bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Treatment Receipt and Hospitalization Among Patients With Stimulant Use Disorder and/or Opioid Use Disorder in the Veterans Health Administration
Authors: Frost Madeline C. , Coughlin Lara N. , Zhang Lan , Lin Lewei (Allison)
Published: June 2024

Objectives

Stimulant use is a growing problem, but little is known about service utilization among patients with stimulant use disorder (StUD). In the context of the overdose crisis, much research has focused on patients with opioid use disorder (OUD). It is unclear how the characteristics, treatment receipt, and hospitalization of patients with StUD differ from patients with OUD.

Methods

Electronic health record data were extracted for national Veterans Health Administration patients with a visit from March 1, 2020, to February 28, 2021 with StUD and/or OUD (N = 132,273). We compared patients with StUD without OUD to those with (1) co-occurring StUD + OUD and (2) OUD without StUD. Patient characteristics, substance use disorder treatment, and hospitalizations in the year following patients’ first study period visit were descriptively compared. Treatment and hospitalization were also compared in adjusted regression models.

Results

Compared with patients with OUD + StUD, those with StUD without OUD were less likely to receive outpatient (adjusted odds ratio [aOR] 0.49, 95% confidence interval [CI] 0.47–0.50) or any treatment (aOR 0.47, 95% CI 0.46–0.49). Compared with patients with OUD without StUD, those with StUD without OUD were less likely to receive outpatient (aOR 0.51, 95% CI 0.49–0.52) or any treatment (aOR 0.56, 95% CI 0.54–0.58) and more likely to receive residential treatment (aOR 2.18, 95% 2.05–2.30) and to be hospitalized (aOR 1.62, 95% 1.56–1.69).

Conclusions

Patients with StUD may be less likely to receive treatment and more likely to be hospitalized than patients with OUD. Efforts focused on mitigating hospitalization and increasing treatment receipt for patients with StUD are needed.
Genome-wide DNA methylation profiles and breast cancer among World Trade Center survivors
Authors: Tuminello Stephanie , Ashebir Yibeltal Arega , Schroff Chanel , Ramaswami Sitharam , Durmus Nedim , Chen Yu , Snuderl Matija , Shao Yongzhao , Reibman Joan , Arslan Alan A.
Published: June 2024

Background:

Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer.

Methods:

WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women’s Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis.

Results:

A total of 64 WTC-exposed (32 cancer free and 32 with breast cancer) and 32 WTC-unexposed (16 cancer free and 16 with prediagnostic breast cancer) participants were included. Hypermethylated cytosine–phosphate–guanine probe sites (defined as β > 0.8) were more common among WTC-exposed versus unexposed participants (14.3% vs. 4.5%, respectively, among the top 5000 cytosine–phosphate–guanine sites). Cancer-related pathways (e.g., human papillomavirus infection, cGMP-PKG) were overrepresented in WTC-exposed groups (breast cancer patients and cancer-free subjects). Compared to the unexposed breast cancer patients, 47 epigenetically dysregulated genes were identified among WTC-exposed breast cancers. These genes formed a network, including Wnt/β-catenin signaling genes WNT4 and TCF7L2, and dysregulation of these genes contributes to cancer immune evasion.

Conclusion:

WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism.
Combined Central Retinal Artery and Vein Occlusion-like Manifestations with Aplastic Anemia: Unveiling Pathophysiological Insights
Authors: de Santana Carlos Rodrigo Damasceno Feitosa , Ferreira Felipe de Queiroz Tavares
Published: June 2024

Purpose:

To report the association of a combined central artery and vein occlusion (CCRAVO)-like pattern with aplastic anemia and discuss the pathophysiology associated with ophthalmologic examinations.

Methods:

We report a female patient with aplastic anemia who presented with retinal hemorrhage, blurred optic disc margins, retinal whitening, peripapillary subretinal fluid, and venous engorgement. The authors described the evolution of ophthalmologic lesions in correlation with improvements in systemic conditions.

Results:

We discuss and correlate the ophthalmological findings of this patient (optic disc edema, vascular engorgement, subretinal fluid, among others) with the pathophysiology of Aplastic Anemia based on current literature.

Conclusion:

These findings provide a better understanding of the pathophysiology of this rare disease. In certain cases, ophthalmologic symptoms can be the first presentation, underscoring the importance of reporting ocular findings for the recognition of this disease, which entails significant systemic involvement.
Genetic etiology study in a large cohort with congenital insensitivity to pain with anhidrosis
Authors: Li Shuang , Ren Xiuzhi , Guan Yun , Zhao Feiyue , Cao Yixuan , Geng Xingzhu , Wang Yanzhou , Wu Nan , Wu Lingqian , Zhao Xiuli
Published: June 2024

Pathogenic variations in the NTRK1 can cause congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive inherited neuropathy. The precise diagnosis of CIPA relies on the identification of pathogenic genotypes. Therefore, it is essential to expand the NTRK1 variation spectrum and improve molecular diagnosis methods. In this study, 74 probands with typical manifestations of CIPA but unknown genotypes were recruited. A comprehensive molecular genetic analysis was performed to identify variations in the NTRK1, using techniques including Sanger and next-generation sequencing, bioinformatic analysis, quantitative polymerase chain reaction (qPCR), gap-PCR, short tandem repeat (STR) genotyping, and reverse-transcription PCR. In addition, functional assays were conducted to determine the pathogenicity of variants of uncertain significance (VUS) and further characterized changes in glycosylation and phosphorylation of 14 overexpressed mutant vectors with variants at different domains in the TrkA protein, which is encoded by NTRK1. A total of 48 variations in the NTRK1 were identified, including 22 novel ones. When combined with data from another 53 CIPA patients examined in our previous work, this study establishes the largest genotypic and phenotypic spectra of CIPA worldwide, including 127 CIPA families. Moreover, functional studies indicated that the pathogenicity of VUS mainly affected insufficient glycosylation in the extracellular domain and abnormal phosphorylation in the intracellular domain. This study not only provides important evidence for precise diagnosis of CIPA but also further enriches our understanding of the pathogenesis of this disease.
Iron Deficiency Among Hospitalized Patients With Congestive Heart Failure
Authors: Foust Rick , Clarkson Stephen , Nordberg Megan , Joly Joanna , Griffin Russell , May Jori
Published: June 2024

Introduction:

Studies have demonstrated the efficacy of intravenous (IV) iron when administered to patients with congestive heart failure (CHF) and iron deficiency (ID). We aimed to better understand the adherence of treatment for ID among a population with CHF, with particular interest in high-risk groups not often studied due to inadequate recruitment.

Methods:

A retrospective chart review at our institution was conducted from January 1, 2012, to July 7, 2021. Analysis included hospitalized patients with CHF and ID and dividing these patients into two time periods based on changes in iron treatment patterns and treatment between sexes.

Results:

Four thousand eight hundred thirteen patients were included in this study. During the “early era,” 7.0% of patients with CHF and ID received IV iron compared with 20.9% of “late-era” patients. Female patients with ID were statistically less likely to receive IV iron when compared with male patients, both unadjusted (0.66, confidence interval [CI] 0.55–0.79, p < .0001) and adjusted (0.72, CI 0.59–0.87, p < .0001) for covariates.

Conclusion:

This study illustrates improved adherence to treatment for ID among hospitalized population with CHF and ID over time but persistent undertreatment remains. Future studies will need to identify the barriers to treating female patients with CHF and ID to reduce these disparities.
Sustainability of a Pediatric Neurointensive Care Unit Model Within a Mixed Pediatric Intensive Care Unit and Its Effect on Nursing Sentiment
Authors: Chang Nathan , Casazza May , Sperber Amelia , Ciraulo Leslie , Rodriguez Jennifer , Marquiss Katherine , D'Anjou Lisa , Teeyagura Prathyusha , Chaillou Anne-Laure , Palmquist Andrew , Rasmussen Lindsey
Published: June 2024

BACKGROUND: Pediatric neurocritical care (PNCC) and pediatric neurointensive care units (neuro-PICU) are growing fields. Although some institutions have established independent neuro-PICUs meeting most Neurocritical Care Society (NCS) standards for neurocritical care units, many centers lack the resources to do so. We describe an alternative neuro-PICU model as a designated unit within a mixed pediatric intensive care unit (PICU) and its effects on nursing sentiment. METHODS: We established a 6-bed neuro-PICU within a 36-bed noncardiac PICU. Charge nurses were tasked with admitting PNCC patients into these beds. For nursing expertise, we used a core group of 12 PNCC specialty nurses and instituted PNCC nursing education to PICU nurses. We observed the number of PNCC patients admitted to neuro-PICU beds and surveyed charge nurses to identify barriers to assigning patients. We surveyed PICU nursing staff to explore sentiment regarding PNCC before and after establishing the neuro-PICU. Nursing criteria were compared with NCS standards. RESULTS: In the 40-month period, our PICU saw 2060 PNCC admissions. Overall, occupied neuro-PICU beds housed PNCC patients 74.1% of the time. The biggest barriers to patient placement were too many competing placement requests, not enough neuro-PICU beds when specialty census was high, and difficulty assigning one nurse to two PNCC patients. In surveys after establishing the neuro-PICU, compared to before, experienced nurses reported being more interested in obtaining Emergency Neurological Life Support certification (94.2% vs 80.6%, P = .0495), and inexperienced nurses reported being more familiar with PNCC clinical pathways (53.5% vs 31.7%, P = .0263). Most NCS criteria related to nursing organization were met. CONCLUSIONS: Focused neuro-PICUs should be developed to complement advances in the field of PNCC. Alternative neuro-PICU models are possible and can increase nursing interest in further education and awareness of clinical pathways, but barriers exist that require institutional commitment to nursing development to sustain the delivery of specialized care to this population.
Noninfectious causes of alopecia in the pediatric population
Authors: Saliba Elie , Shah Asghar , Wahood Samer , Chrabieh Remie
Published: June 2024

Purpose of review

To highlight recent advances in the knowledge base surrounding noninfectious causes of alopecia in the pediatric population.

Recent findings

Recent developments in the literature included assessments of treatment efficacy, diagnostic utility of trichoscopy, and retrospective studies characterizing the clinical picture of pediatric cases.

These findings will equip practitioners with the recent advances in the field's understanding of noninfectious causes of alopecia in the pediatric population.
Plant-based diets, animal agriculture, and the connection with urological and planetary health
Authors: Gupta Natasha , Leapman Michael S. , Loeb Stacy
Published: June 2024

Purpose of review

We summarize the latest evidence regarding the impact of plant-based diets on urological and planetary health to facilitate patient counseling and research regarding dietary intervention.

Recent findings

Studies have highlighted the association of plant-based diets with a lower risk of multiple urological conditions including prostate cancer, erectile dysfunction, benign prostatic hyperplasia, and nephrolithiasis, as well as benefits for planetary health.

Plant-based diets are associated with numerous benefits that co-promote urological and planetary health.
Novel phages of Pseudomonas syringae unveil numerous potential auxiliary metabolic genes
Authors: Feltin Chloé , Garneau Julian R. , Morris Cindy E. , Bérard Annette , Torres-Barceló Clara
Published: June 2024

Relatively few phages that infect plant pathogens have been isolated and investigated. The Pseudomonas syringae species complex is present in various environments, including plants. It can cause major crop diseases, such as bacterial canker on apricot trees. This study presents a collection of 25 unique phage genomes that infect P. syringae. These phages were isolated from apricot orchards with bacterial canker symptoms after enrichment with 21 strains of P. syringae. This collection comprises mostly virulent phages, with only three being temperate. They belong to 14 genera, 11 of which are newly discovered, and 18 new species, revealing great genetic diversity within this collection. Novel DNA packaging systems have been identified bioinformatically in one of the new phage species, but experimental confirmation is required to define the precise mechanism. Additionally, many phage genomes contain numerous potential auxiliary metabolic genes with diversified putative functions. At least three phages encode genes involved in bacterial tellurite resistance, a toxic metalloid. This suggests that viruses could play a role in bacterial stress tolerance. This research emphasizes the significance of continuing the search for new phages in the agricultural ecosystem to unravel novel ecological diversity and new gene functions. This work contributes to the foundation for future fundamental and applied research on phages infecting phytopathogenic bacteria.
Technical and ethical challenges in polygenic embryo selection
Authors: Namba Shinichi , Akiyama Masato , Hamanoue Haruka , Kato Kazuto , Kawashima Minae , Kushima Itaru , Matsuda Koichi , Nakatochi Masahiro , Ogishima Soichi , Sonehara Kyuto , Suzuki Ken , Takata Atsushi , Tamiya Gen , Tanikawa Chizu , Yamamoto Kenichi , Yamamoto Natsuko ,   The BioBank Japan Project, Ozaki Norio , Okada Yukinori
Published: June 2024

Whereas best practice of clinical prediction of human phenotypes by polygenic risk score (PRS) has yet to be fully implemented, commercial industries already offer pre-implantation genetic testing for PRS (PGT-P) to select embryos with ‘desirable’ potential. However, its efficacy is questionable due to the current technical challenges, which also raise ethical concerns. Ourin-silicosimulations utilizing biobank resources revealed that the embryo selected by PGT-P substantially differs depending on the choice of methods and the random fluctuation of the PRS construction. Here, we outline the technical challenges and also the ethical concerns that remain even if the technical challenges are solved, and hope to call on a society-wide discussion for this technology.
Men’s Willingness to Receive Text Messages and Talk with an HIV counselor from the National HIV Hotline in Tanzania for Support with Linkage to Care Following HIV self-testing
Authors: Mhando Frank , Olughu Kelia , Nyankomo Marwa , Ngocho James S. , Teri Ivan , Mbita Gaspar ,   BRIDGE Africa Team, Conserve Donaldson F.
Published: June 2024

Background

Tanzania faces a significant burden of HIV, with particular challenges in reaching men and ensuring timely linkage to care. To address these issues, HIV self-testing (HIVST) has been implemented to increase HIV testing and the National HIV Hotlines are being considered as a strategy to facilitate linkage to care. This study aimed to assess the willingness of Tanzanian men to receive support from use the National HIV Hotline via mobile phones for HIVST and linkage to care.

Methods

Data from 505 men from the baseline survey of a cluster-randomized controlled trial conducted in June 2019 with 18 social networks or “camps” in Dar es Salaam, Tanzania. Participants were 18-year-old or older male camp members who were HIV-negative at the time of enrolment. Logistic regression models were used to assess factors associated with men’s comfort with talking with an HIV counselor over the phone.

Results

There were 505 heterosexual male participants enrolled in the study with an average age of 29 years. Logistic regression demonstrated that comfortability texting a friend about HIV self-testing (OR =3.37, 95% CI [1.97 – 5.76], being comfortable texting a friend about HIV (OR = 3.84, 95% CI [2.20 – 6.72], previous history of receiving HIV related text messages (aOR = 0.55, 95% CI [0.31 – 0.99] were significantly associated with men’s s comfortability talking to a HIV counselor on the National HIV Hotline following HIVST. The factors such as participants’ comfortability texting friend about HIVST (OR = 2.52, 95% CI [1.49 – 4.25]) and comfortability texting friend about HIV (OR = 2.96, 95% CI [1.83 – 4.80] were significantly associated with the probability of participant’s comfortability receiving text message from HIV counselor following HIVST.

Conclusion

These findings suggest an effort to develop and implement a user-friendly digital health intervention that promote comfortability, address private concerns, and deliver tailored support and information to individuals following HIV self-testing.
The Healthy Minds, Thriving Kids Project – a mental health and wellbeing prevention program for young people, results of a survey to understand the perspective of educators on program relevance and potential impact
Authors: Anderson David , Chapman Jeffrey , Domingues Janine , Bobadilla Gabriella , Corcoran Mimi , Koplewicz Harold
Published: June 2024

Background

Healthy Minds Thriving Kids (HMTK) is a free to user mental health prevention program developed by the Child Mind Institute with the aim to normalize conversations about mental health and provide educators with wellness tools.

Methods

The HMTK program was available to view by registrants between 26thJanuary 2022 and 7thSeptember 2022 in the State of California. Participants viewed an introductory video for the program and a minimum of two skills videos before participating in an online survey.

Results

Of 68,861 registrants to the website 64,376 provided survey data. Post-pandemic levels of stress and anxiety were increased and 89.5% of respondents said young people required a greater degree of support than previously. Almost all educators (90%) want additional mental health and wellbeing tools for students and following review of HMTK >80% of respondents said they would use the program in their classrooms. Most (86.6%) found the program engaging and 85.1% found the program relevant to, and representative of, their student cohorts. More than three quarters (79.6%) said their students would find the program engaging and beneficial, and 18.8% more educators believed that HMTK was indicative of commitment to educators by the State of California in supporting students’ social and emotional learning.

Conclusion

This survey demonstrates that the HMTK program is a valuable and complementary resource to school curricula to improve the mental health and wellbeing of young people. It provides an easy to implement framework that school districts and administrators can allocate within their curriculum planning.
An investigation of multisensory perception of surrounding space in aided congenitally hearing impaired
Authors: Snir Adi , Cieśla Katarzyna , Vekslar Rotem , Amedi Amir
Published: June 2024

We tested auditory spatial motion localisation in congenitally hearing impaired adult users of bilateral cochlear implants, and other hearing assistive devices. The group showed severely impaired capabilities despite extensive device use, emphasizing the role ofnaturein sensory development. We then investigate whether the deficit is maintained for other sensory modalities, by using an in-house sensory substitution device that provides weighted vibrotactile cues on fingertips to induce 3D spatial motion perception. The performance was significantly higher, both in the combined audio-tactile task and the tactile task itself, with accuracy comparable to typically hearing subjects. With touch, we also showed considerably fewer front-back and right-left confusions. The rapid audio-tactile binding and availability of 3D space representation through touch, point to the significant role ofnurturein spatial perception development and its amodal nature. The findings show promise towards advancing multisensory solutions for spatial hearing rehabilitation.

Highlights

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Auditory motion localisation is severely impaired in aided congenitally hearing impaired, supporting the role ofnaturetowards spatial development;

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Binding auditory and tactile information enhances auditory spatial performance, supporting the role ofnurture;

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Hearing impaired individuals perform 360° motion localisation through touch with accuracy similar to typically hearing;

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Surrounding spatial representation never before experienced in congenitally hearing impaired is rapidly available through an alternate modality
Germline mutations in young-onset sporadic pituitary macroadenomas: a multigene panel analysis
Authors: Gaspar Leonor M. , Gonçalves Catarina I. , Nobre Ema L. , Fonseca Fernando , Amaral Cláudia , Duarte João S. , Raimundo Luísa , Saraiva Catarina , Cortez Luísa , Marques Olinda , Lemos Manuel C.
Published: June 2024

Objective

Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic pituitary adenomas (i.e. with no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations in these genes, especially in young patients with larger tumours. The aim of this study was to determine the frequency of germline mutations in patients with young-onset sporadic pituitary macroadenomas.

Methods

A cohort of 225 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years was studied by whole exome sequencing (WES) followed by the analysis of a virtual panel of 29 genes that have been associated with predisposition to pituitary adenomas.

Results

Pathogenic and likely pathogenic variants were identified in 16 (7.1%) of patients. The affected genes wereAIP(n=4),PMS2(n=4),MEN1(n=2),VHL(n=2),CDH23(n=1),MSH2(n=1),SDHB(n=1), andTP53(n=1). In patients diagnosed under the ages of 30 and 18 years, the frequency of mutations increased to 9.0% and 12.0%, respectively.

Conclusion

This is so far the largest multigene analysis of patients with young-onset sporadic pituitary macroadenomas. We confirmed theAIPas the most frequently involved gene, but also uncovered rarer genetic causes of pituitary adenomas, including the first independent confirmation of a role of theCDH23gene. The results may contribute to a better understanding of the genetic landscape of these tumours and help to decide which genes to include in the genetic screening of patients with young-onset pituitary macroadenomas.
LncRNA PAN3-AS1 modulates cilium assemble signaling pathway through regulation of RPGR as a potential MS diagnostic biomarker: integrated systems biology investigation
Authors: Mostaghimi Yasaman , Haddadi Mohammad , Hojjati Zohreh
Published: June 2024

Introduction

Multiple sclerosis (MS), an autoimmune condition of the central nervous system (CNS), can lead to demyelination and axonal degeneration in the brain and spinal cord, which can cause progressive neurologic disability. MS symptoms include autonomic dysfunction, such as insomnia, neuropathic and nociceptive pain, cognitive impairment, spasticity, dysesthesia, anxiety, and depression, significantly reducing patient quality of life. These symptoms appear in addition to the progressive decline in the nervous system’s motor abilities. In this investigation, we performed an integrated bioinformatics and experimental approach to find the expression level and interaction of a novel long non-coding RNA (lncRNA), PAN3-AS1, in MS samples.

Methods

Microarray analysis was performed by R Studio using GEOquery and limma packages. lncRNA-mRNA RNA interaction analysis was performed using the lncRRIsearch database. Pathway enrichment analysis was performed by KEGG and Reactome online software through the Enrichr database. Protein-protein interaction analysis was performed by STRING online software. Gene ontology (GO) analysis was performed by Enrichr database.

Results

Based on microarray analysis, lncRNA PAN3-AS1 has a significantly low expression in MS samples compared to the control (logFC: −1.2, adj. P. Val: 0.03). qRT-PCR results approved bioinformatics analyses. ROC analysis revealed that PAN3-AS1 could be considered a potential diagnostic biomarker of MS. Based on lncRNA-mRNA interaction analysis, lncRNA PAN3-AS1 regulates the expression level of RPGR. RPGR and its protein interactome regulate the cilium assembly, chaperon-mediated autophagy, and microarray biogenesis.

Conclusion

lncRNA PAN3-AS1, as a significant low-expressed lncRNA in MS samples, could be a potential diagnostic MS biomarker. PAN3-AS1 might regulate the expression level of cilium assembly and chaperon-mediated autophagy. Dysregulation of PAN3-AS1 might affect the expression of RPGR and its protein interactome.
Dysfunction of proprioceptive sensory synapses is a pathogenic event and therapeutic target in mice and humans with spinal muscular atrophy
Authors: Simon CM , Delestree N , Montes J , Gerstner F , Carranza E , Sowoidnich L , Buettner JM , Pagiazitis JG , Prat-Ortega G , Ensel S , Donadio S , Garcia JL , Kratimenos P , Chung WK , Sumner CJ , Weimer LH , Pirondini E , Capogrosso M , Pellizzoni L , Vivo DC De , Mentis GZ
Published: June 2024

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by a varying degree of severity that correlates with the reduction of SMN protein levels. Motor neuron degeneration and skeletal muscle atrophy are hallmarks of SMA, but it is unknown whether other mechanisms contribute to the spectrum of clinical phenotypes. Here, through a combination of physiological and morphological studies in mouse models and SMA patients, we identify dysfunction and loss of proprioceptive sensory synapses as key signatures of SMA pathology. We demonstrate that SMA patients exhibit impaired proprioception, and their proprioceptive sensory synapses are dysfunctional as measured by the neurophysiological test of the Hoffmann reflex (H-reflex). We further show that loss of excitatory afferent synapses and altered potassium channel expression in SMA motor neurons are conserved pathogenic events found in both severely affected patients and mouse models. Lastly, we report that improved motor function and fatigability in ambulatory SMA patients and mouse models treated with SMN-inducing drugs correlate with increased function of sensory-motor circuits that can be accurately captured by the H-reflex assay. Thus, sensory synaptic dysfunction is a clinically relevant event in SMA, and the H-reflex is a suitable assay to monitor disease progression and treatment efficacy of motor circuit pathology.

One-sentence summary

Sensory-motor circuit dysfunction involving impairment of proprioceptive synapses on motor neurons is a conserved pathogenic event and therapeutic target across animal models and humans with spinal muscular atrophy.
Bulwark Effect of Response in a Causal Model of Disruptive Clinician Behavior
Authors: Fujimoto Manabu , Shimamura Mika , Miyazaki Hiroaki , Inaba Kazuto
Published: June 2024

INTRODUCTION

Disruptive clinician behavior (DCB) refers to unethical and unprofessional behavior that seriously affects patient safety by disrupting relationships among healthcare professionals and causing dysfunctional communication and teamwork. DCB often persists as an organizational culture in Japanese healthcare settings because of problems in the conventional leadership system along with professional and positional hierarchies. Therefore, this study verified a causal model of DCB in Japanese healthcare, including triggers, response, and impact.

METHODS

Staff at two general hospitals (751 and 661 beds) were surveyed using a web-based questionnaire. In total, 256 staff who had experienced victimization and agreed to complete the questionnaire were included in this study. The questionnaire comprised demographic information, a DCB scale, and items covering causal indicators of DCB: triggers, response, and impact (psychological/social and medical/management).

RESULTS

Mediation and moderated mediation analyses showed that: (1) DCB had a negative impact on the medical/managerial state, which was partially mediated by psychological/social impact; and (2) the responses of victims and others acted as a bulwark in reducing the psychological/social impact to some extent.

DISCUSSION

A prompt response to DCB as a bulwark reduces victims’ psychological and social adaptation deterioration. Therefore, occurrences of DCB should not be overlooked, and the victim and those around them should respond positively. However, response as a bulwark cannot protect the organization’s medical care and management. Therefore, it is important to prevent DCB.
Detection of obstetric anal sphincter injuries using machine learning-assisted impedance spectroscopy: a prospective, comparative, multicentre clinical study
Authors: Borycka Katarzyna , Młyńczak Marcel , Rosoł Maciej , Korzeniewski Kacper , Iwanowski Piotr , Heřman Hynek , Janku Petr , Uchman-Musielak Małgorzata , Dosedla Erik , Diaz Enrique Gonzalez , Sudoł-Szopińska Iwona , Mik Michał , Ratto Carlo , Spinelli Antonino
Published: June 2024

Objective

To evaluate the clinical performance and safety of the ONIRY system for obstetric anal sphincter injuries (OASI) detection versus three-dimensional endoanal ultrasound (EAUS).

Design

A prospective, comparative, multicentre, international study. Setting: Poland, Czechia, Slovakia, and Spain.

Population

152 women between the first moments up to 8 weeks after vaginal delivery.

Methods

Participants underwent EAUS and were allocated to groups based on OASIS classification: A (no perineal tear), B (1st or 2nd degree tear), or C (3rd or 4th degree, anal sphincters affected). Electric impedance was measured in the anal canal using the ONIRY system. The primary endpoint was the diagnostic outcome of impedance spectroscopy versus EAUS. Adverse events were collected. Part II involved in silico modelling and 10-time 10-fold cross-validation for automated analysis.

Main Outcome Measures

Accuracy, sensitivity, and specificity.

Results

30 women were allocated to group A, 61 to group B, and 61 to group C. The diagnostic outcome was determined for 147 participants. The accuracy, sensitivity, and specificity of the ML-assisted impedance spectroscopy were 87.0 ± 0.5%, 90.6 ± 2.0%, and 84.6 ± 1.9%, respectively, compared with EAUS. After data cleaning, the performance metrics of the proposed final ML model for ONIRY were: 90.0 ± 0.4%, 90.0 ± 1.2%, and 90.0 ± 0.7%, respectively. No adverse device effects or deficiencies were observed.

Conclusion

ML-assisted impedance spectroscopy offers a safe and accurate method for rapid OASI detection. This approach could effectively complement digital rectal examination in obstetric settings, supporting timely postpartum care.

Funding information

The study was financed by the Polish National Centre for Research and Development (POIR.01.01.01-00-0726/18).

Key Message

With 90% accuracy, the ONIRY system’s ML-assisted impedance spectroscopy offers a reliable, non-invasive method for detecting obstetric anal sphincter injuries, supporting timely postpartum diagnosis.
Complement-dependent virion lysis mediated by dengue-Zika virus cross-reactive antibodies correlates with protection from severe dengue disease
Authors: Dias Antonio G. , Duarte Elias , Zambrana Jose Victor , Cardona-Ospina Jaime A. , Bos Sandra , Roy Vicky , Kuan Guillermina , Balmaseda Angel , Alter Galit , Harris Eva
Published: June 2024

Primary infection with one of four dengue virus serotypes (DENV1-4) may generate antibodies that protect or enhance subsequent secondary heterotypic infections. However, the characteristics of heterotypic cross-reactive antibodies associated with protection from symptomatic infection and severe disease are not well-defined. We selected plasma samples collected before a secondary DENV heterotypic infection that was classified either as dengue fever (DF, n = 31) or dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS, n = 33) from our longstanding pediatric cohort in Nicaragua. We screened various antibody properties to determine the features correlated with protection from DHF/DSS. Protection was associated with high levels of binding of various antibody isotypes, IgG subclasses and effector functions, including antibody-dependent complement deposition, ADCD. Although the samples were derived from DENV-exposed, Zika virus (ZIKV)-naïve individuals, the protective ADCD association was stronger when assays were conducted with recombinant ZIKV antigens. Further, we showed that a complement-mediated virion lysis (virolysis) assay conducted with ZIKV virions was strongly associated with protection, a finding reproduced in an independent sample set collected prior to secondary heterotypic inapparent versus symptomatic DENV infection. Virolysis was the main antibody feature correlated with protection from DHF/DSS and severe symptoms, such as thrombocytopenia, hemorrhagic manifestations, and plasma leakage. Hence, anti-DENV antibodies that cross-react with ZIKV, target virion-associated epitopes, and mediate complement-dependent virolysis are correlated with protection from secondary symptomatic DENV infection and DHF/DSS. These findings may support the rational design and evaluation of dengue vaccines and development of therapeutics.

One Sentence Summary

Complement-dependent virolysis mediated by a subset of ZIKV-cross-reactive antibodies protects from symptomatic DENV infection and severe disease.
Evaluating the Efficacy of Large Language Models for Systematic Review and Meta-Analysis Screening
Authors: Luo Ronald , Sastimoglu Ziya , Faisal Abu Ilius , Deen M. Jamal
Published: June 2024

Background

Systematic reviews and meta-analyses are essential for informed research and policymaking, yet they are typically resource-intensive and time-consuming. Recent advances in artificial intelligence and machine learning offer promising opportunities to streamline these processes.

Objective

To enhance the efficiency of systematic reviews, we explored the automation of various stages using GPT-3.5 Turbo. We assessed the model’s efficacy and performance by comparing it against three expert-conducted reviews across a comprehensive dataset of 24,534 studies.

Methods

The model’s performance was evaluated through a comparison with three expert reviews, utilizing a pseudo-K-folds permutation and a one-tailed ANOVA with an alpha level of 0.05 to ensure statistical validity. Key performance metrics such as accuracy, sensitivity, specificity, predictive values, F1-score, and the Matthews correlation coefficient were analyzed using two sets of prompts.

Results

Our approach significantly streamlined the systematic review process, which typically takes a year, reducing it to a few hours without sacrificing quality. In the initial screening phase, accuracy, specificity, and negative predictive values ranged between 80% and 95%. Sensitivity improved markedly during the second screening phase, demonstrating the model’s robustness when provided with more extensive data.

Conclusion

While ongoing refinements are needed, this tool represents a significant advancement in research methodologies, potentially making systematic reviews more accessible to a wider range of researchers.

Impact Statement

Our manuscript presents a novel review screening protocol built using open-source frameworks, which significantly enhances the systematic review process in terms of efficiency and cost-effectiveness. Leveraging the capabilities of GPT and embedding models, our protocol demonstrates the potential to transform a traditionally time-consuming and expensive task into an accelerated and economical operation, all while maintaining high standards of accuracy and reliability.

Key Points

GPT screening can streamline systematic reviews from a year-long, expensive process to just hours at minimal cost.

Validated across different topics, the protocol exhibits high reliability and consistency in study inclusion.

The AI-driven process reduces human bias, with prompt optimization considerably improving sensitivity.
Acoustic chip for rapid label-free early-stage detection of rare leukemic cells
Authors: Matarèse Bruno F.E. , Flewitt Andrew , Huntly Brian J.P.
Published: June 2024

We present a promising approach for detecting as few as 1% of rare leukemia cells during the early stages of blood cancers. This study demonstrates a novel microfluidic chip utilizing a bulk piezoelectric ceramic device to manipulate cells with sound waves. By analyzing the movement patterns of normal mononuclear cells (MNCs) and abnormal THP-1 acute myeloid leukemia (AML) cells within an acoustic field, we observed distinct behaviors. Our findings suggest a label-free, non-targeted approach for sensitive detection of rare abnormal cells within a mixed population. This method, based on acoustophoresis principles, holds promise for analyzing biophysical properties of individual cells for early cancer diagnosis, potentially leading to earlier intervention and improved patient outcomes for leukemia. While this study focuses on microscopic analysis, we also discuss the potential for developing large-scale acoustophoresis-based methods for high-throughput rare cell detection using high-resolution nanofabrication techniques.
Tackling Anticancer Drug Resistance and Endosomal Escape in Aggressive Brain Tumors Using Bioelectronics
Authors: Jain Akhil , Wade Philippa , Stolnik Snow , Hume Alistair N. , Kerr Ian D. , Coyle Beth , Rawson Frankie
Published: June 2024

Chemotherapy resistance and endosomal entrapment, controlled by intracellular trafficking processes, are major factor in treatment failure. Here, we test the hypothesis that external electrical stimulus can be used to modulate intracellular trafficking of chemotherapeutic drugs in most common malignant brain tumors in childhood (medulloblastoma) and gold nanoparticles (GNPs) in adulthood (glioblastoma). We demonstrate that application of alternating current (AC) with frequencies ranging from KHz-MHz and low strength (1 V/cm) lead to killing of cisplatin and vincristine resistant (mediated by extracellular vesicles) medulloblastoma cell lines. On the other hand, in primary glioblastoma cells high frequency AC (MHz) regulated the endosomal escape of GNPs. No significant effect on the viability of the control medulloblastoma cells (resistant cells cultured in drug free media and non-resistant cells) and glioblastoma cells after AC treatment confirmed targeting of intracellular trafficking process. This work supports future application of AC in drug delivery and brain cancer therapy.
Time-division multiplexing (TDM) sequence removes bias in T2 estimation and relaxation-diffusion measurements
Authors: Liu Qiang , Gagoski Borjan , Shaik Imam Ahmed , Westin Carl-Fredrik , Wilde Elisabeth A. , Schneider Walter , Bilgic Berkin , Grissom William , Nielsen Jon‐Fredrik , Zaitsev Maxim , Rathi Yogesh , Ning Lipeng
Published: June 2024

Purpose

To compare the performance of multi-echo (ME) and time-division multiplexing (TDM) sequences for accelerated relaxation-diffusion MRI (rdMRI) acquisition and to examine their reliability in estimating accurate rdMRI microstructure measures.

Method

The ME, TDM, and the reference single-echo (SE) sequences with six echo times (TE) were implemented using Pulseq with single-band (SB-) and multi-band 2 (MB2-) acceleration factors. On a diffusion phantom, the image intensities of the three sequences were compared, and the differences were quantified using the normalized root mean squared error (NRMSE). For the in-vivo brain scan, besides the image intensity comparison and T2-estimates, different methods were used to assess sequence-related effects on microstructure estimation, including the relaxation diffusion imaging moment (REDIM) and the maximum-entropy relaxation diffusion distribution (MaxEnt-RDD).

Results

TDM performance was similar to the gold standard SE acquisition, whereas ME showed greater biases (3-4× larger NRMSEs for phantom, 2× for in-vivo). T2 values obtained from TDM closely matched SE, whereas ME sequences underestimated the T2 relaxation time. TDM provided similar diffusion and relaxation parameters as SE using REDIM, whereas SB-ME exhibited a 60% larger bias in the  map and on average 3.5× larger bias in the covariance between relaxation-diffusion coefficients.

Conclusion

Our analysis demonstrates that TDM provides a more accurate estimation of relaxation-diffusion measurements while accelerating the acquisitions by a factor of 2 to 3.
Contrasting Rhizosphere Nitrogen Dynamics in Andropogoneae Grasses: Implications for Sustainable Agriculture
Authors: Hsu Sheng-Kai , Emmett Bryan D , Haffke Alexandria J , Costa-Neto Germano , Schulz Aimee J , Lepak Nicholas , La Thuy , AuBuchon-Elder Taylor M , Hale Charles O , Raglin Sierra S , Ojeda-Rivera Jonathan O , Kent Angela D , Kellogg Elizabeth A , Romay M Cinta , Buckler Edward S
Published: June 2024

Background: Nitrogen (N) fertilization in crop production significantly impacts ecosystems, often disrupting natural plant-microbe-soil interactions and causing environmental pollution. Our research tested the hypothesis that phylogenetically related perennial grasses might preserve rhizosphere management strategies conducive to a sustainable N economy for crops. Method: We analyzed the N cycle in the rhizospheres of 36 Andropogoneae grass species related to maize and sorghum, investigating their impacts on N availability and losses. This assay is supplemented with the collection and comparison of native habitat environment data for ecological inference as well as cross-species genomic and transcriptomic association analyses for candidate gene discovery. Result: Contrary to our hypothesis, all examined annual species, including sorghum and maize, functioned as N "Conservationists," reducing soil nitrification potential and conserving N. In contrast, some perennial species enhanced nitrification and leaching ("Leachers"). Yet a few other species exhibited similar nitrification stimulation effects but limited NO3- losses ("Nitrate Keepers"). We identified significant soil characteristics as influential factors in the eco-evolutionary dynamics of plant rhizospheres, and highlighted the crucial roles of a few transporter genes in soil N management and utilization. Conclusion: These findings serve as valuable guidelines for future breeding efforts for global sustainability.
A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1
Authors: Koszela Joanna , Rintala-Dempsey Anne , Salzano Giulia , Pimenta Viveka , Kamarainen Outi , Gabrielsen Mads , Parui Aasna L. , Shaw Gary S. , Walden Helen
Published: June 2024

Mutations in the gene encoding for the E3 ubiquitin ligase Parkin have been linked to early-onset Parkinson’s disease. Besides many other cellular roles, Parkin is involved in clearance of damaged mitochondria via mitophagy - a process of particular importance in dopaminergic neurons. Upon mitochondrial damage, Parkin accumulates at the outer mitochondrial membrane and is activated, leading to ubiquitination of many mitochondrial substrates and recruitment of mitophagy effectors. While the activation mechanisms of autoinhibited Parkin have been extensively studied, it remains unknown how Parkin recognises its substrates for ubiquitination, and no substrate interaction site in Parkin has been reported. Here, we identify a conserved region in the flexible linker between the Ubl and RING0 domains of Parkin, which is indispensable for Parkin interaction with the mitochondrial GTPase Miro1. Our results explain the preferential targeting and ubiquitination of Miro1 by Parkin and provide a biochemical explanation for the presence of Parkin at the mitochondrial membrane prior to activation induced by mitochondrial damage. Our findings are important for understanding mitochondrial homeostasis and may inspire new therapeutic avenues for Parkinson’s disease.
Reversion to sensitivity explains limited transmission of resistance in a hospital pathogen
Authors: Tracy Kevin C. , McKaig Jordan , Kinnear Clare , Millar Jess , King Aaron A. , Read Andrew F. , Woods Robert J.
Published: June 2024

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Bacterial pathogens that are successful in hospital environments must survive times of intense antibiotic exposure and times of no antibiotic exposure. When these organisms are closely associated with human hosts, they must also transmit from one patient to another for the resistance to spread. The resulting evolutionary dynamics have, in some settings, led to rising levels of resistance in hospitals. Here, we focus on an important but understudied aspect of this dynamic: the loss of resistance when the resistant organisms evolve in environments where the antibiotic pressure is removed. Based on prior data, we hypothesize that resistance arising in the context of strong selection may carry a high cost and revert to sensitivity quickly once the selective pressure is removed. Conversely, resistant isolates that persist through times of no antibiotic pressure should carry a lower cost and revert less quickly. To test this hypothesis, we utilize a genetically diverse set of patient-derived, daptomycin-resistantEnterococcus faeciumisolates that include cases of bothde novoemergence of resistance within patients and putatively transmitted resistance. Both of these sets of strains have survived periods of antibiotic exposure, but only putatively transmitted resistant strains have survived extended periods without antibiotic exposure. These strains were then allowed to evolve in antibiotic free laboratory conditions. We find that putatively transmitted resistant strains tended to have lower level resistance but that evolution in antibiotic-free conditions resulted in minimal loss of resistance. In contrast, resistance that arosede novowithin patients was higher level but exhibited greater declines in resistancein vitro. Sequencing of the experimentally evolved isolates revealed that reversal of high level resistance resulted from evolutionary pathways that were frequently genetically associated with the unique resistance mutations of that strain. Thus, the rapid reversal of high-level resistance was associated with accessible evolutionary pathways where an increase in fitness is associated with decreased resistance. We describe how this rapid loss of resistance may limit the spread of resistance within the hospital and shape the diversity of resistance phenotypes across patients.