bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2 Development of CAR-NK Cell Therapy for Hematologic Malignancies
Authors: Stoltzman Carrie , Chandrasekaran Devikha , von Euw Erika , McKay Cyd , Root Christina , Delaney Colleen
Published: September 2022

Introduction

Natural killer (NK) cells can kill tumor cells without priming or prior activation through their complement of activating and inhibitory surface molecules. Chimeric antigen receptor (CAR) expression by engineered NK cells can improve both specificity and potency of the NK cells’ anti-tumor efficacy. CAR-NK cell therapy may be a safer, more clinically accessible, and cost effective allogeneic cellular therapy in comparison to autologous CAR-T cell therapy, as NK cells do not cause graft versus host disease (GvHD) or cytokine release syndrome (CRS).

Objective

We aimed to develop an allogeneic, cryopreserved, off-the-shelf CAR-NK cell product for the treatment of hematologic malignancies.

Methods

Our CD56+ NK cells are generated from cord blood-derived CD34+ cells, which undergo expansion and priming on a proprietary Notch ligand cell culture platform followed by a second culture phase of NK cell differentiation. These cells were transduced using a viral vector to express a CAR specific for an antigen expressed on the cell surface of acute lymphoblastic leukemia (ALL) cells. The CAR-NK cells were assessed for CAR expression, NK cell phenotype, and in vitro cytotoxicity both pre- and post-cryopreservation. An ALL xenograft mouse model was treated using repeat doses of cryopreserved CAR-NK cell product, with readouts of body weight, tumor growth, and survival.

Results

The transduced CAR-NK cell product displayed viability and phenotyping comparable to the untransduced control NK cell product but possessed significantly enhanced cytotoxicity against ALL target cells in vitro. Following cryopreservation and thaw, the CAR-NK cell product retained CAR expression and maintained enhanced anti-tumor function in vitro. Cryopreserved CAR-NK cell product was safely given in up to 8 repeat doses to ALL xenograft mice and significantly inhibited tumor growth as well as increased survival compared with control NK cell product.

Discussion

We have demonstrated in this proof-of-concept study that our cord blood CD34+ cell-derived CAR-NK cell product can maintain CAR expression, with specific and enhanced potency both in vitro and in vivo, following cryopreservation and thaw. Additional preclinical studies are planned to develop CAR-NK off-the-shelf cell therapy for AML and other hematologic malignancies.
Abstract 5 Human Umbilical Cord Blood-Derived Cell Therapy Product, DUOC-01, Promotes Remyelination by Driving the Differentiation of Oligodendrocyte Progenitor Cells
Authors: Xu Li , Saha Arjun , Parrott Roberta , O’Neil Shane , Kurtzberg Joanne , Filiano Anthony
Published: September 2022

Introduction

DUOC-01 is a macrophage-like cell therapy product manufactured by culturing banked human umbilical cord blood cells under GMP conditions. Currently, the safety of DUOC-01 is being tested as a bridging therapy in children with demyelinating leukodystrophies undergoing unrelated donor umbilical cord blood transplantation after myeloablative conditioning. DUOC-01 protects against loss of function in several preclinical models with demyelinating conditions of the central nervous system, making it an attractive therapy for patients with multiple sclerosis (MS) who experience destruction of myelin sheaths as pathology of their disease. The mechanism by which DUOC-01 promotes remyelination and if it directly influences oligodendrocyte lineage cells is untested.

Objective

Using multiple systems (primary oligodendrocyte precursor cell [OPC] cultures, in vitro cerebellar slice cultures, and experimental autoimmune encephalomyelitis [EAE], a mouse model of MS), we examined how DUOC-01 influences numerous steps of pathology and recovery.

Methods

Using a brain slice culture, we added DUOC-01 to the lysophosphatidylcholine (LPC)-treated slices. We quantified myelinated axons by assessing percent co-localization of myelin basic protein and neurofilament in the control, LPC, and LPC+DUOC-01 groups. To test the DUOC-01 effect in the EAE model, we immunized C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55) in complete Freund’s adjuvant. To match clinical protocols, we incubated DUOC-01 in Ringer’s lactate with hydrocortisone (HC) for 2 hours at room temperature. At the onset of EAE disease symptoms, we injected DUOC-01 into the cerebrospinal fluid by a single intra-cisterna magna injection, then recorded clinical scores daily for 2 weeks. To test if DUOC-01 could directly affect OPCs, we set up a primary OPC culture isolated from neonatal mice and added DUOC-01 treatment to the culture.

Results

In the cerebellar slice model, we demonstrated a higher number of myelinated neuron fibers in the DUOC-treated group compared with the LPC-treated group. In the EAE model, compared with mice injected with Ringer’s or HC+Ringer’s, mice injected with DUOC-01 derived clinical benefit with lower clinical scores. In the primary OPC culture, the DUOC-01 treatment drove the maturation of OPC to become myelin producing oligodendrocytes.

Discussion

Our data suggest that DUOC-01 could be beneficial in treating MS and other diverse neurological demyelinating conditions.
Abstract 14 Umbilical Cord Mesenchymal Stromal/Stem Cells Application for Spasticity Treatment in Multiple Sclerosis
Authors: Petriv Taras , Tatarchuk Michael , Tsymbaliyk Yaroslav , Rybachuk Oksana , Tsymbaliuk Yulia , Tsymbaliuk Vitaliy
Published: September 2022

Introduction

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to disability in young patients. Impaired motor function due to spasticity in such patients is significant. Umbilical cord mesenchymal stromal/stem cells (UC-MCS) are promising in the treatment of MS, in particular because they have a positive neurotrophic effect, promote remyelination, and thus, reduce spasticity.

Objective

The objective of the study was to investigate the effect of combined (intrathecal and intravenous) administration of UC-MCS on spasticity reduction.

Methods

Patients with MS (n = 27) underwent general and neurological examinations (Ashworth Scale for spasticity). The mean age of patients was 35.25 ± 13.72 years. Patients in group 1 (n = 12) were treated with cultured UC-MSCs, which met the phenotypic and morphologic criteria of the MCS. Patients in group 1 received a total dose of UC-MSCs at the rate of 1 × 106/kg body weight, 20 × 106 of which was administered intrathecally. Intrathecal administration was performed according to the typical method of performing lumbar puncture in the operation room using local anesthesia. Patients in group 2 (n = 15) were treated according to the National Multiple Sclerosis Treatment Protocol (https://zakon.rada.gov.ua/rada/show/v0487282-07#Text). Repeated clinical examination was performed after 1, 6, and 12 months.

Results

Comparing spasticity in the two groups of patients before treatment, no differences were found (P = .468). No statistically significant difference between the groups was found after 1 month (P = .426). Statistically significant spasticity reduction was observed 6 months after treatment (P = .01) and 1 year after treatment, in favor of group 1 (P = .009). The results indicate no improvement in spasticity reduction in the first month after treatment of patients with UC-MSCs. The positive effect was observed for 6 months after treatment and continued up to 1 year.

Discussion

UC-MSC significantly reduce spasticity in patients with MS and contribute to the regression of movement disorders for 6 months and up to 1 year after treatment. This result is probably achieved due to the immunomodulatory and remyelination properties of MSCs. Study results suggest the need to extend the observation period and conduct larger multicenter randomized studies.
Shaming
Authors: Gee Michelle L. , Copeland Darcy
Published: September 2022

Nurses in a variety of settings frequently use behavior modification strategies to promote health behavior change. Shaming is one such behavior modification tool, but its use in nursing is poorly understood. A concept analysis using Walker and Avant's method was performed. After an extensive literature review, a conceptual definition of shaming is proposed and defining attributes, antecedents, and consequences are presented. Shaming is also differentiated from related concepts often used synonymously such as stigmatization and incivility. Shaming as a behavior modification strategy is incongruous with nursing values and its utilization in nursing warrants further investigation.
Factors Involved in Nurses' Health-Seeking Behaviors
Authors: Najafi Tahereh , Rafii Forough , Rahimi Sara
Published: September 2022

This study aimed to explore the factors involved in Iranian nurses' health-seeking behavior. In this qualitative exploratory descriptive study, 15 nurses from hospitals affiliated to Iran and Qazvin University of Medical Sciences were interviewed from April to March 2020. Data were collected via purposive sampling by unstructured in-depth interviews and analyzed using thematic analysis. Findings identified 5 main themes, “fear,” “trust/distrust,” “excuse,” “accessibility,” and “support” that were involved in nurses' health-seeking behavior. The findings of this study may contribute to a deeper understanding of the factors involved in nurses' health-seeking behavior and pave the way for further research and policy making regarding nursing workforce health.
Analyzing Continuous Physiologic Data to Find Hemodynamic Signatures Associated With New Brain Injury After Congenital Heart Surgery
Authors: Nicoll Jessica , Somer Jonathan , Eytan Danny , Chau Vann , Marini Davide , Lim Jessie Mei , Greer Robert , Aly Safwat , Seed Mike , Miller Steven P. , Laussen Peter C. , Mazwi Mjaye L. , Schwartz Steven M.
Published: September 2022

IMPORTANCE:

Continuous data capture technology is becoming more common. Establishing analytic approaches for continuous data could aid in understanding the relationship between physiology and clinical outcomes.

OBJECTIVES:

Our objective was to design a retrospective analysis for continuous physiologic measurements and their relationship with new brain injury over time after cardiac surgery.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective cohort study in the Cardiac Critical Care Unit at the Hospital for Sick Children in patients after repair of transposition of the great arteries (TGA) or single ventricle (SV) lesions.

MAIN OUTCOMES AND MEASURES:

Continuously acquired physiologic measurements for up to 72 hours after cardiac surgery were analyzed for association with new brain injury by MRI. Distributions of heart rate (HR), systolic blood pressure (BP), and oxygen saturation (Spo2) for SV and TGA were analyzed graphically and with descriptive statistics over postoperative time for data-driven variable selection. Mixed-effects regression analyses characterized relationships between HR, BP, and Spo2 and new brain injury over time while accounting for variation between patients, measurement heterogeneity, and missingness.

RESULTS:

Seventy-seven patients (60 TGA; 17 SV) were included. New brain injury was seen in 26 (34%). In SV patients, with and without new brain injury, respectively, in the first 24 hours after cardiac surgery, the median (interquartile range) HR was 172.0 beats/min (bpm) (169.7–176.0 bpm) versus 159.6 bpm (145.0–167.0 bpm); systolic BP 74.8 (67.9–78.5 mm Hg) versus 68.9 mm Hg (61.6–70.9 mm Hg). Higher postoperative HR (parameter estimate, 19.4; 95% CI, 7.8–31; p = 0.003 and BP, 8.6; 1.3–15.8; p = 0.024) were associated with new brain injury in SV patients. The strength of this relationship decreased with time.

CONCLUSIONS AND RELEVANCE:

Retrospective analysis of continuous physiologic measurements can provide insight into changes in postoperative physiology over time and their relationship with new brain injury. This technique could be applied to assess relationships between physiologic data and many patient interventions or outcomes.
A Rare Case of Monomorphic T-Cell Posttransplant Lymphoproliferative Disorder Presenting as Primary Cutaneous Anaplastic Large Cell Lymphoma, ALK Negative
Authors: Robbins Quinn C. , Schmieg John , Rush Walter L. , Allbritton Jill I.
Published: September 2022

Posttransplant lymphoproliferative disorders are a serious complication of hematopoietic and solid organ transplants secondary to iatrogenic immunosuppression. Most cases present as B-cell proliferations which are often Epstein–Barr virus positive; however, ∼10% of cases are T/NK cell and are less commonly associated with Epstein–Barr virus. Of these, cutaneous T/NK-cell lymphomas are exceedingly rare. We report a case of a 69-year-old male, liver transplant recipient who presented with a tender, bright red papule on the left arm during his annual skin cancer screening. Histopathologic evaluation revealed pleomorphic cells with enlarged nuclei, vesicular chromatin, and frequent mitotic figures, intercalating through the dermis. The tumor formed single strands and small cords without epidermal involvement. A patchy mild mixed inflammatory infiltrate was associated with the tumor. Tumor cells were CD2(+), CD4(+), CD30(+), CD3(−), CD20(−), ALK-1(−), and EBER(−). Molecular studies revealed a monoclonal T-cell receptor gamma gene rearrangement by polymerase chain reaction (PCR); ALK gene rearrangement was negative by fluorescence in situ hybridization (FISH). Taken together, the findings were consistent with an ALK-negative anaplastic large cell lymphoma involving skin, which, given the history of liver transplant, qualified as a monomorphic T-cell posttransplant lymphoproliferative disorder. Follow-up imaging studies showed no evidence of systemic disease, supporting an interpretation of primary cutaneous anaplastic large cell lymphoma.
Cutaneous Malignant Squamomelanocytic Tumor: A Case Report of a Rare Neoplasm
Authors: Zipperer Kate , Good Allison J. , Gibson Bernard R. , Goodwin Brandon
Published: September 2022

Cutaneous squamomelanocytic tumor (SMT) is an exceedingly rare cutaneous malignancy characterized by the presence of both squamous cell carcinoma and malignant melanoma within a single tumor. SMT typically presents clinically as keratotic skin papulonodules, most commonly occurring on the face, scalp, or other sun-exposed areas of middle-aged to elderly White male patients. Owing to the rare nature of this tumor, the histogenesis and prognosis remain relatively unclear. Histopathological examination of the tangential biopsy revealed an invasive cutaneous malignancy consisting of 2 distinct yet closely associated atypical cell populations: (1) a population of atypical squamoid epithelial cells arranged in cords and keratin pearls and (2) a population consisting of atypical, spindled cells with fine melanin pigment arranged in confluent sheets. Both populations of atypical cells emanated in an invasive pattern from the underside of the overlying epidermis into the deep dermis. Squamomelanocytic tumors are among the rarer types of collision tumors between 2 malignant lesions as most are basomelanocytic. For most reported SMTs, the melanoma population comprises epithelioid cell morphology, whereas our tumor is composed of spindled cell morphology. In this article, we exemplify a unique case of SMT in an 87-year-old male patient.
Primary Cutaneous Anaplastic Large-Cell Lymphoma With Aberrant CD20 Expression: Case Report and Review of the Literature
Authors: Mark Erica , Sutton Mark , Gru Alejandro
Published: September 2022

Cutaneous CD20+T-cell lymphomas are exceedingly rare. Differentiating cases of T-cell lymphoma with aberrant expression of the B-cell marker CD20 from B-cell lymphoma may be associated with misdiagnosis or delays in diagnosis. We report, to the authors' knowledge, the first case of CD20+primary cutaneous anaplastic large-cell lymphoma and review the literature to characterize published cases of CD20+cutaneous T-cell lymphoma (n = 40). There is no accepted explanation for this phenomenon; however, it is suspected that these cases may be due to neoplastic transformation of CD20+T cells or that CD20 may represent a T-cell activation marker. Expression of CD20 may have clinical significance in prognostication and consideration of treatment options with anti-CD20 therapies such as rituximab.
Folliculosebaceous Cystic Hamartoma Arising in Miescher-Type Melanocytic Nevi
Authors: Ishihara Yuri , Ogita Azusa , Ito Keigo , Saeki Hidehisa , Ansai Shin-ichi
Published: September 2022

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units associated with mesenchymal elements. Ansai et al reported that distinctive features of Miescher-type melanocytic nevi (MMCNs) accompanied 4.6% of FSCH; however, there have been no data about how often FSCH features accompany MMCNs. In this study, we used 7829 cases that had been histopathologically diagnosed as MMCNs of the face, neck, and scalp at the Department of Dermatopathology, Nippon Medical School Musashi Kosugi Hospital and observed whether features of FSCH accompanied them. Of the resected MMCNs, 274 of 7829 (3%) were accompanied by features of FSCH. The nose was the most common resection site, followed by the eyebrow area, ear, and cheek. The coexistence rate for the nevi on the nose and features of FSCH was as high as 10%–20%, and its rate increased with age. We found that FSCH appears mostly in seborrheic areas, such as the nose and cheek, which are rich in normal sebaceous glands. This suggests that nevi, especially on and around the nose, may induce FSCH or similar lesions.
Autoantibodies and Cardiomyopathy: Focus on Beta-1 Adrenergic Receptor Autoantibodies
Authors: Tang Wai Hong Wilson , Naga Prasad Sathyamangla V.
Published: September 2022

Antibody response to self-antigens leads to autoimmune response that plays a determinant role in cardiovascular disease outcomes including dilated cardiomyopathy (DCM). Although the origins of the self-reactive endogenous autoantibodies are not well-characterized, it is believed to be triggered by tissue injury or dysregulated humoral response. Autoantibodies that recognize G protein-coupled receptors are considered consequential because they act as modulators of downstream receptor signaling displaying a wide range of unique pharmacological properties. These wide range of pharmacological properties exhibited by autoantibodies has cellular consequences that is associated with progression of disease including DCM. Increase in autoantibodies recognizing beta-1 adrenergic receptor (β1AR), a G protein-coupled receptor critical for cardiac function, is observed in patients with DCM. Cellular and animal model studies have indicated pathological roles for the β1AR autoantibodies but less is understood about the molecular basis of their modulatory effects. Despite the recognition that β1AR autoantibodies could mediate deleterious outcomes, emerging evidence suggests that not all β1AR autoantibodies are deleterious. Recent clinical studies show that β1AR autoantibodies belonging to the IgG3 subclass is associated with beneficial cardiac outcomes in patients. This suggests that our understanding on the roles the β1AR autoantibodies play in mediating outcomes is not well-understood. Technological advances including structural determinants of antibody binding could provide insights on the modulatory capabilities of β1AR autoantibodies in turn, reflecting their diversity in mediating β1AR signaling response. In this study, we discuss the significance of the diversity in signaling and its implications in pathology.
The Impact of Environmental Factors on Credit Ratings in Healthcare
Authors: Wadhwani Emily E.
Published: September 2022

At their core, credit ratings are holistic assessments of relative credit risk, inclusive of both quantitative and qualitative factors. Environmental, social, and governance (ESG) considerations have always been implicitly incorporated in credit rating methodology as components of a hospital or health system's wider performance. More recently, however, ESG effects have been explicitly identified. While social and governance considerations are important to credit ratings, the impact of environmental factors on rating outcomes in the healthcare sector continues to expand exponentially. This movement reflects the varied ways in which climate change, resource and materials management, energy management, and water management can affect credit profiles. The shift to a lower carbon-dependent economy also presents opportunities for issuers that make meaningful transitions toward renewable energy sources.
The Value of Sound Environmental Practices in Healthcare Facilities Management
Authors: Flannery Jonathan J.
Published: September 2022

The time has come for healthcare organizations to improve their efforts regarding their impact on the environment, particularly on the communities they serve. For years, healthcare has been at the forefront in addressing social needs with public health initiatives but has lagged on environmental concerns. By carefully reviewing their energy usage and aging infrastructures, healthcare leaders and their facility managers can do a better job of controlling healthcare's environmental impact. Green practices are key indicators of an organization's ethically focused sustainability efforts. So, while healthcare has traditionally focused on its social impact—providing healthcare services is, after all, inherently social—it must expand its community engagement by considering the environmental impact of hospitals and health systems on their communities in the context of climate change.
TECHNIQUE FOR REMOVAL OF A GANCICLOVIR IMPLANT DISLOCATED IN THE VITREOUS CAVITY
Authors: Lenis Tamara L. , Botsford Benjamin E. , Kovacs Kyle D. , Papakostas Thanos D.
Published: September 2022

Purpose:

To report a technique to remove a dislocated ganciclovir implant in the vitreous cavity.

Methods:

Retrospective case series. Two patients with dislocated ganciclovir implants in the vitreous cavity.

Results:

A 6-mm pars plana incision was made; the soft tip was used to elevate the implant behind the intraocular lens and then 0.12-mm forceps were used to externalize the implant. The implant was successfully removed in both patients.

Conclusion:

Removal of a dislocated ganciclovir implant with its encasing strut can be effectively retrieved using a bimanual approach.
Optic perineuritis
Authors: Saitakis George , Chwalisz Bart K.
Published: September 2022

Purpose of review

This review paper aims at discussing pathogenesis, etiology, clinical features, management, and prognosis of OPN.

Recent findings

Optic perineuritis (OPN) is an inflammatory process primarily involving the optic nerve sheath. Clinically, OPN usually presents with unilateral, gradual decline of visual function, eye pain, and/or pain on eye movements, disc edema and various features of optic nerve dysfunction, including visual field defects. It can mimic typical optic neuritis. In most cases of OPN, the disease is isolated with no specific etiology being identified, however, it can also occur secondary to a wide range of underlying systemic diseases. OPN is clinically diagnosed and radiologically confirmed based on the finding of circumferential perineural enhancement of the optic nerve sheath on magnetic resonance imaging (MRI).

Unlike optic nerve, OPN is not typically self-limited without treatment. High-dose oral corticosteroids are the mainstay of treatment in OPN. The initiation of therapy usually causes rapid and dramatic improvement in signs and symptoms. In general, OPN usually has a relatively good visual prognosis, which is influenced by delays between the onset of visual loss and the initiation of steroid therapy as well as the presence of underlying systemic diseases.
To do one and to get more: Part I. Diabetes and bone
Authors: Lee Wen-Ling , Wang Peng-Hui , Yang Szu-Ting , Liu Chia-Hao , Chang Wen-Hsun , Lee Fa-Kung
Published: September 2022

Type 2 diabetes mellitus (T2DM), is a chronic metabolic disease, characterized by the presence of hyperglycemia and insulin resistance. The key treatment strategies for T2DM include modification of lifestyle, medications, and continuous glucose monitoring. DM patients often have DM-associated morbidities and comorbidities; however, disorders of musculoskeletal system are often neglected, compared to other major systems in DM patients. Based on sharing similar pathophysiology of DM and osteoporosis, it is supposed that the use of antidiabetic agents (ADAs) may not only provide the lowering glucose level effect and the maintenance of the sugar homeostasis to directly delay the tissue damage secondary to hyperglycemia but also offer the benefits, such as the prevention of developing osteoporosis and fractures. Based on the current review, evidence shows the positive correlation between DM and osteoporosis or fracture, but the effectiveness of using ADA in the prevention of osteoporosis and subsequent reduction of fracture seems to be inconclusive. Although the benefits of ADA on bone health are uncertain, the potential value of “To do one and to get more” therapeutic strategy should be always persuaded. At least, one of the key treatment strategies as an establishment of healthy lifestyle may work, because it improves the status of insulin resistance and subsequently helps DM control, prevents the DM-related micro- and macrovascular injury, and possibly strengthens the general performance of musculoskeletal system. With stronger musculoskeletal system support, the risk of “fall” may be decreased, because it is associated with fracture. Although the ADA available in the market does not satisfy the policy of “To do one and to get more” yet, we are looking forward to seeing the continuously advanced technology of drug development on diabetic control, and hope to see their extra-sugar–lowering effects.
Effects of Treatment of Acute Major Depressive Episodes in Bipolar I Versus Bipolar II Disorders With Quetiapine
Authors: Miola Alessandro , Tondo Leonardo , Baldessarini Ross J.
Published: September 2022

Background

Several second-generation antipsychotic drugs (SGAs) have evidence of benefit for acute major depressive episodes in bipolar disorder (BD) patients. However, their comparative efficacy in types I vs II BD (BD1 vs BD2) remains uncertain.

Methods

We carried out a systematic literature search for randomized, double-blinded, controlled treatment trials for acute major depressive episodes involving head-to-head comparisons of BD1 versus BD2 subjects, followed by meta-analyses and meta-regression modeling.

Results

Seven reports met out inclusion criteria, yielding 22 comparisons of SGA versus placebo averaging 8.3 weeks in duration. All trials involved quetiapine, which was much more effective than placebo (pooled standardized mean difference [SMD] = 1.76 [95% confidence interval, 1.40–2.12], P < 0.0001). Estimated % improvement averaged 53.5% [46.5–60.5] with quetiapine vs 39.8% [34.2–45.4] with placebo (P < 0.0001); their ratio was somewhat larger with BD1 (1.56 [1.26–1.86]) versus BD2 subjects (1.22 [1.07–1.37], P = 0.04; as was SMD (BD1: 2.35 [1.83–2.86]; BD2: SMD = 1.44 [1.05–1.82]). Meta-regression found diagnosis (BD1 > BD2) to be the only factor significantly associated with the meta-analytic outcome.

Conclusions

Although data are limited, depressed BD1 patients may respond somewhat better to quetiapine than BD2. Additional head-to-head diagnostic comparisons are needed with other SGAs, as well as evaluation of monotherapy versus various combinations that include SGAs in both short- and long-term use.
Factors Associated With Follow-Up Visits in Parents With Myopic Children Wearing Orthokeratology Lens
Authors: HUNG Li-Ling , LIAO Li-Ling , CHEN Hsiao-Jung , LIN Hui-Ling , CHANG Li-Chun
Published: September 2022

Background

Orthokeratology (Ortho-k) is an effective method for slowing the progression of myopia and correcting refractive error in school children. Although parents of children aged < 10 years play a major role in Ortho-k lens care, they have a generally low level of compliance in performing regular follow-up visits.

Purpose

This study was developed to analyze the associations between follow-up visits by parents of Ortho-k lens wearers aged < 10 years and, respectively, the Ortho-k-related knowledge of these parents and information resources promoting Ortho-k use.

Methods

A cross-sectional study design was used. Parents of children who wear Ortho-k lenses were recruited through a private Facebook group with 3,500 members in 2020 that was created in 2018 for information sharing and exchange among parents of these children. The following data were collected: demographics of the parents and their children, four-item Ortho-k-related knowledge, information resources that prompted the decision to use Ortho-k, and the regularity of follow-up visits. These data were presented in terms of means, standard deviations, and percentages. Logistic regression was performed to compute the odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The study showed that 83.11% had regular follow-up visits. The correct response rate on Ortho-k-related knowledge was > 80%. However, 15.51% of the participants did not recognize axial length as an indicator for monitoring myopia progress, and 10.76% did not know that at least 6 hours of nighttime sleep is required for myopia control with Ortho-k. The most common information resource leading to Ortho-k use was self-acquisition from Internet sources. The spherical equivalent refraction of < −2.0 D was 2.58 times higher in participants with regular follow-up visits than in their peers with irregular follow-up visits (OR = 2.58, 95% CI [0.22, 5.63]). In addition, acknowledgment of “There is no need to change the Ortho-k lenses regularly as long as there is no discomfort” was 7.19 times higher in participants with regular follow-up visits than in their peers with irregular follow-up visits (OR = 7.19, 95% CI [1.26, 13.93]). However, participants with regular follow-up visits did not receive Internet ophthalmology advertisements prompting their decision to use Ortho-k 2.62 times higher than their peers with irregular follow-up visits (OR = 2.62, 95% CI [0.04, 4.29]).

Conclusions

The results support that both information sources and knowledge of Ortho-k use influence the frequency of follow-up visits among parents of Ortho-k lens wearers aged < 10 years. Related support from health professionals in terms of providing appropriate information and guidance is recommended to promote higher rates of regular follow-up visit attendance.
The Effect of Buzzy Application on Pain Level During Vaccine Injection in Infants
Authors: Şıktaş Özge , Uysal Gülzade
Published: September 2022

Background:

Nonpharmacological interventions are needed to reduce pain during vaccine administration in infants.

Purpose:

To determine the effect of the Buzzy device, which is a combination of cold and vibration, on pain during measles-mumps-rubella (MMR) vaccine administration in 12-month-old infants.

Methods:

A prospective randomized controlled experimental research design was used.

Results:

A total of 60 infants were included in the study. During and after vaccine injection, pain scores of infants who had the Buzzy device were significantly lower than those of infants in the control group (P = .001).

Conclusions:

Buzzy application may be an effective method in reducing pain during MMR vaccine administration. Use of the device is recommended for infants receiving vaccinations.
Engaging Students and Faculty in a Collaborative Learning Environment
Authors: Marquez Beth , Gannon Marianne E. , Rocafort Terri
Published: September 2022

Background:

The increasing move to distance education has exposed gaps in the implementation and sustainability of collaborative learning. Collaborative learning requires a mutual approach to knowledge building, which includes both students and faculty.

Purpose:

This quality improvement pilot focused on providing additional socialization and collaborative learning in an asynchronous environment.

Methods:

A review of the literature identified opportunities to address the social and academic needs of students pursuing an online degree, along with strategies to address feelings of isolation experienced by some students in a distance learning environment. The Let's Check-In: Tips for Success webinars were developed and integrated throughout the graduate curriculum.

Results:

Students provided positive feedback verbally and in end-of-course evaluations. Course faculty reported a more synergistic approach to teaching.

Conclusion:

Let's Check-In: Tips for Success provided an environment where student communication and understanding of course content increased.
Correction of Presbyopia Alone Does Not Adequately Protect against Digital Eye Strain from Handheld Devices
Authors: Mylona Ioanna , Floros Georgios D.
Published: September 2022

SIGNIFICANCE

The use of screen-enabled handheld devices has increased exponentially during the last few years among the older adults. Up until now, a general suggestion for preventing symptoms of digital eye strain with large screen use was to address any existing refractive error, including presbyopia. It is unclear whether this advice is of consequence in the case of smaller handheld devices.

PURPOSE

The aim of this study was to examine whether correcting presbyopia ameliorates the negative effect on digital screen use, examining handheld devices where these issues are expected to be more acute with presbyopic individuals.

METHODS

This is a cross-sectional study of 120 consecutive participants who had received correction for presbyopia during the past month and returned for a routine follow-up examination. The participants filled in a demographics questionnaire, questions on time spent online and using devices with digital screens, data on their eye complaints, and the validated Digital Eye Strain Questionnaire (DESQ).

RESULTS

The DESQ factor scores and total score correlated with the near addition (P < .001). Higher DESQ scores were associated (by order of magnitude) with higher near addition and a lower amount of time spent using a handheld screen-enabled device (P < .001) while controlling for age and type of corrective lenses.

CONCLUSIONS

Results indicate that older adults are at an additional disadvantage while using handheld screen-enabled devices compared with younger adults: they are more likely to be presbyopes and need higher near addition, yet increasing near addition does not guarantee greater comfort in the use of smartphones but rather increase the likelihood of experiencing digital eye strain symptoms.
Telerehabilitation Training to Facilitate Improved Reading Ability with New Magnification Devices for Low Vision
Authors: Bittner Ava Katherine , Kaminski John E. , Ross Nicole C. , Shepherd John D. , Thoene Stacy J. , Bui Sarah Z. , Yoshinaga Patrick D. ,   for the BeST-AID Study Team
Published: September 2022

SIGNIFICANCE

This pilot study provides some insight about the potential benefits of telerehabilitation training to improve the reading ability of adults with low vision using magnifiers, to spur future work with larger groups. Telerehabilitation services can be implemented clinically to facilitate access to follow-up care for low vision.

PURPOSE

A recent Cochrane systematic review revealed that there are no published visual function outcomes for telerehabilitation with handheld magnification devices for low vision; thus, this study aimed to provide evidence for its preliminary efficacy.

METHODS

One to 4 months after receiving a new magnification device (i.e., handheld or stand optical magnifier or portable electronic magnifier), 14 adult low vision patients (with any visual acuity level or ocular diagnosis) received two training sessions at home via telerehabilitation with their vision rehabilitation provider located remotely in-office. Telerehabilitation included a loaner smartphone for Zoom videoconferencing with remote control access software. The Minnesota Low-Vision Reading Test was administered during each of the telerehabilitation sessions to assess near reading (acuity and speed) with the new magnifier.

RESULTS

Mean reading acuity with the magnifier was 0.17 logMAR across subjects before training at telerehabilitation session 1, which significantly improved to 0.09 on average a few weeks later at telerehabilitation session 2 (95%confidence interval, −0.001 to −0.16; P = .047). Logarithm reading speed with the magnifier for the reading acuity level at session 1 improved significantly by 0.18 log words per minute on average for the same text size at session 2 (95% confidence interval, 0.06 to 0.29; P = .002). With the magnifier at session 2, 71% of participants gained at least 0.1 log unit in reading acuity, and half improved by >0.01 in log reading speed; all participants with increased reading speed also improved in reading acuity (P = .02).

CONCLUSIONS

These preliminary data support that telerehabilitation can enhance reading ability and efficiency with newly prescribed magnifiers as an alternative option to in-office vision rehabilitation.
Adolescent Substance Use Disorder Diagnosis Correlates With Hospitalization After an Emergency Department Visit
Authors: Thurstone Christian , Loh Ryan , Piatz Christopher , Simpson Scott A.
Published: September 2022

Introduction

The purpose of this study is to compare the prevalence of hospitalization after an emergency department (ED) visit at an urban safety net hospital for youth with and without a substance use disorder.

Methods

This study used a retrospective cohort design of adolescents (aged 15–21 y; n = 14,852) treated in the ED and compared the risk of hospitalization within 90 days.

Results

A substance use disorder diagnosis in the ED more than doubled the risk of 90-day hospitalization (5.4% vs 2.38%; P < 0.0001).

Conclusions

Compared with youth without a substance use disorder, youth with substance use disorders are likely to require additional services after an ED visit.
How to read ‘Reading the Mind in the Eyes’
Authors: Silverman Chloe
Published: September 2022

Reading the Mind in the Eyes is a psychometric test first published by Simon Baron-Cohen and colleagues in 1997 and revised in 2001. It was designed to measure subjects' ‘mentalizing’ ability, or their capacity to attribute cognitive and emotional states to others. Although originally developed and used for autistic adults, this instrument has proven remarkably durable in the succeeding two decades. This is notable for several reasons. The instrument itself is a historical artefact composed of cropped photographs from 1990s-era commercial magazines. Researchers have also noted that it may measure emotional vocabulary better than emotion recognition. In the decades following its publication, the theory underpinning the test, that autistics lack components of the ability to empathize, has been critiqued both by autism researchers and by autistics themselves. Despite these potential shortcomings, researchers in numerous fields have used it to assess a broad range of diagnostically defined groups, including those with substance use disorders, eating disorders and personality and neurodevelopmental disorders. Indeed, it is cited far more frequently now than it was in the decade following its publication. This essay considers how this instrument defines autism as a particular type of disability, and how the capacities purportedly associated with the ability to read minds through eyes are then used to characterize a range of human differences.
Fractionated brain irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior and cognition in mice
Authors: Kuil L.E. , Seigers R. , Loos M. , de Gooijer M.C. , Compter A. , Boogerd W. , Van Tellingen O. , Smit A.B. , Schagen S.B.
Published: September 2022

Whole brain radiotherapy (WBRT) is used to treat patients with primary brain tumors, or brain metastasis from various primary tumors to improve tumor control. However, WBRT can lead to cognitive decline. We treated mice with fractionated WBRT (fWBRT) to establish a model system to study the mechanisms underlying cognitive decline. Besides a series of traditional cognitive tests, we also assessed the effect on spontaneous behavior as measured in automated home cages.

Male C57Bl/6j mice (n=11 per group) received bi-lateral fWBRT at a dosage of 4 Gy/day on 5 consecutive days. In line with previous reports, immunohistochemical analysis of doublecortin (DCX) positive cells in the dentate gyrus showed a profound reduction in immature neurons at 4 weeks after fWBRT. Surprisingly, spontaneous behavior as measured in automated home cages was not affected. Moreover, learning and memory measured with traditional tasks - including the novel object recognition task, novel location recognition task, Barnes maze, and fear conditioning - was also not affected at 4-6 weeks after fWBRT. At 10-11 weeks after fWBRT a difference in escape latency during the learning phase, but not in the probe phase of the Barnes maze was observed.

In conclusion, although we confirmed the effect of fWBRT on neurogenesis at 4 weeks after fWBRT, we did not find clear effects on spontaneous behavior in the automated home cage nor on learning abilities as measured by traditional cognitive tasks. The relationship between the neurobiological effects of fWBRT and cognition seems more complex than often assumed and the choice of animal model, cognitive tasks, neurobiological parameters, and experimental set-up might be important factors in these types of experiments.
Resting EEG power spectra across middle to late life: Associations with age, cognition, APOE-ε4 carriage and cardiometabolic burden
Authors: Smith Ashleigh E. , Chau Anson , Greaves Danielle , Keage Hannah A.D. , Feuerriegel Daniel
Published: September 2022

We investigated how resting EEG measures are associated with risk factors for late-life cognitive impairment and dementia, including age, Apolipoprotein E ε4 (APOE-ε4) carriage and cardiometabolic burden. Resting EEG was recorded from 86 adults (50-80 years of age). Participants additionally completed the Addenbrooke’s Cognitive Examination (ACE) III and had blood drawn to assess APOE-ε4 carriage status and cardiometabolic burden. EEG power spectra were decomposed into sources of periodic and aperiodic activity to derive measures of aperiodic component slope and alpha (7-14 Hz) and beta (15-30 Hz) peak power and peak frequency. Alpha and beta peak power measures were corrected for aperiodic activity. The aperiodic component slope was correlated with ACE-III scores but not age. Alpha peak frequency decreased with age. Individuals with higher cardiometabolic burden had lower alpha peak frequencies and lower beta peak power. APOE-ε4 carriers had lower beta peak frequencies. Our findings suggest that the slope of the aperiodic component of resting EEG power spectra is more closely associated with measures of cognitive performance rather than chronological age in older adults.
Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration
Authors: Salinas-Saavedra Miguel , Febrimarsa  , Krasovec Gabriel , Horkan Helen R , Baxevanis Andreas D , Frank Uri
Published: September 2022

Cell fate stability is essential to maintaining ‘law and order’ in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevented reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context resulted in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide a new avenue to enhance regeneration.
Ultrafast (>400 Hz) network oscillations induced in thalamorecipient cortical layers by optogenetic activation of thalamocortical axons
Authors: Hu Hang , Hostetler Rachel E. , Agmon Ariel
Published: September 2022

Oscillations of extracellular voltage, reflecting synchronous rhythmic activity in large populations of neurons, are a ubiquitous feature in the mammalian brain and are thought to subserve critical, if not fully understood cognitive functions. Oscillations at different frequency bands are hallmarks of specific brain or behavioral states. At the higher end of the scale, ultrafast (400-600 Hz) oscillations in the somatosensory cortex, in response to peripheral stimulation, were observed in human and a handful of animal studies; however, their synaptic basis and functional significance remain largely unexplored. Here we report that brief optogenetic activation of thalamocortical axons ex-vivo elicited precisely reproducible, ~410 Hz local field potential wavelets (“ripplets”) in middle layers of mouse somatosensory (barrel) cortex. Fast-spiking (FS) inhibitory interneurons were exquisitely synchronized with each other and fired spike bursts in anti-phase with ripplets, while excitatory neurons fired only 1-2 spikes per stimulus. Both subtypes received shared excitatory inputs at ripplet frequency, and bursts in layer 5 FS cells required intact connection with layer 4, suggesting that layer 4 excitatory cells were driving FS bursts in both layers. Ripplets may be a ubiquitous cortical response to exceptionally salient sensory stimuli, and could provide increased bandwidth for encoding and transmitting sensory information. Lastly, optogenetically-induced ripplets are a uniquely accessible model system for studying synaptic mechanisms of fast and ultrafast oscillations.
Gene Expression Profiles Reveal Potential Targets for Breast Cancer Diagnosis and Treatment
Authors: Nasirpour Mohammad Hossein , Sabery Anvar Mohammad , Alireza Nasirpour , Mahdieh Salimi , Soheil Sepahyar , Zarrin Minuchehr
Published: September 2022

Figuring out the molecular mechanisms underlying breast cancer is essential for the diagnosis and treatment of this invasive disorder. Hence it is important to identify the most significant genes correlated with molecular events and to study their interactions in order to identify breast cancer mechanisms. Here we focus on the gene expression profiles, which we have detected in breast cancer. High-throughput genomic innovations such as microarray have helped us understand the complex dynamics of multisystem diseases such as diabetes and cancer. We performed an analysis using microarray datasets by the Networkanalyst bioinformatics tool, based on a random effect model (REM). We achieved pivotal differential expressed genes like ADAMTS5, SCARA5, IGSF10, and C2orf40 that had the most down-regulation, and also COL10A1, COL11A1, and UHRF1 that they had the most up-regulation in four-stage of breast cancer. We used CentiScape and AllegroMCODE plugins in CytoScape software in order to figure out hub genes in the protein-protein interactions network. Besides, we utilized DAVID online software to find involved biological pathways and Gene ontology, also used Expression2kinase software in order to find upstream regulatory transcription factors and kinases. In conclusion, we have found that the statistical network inference approach is useful in gene prioritization and is capable of contributing to practical network signature discovery and providing insights into the mechanisms relevant to the disease. Our research has also identified novel transcription factors, kinases, pathways, and genes that may serve as important targets for the development of diagnostic biomarkers and treatments.