bluuebunny/crossref_metadata_2025 huggingface dataset:
Two interacting ethylene response factors negatively regulate peach resistance to Lasiodiplodia theobromae
Authors: Zhang Dongmei , Zhu Kaijie , Shen Xingyi , Meng Jian , Huang Xue , Tan Yuqi , Cardinale Francesca , Liu Jihong , Li Guohuai , Liu Junwei
Published: May 2023

Gummosis is 1 of the most common and destructive diseases threatening global peach (Prunus persica) production. Our previous studies have revealed that ethylene and methyl jasmonate enhance peach susceptibility to Lasiodiplodia theobromae, a virulent pathogen inducing gummosis; however, the underlying molecular mechanisms remain obscure. Here, 2 ethylene response factors (ERFs), PpERF98 and PpERF1, were identified as negative regulators in peach response to L. theobromae infection. Expression of 2 putative paralogs, PpERF98-1/2, was dramatically induced by ethylene and L. theobromae treatments and accumulated highly in the gummosis-sensitive cultivar. Silencing of PpERF98-1/2 increased salicylic acid (SA) content and pathogenesis-related genes PpPR1 and PpPR2 transcripts, conferring peach resistance to L. theobromae, whereas peach and tomato (Solanum lycopersicum) plants overexpressing either of PpERF98-1/2 showed opposite changes. Also, jasmonic acid markedly accumulated in PpERF98-1/2-silenced plants, but reduction in PpPR3, PpPR4, and PpCHI (Chitinase) transcripts indicated a blocked signaling pathway. PpERF98-1 and 2 were further demonstrated to directly bind the promoters of 2 putative paralogous PpERF1 genes and to activate the ERF branch of the jasmonate/ethylene signaling pathway, thus attenuating SA-dependent defenses. The lesion phenotypes of peach seedlings overexpressing PpERF1-1/2 and PpERF98-1/2 were similar. Furthermore, PpERF98-1/2 formed homodimers/heterodimers and interacted with the 2 PpERF1 proteins to amplify the jasmonate/ethylene signaling pathway, as larger lesions were observed in peach plants cooverexpressing PpERF98 with PpERF1 relative to individual PpERF98 overexpression. Overall, our work deciphers an important regulatory network of ethylene-mediated peach susceptibility to L. theobromae based on a PpERF98-PpERF1 transcriptional cascade, which could be utilized as a potential target for genetic engineering to augment protection against L. theobromae-mediated diseases in crops and trees.
Highly efficient cell-microbead encapsulation using dielectrophoresis-assisted dual-nanowell array
Authors: Tian Zuyuan , Yuan Zhipeng , Duarte Pedro A , Shaheen Mohamed , Wang Shaoxi , Haddon Lacey , Chen Jie
Published: May 2023

Recent advancements in micro/nanofabrication techniques have led to the development of portable devices for high-throughput single-cell analysis through the isolation of individual target cells, which are then paired with functionalized microbeads. Compared with commercially available benchtop instruments, portable microfluidic devices can be more widely and cost-effectively adopted in single-cell transcriptome and proteome analysis. The sample utilization and cell pairing rate (∼33%) of current stochastic-based cell–bead pairing approaches are fundamentally limited by Poisson statistics. Despite versatile technologies having been proposed to reduce randomness during the cell–bead pairing process in order to statistically beat the Poisson limit, improvement of the overall pairing rate of a single cell to a single bead is typically based on increased operational complexity and extra instability. In this article, we present a dielectrophoresis (DEP)-assisted dual-nanowell array (ddNA) device, which employs an innovative microstructure design and operating process that decouples the bead- and cell-loading processes. Our ddNA design contains thousands of subnanoliter microwell pairs specifically tailored to fit both beads and cells. Interdigitated electrodes (IDEs) are placed below the microwell structure to introduce a DEP force on cells, yielding high single-cell capture and pairing rates. Experimental results with human embryonic kidney cells confirmed the suitability and reproducibility of our design. We achieved a single-bead capture rate of >97% and a cell–bead pairing rate of >75%. We anticipate that our device will enhance the application of single-cell analysis in practical clinical use and academic research.
What They Have but Also Who They Are: Avarice, Elitism, and Public Support for Taxing the Rich
Authors: Kane John V , Newman Benjamin J
Published: May 2023

Scholarship evaluating public support for redistribution has emphasized that stereotypical perceptions of low-income people inform citizens’ willingness to redistribute wealth to the poor. Less understood, however, is the extent to which stereotypical perceptions of high-income people lead to greater willingness to raise taxes on high-income individuals. These perceptions likely involve resource-based considerations (i.e., what rich people have). However, following recent scholarship, perceptions of the wealthy may also involve more fundamental, trait-based considerations (i.e., who the rich are as people). In this Research Note, we isolate causal effects, utilizing conjoint experiments, of both resource-based and character-based attributes of the rich on support for taxing wealthy people. We find evidence that two character traits—avarice and elitism—significantly increase support for raising taxes on wealthy individuals, and this pattern appears to be the case even among groups generally opposed to redistribution (e.g., Republicans and conservatives). We conclude that, while resource-based considerations remain important, the scholarly literature on redistribution may also benefit from a deeper understanding of the trait-based foundations of public attitudes toward taxing the wealthy.
Mutual Efficacy, Self-Efficacy, and Collective Efficacy Theory: An Examination of Empowerment and Activism
Authors: Gearhart Michael C
Published: May 2023

Empowerment refers to the ways in which individuals and groups gain greater control over their lives. To date, the majority of studies focus on empowerment at the individual level. Further, research typically focuses on how to make people feel empowered and not how communities exercise their power. The present study utilizes collective efficacy, a community-level theory, to explore community characteristics that may empower individuals to engage in household activism, and communities to participate in neighborhood activism. The findings suggest that mutual efficacy and social cohesion are key drivers of participation in both household and neighborhood activism. Self-efficacy is associated with household activism only. Findings suggest that it is important to use individual-level skill-building opportunities as a method for fostering a collective identity and train community members to recruit others. In addition, community-building initiatives are more likely to result in activism if they focus on building mutual efficacy in the community.
The role of tissue biomechanics in the implantation and performance of inflatable penile prostheses: current state of the art and future perspective
Authors: Bose Shirsha , Fereidoonnezhad Behrooz , Akbarzadeh Khorshidi Majid , Watschke Brian , Mareena Evania , Nolan Daragh , Cooney Sean , Cullen Ivor M , Lally Caitríona
Published: May 2023

Introduction

Erectile dysfunction (ED) affects to some degree approximately 52% of the male population aged 40–70 years. Many men do not respond to, or are precluded from using, pharmaceutical treatments for ED and are therefore advised to consider penile prostheses. Different types of penile prosthesis are available, such as inflatable penile prostheses (IPPs). IPPs consist of a pair of inflatable cylinders inserted into the corpora cavernosa (CC). During inflation/deflation of these cylinders, the CC and other surrounding tissues such as the tunica albuginea (TA) are highly impacted. Therefore, it is critical to understand the mechanics of penile tissues for successful implantation of IPPs and to reduce tissue damage induced by IPPs.

Objectives

We explored the importance of the biomechanics of penile tissues for successful IPP function and reviewed and summarized the most significant studies on penile biomechanics that have been reported to date.

Methods

We performed an extensive literature review of publications on penile biomechanics and IPP implantation.

Results

Indenters have been used to characterize the mechanical behavior of whole penile tissue; however, this technique applied only local deformation, which limited insights into individual tissue components. Although one reported study addressed the mechanical behavior of TA, this investigation did not consider anisotropy, and there is a notable absence of biomechanical studies on CC and CS. This lack of understanding of penile tissue biomechanics has resulted in computational models that use linear-elastic materials, despite soft tissues generally exhibiting hyperelastic behavior. Furthermore, available benchtop/synthetic models do not have tissue properties matched to those of the human penis, limiting the scope of these models for use as preclinical testbeds for IPP testing.

Conclusion

Improved understanding of penile tissue biomechanics would assist the development of realistic benchtop/synthetic and computational models enabling the long-term performance of IPPs to be better assessed.
Increasing Information Content and Diagnosability in Family-Level Classifications
Authors: Kuntner Matjaž , Čandek Klemen , Gregorič Matjaž , Turk Eva , Hamilton Chris A , Chamberland Lisa , Starrett James , Cheng Ren-Chung , Coddington Jonathan A , Agnarsson Ingi , Bond Jason E
Published: May 2023

Higher-level classifications often must account for monotypic taxa representing depauperate evolutionary lineages and lacking synapomorphies of their better-known, well-defined sister clades. In a ranked (Linnean) or unranked (phylogenetic) classification system, discovering such a depauperate taxon does not necessarily invalidate the rank classification of sister clades. Named higher taxa must be monophyletic to be phylogenetically valid. Ranked taxa above the species level should also maximize information content, diagnosability, and utility (e.g., in biodiversity conservation). In spider classification, families are the highest rank that is systematically catalogued, and incertae sedis is not allowed. Consequently, it is important that family-level taxa be well defined and informative. We revisit the classification problem of Orbipurae, an unranked suprafamilial clade containing the spider families Nephilidae, Phonognathidae, and Araneidae sensu stricto. We argue that, to maximize diagnosability, information content, conservation utility, and practical taxonomic considerations, this “splitting” scheme is superior to its recently proposed alternative, which lumps these families together as Araneidae sensu lato. We propose to redefine Araneidae and recognize a monogeneric spider family, Paraplectanoididae fam. nov. to accommodate the depauperate lineage Paraplectanoides. We present new subgenomic data to stabilize Orbipurae topology which also supports our proposed family-level classification. Our example from spiders demonstrates why classifications must be able to accommodate depauperate evolutionary lineages, for example, Paraplectanoides. Finally, although clade age should not be a criterion to determine rank, other things being equal, comparable ages of similarly ranked taxa do benefit comparative biology. [Classification, family rank, phylogenomics, systematics, monophyly, spider phylogeny.]
An update on treatments for autosomal dominant polycystic kidney disease
Authors: Patel Suhani Janak , Sadowski Catherine K.
Published: May 2023

Autosomal dominant polycystic kidney disease (ADPKD) is less common than primary hypertension or diabetes but should be considered as a possible cause of end-stage renal disease, especially in young patients without comorbidities. Because of ADPKD's nonspecific symptoms, the diagnosis, treatment, and pertinent patient education may be delayed. This article describes ADPKD and its management, including tolvaptan, a new treatment with the potential to reduce or delay morbidity. However, only a subset of patients qualifies for this expensive treatment.
Suicide and homicide deaths of PAs
Authors: Robiner William N. , Dorzinski Collin A.
Published: May 2023

Objective:

This study describes physician associate/assistant (PA) deaths in the US CDC's National Violent Death Reporting System (NVDRS) from 2003 to 2020.

Methods:

PAs' violent deaths were analyzed and summarized in terms of decedents' numbers and demographics, methods of death, locations of death, and relationships with assailants.

Results:

The NVDRS identified 93 suicides and 9 homicides in this period. PAs who died by suicide were mostly White (93.5%) and male (67.7%); mean age was 49.7 years. A third of the PAs who died by homicide were Black; most were female (55.6%), and the mean age was 48.7 years. Firearms (41.7%) were most commonly involved in deaths by suicide, and blunt impact (33.3%) was most commonly seen in deaths by homicide. A plurality (46.1%) of suicides and homicides occurred in the South. Homes (72.5%) were the most frequent location. No homicides were reported in medical settings. Known perpetrators were mainly relatives and male; none were patients.

Conclusions:

Incidence of PA death by suicide or homicide is low relative to the general population. These deaths generally are not related to PAs' work. Delineating the incidence of violent deaths is a step toward informing preventive efforts.
Therapeutic Effect of Argatroban During Cardiopulmonary Resuscitation and Streptokinase During Extracorporeal Cardiopulmonary Resuscitation in a Porcine Model of Prolonged Cardiac Arrest
Authors: VanZalen Jensyn J. , Harvey Stephen , Hála Pavel , Phillips Annie , Nakashima Takahiro , Gok Emre , Tiba Mohamad Hakam , McCracken Brendan M. , Hill Joseph E. , Liao Jinhui , Jung Joshua , Mergos Joshua , Stacey William C. , Bartlett Robert H. , Hsu Cindy H. , Rojas-Peña Alvaro , Neumar Robert W.
Published: May 2023

OBJECTIVE:

Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during ECPR improve recovery of brain and heart function in a porcine model of prolonged out-of-hospital CA.

DESIGN:

Randomized interventional trial.

SETTING:

University laboratory.

SUBJECTS:

Swine.

INTERVENTIONS:

In a blinded study, 48 swine were subjected to 8 minutes of ventricular fibrillation CA followed by 30 minutes of goal-directed CPR and 8 hours of ECPR. Animals were randomized into four groups (n = 12) and given either placebo (P) or argatroban (ARG; 350 mg/kg) at minute 12 of CA and either placebo (P) or streptokinase (STK, 1.5 MU) at the onset of ECPR.

MEASUREMENTS AND MAIN RESULTS:

Primary outcomes included recovery of cardiac function measured by cardiac resuscitability score (CRS: range 0–6) and recovery of brain function measured by the recovery of somatosensory-evoked potential (SSEP) cortical response amplitude. There were no significant differences in recovery of cardiac function as measured by CRS between groups (p = 0.16): P + P 2.3 (1.0); ARG + P = 3.4 (2.1); P + STK = 1.6 (2.0); ARG + STK = 2.9 (2.1). There were no significant differences in the maximum recovery of SSEP cortical response relative to baseline between groups (p = 0.73): P + P = 23% (13%); ARG + P = 20% (13%); P + STK = 25% (14%); ARG + STK = 26% (13%). Histologic analysis demonstrated reduced myocardial necrosis and neurodegeneration in the ARG + STK group relative to the P + P group.

CONCLUSIONS:

In this swine model of prolonged CA treated with ECPR, early intra-arrest anticoagulation during goal-directed CPR and thrombolytic therapy during ECPR did not improve initial recovery of heart and brain function but did reduce histologic evidence of ischemic injury. The impact of this therapeutic strategy on the long-term recovery of cardiovascular and neurological function requires further investigation.
Sounding the Alarm: What Clinicians Need to Know about Physical, Emotional, and Cognitive Recovery After Venoarterial Extracorporeal Membrane Oxygenation*
Authors: Higa Kelly C. , Mayer Kirby , Quinn Christopher , Jubina Lindsey , Suarez-Pierre Alejandro , Colborn Kathryn , Jolley Sarah E. , Enfield Kyle , Zwischenberger Joseph , Sevin Carla M. , Rove Jessica Y.
Published: May 2023

OBJECTIVE:

We summarize the existing data on the occurrence of physical, emotional, and cognitive dysfunction associated with postintensive care syndrome (PICS) in adult survivors of venoarterial extracorporeal membrane oxygenation (VA-ECMO).

DATA SOURCES:

MEDLINE, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched.

STUDY SELECTION:

Peer-reviewed studies of adults receiving VA-ECMO for any reason with at least one measure of health-related quality of life outcomes or PICS at long-term follow-up of at least 6 months were included.

DATA EXTRACTION:

The participant demographics and baseline characteristics, in-hospital outcomes, long-term health outcomes, quality of life outcome measures, and prevalence of PICS were extracted.

DATA SYNTHESIS:

Twenty-seven studies met inclusion criteria encompassing 3,271 patients who were treated with VA-ECMO. The studies were limited to single- or two-center studies. Outcomes variables and follow-up time points evaluated were widely heterogeneous which limits comprehensive analysis of PICS after VA-ECMO. In general, the longer-term PICS-related outcomes of survivors of VA-ECMO were worse than the general population, and approaching that of patients with chronic disease. Available studies identified high rates of abnormal 6-minute walk distance, depression, anxiety, and posttraumatic stress disorder that persisted for years. Half or fewer survivors return to work years after discharge. Only 2 of 27 studies examined cognitive outcomes and no studies evaluated cognitive dysfunction within the first year of recovery. No studies evaluated the impact of targeted interventions on these outcomes.

CONCLUSIONS:

Survivors of VA-ECMO represent a population of critically ill patients at high risk for deficits in physical, emotional, and cognitive function related to PICS. This systematic review highlights the alarming reality that PICS and in particular, neurocognitive outcomes, in survivors of VA-ECMO are understudied, underrecognized, and thus likely undertreated. These results underscore the imperative that we look beyond survival to focus on understanding the burden of survivorship with the goal of optimizing recovery and outcomes after these life-saving interventions. Future prospective, multicenter, longitudinal studies in recovery after VA-ECMO are justified.
Recent advances of osteoimmunology research in rheumatoid arthritis: From single-cell omics approach
Authors: Hu Nan , Wang Jing , Ju Bomiao , Li Yuanyuan , Fan Ping , Jin Xinxin , Kang Xiaomin , Wu Shufang
Published: May 2023

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.
Fatigue amongst anaesthesiology and intensive care trainees in Europe
Authors: Abramovich Igor , Matias Bernardo , Norte Gustavo , Zawadka Mateusz , Bilotta Federico , Buzincu Iulian , Camilleri Podesta Anne Marie , De Hert Stefan , Grigoras Ioana , Pintilie Georgiana , Smallwood Aidan , Trinks Alexandra , Redfern Nancy
Published: May 2023

BACKGROUND

There is a growing awareness of the effects of fatigue on trainee wellbeing and health. Trainees in anaesthesiology and intensive care work long hours, switching work schedules frequently with insufficient rest. This may have unwanted long-term effects on mental and physical health and emotional well being, resulting in burnout and affecting patient safety.

OBJECTIVE

The study aimed to evaluate the prevalence, severity, causes and effects of work-related fatigue in trainees in anaesthesiology and intensive care.

DESIGN

Online survey of trainees in anaesthesiology and intensive care.

SETTINGS

A total of 31 countries within Europe were included in the survey.

PARTICIPANTS

European anaesthesiology and intensive care trainees who responded to an invitation to take part by electronic mail or through social media.

MAIN OUTCOME MEASURES

Responses from a 29-item online survey to assess the realities within European countries with regards to work-related fatigue.

RESULTS

One thousand and two hundred trainees from 31 European countries answered the survey demonstrating that an alarming number of trainees were fatigued by their working patterns and night shifts. Trainees reported effects on personal well being, safe commuting and potential for clinical errors. Respondents described a lack of support from hospitals and management for recovery during and after night shifts.

CONCLUSION

Fatigue among trainees in anaesthesiology and intensive care has a significant impact on their well being and potentially, on the incidence of clinical errors. Current measures from authorities and hospital management are not sufficient to prevent serious fatigue, and therefore a fatigue risk management system should be considered. Failure to address this issue might lead to a further decline in trainees’ wellbeing, their capacity to work in the speciality in the future, and potentially increase patient care errors.
Corneal Culture and Antibiotic Susceptibility Results for Microbial Keratitis in the Mid-Atlantic Region of the United States, 2016 to 2020
Authors: Shekhawat Nakul S. , Hall Leangelo N. , Sulewski Michael E. , Woreta Fasika , Wang Jiangxia , Smith Kerry , Kuo Irene C.
Published: May 2023

Objective:

To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States.

Methods:

Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020.

Results:

Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; ∼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin.

Conclusions:

Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.
A Retrospective Analysis of Tear Film and Blink Parameters in Patients With Ocular Surface Disease
Authors: Brahmbhatt Puja , Khanna Sheena , Griffin Sarah , Bouchard Charles S.
Published: May 2023

Objectives:

We had two objectives: (1) to investigate differences in tear film and blink parameters in patients with six ocular surface diseases (OSD): ocular graft versus host disease (oGVHD), Stevens–Johnson syndrome (SJS), lax eyelid syndrome, meibomian gland dysfunction (MGD), obstructive sleep apnea, and dry eye disease; and (2) to characterize the relationships between lipid layer thickness (LLT), meiboscore, Schirmer I test, and three blink parameters: partial blink rate (PBR), interblink interval (IBI), and interpalpebral fissure height (IPFH) in this group of patients.

Methods:

This is a single-site retrospective analysis of 228 patients (456 eyes) with six different primary OSD at Loyola University Medical Center between January 2018 and July 2020. Objective parameters included: LLT, IBI, PBR, IPFH, Pult meiboscore, and Schirmer I score. Linear mixed effects models were used to analyze the relationships between these parameters.

Results:

The meiboscore was highest in patients with SJS compared with the other five groups. There was significant variability in IPFH across different groups, with patients with oGVHD having the smallest height. An increase in IPFH was associated with increases in IBI, PBR, and Schirmer score. Patients with no partial blinks demonstrated a statistically significant higher IBI than patients who showed 1%–50% partial blinks. Finally, no statistically significant relationship was found between the following: (1) meiboscore and LLT, (2) OSDI and IPFH, (3) Schirmer score and IBI, or (4) LLT and IBI.

Conclusions:

There were fewer than anticipated differences in objective tear film and blink parameters between patients with six different OSD. A statistically significant association was found between IPFH and Schirmer score and IPFH and IBI, representing new findings in tear film research. Further investigation of the relationship between IPFH and IBI is needed.
Time Series Analysis of the Acute Effect of Atmospheric Fine Particulate Matter on Hospitalization for Heart Failure in Lanzhou, China
Authors: Zhang Wancheng , Zhang Runping , Ling Jianglong , Tian Tian , Liu Tong , Dong Jiyuan , Ruan Ye
Published: May 2023

Objective

The purpose of this study was to investigate the correlation between environmental PM2.5 and heart failure (HF) hospitalization in Lanzhou, China.

Method

The correlation between atmospheric PM2.5 and HF hospitalization was evaluated using a distributed lag nonlinear model.

Result

During the study period, 16,122 HF patients were hospitalized. The average concentration of PM2.5 is 45.24 μg/m3. PM2.5 was positively correlated with HF hospitalization with single lag (lag0) and cumulative lag (lag01, lag02, lag03). The maximum lag effect is estimated to occur in lag03, and with the PM2.5 concentration increasing by 10 μg/m3, HF hospitalization risk increased by 1.023 (95% confidence interval, 1.006–1.039). The risk of hospitalization for HF in the male group, the age group 65 years or older, and the cold season was statistically significant and more positively correlated.

Conclusion

PM2.5 exposure increases the risk of HF admission in Lanzhou.
Current insight into enteropathogens in flare-up ulcerative colitis. An observational study
Authors: Hassan Elham Ahmed , Abdel Rehim Abeer Sharaf El-Din , Ahmed Asmaa Omar , Salim Shaimaa Mahmoud Abd Elmouez , Soliman Asmaa M.A. , Rashed Hebatallah G. , Abd El-Kareem Doaa M.
Published: May 2023

Objective

Incidence of ulcerative colitis is globally increased. Enteric infections and their role in ulcerative colitis flares present a common health problem and a unique clinical challenge. We aimed to identify enteropathogens in flared ulcerative colitis patients and their antimicrobial susceptibilities and relation with the disease activity.

Methods

Stool samples were collected from 95 patients with ulcerative colitis (17 inactive cases and 78 active cases) according to the Mayo score assessment of ulcerative colitis severity. Enteropathogens were examined using an automated VITEK2 system and FilmArray gastrointestinal pathogen panel.

Results

Enteric infections were found in 81 patients (85.3%) with a significantly higher percentage in active ulcerative colitis (96.2% vs. 35.3%, P < 0.001). In 78 symptomatic patients, (78.7%) of bacteria as enteroaggregative and enteropathogenic E. coli, (11.5%) parasitic as Cryptosporidium and (7.7%) viral as Norovirus were the most detected microbial pathogens. Mixed, multidrug-resistant organisms (MDROs) and opportunistic infections were reported in 70.7%, 52.9% and 46.7% respectively. Raoultella ornithinolytica was reported for the first time as an enteropathogen in ulcerative colitis flare. Multiple organisms, MDROs, extended-spectrum beta-lactamases-producing and AmpC-resistant bacteria were significantly associated with disease severity.

Conclusion

Identifying enteropathogens especially opportunistic and MDR organisms as a cause of ulcerative colitis flare-ups is a matter of worry increasing their diagnostic and therapeutic burden. Periodic studies evaluating changes in microbial profiles and their antimicrobial susceptibilities are needed to achieve antibiotic stewardship and improve management.
Salvage lymphadenectomy after primary therapy with curative intent for prostate cancer
Authors: Quhal Fahad , Bryniarski Piotr , Rivas Juan Gomez , Gandaglia Giorgio , Shariat Shahrokh F. , Rajwa Pawel
Published: May 2023

Purpose of review

To provide a summary of the current literature on salvage lymph node dissection (sLND) in patients with nodal recurrent prostate cancer (PCa) with focus on imaging, the extent of sLND and oncologic outcomes.

Recent findings

The clinical practice guidelines recommend performing PET/CT in patients with biochemical recurrence (BCR) after primary therapy. PSMA PET/CT has demonstrated superiority over choline PET/CT and MRI, especially at low prostate-specific antigen (PSA) levels. Although the heterogeneity in available literature does not allow standardization of surgical templates for sLND and PET/CT scan can guide the extent of surgical dissection, an anatomically defined extended template is typically considered. Radio-guided surgery (RGS) suggests an improved positive lymph node yield compared with standard sLND. However, long-term data are needed to evaluate the oncologic impact of sLND. The main aims of sLND are to delay recurrence and to postpone the need for systemic therapy. Available evidence suggests that around 40–80% of men can achieve complete biochemical response after sLND and 10–30% remain BCR free after 5 years. Robotic sLND might represent an option to reduce the risk of complications without compromising oncological outcomes; validation in controlled prospective studies is, however, needed.

sLND is a valid treatment option for patients with nodal recurrence only after primary therapy for PCa. Further optimization of patient selection based on highly sensitive and specific imaging and clinical factors remains an unmet need. To maximize the benefit of this approach, sLND should be discussed with patients who harbor lymph node-only recurrence after primary therapy in a shared decision-making.
The 100 Most-Cited Articles on Optic Neuritis: Trends of Subtypes, Authorship, and Time
Authors: Assayag Elishai , Weill Yishay , Rappoport Daniel
Published: May 2023

Background:

Optic neuritis (ON) is an optic nerve inflammation that may lead to different degrees of vision loss. In recent decades, ON research facilitated a better understanding of the disease and its subtypes. This bibliometric analysis aimed to detect the 100 most-cited medical articles related to ON in the last 50 years (1972–2021) and describe publication trends arising from the list.

Methods:

The Scopus database was used to locate and screen the 100 most influential ON papers based on the number of citations per article. Each entry was reviewed for the first author (name, gender, institution, and country), year of publication, journal, number of citations, ON subtype, and study design. The mean impact factor (IF) of each journal was calculated.

Results:

The median number of citations was 265 (range 182–2,396). Observational studies on neuromyelitis optica-associated ON were the most common (27%), and the most influential decade was 2002–2011 (54 papers). Seventy-nine percent of articles were published in neurology journals, and a positive correlation between the mean number of citations per article and the journal mean IF was observed (r = 0.62, P < 0.001). Between 2009 and 2021, female authors led more ON studies (52%), and more publications originated outside the USA (68%), compared with previous years.

Conclusions:

This analysis summarizes the impact and shifting trends of ON research in the last decades.
Patch Technique for Primary Treatment of Type A Carotid Cavernous Fistula: A Case Series and Technical Notes
Authors: Al-Smadi Anas S. , Ali Rehan , Kappel Ari D. , Intikhab Osama , Rajah Gary B. , Luqman Ali
Published: May 2023

Background:

The utilization of flow diverters (FDs) in the treatment of high-flow Type A carotid cavernous fistulas (CCFs) has been described before mainly as an adjunct to the traditional endovascular techniques and rarely as a stand-alone treatment. In this study, we retrospectively evaluated our experience with FDs as the solo nonadjunctive treatment of Type A CCF with severe cortical venous reflux (CVR).

Methods:

A retrospective review was performed of patients with Type A CCFs who were treated using FDs' patch technique (PT). Patients' demographics, clinical data, and preoperative and postoperative ocular examination were recorded. The procedure technique, pipeline embolization device (PED) diameters, and immediate and late procedure outcomes were described.

Results:

Three patients were included in this case series. All patients had history of trauma and presented with decreased visual acuity, cranial nerve II deficit, limited extraocular muscles' movement, and increased intraocular pressure (IOP). Diagnostic angiography was performed, which confirmed high-flow Type A CCF. Endovascular treatment was performed through distal radial access in 2 patients and femoral access in 1 patient by deploying 4 sequentially enlarging PEDs with immediate resolution of the ocular symptoms. Follow-up angiography confirmed complete resolution of CCF in 2 patients. One patient was lost to follow-up; however, angiogram at 4 months demonstrated residual small CCF with significant improvement from postprocedure angiogram.

Conclusions:

The patch technique using sequentially enlarging FDs is a reasonable alternative solo technique for the treatment of direct CCF symptoms and results in immediate resolution of CVR while preserving the cavernous sinus anatomy.
A guide to Agrobacterium-mediated transformation of the chytrid fungus Spizellomyces punctatus
Authors: Prostak Sarah M. , Medina Edgar M. , Kalinka Erik , Fritz-Laylin Lillian K.
Published: May 2023

Chytrid fungi play key ecological roles in aquatic ecosystems, and some species cause a devastating skin disease in frogs and salamanders. Additionally, chytrids occupy a unique phylogenetic position– sister to the well-studied Dikarya (the group including yeasts, sac fungi, and mushrooms) and related to animals– making chytrids useful for answering important evolutionary questions. Despite their importance, little is known about the basic cell biology of chytrids. A major barrier to understanding chytrid biology has been a lack of genetic tools with which to test molecular hypotheses. Medina and colleagues recently developed a protocol for

Agrobacterium

-mediated transformation of Spizellomyces punctatus. In this manuscript, we describe the general procedure including planning steps and expected results. We also provide in-depth, step-by-step protocols and video guides for performing the entirety of this transformation procedure on protocols.io (dx.doi.org/10.17504/protocols.io.x54v9dd1pg3e/v1).
Vibrio eleionomae sp. nov., isolated from shrimp (Penaeus vannamei) pond water
Authors: Enciso-Ibarra Julissa , Roque Ana , Bolán-Mejia Carmen , Enciso-Ibarra Karen , González-Castillo Adrián , Gomez-Gil Bruno
Published: May 2023

A novel

Vibrio

strain (CAIM 722T=SW9T=DSM 24596T) was isolated in 2003 from water of a shrimp (Penaeus vannamei) culture pond located in Los Mochis, Sinaloa, Mexico, and taxonomically characterized using a polyphasic approach. The 16S rRNA gene sequence clustered within those of the genus

Vibrio

, showing high similarity to the type strains of the Porteresiae clade. Multilocus sequence analysis using eight housekeeping genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA, topA and 16S rRNA) and phylogenetic analysis with 139 single-copy genes showed that the strain forms an independent branch. Whole genome sequencing and genomic analyses (average nucleotide identity, OrthoANI, average amino acid identity and in silico DNA–DNA hybridization) produced values well below the thresholds for species delineation with all methods tested. In addition, a phenotypic characterization was performed to support the description and differentiation of the novel strain from related taxa. The results obtained demonstrate that the strain represent a novel species, for which the name Vibrio eleionomae sp. nov. is proposed.
Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus
Authors: Fung Ho Yee Joyce , Jiou Jenny , Neisman Ashley B. , Bernardes Natalia E. , Chook Yuh Min
Published: May 2023

Core histones are synthesized and processed in the cytoplasm before transport into the nucleus for assembly into nucleosomes; however, they must also be chaperoned as free histones are toxic. The importin Kap114 binds and transports histone H2A-H2B into the yeast nucleus, where RanGTPfacilitates H2A-H2B release. Kap114 and H2A-H2B also bind the Nap1 histone chaperone, which is found in both the cytoplasm and the nucleus, but how Nap1 and Kap114 cooperate in H2A-H2B processing and nucleosome assembly has been unclear. To understand these mechanisms, we used biochemical and structural analyses to reveal how Nap1, Kap114, H2A-H2B and RanGTPinteract. We show that Kap114, H2A-H2B and a Nap1 dimer (Nap12) assemble into a 1:1:1 ternary complex. Cryogenic electron microscopy revealed two distinct Kap114/Nap12/H2A-H2B structures: one of H2A-H2B sandwiched between Nap12and Kap114, and another in which Nap12bound to the Kap114•H2A-H2B complex without contacting H2A-H2B. Another Nap12•H2A-H2B•Kap114•RanGTPstructure reveals the nuclear complex. Mutagenesis revealed shared critical interfaces in all three structures. Consistent with structural findings, DNA competition experiments demonstrated that Kap114 and Nap12together chaperone H2A-H2B better than either protein alone. When RanGTPis present, Kap114’s chaperoning activity diminishes. However, the presence of Nap12within the Nap12•H2A-H2B•Kap114•RanGTPquaternary complex restores its ability to chaperone H2A-H2B. This complex effectively deposits H2A-H2B into nucleosomes. Together, these findings suggest that Kap114 and Nap12provide a sheltered path from cytoplasm to nucleus, facilitating the transfer of H2A-H2B from Kap114 to Nap12, ultimately directing its specific deposition into nucleosomes.

Significance Statement

Free histones are toxic and must be sequestered by other macromolecules in the cell. Nuclear import receptor Kap114 imports H2A-H2B into the nucleus while also chaperoning it. The histone chaperone Nap1 also chaperones H2A-H2B, but it is unclear how Nap1 and Kap114 cooperate to process H2A-H2B. We present biochemical and structural results that explain how Kap114, Nap1 and H2A-H2B assemble in the absence and presence of RanGTP, how Nap1 and Kap114 co-chaperone H2A-H2B, and how RanGTPand Nap1 coordinate the transfer of H2A-H2B from Kap114 to assembling nucleosomes in the nucleus.
Palmitoylation regulates human serotonin transporter activity, trafficking, and expression and is modulated by escitalopram
Authors: Brown Christopher R. , Foster James D.
Published: May 2023

In the central nervous system, serotonergic signaling modulates sleep, mood, and cognitive control. During neuronal transmission, the synaptic concentration of serotonin is tightly controlled in a spatial and temporal manner by the serotonin transporter (SERT). Dysregulation of serotonergic signaling is implicated in the pathogenesis of major-depressive, obsessive-compulsive, and autism-spectrum disorders, which makes SERT a primary target for prescription therapeutics, most notably selective-serotonin reuptake inhibitors (SSRIs). S-palmitoylation is an increasingly recognized dynamic post-translational modification, regulating protein kinetics, trafficking, and localization patterns upon physiologic/cellular stimuli. In this study, we reveal that human SERTs are a target for palmitoylation, and using the irreversible palmitoyl acyl-transferase inhibitor, 2-bromopalmitate (2BP) we have identified several associated functions. Using a lower dose of 2BP in shorter time frames, inhibition of palmitoylation was associated with reductions in SERT Vmax, without changes in Kmor surface expression. With higher doses of 2BP for longer time intervals, inhibition of palmitoylation was consistent with the loss of cell surface and total SERT protein, suggesting palmitoylation is an important mechanism in regulating SERT trafficking and maintenance of SERT protein through biogenic or anti-degradative processes. Additionally, we have identified that treatment with the SSRI escitalopram decreases SERT palmitoylation analogous to 2BP, reducing SERT surface expression and transport capacity. Ultimately, these results reveal palmitoylation is a major regulatory mechanism for SERT kinetics and trafficking and may be the mechanism responsible for escitalopram-induced internalization and loss of total SERT protein.
BONEcheck: a digital tool for personalized bone health assessment
Authors: Nguyen Dinh Tan , Ho-Le Thao P. , Pham Liem , Ho-Van Vinh P. , Hoang Tien Dat , Tran Thach S. , Frost Steve , Nguyen Tuan V.
Published: May 2023

Background and Aim

Osteoporotic fracture is a significant public health burden associated with increased mortality risk and substantial healthcare costs. Accurate and early identification of high-risk individuals and mitigation of their risks is a core part of the treatment and prevention of fractures. We aimed to introduce a digital tool called ’BONEcheck’ for personalized bone health assessment.

Methods

The development of BONEcheck primarily utilized data from the prospective population-based Dubbo Osteoporosis Epidemiology Study and the Danish Nationwide Registry. BONEcheck has 3 modules: input data, risk estimates, and risk context. Input variables include age, gender, prior fracture, fall incidence, bone mineral density (BMD), comorbidities, and genetic variants associated with BMD. By utilizing published methodologies, BONEcheck generates output related to the likelihood of fracture and its associated outcomes. The vocabulary utilized to convey risk estimation and management is tailored to individuals with a reading proficiency at level 8 or above.

Results

The tool is designed for men and women aged 50 years and older who either have or have not sustained a fracture. Based on the input variables, BONEcheck estimates the probability of any fragility and hip fracture within 5 years, skeletal age, subsequent fracture, genetic risk score, and recommended interval for repeating BMD. The probability of fracture is shown in both numeric and human icon array formats. The risk is also presented in the context of treatment and management options based on Australian guidelines. Skeletal age was estimated as the sum of chronological age and years of life lost due to a fracture or exposure to risk factors that elevate mortality risk. In its entirety, BONEcheck is a system of algorithms translated into a single platform for personalized osteoporosis and fracture risk assessment.

Conclusions

BONEcheck is a new system of algorithms that aims to offer not only fracture risk probability but also contextualize the efficacy of anti-fracture measures concerning the survival benefits. The tool can enable doctors and patients to engage in well-informed discussions and make decisions based on the patient’s risk profile. Public access to BONEcheck is available viahttps://bonecheck.organd in Apple Store (iOS) and Google Play (Android).
PredictingBlomia tropicalisallergens using a multiomics approach
Authors: Hubert Jan , Vrtala Susanne , Sopko Bruno , Dowd Scot E. , He Qixin , Klimov Pavel B. , Harant Karel , Talacko Pavel , Erban Tomas
Published: May 2023

The domestic miteBlomia tropicalisis a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite is not sufficiently studied. Only 14 allergen groups have been identified inB. tropicalisso far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by WHO/IUIS in domestic astigmatid mites, suggest that a large set of additional allergens may be present. Here, we use a multiomics approach to assess the allergome ofB. tropicalisusing genomic, transcriptomic sequence data, and a highly sensitive protein abundance quantification. Out of 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was found to be a contaminant originated from a nematode) and identified 16 potentially novel allergens using sequence similarity. These data indicate thatB. tropicalisshares 27 known/deduced allergen groups with pyroglyphid house dust mites (genusDermatophagoides). Among them, five allergen-encoding genes were highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces). We show the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label-free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that expression levels of allergen-encoding genes may not be strictly correlated with the actual allergenic protein abundance in the mite bodies.