bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving partnership synergy: resource inputs, shared mission and interdependencies in Danish health promotion partnerships
Authors: Holt Ditte Heering , Aveling Emma-Louise
Published: February 2023

Intersectoral partnerships have the potential to co-produce ‘synergistic’ solutions to complex public health problems, exceeding what any single organization acting alone might achieve. Synergy requires shared decision-making and equitable co-construction by partners. However, many partnerships struggle to realize such synergistic potential. Building on the Bergen Model of Collaborative Functioning, this study offers insights for optimizing partnership synergy by examining interactions between ‘inputs’ to the partnership—shared mission, and partner resources. Specifically, we introduce the concept of ‘dependency structure’ to draw attention to how these input interactions shape the balance of power and hence the potential for shared decision-making and co-construction. Findings are based on qualitative data from 10 intersectoral, health promotion partnerships in Denmark, including 27 interviews, 10 focus groups, partnership documents and meeting observations. We identified eight distinct types of ‘input resources’, which were important in shaping the potential balance of power between partners in more or less productive ways. However, the dependency structure that materialized—and its synergistic potential—was contingent on how these inputs interacted with the partnership mission. Our findings suggest a well-developed shared mission serves three functions—(i) foregrounding a common purpose, (ii) aligning individual partner’s self-interests and (iii) enabling action. The extent to which partnerships developed a shared mission serving all three functions influenced realization of a balanced dependency structure in which collaborators recognized their interdependencies, in turn promoting shared decision-making. To ensure the greatest potential for synergy, early and ongoing discursive processes to co-develop the partnership mission were particularly important.
Protease inhibitor ASP enhances freezing tolerance by inhibiting protein degradation in kumquat
Authors: Yang Hua , Qiao Ke-wei , Teng Jin-jing , Chen Jia-bei , Zhong Ying-li , Rao Li-qun , Xiong Xing-yao , Li Huang
Published: February 2023

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants. In this study, we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat [Fortunella margarita (Lour.) Swingle] contributes to its freezing tolerance by minimizing protein degradation. Firstly, we found that only cold-acclimated kumquat plants, despite extensive leaf cellular damage during freezing, were able to resume their normal growth upon stress relief. To dissect the impact of cold acclimation on this anti-freezing performance, we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation (4°C), freezing treatment (−10°C) and post-freezing recovery (25°C). FmASP (Against Serine Protease) and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment. FmASP was further characterized as a robust inhibitor of multiple proteases. In addition, heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance. Finally, we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation, thereby maintaining essential cellular function for post-freezing recovery. These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.
Investigation and thermo-economic analysis of solar condensation refrigeration
Authors: Abed Azher M , Hadrawi Salema K , Smaisim Ghassan F , Muftah Ali F , Jahanbin Farnaz
Published: February 2023

Today, the use of solar energy is expanding and developing because this energy is easily available and there are various technologies for producing thermal and electrical energy and cooling. One of the most energy-consuming parts is heating and cooling systems in residential buildings, which include the major part of energy consumption in buildings. Therefore, the purpose of this research is to produce thermal energy for the cooling system using solar energy, which was used for analysis using Trnsys software. The purpose of the simulation is to check the thermodynamic parameters of the fluid and economic analysis, taking into account biological pollutants. The environment of the system has been considered. One of the important results of this research is the return on investment of 4 years, in which the required amount of energy supply through the solar system is 0.94.
A hierarchical multilabel graph attention network method to predict the deterioration paths of chronic hepatitis B patients
Authors: Wu Zejian (Eric) , Xu Da , Hu Paul Jen-Hwa , Huang Ting-Shuo
Published: February 2023

Objective

Estimating the deterioration paths of chronic hepatitis B (CHB) patients is critical for physicians’ decisions and patient management. A novel, hierarchical multilabel graph attention-based method aims to predict patient deterioration paths more effectively. Applied to a CHB patient data set, it offers strong predictive utilities and clinical value.

Materials and Methods

The proposed method incorporates patients’ responses to medications, diagnosis event sequences, and outcome dependencies to estimate deterioration paths. From the electronic health records maintained by a major healthcare organization in Taiwan, we collect clinical data about 177 959 patients diagnosed with hepatitis B virus infection. We use this sample to evaluate the proposed method’s predictive efficacy relative to 9 existing methods, as measured by precision, recall, F-measure, and area under the curve (AUC).

Results

We use 20% of the sample as holdouts to test each method’s prediction performance. The results indicate that our method consistently and significantly outperforms all benchmark methods. It attains the highest AUC, with a 4.8% improvement over the best-performing benchmark, as well as 20.9% and 11.4% improvements in precision and F-measures, respectively. The comparative results demonstrate that our method is more effective for predicting CHB patients’ deterioration paths than existing predictive methods.

Discussion and Conclusion

The proposed method underscores the value of patient-medication interactions, temporal sequential patterns of distinct diagnosis, and patient outcome dependencies for capturing dynamics that underpin patient deterioration over time. Its efficacious estimates grant physicians a more holistic view of patient progressions and can enhance their clinical decision-making and patient management.
Impairment of autophagy promotes human conjunctival fibrosis and pterygium occurrence via enhancing the SQSTM1–NF-κB signaling pathway
Authors: He Qin , Cai Yiting , Huang Jiani , He Xiaoying , Han Wei , Chen Wei
Published: February 2023

Pterygium is a common ocular disease with a high recurrence rate, characterized by hyperplasia of subconjunctival fibrovascular tissue. Autophagy, an important process to maintain cellular homeostasis, participates in the pathogenic fibrosis of different organs. However, the exact role of autophagy in pterygium pathogenesis remains unknown. Here, we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues. The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts (ConFB) treated with transforming growth factor-β1 (TGF-β1), evidenced by increased fibrotic level and strong proliferative and invasive capabilities. The autophagic activity was suppressed during TGF-β1- or ultraviolet-induced fibrosis of ConFB. Activating autophagy dramatically retarded the fibrotic progress of ConFB, while blocking autophagy exacerbated this process. Furthermore, SQSTM1, the main cargo receptor of selective autophagy, was found to significantly promote the fibrosis of ConFB through activating the PKCι–NF-κB signaling pathway. Knockdown of SQSTM1, PKCι, or p65 in ConFB delayed TGF-β1-induced fibrosis. Overexpression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-β1-induced fibrosis. Collectively, our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1–PKCι–NF-κB signaling cascades. This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.
Historical redlining and breast cancer treatment and survival among older women in the United States
Authors: Bikomeye Jean C , Zhou Yuhong , McGinley Emily L , Canales Bethany , Yen Tina W F , Tarima Sergey , Ponce Sara Beltrán , Beyer Kirsten M M
Published: February 2023

Background

Breast cancer (BC) is the most common cancer among US women, and institutional racism is a critical cause of health disparities. We investigated impacts of historical redlining on BC treatment receipt and survival in the United States.

Methods

Home Owners’ Loan Corporation (HOLC) boundaries were used to measure historical redlining. Eligible women in the 2010-2017 Surveillance, Epidemiology, and End Results–Medicare BC cohort were assigned a HOLC grade. The independent variable was a dichotomized HOLC grade: A and B (nonredlined) and C and D (redlined). Outcomes of receipt of various cancer treatments, all-cause mortality (ACM), and BC-specific mortality (BCSM) were analyzed using logistic or Cox models. Indirect effects by comorbidity were examined.

Results

Among 18 119 women, 65.7% resided in historically redlined areas (HRAs), and 32.6% were deceased at a median follow-up of 58 months. A larger proportion of deceased women resided in HRAs (34.5% vs 30.0%). Of all deceased women, 41.6% died of BC; a larger proportion resided in HRAs (43.4% vs 37.8%). Historical redlining is a statistically significant predictor of poorer survival after BC diagnosis (hazard ratio = 1.09, 95% confidence interval [CI] = 1.03 to 1.15 for ACM, and hazard ratio = 1.26, 95% CI = 1.13 to 1.41 for BCSM). Indirect effects via comorbidity were identified. Historical redlining was associated with a lower likelihood of receiving surgery (odds ratio = 0.74, 95% CI = 0.66 to 0.83, and a higher likelihood of receiving palliative care odds ratio = 1.41, 95% CI = 1.04 to 1.91).

Conclusion

Historical redlining is associated with differential treatment receipt and poorer survival for ACM and BCSM. Relevant stakeholders should consider historical contexts when designing and implementing equity-focused interventions to reduce BC disparities. Clinicians should advocate for healthier neighborhoods while providing care.
Infrastructures of migration and the ordering of privilege in mobility
Authors: Cranston Sophie , Duplan Karine
Published: February 2023

This article explores privilege in migration. Rather than focus on practices of privilege at micro-scales, the article examines how privilege in migration is ordered and disciplined through meso- and macro-level infrastructures (transnational organisations, higher education institutes, and governmental visa policies). The article questions where a pervasive discourse of mobility as achievement comes from and how it becomes materialised in the promotion and facilitation of forms of mobility. It argues that privilege in mobility becomes disciplined through neoliberal discourses of globalisation that idealise mobility as cosmopolitanism, whilst simultaneously producing this as an elite subject positioning.
Fall Prevention Training for Service Members With an Amputation or Limb Salvage Following Lower Extremity Trauma
Authors: Kaufman Kenton R , Miller Emily J , Deml Christine M , Sheehan Riley C , Grabiner Mark D , Wyatt Marilynn , Zai Claire Z , Kingsbury Trevor , Tullos Meghan L , Acasio Julian C , Mahon Caitlin E , Hendershot Brad D , Dearth Christopher L
Published: February 2023

Introduction

Recent military conflicts have resulted in a significant number of lower extremity injuries to U.S. service members that result in amputation or limb preservation (LP) procedures. Service members receiving these procedures report a high prevalence and deleterious consequences of falls. Very little research exists to improve balance and reduce falls, especially among young active populations such as service members with LP or limb loss. To address this research gap, we evaluated the success of a fall prevention training program for service members with lower extremity trauma by (1) measuring fall rates, (2) quantifying improvements in trunk control, and (3) determining skill retention at 3 and 6 months after training.

Materials and Methods

Forty-five participants (40 males, mean [±SD] age, 34 ± 8 years) with lower extremity trauma (20 with unilateral transtibial amputation, 6 with unilateral transfemoral amputation, 5 with bilateral transtibial amputation, and 14 with unilateral LP procedures) were enrolled. A microprocessor-controlled treadmill was used to produce task-specific postural perturbations which simulated a trip. The training was conducted over a 2-week period and consisted of six 30-minute sessions. The task difficulty was increased as the participant’s ability progressed. The effectiveness of the training program was assessed by collecting data before training (baseline; repeated twice), immediately after training (0 month), and at 3 and 6 months post-training. Training effectiveness was quantified by participant-reported falls in the free-living environment before and after training. Perturbation-induced recovery step trunk flexion angle and velocity was also collected.

Results

Participants reported reduced falls and improved balance confidence in the free-living environment following the training. Repeated testing before training revealed that there were no pre-training differences in trunk control. The training program improved trunk control following training, and these skills were retained at 3 and 6 months after training.

Conclusion

This study showed that task-specific fall prevention training reduced falls across a cohort of service members with diverse types of amputations and LP procedures following lower extremity trauma. Importantly, the clinical outcome of this effort (i.e., reduced falls and improved balance confidence) can lead to increased participation in occupational, recreational, and social activities and thus improved quality of life.
Body Fat Percentage and Blood Donation are the Strongest Determinants of Iron Stores in Premenopausal Women Joining the New Zealand Army
Authors: Martin Nicola M , von Hurst Pamela R , Conlon Cathryn A , Smeele Rebecca J M , Mugridge Owen A R , Beck Kathryn L
Published: February 2023

Introduction

Suboptimal iron status is an issue for women joining the military because of its association with impaired aerobic performance, yet no studies have investigated dietary and non-dietary determinants of iron status simultaneously in this population. The purpose of this study was to explore associations between iron stores, dietary patterns (DPs), and potential non-dietary determinants of iron status in premenopausal women at the commencement of basic military training (BMT) in the New Zealand Army.

Methods

During week 1 of BMT, demographic, body composition, lifestyle, medical history, and dietary data were measured as potential determinants of serum ferritin (SF) in 101 participants. Following univariate analysis, age, body fat percentage, previous blood donation, at least 6 h of exercise per week that raised the heart rate, and a vegetarian DP were analyzed using a multiple linear regression model.

Results

An increase in body fat percentage was associated with increased SF (P < .009), although blood donation in the past year decreased SF (P < .011) compared to those participants who did not donate blood. There was no association between SF and a vegetarian DP or hours of exercise per week. The model explained 17.5% of the variance in SF at the commencement of BMT.

Conclusion

Body fat percentage and blood donation in the past year were the strongest determinants of iron stores in healthy premenopausal women commencing BMT. It is recommended that women joining the New Zealand Army are provided information to maintain or improve their iron status based on these findings. This includes clinical screening of iron status, advice for women considering blood donation, and dietary advice regarding total energy requirements and iron bioavailability.
Late to Palliate? Inpatient Palliative Care Consultation at an Academic Veterans Affairs Hospital
Authors: Allaudeen Nazima , Millhouse Christopher F , Huberman David B , Wang Hui , Heidenreich Paul A
Published: February 2023

Introduction

Despite robust evidence describing the benefits of palliative care consultation (PCC), this service is underutilized. Hospital admission provides an important opportunity to obtain PCC.

Methods

We evaluated all inpatients who received PCC at a Veterans Affairs academic hospital from January 1, 2019 to December 31, 2019. Logistic regression was used to determine factors associated with early versus late PCC, with early defined as >30 days from consult to death and late defined as ≤30 days.

Results

The median time from PCC to death was 37 days. The majority of PCCs were early (58.4%). Of all patients receiving inpatient PCC, 13.2% died that admission. Cardiac (odds ratio = 0.3, 95% CI = 0.11-0.73) and neurological (odds ratio = 0.21, 95% CI = 0.05-0.70) diagnoses were more likely to receive early PCC compared to malignancy. Of the late PCCs receiving first-time consults, 58.9% had at least one admission during the last year.

Conclusions

Many patients are introduced to palliative care services within a month of death. These patients were often admitted during the prior year, presenting a missed opportunity to involve inpatient PCC earlier.
Putative Signals of Generalist Plant Species Adaptation to Local Pollinator Communities and Abiotic Factors
Authors: Frachon Léa , Arrigo Luca , Rusman Quint , Poveda Lucy , Qi Weihong , Scopece Giovanni , Schiestl Florian P
Published: February 2023

The reproductive success of flowering plants with generalized pollination systems is influenced by interactions with a diverse pollinator community and abiotic factors. However, knowledge about the adaptative potential of plants to complex ecological networks and the underlying genetic mechanisms is still limited. Based on a pool-sequencing approach of 21 natural populations of Brassica incana in Southern Italy, we combined a genome-environmental association analysis with a genome scan for signals of population genomic differentiation to discover genetic variants associated with the ecological variation. We identified genomic regions putatively involved in the adaptation of B. incana to the identity of local pollinator functional categories and pollinator community composition. Interestingly, we observed several shared candidate genes associated with long-tongue bees, soil texture, and temperature variation. We established a genomic map of potential generalist flowering plant local adaptation to complex biotic interactions, and the importance of considering multiple environmental factors to describe the adaptive landscape of plant populations.
Localized modulation of DNA supercoiling, triggered by the Shigella anti-silencer VirB, is sufficient to relieve H-NS-mediated silencing
Authors: Picker Michael A , Karney Monika M A , Gerson Taylor M , Karabachev Alexander D , Duhart Juan C , McKenna Joy A , Wing Helen J
Published: February 2023

In Bacteria, nucleoid structuring proteins govern nucleoid dynamics and regulate transcription. In Shigella spp., at ≤30°C, the histone-like nucleoid structuring protein (H-NS) transcriptionally silences many genes on the large virulence plasmid. Upon a switch to 37°C, VirB, a DNA binding protein and key transcriptional regulator of Shigella virulence, is produced. VirB functions to counter H-NS-mediated silencing in a process called transcriptional anti-silencing. Here, we show that VirB mediates a loss of negative DNA supercoils from our plasmid-borne, VirB-regulated PicsP-lacZ reporter in vivo. The changes are not caused by a VirB-dependent increase in transcription, nor do they require the presence of H-NS. Instead, the VirB-dependent change in DNA supercoiling requires the interaction of VirB with its DNA binding site, a critical first step in VirB-dependent gene regulation. Using two complementary approaches, we show that VirB:DNA interactions in vitro introduce positive supercoils in plasmid DNA. Subsequently, by exploiting transcription-coupled DNA supercoiling, we reveal that a localized loss of negative supercoils is sufficient to alleviate H-NS-mediated transcriptional silencing independently of VirB. Together, our findings provide novel insight into VirB, a central regulator of Shigella virulence and, more broadly, a molecular mechanism that offsets H-NS-dependent silencing of transcription in bacteria.
PANTOTHENATE KINASE4, LOSS OF GDU2, and TRANSPOSON PROTEIN1 affect the canalization of tomato fruit metabolism
Authors: Wijesingha Ahchige Micha , Fernie Alisdair R , Alseekh Saleh
Published: February 2023

Most studies investigating quantitative traits focus on mean levels per genotype rather than the variation between different individuals of one genotype or the variation elicited by different environments. Consequently, the genes that govern this effect are not well understood. The concept, named canalization, which describes a lack of variation, is well known in the context of developmental processes but is poorly studied for quantitative traits such as metabolism. In this study, we selected 8 putative candidate genes from previously identified canalized metabolic quantitative trait loci and created genome-edited tomato (Solanum lycopersicum) mutants of these genes for experimental validation. Most lines showed wild-type morphology, except for an ARF-like protein mutant showing aberrant phenotypes in the form of scarred fruit cuticles. In greenhouse trials with different irrigation conditions, whole-plant traits showed a general increase of their level toward the more optimal irrigation conditions, whereas most metabolic traits showed an increase toward the other end of the gradient. Mutants of a PANTOTHENATE KINASE 4, the AIRP ubiquitin gene LOSS OF GDU2, and TRANSPOSON PROTEIN 1 grown under these conditions showed an overall improved plant performance. Additional effects, on both target and other metabolites in tomato fruits, regarding the mean level at specific conditions and, ergo, the cross-environment coefficient of variation, were observed. However, variation between individuals remained unaffected. In conclusion, this study supports the idea of distinct sets of genes regulating different types of variation.
Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells
Authors: Zhong Liangwen , Gordillo Miriam , Wang Xingyi , Qin Yiren , Huang Yuanyuan , Soshnev Alexey , Kumar Ritu , Nanjangud Gouri , James Daylon , David Allis C , Evans Todd , Carey Bryce , Wen Duancheng
Published: February 2023

While Mek1/2 and Gsk3β inhibition (“2i”) supports the maintenance of murine embryonic stem cells (ESCs) in a homogenous naïve state, prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential. Additionally, 2i fails to support derivation and culture of fully potent female ESCs. Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin (AlbuMAX) undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture. Mechanistically, lipids in AlbuMAX impact intracellular metabolism including nucleotide biosynthesis, lipid biogenesis, and TCA cycle intermediates, with enhanced expression of DNMT3s that prevent DNA hypomethylation. Lipids induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation, which also alleviates X chromosome loss in female ESCs. Importantly, both male and female “all-ESC” mice can be generated from de novo derived ESCs using AlbuMAX-based media. Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.
Long-term Outcomes of People With DSM Psychotic Disorder NOS
Authors: Widing Line , Simonsen Carmen , Bjella Thomas , Engen Magnus Johan , Flaaten Camilla Bärthel , Gardsjord Erlend , Haatveit Beathe , Haug Elisabeth , Lyngstad Siv Hege , Svendsen Ingrid Hartveit , Vik Ruth Kristine , Wold Kristin Fjelnseth , Åsbø Gina , Ueland Torill , Melle Ingrid
Published: February 2023

Introduction

The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic category “Psychotic disorder not otherwise specified” (PNOS) is seldom investigated, and we lack knowledge about long-term outcomes. We examined long-term symptom severity, global functioning, remission/recovery rates, and diagnostic stability after the first treatment for PNOS.

Methods

Participants with first-treatment PNOS (n = 32) were reassessed with structured interviews after 7 to 10 years. The sample also included narrow schizophrenia spectrum disorders (SSD, n = 94) and psychotic bipolar disorders (PBD, n = 54). Symptomatic remission was defined based on the Remission in Schizophrenia Working Group criteria. Clinical recovery was defined as meeting the criteria for symptomatic remission and having adequate functioning for the last 12 months.

Results

Participants with baseline PNOS or PBD had lower symptom severity and better global functioning at follow-up than those with SSD. More participants with PNOS and PBD were in symptomatic remission and clinical recovery compared to participants with SSD. Seventeen (53%) PNOS participants retained the diagnosis, while 15 participants were diagnosed with either SSD (22%), affective disorders (19%), or substance-induced psychotic disorders (6%). Those rediagnosed with SSD did not differ from the other PNOS participants regarding baseline clinical characteristics.

Conclusions

Long-term outcomes are more favorable in PNOS and PBD than in SSD. Our findings confirm diagnostic instability but also stability for a subgroup of participants with PNOS. However, it is challenging to predict diagnostic outcomes of PNOS based on clinical characteristics at first treatment.
Accessoriness of Cape Town international interest
Authors: Tomczak Tomasz
Published: February 2023

This article assesses the accessory nature of the Cape Town Convention (CTC) international interest. It examines how certain aspects in which the accessoriness of a security right can manifest itself look in the case of this international institution. The conclusion is reached that the CTC international interest is a very accessory-flexible security right.
New Endothelial Corneal Dystrophy in a Chinese Family
Authors: Ye Minjie , Lu Qinyi , Zhao Duran , Zhao Bingying , Zhang Shengquan , Liao Yi , Liao Rongfeng
Published: February 2023

Purpose:

The aim of this study was to characterize the clinical presentation of atypical endothelial corneal dystrophy (ECD) and to identify possible associated genetic variants in a Chinese family.

Methods:

Six affected members, 4 unaffected first-degree relatives, and 3 spouses who were enrolled in this study underwent ophthalmic examinations. Genetic linkage analysis was performed for 4 affected and 2 unaffected members, and whole-exome sequencing (WES) was performed for 2 patients to identify disease-causing variants. Candidate causal variants were verified using Sanger sequencing in family members and 200 healthy controls.

Results:

The mean age at disease onset was 16.5 years. The early phenotype of this atypical ECD was characterized by multiple small white translucent spots located in Descemet membrane of the peripheral cornea. These spots coalesced to form opacities with variable shapes, and eventually merged along the limbus. Subsequently, translucent spots appeared in central Descemet membrane and accumulated, causing diffuse polymorphous opacities over time. Finally, significant endothelial decompensation led to diffuse corneal edema. A heterozygous missense variant in the KIAA1522 gene (c.1331G>A; p.R444Q) was identified by WES, which was present in all 6 patients but was absent in the unaffected members and healthy controls.

Conclusions:

The clinical features of atypical ECD are unique compared with those of known corneal dystrophies. Moreover, genetic analysis identified the c.1331G>A variant in KIAA1522, which may be responsible for the pathogenesis of this atypical ECD. Thus, we propose this is a new form of ECD based on our clinical findings.
Novel Animal Model of Limbal Stem Cell Deficiency Induced by Forcing Eye-Open at Birth
Authors: Wang He , Han Jiaxin , Hu Fen , Zhang Can , Zhao Kai , Mu Ning , Guo Jianxin , Zhu Han , Li Mingxin
Published: February 2023

Purpose:

The aim of this study was to develop a rat model of limbal stem cell deficiency (LSCD) by forcing eye-open at birth (FEOB).

Methods:

A total of 200 Sprague-Dawley neonatal rats were randomly divided into the control group and the experimental group, which received eyelid open surgery on postnatal day 1 (P1). Observation time points were defined as P1, P5, P10, P15, and P30. Slit-lamp microscope and corneal confocal microscope were used to observe the clinical features of the model. The eyeballs were collected for hematoxylin and eosin staining and periodic acid–Schiff staining. Proliferating cell nuclear antigen, CD68/polymorphonuclear leukocytes, and cytokeratin 10/12/13 immunostaining were performed, while the ultrastructure of the cornea was observed by scanning electron microscopy. Real-time polymerase chain reactions (PCRs), western blot, and immunohistochemical staining of activin A receptor-like kinase-1/5 were used to analyze the possible pathogenesis.

Results:

FEOB could successfully induce the typical manifestations of LSCD, including corneal neovascularization, severe inflammation, and corneal opacity. In the FEOB group, goblet cells could be detected in the corneal epithelium by periodic acid–Schiff staining. The expression of cytokeratins was also different between the 2 groups. Furthermore, proliferating cell nuclear antigen immunohistochemical staining revealed the weak proliferation and differentiation ability of limbal epithelial stem cells in the FEOB group. Real-time PCRs, western blot, and immunohistochemical staining of activin A receptor-like kinase-1/activin A receptor-like kinase-5 in the FEOB group showed different expression patterns than those of the control group.

Conclusions:

FEOB in rats induces ocular surface changes resembling LSCD in humans, representing a novel model of LSCD.
Outcomes of the TissueTuck Surgical Technique for Recurrent Pterygium
Authors: Desai Neel R. , Adams Bryan
Published: February 2023

Purpose:

The objective of this study was to evaluate the clinical outcomes of the TissueTuck technique in the treatment of eyes with recurrent pterygium.

Methods:

A retrospective review was performed on patients with recurrent pterygium who underwent surgical excision, followed by the application of cryopreserved amniotic membrane, using the TissueTuck technique between January 2012 and May 2019. Only patients with at least 3 months of follow-up were included for analysis. Baseline characteristics, operative time, best-corrected visual acuity, and complications were assessed.

Results:

A total of 44 eyes of 42 patients (age 60.5 ± 10.9 yrs) with single-headed (84.1%) or double-headed (15.9%) recurrent pterygium were included for analysis. The average surgical duration was 22.4 ± 8.0 minutes, and mitomycin C was administered intraoperatively in 31 eyes (72.1%). During a mean postoperative follow-up of 24.6 ± 18.3 months, there was only 1 case of recurrence (2.3%). Other complications include scarring (9.1%), granuloma formation (20.5%), and corneal melt in 1 patient with preexisting ectasia (2.3%). Best-corrected visual acuity significantly improved from 0.16 Logarithm of the Minimum Angle of Resolution at baseline to 0.10 Logarithm of the Minimum Angle of Resolution at the last postoperative follow-up (P = 0.014).

Conclusions:

TissueTuck surgery with cryopreserved amniotic membrane is safe and effective for recurrent pterygium cases with a low risk of recurrence and complications.
Accessibility and Cultural Inclusivity of Online Glaucoma-Based Video Content for Patient Education
Authors: Dahshan Deena , Johnson Nicholas , El-Hamdani Rawan , Muir Kelly W.
Published: February 2023

Précis:

This study is the first to evaluate the ease of access, understandability, and cultural inclusivity of online glaucoma-related video content for patient education. Overall, materials were found to be poorly understandable and not culturally representative.

Purpose:

The purpose of this study is to assess the ease of access, readability, actionability, and cultural inclusivity of glaucoma-specific patient education videos found online.

Design:

Cross-sectional study.

Subjects:

Twenty-two glaucoma-based patient education videos were reviewed for this study.

Methods:

A survey of glaucoma specialists identified commonly recommended patient education Web sites, which were analyzed for video content. Web sites were reviewed by 2 independent reviewers for glaucoma-based patient education videos. Videos with content designated for medical providers, dedicated to research, or affiliated with private practices were excluded. Videos that were not glaucoma-specific or longer than 15 minutes were also excluded. The Patient Education Materials Assessment Tool was used to score videos for understandability and actionability reviewing content, word choice, organization, layout, and use of visual aids. Videos were also reviewed for cultural inclusivity and accessibility measures including language availability. Agreement analysis with a kappa coefficient (κ) over 0.6 was established with the first 5 videos between 2 independent reviewers and scoring discrepancies were resolved via a third independent reviewer.

Results:

From 10 recommended Web sites, 22 videos met inclusion criteria for evaluation. The average Patient Education Materials Assessment Tool score was 68.3% (SD = 18.4) for understandability (κ=0.63). Most videos (64%) were accessed within 3 clicks from the homepage. Only 3 videos were available in another language (Spanish). Most actors and images were White individuals (68.9%), followed by Black (22.1%), then Asian (5.7%) and other/ambiguous (3.3%).

Conclusions:

There is room for improvement regarding language accessibility, understandability, and cultural inclusivity of glaucoma-based, publicly available patient education video content.
Valproate-Associated Hyperammonemic Encephalopathy
Authors: Vaidyanathan Sivapriya , Chatorikar Shalaka , Praharaj Samir Kumar , Munoli Ravindra Neelakanthappa , Udupa Suma T.
Published: February 2023

Background

Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center.

Methods

In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done.

Results

The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated

Conclusions

This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management.
Validation of the Aktiia blood pressure cuff for clinical use according to the ANSI/AAMI/ISO 81060-2:2013 protocol
Authors: Alexandre Jérémy , Tan Kevin , Almeida Tiago P. , Sola Josep , Alpert Bruce S. , Shah Jay
Published: February 2023

Objective

Assess the accuracy and precision of the Aktiia initialization oscillometric upper-arm cuff device (Aktiia SA, Neuchâtel, Switzerland) for home blood pressure (BP) monitoring in the general population according to the American National Standards Institute / Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard.

Methods

Three trained observers validated BP measurements performed using the Aktiia cuff versus BP measurements performed using a standard mercury sphygmomanometer. Two ISO 81060-2 criteria were used to validate the Aktiia cuff. Criterion 1 evaluated, for both SBP and DBP, whether the mean error between BP readings performed by the Aktiia cuff and auscultation was ≤±5 mmHg, and whether the SD of the error was ≤8 mmHg. Criterion 2 assessed whether, for the SBP and DBP of each individual subject, the SD of the averaged paired determinations per subject of the Aktiia cuff and of the auscultation met the criteria listed in the table of Averaged Subject Data Acceptance.

Results

Mean differences between the Aktiia cuff and the standard mercury sphygmomanometer (criterion 1) were 1.3 ± 7.11 mmHg for SBP and −0.2 ± 5.46 mmHg for DBP. The SD of the averaged paired differences per subject (criterion 2) was 6.55 mmHg for SBP and 5.15 mmHg for DBP.

Conclusion

Aktiia initialization cuff complies with the requirements of the ANSI/AAMI/ISO guidelines and can be safely recommended for BP measurements in the adult population.
A Retrospective Study to Determine the Impact of Psychedelic Therapy for Dimensional Measures of Wellness: A Qualitative Analysis of Response Data
Authors: Virgilio Victoria Di , Minerbi Amir , Fletcher Jenna , Virgilio Anthony Di , Aggerwal Salena , Sheen Luke , Deol Jagpaul Kaur , Gupta Gaurav
Published: February 2023

Background

The World Health Organization (WHO) defines wellness as the optimal state of health of individuals and groups. No study to date has identified the impact of psychedelic medicines for optimizing wellness using a dimensional approach. Treatment effects can be measured more broadly using a composite score of participants’ global perceptions of change for pain, function, and mood scores. Given the precedence in previous work for retrospective study of participants’ self-medicating with these substances, the nature of this study design allows for a safe way to develop further evidence in this area of care, with wellness as the broad indication.

Methods

65 civilian or military veterans between the ages of 18-99 self-identifying as having used psychedelic medicines for non-recreational therapeutic purposes in the last 3 years were recruited for this study. Participants completed various standardized questionnaires that will be analyzed in a separate study, while this study analyzed the qualitative experiences described in relation to the medicines used and coded them according to themes developed from review of previous literature.

Results

A total of 93 comments were analyzed. Participant comments were classified into these categories: mysticism and spirituality, functional improvement and self awareness, social connection and cultural impact, impact on medical and mental health conditions, neutral impressions, sensations or difficult experiences. Participants described impacts in these categories related to spiritual, physiological, psychological, and social improvements, as well as difficulties and complex emotions regarding the experience of using psychedelic medicines.

Discussion

Wellness of individuals or groups is not simply an absence of disease, symptoms, or impairments. Rather, it reflects the outcome of numerous personal characteristics, psychophysiology, and choices, expressed throughout one’s lifespan, unfolding in dynamic interaction with a complicated socio-cultural and physical environment. Participants that used psychedelic medicines described improvement of medical and mental health conditions, social interaction, spirituality, and overall function. In general, quality of life and wellness consequently improved after the use of these medicines based on established multidimensional factors.

Conclusion

The use of various psychedelic medicines appears to be associated with a broad range of qualitative experiences that could help clarify the mechanism of how they impact wellness in the future.
Beta-catenin mediates growth defects induced by centrosome loss in APC mutant colorectal cancer independently of p53
Authors: Bourmoum Mohamed , Radulovich Nikolina , Tsao Ming-Sound , Pelletier Laurence
Published: February 2023

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths worldwide. The centrosome is the main microtubule-organizing center in animal cells and centrosome amplification is a hallmark of cancer cells. To investigate the importance of centrosomes in colorectal cancer, we induced centrosome loss in normal and cancer human-derived colorectal organoids using centrinone B, a Polo-like kinase 4 (Plk4) inhibitor. We show that centrosome loss represses human normal colorectal organoid growth in a p53-dependent manner in accordance with previous studies in cell models [1]. However, cancer colorectal organoid lines exhibited different sensitivities to centrosome loss independently of p53. Centrinone-induced cancer organoid growth defect/death positively correlated with a loss of function mutation in the APC gene, suggesting a causal role of the hyperactive WNT pathway. Consistent with this notion, β-catenin inhibition using XAV-939 or ICG-001 partially prevented centrinone-induced death and rescued the growth of APC-mutant organoid lines. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in APC-mutant colorectal cancer independently of the classical p53 pathway.
Optical tools for visualizing and controlling human GLP-1 receptor activation with high spatiotemporal resolution
Authors: Duffet Loïc , Williams Elyse T. , Gresch Andrea , Chen Simin , Bhat Musadiq A. , Benke Dietmar , Hartrampf Nina , Patriarchi Tommaso
Published: February 2023

The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well as of the blockbuster weight-loss drugs semaglutide and liraglutide. Despite its large clinical relevance, tools to investigate the precise activation dynamics of this receptor with high spatiotemporal resolution are limited. Here we introduce a novel genetically-encoded sensor based on the engineering of a circularly-permuted green fluorescent protein into the human GLP1R, named GLPLight1. We demonstrate that fluorescence signal from GLPLight1 accurately reports the expected receptor conformational activation in response to pharmacological ligands with high sensitivity (max ΔF/F0= 528%) and temporal resolution (τON= 4.7 sec). We further demonstrated that GLPLight1 shows comparable responses to GLP-1 derivatives as observed for the native receptor. Using GLPLight1, we established an all-optical assay to characterize a novel photocaged GLP-1 derivative (photo-GLP1) and to demonstrate optical control of GLP1R activation. Thus, the new all-optical toolkit introduced here enhances our ability to study GLP1R activation with high spatiotemporal resolution.
Underreporting of SARS-CoV-2 infections during the first wave of the 2020 COVID-19 epidemic in Finland - Bayesian inference based on a series of serological surveys
Authors: Nieminen Tuomo A. , Auranen Kari , Kulathinal Sangita , Härkänen Tommi , Melin Merit , Palmu Arto A. , Jokinen Jukka
Published: February 2023

In Finland, the first wave of the COVID-19 epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took place from March to June 2020, with the majority of COVID-19 cases diagnosed in the extended capital region. The magnitude and trend in the incidence of COVID-19 is one way to monitor the course of the epidemic. The diagnosed COVID-19 cases are a subset of the infections and therefore the COVID-19 incidence underestimates the SARS-CoV-2 incidence. The likelihood that an individual with SARS-CoV-2 infection is diagnosed with COVID-19 depends on the clinical manifestation as well as the infection testing policy and capacity. These factors may fluctuate over time and the underreporting of infections changes accordingly. Quantifying the extent of underreporting allows the assessment of the true incidence of infection. To obtain information on the incidence of SARS-CoV-2 infection in Finland, a series of serological surveys was initiated in April 2020. We develop a Bayesian inference approach and apply it to data from the serological surveys, registered COVID-19 cases, and external data, to estimate the time-dependent underreporting of SARS-Cov-2 infections during the first wave of the COVID-19 epidemic in Finland. There were 1 to 5 (95% probability) SARS-CoV-2 infections for every COVID-19 case during the first wave of the COVID-19 epidemic in Finland. The underreporting was highest before April when there were 4 to 17 (95% probability) infections for every COVID-19 case. It is likely that between 0.5%–1.0% (50% probability) and no more than 1.5% (95% probability) of the population in the extended capital region were infected with SARS-CoV-2 by the beginning of July 2020.
On the Impact of Mass Screening for SARS-CoV-2 through Self-Testing in Greece
Authors: Gilmour Samuel , Sapounas Spyros , Drakopoulos Kimon , Jaillet Patrick , Magiorkinis Gkikas , Trichakis Nikolaos
Published: February 2023

The emergence of COVID-19 stressed country health systems up to the point of triggering compulsory public health interventions to flatten the epidemic curve. Most of the interventions during the first year of the pandemic were non-pharmaceutical and aimed to reduce the contact rate of the people, which reduced the transmission rate of all respiratory pathogens, but had a large social and financial burden. SARS-CoV-2 specific interventions included screening, that is testing of asymptomatic people, which was largely facilitated by the availability of self-testing lateral flow antigen detection devices. The importance of self-testing interventions in controlling COVID-19 epidemic is not well-documented. We study as a paradigm-model the self-testing COVID-19 mass screening program that was implemented in Greece, involving large, susceptible populations taking tests routinely and pre-emptively so as to enable early detection of infections. Using a novel compartmental model we quantify the effectiveness of the program in curbing the COVID-19 pandemic. Conservative estimates indicate that the program reduced the reproductive number by 4%, hospital admissions by 25% and deaths by 20%, which translated into approximately 20,000 averted hospitalizations and 2,000 averted deaths between April-December 2021. Self-testing mass screening programs are efficient interventions with minimal social and financial burden, thus they are invaluable tools to be considered in pandemic preparedness.