bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phage-host co-evolution has led to distinct generalized transduction strategies
Authors: Wolput Sanne , Lood Cédric , Fillol-Salom Alfred , Casters Yorben , Albasiony Alaa , Cenens William , Vanoirbeek Kristof , Kerremans Alison , Lavigne Rob , Penadés José R , Aertsen Abram 
Published: June 2024

Abstract
Generalized transduction is pivotal in bacterial evolution but lacks comprehensive understanding regarding the facilitating features and variations among phages. We addressed this gap by sequencing and comparing the transducing particle content of three different Salmonella Typhimurium phages (i.e. Det7, ES18 and P22) that share a headful packaging mechanism that is typically initiated from a cognate pac site within the phage chromosome. This revealed substantial disparities in both the extent and content of transducing particles among these phages. While Det7 outperformed ES18 in terms of relative number of transducing particles, both phages contrasted with P22 in terms of content. In fact, we found evidence for the presence of conserved P22 pac-like sequences in the host chromosome that direct tremendously increased packaging and transduction frequencies of downstream regions by P22. More specifically, a ca. 561 kb host region between oppositely oriented pac-like sequences in the purF and minE loci was identified as highly packaged and transduced during both P22 prophage induction and lytic infection. Our findings underscore the evolution of phage transducing capacity towards attenuation, promiscuity or directionality, and suggest that pac-like sequences in the host chromosome could become selected as sites directing high frequency of transduction.
Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres
Authors: Khayat Freddy , Alshmery Majedh , Pal Mohinder , Oliver Antony W , Bianchi Alessandro 
Published: June 2024

Abstract
Telomeres protect chromosome ends from unscheduled DNA repair, including from the MRN (MRE11, RAD50, NBS1) complex, which processes double-stranded DNA breaks (DSBs) via activation of the ATM kinase, promotes DNA end-tethering aiding the non-homologous end-joining (NHEJ) pathway, and initiates DSB resection through the MRE11 nuclease. A protein motif (MIN, for MRN inhibitor) inhibits MRN at budding yeast telomeres by binding to RAD50 and evolved at least twice, in unrelated telomeric proteins Rif2 and Taz1. We identify the iDDR motif of human shelterin protein TRF2 as a third example of convergent evolution for this telomeric mechanism for binding MRN, despite the iDDR lacking sequence homology to the MIN motif. CtIP is required for activation of MRE11 nuclease action, and we provide evidence for binding of a short C-terminal region of CtIP to a RAD50 interface that partly overlaps with the iDDR binding site, indicating that the interaction is mutually exclusive. In addition, we show that the iDDR impairs the DNA binding activity of RAD50. These results highlight direct inhibition of MRN action as a crucial role of telomeric proteins across organisms and point to multiple mechanisms enforced by the iDDR to disable the many activities of the MRN complex.
Reinventing gene expression connectivity through regulatory and spatial structural empowerment via principal node aggregation graph neural network
Authors: Yan Fengyao , Jiang Limin , Chen Danqian , Ceccarelli Michele , Guo Yan 
Published: June 2024

Abstract
The intricacies of the human genome, manifested as a complex network of genes, transcend conventional representations in text or numerical matrices. The intricate gene-to-gene relationships inherent in this complexity find a more suitable depiction in graph structures. In the pursuit of predicting gene expression, an endeavor shared by predecessors like the L1000 and Enformer methods, we introduce a novel spatial graph-neural network (GNN) approach. This innovative strategy incorporates graph features, encompassing both regulatory and structural elements. The regulatory elements include pair-wise gene correlation, biological pathways, protein–protein interaction networks, and transcription factor regulation. The spatial structural elements include chromosomal distance, histone modification and Hi-C inferred 3D genomic features. Principal Node Aggregation models, validated independently, emerge as frontrunners, demonstrating superior performance compared to traditional regression and other deep learning models. By embracing the spatial GNN paradigm, our method significantly advances the description of the intricate network of gene interactions, surpassing the performance, predictable scope, and initial requirements set by previous methods.
The Potential Impact of Oral Nicotine Pouches on Public Health: A Scoping Review
Authors: Travis Nargiz , Warner Kenneth E , Goniewicz Maciej L , Oh Hayoung , Ranganathan Radhika , Meza Rafael , Hartmann-Boyce Jamie , Levy David T 
Published: June 2024

Abstract

Introduction
Oral nicotine pouches (ONPs) are a new class of nicotine products. This scoping review summarizes evidence on ONPs and explores their potential public health impact.

Aims and Methods
We conducted a structured literature search for empirical studies across three electronic databases through January 10, 2024. Outcomes included ONP product characteristics, use patterns, beliefs and perceptions, toxicity, and marketing and sales.

Results
Sixty-two studies were included, 17 were industry-funded. Most studies were from the United States. While large variations across studies were observed in ONP youth prevalence estimates, nationally representative U.S. studies find current use at 1.5% and lifetime use below 2.5% through 2023. Between 35% and 42% of U.S. adolescents and young adults have heard of ONPs, and 9-21% of tobacco-naïve youth were susceptible to trying them. U.S. adult-use estimates varied widely (0.8%–3% current; 3%–16% lifetime use) and were limited to populations with a history of tobacco use. The chemical composition of ONPs suggests fewer harmful/potentially harmful compounds at lower levels than cigarettes and smokeless tobacco (SLT), except formaldehyde. Industry-funded studies find substantially less cytotoxicity compared to cigarettes and suggest that higher nicotine-strength ONPs can deliver nicotine at levels comparable to or higher than SLT or cigarettes, although with slower nicotine release than cigarettes. Evidence on the cytotoxicity of ONPs relative to SLT is mixed.

Conclusions
ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users, although key data are mainly available from industry-funded studies. Data from independent research is critically needed. Industry marketing of ONPs may encourage initiation in youth and situational and dual use in adults.

Implications
The review provides an initial assessment of the potential role of ONPs in harm reduction and aims to determine unintended consequences of their use (youth uptake and dual-use) and identify populations that disproportionately use the product. This information is essential for tobacco regulatory bodies in determining the net public health impact of nicotine pouches.
Assessment of damage in Takayasu’s arteritis
Authors: Kermani Tanaz A , Sreih Antoine G , Cuthbertson David , Khalidi Nader A , Koening Curry L , Langford Carol A , McAlear Carol A , Monach Paul A , Moreland Larry , Pagnoux Christian , Rhee Rennie L , Seo Philip , Warrington Kenneth J , Merkel Peter A 
Published: June 2024

Abstract

Objectives
To evaluate damage and clinical characteristics associated with damage in Takayasu’s arteritis (TAK).

Methods
Patients with TAK enrolled in a multicentre, prospective, observational study underwent standardized damage assessment every 6 months using the Vasculitis Damage Index (VDI) and the Large-Vessel Vasculitis Index of Damage (LVVID).

Results
The study included 236 patients with TAK: 92% female, 81% Caucasian; median (25th, 75th percentile) disease duration = 2.6 (0.12, 6.9) years. Eighty-four percent had follow-up: median (25th, 75th) duration 4.1 (1.9, 7.5) years. Items of damage were present in 89% on VDI, 87% on LVVID, in the peripheral vascular (76% VDI, 74% LVVID) and cardiac (40% VDI, 45% LVVID) systems. During follow-up, 42% patients had new damage, including major vessel stenosis/arterial occlusion (8%), limb claudication (6%), hypertension (7%), aortic aneurysm (4%) and bypass surgery (4%). Disease-specific damage accounted for &gt;90% of new items. Older age, relapse and longer duration of follow-up were associated with new damage items; a higher proportion of patients without new damage were on MTX (P &lt;0.05). Among 48 patients diagnosed with TAK within 180 days of enrolment, new damage occurred in 31% on VDI and 52% on LVVID. History of relapse was associated with new damage in the entire cohort while in patients with a recent diagnosis, older age at diagnosis was associated with new damage.

Conclusion
Damage is present in &gt;80% of patients with TAK even with recent diagnosis and &gt;40% of patients accrue new, mainly disease-specific damage. Therapies for TAK that better control disease activity and prevent damage should be prioritized.
“Nobody Becomes a Criminal to Work 9 to 5”: Unpaid Labor, Stigma, and Hegemony in Addiction Treatment
Authors: Hatton Erin 
Published: June 2024

Abstract
Is compulsory unpaid labor essential “therapy” or unjust exploitation? The informants of this study do not agree, but most believe the former: that the 40 hours a week they worked without pay for the Salvation Army’s multimillion-dollar thrift store enterprise was not unjustly exploitative. Yet how can such seemingly overt exploitation be justified in this way? The answer, this article argues, is stigma. This study’s 40 informants were residents of the Salvation Army’s addiction programs, where “work therapy”—compulsory unpaid labor—is the primary form of addiction “treatment.” Because people with addiction are stigmatized as unproductive and immoral, even by people who have themselves struggled with addiction, their exploitation is deemed legitimate. They need to learn the value of work and even how to work, informants argue, and so unpaid labor becomes much-needed “therapy.” This article offers new answers to longstanding sociological questions about why workers consent to their own exploitation. While scholars have identified how exploitation is both obfuscated and legitimated in the workplace, little attention has been paid to dynamics beyond the workplace. This article shows that stigma is a powerful tool of labor hegemony, wielded even by those who are themselves stigmatized.
Incidence of Tibial Tubercle Fractures in Patients With and Without Osgood-Schlatter Disease
Authors: Milner John D. , Albright J. Alex , Callanan Tucker C. , Hall Rigel P. , Zhang Helen , Daniels Alan H. , Cruz Aristides I. 
Published: June 2024

Background:
Patients with Osgood-Schlatter disease (OSD) may be at increased risk of tibial tubercle fractures due to an underlying weakness of the tibial tubercle apophysis relative to the patellar tendon as a result of repetitive microtrauma.

Hypothesis/Purpose:
The purpose of this study is to analyze the incidence of tibial tubercle fractures in patients with and without Osgood-Schlatter disease. We hypothesized that the incidence of tibial tubercle fractures would be higher in patients with Osgood-Schlatter disease.

Methods:
A retrospective cohort analysis of the PearlDiver database was performed by querying all patients diagnosed with Osgood-Schlatter disease between January 2010 and October 2022. An OSD cohort of 146,672 patients was captured using International Classification of Diseases, Ninth Revision (ICD-9), Tenth Revision (ICD-10) billing codes, and age as inclusion/exclusion criteria. The Student t test and the χ2 analyses were used to compare the demographics and obesity between the OSD and control cohorts. Multivariable logistic regressions, controlling for residual differences in age, sex, and obesity, were used to compare rates of tibial tubercle fractures.

Results:
Patients with a recent history of OSD were found to have higher rates of tibial tubercle fractures than the control group at all measured time points (P<0.001). The 1-year rate of tibial tubercle fractures was 0.62% in the OSD group. The incidence of tibial tubercle fractures in the OSD group was 627.3 cases per 100,000 person-years compared with 42.7 cases per 100,000 person-years in the control group (P<0.001). Male sex and obesity were also associated with an increased risk of sustaining a tibial tubercle fracture within these patient populations (P<0.001).

Conclusion:
We report a significantly higher incidence of tibial tubercle fractures among patients with OSD compared with controls. This increase was most significant at 1 month following OSD diagnosis, however, held true for all measured time points. In addition, male patients and those with obesity were also noted to have increased incidence of tibial tubercle fractures regardless of an OSD diagnosis.
Atmospheric particulate matter and hypoxaemia in Korean children receiving general anaesthesia
Authors: Park Jung-Bin , Kang Pyoyoon , Ji Sang-Hwan , Jang Young-Eun , Lee Ji-Hyun , Kim Jin-Tae , Kim Hee-Soo , Kim Eun-Hee 
Published: June 2024

BACKGROUND
The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear.

OBJECTIVE
To investigate the association between the exposure to of particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1 min, in children.

DESIGN
Retrospective study.

SETTING
Single-centre.

PARTICIPANTS
Children aged 18 years or younger who received general anaesthesia between January 2019 and October 2020.

INTERVENTION
Information on daily levels of particulate matter with a diameter 10 μm or less and 2.5 μm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data.

MAIN OUTCOME MEASURES
The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1 min, manually verified by anaesthesiologists using vital sign registry data extracted at 2 s intervals.

RESULTS
Of the patients finally analysed, 3.85% (489/13 175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10 μm or less in diameter (≥81 μg m−3, 472/12 900, 3.7%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81 μg m−3, 17/275, 6.2%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P = 0.035].

CONCLUSION
The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10 μm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.
Simulation-Based Optimization of Sampling Schedules for Model-Informed Precision Dosing of Once-Daily and 4-Times-Daily Busulfan in Pediatric Patients
Authors: Ben Hassine Khalil , Daali Youssef , Gloor Yvonne , Nava Tiago , Théorêt Yves , Krajinovic Maja , Bittencourt Henrique , Satyanarayana Uppugunduri Chakradhara Rao , Ansari Marc 
Published: June 2024

Background:
Therapeutic drug monitoring (TDM) is crucial in optimizing the outcomes of hematopoietic stem cell transplantation by guiding busulfan (Bu) dosing. Limited sampling strategies show promise for efficiently adjusting drug doses. However, comprehensive assessments and optimization of sampling schedules for Bu TDM in pediatric patients are limited. We aimed to establish optimal sampling designs for model-informed precision dosing (MIPD) of once-daily (q24h) and 4-times-daily (q6h) Bu administration in pediatric patients.

Methods:
Simulated data sets were used to evaluate the population pharmacokinetic model-based Bayesian estimation of the area under the concentration–time curve (AUC) for different limited sampling strategy designs. The evaluation was based on the mean prediction error for accuracy and root mean square error for precision. These findings were validated using patient-observed data. In addition, the MIPD protocol was implemented in the Tucuxi software, and its performance was assessed.

Results:
Our Bayesian estimation approach allowed for flexible sampling times while maintaining mean prediction error within ±5% and root mean square error below 10%. Accurate and precise AUC0–24h and cumulative AUC estimations were obtained using 2-sample and single-sample schedules for q6h and q24h dosing, respectively. TDM on 2 separate days was necessary to accurately estimate cumulative exposure, especially in patients receiving q6h Bu. Validation with observed patient data confirmed the precision of the proposed limited sampling scenarios. Implementing the MIPD protocol in Tucuxi software yielded reliable AUC estimations.

Conclusions:
Our study successfully established precise limited sampling protocols for MIPD of Bu in pediatric patients. Our findings underscore the importance of TDM on at least 2 occasions to accurately achieve desired Bu exposures. The developed MIPD protocol and its implementation in Tucuxi software provide a valuable tool for routine TDM in pediatric hematopoietic stem cell transplantation.
Mohs Micrographic Surgery With Immunohistochemistry for the Treatment of Periocular Melanoma In Situ
Authors: McInnis-Smith Kerri M. , Asamoah Eucabeth M. , Demer Addison M. , Sharma Kannan , Yu Caroline Y. , Bradley Elizabeth A. , Tooley Andrea A. , Wagner Lilly H. 
Published: June 2024

Purpose:
Mohs micrographic surgery with immunohistochemistry allows for same-day comprehensive margin assessment of melanoma in situ prior to subspecialty reconstruction. This study describes the oncologic and reconstructive outcomes of eyelid and periorbital melanoma in situ and identifies risk factors for complex reconstructive demands.

Methods:
Retrospective case series of all patients treated with Mohs micrographic surgery with immunohistochemistry for melanoma in situ affecting the eyelids or periorbital region from 2008 to 2018 at a single institution. Tumors were assigned to the eyelid group if the clinically visible tumor involved the skin inside the orbital rim. Reconstructive variables were compared between the eyelid and periorbital cohorts.

Results:
There were 24 eyelid and 141 periorbital tumors included. The initial surgical margin for all tumors was 5.34 ± 1.54 mm and multiple Mohs stages were required in 24.2% of cases. Eyelid tumors included more recurrences (p = 0.003), and the average defect size was larger (14.0 ± 13.3 cm2 vs. 7.7 ± 5.4 cm2, p = 0.03). Risk factors for complex reconstruction included: initial tumor diameter >2 cm (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 1.95–7.57) and eyelid involved by initial tumor (OR: 4.88, 95% CI: 1.94–12.28). At an average follow-up of 4.8 years, there were no melanoma-related deaths and 1 local recurrence (0.6% recurrence rate).

Conclusions:
Mohs micrographic surgery with immunohistochemistry achieves excellent local control rates for periocular melanoma in situ. An initial surgical margin of 5 mm is frequently insufficient to achieve clear margins. The resulting defects are large, and the complexity of reconstruction can be predicted by tumor size and clinical involvement of eyelid skin.
Bilateral spontaneous Descemet membrane detachment after uneventful immediate sequential bilateral cataract surgery
Authors: Erikitola Ore-oluwa Catherine , Sekaran Anisha , Zhang Vera , Diaper Charles , Anijeet Deepa 
Published: June 2024

Introduction:
Immediate sequential bilateral cataract surgery (ISBCS) is a practice on the rise. To the authors' knowledge, this is the first reported case of bilateral Descemet membrane detachment (DMD) after uneventful same-day ISBCS, with emphasis on diagnosis and management.

Patient and Clinical Findings:
The case of a 66-year-old diabetic woman with chronic obstructive pulmonary disease and obstructive sleep apnea on home oxygen who developed spontaneous bilateral DMD after uneventful ISBCS for visually significant cataracts is presented. Although spontaneous DMD after uneventful phacoemulsification has been reported before, it has not been reported after same-day ISBCS to the authors' knowledge. The success rates with air pneumatic descemetopexy are excellent, with ranges between 90% and 95%. In this case, surgical intervention with gas injection in the anterior chamber and surgical peripheral iridotomies resulted in excellent visual acuity restoration in the patient.

Diagnosis, Intervention, and Outcomes:
Patient underwent same-day ISBCS under local anesthesia by different surgeons in either eye. Standard phacoemulsification techniques were used, and no intraoperative complications were noted. The patient returned with bilateral counting fingers vision 4 weeks postoperatively and reported her vision never improved after her cataract extraction. Anterior segment optical coherence tomography (AS-OCT) confirmed the presence of bilateral DMDs. Because of the patient's severely impaired vision, bilateral air descemetopexies were performed with clinical resolution of the DMD and excellent restoration of vision in both eyes.

Conclusions:
Sufficient evidence supports that performing ISBCS using internationally agreed protocols minimizes the risk of experiencing bilateral complications to a negligible level when compared with staged surgery. However, with ISBCS being on the rise, spontaneous bilateral DMDs may also be seen increasingly in those eyes with no underlying commonly recognized risk factors for spontaneous DMD. With unilateral DMD, watch and wait is a viable option. However, in bilateral DMD cases, earlier air or gas descemetopexy may be preferable to increase the likelihood of success and reduce the patient's period of decreased vision.
Optimizing the Team Approach: Designing a Clinical Care Pathway for Functional Neurological Disorder
Authors: Brown Laurey , Norwood Meredith , Thompson Laurie G. 
Published: June 2024

ABSTRACT
Functional neurological disorder (FND) sits at the intersection of neurology and psychology and has a variety of presentations, severity, and symptomatology. It affects a considerable number of pediatric patients and overwhelmingly influences healthcare spending. Diagnosis, treatment, and outcomes are varied, challenging, and lack standardization, often leading to frustration from patients, caregivers, and providers. Multidisciplinary care is essential though communication is often complex and disjunct. Using quality improvement tools and experiences from one institution, a team was established to ameliorate these concerns. A clinical care pathway was designed for the diagnosis and treatment of FND in the pediatric inpatient setting. This pathway was the result of the multidisciplinary team effort and an outcome, highlighting the need for early and intentional diagnosis with diagnosing provider specified, provider education and consistent language, patient and caregiver education, and clear and thorough discharge planning. Through the implementation of this pathway, it is anticipated that patient and provider satisfaction will improve as will the outcomes and care given to affected individuals. This work can be applied to the global treatment of FND and raise awareness to effectively managed care as well as the opportunity for clinicians to drive institutional change.