bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral Pyrometry for Practical Temperature Measurement in the TEM
Authors: Coffman D Keith , Hattar Khalid , Luo Jian , Dillon Shen
Published: November 2024

Recent work in ultra-high temperature in situ electron microscopy has presented the need for accurate, contact-free temperature determination at the microscale. Optical measurement based on thermal radiation (pyrometry) is an attractive solution but can be difficult to perform correctly due to effects, such as emissivity and optical transmission, that must be accounted for. Here, we present a practical guide to calibrating and using a spectral pyrometry system, including example code, using a Czerny-Turner spectrometer attached to a transmission electron microscope. Calibration can be accomplished using a thermocouple or commercial heated sample holder, after which arbitrary samples can be reliably measured for temperatures above ∼600∘C. An accuracy of 2% can be expected with the possibility of sub-second temporal resolution and sub-Kelvin temperature resolution. We then demonstrate this capability in conjunction with traditional microscopic techniques, such as diffraction-based strain measurement for thermal expansion coefficient, or live-video sintering evolution.
Attachments on Display: Music Analysis in the Public Sphere
Authors: Tan Daphne
Published: November 2024

In this article, I reflect on the nature of attachment within academic and public music theory. I focus on music analysis as a powerful activity that engenders attachments to musics, to methods, and often, to people. A key distinction between the scholarly and public spheres is how overtly affections and emotional commitments are expressed. Drawing first on academic writing and then turning to examples from YouTube, the podcasting world, and remarks from public music theorists, I contemplate the rewards and repercussions of putting one’s attachments on display.
PHI-base – the multi-species pathogen–host interaction database in 2025
Authors: Urban Martin , Cuzick Alayne , Seager James , Nonavinakere Nagashree , Sahoo Jahobanta , Sahu Pallavi , Iyer Vijay Laksmi , Khamari Lokanath , Martinez Manuel Carbajo , Hammond-Kosack Kim E
Published: November 2024

The Pathogen–Host Interactions Database (PHI-base) has, since 2005, provided manually curated genes from fungal, bacterial and protist pathogens that have been experimentally verified to have important pathogenicity, virulence and/or effector functions during different types of interactions involving human, animal, plant, invertebrate and fungal hosts. PHI-base provides phenotypic annotation and genotypic information for both native and model host interactions, including gene alterations that do not alter the phenotype of the interaction. In this article, we describe major updates to PHI-base. The latest version of PHI-base, 4.17, contains a 19% increase in genes and a 23% increase in interactions relative to version 4.12 (released September 2022). We also describe the unification of data in PHI-base 4 with the data curated from a new curation workflow (PHI-Canto), which forms the first complete release of PHI-base version 5.0. Additionally, we describe adding support for the Frictionless Data framework to PHI-base 4 datasets, new ways of sharing interaction data with the Ensembl database, an analysis of the conserved orthologous genes in PHI-base, and the increasing variety of research studies that make use of PHI-base. PHI-base version 4.17 is freely available at www.phi-base.org and PHI-base version 5.0 is freely available at phi5.phi-base.org.
Bacterial WYL domain transcriptional repressors sense single-stranded DNA to control gene expression
Authors: Blankenchip Chelsea L , Corbett Kevin D
Published: November 2024

Bacteria encode a wide array of immune systems to protect themselves against ubiquitous bacteriophages and foreign DNA elements. While these systems’ molecular mechanisms are becoming increasingly well known, their regulation remains poorly understood. Here, we show that an immune system-associated transcriptional repressor of the wHTH–WYL–WCX family, CapW, directly binds single-stranded DNA to sense DNA damage and activate expression of its associated immune system. We show that CapW mediates increased expression of a reporter gene in response to DNA damage in a host cell. CapW directly binds single-stranded DNA by-products of DNA repair through its WYL domain, causing a conformational change that releases the protein from double-stranded DNA. In an Escherichia coli CBASS system with an integrated capW gene, we find that CapW-mediated transcriptional activation is important for this system’s ability to prevent induction of a λ prophage. Overall, our data reveal the molecular mechanisms of WYL-domain transcriptional repressors, and provide an example of how bacteria can balance the protective benefits of carrying anti-phage immune systems against the inherent risk of these systems’ aberrant activation.
Retargeting target-directed microRNA-decay sites to highly expressed viral or cellular miRNAs
Authors: Ortega Jesus A , Liang Ziyan , Xu Junpeng Kenny , Gottwein Eva
Published: November 2024

MicroRNAs (miRNAs) are pervasive regulators of gene expression, necessitating the development of tools to inhibit individual miRNAs for functional studies or therapeutic targeting. Specialized base-pairing configurations between a miRNA and an RNA target site can trigger the degradation of the targeting miRNA through target-directed miRNA decay (TDMD). Previous work has identified several natural sites that induce TDMD of specific miRNAs. We explored retargeting known TDMD sites for the inhibition of heterologous miRNAs, including several encoded by Kaposi's Sarcoma-associated herpesvirus (KSHV). We focused particularly on miR-K11, a viral mimic of the oncogenic miRNA miR-155. miRNA pairing architectures based on the TDMD site in the long non-coding RNA Cyrano outperformed other retargeted sites. Cyrano-like inhibitors were specific for viral miR-K11 over cellular miR-155 and vice versa. Lentiviral delivery of a Cyrano-like miR-K11 inhibitor into KSHV-transformed primary effusion lymphoma (PEL) cells impaired their viability, showing that miR-K11 promotes KSHV-dependent PEL cell survival. Surprisingly, inactivation of ZSWIM8, a key mediator of TDMD, did not substantially affect miRNA inhibition by retargeted Cyrano-based inhibitors in 293T or PEL cells. Together, our results demonstrate the feasibility of retargeting natural TDMD sites to highly expressed viral or cellular miRNAs and further define features of effective encoded miRNA inhibitors.
Identification of a reduced rate combination of a plant growth inhibitor with a plant defense inducer for the management of the shoot blight phase of fire blight
Authors: Slack Suzanne M. , Yuan Xiaochen , Outwater Cory , Sundin George W.
Published: November 2024

The secondary shoot blight phase of fire blight is a critical component of disease epidemics in apples, pears, and other Rosaceae family plants with infection occurring at the tips of vigorously growing branches. Shoot blight infections are exacerbated in modern high-density apple plantings, where growers emphasize maximizing tree growth to recapture planting costs and increase yields of high-quality fruit. The overarching goal of this study was to develop new strategies for shoot blight management that do not impact the growth and yield of young apple trees. 'Gala' apple trees of various ages were inoculated with the fire blight pathogen Erwinia amylovora. Being treated with a combination of reduced rate mixtures of prohexadione calcium (ProCa; 6-12× rate reduction) with acibenzolar-S-methyl (ASM; 2× reduction) resulted in a significant decrease in shoot blight incidence and severity without significant impacts on branch growth. The systemic spread of E. amylovora was significantly reduced in trees sprayed with these lower-rate mixtures. Comparable rates of either treatment alone were not as effective in reducing lesion length. A transcriptomic analysis revealed a synergistic effect in which the expression of marker genes associated with systemic acquired resistance was higher in apple trees sprayed with the low-rate mixture of ProCa + ASM than with either compound alone. We conclude that the combination of ProCa + ASM at reduced rates is an effective treatment for the shoot blight phase of fire blight without impacting horticultural practices associated with high-density apple production.
Perioperative Extracorporeal Cardiopulmonary Resuscitation in Adults: A Single-center Retrospective Review and Analysis
Authors: Kapoor Ashie , Wolfe Michael W. , Chen Weiting , Benharash Peyman , Gudzenko Vadim
Published: November 2024

Background:

Extracorporeal cardiopulmonary resuscitation (CPR) for refractory in-hospital cardiac arrest has been associated with improved survival compared with conventional CPR. Perioperative patients represent a unique cohort of the inpatient population. This study aims to describe and analyze the characteristics and outcomes of patients who received extracorporeal CPR for perioperative cardiac arrest.

Methods:

A single-center retrospective review of perioperative extracorporeal CPR in adults from January 2015 to August 2022 was performed. Patient demographics, cardiac arrest variables, and outcome data were obtained and analyzed. The primary study outcome was survival with favorable neurologic outcome.

Results:

A total of 33 patients received extracorporeal CPR for perioperative cardiac arrest. Of the 33 patients, 24 (73%) had a cardiac arrest in the cardiac catheterization laboratory, while 9 (27%) had a cardiac arrest in the operating room or interventional radiology suite. Survival to discharge was 57.6%, of whom 17 (89.5%) had neurologically favorable outcomes with cerebral performance category scores of 1 or 2 at discharge. The mean total CPR time was significantly lower in the survivor group than in the nonsurvivor group (16.5 vs. 25.0 min; P < 0.05). Survivors had significantly lower lactate levels (73 mg/dl vs. 115 mg/dl; P = 0.005) and higher pH levels (7.17 vs. 7.03; P = 0.005) compared with nonsurvivors.

Conclusions:

The use of extracorporeal CPR for adults with perioperative cardiac arrest can be associated with excellent survival with neurologically favorable outcomes in carefully selected patients. Longer CPR time, higher lactate levels, and lower pH were associated with increased mortality. Given the small sample size, no other prognostic factors were identified, although certain trends were detected between survival groups.
Minimally Invasive Arthroscopic–Assisted Treatment for Isolated Scaphoid Fossa Die Punch Nascent Malunion
Authors: Marcovici Lucian Lior , Greco Alessandro , Muscatiello Antonio Luca , Chiossi Beatrice , Pagnotta Alessia
Published: November 2024

A die punch fracture is an intra-articular fracture of the distal radius characterized by a localized depression of the articular surface, typically occurring in the lunate fossa. Misdiagnosis or incorrect management can lead to articular malunion. While die punch fractures in the scaphoid fossa are less common, their nascent malunions pose significant treatment challenges. Traditionally, these fractures are treated with an open dorsal and volar approach, combined with osteotomy and internal fixation. Arthroscopic-assisted osteotomy has emerged as a promising technique due to its precision and minimally invasive nature. We present a new arthroscopic assisted minimally invasive technique for treating isolated dislocated die punch fracture nascent malunion of the scaphoid fossa. We treated an isolated scaphoid die punch nascent malunion, with a 5 mm joint surface depression. Using a 3-4 portal and a 30-degree curved mini osteotome, we performed an intra-articular osteotomy of the fragment. A small 2 cm skin incision over the Lister tubercle and a 1 cm bone window facilitated the introduction of a 30-degree curved curette to elevate and anatomically reduce the fragment under arthroscopic guidance. Definitive fixation was achieved with 3 K-wires. Postoperative x-rays at 6 weeks show complete fracture consolidation, confirmed by a subsequent computed tomography scan. At 3 months, patients demonstrated satisfactory clinical recovery with wrist range of motion and grip strength equal to the contralateral wrist, returning to normal activities.

This technique is feasible and safe, minimizing soft tissue damage, preserving proprioception and vascularity, and enabling faster recovery.
Improving Executive Function in Children and Adolescents with Cognitive-Engaging Physical Activity: A Systematic Review and Multilevel Meta-Analysis
Authors: Teng Gesi , Xia Haishuo , Li Qing , Chen Antao
Published: November 2024

Executive function (EF) development is vital for children and adolescents, with physical activity (PA) playing a key role in its enhancement. Through a systematic review and multilevel meta-analysis, this study investigates the effectiveness of cognitively engaging physical activity (CEPA) over traditional PA in fostering EF in children and adolescents. The research involved 1671 participants across 15 studies to determine if CEPA is superior to PA in enhancing EF and to analyze interventions and dose-response effects. Results demonstrated that CEPA had a more pronounced impact on EF development compared with PA, with a Hedges' g of 0.50 (95% confidence interval, 0.10–0.48), although potentially overestimated due to small-study effects and publication bias. Subgroup analyses did not find notable differences in effectiveness among various intervention types. The most substantial effect was observed with 45-minute interventions, while frequencies less than twice weekly and durations beyond 12 weeks were less effective. These findings suggest that CEPA could be a more efficacious method for advancing EF in youth, indicating a need for larger-scale randomized controlled trial (RCTs) to confirm the results and more accurately estimate their magnitude.
Selective Mutism in the Context of Autism and Bilingualism
Authors: Carroll Bridgette , Bordes Edgar Veronica , Bar Sari H. , Call Cynthia R. , Nyp Sarah S.
Published: November 2024

CASE:

Juan is a 5-year-old boy who has been followed by a developmental-behavioral pediatrician and pediatric neuropsychologist since being diagnosed with language delay and autism spectrum disorder at age 2 years. He is otherwise healthy and was born at term after a healthy pregnancy. His primary language is Spanish, and he has minimal interactions in English. His first words were at 20 months; they were not functional but rather words related to his interests such as “train.” He began using 2 to 3-word phrases shortly after but only to request needs. He began speaking in complete sentences at age 4 years.

A neuropsychological evaluation was conducted at age 2 years during which Juan demonstrated repetitive behaviors such as hand-flapping, toe-walking, body rocking, and head banging. He displayed sensory seeking behaviors such as rubbing items on his face and close visual inspection. He did not respond to his name and his use of eye contact was inconsistent. He demonstrated rigidity and difficulty transitioning between activities. He did not engage in social reciprocity, and his facial expressions were limited. Minimal spontaneous language was observed, and expressive language largely consisted of echolalia in both languages. Juan was diagnosed with autism spectrum disorder and applied behavior analysis, speech and language therapy, and occupational therapy were recommended.

Developmental-behavioral follow-up over the next 2 years noted improvements in behavior, transitions, and social interactions. He participated in early childhood intervention and early childhood special education with significant advances for speech and language in English and Spanish, demonstrating a large vocabulary. At 4 years, parents noted Juan to have reluctance to speak in English. He stopped speaking in English entirely for 3 weeks, though he continued to speak in Spanish. When he resumed speaking in English, it was only with people he knew well (e.g., parents, teachers, babysitter). In clinic, he did not speak to the English-speaking developmental-behavioral pediatrician but spoke in short sentences to the Spanish-speaking neuropsychologist.

A repeat neuropsychological evaluation completed at age 5 years revealed that Juan had stopped speaking in English completely, even among those previously deemed “safe.” Results were consistent with average cognitive abilities with a strength in verbal skills. Juan's single-word vocabulary in Spanish was exceptionally high. He did not provide expressive responses in English, but his receptive English vocabulary was high average. He responded to English language with nonverbal gestures or spoken language in Spanish. Parents reported Juan to display increased anxiety accompanied by extreme school refusal, behavioral difficulties, and reluctance to leave the home.

Given this information, what are your diagnostic considerations and treatment recommendations?
Subclinical target organ damage in a sample of children and adolescents with solitary functioning kidney. A pilot study
Authors: Tagetti Angela , Cattazzo Filippo , Marcon Denise , Romano Simone , Giontella Alice , Bortolotti Stefano , Minuz Pietro , Pecoraro Luca , Brugnara Milena , Fava Cristiano
Published: November 2024

Background:

Patients with solitary functioning kidney appear to be exposed to an increased cardiovascular risk. This study aimed to evaluate the impact of peripheral and central blood pressure on subclinical cardiovascular organ damage in a sample of children and adolescents with solitary functioning kidney.

Methods:

Carotid ultrasonography was performed to measure the carotid intima-media thickness (cIMT) and the carotid distensibility coefficient. The carotid-femoral pulse wave velocity (PWV) was assessed by tonometry. Cardiac mass and remodeling were estimated using transthoracic echocardiography. Central and peripheral (both office and 24-h ambulatory) BP measurements were collected.

Results:

Forty-four patients were included. Eighteen subjects (45%) were hypertensive as assessed by 24-h ABPM, with a prevalence of masked hypertension of 43%. Twenty-three subjects (52%) had an increased cIMT, while 2 and 3 patients (5% and 7%) demonstrated an impaired carotid distensibility coefficient and PWV, respectively. Nineteen subjects (43%) showed concentric cardiac remodeling. Central systolic blood pressure (cSBP) correlated with cIMT (r = 0.35) and left ventricular mass index (LVMi) (r = 0.32) demonstrating a positive independent association with an increased cIMT (odds ratio 1.14, 95% confidence interval 1.01–1.29) in multivariate regression analysis.

Conclusion:

Children and adolescents with solitary functioning kidney exhibited a high prevalence of masked hypertension and subclinical cardiovascular organ damage. These findings support the use of 24-h ABPM to identify patients with a higher cardiovascular risk who would benefit from hypertension treatment and closer monitoring during growth and into adulthood. Additionally, cSBP measurement should be considered as part of a more detailed cardiovascular risk assessment in these patients.
Early Sterile Keratolysis Complication With Decellularized Porcine Corneal Inlay Implant: A Case Report and Cautionary Tale
Authors: Borgia Alfredo , Airaldi Matteo , Lagali Neil , Ahmad Mohammad , Riaz Amina , Kaye Stephen , Romano Vito
Published: November 2024

Purpose:

To describe an early sterile keratolysis associated with a decellularized porcine corneal inlay implant for keratoconus.

Methods:

This is a case report of a 23-year-old man with keratoconus who underwent lenticular intrastromal keratoplasty in his OD. Within 4 weeks, the patient presented with anterior sterile keratolysis and partial inlay extrusion, leading to surgical inlay removal.

Results:

After inlay removal, despite aggressive topical treatment including steroid drops, antibiotic ointment, and bandage contact lenses, the patient developed severe anterior scarring and corneal flattening, resulting in decreased visual acuity. Over a period of 4 months, the cornea underwent long-term remodeling, with vision improving to a best-corrected distance visual acuity of 0.1 logarithm of the minimum angle of resolution.

Conclusions:

The removal of the porcine corneal inlay because of severe keratolysis highlights the potential risks of this procedure. In addition, the spontaneous improvement in visual acuity over 4 months emphasizes the need for adequate healing time before further surgeries, such as keratoplasty.
The Use of Classic Psychedelics for Depressive and Anxiety-Spectrum Disorders
Authors: Kim Vivian , Wilson Scott M. , Woesner Mary E.
Published: November 2024

Following a decades-long decline in psychedelic research resulting from social, political, and legislative factors, there has been greatly renewed interest in these compounds' ability to treat psychiatric disorders. Classic psychedelics, encompassing both natural and synthetic psychoactive compounds, are characterized by their action as agonists or partial agonists of serotonin 5-hydroxytryptamine 2A receptors. In this comprehensive review, we summarize the latest clinical trials of classic psychedelics on depression and anxiety, attending to the patient demographics and methodology of each study. Overall, studies published since 2020 affirm the potential for classic psychedelics to treat major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, findings are limited by short follow-up durations and nonstandard dosing and study designs. Given that many of the studies identified were post hoc analyses or follow-up studies from a select few parent studies, it is recommended that more original research be undertaken, with more diverse and larger sample sizes, standardized methodologies including blinding assessment, and long-term follow-up to identify duration of benefits and adverse reactions. It is also important to consider the role of psychological support and the therapeutic alliance in the psychedelic treatment of psychiatric disorders.
Present and future of fecal microbiome transplantation in cirrhosis
Authors: Tafader Asiya , Bajaj Jasmohan S.
Published: November 2024

Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follow. Progressive dysbiosis and immune dysregulation occur in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted toward potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.
Association between lactate-to-albumin ratio and short-term prognosis of acute-on-chronic liver failure treated with artificial liver support system
Authors: Ma Yuanji , Du Lingyao , Bai Lang , Tang Hong
Published: November 2024

Background

The impact of lactate-to-albumin ratio (LAR) on the outcome of acute-on-chronic liver failure (ACLF) is scant.

Aims

To investigate the relationship between LAR and short-term prognosis in patients with COSSH (Chinese Group on the Study of Severe Hepatitis B) ACLF.

Methods

A retrospective cohort study was conducted in patients with COSSH ACLF treated with an artificial liver support system. Restricted cubic splines, linear regression models, and Cox regression models were used to investigate the relationships of LAR with disease severity and 28-day prognosis.

Results

The 28-day transplant-free and overall survival rates in the 258 eligible patients were 76.4% and 82.2%, respectively. The LAR in 28-day transplant-free survivors was lower than that in transplant or death patients [0.74 (0.58–0.98) vs. 1.03 (0.79–1.35), P < 0.001]. The LAR was positively associated with disease severity, 28-day transplant-free survival [adjusted hazard ratio (HR) (95% confidence interval (CI)) for transplant or death: 2.18 (1.37–3.46), P = 0.001], and overall survival [adjusted HR (95% CI) for death: 2.14 (1.21–3.80), P = 0.009]. Compared with patients with LAR < 1.01, patients with LAR ≥ 1.01 had poor 28-day prognosis [all adjusted HR (95% CI) > 1, P < 0.05]. Lactate was not a potential modifier of the relationship between LAR and short-term prognosis.

Conclusion

LAR was positively associated with disease severity and poor short-term prognosis in patients with COSSH ACLF.
Utility of preoperative 18F-flurodeoxyglucose PET/CT scanning in preoperative evaluation and surgical planning for pulmonary tuberculosis
Authors: Li Lei-Lei , Wang Lin , Li Hong-Wei , Chen Hui , Shi Lei , Wan Lai-Yi , Song Yan-Zheng
Published: November 2024

Objective

The objective of this study was to investigate the utility of preoperative 18F-FDG PET/CT scanning in preoperative evaluation and surgical planning for pulmonary tuberculosis.

Methods

The study involved a retrospective analysis of clinical data and preoperative chest 18F-FDG PET/CT data of 24 patients with pulmonary tuberculosis who underwent pneumonectomy at the Shanghai Public Health Clinical Center between December 2017 and January 2022.

Results

All 24 patients successfully underwent chest 18F-FDG PET/CT imaging, and complete data pertaining to the maximum standardized uptake value, mean standardized uptake value, minimum standardized uptake value, total lesion glycolysis, and metabolic tumor volume were obtained. Surgical excision plans were finalized using the chest 18F-FDG PET/CT findings along with the conventional chest CT scans. Pneumonectomy was successfully completed in all 24 patients, and these included 13 cases of pulmonary lobectomy, two cases of total pneumonectomy, one case of combined pulmonary lobectomy, one case of segmentectomy, and seven cases of pulmonary wedge resection. The actual surgical procedures had a conformity rate of 100% to the preoperative surgical plans that were made. The intraoperative bronchial stump embedding rate was 69% (11/18 cases), the incidence rate of postoperative air leakage was 3.8% (1/24 cases), and there were no reported cases of postoperative bronchopleural fistula or death.

Conclusion

Preoperative 18F-FDG PET/CT scans had significant utility in surgical planning, the selection of surgical methods, and the formulation of postoperative antituberculosis treatment courses for patients with pulmonary tuberculosis. The use of 18F-FDG PET/CT shows considerable promise in being promoted clinically for the surgical management of patients with pulmonary tuberculosis.
HCT in the widening spectrum of congenital immunodeficiencies
Authors: Muratori Rafaella , Bonfim Carmem
Published: November 2024

Purpose of review

Hematopoietic stem cell transplantation (HSCT) and inborn errors of immunity (IEI) have been closely linked since transplantation was first used to cure severe combined immunodeficiency (SCID) in 1968. Since then, novel genes and diseases have been continually added to the ongoing list of IEI, and new data on indications and outcomes have emerged. We review recent data and progress in the field of hematopoietic cell transplantation (HCT) for IEI including new diseases and complications.

Recent findings

Emerging data from haploidentical transplants, newborn screening results, and multicentric studies reveals promising outcomes for IEI. Immune dysregulation diseases deserve special attention regarding disease control and may require additional drugs pretransplant. Female carriers of X-linked Chronic granulomatous may present with a severe phenotype warranting the need for HCT. Insights from infectious complications and long-term comorbidities should help guide decisions to treat IEI patients.

From classical indications to recently described diseases, HCT for immunodeficiencies is a rapidly growing field. Novel data regarding alternative donor transplants, results from large cohorts, and long-term complications provide valuable knowledge for clinical practice.
Implementation science and genetic testing for familial hypercholesterolemia
Authors: Birkenhead Karen , Sullivan David , Watts Gerald F. , Sarkies Mitchell N.
Published: November 2024

Purpose of review

Familial hypercholesterolemia is a treatable genetic disorder of cholesterol metabolism. Genetic testing is the most specific method for diagnosing familial hypercholesterolemia, but it remains underutilized. Implementation science aims to bridge the gap between evidence and practice and, thereby, support improved familial hypercholesterolemia care. This review presents the current evidence on the use of implementation science to improve the use of genetic testing for familial hypercholesterolemia.

Recent findings

Recent research has focused on developing implementation strategies to improve the use of genetic testing, particularly cascade testing of at-risk blood relatives of known familial hypercholesterolemia cases. Stakeholder informed strategies aimed at improving communication between families and detection of familial hypercholesterolemia in primary care have been developed and implemented. Findings demonstrate implementation science methods can help remove barriers and improve the uptake of cascade genetic testing.

Significant gaps in familial hypercholesterolemia care emphasize the importance of practical and realistic approaches to improve the detection of this preventable cause of premature heart disease, and recent efforts using implementation science have shown some promising results. More implementation science studies are needed that address the considerable gaps in familial hypercholesterolemia care, including the underutilization of genetic testing, so that all individuals receive the best clinical care.
Enhancing Pancreatic Cancer Therapy With Targeted CD133-Exosome Delivery of PD-L1 siRNA
Authors: Yoon Young Chul , Lee Dosang , Park Jung Hyun , Kim Ok-Hee , Choi Ho Joong , Kim Say-June
Published: November 2024

Objectives

This study assessed the anticancer potential of genetically modified exosomes engineered to express CD133-binding peptides on their surface and carry PD-L1 siRNA for the treatment of murine model of metastatic pancreatic cancer.

Materials and Methods

CD133-targeting exosomes (tEx) were generated by harvesting conditioned media from adipose-derived stem cells (ASCs) that had undergone transformation using pDisplay vectors encoding CD133-binding peptide sequences. Subsequently, siPD-L1-loaded CD133-targeting Exosomes, referred to as tEx(s), were created by incorporating PD-L1 siRNA into the tEx using Exofect kit

Results

tEx(s) demonstrated superior targetability compared to other materials, including Ex, Ex(p), and tEx. This was substantiated by higher total radiant efficiency (TRE) observed in metastatic liver and pancreatic tissues following intravenous administration of tEx(s) (P < 0.05). Furthermore, the intravenous delivery of tEx(s) resulted in the most pronounced upregulation of proapoptotic markers (BIM and c-caspase 3) and the least downregulation of the antiapoptotic markers (Mcl-1 and Bcl-xL), which has been demonstrated in various methods, including real-time polymerase chain reaction, western blot analysis, and immunohistochemistry in the metastatic lesions in the livers (P < 0.05).

Conclusions

PD-L1 siRNA-loaded CD133-tEx demonstrated remarkable anticancer efficacy, characterized by specific binding to CD133-positive pancreatic cancer cells and suppression of PD-L1 expression within these cells.
The effect of antidepressant treatment on viral suppression among people with HIV diagnosed with depression in an urban clinic
Authors: Lesko Catherine R. , Fojo Anthony T. , Hutton Heidi E. , Falade-Nwulia Oluwaseun O. , Zalla Lauren C. , Seamans Marissa J. , Jones Joyce L. , Schweizer Nicholas P. , Moore Richard D. , Snow LaQuita N. , Keruly Jeanne C. , Chander Geetanjali
Published: November 2024

Objective:

To estimate the effect of antidepressant initiation on viral nonsuppression among people with HIV (PWH) with clinically recognized, untreated depression.

Design:

Retrospective, observational cohort study.

Methods:

We included clinical diagnoses of depression from January 2012 to June 2022 among PWH in the Johns Hopkins HIV Clinical Cohort without another serious psychiatric illness who had initiated antiretroviral therapy. We excluded diagnoses less than 90 days from a prior diagnosis, antidepressant prescription, or greater than one mental health visits. We estimated the association between initiating an antidepressant within 1 month of the index depression diagnosis and viral load nonsuppression (>200 copies/ml) on the first viral load 3–12 months subsequent. We adjusted for a comprehensive set of demographic and clinical confounders.

Results:

We included 2346 depression diagnoses among 946 patients; patients initiated an antidepressant following 16%. The risk of viral nonsuppression in the absence of antidepressant treatment was 15.6% [95% confidence interval (CI): 13.1–18.4]. Antidepressant initiation was not associated with viral nonsuppression (risk difference: 0.5%; 95% CI: −3.7 to 4.8) or secondary outcomes: improvement or resolution of depressive symptoms or adherence to scheduled clinic visits.

Conclusion:

In this sample of patients with as-yet-untreated depression, in a setting with co-located, low-barrier psychiatric services, antidepressant treatment was not associated with improved viral suppression. Pharmacologic management of depression has documented benefits in other studies. However, there may be a subset of PWH with depression who have been previously unsuccessfully treated with antidepressants who are less likely to respond to approved pharmacologic options and who require different interventions to improve their viral suppression.
Differential immunophenotype and proviral composition in young adults with perinatally acquired HIV
Authors: Baquero Lucia , Stover Sofia , Armani-Tourret Marie , Perbeils Ailen Daniela , Urioste Alejandra , Osegueda Peña Ariel Amadeo , Cruces Leonel Hernán , Coll Cardenas Patricia , Lattner Jorge , Sisto Alicia , Rolón María José , Arazi Solange , Ghiglione Yanina , Polo Maria Laura , Yu Xu G. , Lichterfeld Mathias , Turk Gabriela , Laufer Natalia
Published: November 2024

Objective:

To characterize the immune functionality and phenotype and the proviral composition of a cohort of young adults with perinatally acquired HIV (p-YA) from Argentina.

Design:

Cross-sectional study of 18 p-YA, 15 young adults with nonperinatally acquired HIV matched by age with p-YA and 14 adults with nonperinatally acquired HIV, matched by time from HIV diagnosis with p-YA, all from Argentina.

Methods:

Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on natural killer (NK) and T cells. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4+ T cells by IPDA. Soluble markers were determined by ELISA.

Results:

p-YA displayed lower expression of PD-1, higher levels of CD38+ CD4+ T cells and increased levels of naive T cells than control groups. Also, a trend of lower levels of IP HIV-DNA normalized to CD4+ T-cell counts and to the proportion of naive T cells was found in p-YA.

Conclusion:

The higher frequency of naive CD4+ T cells in p-YA cannot be explained by elevated thymic activity nor by a higher T-cell proliferation rate. This imbalance could have been generated early in life and persisted during adulthood. Naive CD4+ T cells may not serve as a major viral reservoir in p-YA. Also, the lower PD-1+ CD4+ T-cell count suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for proviral eradication.
Unusual FDG PET Appearances in a Patient With Metastatic Breast Carcinoma
Authors: Kaleemi Raima , Dudek Alexandra , Priftakis Dimitris , Bomanji Jamshed
Published: November 2024

This was a case of a 52-year-old woman with a history of multiorgan, metastatic breast cancer, who underwent several lines of treatment. She had brain metastases, which were treated with gamma knife. She progressed at other organ sites with additional recurrence of brain metastases and leptomeningeal disease, which demonstrated an interesting pattern of intracranial FDG uptake with further seizure-related muscular uptake.
“Motion Capture Suit Sign” for Immunotherapy-Induced Inflammatory Arthritis on 99mTc-MDP Bone Scintigraphy
Authors: Yew Dallas Shun-Yu , Lai Chun-Liang
Published: November 2024

We report the 99mTc-MDP bone scan of a 44-year-old man with a history of lung adenocarcinoma and recent multiple joint pain after completing pembrolizumab immunotherapy treatment. This interesting image of symmetric uptakes around bilateral joints throughout the skeleton resembles the ball sensors on a motion capture suit. Hence, we recommend naming this distinctive imaging appearance as the “motion capture suit” sign.
Analysis of Added Postoperative Diplopia After Transnasal Endoscopic Inferomedial Wall Decompression for Thyroid-Associated Ophthalmopathy
Authors: Zhu Suhui , Deng Rongjin , Wu Jianhao , Dai Baozhu , Gu Kaiming , Chen Xiaohu , Dai Yan
Published: November 2024

Background:

The authors retrospectively analyzed the reported rate of added diplopia and associated factors in patients with thyroid-associated ophthalmopathy (TAO) after transnasal endoscopic inferomedial wall decompression, to illuminate the issue and look for ways to improve prognosis.

Methods:

Retrospective analysis was done on the medical records of patients with moderate-to-severe TAO between 2023-01 and 2024-01. Under general anesthesia, transnasal endoscopic inferomedial wall decompression was carried out on each subject. Clinical outcomes included postoperative added diplopia (including new-onset and aggravated), strabismus, and alterations in the extraocular muscles.

Results:

Sixty-five eyes in 65 patients received treatment. Nineteen patients (29.3%) had new-onset horizontal diplopia at 1 month and 10 patients (15.4%) at 6 months postoperatively; 9 patients (13.8%) experienced aggravated horizontal diplopia at 1 month and 6 patients (9.2%) at 6 months (C2=4.947, P<0.05). The average volume of the medial rectus muscle was the only one to increase in the extraocular muscles (F=34.131, P<0.001), and the preoperative medial rectus muscle volume was higher in the added diplopia patients than in the no-added diplopia patients (F=267.405, P<0.001).

Conclusions:

Postoperative diplopia (both new-onset and aggravated) increased in TAO with transnasal endoscopic inferomedial wall decompression. Most added diplopia was horizontal and most added strabismus was esotropia. They were closely associated with changes in the medial rectus’s thickness, displacement, and structural alterations. The preoperative medial rectus volume is one of the possible markers of further postoperative diplopia.
The Readability, Understandability, and Suitability of Online Resources for Ostomy Care
Authors: Ficarino Hannah , Moses Cara , Wood Lauren , Byrd Gabby , Bhatia Smita , Chu Daniel , Hollis Robert
Published: November 2024

PURPOSE

the purpose of this study was to evaluate the content, readability, understandability, and suitability of online resources for patient specific ostomy care.

DESIGN

Retrospective cohort study

SUBJECT AND SETTING

Online websites for ostomy care designed for patients.

METHODS

Ostomy care websites designed for patients were identified by querying three online search engines. Content areas were established following assessment of all websites by two reviewers. Readability of each website was determined using the Flesch Reading Ease Test and the Simple Measure of Gobbledygook (SMOG) index. Understandability was measured using the Patient Education Materials Assessment Tool (PEMAT), and suitability was determined using the Suitability Assessment of Materials (SAM). Chi-Square and rank sum tests were used to compare these measures across website type and by number of content areas.

RESULTS

Twenty-three websites met inclusion criteria; 26.1% were for-profit, 13% were government, 26.1% were academic, and 34.8% were non-profit. Nineteen content areas were identified including themes related to pouching, bathing, physical activity, managing output, lifestyle, mental health, and eating. The median number of content areas covered was 8.5 [interquartile range (IQR) 4-13]. The most common content areas were changing/emptying a pouching system (82.6% of websites), preventing/managing peristomal skin irritation (78.3%), eating (60.9%), and odor management (60.9%). Less than 27% of websites had content on irrigation, blockage/constipation, and body image. Readability scores using the Flesch Reading Ease (mean 58, IQR 54.7-69.5) and SMOG Index (mean 9.1, IQR 7.6-9.9) correlated to a high-school or “fairly difficult” reading level. The mean PEMAT measuring understandability was 80 (IQR 78.9-84.0). The mean SAM score checking for suitability (literacy demand, graphics, layout and type, learning stimulation and motivation and cultural appropriateness) was 55% (IQR 48.4%-61.3%), indicating “adequate material.” A greater number of content areas on the websites were associated with worse readability (SMOG and Flesch Reading Ease scores) than websites presenting fewer content areas (P = .001 & P < .001, respectively).

CONCLUSIONS

We found significant variability in the content, readability, understandability, and suitability of online materials for ostomy care. Websites with more content areas were associated with worse readability.
Effects of Skin Microclimate Changes on Skin Condition in Healthy Adults
Authors: Borzdynski Caroline , Miller Charne , McGuinness William
Published: November 2024

PURPOSE

The purpose of this study was to examine the effects of moisture, as a skin microclimate variable, at the skin-support surface interface on repeated measures of skin erythema, stratum corneum hydration and skin temperature at pressure-prone areas of healthy adults.

DESIGN

Quasi-experimental repeated measures study.

SUBJECTS AND SETTING

Forty-eight healthy adults participated in a single center-controlled study conducted in a simulated hospital setting in an urban setting (Melbourne, Australia). This research project was conducted from November 2021 to June 2022.

METHODS

The effects of moisture and intermittent pressure-loading on skin overlying the sacrum, heels, and elbows were investigated. Participants followed a standardized immobilization protocol of 60 minutes, with 10-minute brief pressure off-loading, in the semi-recumbent position on a standard hospital bed/mattress. The intervention comprised laying with the sacrum in contact with an absorbent pad saturated with normal saline; control skin sites (elbows and heels) were not exposed to the moistened absorbent pad. Skin measures were obtained consecutively at each anatomical testing site upon brief off-loading. Linear mixed models (LMMs) were used to compare skin parameters over time and between conditions.

RESULTS

Differences in stratum corneum hydration scores between control and intervention conditions at the sacrum were significant (P = .001). Differences in erythema and skin temperature scores between control and intervention conditions at the sacrum did not significantly differ; however, significant changes in skin temperature (P = .025) at the sacrum were observed at the 10-minute measurement intervals over 1 hour in the sample, suggesting change in skin temperature over time. No participant displayed non-blanching erythema as a subjective indicator of skin injury in any of the testing conditions.

CONCLUSIONS

Skin moisture/wetness, over a period of 1 hour, does not appear to impact erythema and skin temperature at the sacrum. In contrast, the introduction of moisture at the sacrum significantly increases sacral stratum corneum hydration. Study findings suggest that more frequent monitoring cycles of wet sacral skin may be required to identify moisture-associated skin changes.
Geographic Variation in Receipt of Electroconvulsive Therapy Among US Department of Veterans Affairs Patients
Authors: Teja Nikhil , Gottlieb Daniel , Shiner Brian , Peltzman Talya , Watts Bradley V.
Published: November 2024

Objective

The aim of the study is to characterize geographic variation in electroconvulsive therapy (ECT) receipt across the United States (US) Veterans Administration (VA) healthcare system and explore potential explanatory variables.

Background

ECT is a highly effective and rapidly acting treatment for multiple mental disorders. However, there may be geographic disparities in access to ECT across the US.

Methods

We conducted a retrospective, cross-sectional study of all VA patients from 2003 to 2019 to describe rates of ECT within previously defined mental health referral regions (MHRRs). We investigated differences between the population that received ECT and other patients with a mental health condition severe enough to warrant inpatient hospitalization. We analyzed crude as well as age, sex, race, and ethnicity-adjusted ECT rates and explored potential explanatory variables. We compared MHRRs in the highest and lowest tertiles of ECT receipt.

Results

The rate of ECT receipt among VA patients was 1.7 individuals per 10,000 (SD = 1.6) annually. Among 115 MHRRs, the rate ranged from a minimum of 0 (effectively no utilization in some areas) to a maximum of 8.9. Regression analysis revealed few significant explanatory variables.

Conclusions

There is significant geographic variation in ECT receipt among VA patients that is not well explained by population characteristics and may be indicative of suboptimal treatment for several mental health conditions.
Signatures of glassy dynamics in highly ordered lipid bilayers with emergence of soft dynamic channels
Authors: Sureshkumar Harini , Iyer Sahithya , Banerjee Atreyee , Poduval Pratyush , Lyman Edward , Srivastava Anand
Published: November 2024

Over the last few decades, extensive investigations on spatial and dynamic heterogeneity have been performed on carefully reconstituted biological lipid membranes. Characterising the molecular features in heterogeneous membranes is extremely challenging due to experimentally inaccessible time- and length-scales of these emergent systems. In this context, simulations can provide important insights into molecular-level interactions leading to membrane heterogeneity and associated functions. To that end, we use the non-affine displacement (NAD) framework (a concept borrowed from Physics of granular material) to faithfully capture molecular-scale local membrane order in simulated heterogeneous bilayers. In our latest application of NAD, we investigate the temperature-dependent spatial and temporal organisation on microseconds trajectories of liquid-ordered bilayer systems at all-atom resolution (DPPC/DOPC/CHOL: 0.55:0.15:0.30; 40 nm x 40 nm with a total of 5600 lipids and 2 million atoms). Lateral organisation in these large bilayer patches show noticeable dynamic heterogeneity despite their liquid-ordered nature. Moreover, our NAD analyses reveal soft fluid channels within the tightly packed membrane reminiscent of the classical two-component Kob-Andersen glass-forming binary mixture. Hence, we characterised these systems using classical glass physics markers for dynamic heterogeneities such as Overlap, Four-point Susceptibility, van Hove, and Intermediate Scattering functions to quantify the multiple time scales underlying the lipid dynamics. Our analyses reveal that highly ordered membrane systems can have glass-like dynamics with distinct soft fluid channels inside them. Biologically, these dynamic channels could act as conduits for facilitating molecular encounters for biological functions even in highly ordered phases such as lipid nanodomains and rafts.