bluuebunny/crossref_metadata_2025 huggingface dataset:
Ampicillin-sulbactam against Acinetobacter baumannii infections: pharmacokinetic/pharmacodynamic appraisal of current susceptibility breakpoints and dosing recommendations
Authors: Abouelhassan Yasmeen , Kuti Joseph L , Nicolau David P , Abdelraouf Kamilia
Published: July 2024

Background

Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics/pharmacodynamics (PK/PD) data. Herein, we report a comprehensive PK/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia.

Methods

Twenty-one A. baumannii clinical isolates were tested in the neutropenic murine pneumonia model. For dose-ranging studies, groups of mice were administered escalating doses of ampicillin-sulbactam. Changes in log10cfu/lungs relative to 0 h were assessed. Dose-fractionation studies were performed. Estimates of the percentage of of time during which the unbound plasma sulbactam concentrations exceeded the MIC (%fT > MIC) required for different efficacy endpoints were calculated. The probabilities of target attainment (PTA) for the 1-log kill plasma targets were estimated following clinically utilized sulbactam regimens.

Results

Dose-fractionation studies demonstrated time-dependent kill. Isolates resistant to both sulbactam and meropenem required three times the exposures to achieve 1-log kill; median [IQR] %fT > MIC of 60.37% [51.6–66.8] compared with other phenotypes (21.17 [16.0–32.9] %fT > MIC). Sulbactam standard dose (1 g q6h, 0.5 h infusion) provided >90% PTA up to MIC of 4 mg/L. Sulbactam 3 g q8h, 4 h inf provided greater PTA for isolates with sulbactam-intermediate susceptibility (8 mg/L, 100% versus 86% following the standard dose). Despite the higher exposure following 3 g q8h, 4 h inf, PTA was ≤57% among sulbactam-resistant/meropenem-resistant isolates.

Conclusion

Sulbactam standard dose is a valuable regimen across sulbactam-susceptible isolates while the high-dose extended-infusion provides additional benefit against sulbactam-intermediate isolates. Given that most of the sulbactam-resistant A. baumannii isolates are meropenem-resistant, high-dose prolonged-infusion regimens are not expected to be effective as monotherapy against infections due to these isolates.
Prompt engineering on leveraging large language models in generating response to InBasket messages
Authors: Yan Sherry , Knapp Wendi , Leong Andrew , Kadkhodazadeh Sarira , Das Souvik , Jones Veena G , Clark Robert , Grattendick David , Chen Kevin , Hladik Lisa , Fagan Lawrence , Chan Albert
Published: July 2024

Objectives

Large Language Models (LLMs) have been proposed as a solution to address high volumes of Patient Medical Advice Requests (PMARs). This study addresses whether LLMs can generate high quality draft responses to PMARs that satisfies both patients and clinicians with prompt engineering.

Materials and Methods

We designed a novel human-involved iterative processes to train and validate prompts to LLM in creating appropriate responses to PMARs. GPT-4 was used to generate response to the messages. We updated the prompts, and evaluated both clinician and patient acceptance of LLM-generated draft responses at each iteration, and tested the optimized prompt on independent validation data sets. The optimized prompt was implemented in the electronic health record production environment and tested by 69 primary care clinicians.

Results

After 3 iterations of prompt engineering, physician acceptance of draft suitability increased from 62% to 84% (P <.001) in the validation dataset (N = 200), and 74% of drafts in the test dataset were rated as “helpful.” Patients also noted significantly increased favorability of message tone (78%) and overall quality (80%) for the optimized prompt compared to the original prompt in the training dataset, patients were unable to differentiate human and LLM-generated draft PMAR responses for 76% of the messages, in contrast to the earlier preference for human-generated responses. Majority (72%) of clinicians believed it can reduce cognitive load in dealing with InBasket messages.

Discussion and Conclusion

Informed by clinician and patient feedback synergistically, tuning in LLM prompt alone can be effective in creating clinically relevant and useful draft responses to PMARs.
Sclerotic prostate cancer bone metastasis: woven bone lesions with a twist
Authors: Eltit Felipe , Wang Qiong , Jung Naomi , Munshan Sheryl , Xie Dennis , Xu Samuel , Liang Doris , Mojtahedzadeh Bita , Liu Danmei , Charest-Morin Raphaële , Corey Eva , True Lawrence D , Morrissey Colm , Wang Rizhi , Cox Michael E
Published: July 2024

Bone metastases are the most severe and prevalent consequences of prostate cancer (PC), affecting more than 80% of patients with advanced PC. PCBMs generate pain, pathological fractures, and paralysis. As modern therapies increase survival, more patients are suffering from these catastrophic consequences. Radiographically, PCBMs are predominantly osteosclerotic, but the mechanisms of abnormal bone formation and how this pathological increase in bone density is related to fractures are unclear. In this study, we conducted a comprehensive analysis on a cohort of 76 cadaveric PCBM specimens and 12 cancer-free specimens as controls. We used micro-computed tomography to determine 3D organization and quantify bone characteristics, quantitative backscattering electron microscopy to characterize mineral content and details in bone structure, nanoindentation to determine mechanical properties, and histological and immunohistochemical analysis of bone structure and composition. We define 4 PCBM phenotypes: osteolytic, mixed lytic-sclerotic, and 2 subgroups of osteosclerotic lesions—those with residual trabeculae, and others without residual trabeculae. The osteosclerotic lesions are characterized by the presence of abnormal bone accumulated on trabeculae surfaces and within intertrabecular spaces. This abnormal bone is characterized by higher lacunae density, abnormal lacunae morphology, and irregular lacunae orientation. However, mineral content, hardness, and elastic modulus at micron-scale were indistinguishable between this irregular bone and residual trabeculae. The collagen matrix of this abnormal bone presents with irregular organization and a prominent collagen III composition. These characteristics suggest that osteosclerotic PCBMs initiate new bone deposition as woven bone; however, the lack of subsequent bone remodeling, absence of lamellar bone deposition on its surface, and presence of collagen III distinguish this pathologic matrix from conventional woven bone. Although the mineralized matrix retains normal bone hardness and stiffness properties, the lack of fibril anisotropy presents a compromised trabecular structure, which may have clinical implications.
The enigmatic AHRR: beyond aryl hydrocarbon receptor repression
Authors: Hahn Mark E , Sherr David H
Published: July 2024

Many roles of aryl hydrocarbon receptor repressor in intestinal immune homeostasis are discussed.
Non-Traditional Finance and the Infrastructural Imagination of Geoeconomic Hegemony: The Case of Russia’s War in Ukraine
Authors: Langenohl Andreas , Burghardt Kevin
Published: July 2024

Against the background of the war waged by Russia against Ukraine, this paper addresses the role of non-traditional financial infrastructures in geopolitical struggles that are conducted by geoeconomic means. Non-traditional finance (in the following: NTF),1 like cryptocurrencies, crypto exchanges, and related services, promises to provide financial security—for instance, in terms of payments—outside of traditional financial infrastructures. NTF gains geopolitical significance in the wake of the US and EU-led financial sanctions against Russian institutions and individuals. The paper investigates this potentially new role of NTF through a theoretical and conceptual architecture that views hegemony, including geopolitical hegemony, from a social-theoretical standpoint: Hegemony is conceptualized as the result of “articulations”—that is, contingent interrelations encompassing both linkages and distinctions—between heterogeneous elements in which the respective role and function of those elements is re-defined through the articulation. With regard to the emerging role of NTF in geopolitical conflicts, the question is how political perceptions of geopolitical conflict and agency are iterated in terms of non-traditional financial infrastructures, and how, in turn, those infrastructures are articulated with respect to their political weight. The paper empirically analyzes the ways in which NTF agents and organizations have been addressed as geopolitical factors in the war confrontation between Russia and Ukraine by political institutions (focusing on the United States, the EU, Russia, and Ukraine), and how they understand their role themselves. Findings show that NTF, in spite of its rising prominence, use, and promise of autonomy, has effectively been articulated as an infrastructure whose concerns with financial and payment security must be subordinated to considerations of political security and international supremacy. In that articulation, Western, Russian, and Ukrainian governments significantly differ with respect to the ways they deploy an infrastructural imagination to define their interests and their views on NTF in the conflict.
Differential item functioning of the revised Multigroup Ethnic Identity Measure (MEIM-R) in racially and income diverse youth with type 1 diabetes
Authors: Choquette Adora E , Berlin Kristoffer S , Desai Kishan R , Ankney Rachel L , Tillery-Webster Rachel , Harry Kasey R , Holden LaTasha , Cook Jessica L , Keenan-Pfeiffer Mary E , Semenkovich Katherine A , Klages Kimberly L , Rybak Tiffany J , Banks Gabrielle G , Sumpter Kathryn , Eddington Angelica R
Published: July 2024

Objective

Racially minoritized youth with T1D are made vulnerable to disproportionately adverse health outcomes compared to White peers due to enduring systems of oppression. Thus, understanding modifiable psychosocial factors associated with diabetes-related outcomes in racially minoritized youth may help to buffer deleterious effects of racism. One factor meriting exploration is racial-ethnic identity. There is currently limited research on measures fit to assess ethnic identity in youth with chronic illnesses. This study’s purpose is to examine the factor structure, reliability, and validity of the revised Multigroup Ethnic Identity Measure (MEIM-R) in a racially- and income-diverse sample of youth with T1D across sociodemographic and illness-related proxies for one’s positionality in oppressive systems.

Method

As part of a larger study examining resilience, 142 youth with T1D ages 12–18 (Mage = 14.66, SDage = 1.62, 55.6% Black/African-American, 44.4% White) completed the MEIM-R and various psychosocial measures. HbA1c levels and illness duration were extracted from medical records and caregivers reported income information. Confirmatory factor analyses compared the structural validity of competing MEIM-R models, and uniform and non-uniform differential item functioning (DIF) was explored across sociodemographic and illness-related factors.

Results

While a bifactor structure was supported, the MEIM-R was found to exhibit DIF by race and gender on multiple MEIM-R items and did not demonstrate linear bivariate relations with other psychosocial factors.

Conclusions

Since different MEIM-R item response patterns were observed across racial/ethnic and gender groups, caution is warranted in using this measure in racially and gender diverse youth with T1D.
Invasion of the stigma by oomycete pathogenic hyphae or pollen tubes: striking similarities and differences
Authors: Riglet Lucie , Hok Sophie , Kebdani-Minet Naïma , Le Berre Joëlle , Gourgues Mathieu , Rozier Frédérique , Bayle Vincent , Bancel-Vallée Lesli , Allasia Valérie , Keller Harald , Da Rocha Martine , Attard Agnés , Fobis-Loisy Isabelle
Published: July 2024

Both the pollen tube and hyphae of filamentous pathogens penetrate the outer layer of the host and then grow within host tissues. Early epidermal responses are decisive for the outcome of these two-cell interaction processes. We identified a single cell type, the papilla in the stigma of Arabidospis, as a tool to conduct a comprehensive comparative analysis on how an epidermal cell responds to the invasion of an unwanted pathogen or a welcome pollen tube. We showed that Phytophthora parasitica, a root oomycete, effectively breaches the stigmatic cell wall and develops as a biotroph within the papilla cytoplasm. These invasive features resemble the behaviour exhibited by the pathogen within its natural host cell, but diverge from the manner in which the pollen tube progresses, being engulfed within the papilla cell wall. Quantitative analysis revealed that both invaders trigger reorganization of the stigmatic endomembrane system and the actin cytoskeleton. While some remodelling processes are shared between the two interactions, others appear more specific towards the respective invader. These findings underscore the remarkable ability of an epidermal cell to differentiate between two types of invaders, thereby enabling it to trigger the most suitable response during the onset of invasion.
Probing Defectivity Beneath the Hydrocarbon Blanket in 2D hBN Using TEM-EELS
Authors: Byrne Dana O , Ciston Jim , Allen Frances I
Published: July 2024

The controlled creation and manipulation of defects in 2D materials has become increasingly popular as a means to design and tune new material functionalities. However, defect characterization by direct atomic-scale imaging is often severely limited by surface contamination due to a blanket of hydrocarbons. Thus, analysis techniques that can characterize atomic-scale defects despite the contamination layer are advantageous. In this work, we take inspiration from X-ray absorption spectroscopy and use broad-beam electron energy loss spectroscopy (EELS) to characterize defect structures in 2D hexagonal boron nitride (hBN) based on averaged fine structure in the boron K-edge. Since EELS is performed in a transmission electron microscope (TEM), imaging can be performed in-situ to assess contamination levels and other factors such as tears in the fragile 2D sheets, which can affect the spectroscopic analysis. We demonstrate the TEM-EELS technique for 2D hBN samples irradiated with different ion types and doses, finding spectral signatures indicative of boron–oxygen bonding that can be used as a measure of sample defectiveness depending on the ion beam treatment. We propose that even in cases where surface contamination has been mitigated, the averaging-based TEM-EELS technique can be useful for efficient sample surveys to support atomically resolved EELS experiments.
A statistical framework for recovering intensity mapping autocorrelations from cross-correlations
Authors: McBride Lisa , Liu Adrian
Published: July 2024

Intensity mapping experiments will soon have surveyed large swathes of the sky, providing information about the underlying matter distribution of our early Universe. The resulting maps can be used to recover statistical information, such as the power spectrum, about the measured spectral lines (for example, H i, [C ii], and [O iii]). However precise power spectrum measurements, such as the 21 cm autocorrelation, continue to be challenged by the presence of bright foregrounds and non-trivial systematics. By cross-correlating different data sets, it may be possible to mitigate the effects of both foreground uncertainty and uncorrelated instrumental systematics. Beyond their own merit, cross-correlations could also be used to recover autocorrelation information. Such a technique has been proposed in the literature for recovering the 21 cm power spectrum. Generalizing this result, we develop a statistical framework for combining multiple cross-correlation signals in order to infer information about the corresponding autocorrelations. We do this first within the least squares estimator framework, and show how one can derive their estimator, along with several alternative estimators. We also investigate the posterior distribution of recovered autocorrelation and associated model parameters. We find that for certain noise regimes and cosmological signal modelling assumptions this procedure is effective at recovering autospectra from a set of cross-correlations. Finally, we showcase our framework in the context of several near-future line intensity mapping experiments.
DNA-encoded probe-based assay for profiling plant kinase activities
Authors: Chien Yuan-Chi , Valencia C Alexander , Lee Han Yong , Yoon Gyeong Mee , Kim Dongwook
Published: July 2024

Elucidating kinase–substrate relationships is pivotal for deciphering cellular signaling mechanisms, yet it remains challenging due to the complexity of kinase networks. Herein, we report the development of a versatile DNA-based kinase assay platform for high-throughput profiling of plant protein kinase activities and substrate preferences. Our approach employs DNA-linked peptide substrates, facilitating quantitative and specific kinase activity detection through next-generation DNA sequencing. Leveraging DNA barcodes as quantitative readouts, our approach establishes a high-throughput, sensitive, and specific platform for dissecting kinase–substrate networks in plants, representing a powerful tool for elucidating signaling mechanisms in plants.
Topology Testing and Demographic Modeling Illuminate a Novel Speciation Pathway in the Greater Caribbean Sea Following the Formation of the Isthmus of Panama
Authors: Titus Benjamin M , Gibbs H Lisle , Simões Nuno , Daly Marymegan
Published: July 2024

Recent genomic analyses have highlighted the prevalence of speciation with gene flow in many taxa and have underscored the importance of accounting for these reticulate evolutionary processes when constructing species trees and generating parameter estimates. This is especially important for deepening our understanding of speciation in the sea where fast-moving ocean currents, expanses of deep water, and periodic episodes of sea level rise and fall act as soft and temporary allopatric barriers that facilitate both divergence and secondary contact. Under these conditions, gene flow is not expected to cease completely while contemporary distributions are expected to differ from historical ones. Here, we conduct range-wide sampling for Pederson’s cleaner shrimp (Ancylomenes pedersoni), a species complex from the Greater Caribbean that contains three clearly delimited mitochondrial lineages with both allopatric and sympatric distributions. Using mtDNA barcodes and a genomic ddRADseq approach, we combine classic phylogenetic analyses with extensive topology testing and demographic modeling (10 site frequency replicates × 45 evolutionary models × 50 model simulations/replicate = 22,500 simulations) to test species boundaries and reconstruct the evolutionary history of what was expected to be a simple case study. Instead, our results indicate a history of allopatric divergence, secondary contact, introgression, and endemic hybrid speciation that we hypothesize was driven by the final closure of the Isthmus of Panama and the strengthening of the Gulf Stream Current ~3.5 Ma. The history of this species complex recovered by model-based methods that allow reticulation differs from that recovered by standard phylogenetic analyses and is unexpected given contemporary distributions. The geologically and biologically meaningful insights gained by our model selection analyses illuminate what is likely a novel pathway of species formation not previously documented that resulted from one of the most biogeographically significant events in Earth’s history.
Supplementing a Bacillus-based direct-fed microbial improves feed efficiency in lactating dairy cows
Authors: Terré Marta , Prat Norbert , Sabrià Daniel , Queiroz Oscar , Joergensen Jens N , Copani Giuseppe , Cappellozza Bruno I
Published: July 2024

This experiment was conducted to evaluate the effects of feeding a Bacillus-based direct-fed microbial (DFM) on performance and nutrient digestibility of lactating dairy cows. Seventy-six lactating (42 ± 6 days in milk [DIM]) Holstein–Friesian primiparous and multiparous cows were enrolled to a 16-wk experiment. Cows were blocked by lactation number and DIM and within blocks, assigned to 1 of the 2 treatments: 1) basal partial-mixed ration (PMR) without DFM addition (n = 38; CON) or 2) basal PMR with the addition of 3 g/head/d of a DFM containing B. licheniformis 809 and B. subtilis 810 (n = 38; BOVACILLUS, Chr. Hansen A/S, Hørsholm, Denmark; DFM). The DFM was mixed in a protein-based pellet, whereas the CON group was fed the same pellet without DFM (0.6 kg/cow/d). The PMR contained (dry matter [DM] basis) 50% of forage and 48% of a concentrate feed based on corn meal, soybean meal, wheat meal, wheat middlings, and a mineral–vitamin premix, with the remaining part of the diet being represented by the pellet used as a carrier for the treatments (CON and DFM). Dry matter intake (DMI), milk yield, and production efficiency were recorded daily, whereas milk protein and fat concentrations were recorded using electronic milk meters. An additional milk sample was collected every second week of the study for milk composition. On week 15 of the study, fecal samples were collected from each cow for apparent nutrient digestibility calculation. All data were analyzed using the MIXED procedure of SAS (version 9.4; SAS Inst. Inc., Cary, NC). No treatment effects were observed on cow final body weight, daily DMI, milk yield, energy-corrected milk (ECM), ECM efficiency, milk composition (yield or content), and somatic cell count (SCC) (P ≥ 0.12). However, cows fed DFM had a greater feed and N efficiency (P ≤ 0.03) compared to cows fed CON. Moreover, DM digestibility tended to be greater for DFM-fed cows when compared to CON (P = 0.10), whereas no further nutrient digestibility differences were observed (P ≥ 0.24). In summary, supplementing a DFM containing Bacillus licheniformis and B. subtilis benefited feed efficiency of lactating dairy cows fed a PMR, while also tending to improve the digestibility of DM.
An innovative and effective approach of cervical canal penetration in patients diagnosed with type II vaginal atresia with adequate uterine corpus development: A case series
Authors: Xue Lujie , Zhang Lu , Sun Chenyang , Yang Xiaomei , Li Bin , Liu Li , Jiang Xiangyang , Chen Lihong
Published: July 2024

We introduced our experience for an innovative and effective approach for cervical canal penetration in patients diagnosed with type II vaginal atresia with adequate uterine corpus development. The uterine cavity and neovagina was connected through the puncture set for percutaneous nephrostomy while maintaining the integrity of the uterus and cervix under laparoscopic and transvaginal ultrasound monitoring. A porcine small intestine submucosal graft was fitted into the artificial vaginal wall. There were few side effects and no obvious sequelae.
Immunoglobulin-Mediated Cardiac Protection From Ischemia/Reperfusion Injury in Diabetic Rats Is Associated With Endothelial Nitric Oxide Synthase/Glucose Transporter-4 Signaling Pathway
Authors: Babiker Fawzi , Al-Kouh Aisha
Published: July 2024

The role of intravenous immunoglobulin in protecting the diabetic heart from ischemia/reperfusion (I/R) injury is unclear. Hearts isolated from adult diabetic and nondiabetic Wistar rats (n = 8 per group) were treated with intravenous immunoglobulin (IVIG) either 2 hours before euthanasia, before ischemia, or at reperfusion. Hemodynamic data were acquired using the Isoheart software version 1.524-S. Ischemia/reperfusion (I/R) injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining and troponin T levels. The levels of apoptosis markers, caspases-3/8, antioxidant enzymes, superoxide dismutase and catalase, glucose transporters, GLUT-1 and GLUT-4, phosphorylated ERK1/2, and phosphorylated eNOS were estimated by Western blotting. Proinflammatory and anti-inflammatory cytokine levels were evaluated using enzyme-linked immunosorbent assays. Intravenous immunoglobulin administration abolished the effects of I/R injury in hearts subjected to hyperglycemia when infused at reperfusion, before ischemia, or at reperfusion in 4-week diabetic rat hearts and only at reperfusion in 6-week diabetic rat hearts. IVIG infusion resulted in a significant (P < 0.05) recovery of cardiac hemodynamics and decreased infarct size. IVIG also reduced the levels of troponin T, apoptotic enzymes, and proinflammatory cytokines. IVIG significantly (P < 0.05) increased the levels of anti-inflammatory cytokines, antioxidant enzymes, GLUT-4, and phosphorylated eNOS. Intravenous immunoglobulin protected the hearts from I/R injury if infused at reperfusion in the presence of hyperglycemia, in 4- and 6-week diabetic rat hearts, and when infused before ischemia in 4-week diabetic rat hearts. IVIG exerts its cardioprotective effects associated with the upregulated phosphorylated eNOS/GLUT-4 pathway.
Original Antigenic Sin on Antibody Response in SARS-CoV-2 Infection
Authors: Wang Miao , Guo Huimin , Ju Bin , Zhang Zheng
Published: July 2024

Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.
Quantifying Population Characteristics Within and Outside a 30-Minute Drive-Time to Health Resources and Services Administration-Supported Health Centers
Authors: Rankin Jennifer L. , McCann Jessica , Topmiller Michael , Grolling Dave , Benjamin Troyana , Yu-Lefler Helen , Hoang Hank , Sripipatana Alek
Published: July 2024

The Health Resources and Services Administration’s (HRSA) Health Center Program provides health care to vulnerable persons across the US, regardless of their ability to pay for health care. We examined characteristics of populations living within and outside a 30-minute drive-time to HRSA-supported health centers to establish a baseline to better understand the differences in these populations. Using a descriptive, cross-sectional study design and geographic information systems, we found that 94% of persons in the US live within a 30-minute drive-time of a health center. Of those outside a 30-minute drive-time to a health center, 11.7 million (60.11%) are rural and over 1.5 million households (20.32%) lack broadband internet access.
Autism Identification and Referral: How Best to Equip Physician Assistant Students for Successful Practice
Authors: Blome Leslie , Sivahop Jacqueline
Published: July 2024

Introduction

Although physician assistants (PAs) are increasingly well-positioned to identify autism and provide appropriate referrals, little research has focused on their preparation to do so. The purpose of this study was to understand PA students' perspectives about what would help them feel more confident to identify autism and talk with families about it. Advantages and constraints to embedding autism training within the curriculum were also explored. Implications for practice are identified.

Methods

In this qualitative case study, robust thematic analysis was used to extricate the codes and themes from document review and semistructured interviews with 9 PA students and the program director (PD), from one PA program.

Results

One primary theme, refresher needed, emerged from the student interviews. Three subthemes reflected potential formats for a refresher: conversational role-play, verbiage for talking about autism and addressing vaccine hesitancy, and experiential learning opportunities. Two themes emerged from the interview with the PD: challenges to embedding autism in the curriculum and benefits of addressing autism.

Discussion

This study highlights the importance of incorporating robust, nuanced information about autism into PA training programs. Students desired brief role-plays and experiential activities to augment the basic autism information they received from their didactic lecture. Embedding autism into the curriculum can develop students' critical thinking skills while addressing the rising prevalence of this condition. Given the importance of targeted early intervention for this population and the expanding role of PAs in primary care, it is incumbent on PA education programs to provide students with the knowledge they need to provide autism care with confidence and compassion.
The association of depression and sleep disorders in patients with type 1 diabetes in Taiwan
Authors: Ni Meng-Han , Yang Yi-Sun , Huang Jing-Yang , Lo Shih-Chang , Huang Chien-Ning , Kornelius Edy
Published: July 2024

The association between depression and sleep disorders in patients with type 1 diabetes mellitus (T1DM) in Taiwan is underexplored. We used a nationwide population-based dataset to evaluate the association of T1DM with these conditions in Taiwan from 2001 to 2019. Patients with T1DM were identified as cases, and 2 control groups were used for comparison: patients with type 2 diabetes mellitus (T2DM) and nondiabetic patients. Age, sex, date of diagnosis, and multiple comorbidities were included and matched using propensity score matching between cases and controls. The primary outcome of this study was to identify new occurrences of the first diagnosis of depression or sleep disorders. After matching, this study included 27,029 T1DM cases, 54,058 T2DM controls, and 108,116 nondiabetic controls. Patients with T1DM exhibited a 1.55-fold higher risk of developing depression (hazard ratio [HR] 1.55, 95% confidence intervals [CI] 1.48–1.61) and a 1.41-fold higher risk of experiencing sleep disorders (HR 1.41, 95% CI 1.37–1.46) compared to nondiabetic controls. Similarly, patients with T2DM displayed elevated risks of both depression (HR 1.39, 95% CI 1.34–1.43) and sleep disorders (HR 1.40, 95% CI 1.37–1.44) relative to non-diabetic controls. When comparing the T1DM and T2DM groups, T1DM patients demonstrated a slightly higher risk of depression (HR 1.11, 95% CI 1.07–1.16) but no significant difference in the risk of sleep disorders compared to T2DM patients. These results were consistent regardless of different ages or sexes. This study demonstrates a significant association between diabetes mellitus and the risk of depression and sleep disorders in a large cohort of Taiwanese patients.
Advancing Professional Governance to Improve Health Outcomes
Authors: Porter-O'Grady Tim , Hancock Beverly , Start Rachel E.
Published: July 2024

Developing the skills and behaviors needed for nurses to lead in professional governance has long been a priority at the American Organization for Nursing Leadership (AONL). The annual AONL Professional Governance Leadership Conference is an important part of advancing nursing professional governance, convening nurses in all roles to discuss professional governance concepts and leadership practices. AONL has produced publications and podcasts exploring the professional governance foundations, roles, and behaviors, available on its website. This article discusses AONL's partnership in the development of a new book, Professional Governance for Nursing: The Framework for Accountability, Engagement, and Excellence, edited by AONL faculty and former staff.
High Above-Knee Amputations for Femoral Osteosarcomas Treated with Free Microsurgical Tibial Reconstruction in the Pediatric Population
Authors: Wilkes Courtney G. , Huang Andrew H. , McCombe David B. , Coombs Christopher J.
Published: July 2024

Improvements in the management of pediatric sarcoma, including imaging, neo- and adjuvant therapy, and surgical technique, have enhanced long-term survival. Pediatric patients diagnosed with a femoral osteosarcoma undergoing oncologic resection who are ineligible for limb-preservation reconstruction or rotationplasty are offered an above-knee amputation (AKA). Limb amputation in the skeletally immature patient poses particular problems specific to endosteal bone overgrowth and spiking. Approximately half of these patients undergo revision of their amputation site. Furthermore, a high AKA often requires a hip-based prosthesis, which can be uncomfortable, leading to poorer outcomes and higher energy expenditures. The authors have completed 4 “spare parts” microvascular free tibial transfers for pediatric patients diagnosed with femoral osteosarcoma who were treated with an AKA. Two of these patients are ambulatory with their prosthesis and have not required long-term revision of their amputation site. One patient demonstrated radiographic evidence of bony union 4 months postoperatively, but subsequently died of chemotherapy-resistant metastases. The fourth patient is in the process of prosthetic fitting and rehabilitation. This is a novel technique, and the authors present the first series describing both proximal and distal free microvascular tibial bone transfers as a reconstructive option for pediatric patients with femoral osteosarcomas. This reliable flap, which has possible variations in vascular anatomy, offers multiple benefits, including prevention of bony spiking, AKA stump augmentation, and facilitation of appropriate prosthetic fitting, improving functional outcomes and leading to decreased energy expenditure. The soft-tissue coverage must be well-planned.
Regional Brain Entropy During Movie-watching
Authors: Song Dong-Hui , Wang Ze
Published: July 2024

Brain entropy (BEN) measures the irregularity or unpredictability of brain activity. Our previous studies have showcased the neurocorrelates and disease sensitivity of regional BEN. Task performance and neuromodulations as well as medications can modulate regional BEN. Movie-watching engages multiple-domain cognitions and complex brain activities mimicking the complex real world and has been increasingly used to probe brain state dynamics. The sustained multiple-domain cognitive activities would cause sustained changes to regional BEN, which however remains unknown. The purpose of this study was to address this gap. We first aimed to examine whether the fMRI-derived regional BEN represents a stable brain activity index during repeated measurement with or without movie-watching. We then assessed the movie-watching-induced regional BEN changes compared to resting state and regional BEN differences between different movie clips. we found higher reliability during movie-watching and movie-watching induced lower BEN in the sensory cortex and higher BEN in the association cortex compared to the resting state. We replicated and validated all findings in test-retest clips. This work systematically evaluated the regional BEN during movie-watching, providing a new direction for exploring brain activity under natural paradigms using BEN.
Endothelial Cell Dysfunction and Retinal Arteriolar Narrowing in Young Adults With Elevated Blood Pressure
Authors: Tan Cheryl M. J. , Lewandowski Adam J. , Hanssen Henner , Streese Lukas , Huckstep Odaro J. , Fischer Roman , Alsharqi Maryam , Mohamed Afifah , Williamson Wilby , Leeson Paul , Bertagnolli Mariane
Published: July 2024

Background

Young-adults with endothelial cell dysfunction are more likely to develop elevated blood pressure. We tested the hypothesis that this relates to development of structural microvascular impairments by studying associations between circulating endothelial colony-forming cell (ECFC) dysfunction and microvascular markers, as well as identifying related endothelial molecular mechanisms.

Methods

Peripheral blood ECFCs were isolated from 32 subjects (53% men, 28±4 years old) using the Ficoll density gradient centrifugation method. Participants with blood pressure ≥120/80 mm Hg were included in the elevated blood pressure (BP) group, whereas ≤120/80 mm Hg were classed as normotensive. Retinal microvasculature was assessed by Static Retinal Vessel Analyzer (SVA-T).

Results

Subjects with elevated BP had impaired in vitro ECFC colony-forming growth, cell proliferation and angiogenesis assessed by tube formation potential. There was a graded inverse association between ECFC colony-forming capacity (days taken for ECFC colony growth) and retinal arteriolar diameter, as well as arteriolar/venular ratio. Proteomic analysis of ECFCs identified differences in extracellular matrix organization, blood coagulation, exocytosis and vesicle transport proteins in subjects with elevated blood pressure, revealing the adaptor protein GRB2 as a potential link between endothelial cell and microvascular abnormalities.

Conclusions

Endothelial cell dysfunction associates with retinal arteriolar narrowing in men and women with elevated blood pressure. Endothelial molecular mechanisms linked to reduced adaptive postnatal angiogenesis capacity, rather than vascular development, may contribute to early microvascular changes.

HIGHLIGHTS

Subjects with elevated blood pressure had impaired in vitro endothelial cell growth and angiogenesis in comparison to normotensive subjects.

There was an association between impaired endothelial cell growth capacity and reduced retinal arteriolar diameter.

Different endothelial proteome signatures were identified, revealing the adaptor protein GRB2 as a potential link between endothelial and microvascular abnormalities in subjects with elevated blood pressure.

GRAPHICAL ABSTRACT
Autoimmune Encephalitis, Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Analysis of the Vaccine Adverse Event Reporting System (VAERS)
Authors: Garcia-Dominguez Maria A. , Kaur Taranjit , Kipkorir Vincent , Cheruto Doreen C. , Rugut Clinton , Udochukwu Anosike , Singh Harsimran , S. Srichawla Bahadar
Published: July 2024

Introduction

Autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are complex and debilitating neurological disorders.

Methods

This study uses the Vaccine Adverse Event Reporting System (VAERS) to investigate the potential relationship between vaccinations and the incidence of NMOSD, AE, and MOGAD. Potential risk factors, such as age, sex, type of vaccine, and previous history of autoimmune diseases, were examined using multivariate logistic regression analysis.

Results

Our analysis included 161 cases: 72 NMOSD, 82 AE, and 7 MOGAD. The COVID-19 vaccine was implicated in 19/72 (26.3%) NMOSD, 43/82 (52.4%) of AE and 6/7 (85.7%) of MOGAD. The subacute temporal profile (OR 24.4, p = 0.004) and the presence of any comorbidity (OR 12.49, p = 0.004) were significantly associated with hospitalization for those with NMOSD. The subacute onset of symptoms and encephalopathy was statistically significant for hospitalization (OR 6.15, p = 0.048) and (OR 10.3, p = 0.005) respectively for patients with AE. Anti-NMDAR (N-methyl D-aspartate) antibodies were observed in 16/24 (66.7%) of AE. Treatment often involved high-dose corticosteroids or intravenous immunoglobulin (IVIG).

Conclusions

Most cases of vaccine induced NMOSD, AE, and MOGAD occurred secondary to the SARS-CoV-2 vaccine. The subacute onset of symptoms and the presence of encephalopathy was most associated with hospitalization.
Wireless, Multimodal Monitoring of Organ Health Using 3D-Printed, Barbed, Bioresorbable Stretchable Microneedle Sensor Arrays
Authors: Li Xiangling , Liu Shibo , Mo Jingshan , Yang Cheng , Morales Matthew , Ouyang Wei
Published: July 2024

Comprehensive and continuous assessment of organ physiology and biochemistry, beyond the capabilities of conventional monitoring tools, can enable timely interventions for intraoperative complications like organ ischemia and nerve injuries and postoperative conditions such as organ dysfunction and transplant rejection. Here, we report a wireless implant with a 3D-printed, barbed, bioresorbable stretchable microneedle sensor array that offers multimodal monitoring of organ metabolism, oxygenation, and electrophysiology as well as spatiotemporal mapping of biomarkers across different organ regions. The development of a deformation-coupled 3D-printing technique enables 3D-programmable manufacturing of microneedles with monolithic backward-facing barbs, offering conformal yet robust 3D probing of organs with dynamic mechanics. Electrochemical functionalization of microneedle tips serves as a universal approach for localized sensing of physiological and biochemical parameters, enabling concurrent monitoring of up to 36 parameters (glucose, uric acid, oxygen,etc.) and spatiotemporal mapping of up to 32 sites. An electrically programmable self-destruction mechanism based on crevice corrosion and bioresorption eliminates the need for traumatic retrieval of microneedles. Demonstrations in clinically relevant complications like kidney ischemia and gut disorders in animal models highlight the broad applications of this device in intra- and postoperative monitoring.
Flexynesis: A deep learning framework for bulk multi-omics data integration for precision oncology and beyond
Authors: Uyar Bora , Savchyn Taras , Wurmus Ricardo , Sarigun Ahmet , Shaik Mohammed Maqsood , Franke Vedran , Akalin Altuna
Published: July 2024

Accurate decision making in precision oncology depends on integration of multimodal molecular information, such as the genetic data, gene expression, protein abundance, and epigenetic measurements. Deep learning methods facilitate integration of heterogeneous datasets. However, almost all published deep learning-based bulk multi-omics integration methods have constrained usability. They suffer from lack of transparency, modularity, deployability, and are applicable exclusively to narrow tasks. To address these limitations, we introduce Flexynesis, a versatile tool designed with usability, and adaptability in mind. Flexynesis streamlines data processing, enforces structured data splitting, and ensures rigorous model evaluation. It offers unsupervised feature selection, different omics layer fusion options, and hyperparameter tuning. Users can choose from distinct architectures: fully connected networks, variational autoencoders, multi-triplet networks, graph neural networks, and cross-modality encoding networks. Each model is complemented with a straightforward input interface and standardized training, evaluation, and feature importance quantification methods, enabling easy incorporation into data integration pipelines. For improved user experience, Flexynesis supports features such as on-the-fly task determination and compatibility with regression, classification, and survival modeling. It accommodates multi-task prediction of a mixture of numerical/categorical outcome variables with a tolerance for missing labels. We also developed an extensive benchmarking pipeline, showcasing the tool's capability across diverse real-life datasets. This toolset should make deep-learning based bulk multi-omics data integration in the context of clinical/pre-clinical data analysis and marker discovery more accessible to a wider audience with or without experience in deep-learning development. Flexynesis is available at https://github.com/BIMSBbioinfo/flexynesis and can be installed from https://pypi.org/project/flexynesis/.
An epidemiological description of rabies outbreaks in Zambia from 2013 to 2023
Authors: Banda Humphrey , Hamukale Amos , Makungu Chitwambi , Ngoma Masuzyo , Chazya Ricky , Mataa Liywalii , Mulenga Chilufya , Banda James Blazer , Muleya Walter , Sialubanje Cephas , Banda Dabwitso , Sinyange Nyambe , Kachinda Wezi
Published: July 2024

Background

In Zambia, a dog bite is the most common rabies exposure. There is limited information on rabies outbreaks in jackals in Zambia. We investigated all rabies cases in Zambia and narrowed down on jackal bites in Mungwi district to determine a temporal trend and buffer zones for rabies.

Methods

The risk of exposure included all humans and animals bitten by jackals, data were collected by interviewing jackal bite victims and collecting brain specimen samples from animals. Risk of spread was determined by estimating the distance jackals strayed into human population and the Rabies Vaccination Coverage (RVC) in the district. The RVC was determined by dividing vaccinated dogs by dog population. The incidence rate (IR) and a Sen’s slope was used to determine a trend of RVC and the rabies cases in Zambia. QGIS was used to produce a heatmap and rabies risk zones. Direct Fluorescent Antibody technique was used to test for rabies.

Results

Zambia had recorded a total of 224 rabies cases with a mean (SD) of 22.4 (16) rabies cases and a positivity rate of 65.4% (25.7) per year from 2013 to 2022. Lusaka and Copperbelt provinces recorded the highest rabies cases. The rabies incidence rate was 2.3 rabies cases per 10,000 dogs in Zambia. The cases had reduced from 2013 to 2021 with a Sen’s slope of -0.74 (p = 0.02). At least 227 animal bites were recorded (two jackals and 225 dog bites) in Mungwi District. 94% (213) of the victims needed Post Exposure Prophylaxis. The victim’s median age was 20 (Interquartile range=12-38) years. The accumulative RVC from 2018-2022 (611/7777), was 0.11 (95% CI: −0.4-0.7, p=0.46) annual slope increase with 1.60% mean (Standard deviation = 0.34). One rabies heatmap and three risk-level zones (low, medium and high) were produced, and two jackals and one goat specimens were positive.

Conclusions

A risk-based surveillance and enhanced vaccination of dogs in high-risk areas through a one health approach is critical for rabies control in Zambia.