighters and 76% of those who accessed the electronic anonymous survey). The Duty-Related Incident Stressors scale was used to assess exposure to 25 potentially traumatic events (event load) and self-appraisal of the stress associated with these events, grouped by type of event (indirect, direct and colleague-related). The Post-Traumatic Stress Disorder Checklist was used to assess PTSD symptoms.

Results

Firefighters rated colleague-related events as the most stressful, followed by indirect and direct events. Event load (r = 0.25) and indirect, direct and colleague-related events stress (r = 0.32–0.35) were positively associated with PTSD symptoms. Results of moderation analyses indicated that event load served as a risk factor in the relation of indirect events stress to PTSD symptoms, and as a buffer in the relation of direct events stress to PTSD symptoms. Years in the fire service were not associated with PTSD symptoms nor moderated the relation of event stress to PTSD symptoms.

Conclusions

Findings underscored the importance of considering the differential effects that types of duty-related traumatic events and cumulative exposure to trauma may have on firefighters’ PTSD symptoms.
Thermosensitive SUMOylation of TaHsfA1 defines a dynamic ON/OFF molecular switch for the heat stress response in wheat
Authors: Wang Haoran , Feng Man , Jiang Yujie , Du Dejie , Dong Chaoqun , Zhang Zhaoheng , Wang Wenxi , Liu Jing , Liu Xiangqing , Li Sufang , Chen Yongming , Guo Weilong , Xin Mingming , Yao Yingyin , Ni Zhongfu , Sun Qixin , Peng Huiru , Liu Jie
Published: July 2023

Dissecting genetic components in crop plants associated with heat stress (HS) sensing and adaptation will facilitate the design of modern crop varieties with improved thermotolerance. However, the molecular mechanisms underlying the ON/OFF switch controlling HS responses (HSRs) in wheat (Triticum aestivum) remain largely unknown. In this study, we focused on the molecular action of TaHsfA1, a class A heat shock transcription factor, in sensing dynamically changing HS signals and regulating HSRs. We show that the TaHsfA1 protein is modified by small ubiquitin–related modifier (SUMO) and that this modification is essential for the full transcriptional activation activity of TaHsfA1 in triggering downstream gene expression. During sustained heat exposure, the SUMOylation of TaHsfA1 is suppressed, which partially reduces TaHsfA1 protein activity, thereby reducing the intensity of downstream HSRs. In addition, we demonstrate that TaHsfA1 interacts with the histone acetyltransferase TaHAG1 in a thermosensitive manner. Together, our findings emphasize the importance of TaHsfA1 in thermotolerance in wheat. In addition, they define a highly dynamic SUMOylation-dependent “ON/OFF” molecular switch that senses temperature signals and contributes to thermotolerance in crops.
Molecular bases of strawberry fruit quality traits: Advances, challenges, and opportunities
Authors: Liu Zhongchi , Liang Tong , Kang Chunying
Published: July 2023

The strawberry is one of the world's most popular fruits, providing humans with vitamins, fibers, and antioxidants. Cultivated strawberry (Fragaria × ananassa) is an allo-octoploid and highly heterozygous, making it a challenge for breeding, quantitative trait locus (QTL) mapping, and gene discovery. Some wild strawberry relatives, such as Fragaria vesca, have diploid genomes and are becoming laboratory models for the cultivated strawberry. Recent advances in genome sequencing and CRISPR-mediated genome editing have greatly improved the understanding of various aspects of strawberry growth and development in both cultivated and wild strawberries. This review focuses on fruit quality traits that are most relevant to the consumers, including fruit aroma, sweetness, color, firmness, and shape. Recently available phased-haplotype genomes, single nucleotide polymorphism (SNP) arrays, extensive fruit transcriptomes, and other big data have made it possible to locate key genomic regions or pinpoint specific genes that underlie volatile synthesis, anthocyanin accumulation for fruit color, and sweetness intensity or perception. These new advances will greatly facilitate marker-assisted breeding, the introgression of missing genes into modern varieties, and precise genome editing of selected genes and pathways. Strawberries are poised to benefit from these recent advances, providing consumers with fruit that is tastier, longer-lasting, healthier, and more beautiful.
Rice transformation treatments leave specific epigenome changes beyond tissue culture
Authors: Hsieh Jo-Wei Allison , Chang Pearl , Kuang Lin-Yun , Hsing Yue-Ie C , Chen Pao-Yang
Published: July 2023

During transgenic plant production, tissue culture often carries epigenetic, and genetic changes that underlie somaclonal variations, leading to unpredictable phenotypes. Additionally, specific treatments for rice (Oryza sativa) transformation processes may individually or jointly contribute to somaclonal variations, but their specific impacts on rice epigenomes toward transcriptional variations remain unknown. Here, the impact of individual transformation treatments on genome-wide DNA methylation and the transcriptome were examined. In addition to activating stress-responsive genes, individual transformation components targeted different gene expression modules that were enriched in specific functional categories. The transformation treatments strongly impacted DNA methylation and expression; 75% were independent of tissue culture. Furthermore, our genome-wide analysis showed that the transformation treatments consistently resulted in global hypo-CHH methylation enriched at promoters highly associated with downregulation, particularly when the promoters were colocalized with miniature inverted-repeat transposable elements. Our results clearly highlight the specificity of impacts triggered by individual transformation treatments during rice transformation with the potential association between DNA methylation and gene expression. These changes in gene expression and DNA methylation resulting from rice transformation treatments explain a significant portion of somaclonal variations, that is, way beyond the tissue culture effect.
Relative role of community transmission and campus contagion in driving the spread of SARS-CoV-2: Lessons from Princeton University
Authors: Park Sang Woo , Daskalaki Irini , Izzo Robin M , Aranovich Irina , te Velthuis Aartjan J W , Notterman Daniel A , Metcalf C Jessica E , Grenfell Bryan T
Published: July 2023

Mathematical models have played a crucial role in exploring and guiding pandemic responses. University campuses present a particularly well-documented case for institutional outbreaks, thereby providing a unique opportunity to understand detailed patterns of pathogen spread. Here, we present descriptive and modeling analyses of SARS-CoV-2 transmission on the Princeton University (PU) campus—this model was used throughout the pandemic to inform policy decisions and operational guidelines for the university campus. Epidemic patterns between the university campus and surrounding communities exhibit strong spatiotemporal correlations. Mathematical modeling analysis further suggests that the amount of on-campus transmission was likely limited during much of the wider pandemic until the end of 2021. Finally, we find that a superspreading event likely played a major role in driving the Omicron variant outbreak on the PU campus during the spring semester of the 2021–2022 academic year. Despite large numbers of cases on campus in this period, case levels in surrounding communities remained low, suggesting that there was little spillover transmission from campus to the local community.
Neuro- and cognitive diversity in surgery and allied professions: celebrating difference and optimising performance
Authors: Bowman Chris R , Lewis Wyn G
Published: July 2023

Neurotypicality (NT) and neurodiversity (ND) are two terms used to describe separate ways of thinking and experiencing the world. The prevalence of ND within surgery and allied professions is poorly studied or understood but is likely to be significant and increasing. If our aim is to be truly inclusive, ND's effects on teams and our willingness and ability to adapt adequately must improve.
Geographic disparities of cardiovascular and cancer mortality in the USA: 1981–2019
Authors: Lebakula V , Cosby A G
Published: July 2023

Background

Cardiovascular and cancer mortality are the two leading causes of death in the developed world including the USA. However, mortality trends for these diseases are highly dynamic, and the geographic landscape is in transition. We analyze patterns of mortality improvement at county level during recent decades focusing on mortality decline and geographic diversity.

Methods

We grouped age-adjusted mortality rates of cardiovascular and cancer diseases from CDC WONDER for 2959 US counties into 3-year time periods to improve reliability. We calculated percent mortality decrease between 1981–83 and 2016–19 for both causes to quantify mortality improvements for counties.

Results

Using standard deviation as an index of disparities, place-based cancer mortalities were 68% larger than cardiovascular disparities. Significantly, 566 US counties had same or higher rates of cancer mortality in 2019 as in 1981. The geographic distribution of mortality improvement in either cause tends to favor largely populated areas along coasts. Less-populated, rural places in the interior and southeastern regions were experiencing less improvement.

Conclusions

At the county level, large place-based disparities exist for both causes of death with the magnitude of disparities being substantially larger for the reduction in cancer deaths. Put differently, place matters, more for cancer than cardiovascular mortality.
Lung ultrasound compared to computed tomography detection and automated quantification of systemic sclerosis-associated interstitial lung disease: preliminary study
Authors: Mohammad Reza Beigi Davide , Pellegrino Greta , Loconte Michele , Landini Nicholas , Mattone Monica , Paone Gregorino , Truglia Simona , Di Ciommo Francesca Romana , Bisconti Ilaria , Cadar Marius , Stefanantoni Katia , Panebianco Valeria , Conti Fabrizio , Riccieri Valeria
Published: July 2023

Background

Lung ultrasound (LUS) is a promising tool for detecting SSc-associated interstitial lung disease (SSc-ILD). Currently, consensus on the best LUS findings and execution technique is lacking.

Objectives

To compare qualitative and quantitative assessment of B-lines and pleural line (PL) alterations in SSc-ILD with chest CT analysis.

Methods

During 2021–2022, consecutive SSc patients according to 2013 ACR/EULAR classification criteria underwent pulmonary functional tests (PFTs). On the same day, if a CT was performed over a ± 6 months period, LUS was performed by two certified blinded operators using a 14-scans method. The ≥10 B-lines cut-off proposed by Tardella and the Fairchild’s PL criteria fulfilment were selected as qualitative findings. As quantitative assessment, total B-lines number and the quantitative PL score adapted from the semi-quantitative Pinal-Fernandez score were collected. CT scans were evaluated by two thoracic radiologists for ILD presence, with further processing by automated texture analysis software (QCT).

Results

Twenty-nine SSc patients were enrolled. Both qualitative LUS scores were significantly associated to ILD presence on CT, with Fairchild’s PL criteria resulting in slightly more accuracy. Results were confirmed on multivariate analysis. All qualitative and quantitative LUS findings were found to be significantly associated with QCT ILD extension and radiological abnormalities. Mid and basal PL quantitative score correlated with mid and basal QCT ILD extents. Both B-lines and PL alterations differently correlated with PFTs and clinical variables.

Conclusion

This preliminary study suggests the utility of a comprehensive LUS assessment for SSc-ILD detection compared with CT and QCT.
Diversity and Pathobiology of an Ilarvirus Unexpectedly Detected in Diverse Plants and Global Sequencing Data
Authors: Rivarez Mark Paul Selda , Faure Chantal , Svanella-Dumas Laurence , Pecman Anja , Tušek-Žnidaric Magda , Schönegger Deborah , De Jonghe Kris , Blouin Arnaud , Rasmussen David A. , Massart Sebastien , Ravnikar Maja , Kutnjak Denis , Marais Armelle , Candresse Thierry
Published: July 2023

High-throughput sequencing (HTS) and sequence mining tools revolutionized virus detection and discovery in recent years, and implementing them with classical plant virology techniques results in a powerful approach to characterize viruses. An example of a virus discovered through HTS is Solanum nigrum ilarvirus 1 (SnIV1) ( Bromoviridae), which was recently reported in various solanaceous plants from France, Slovenia, Greece, and South Africa. It was likewise detected in grapevines ( Vitaceae) and several Fabaceae and Rosaceae plant species. Such a diverse set of source organisms is atypical for ilarviruses, thus warranting further investigation. In this study, modern and classical virological tools were combined to accelerate the characterization of SnIV1. Through HTS-based virome surveys, mining of sequence read archive datasets, and a literature search, SnIV1 was further identified from diverse plant and non-plant sources globally. SnIV1 isolates showed relatively low variability compared with other phylogenetically related ilarviruses. Phylogenetic analyses showed a distinct basal clade of isolates from Europe, whereas the rest formed clades of mixed geographic origin. Furthermore, systemic infection of SnIV1 in Solanum villosum and its mechanical and graft transmissibility to solanaceous species were demonstrated. Near-identical SnIV1 genomes from the inoculum ( S. villosum) and inoculated Nicotiana benthamiana were sequenced, thus partially fulfilling Koch's postulates. SnIV1 was shown to be seed-transmitted and potentially pollen-borne, has spherical virions, and possibly induces histopathological changes in infected N. benthamiana leaf tissues. Overall, this study provides information to better understand the diversity, global presence, and pathobiology of SnIV1; however, its possible emergence as a destructive pathogen remains uncertain.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Colorectal cancer screening
Authors: Mollman Burton James
Published: July 2023

Because an estimated 10.5% of new colorectal cancer (CRC) cases occur in patients under age 50 years, the US Preventive Services Task Force in 2021 recommended CRC screening for adults ages 45 to 49 years. The prevalence of up-to-date CRC screening with any recommended test among patients age 45 years and older in the United States is only 59% in 2023, indicating that existing screening practices are ineffective. Screening options now include invasive and noninvasive measures. Multi-target stool DNA (MT-sDNA) testing is a simple, low-risk, noninvasive test that provides excellent sensitivity and specificity, is cost-effective, and may increase patient screening rates. CRC screening guideline recommendations and alternative screening methods may help improve patient outcomes and reduce morbidity and mortality. This article describes MT-sDNA testing, its effectiveness, recommended use, and potential expanding role as a screening option.
The changing employment of physicians, NPs, and PAs
Authors: Hooker Roderick S. , Christian Robert L.
Published: July 2023

Information on the employment of patient-care clinicians is needed for policy planning and human resource management. The 2021 Bureau of Labor Statistics (BLS) employment data were probed for occupational settings of 698,700 physicians and surgeons, 246,690 NPs, and 139,100 physician associates/assistants (PAs). These three healthcare professionals accounted for about 1.1 million medical and surgical clinicians serving a US population of 331.5 million. Clinician demographics differ—in 2021, the median age of physicians was 45 years; NPs, 43 years; and PAs, 39 years. The largest employment location is “office of a physician” (physician, 53%; NP, 47%; PA, 51%), followed by hospitals (physician, 25%; NP, 25%; PA, 23%), and outpatient centers (physician, 4%; NP, 9%; PA, 10%). The 10-year job outlook predicts physician growth at 3%, NPs at 46%, and PAs at 28%. NP and PA employment is growing more than that of physicians because of constrained physician postgraduate education funding. Other factors influencing employment changes include medical practice mergers, the rising value of team-based care, the cost of new medical schools, and task shifting.
Reliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008–2017*
Authors: Lawandi Alexander , Oshiro Marissa , Warner Sarah , Diao Guoqing , Strich Jeffrey R. , Babiker Ahmed , Rhee Chanu , Klompas Michael , Danner Robert L. , Kadri Sameer S.
Published: July 2023

OBJECTIVES:

Serum procalcitonin is often ordered at admission for patients with suspected sepsis and bloodstream infections (BSIs), although its performance characteristics in this setting remain contested. This study aimed to evaluate use patterns and performance characteristics of procalcitonin-on-admission in patients with suspected BSI, with or without sepsis.

DESIGN:

Retrospective cohort study.

SETTING:

Cerner HealthFacts Database (2008–2017).

PATIENTS:

Adult inpatients (≥ 18 yr) who had blood cultures and procalcitonin drawn within 24 hours of admission.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Testing frequency of procalcitonin was determined. Sensitivity of procalcitonin-on-admission for detecting BSI due to different pathogens was calculated. Area under the receiver operating characteristic curve (AUC) was calculated to assess discrimination by procalcitonin-on-admission for BSI in patients with and without fever/hypothermia, ICU admission and sepsis defined by Centers for Disease Control and Prevention Adult Sepsis Event criteria. AUCs were compared using Wald test and p values were adjusted for multiple comparisons. At 65 procalcitonin-reporting hospitals, 74,958 of 739,130 patients (10.1%) who had admission blood cultures also had admission procalcitonin testing. Most patients (83%) who had admission day procalcitonin testing did not have a repeat procalcitonin test. Median procalcitonin varied considerably by pathogen, BSI source, and acute illness severity. At a greater than or equal to 0.5 ng/mL cutoff, sensitivity for BSI detection was 68.2% overall, ranging between 58.0% for enterococcal BSI without sepsis and 96.4% for pneumococcal sepsis. Procalcitonin-on-admission displayed moderate discrimination at best for overall BSI (AUC, 0.73; 95% CI, 0.72–0.73) and showed no additional utility in key subgroups. Empiric antibiotic use proportions were not different between blood culture sampled patients with a positive procalcitonin (39.7%) and negative procalcitonin (38.4%) at admission.

CONCLUSIONS:

At 65 study hospitals, procalcitonin-on-admission demonstrated poor sensitivity in ruling out BSI, moderate-to-poor discrimination for both bacteremic sepsis and occult BSI and did not appear to meaningfully alter empiric antibiotic usage. Diagnostic stewardship of procalcitonin-on-admission and risk assessment of admission procalcitonin-guided clinical decisions is warranted.
Utilization of Transthoracic Echocardiography Is Associated with a Decreased 6-month Readmission Rate in Hospitalized Heart Failure: A Propensity Score-matched Analysis
Authors: Fu Zhiqing , Li Shan , Zhao Xiaoning , Wang Qiang
Published: July 2023

Objective:

Repeated hospitalization due to congestion is a characteristic of the whole course of heart failure. Echocardiography can be used to assess cardiac function and volume status. However, whether echocardiography can reduce the rehospitalization rate remains unclear. This study aimed to evaluate the impact of transthoracic echocardiography (TTE) use on readmission rates in hospitalized patients with heart failure.

Methods:

The study was based on the Zigong heart failure database, which contained information on 2,008 adult patients with heart failure admitted to the Zigong Fourth People’s Hospital (Sichuan Province, China) from December 2016 to June 2019. Patients were divided into 2 groups according to the usage of TTE on the day of hospital admission (TTE group (1,371 patients) and no TTE group (637 patients), respectively). The primary outcome was the 6-month readmission rate. The statistical approaches used included multivariate Cox regression, propensity score analysis, and an inverse probability weighting model to ensure the robustness of the findings.

Results:

A significant reduction in 6-month readmission rate was observed among the TTE group compared with the no TTE group (hazard ratio = 0.60, 95% confidence interval (CI) = 0.52–0.69, P < 0.001). The frequencies of intravenous nitrates, diuretics, and inotropes during hospitalization were significantly higher in the TTE group compared with those in the no TTE group (10.9% vs. 8.3%, 88.5% vs. 86.2%, and 66.9% vs. 65.6%, respectively, all P < 0.001). The proportion of patients returning to the emergency department within 6 months was significantly lower in the TTE group compared with the no TTE group (35.6% vs. 50.3%, P < 0.001).

Conclusions:

Utilization of TEE on admission day was associated with a reduced 6-month readmission rate in hospitalized patients with heart failure.
Persistent increase and improved survival of stage I lung cancer based on a large-scale real-world sample of 26,226 cases
Authors: Wang Chengdi , Shao Jun , Song Lujia , Ren Pengwei , Liu Dan , Li Weimin
Published: July 2023

Background:

Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes.

Methods:

Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated usingχ2tests. Overall survival (OS) was calculated through the Kaplan–Meier method.

Results:

A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations includingEGFR(52.14%),KRAS(12.14%), andALK(8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutatedEGFRhad better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009–2013, the prognosis of stage I patients in 2014–2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports.

Conclusions:

Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.
Regional anaesthesia practices: insights from a European survey
Authors: Konijn Arjan , Aldecoa Cesar , Benhamou Dan , Frkovic Vedran , Kessler Paul , Marhofer Peter
Published: July 2023

BACKGROUND

The use of regional anaesthesia has increased and evolved over the past two decades but to what extent is unclear. Moreover, there is no clear standardisation of best practice in the current European landscape, which could result in inconsistencies in regional anaesthesia in practice.

OBJECTIVES

The objective of this survey was to explore regional anaesthesia practices across Europe, including the differences in procedures, use of ultrasound, reporting of complications, guidelines, training and patient safety implementation.

DESIGN

A Faculty of European regional anaesthesia experts developed a survey of 27 questions focused on respondent and institution profile, anaesthesia services, patient and safety management, training, use of guidelines, and the implementation of NRFitTM [neuraxial device connectors that meet the International Organisation for Standardisation (ISO) requirements].

SETTINGS

The survey was disseminated across several European countries via professional networks.

PARTICIPANTS

There were 794 respondents from 36 European countries.

RESULTS

The survey demonstrated that use of regional anaesthesia is growing in Europe and is supported by new technologies. Although some results are consistent with expected trends and applications (e.g. procedures predominantly performed by anaesthesiologists), there are inconsistencies in practice across European countries, especially in the specific regional anaesthesia procedures utilised for different clinical applications and the recording and reporting of regional anaesthesia complications. These inconsistencies also extended to which guidelines are primarily followed and how training is implemented. There were also variations in the general awareness and uptake of the ISO standard for NRFit.

CONCLUSION

The survey results highlight a clear need for standardisation and consistency in the use and management of regional anaesthesia across Europe. The faculty put forth several calls to action that could provide major steps in the right direction towards meeting that goal, including the establishment of European best practices, development of a complication reporting system and implementation of educational programmes to highlight the importance of NRFit.
Systemic diffuse large B-cell lymphoma manifesting initially as scalp hematoma after an acute head injury: Case report and literature review
Authors: Huang Peng-Chan , Yao Wen-Teng , Jhuang Jie-Yang , Tsai Cheng-Chia , Chen Shiu-Jau , Yang Chih-Chuan
Published: July 2023

Systemic diffuse large B-cell lymphoma (DLBCL) manifesting as a scalp mass is rare but serious and must be treated aggressively, with neurosurgical intervention. We report a rare case of 56-year-old woman with a 1-month history of persistent scalp hematoma over the left parietal and occipital regions of the scalp after blunt head injury which was diagnosed as DLBCL after the excision.
Trends in the incidence of adrenocortical carcinoma and pheochromocytoma/paraganglioma in Taiwan
Authors: Tsai Chung-Hsin , Huang Tun-Sung , Cheng Shih-Ping
Published: July 2023

Background

Adrenal malignancies are rare endocrine tumors. Recent epidemiological studies suggest that incidence rates of adrenal malignancies are increased in certain countries. In this study, we aimed to analyze temporal trends in the incidence of adrenocortical carcinoma and pheochromocytoma/paraganglioma (PPGL).

Methods

Cases of adrenal malignancies were identified from the Taiwan cancer registry, and age-standardized incidence rates (ASRs) were calculated. Annual percent change (APC) or average APC was obtained using joinpoint regression models.

Results

The ASRs of adrenocortical carcinoma ranged from 0.021 to 0.135 per 100 000 person-years. The average APC between 1995 and 2020 was 6.633% (95% confidence interval, 2.740 to 9.403). The ASRs of PPGL ranged from 0.005 to 0.056 per 100 000 person-years before 2017 and, because of changes in diagnostic criteria, the median ASR of PPGL rose to 0.314 per 100 000 person-years after 2017. The APC between 1996 and 2016 was 3.554% (95% confidence interval, -1.103 to 8.264).

Conclusions

The annual incidence of adrenocortical carcinoma has significantly increased in Taiwan over the past two decades. The incidence of malignant PPGL remained stable over this time period.
The Impact of Reference Standard on Diagnostic Testing Characteristics for Carpal Tunnel Syndrome: A Systematic Review
Authors: Bennett Olivia M. , Sears Erika D.
Published: July 2023

Background:

Lack of a reliable reference standard for carpal tunnel syndrome (CTS) diagnosis could impact the diagnostic test characteristics. This systematic review sought to evaluate differences in the accuracy of CTS diagnostic modalities based on the reference standard used.

Methods:

A systematic review was performed following PRISMA guidelines to investigate diagnostic modalities used in CTS. A literature search of Embase, PubMed, and Cochrane Reviews was conducted for the years of 2010–2021 for primary data, and 113 studies met final inclusion criteria. Studies were stratified based on the reference standard utilized and diagnostic modality assessed, and the weighted means of the sensitivities and specificities were calculated.

Results:

Thirty-five studies used clinical diagnosis alone as a reference standard, and 78 studies used electrodiagnostic study (EDS). The specificity for MRI and ultrasound (US) were substantially lower when EDS was used as the reference standard. MRI was the test most affected by the reference standard used, showing increased sensitivity when using EDS as the reference compared to clinical diagnosis (77.1% versus 60.9%) and decreased specificity (87.6% versus 99.2%). Regardless of the reference standard used, all tests had anticipated false-positive and/or false-negative rates of at least 10%.

Conclusions:

Testing characteristics vary greatly based on the choice of reference standard, with the sensitivity of MRI most affected. Regardless of reference standard used, EDS, US, and MRI each had false-positive and/or false-negative rates too great to be appropriate for use as a screening examination.
Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis
Authors: Behari Jaideep , Gougol Amir , Wang Renwei , Luu Hung N. , Paragomi Pedram , Yu Yi-Chuan , Molinari Michele , Chopra Kapil , Malik Shahid M. , Geller David , Yuan Jian-Min
Published: July 2023

Background:

HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis.

Methods:

We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis.

Results:

Of 47,165 patients with NAFLD aged 40–89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3–43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex.

Conclusions:

Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC.
Histology, dimensions, and fluorescein staining characteristics of nodular and cuticular drusen in age-related macular degeneration
Authors: Evers Charles D. , Chen Ling , Messinger Jeffrey D. , Killingsworth Murray , Freund K. Bailey , Curcio Christine A.
Published: July 2023

Purpose:

To enable in vivo analysis of drusen composition and lifecycle, we assessed macular nodular and cuticular drusen using histology.

Methods:

Median and interquartile range (IQR) of base widths of single (non-confluent) nodular drusen in 3 sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography (FA); and two eyes of one patient with bilateral “starry sky” cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy.

Results:

All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of Bruch’s membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 µm (Source 1, N=128 drusen, IQR 7.7, 20.0 µm), 15.3 µm (Source 2, N=87, IQR 10.6, 20.5 µm), and 7.3 µm (Source 3, N=78, IQR 3.9, 14.1 µm).

Conclusions:

In three samples, >90% of solitary nodular drusen were <30 µm, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in FA. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include FA.
Scleral Fixation of Carlevale Intraocular Lens: A Systematic Review And Meta-Analysis
Authors: Ripa Matteo , Angunawela Romesh , Motta Lorenzo
Published: July 2023

Purpose:

The mean change in best-corrected visual acuity (BCVA), intraocular pressure (IOP), and endothelial cell counts (ECD) after intraocular lens (IOL) implantation and the incidence rate of postoperative complications were estimated by systematic review and meta-analysis to assess the surgical and refractive outcomes of the sutureless scleral fixation (SSF) Carlevale IOL.

Methods:

A literature search was conducted using PubMed, Embase, and Scopus. The weighted mean difference (WMD) was used to present the mean change in BCVA, IOP, and ECD after IOL implantation, whereas a proportional meta-analysis was used to estimate the pooled incidence rate of postoperative complications.

Results:

In the meta-analysis of thirteen studies involving 550 eyes, the pooled WMD of the mean change in BCVA showed a significant improvement in BCVA in patients who underwent Carlevale IOL implantation (WMD = 0.38, 95% CI: 0.30 to 0.46, p <0.001; heterogeneity (I2) =52.02%). The subgroup analyses indicated that the mean change in BCVA was not significantly higher according to the last follow-up visit, with no statistically significant subgroup effect. (p=0.21). (WMD up to six months: 0.34, 95% CI: 0.23 to 0.45, I2 = 58.32%, WMD up to twenty-four months: 0.42, 95% CI: 0.34 to 0.51, I2 = 38.08 %). In the meta-analysis of sixteen studies involving 608 eyes, the pooled incidence rate of postoperative complications was equal to 0.22 (CI: 0.13–0.32, I2 = 84.87, p ≤ 0.001).

Conclusions:

Carlevale IOL implantation represents a reliable method of restoring vision in eyes with missing capsular or zonular support.
Incidence of Graft Rejection in Descemet Membrane Endothelial Keratoplasty After COVID-19 mRNA Vaccination
Authors: Igarashi Ami , Shimizu Toshiki , Takeda Masato , Ida Yasutsugu , Ishida Atsuyuki , Yuda Kenji , Yuda Kentaro , Wajima Haguku , Kobayashi Akira , Nakashizuka Hiroyuki , Yamagami Satoru , Hayashi Takahiko
Published: July 2023

Purpose:

The aim of this study was to investigate the Descemet membrane endothelial keratoplasty (DMEK) rejection rate after COVID-19 vaccination with an mRNA vaccine.

Methods:

This was a multicenter, retrospective cohort study. A total of 198 patients who underwent DMEK between January 2006 and December 2020 were divided into 2 cohorts: consecutive patients who received at least 1 COVID-19 vaccination in 2021 (vaccination started from February 2021 in Japan) and nonvaccinated patients (control cohort). Patients who had a postoperative observation period of less than 90 days were excluded. The main outcome measurement was the incidence of graft rejection. A Cox proportional hazards regression model was used for comparisons with the nonvaccinated group.

Results:

Six rejection episodes were observed in 198 patients (124 nonvaccinated and 74 vaccinated patients), with 1 occurring in the nonvaccinated group and 5 in the vaccinated group. In the univariate model, vaccination had a significant effect on rejection episodes (P = 0.003). The effect of vaccination was also significant (P = 0.004) after adjusting for covariates.

Conclusions:

This study suggests that there may be a higher rejection rate after COVID-19 vaccination in patients who underwent DMEK. Patients should be warned of the rejection risk and its typical symptoms before receiving an mRNA COVID-19 vaccine, although further larger studies are needed to confirm the involvement of vaccination.
Educational disparities in joint pain within and across US states: do macro sociopolitical contexts matter?
Authors: Huang Rui , Yang Yulin , Zajacova Anna , Zimmer Zachary , Li Yuhang , Grol-Prokopczyk Hanna
Published: July 2023

Despite growing recognition of the importance of social, economic, and political contexts for population health and health inequalities, research on pain disparities relies heavily on individual-level data, while neglecting overarching macrolevel factors such as state-level policies and characteristics. Focusing on moderate or severe arthritis-attributable joint pain—a common form of pain that considerably harms individuals' quality of life—we (1) compared joint pain prevalence across US states; (2) estimated educational disparities in joint pain across states; and (3) assessed whether state sociopolitical contexts help explain these 2 forms of cross-state variation. We linked individual-level data on 407,938 adults (ages 25-80 years) from the 2017 Behavioral Risk Factor Surveillance System with state-level data on 6 measures (eg, the Supplemental Nutrition Assistance Program [SNAP], Earned Income Tax Credit, Gini index, and social cohesion index). We conducted multilevel logistic regressions to identify predictors of joint pain and inequalities therein. Prevalence of joint pain varies strikingly across US states: the age-adjusted prevalence ranges from 6.9% in Minnesota to 23.1% in West Virginia. Educational gradients in joint pain exist in all states but vary substantially in magnitude, primarily due to variation in pain prevalence among the least educated. At all education levels, residents of states with greater educational disparities in pain are at a substantially higher risk of pain than peers in states with lower educational disparities. More generous SNAP programs (odds ratio [OR] = 0.925; 95% confidence interval [CI]: 0.963-0.957) and higher social cohesion (OR = 0.819; 95% CI: 0.748-0.896) predict lower overall pain prevalence, and state-level Gini predicts higher pain disparities by education.