Analysis of Top 100 Articles Cited in Top Pain Journals: A Comprehensive Two Decade Bibliometric Analysis.

PURPOSE OF REVIEW: A bibliometric analysis was performed to analyze and compare the top 100 articles from the most well-known five pain journals: Pain, Pain Physician, Pain Medicine, Regional Anesthesia & Pain Medicine, and Journal of Pain. A query of the Scopus database was performed to filter the top 200 most cited articles from each journal. CY score was calculated for the top 200 articles from each journal by dividing the total number of citations by the number of years the article has been published. RECENT FINDINGS: All articles had a collective analysis of the top CY scores, the top 100 of which were further analyzed. The pain subtype, type of publication, country of origin, and senior author were extrapolated from these top 100 articles. Frequency tables were organized, revealing Pain Journal as the highest publishing journal out of the top 100 articles. Chronic pain was the most studied subtype of pain and narrative reviews were the most common type of evidence. Studies were also organized in five-year epochs to analyze the frequency of publications in these intervals. Results show that 2010-2014 had the highest frequency of articles published overall. Journal Impact Factor (JIF) is also an objective indicator of the average number of citations per published article from each journal. The journal with the highest JIF was Pain with an impact factor of 7.926. (6).

Syringocystadenocarcinoma papilliferum: a systematic review of clinical characteristics, reappraisal of associations, diagnostic pitfalls and management challenges.

Syringocystadenocarcinoma papilliferum (SCACP) is a rare and aggressive malignant adnexal tumor originating from apocrine or pluripotent appendageal glands, often associated with a preceding syringocystadenoma papilliferum (SCAP) or nevus sebaceus (NS). This systematic review rigorously examines SCACP through an analysis of 78 cases documented between 1980 and 2024. The study aims to provide a comprehensive review of the clinical manifestations, diagnosis, treatment modalities, and outcomes associated with SCACP, while also reappraising its associations, particularly with NS. SCACP predominantly affects older adults, with an average age of 66.3 years and a slight male predominance, commonly presenting as ulcerated nodules or plaques on the scalp. This review highlights the aggressive nature of SCACP, evidenced by significant rates of metastasis and recurrence. Treatment is primarily surgical, with Mohs micrographic surgery offering potential benefits in terms of margin control and cosmetic outcomes. The association of SCACP with NS is critically evaluated, suggesting a complex etiopathogenesis and underscoring the importance of recognizing this association for timely diagnosis and management. Our review also briefly discusses potential pitfalls faced by clinicians in the diagnosis of SCACP. Our findings emphasize the need for standardized treatment protocols and further research into targeted therapies to improve patient outcomes in SCACP.

Cost-Effective Surgical Management of Pterygium: A Blood-Based Adhesion Technique Substituting Fibrin Glue.

Pterygium is a degenerative eye condition marked by the abnormal growth of conjunctival tissue over the cornea, primarily affecting individuals near the equator. When it reaches the cornea's center, patients may experience obstructed and blurry vision, necessitating pterygium surgery. The standard surgical approach involves excision with a blade, using a conjunctival autograft to address the defect, and securing it with fibrin glue. Recurrence rates exhibit variability, with approximately half occurring within the initial three months. In this case, we present a more cost-effective surgical approach, avoiding the use of a blade to minimize intraoperative complications. Additionally, autologous blood is employed instead of fibrin glue. We evaluate immediate and post-operative complications, as well as the incidence of recurrence rates at the three-month mark.

Biomechanical Modeling of Cell Chirality and Symmetry Breaking of Biological Systems.

Accumulating evidence strongly suggests that cell chirality plays a pivotal role in driving left-right (LR) symmetry breaking, a widespread phenomenon in living organisms. Whole embryos and excised organs have historically been employed to investigate LR symmetry breaking and have yielded exciting findings. In recent years, in vitro engineered platforms have emerged as powerful tools to reveal cellular chiral biases and led to uncovering molecular and biophysical insights into chiral morphogenesis, including the significant role of the actin cytoskeleton. Establishing a link between observed in vivo tissue chiral morphogenesis and the determined chiral bias of cells in vitro has become increasingly important. In this regard, computational mathematical models hold immense value as they can explain and predict tissue morphogenic behavior based on the chiral biases of individual cells. Here, we present the formulations and discoveries achieved using various computational models spanning different biological scales, from the molecular and cellular levels to tissue and organ levels. Furthermore, we offer insights into future directions and the role of such models in advancing the study of asymmetric cellular mechanobiology.

A systematic review of basal cell carcinoma on the scrotum-reviewing presentation and identifying challenges in management.

Since the scrotum is rarely exposed to sunlight, basal cell carcinoma (BCC) development in this area is an uncommon occurrence. As result, there is a scarcity of research covering this particular presentation, which poses a diagnostic and therapeutic challenge for clinicians. The objective of this systematic review is to provide a thorough overview of scrotal BCC, including a summary of its clinical characteristics, and microscopic subtypes. It also seeks to discuss the many techniques used in the management of this uncommon clinical presentation. Utilizing data from 1957 to October 2023, a systematic review of PubMed and Wiley Online Library was conducted to identify all cases of scrotal BCC with various presentations and managements. A total of 73 patients were included. The median patient age was 65.9 years (range 42 to 87). All studies were either case reports or case series. Our review shows that treatment with Mohs micrographic surgery (MMS), leads to a superior patient outcome based on anecdotal evidence in select cases. To deepen our understanding of Mohs surgery's efficacy in treating scrotal BCC, it is imperative to conduct more robust research in the form of randomized clinical trials.

Engineered platforms for mimicking cardiac development and drug screening.

Congenital heart defects are associated with significant health challenges, demanding a deep understanding of the underlying biological mechanisms and, thus, better devices or platforms that can recapitulate human cardiac development. The discovery of human pluripotent stem cells has substantially reduced the dependence on animal models. Recent advances in stem cell biology, genetic editing, omics, microfluidics, and sensor technologies have further enabled remarkable progress in the development of in vitro platforms with increased fidelity and efficiency. In this review, we provide an overview of advancements in in vitro cardiac development platforms, with a particular focus on technological innovation. We categorize these platforms into four areas: two-dimensional solid substrate cultures, engineered substrate architectures that enhance cellular functions, cardiac organoids, and embryos/explants-on-chip models. We conclude by addressing current limitations and presenting future perspectives.

Through the Eyes of Uncertainty: Giant Cell Arteritis and Lyme Neuroborreliosis in a Story of Vision Loss.

Acute vision loss is a prevalent clinical manifestation associated with a broad spectrum of differential diagnoses, encompassing demyelinating diseases, neoplastic processes, autoimmune disorders, and infectious conditions. A rare but noteworthy infectious etiology contributing to acute vision loss is neurological Lyme disease (Lyme neuroborreliosis)-induced optic neuritis. Lyme disease, a vector-borne illness caused by the spirochete Borrelia burgdorferi, has the potential to affect multiple physiological systems and unfolds in three distinct stages. Another significant contributor to acute vision loss is giant cell arteritis, an autoimmune vasculitis that commonly affects large- and medium-sized vessels, including the temporal and ophthalmic arteries. This relatively common condition may manifest with symptoms, such as jaw claudication, headaches, and visual disturbances. The precise identification of the underlying cause of acute visual loss is of utmost importance for physicians, as it is instrumental in averting undesirable complications. An 80-year-old female presents to the emergency room with a sudden onset of blurry vision of the left eye, right-sided weakness, dysarthria, jaw pain, headache, and left facial droop. Following consultations with rheumatology and ophthalmology specialists, giant cell arteritis emerged as a primary consideration in the differential diagnosis for the observed vision loss. Subsequently, a temporal artery biopsy was conducted, definitively confirming the diagnosis of giant cell arteritis. Considering the patient's residence in an area endemic to Lyme disease, a Lyme immunoglobulin G (IgG) titer was ordered. The results returned positive, suggesting the presence of Lyme neuroborreliosis.

Asymmetrical positioning of cell organelles reflects the cell chirality of mouse myoblast cells.

Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical-basal, front-rear, and left-right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left-right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left-right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a "T"-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus-centrosome axis pointing toward the top-right direction of the "T." Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left-right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left-right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left-right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.

Helical vasculogenesis driven by cell chirality.

The cellular helical structure is well known for its crucial role in development and disease. Nevertheless, the underlying mechanism governing this phenomenon remains largely unexplored, particularly in recapitulating it in well-controlled engineering systems. Leveraging advanced microfluidics, we present compelling evidence of the spontaneous emergence of helical endothelial tubes exhibiting robust right-handedness governed by inherent cell chirality. To strengthen our findings, we identify a consistent bias toward the same chirality in mouse vascular tissues. Manipulating endothelial cell chirality using small-molecule drugs produces a dose-dependent reversal of the handedness in engineered vessels, accompanied by non-monotonic changes in vascular permeability. Moreover, our three-dimensional cell vertex model provides biomechanical insights into the chiral morphogenesis process, highlighting the role of cellular torque and tissue fluidity in its regulation. Our study unravels an intriguing mechanism underlying vascular chiral morphogenesis, shedding light on the broader implications and distinctive perspectives of tubulogenesis within biological systems.

Classic Kaposi Sarcoma: A Comprehensive Case Report on Multisite Involvements and Therapeutic Strategies.

Classic Kaposi sarcoma (CKS), a variant of Kaposi sarcoma (KS), predominantly affects elderly men of Mediterranean and Ashkenazi descent. It is primarily seen in immunocompetent patients, often as cutaneous manifestations in the lower extremities. Treatment of CKS ranges from radiation therapy, chemotherapeutic agents, surgical excision, cryosurgery, and immunotherapy, and the treatment selection is contingent on disease-specific manifestations. This study presents the case of an 83-year-old immunocompetent male of Mediterranean descent, diagnosed with CKS five years ago, exhibiting an onset of painful violaceous papulonodular lesions on the right medial plantar surface and painless papulonodular lesions on the right upper arm and medial thigh. The case highlights the intricacies of CKS diagnosis and management, shedding light on the diverse treatments targeted for lesions across various anatomical locations.

A Case Report of Steroid-Induced Angioedema and Urticaria.

Physicians regularly use corticosteroids to treat various conditions, attributing their anti-inflammatory and immunosuppressive properties. Cases of allergic sensitivity reactions and dermatitis induced by corticosteroids are relatively uncommon. We present a case regarding an 81-year-old male with a history of actinic keratosis, atopic dermatitis, and psoriasis, who experienced a Type I hypersensitivity reaction with facial angioedema and urticaria on his axilla, torso, and popliteal fossa that developed after treatment with oral prednisolone. This episode also exacerbated his previously diagnosed psoriasis. To treat psoriasis, a dermatologist prescribed clobetasol topical ointment, which did not alleviate the symptoms; instead, it only exacerbated the rash, and he was subsequently referred for corticosteroid allergy testing. North American 85 Comprehensive Series patch testing revealed a positive test for various classes of steroids, including clobetasol-17-propionate, budesonide, and dexamethasone, thus proving a T cell-mediated allergy to corticosteroids.

A Case Report of Allergic Hypersensitivity to Color Additives in Slurpee® Beverages.

Introduction: Many commercially available foods and beverages contain color additives to which patients may develop allergic hypersensitivity. Several color additives currently approved for commercial sale in the United States have raised health concerns to a varying degree as testing and evidence of carcinogenicity, genotoxicity, and hypersensitivity has thus far been inadequate. Common uses for color additives include baked goods (eg, cakes, pastries, candy), flavored dairy products such as yogurt, sports-themed drinks (eg, Gatorade® Fruit Punch), and red-dyed Slurpee® beverages. Methods: We present the case of a patient who experienced color additive-related allergic hypersensitivity reactions after consumption of Slurpee® beverages, which may place her at risk when consuming other commercially available beverages and food products containing color additives. Percutaneous skin testing and an oral challenge were administered using three different red color additives (two color additives for skin testing and one color additive for the oral challenge). Results: The specific color additive precipitating her symptoms was not conclusively identified. Review of the literature acknowledges the idea that further research into color additive-related allergy should be conducted as there are many commercially available color additives that can elicit hypersensitivity reactions after consumption. Conclusion: Current research shows that of the red color additives available, Citrus Red, Red No. 3, and Red No. 40 are recognized to elicit such reactions. In order to lessen the burden of color additive-related hypersensitivity in the general population, public education, increased research, and subsequent regulations should be implemented.

Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review.

BACKGROUND: Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. METHODS: We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. RESULTS: Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. CONCLUSION: Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

Cell jamming regulates epithelial chiral morphogenesis.

Internal organs such as the heart demonstrate apparent left-right (LR) asymmetric morphology and positioning. Cellular chirality and associated LR biased mechanical behavior such as cell migration have been attributed to LR symmetry breaking during embryonic development. Mathematical models have shown that chiral directional migration can be driven by cellular intrinsic torque. Tissue jamming state (i.e., solid-like vs fluid-like state) strongly regulates collective migratory behavior, but how it might affect chiral morphogenesis is still unknown. Here, we develop a cell vertex model to study the role of tissue rigidity or jamming state on chiral morphogenesis of the cells on a patterned ring-shaped tissue, simulating a previously reported experimental setup for measuring cell chirality. We simulate chirality as torsional forces acting on cell vertices. As expected, the cells undergo bidirectional migration at the opposing (inner and outer) boundaries of the ring-shaped tissue. We discover that more fluid-like tissues (unjammed) demonstrate a stronger chiral cell alignment and elongation than more solid-like (jammed) tissues and maintain a bigger difference in migration velocity between opposing tissue boundaries. Finally, we find that fluid-like tissues undergo more cell-neighbor exchange events. This study reveals that chiral torque is sufficient to achieve a biased cellular alignment as seen in vitro. It further sheds light on the mechanical regulation of chiral morphogenesis of tissues and reveals a role of cell density-independent tissue rigidity in this process.

The Actin Crosslinker Fascin Regulates Cell Chirality.

The left-right (L-R) asymmetry of the cells, or cell chirality, is a well-known intrinsic property derived from the dynamic organization of the actin cytoskeleton. Cell chirality can be regulated by actin-binding proteins such as α-actinin-1 and can also be mediated by certain signaling pathways, such as protein kinase C (PKC) signaling. Fascin, an actin crosslinker known to mediate parallel bundling of actin filaments, appears as a prominent candidate in cell chirality regulation, given its role in facilitating cell migration as an important PKC substrate. Here, it is shown that the chirality of NIH/3T3 cells can be altered by PKC activation and fascin manipulation. With either small-molecule drug inhibition or genetic knockdown of fascin, the chirality of 3T3 cells is reversed from a clockwise (CW) bias to a counterclockwise (CCW) bias on ring-shaped micropatterns, accompanied by the reversal in cell directional migration. The Ser-39 fascin-actin binding sites are further explored in cell chirality regulation. The findings of this study reveal the critical role of fascin as an important intermediator in cell chirality, shedding novel insights into the mechanisms of L-R asymmetric cell migration and multicellular morphogenesis.

Interacting with tumor cells weakens the intrinsic clockwise chirality of endothelial cells.

Endothelial cells (ECs) possess a strong intrinsic clockwise (CW, or rightward) chirality under normal conditions. Enervating this chirality of ECs significantly impairs the function of the endothelial barrier. Malignant tumor cells (TCs) undergo metastasis by playing upon the abnormal leakage of blood vessels. However, the impact of TCs on EC chirality is still poorly understood. Using a transwell model, we co-cultured the human umbilical vein endothelial cells or human lung microvascular endothelial cells and breast epithelial tumor cell lines to simulate the TC-EC interaction. Using a micropatterning method, we assessed the EC chirality changes induced by paracrine signaling of and physical contact with TCs. We found that the intrinsic clockwise chirality of ECs was significantly compromised by the TC's physical contact, while the paracrine signaling (i.e., without physical contact) of TCs causes minimal changes. In addition, ECs neighboring TCs tend to possess a left bias, while ECs spaced apart from TCs are more likely to preserve the intrinsic right bias. Finally, we found the chirality change of ECs could result from physical binding between CD44 and E-selectin, which activates protein kinase C alpha (PKCα) and induces pseudopodial movement of EC toward TC. Our findings together suggest the crucial role of EC-TC physical interaction in EC chirality and that weakening the EC chirality could potentially compromise the overall endothelial integrity which increases the probability of metastatic cancer spread.

A Micropatterning Assay for Measuring Cell Chirality.

Chirality is an intrinsic cellular property, which depicts the asymmetry in terms of polarization along the left-right axis of the cell. As this unique property attracts increasing attention due to its important roles in both development and disease, a standardized quantification method for characterizing cell chirality would advance research and potential applications. In this protocol, we describe a multicellular chirality characterization assay that utilizes micropatterned arrays of cells. Cellular micropatterns are fabricated on titanium/gold-coated glass slides via microcontact printing. After seeding on the geometrically defined (e.g., ring-shaped), protein-coated islands, cells directionally migrate and form a biased alignment toward either the clockwise or the counterclockwise direction, which can be automatically analyzed and quantified by a custom-written MATLAB program. Here we describe in detail the fabrication of micropatterned substrates, cell seeding, image collection, and data analysis and show representative results obtained using the NIH/3T3 cells. This protocol has previously been validated in multiple published studies and is an efficient and reliable tool for studying cell chirality in vitro.

Cell Chirality as a Novel Measure for Cytotoxicity.

Cytotoxicity assessment has great importance in both research and pharmaceutical development. The mainstream in vitro cytotoxicity assays are mostly biochemical assays that evaluate a specific cellular activity such as proliferation and apoptosis. Few assays assess toxicity by characterizing overall functional outcomes in cellular physiology such as multicellular morphogenesis. The intrinsic cellular chiral bias (also known as cell chirality, left-right asymmetry, or handedness), which determines cellular polarization along the left-right axis, is demonstrated to play important roles in development and disease. This chiral property of cells gives insights not only into functions of individual cells, such as motility and polarity but also into emerging behaviors of cell clusters, such as collective cell migration. Therefore, cell chirality characterization can be potentially used as a biomarker for assessing the overall effects of pharmaceutical drugs and environmental factors on the health of the cell. In this review article, the current in vitro techniques for cell chirality characterization and their applications are discussed and the advantages and limitations of these cell chirality assays as potential tools for detecting cytotoxicity are discussed.

Effects of Alzheimer's Disease-Related Proteins on the Chirality of Brain Endothelial Cells.

INTRODUCTION: Cell chirality is an intrinsic cellular property that determines the directionality of cellular polarization along the left-right axis. We recently show that endothelial cell chirality can influence intercellular junction formation and alter trans-endothelial permeability, depending on the uniformity of the chirality of adjacent cells, which suggests a potential role for cell chirality in neurodegenerative diseases with blood-brain barrier (BBB) dysfunctions, such as Alzheimer's disease (AD). In this study, we determined the effects of AD-related proteins amyloid-ß (Aß), tau, and apolipoprotein E4 (ApoE4) on the chiral bias of the endothelial cell component in BBB. METHODS: We first examined the chiral bias and effects of protein kinase C (PKC)-mediated chiral alterations of human brain microvascular endothelial cells (hBMECs) using the ring micropattern chirality assay. We then investigated the effects of Aß, tau, and ApoE4 on hBMEC chirality using chirality assay and biased organelle positions. RESULTS: The hBMECs have a strong clockwise chiral bias, which can be reversed by protein kinase C (PKC) activation. Treatment with tau significantly disrupted the chiral bias of hBMECs with altered cellular polarization. In contrast, neither ApoE4 nor Aß-42 caused significant changes in cell chirality. CONCLUSIONS: We conclude that tau might cause BBB dysfunction by disrupting cell polarization and chiral morphogenesis, while the effects of ApoE4 and Aß-42 on BBB integrity might be chirality-independent. The potential involvement of chiral morphogenesis in tau-mediated BBB dysfunction in AD provides a novel perspective in vascular dysfunction in tauopathies such as AD, chronic traumatic encephalopathy, progressive supranuclear palsy, and frontotemporal dementia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00669-w.

Recent Advances in Cellular and Molecular Bioengineering for Building and Translation of Biological Systems.

In January of 2020, the Biomedical Engineering Society (BMES)- Cellular and Molecular Bioengineering (CMBE) conference was held in Puerto Rico and themed "Vision 2020: Emerging Technologies to Elucidate the Rule of Life." The annual BME-CMBE conference gathered worldwide leaders and discussed successes and challenges in engineering biological systems and their translation. The goal of this report is to present the research frontiers in this field and provide perspectives on successful engineering and translation towards the clinic. We hope that this report serves as a constructive guide in shaping the future of research and translation of engineered biological systems.