bluuebunny/crossref_metadata_2025 huggingface dataset:
Coyolxauqui’s Bent Heart: An Interview with Richard Villegas, Jr.
Authors: Fernández Audrey Harris
Published: August 2024

This article is an interview with Richard Villegas, Jr. about his self-published short story collection, I (Heart) Babylon, Tenochtitlán, and Ysteléi (2011) and the hit Starz series it inspired, Vida (2018-20) about two sisters struggling to save their mother’s lesbian bar in the gentrifying Boyle Heights district of Los Angeles. The interview discusses Villegas’s education in the pioneering César E. Chávez Department of Chicana/o Studies at UCLA in the activist 90s; the Los Angeles public school system in which he taught for twenty years; East LA as literary landscape and Mexico City/Tenochtitlán as creative inspiration; Indigenous iconography and revisionist mythmaking; Latinx representation in Hollywood, including the pressure to stereotype and the struggle to tell authentic stories; family struggles; humor as a life strategy, and solidarities between the queer and feminist Chicano/a sensibilities. The interview also discusses Vida in the context of current debates around gente-fication, or the movement of middle-class Latinos home to revitalize the barrio.
Fission and fusion of heavy nuclei induced by the passage of a radiation-mediated shock in BNS mergers
Authors: Granot Alon , Levinson Amir , Nakar Ehud
Published: August 2024

We compute the structure of a Newtonian, multi-ion radiation-mediated shock (RMS) for different compositions anticipated in various stellar explosions. We use a multifluid RMS model that incorporates electrostatic coupling between the different plasma constituents as well as Coulomb friction in a self-consistent manner, and approximates the effect of pair creation and the presence of free neutrons in the shock upstream on the shock structure. We find that under certain conditions a significant velocity separation is developed between different ions in the shock downstream and demonstrate that in fast enough shocks ion–ion collisions may trigger fusion and fission events at a relatively high rate. Our analysis ignores anomalous coupling through plasma microturbulence, which might reduce the velocity spread downstream below the activation energy for nuclear reactions. A rough estimate of the scale separation in RMS suggests that for shocks propagating in binary neutron star (BNS) merger ejecta, the anomalous coupling length may exceed the radiation length, allowing a considerable composition change behind the shock via inelastic collisions of $\alpha$ particles with heavy elements at shock velocities $\beta _\mathrm{ u}\gtrsim 0.25$. A sufficient abundance of free neutrons in the shock upstream, as expected during the first second after the merger, is also expected to alter the ejecta composition through neutron capture downstream. The resultant change in the composition profile may affect the properties of the early kilonova emission. The generation of microturbulence due to velocity separation can also give rise to particle acceleration that might alter the breakout signal in supernovae and other systems.
Blind QSO reconstruction challenge: exploring methods to reconstruct the Ly α emission line of QSOs
Authors: Greig Bradley , Bosman S E I , Davies F B , Ďurovčíková D , Fathivavsari H , Liu B , Meyer R A , Sun Z , D’Odorico V , Gallerani S , Mesinger A , Ting Y -S
Published: August 2024

Reconstructing the intrinsic Ly $\alpha$ line flux from high-z QSOs can place constraints on the neutral hydrogen content of the intergalactic medium during reionization. There are now $\gtrsim 10$ different Ly $\alpha$ reconstruction pipelines using different methodologies to predict the Ly $\alpha$ line flux from correlations with the spectral information redwards of Ly $\alpha$. However, there have been few attempts to directly compare the performance of these pipelines. Therefore, we devised a blind QSO challenge to compare these reconstruction pipelines on a uniform set of objects. Each author was provided de-identified, observed rest-frame QSO spectra with spectral information only redwards of 1260 Å rest-frame to ensure unbiased reconstruction. We constructed two samples of 30 QSOs, from X-Shooter and Sloan Digital Sky Survey (SDSS) both spanning $3.5\lt z\lt 4.5$. Importantly, the purpose of this comparison study was not to champion a single, best-performing reconstruction pipeline but rather to explore the relative performance of these pipelines over a range of QSOs with broad observational characteristics to infer general trends. In summary, we find machine-learning approaches in general provide the strongest ‘best guesses’ but underestimate the accompanying statistical uncertainty, although these can be recalibrated, while pipelines that decompose the spectral information, for example principal component or factor analysis, generally perform better at predicting the Ly $\alpha$ profile. Further, we found that reconstruction pipelines trained on SDSS QSOs performed similarly on average for both the X-Shooter and SDSS samples indicating no discernible biases owing to differences in the observational characteristics of the training set or QSO being reconstructed, although the recovered distributions of reconstructions for X-Shooter were broader likely due to an increased fraction of outliers.
Rational design of base, sugar and backbone modifications improves ADAR-mediated RNA editing
Authors: Lu Genliang , Shivalila Chikdu , Monian Prashant , Yu Hui , Harding Ian , Briem Stearne , Byrne Michael , Faraone Alyse , Friend Stephen , Huth Olivia , Iwamoto Naoki , Kawamoto Tomomi , Kumarasamy Jayakanthan , Lamattina Anthony , Longo Kenneth , McCarthy Leah , McGlynn Andrew , Molski Allison , Pan Qianli , Pu Tom , Purcell-Estabrook Erin , Rossi Jeff , Standley Stephany , Thomas Carina , Walen Alexandra , Yang Hailin , Kandasamy Pachamuthu , Vargeese Chandra
Published: August 2024

AIMers are short, chemically modified oligonucleotides that induce A-to-I RNA editing through interaction with endogenous adenosine deaminases acting on RNA (ADAR) enzymes. Here, we describe the development of new AIMer designs with base, sugar and backbone modifications that improve RNA editing efficiency over our previous design. AIMers incorporating a novel pattern of backbone and 2′ sugar modifications support enhanced editing efficiency across multiple sequences. Further efficiency gains were achieved through incorporation of an N-3-uridine (N3U), in place of cytidine (C), in the ‘orphan base’ position opposite the edit site. Molecular modeling suggests that N3U might enhance ADAR catalytic activity by stabilizing the AIMer-ADAR interaction and potentially reducing the energy required to flip the target base into the active site. Supporting this hypothesis, AIMers containing N3U consistently enhanced RNA editing over those containing C across multiple target sequences and multiple nearest neighbor sequence combinations. AIMers combining N3U and the novel pattern of 2′ sugar chemistry and backbone modifications improved RNA editing both in vitro and in vivo. We provide detailed N3U synthesis methods and, for the first time, explore the impact of N3U and its analogs on ADAR-mediated RNA editing efficiency and targetable sequence space.
A new perspective on microRNA-guided gene regulation specificity, and its potential generalization to transcription factors and RNA-binding proteins
Authors: Seitz Hervé
Published: August 2024

Our conception of gene regulation specificity has undergone profound changes over the last 20 years. Previously, regulators were considered to control few genes, recognized with exquisite specificity by a ‘lock and key’ mechanism. However, recently genome-wide exploration of regulator binding site occupancy (whether on DNA or RNA targets) revealed extensive lists of molecular targets for every studied regulator. Such poor biochemical specificity suggested that each regulator controls many genes, collectively contributing to biological phenotypes. Here, I propose a third model, whereby regulators’ biological specificity is only partially due to ‘lock and key’ biochemistry. Rather, regulators affect many genes at the microscopic scale, but biological consequences for most interactions are attenuated at the mesoscopic scale: only a few regulatory events propagate from microscopic to macroscopic scale; others are made inconsequential by homeostatic mechanisms. This model is well supported by the microRNA literature, and data suggest that it extends to other regulators. It reconciles contradicting observations from biochemistry and comparative genomics on one hand and in vivo genetics on the other hand, but this conceptual unification is obscured by common misconceptions and counter-intuitive modes of graphical display. Profound understanding of gene regulation requires conceptual clarification, and better suited statistical analyses and graphical representation.
Ubiquitinated histone H2B as gatekeeper of the nucleosome acidic patch
Authors: Hicks Chad W , Rahman Sanim , Gloor Susan L , Fields James K , Husby Natalia Ledo , Vaidya Anup , Maier Keith E , Morgan Michael , Keogh Michael-Christopher , Wolberger Cynthia
Published: August 2024

Monoubiquitination of histones H2B-K120 (H2BK120ub) and H2A-K119 (H2AK119ub) play opposing roles in regulating transcription and chromatin compaction. H2BK120ub is a hallmark of actively transcribed euchromatin, while H2AK119ub is highly enriched in transcriptionally repressed heterochromatin. Whereas H2BK120ub is known to stimulate the binding or activity of various chromatin-modifying enzymes, this post-translational modification (PTM) also interferes with the binding of several proteins to the nucleosome H2A/H2B acidic patch via an unknown mechanism. Here, we report cryoEM structures of an H2BK120ub nucleosome showing that ubiquitin adopts discrete positions that occlude the acidic patch. Molecular dynamics simulations show that ubiquitin remains stably positioned over this nucleosome region. By contrast, our cryoEM structures of H2AK119ub nucleosomes show ubiquitin adopting discrete positions that minimally occlude the acidic patch. Consistent with these observations, H2BK120ub, but not H2AK119ub, abrogates nucleosome interactions with acidic patch-binding proteins RCC1 and LANA, and single-domain antibodies specific to this region. Our results suggest a mechanism by which H2BK120ub serves as a gatekeeper to the acidic patch and point to distinct roles for histone H2AK119 and H2BK120 ubiquitination in regulating protein binding to nucleosomes.
GEGA (Gallus Enriched Gene Annotation): an online tool providing genomics and functional information across 47 tissues for a chicken gene-enriched atlas gathering Ensembl and Refseq genome annotations
Authors: Degalez Fabien , Bardou Philippe , Lagarrigue Sandrine
Published: August 2024

GEGA is a user-friendly tool designed to navigate through various genomic and functional information related to an enriched gene atlas in chicken that integrates the gene catalogues from the two reference databases, NCBI-RefSeq and EMBL-Ensembl/GENCODE, along with four additional rich resources such as FAANG and NONCODE. Using the latest GRCg7b genome assembly, GEGA encompasses a total of 78 323 genes, including 24 102 protein-coding genes (PCGs) and 44 428 long non-coding RNAs (lncRNAs), significantly increasing the number of genes provided by each resource independently. However, GEGA is more than just a gene database. It offers a range of features that allow us to go deeper into the functional aspects of these genes. Users can explore gene expression and co-expression profiles across 47 tissues from 36 datasets and 1400 samples, discover tissue-specific variations and their expression as a function of sex or age and extract orthologous genes or their genomic configuration relative to the closest gene. For the communities interested in a specific gene, a list of genes or a quantitative trait locus region in chicken, GEGA’s user-friendly interface facilitates efficient gene analysis, easy downloading of results and a multitude of graphical representations, from genomic information to detailed visualization of expression levels.
SpanSeq: similarity-based sequence data splitting method for improved development and assessment of deep learning projects
Authors: Ferrer Florensa Alfred , Almagro Armenteros Jose Juan , Nielsen Henrik , Aarestrup Frank Møller , Clausen Philip Thomas Lanken Conradsen
Published: August 2024

The use of deep learning models in computational biology has increased massively in recent years, and it is expected to continue with the current advances in the fields such as Natural Language Processing. These models, although able to draw complex relations between input and target, are also inclined to learn noisy deviations from the pool of data used during their development. In order to assess their performance on unseen data (their capacity to generalize), it is common to split the available data randomly into development (train/validation) and test sets. This procedure, although standard, has been shown to produce dubious assessments of generalization due to the existing similarity between samples in the databases used. In this work, we present SpanSeq, a database partition method for machine learning that can scale to most biological sequences (genes, proteins and genomes) in order to avoid data leakage between sets. We also explore the effect of not restraining similarity between sets by reproducing the development of two state-of-the-art models on bioinformatics, not only confirming the consequences of randomly splitting databases on the model assessment, but expanding those repercussions to the model development. SpanSeq is available at https://github.com/genomicepidemiology/SpanSeq.
Defining the Landscape of Educational Experiences in Transplant Infectious Diseases: A National Survey of Infectious Diseases Fellows in the United States
Authors: Phadke Varun K , Nematollahi Saman , Steinbrink Julie M , Bartash Rachel , Morales Megan K , Roberts Scott C , Ardura Monica I , Theodoropoulos Nicole M
Published: August 2024

Background

Transplant infectious diseases (TID) is a growing area of expertise within infectious diseases (ID), but TID training is not standardized. Previous surveys of fellows identified opportunities to improve TID education resources but did not explore didactic, clinical, and nonclinical experiences comprehensively.

Methods

The American Society of Transplantation ID Community of Practice surveyed adult and pediatric fellows in US-based general ID or dedicated TID training programs to explore their didactic exposure, clinical experiences, and non–direct patient care activities in TID.

Results

A total of 234 fellows initiated the survey, and 195 (83%) (190 general ID and 19 TID fellows, including 125 adult, 76 pediatric, and 8 combined adult-pediatric fellows) completed the entire survey. More than half of the fellows described receiving no formal curricular content on most foundational topics in transplant medicine. Almost all respondents (>90%) had some inpatient TID experience, but for >60% of fellows this was <12 weeks annually. Clinical exposure varied by fellow and patient type—in an average month rotating on an inpatient TID service, more than half of adult fellows had evaluated ≥10 kidney, liver, or hematopoietic stem cell transplant recipients but <10 heart, lung, pancreas, or intestinal recipients; pediatric fellows saw <10 of all patient types. Nearly half (46%) of general ID fellows had not spent any time in the dedicated TID clinic at their program. Few fellows had participated in protocol development, organ selection meetings, or donor evaluations.

Conclusions

This survey highlights important gaps in TID training. Given the increasing need for TID specialists, updated curricula and educational resources are needed.
Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology
Authors: Cheng Kar On , Montaño Dolly E , Zelante Teresa , Dietschmann Axel , Gresnigt Mark S
Published: August 2024

Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by Candida species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.
Long-term spectral variations of V Sagittae: Two spectroscopic states with red- or blue-shifted emission wings of H i and He ii
Authors: Iijima Takashi , Naito Hiroyuki , Narusawa Sin-ya
Published: August 2024

The spectral variation in the optical region of a peculiar variable star V Sagittae was monitored in the recent three decades. The main aim of this article is to report several interesting phenomena discovered in the monitoring; we briefly discuss interpretations of them. Emission lines of H i and He ii were decomposed into narrow components and wide wings. The radial velocities of the wings were related to the orbital motion of the hot primary, but did not reflect it directly. Widely red-shifted sinusoidal variations according to the orbital period were detected in 1993–2005 (e.g., $K = 195$ km s$^{-1}$ and $\gamma = +252$ km s$^{-1}$ for He ii 4686). Sporadic blue-shifts were also observed. The mode of the radial velocity variation drastically changed between 2005 and 2007. Red-shifted sinusoidal variations ($K = 224$ km s$^{-1}$ and $\gamma = +260$ km s$^{-1}$ idem) or blue-shifted ones ($K =206$ km s$^{-1}$ and $\gamma = -289$ km s$^{-1}$ idem) appeared alternately in 2007–2019. One red- or blue-shift state lasted several years. The radial velocities of O iii 5592 and the doublet C iv 5805 exhibited sinusoidal variations without large red- or blue-shifts (e.g., $K =215$ km s$^{-1}$ and $\gamma = -18$ km s$^{-1}$ for C iv 5805). The widths of emission lines He ii 5412 and C iv in the doublet 5805 suggest that helium and carbon ions contained nearly the same kinetic energy, because the former line was wider than the latter by a factor of about $\surd {3}$ on most spectra. It is probable that there was no large-scale mass motion in such a thermal-equilibrium-like condition. The C iv lines and He ii 5412 had roughly same widths, like the spectra of Wolf–Rayet stars, only three times in 2007–2019 on which there were likely large-scale mass outflows.
Informed Voting
Authors: Gao Meng , Huang Jiekun
Published: August 2024

Information production by shareholders is essential for proxy voting to produce efficient outcomes. We propose a stock return-based measure to capture informed voting. Our measure, the vote alpha, quantifies the extent to which a shareholder votes in the direction that the market perceives as value increasing. Using data on mutual funds’ proxy voting records, we find that the vote alpha exhibits persistence. Our main result shows that the voting pattern of high vote alpha funds positively predicts long-run abnormal stock returns following contentious votes, suggesting that these funds possess information about the shareholder value implication of contentious governance proposals.
A Transdiagnostic Network Analysis of Childhood Trauma and Psychopathology
Authors: Huang Yi-hang , Liu Chao , Zhang Jian-biao , Li Shuai-biao , Wang Ling-ling , Hu Hui-xin , Cai Yuan , Zhu Zhenhua , Chu Min-yi , Wang Yi , Lv Qin-yu , Lui Simon S Y , Yi Zheng-hui , Hui Li , Chan Raymond C K
Published: August 2024

Background and Hypothesis

Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample.

Study Design

This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups.

Study Results

The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks.

Conclusions

Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.
Governance by Gaslight: The Reproductive Politics of the Two-Child Limit
Authors: Hewer Rebecca
Published: August 2024

In 2017, the UK government limited the number of children for a whom a low-income family could claim a means tested benefit (the “child element” of “Universal Credit”) to two. Since then, over 400,000 families—including 1.5 million children—have been affected by the “two-child limit.” Emerging research indicates that the limit has done little to influence fertility rates, nothing to influence workforce participation, and a great deal to increase financial hardship and poverty. Via a synthesis of existing research, and a critical analysis of formal policy dialogue, I explore the specifically reproductive politics of the two-child limit. I cast the limit as “successful” reproductive governance, a “technology of discipline” with complementary effects and rationales, which works by further marginalizing intersectionally marginalized women. In concluding, I argue that the state justifies this abject outcome via what has been termed “cultural gaslighting.”
An implementation evaluation of a sports-based health intervention for underrepresented middle school youth in Philadelphia
Authors: Joyce Cara R , McLoughlin Gabriella M , Tripicchio Gina L , Jones Gareth J
Published: August 2024

Multicomponent, community-based programs aiming to improve health behaviors in youth are needed but can be challenging to implement. Research is needed to better understand the factors that facilitate and inhibit effective implementation of these programs especially for youth at increased risk of health disparities. This study aimed to identify and explore the implementation determinants and outcomes of a multicomponent health intervention conducted from 2021 to 2022 for middle school students living in underserved communities in Philadelphia, PA, USA. Mixed methods approaches, including self-report surveys and semi-structured qualitative interviews, were administered to 18 members of the implementation staff at the end of the program, including coaches (n = 7), assistant coaches (n = 2), school champions (n = 6), administrative leaders (n = 2), and a school district administrator (n = 1). Survey and interview questions were guided by the Consolidated Framework for Implementation Research (CFIR), and interviews were thematically coded following transcription based on 26 CFIR constructs. Innovation source, evidence strength and quality, cosmopolitanism, and the personal attributes of individuals were key constructs associated with implementation effectiveness. Data revealed three multidimensional themes that highlighted broader challenges influencing implementation: (i) broad consensus, different interpretations, (ii) staffing challenges, and (iii) continuity is key. The need for the program was clearly recognized and overall belief in the purpose of the intervention was strong among key program staff and administration. However, issues including limited engagement with training, staffing turnover, and the rotational programming design hindered implementation. Future projects aiming to implement multicomponent after-school time interventions must ensure a consistent vision among partners and continuity in program delivery.
Diverse biophysical mechanisms in voltage‐gated sodium channel Nav1.4 variants associated with myotonia
Authors: Tikhonova Tatiana B. , Sharkov Artem A. , Zhorov Boris S. , Vassilevski Alexander A.
Published: August 2024

Mutations in SCN4A gene encoding Nav1.4 channel α‐subunit, are known to cause neuromuscular disorders such as myotonia or paralysis. Here, we study the effect of two amino acid replacements, K1302Q and G1306E, in the DIII–IV loop of the channel, corresponding to mutations found in patients with myotonia. We combine clinical, electrophysiological, and molecular modeling data to provide a holistic picture of the molecular mechanisms operating in mutant channels and eventually leading to pathology. We analyze the existing clinical data for patients with the K1302Q substitution, which was reported for adults with or without myotonia phenotypes, and report two new unrelated patients with the G1306E substitution, who presented with severe neonatal episodic laryngospasm and childhood‐onset myotonia. We provide a functional analysis of the mutant channels by expressing Nav1.4 α‐subunit in Xenopus oocytes in combination with β1 subunit and recording sodium currents using two‐electrode voltage clamp. The K1302Q variant exhibits abnormal voltage dependence of steady‐state fast inactivation, being the likely cause of pathology. K1302Q does not lead to decelerated fast inactivation, unlike several other myotonic mutations such as G1306E. For both mutants, we observe increased window currents corresponding to a larger population of channels available for activation. To elaborate the structural rationale for our experimental data, we explore the contacts involving K/Q1302 and E1306 in the AlphaFold2 model of wild‐type Nav1.4 and Monte Carlo‐minimized models of mutant channels. Our data provide the missing evidence to support the classification of K1302Q variant as likely pathogenic and may be used by clinicians.
Medications for Opioid Use Disorder After Entering Residential Treatment: Evidence From Louisiana Medicaid
Authors: Li Wenshu , Eisenberg Matthew , Song Minna , Kennedy-Hendricks Alene , Saloner Brendan
Published: August 2024

Objective

Policies have attempted to increase the use of medication for opioid use disorder (MOUD) during an admission to a residential treatment program, but little is known about the association of residential admission with subsequent MOUD use.

Methods

In a cohort study of Louisiana Medicaid beneficiaries age 18-64 with diagnosed opioid use disorder (OUD), weekly MOUD use and overdose for 20 weeks before and after an admission to residential treatment was analyzed using comparative interrupted time series regression. Participants with residential treatment admission between January 1, 2018, and December 31, 2020 (N = 12,222) were compared against a demographically similar group of people with OUD without residential treatment during the study period.

Results

The samples with residential treatment were largely male (61.9%), White (47.2%), and aged 30 to 39 years (41.4%). At baseline, people admitted to residential treatment were much less likely to use MOUD than the comparison group (4.2% lower, CI: 3.8%, 4.5%, P < 0.01). After admission, use of any MOUD initially increased by 3.1% (P < 0.01) relative to the comparison group, which reverted to the counterfactual trend by 20 weeks. Post-admission MOUD use differed widely by medication. Overdose incidence was highest in the weeks right before admission, but otherwise, it did not change during the study period.

Conclusions

Admission to residential treatment for OUD was associated with a temporary increase in MOUD use. Policy initiatives should focus on both boosting use of MOUD during residential treatment and sustaining access to MOUD in outpatient care in the weeks following discharge.
The Essex-Lopresti Injury
Authors: Heifner John J. , Gray Robert R.L.
Published: August 2024

The classic Essex-Lopresti injury (ELI) pattern is a radial head fracture and disruption of the central band, which compromises the longitudinal radioulnar relationship. Delayed recognition and inappropriate treatment of ELI can be devasting to a patient's function. The recent literature has demonstrated an improved understanding of the mechanism of ELI. This has facilitated early diagnosis, appropriate treatment, and compelling outcomes. Further investigation will contribute to the standardization of treatment methods and algorithms for concomitant injury.
Distal Radioulnar Joint Instability
Authors: Kolovich Gregory P. , Heifner John J. , Falgiano Peter A. , Mahoney Brendan
Published: August 2024

The distal radioulnar joint (DRUJ) is vital to the stability and function of the wrist and forearm. The osseous morphology is variable and provides little stability. A complex of confluent soft tissues is the primary stabilizer; however, the contribution of each component has yet to be elucidated. It has become increasingly clear that the anatomic fixation of distal radius fractures restores DRUJ stability, obviating the need for additional DRUJ stabilization. This review will describe the anatomy and biomechanics of the DRUJ and discuss injury patterns, treatments, and clinical results.
Percutaneous Titanium Elastic Nail Stabilization for Pelvic and Acetabular Fractures: Surgical Technique and Case Series
Authors: Murphy Nicholas J. , Graan David , Balogh Zsolt J.
Published: August 2024

The stabilization of fractures of the anterior pelvic ring and anterior column of the acetabulum with antegrade or retrograde intramedullary screws has been frequently described. However, these narrow and nonlinear bony corridors can be challenging and dangerous to accommodate with rigid linear implants. Titanium elastic nails (TEN) are ideal implants to navigate in the narrow, irregular medullary canal in this anatomical location. This study aims to describe this surgical technique and its preliminary results. From April 2018 to October 2023, patients who underwent acute TEN stabilization of their pelvic or acetabular fractures were identified from a review of medical records at a Level 1 trauma center. A focused review of their clinical documentation was performed to describe their demographics, injury patterns, the surgical techniques used in their treatment, and their clinical and radiographic outcomes. During the almost 6-year period, 19 patients were identified (age: 39 ± 22 years; 74% male). There were 3 acetabulum and 16 pelvic ring fractures stabilized. One of the 19 patients underwent bilateral TEN fixation of the superior pubic rami. Patients were followed-up through hospital outpatient clinics postoperatively (median follow-up 14 months, IQR: 8–24 months). No fractures were complicated by nonunion or secondary displacement of the reduction. A 14-year-old patient required hardware removal due to irritation, and a 19-month-old patient underwent planned hardware removal due to her age. No patients have undergone hip arthroplasty to date, and there were no instances of infection or neurovascular injury. These preliminary results are promising and suggest that larger scale assessment of the indications and feasibility of TEN stabilization in pelvic and acetabular surgery is warranted.
Evaluating the Quality and Impact of TikTok Videos on Autologous Breast Reconstruction with Deep Inferior Epigastric Perforator Artery Flaps
Authors: Adepoju Jubril , Toms John A. , Webb Yvonne Clifvonne G. , Jones Kiana , Hercule Wilmene S. , Jeffreys Katharine E. , Raj Mamtha
Published: August 2024

Background:

With the rising influence of social media on healthcare perceptions, this study investigates TikTok’s role in educating the public about autologous breast reconstruction, specifically focusing on deep inferior epigastric perforator flaps.

Methods:

We conducted a systematic analysis of 152 TikTok videos related to deep inferior epigastric perforator flap procedures, evaluating the accuracy of the content, viewer engagement metrics, and the influence of content creator characteristics on viewer interactions.

Results:

Our analysis identified a wide variance in the quality of information, with many videos lacking in-depth educational content, thereby posing a risk of misinformation. Despite the presence of high-quality educational videos, there was a discrepancy between the educational value provided and viewer engagement levels. Thematic analysis highlighted common concerns among patients, providing insights for healthcare professionals to better tailor their social media content.

Conclusions:

The study underscores the significant impact of platforms like TikTok on patient education and emphasizes the need for healthcare professionals to guide the narrative on social media and ensure the dissemination of accurate and helpful information, ultimately aiding patients in making informed decisions about their healthcare.
RETINAL ARTERIAL MACROANEURYSM COMBINED WITH BRANCH RETINAL ARTERY OCCLUSION
Authors: Zhou Zigan , Lin Zhong , Guo Binghua , Yang Chen , Wu Xingyi , Sun Bi , Liu Yuhao , Wu Ronghan
Published: August 2024

Purpose:

To summarize the causes of retinal arterial microaneurysm combined with branch retinal artery occlusion.

Methods:

The case reports of retinal arterial microaneurysm combined with branch retinal artery occlusion were searched in PubMed, Web of Science, and CNKI databases before May 1, 2024. A total of nine participants from nine case reports were included to analyze factors leading to complications.

Results:

The reasons for this complication are as follows: complications during photocoagulation therapy. Intraretinal hemorrhage and exudation result in compression of adjacent or distal arteries, resulting in branch retinal artery occlusion. Embolus dislodgement or intraarterial embolus formation can block the artery, damage the wall, and provide conditions for the development of retinal arterial microaneurysm. In addition, it is necessary to be alert to the optic disk macroaneurysm, if hemorrhage or embolus formation in the macroaneurysm will affect the blood supply of the downstream artery, affecting a large range of the retina.

Conclusion:

Based on the review of case reports, we found that retinal arterial microaneurysm and branch retinal artery occlusion can cause each other. Acute vision loss can result when a complication occurs. In addition, retinal vascular diseases can reflect the whole body, suggesting that ophthalmologists need to pay attention not only to the patient's fundus but also to the patient's systemic diseases.
HIGH-RISK HISTOPATHOLOGICAL FEATURES OF RETINOBLASTOMA FOLLOWING PRIMARY ENUCLEATION
Authors: Kaliki Swathi , Vempuluru Vijitha S. , Bakal Komal Rajendra , Dorji Samten , Tanna Vishakha , Shields Charlotte N. , Fallon Samuel J. , Raval Vishal , Ahmad Alia , Mushtaq Asma , Hussain Mahvish , Yousef Yacoub A. , Mohammad Mona , Roy Soma Rani , Huque Fahmida , Tatiana Ushakova , Yuri Serov , Vladimir Polyakov , Zambrano Sandro Casavilca , Alarcón-León Sandra , Valdiviezo-Zapata Cinthya , Vargas-Martorellet Maria , Gutierrez-Chira Cynthia , Buitrago Mario , Ortiz Joana Sánchez , Diaz-Coronado Rosdali , Tripathy Devjyoti , Rath Suryasnata , Patil Gaurav , Berry Jesse L. , Pike Sarah , Brown Brianne , Tanabe Mika , Frenkel Shahar , Eiger-Moscovich Maya , Pe'er Jacob , Shields Carol L. , Eagle Ralph C. , Laiton Andrea , Velasco Ana Maria , Vega Katherine , DeSimone Joseph , Bejjanki Kavya Madhuri , Kapoor Anasua Ganguly , Venkataraman Anusha , Bryant Victoria , Reddy M. Ashwin , Sagoo Mandeep S. , Hubbard G. Baker , Azarcon Corrina P. , Olson Thomas A. , Grossniklaus Hans , Rolfe Olivia , Staffieri Sandra E. , O'Day Roderick , Mathew Anu A. , Elder James E. , McKenzie John D. , Fabian Ido Didi , Shemesh Rachel , Vishnevskia-Dai Vicktoria , Ali Mohammed Hasnat , Jakati Saumya , Mishra Dilip K. , Palkonda Vijay Anand Reddy ,   High-Risk Retinoblastoma Collaborative Study Group
Published: August 2024

Purpose:

To evaluate high-risk histopathological features following primary enucleation of eyes with retinoblastoma and assess the patient outcomes across continents.

Methods:

A retrospective study of 1,426 primarily enucleated retinoblastoma eyes from five continents.

Results:

Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathological features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, P = 0.001), postlaminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, P = 0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, P = 0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, P = 0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given to 761 (53%) patients. Based on Kaplan–Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% versus 2% versus 0% versus 0% versus 12% (P < 0.001), systemic metastasis was reported in 8% versus 5% versus 2% versus 0% versus 13% (P = 0.001), and death in 10% versus 3% versus 2% versus 0% versus 11% (P < 0.001) patients.

Conclusion:

There is a wide variation in the infiltrative histopathological features of retinoblastoma across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.
Integrating Genetics in Glaucoma Screening
Authors: Mackey David Anthony , Bigirimana Deus , Staffieri Sandra Elfride
Published: August 2024

Précis:

As additional glaucoma genes are identified and classified, polygenic risk scores will be refined, facilitating early diagnosis and treatment. Ensuring genetic research is equitable to prevent glaucoma blindness worldwide is crucial.

Purpose:

To review the progress in glaucoma genetics over the past 25 years, including the identification of genes with varying contributions to the disease and the development of polygenic risk scores.

Methods/Results:

Over the last 2 and a half decades, glaucoma genetics has evolved from identifying genes with Mendelian inheritance patterns, such as myocilin and CYP1B1, to the discovery of hundreds of genes associated with the disease. Polygenic risk scores have been developed, primarily based on research in Northern European populations, and efforts to refine these scores are ongoing. However, there is a question regarding their applicability to other ethnic groups, especially those at higher risk of primary open angle glaucoma, like individuals of African ancestry. Glaucoma is highly heritable and family history can be used for cascade clinical screening programs, but these will not be feasible in all populations. Thus, cascade genetic testing using well-established genes such as myocilin may help improve glaucoma diagnosis. In addition, ongoing investigations seek to identify pathogenic genetic variants within genes like myocilin.

Conclusions:

The expanding availability of genetic testing for various diseases and early access to genetic risk information necessitates further research to determine when and how to act on specific genetic results. Polygenic risk scores involving multiple genes with subtle effects will require continuous refinement to improve clinical utility. This is crucial for effectively interpreting an individual’s risk of developing glaucoma and preventing blindness.
Screening Strategies and Methodologies
Authors: Founti Panagiota , Stuart Kelsey , Nolan Winifred P. , Khawaja Anthony P. , Foster Paul J.
Published: August 2024

Précis:

While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease.

Purpose:

To review the current evidence and concepts around screening for glaucoma.

Methods/Results:

A group of glaucoma-focused clinician scientists drew on knowledge and experience around glaucoma, its etiology, and the options for screening. Glaucoma is a chronic progressive optic neuropathy affecting around 76 million individuals worldwide and is the leading cause of irreversible blindness globally. Early stages of the disease are asymptomatic meaning a substantial proportion of cases remain undiagnosed. Early detection and timely intervention reduce the risk of glaucoma-related visual morbidity. However, imperfect tests and a relatively low prevalence currently limit the viability of population-based screening approaches. The diagnostic yield of opportunistic screening strategies, relying on the identification of disease during unrelated health care encounters, such as cataract clinics and diabetic retinopathy screening programs, focusing on older people and/or those with a family history, are hindered by a large number of false-positive and false-negative results. Polygenic risk scores (PRS) offer personalized risk assessment for adult-onset glaucoma. In addition, artificial intelligence (AI) algorithms have shown impressive performance, comparable to expert humans, in discriminating between potentially glaucomatous and non-glaucomatous eyes. These emerging technologies may offer a meaningful improvement in diagnostic yield in glaucoma screening.

Conclusions:

While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease.
Implementation and Consensus
Authors: Cioffi George A. , Liebmann Jeffrey M. , Friedman David , Pasquale Louis
Published: August 2024

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Sentinel Lymph Node Mapping in Prostate Cancer: Magnetic Route
Authors: Molenaar Lennert , Roelink Herman J. H. , Stomps Saskia , Haken Bennie ten , Hulsbergen-van de Kaa Christina , Braak Sicco , Veltman Jeroen , Alic Lejla , Broeders Ivo A. M. J.
Published: August 2024

Purpose:

Prostate cancer is the predominant cancer type among Western men. Despite the application of radical treatments, a notable recurrence risk is linked to metastatic lymph nodes (LNs) beyond the standard resection area. Consequently, the concept of sentinel LN biopsy (SLNB) was introduced to pinpoint LNs draining from the primary tumor. The magnetic nanoparticles (MNPs) as a tracer facilitating SLNB hold promise for preoperative LN staging. Therefore, the primary objective of this pilot study was to explore the potential of MNPs in aiding preoperative LN staging and detecting perioperative LNs.

Materials and Methods:

One day before the surgery, patients received ultrasound-guided transrectal injection of a magnetic tracer. MRI was acquired 1 hour after the injection. Magnetic measurements were conducted using 2 handheld probes on the resected material, following laparoscopic radical prostatectomy. Follow-up MRI was acquired 12 weeks postsurgery.

Results:

Two of the 12 patients had histopathologic-confirmed metastatic lymph nodes. Magnetic detectors identified a total of 113 lymph nodes, with 105 containing magnetic tracer at histopathology. Both magnetic detectors exhibited similar performance. Preoperative MNP-enhanced MRI revealed 166 lymph nodes, with 104 within and 62 outside the extended pelvic lymph node dissection (ePLND) area. Postoperative MRI displayed 95 lymph nodes, with 48 within and 47 outside the ePLND.

Conclusions:

This pilot study has proven the feasibility of a thorough magnetic procedure, evaluating its essential components: tracer injection, dispersion of sentinel lymph nodes in the pelvic region, identification of lymph nodes by magnetic nanoparticle MNP-enhanced MRI, and magnetic lymph node detection using two distinct devices.
Subgroup analyses and heterogeneity of treatment effects in randomized trials: a primer for the clinician
Authors: Spicer Alexandra B. , Cavalcanti Alexandre B. , Zampieri Fernando G.
Published: August 2024

Purpose of review

To date, most randomized clinical trials in critical care report neutral overall results. However, research as to whether heterogenous responses underlie these results and give opportunity for personalized care is gaining momentum but has yet to inform clinical practice guidance. Thus, we aim to provide an overview of methodological approaches to estimating heterogeneity of treatment effects in randomized trials and conjecture about future paths to application in patient care.

Recent findings

Despite their limitations, traditional subgroup analyses are still the most reported approach. More recent methods based on subphenotyping, risk modeling and effect modeling are still uncommonly embedded in primary reports of clinical trials but have provided useful insights in secondary analyses. However, further simulation studies and subsequent guidelines are needed to ascertain the most efficient and robust manner to validate these results for eventual use in practice.

There is an increasing interest in approaches that can identify heterogeneity in treatment effects from randomized clinical trials, extending beyond traditional subgroup analyses. While prospective validation in further studies is still needed, these approaches are promising tools for design, interpretation, and implementation of clinical trial results.