bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUATING MHEALTH APPLICATIONS FOR OLDER ADULTS WITH DIABETES: SYSTEMATIC META-ANALYSIS OF CLINICAL TRIALS
Authors: Azevedo Renato Ferreira Leitao , Varzino Michael , Steinman Erika , Rogers Wendy
Published: December 2023

Diabetes is a common chronic condition among older adults and health technology interventions for diabetes management have the potential to support their self-management. However there is no systematic review and meta-analysis of the effects of mobile health applications (mHealth apps) for older adults. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the effectiveness of mHealth apps for improving older adults’ diabetes outcomes. We searched the EBSCO, Clinical Trials, Cochrane Library, ProQuest, PubMed, ScienceDirect, Scopus, and Web of Science databases for relevant studies. We retrieved 4247 papers and two reviewers completed a full screen review of 257. We excluded papers if the study was not a RCT, did not examine the effect of mHealth apps, or was not conducted with older adults, resulting in 7 papers included in the final analysis. Our results indicate that mHealth apps can be effective for older adults managing diabetes, with significant reductions in glycated hemoglobin (HbA1C) (Hedge’s g: -0.40, 95% CI [-0.75 to -0.06]), and fasting blood sugar (FBS) levels (g: -0.29, 95% CI [-1.52 to 0.42]), as well as improvements in medication adherence (g: 0.93, 95% CI [0.53 to 1.28]). These effect sizes are comparable with other meta-analysis conducted across different aging groups. We describe each intervention and evaluate the risk of bias and the app components that could relate to effectiveness to inform the design of other diabetes management RCTs, and more broadly, the design of other mHealth tools for older adults. Pre-registration: http://doi.org/10.17605/OSF.IO/AWVCX
BRIDGING RESEARCH AND POLICY TO EXPAND SUPPORTS TO OLDER ADULTS LIVING ALONE WITH COGNITIVE IMPAIRMENT IN THE US
Authors: Portacolone Elena , Stone Robyn
Published: December 2023

Bridging research and policy allows research findings to have a lasting impact in the wellbeing of vulnerable population such as the estimated 4.3 million older adults living alone with cognitive impairment in the United States. For example, a lasting impact comes from healthcare and social services provided by Medicare and Medicaid tailored to address unmet needs of these populations identified via rigorous research. Despite the importance of bridging research with policy, researchers seldom collaborate with policy makers, thus missing the opportunity of influencing policies. Reasons for these limited collaborations include limited knowledge on methods for researchers to collaborate with policy makers. This session will draw from the expertise gained by the research team of the 5-year Living Alone with Cognitive Impairment Project to involve policy experts in the design of their mixed-method study. Regular interactions between the research team and the Policy Advisory Group led to: 1) a mixed-method design aligned with policy priorities; 2) a report highlighting the priorities of PAG members with regard to policies to enhance the wellbeing of older adults living alone in the US; 3) a series of policy briefs highlighting key findings and related policy recommendations. The oversight of a Policy Advisory Group allowed the Living Alone with Cognitive Impairment Project to focus research activities that are likely to be translated into policy solutions, thus likely to mostly benefit older adults living alone with cognitive impairment, with emphasis on communities of color. These practices can be replicated by researchers in studies supporting underserved populations.
THE IMPACT OF 3 GENERATIONS OF VIOLENCE ON THE MENTAL HEALTH OF COLOMBIAN OLDER ADULTS: COMPARATIVE MULTI-SITE SURVEY
Authors: Gabbay Mark , Zuluaga Maria Isabel , Saldarriaga-ruiz gabriel , Montoya Erika , Giebel Clarissa
Published: December 2023

Endemic violence across Colombia for 70 years has displaced generations of the poorest among Colombian society particularly in (semi)rural and peri-urban settings, approximately (10m- 20% total population). In 2022, 12.5% (1.2m) were older adults living with the health and socioeconomic consequences, losses and life-changing disruptions. Our joint Colombian UK-funded project in Turbo explores ways to co-produce and pilot an intervention to help mitigate impacts older-adults’ mental-health and wellbeing. This survey explores their burden of ill-health and adversity. We compared our 2022 older-adults survey in Turbo ( n=611) with 2016 (n=~0.5m) survey findings from three other Colombian regions with different exposures to ‘La Violencia’. Both surveys measured Cognitive status, Functionality, Autonomy, Depression, Anxiety, Alcohol-use, Well-being, Social support, Loneliness, Nutrition and Maltreatment plus demographics and used probability cluster two-stage sampling to enhance representativeness. Mental health is not a concept used by older adults, ‘depression’ (5-28%) and ‘anxiety’ (4-21%) were lower than anticipated. An unexpectedly high proportion in Turbo respondents had at least some cognitive deficit (62%), much higher than elsewhere (1.3-5.1%). Most respondents were living in significant poverty with low educational attainment, low or minimal income, low nutrition, poor housing and social isolation. Reported elder abuse rates ranged from 4-30% across sites. The survey findings confirm high rates of vulnerability among older adults living with the severe consequences of ’La Violencia’ upon mental-health. Our project co-producing and delivering affordable and sustainable interventions, seeks to improve mental health and wellbeing, self-esteem and belonging, within a society that largely neglects older adults.
The effect of shear strain and shear localization on fault healing
Authors: Noël Corentin , Giorgetti Carolina , Collettini Cristiano , Marone Chris
Published: December 2023

The seismic cycle of repeated earthquake failure requires that faults regain frictional strength during the interseismic phase, when the fault is locked or undergoing quasi-static creep. Fault healing plays a central role in determining earthquake stress drop, recurrence interval, elastic radiation frequency and other source parameters. In particular, the longer a fault remains quasi-stationary, the stronger it becomes and the larger the potential stress drop can be for the next event. Here, we address the role of shear strain and strain localization on fault healing and healing rate. We performed slide-hold-slide friction experiments on quartz gouge in the double-direct shear configuration for shear strain up to 25 and hold times from 10 to 1000 s. The results show that both healing and healing rate increase nonlinearly with increasing shear strain. Frictional healing scales with volumetric strain within the laboratory fault zone. Using the volumetric strain upon reshear as a proxy for strain localization, we demonstrate that the capacity of a fault to heal is directly proportional to shear bandwidth and degree of strain localization. The more the deformation is localized, the higher are the healing and healing rate, and thus, the fault strength. Our data provide a framework for understanding variations in fault strength over the seismic cycle and the role of brecciation and strain localization on spatiotemporal variations in fault strength.
Mean Field Approximations via Log-Concavity
Authors: Lacker Daniel , Mukherjee Sumit , Yeung Lane Chun
Published: December 2023

We propose a new approach to deriving quantitative mean field approximations for any probability measure $P$ on $\mathbb {R}^{n}$ with density proportional to $e^{f(x)}$, for $f$ strongly concave. We bound the mean field approximation for the log partition function $\log \int e^{f(x)}dx$ in terms of $\sum _{i \neq j}\mathbb {E}_{Q^{*}}|\partial _{ij}f|^{2}$, for a semi-explicit probability measure $Q^{*}$ characterized as the unique mean field optimizer, or equivalently as the minimizer of the relative entropy $H(\cdot \,|\,P)$ over product measures. This notably does not involve metric-entropy or gradient-complexity concepts which are common in prior work on nonlinear large deviations. Three implications are discussed, in the contexts of continuous Gibbs measures on large graphs, high-dimensional Bayesian linear regression, and the construction of decentralized near-optimizers in high-dimensional stochastic control problems. Our arguments are based primarily on functional inequalities and the notion of displacement convexity from optimal transport.
Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials
Authors: Elliot Emilie R , Polli Joseph W , Patel Parul , Garside Louise , Grove Richard , Barnett Vincent , Roberts Jeremy , Byrapuneni Sri , Crauwels Herta , Ford Susan L , Van Solingen-Ristea Rodica , Birmingham Eileen , D’Amico Ronald , Baugh Bryan , van Wyk Jean
Published: December 2023

Background

Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (HIV-1) virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among phase 3/3b trial participants.

Methods

Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30 kg/m2, lower; ≥30 kg/m2, higher).

Results

Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30 kg/m2. At week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV-1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories.

Conclusions

CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category.

Clinical Trials Registration

NCT02938520, NCT02951052, and NCT03299049.
Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques
Authors: Makarova Natalia , Singletary Tyana , Peet M Melissa , Mitchell James , Bachman Shanon , Holder Angela , Dinh Chuong , Lipscomb Jonathan , Agrahari Vivek , Mendoza Maria , Pan Yi , Heneine Walid , Clark Meredith R , García-Lerma J Gerardo , Doncel Gustavo F , Smith James M
Published: December 2023

Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.
Seroreversion to Chlamydia trachomatis Pgp3 Antigen Among Children in a Hyperendemic Region of Amhara, Ethiopia
Authors: Tedijanto Christine , Aragie Solomon , Gwyn Sarah , Wittberg Dionna M , Zeru Taye , Tadesse Zerihun , Chernet Ambahun , Thompson Isabel J B , Nash Scott D , Lietman Thomas M , Martin Diana L , Keenan Jeremy D , Arnold Benjamin F
Published: December 2023

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6–3.5).

Clinical Trials Registration NCT02754583.
Modulatory role of SmeQ in SmeYZ efflux pump-involved functions in Stenotrophomonas maltophilia
Authors: Hu En-Wei , Lu Hsu-Feng , Lin Yi-Tsung , Yang Tsuey-Ching , Li Li-Hua
Published: December 2023

Background

SmeYZ is a constitutively expressed efflux pump in Stenotrophomonas maltophilia. Previous studies demonstrated that: (i) smeYZ inactivation causes compromised swimming, oxidative stress tolerance and aminoglycoside resistance; and (ii) the ΔsmeYZ-mediated pleiotropic defects, except aminoglycoside susceptibility, result from up-regulation of entSCEBB′FA and sbiAB operons, and decreased intracellular iron level.

Objectives

To elucidate the modulatory role of SmeQ, a novel cytoplasmic protein, in ΔsmeYZ-mediated pleiotropic defects.

Methods

The presence of operons was verified using RT–PCR. The role of SmeQ in ΔsmeYZ-mediated pleiotropic defects was assessed using in-frame deletion mutants and functional assays. A bacterial adenylate cyclase two-hybrid assay was used to investigate the protein–protein interactions. Gene expression was quantified using quantitative RT–PCR (RT–qPCR).

Results

SmeYZ and the downstream smeQ formed an operon. SmeQ inactivation in the WT KJ decreased aminoglycoside resistance but did not affect swimming and tolerance to oxidative stress or iron depletion. However, smeQ inactivation in the smeYZ mutant rescued the ΔsmeYZ-mediated pleiotropic defects, except for aminoglycoside susceptibility. In the WT KJ, SmeQ positively modulated SmeYZ pump function by transcriptionally up-regulating the smeYZQ operon. Nevertheless, in the smeYZ mutant, SmeQ exerted its modulatory role by up-regulating entSCEBB′FA and sbiAB operons, decreasing intracellular iron levels, and causing ΔsmeYZ-mediated pleiotropic defects, except for aminoglycoside susceptibility.

Conclusions

SmeQ is the first small protein identified to be involved in efflux pump function in S. maltophilia. It exerts modulatory effect by transcriptionally altering the expression of target genes, which are the smeYZQ operon in the WT KJ, and smeYZQ, entSCEBB′FA and sbiAB operons in smeYZ mutants.
Unveiling galaxy morphology through an unsupervised-supervised hybrid approach
Authors: Kolesnikov I , Sampaio V M , de Carvalho R R , Conselice C , Rembold S B , Mendes C L , Rosa R R
Published: December 2023

Galaxy morphology offers significant insights into the evolutionary pathways and underlying physics of galaxies. As astronomical data grow with surveys such as Euclid and Vera C. Rubin, there is a need for tools to classify and analyse the vast numbers of galaxies that will be observed. In this work, we introduce a novel classification technique blending unsupervised clustering based on morphological metrics with the scalability of supervised Convolutional Neural Networks. We delve into a comparative analysis between the well-known CAS (Concentration, Asymmetry, and Smoothness) metrics and our newly proposed EGG (Entropy, Gini, and Gradient Pattern Analysis). Our choice of the EGG system stems from its separation-oriented metrics, maximizing morphological class contrast. We leverage relationships between metrics and morphological classes, leading to an internal agreement between unsupervised clustering and supervised classification. Applying our methodology to the Sloan Digital Sky Survey data, we obtain ∼95  per cent of Overall Accuracy of purely unsupervised classification and when we replicate T-Type and visually classified galaxy catalogues with accuracy of ∼88 and ∼89 per cent, respectively, illustrating the method’s practicality. Furthermore, the application to Hubble Space Telescope data heralds the potential for unsupervised exploration of a higher redshift range. A notable achievement is our ∼95  per cent accuracy in unsupervised classification, a result that rivals when juxtaposed with Traditional Machine Learning and closely trails when compared to Deep Learning benchmarks.
FlexKnot and Gaussian Process for 21 cm global signal analysis and foreground separation
Authors: Heimersheim Stefan , Rønneberg Leiv , Linton Henry , Pagani Filippo , Fialkov Anastasia
Published: December 2023

The cosmological 21 cm signal is one of the most promising avenues to study the Epoch of Reionization. One class of experiments aiming to detect this signal is global signal experiments measuring the sky-averaged 21 cm brightness temperature as a function of frequency. A crucial step in the interpretation and analysis of such measurements is separating foreground contributions from the remainder of the signal, requiring accurate models for both components. Current models for the signal (non-foreground) component, which may contain cosmological and systematic contributions, are incomplete and unable to capture the full signal. We propose two new methods for extracting this component from the data: First, we employ a foreground-orthogonal Gaussian Process to extract the part of the signal that cannot be explained by the foregrounds. Secondly, we use a FlexKnot parametrization to model the full signal component in a free-form manner, not assuming any particular shape or functional form. This method uses Bayesian model selection to find the simplest signal that can explain the data. We test our methods on both, synthetic data and publicly available EDGES low-band data. We find that the Gaussian Process can clearly capture the foreground-orthogonal signal component of both data sets. The FlexKnot method correctly recovers the full shape of the input signal used in the synthetic data and yields a multimodal distribution of different signal shapes that can explain the EDGES observations.
Global deletome profile of Saccharomyces cerevisiae exposed to lithium
Authors: Fierling Nicolas , Billard Patrick , Bauda Pascale , Blaudez Damien
Published: December 2023

The increasing use of lithium (Li) in new technologies raises the question of its impact on living microorganisms. In the present study, we aimed to identify putative Li targets and resistance mechanisms in the yeast model Saccharomyces cerevisiae using a deletomic approach based on the screening of a collection of 4733 knockout mutants under Li exposure. This screening highlighted 60 mutants resistant to Li and 124 mutants sensitive to Li. Through functional enrichment analyses, transport systems were identified as playing a central role in cell resistance to toxic concentrations of Li. In contrast, the AKT/protein kinase B family, signal transduction or cell communication were identified as potential toxic targets of Li. The majority of the mutants with a Li-sensitive phenotype were also sensitive to other alkali and alkaline earth metals, whereas the Li-resistance phenotype was mostly resistant to Na but poorly resistant to other metals. A comparison with the results of deletomics studies carried out in the presence of other metals highlighted Li-specific phenotypes. Three genes (NAM7, NMD2, UPF3) of the nonsense-mediated decay pathway were specifically involved in resistance to Li. In contrast, mutants with the NCA2, SPT20, GCN5, YOR376W, YPK3, and DCW1 genes deleted were specifically resistant to Li. These genes encode various functions from putative mannosidase to constitution of the Spt-Ada-Gcn5 acetyltransferase complex. This work provides a better understanding of potential specific resistance mechanisms and cellular targets of Li in yeast.
Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022
Authors: Shen Yanhan , Robertson McKaylee M , Kulkarni Sarah G , Puzniak Laura , Zamparo Joann M , Allen Kristen E , Porter Thomas M , Qasmieh Saba A , Grov Christian , Srivastava Avantika , Zimba Rebecca , McLaughlin John M , Nash Denis
Published: December 2023

Background

We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022.

Methods

We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID).

Results

NMV/r uptake was 13.6% (95% CI, 11.9%–15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%–2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%–2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%–20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%–29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%–12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%–13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P = .001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%–70%) reported that NMV/r was helpful for reducing COVID-19 symptoms.

Conclusions

Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed.
Clinical Setting Comparative Analysis of Uropathogens and Antibiotic Resistance: A Retrospective Study Spanning the Coronavirus Disease 2019 Pandemic
Authors: Young Alexandra M , Tanaka Mark M , Yuwono Christopher , Wehrhahn Michael C , Zhang Li
Published: December 2023

Background

Antimicrobial resistance (AMR) in uropathogens has been increasing in Australia. Many nations observed heightened AMR during the coronavirus disease 2019 (COVID-19) pandemic, but it is not known how this may vary across clinical settings and in nations with lower infection rates.

Methods

We investigated the uropathogen composition and corresponding antibiotic resistance of 775 559 Australian isolates from the community, hospitals, and aged care facilities before (2016–2019) and during (2020–2022) the COVID-19 pandemic. A mathematical model was developed to predict the likelihood of resistance to currently recommended antibiotics for treating urinary tract infections (UTIs).

Results

Among uropathogens originating from the community, hospitals, and aged care facilities, Escherichia coli accounted for 71.4%, 57.6%, and 65.2%, respectively. During the COVID-19 pandemic period, there was an increase in UTIs caused by E coli across all settings. Uropathogens from aged care and hospitals frequently showed higher resistance to antibiotics compared to those isolated from the community. Interestingly, AMR among uropathogens showed a declining trend during the COVID-19 pandemic. Based on the resistance patterns of the past 3 years, our modeling predicted that 30%, 42.6%, and 38.8% of UTIs in the community, hospitals, and aged care facilities, respectively, would exhibit resistance to trimethoprim treatment as empirical therapy. In contrast, resistance to nitrofurantoin was predicted to be 14.6%, 26%, and 24.1% from these 3 respective settings.

Conclusions

Empirical therapy of UTIs in Australia with trimethoprim requires evaluation due to high rates of resistance observed across clinical settings.
Transarterial Radioembolization for Management of Hepatocellular Carcinoma
Authors: Badar Wali , Yu Qian , Patel Mikin , Ahmed Osman
Published: December 2023

Transarterial radioembolization (TARE) with Yttrium-90 (Y90) is a growing area of study due to its benefits in early-, intermediate-, and late-stage hepatocellular carcinoma. Treatment intent, including curative therapy, bridging to transplant, and downstaging disease, informs treatment approach and dosimetry goals. Radiation lobectomy (RL) and radiation segmentectomy (RS) are the 2 main forms of Y90 administration which have shown improved survival outcomes with the development of personalized dosimetry. RS aims to achieve complete pathological necrosis with dose escalation and RL aims for local disease control as well as induction of contralateral lobe hypertrophy to improve hepatic reserve. Furthermore, TARE has been validated in head-to-head comparison to other locoregional and systemic therapies. Lastly, early potential exists for combination therapy between TARE and immune checkpoint inhibitors for advanced stage disease.
Foreign Irrevocable Trusts and Taxes on Wealth in Argentina: Comment on Volij, Gabriela V. v Argentine Tax Authorities on Law Nr. 27,605, of the First Instance Federal Contentious Administrative Court Nr. 8 of Buenos Aires City
Authors: Malumián Nicolás
Published: December 2023

An Argentine individual created an irrevocable trust in New Zealand with three protectors. Argentina enacted a one-time extraordinary tax over the assets of all individuals on 18 December 2020. This tax included in its base for calculation all assets transferred to trusts abroad. The Judge declared that assets transferred to irrevocable trusts are no longer property of the settlor and could not be taxed.
Characterization of the molecular mechanisms that govern anti‐Müllerian hormone synthesis and activity
Authors: Stocker William A. , Howard James A. , Maskey Shreya , Luan Haitong , Harrison Sophie G. , Hart Kaitlin N. , Hok Lucija , Thompson Thomas B. , Walton Kelly L. , Harrison Craig A.
Published: December 2023

The roles of anti‐Müllerian hormone (AMH) continue to expand, from its discovery as a critical factor in sex determination, through its identification as a regulator of ovarian folliculogenesis, its use in fertility clinics as a measure of ovarian reserve, and its emerging role in hypothalamic–pituitary function. In light of these actions, AMH is considered an attractive therapeutic target to address diverse reproductive needs, including fertility preservation. Here, we set out to characterize the molecular mechanisms that govern AMH synthesis and activity. First, we enhanced the processing of the AMH precursor to >90% by introducing more efficient proprotein convertase cleavage sites (RKKR or ISSRKKRSVSS [SCUT]). Importantly, enhanced processing corresponded with a dramatic increase in secreted AMH activity. Next, based on species differences across the AMH type II receptor‐binding interface, we generated a series of human AMH variants and assessed bioactivity. AMHSCUT potency (EC50 4 ng/mL) was increased 5‐ or 10‐fold by incorporating Gln484Met/Leu535Thr (EC50 0.8 ng/mL) or Gln484Met/Gly533Ser (EC50 0.4 ng/mL) mutations, respectively. Furthermore, the Gln484Met/Leu535Thr double mutant displayed enhanced efficacy, relative to AMHSCUT. Finally, we identified residues within the wrist pre‐helix of AMH (Trp494, Gln496, Ser497, and Asp498) that likely mediate type I receptor binding. Mutagenesis of these residues generated gain‐ (Trp494Phe or Gln496Leu) or loss‐ (Ser497Ala) of function AMH variants. Surprisingly, combining activating type I and type II receptor mutations only led to modest additive increases in AMH potency/efficacy. Our study is the first to characterize AMH residues involved in type I receptor binding and suggests a step‐wise receptor‐complex assembly mechanism, in which enhancement in the affinity of the ligand for either receptor can increase AMH activity beyond the natural level.
Orthopaedic Surgery Subspecialty Podcast Effectively Disseminates Peer-reviewed Articles Relative to Traditional Online Publishing
Authors: Paulson Ambika E. , Clement Rutledge Carter , Holt Joshua B. , Sanders Julia S. , Louer Craig R.
Published: December 2023

Background:

Podcasts have become increasingly utilized in medical education over the past decade, especially in orthopaedic surgery. Compared with more traditional learning tools, podcasts are easily accessible, free, and capable of use while multitasking. Despite these apparent benefits, the effectiveness of podcasts as a dissemination tool for emerging peer-reviewed literature is not well understood. The Peds Ortho Podcast is the official podcast of Pediatric Orthopedic Society of North America that highlights recently published peer-reviewed articles through author interviews and executive summaries of featured articles. The purpose of this study was to compare the distribution of the Peds Ortho Podcast to traditional media by comparing electronic access statistics between the podcast episodes and the journal articles they summarize.

Methods:

Podcast episodes were reviewed to catalog the abstracts and articles discussed therein. Because podcasts and articles utilize different electronic metrics to track distribution, we established a common metric of an “access,” which we defined as an “intent to consume the media.” For articles, we defined an “access” as the largest value of a publisher’s online metrics, be it abstract views, full text views, or article downloads. For podcast episodes, we defined an “access” as any play >0 seconds. Access data were analyzed using independent samples t test and analyses of variance.

Results:

Eighty episodes of the Peds Ortho Podcast have featured 333 published, peer-reviewed articles to date, with 303 included in the final analysis with available article metrics. There were significantly more mean electronic accesses per podcast episode than featured articles (1236 vs. 482, P<0.001). Podcast consumption greatly varies in the first 30 days following episode release; however, recent episodes have a substantial proportion of accesses soon after publication.

Conclusions:

Given that podcast electronic access is greater than traditional media, podcasts appear to be a valuable tool for health care providers and trainees. Podcasts serve a complementary role to traditional media by quickly disseminating main points and raising awareness of emerging research.
Clinical and Histopathologic Spectrum of Toxic Erythema of Chemotherapy: A Series of 56 Cases From a Single Institution
Authors: Cole Daniel W. , Menge Tyler D. , Lowe Lori , Chan May P. , Bresler Scott C.
Published: December 2023

Introduction:

Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood.

Objective:

To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings.

Methods:

We searched our electronic medical record for “toxic erythema of chemotherapy” or “neutrophilic eccrine hidradenitis.” Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin–stained slides were retrospectively reviewed.

Results:

The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%).

Limitations:

As a retrospective study, it is subject to information bias.

Conclusion:

This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.
Lymphatic-based Lymphosome: A Novel Hypothesis with Clinical Implication for Supermicrosurgical Lymphaticovenous Anastomosis
Authors: Yang Johnson Chia-Shen
Published: December 2023

Understanding the anatomical territories drained by lymphatic vessels (LVs) is essential for a better comprehension of lymphatic anatomy and functionality, and for performing lymphatic procedures such as lymphaticovenous anastomosis (LVA). However, current concepts regarding the lymphatic territory are insufficient to explain some of the clinical observations. As shown in the figures, within one incision for the LVA, one to two lymphatic vessels (LV) remained unenhanced on indocyanine green (ICG) lymphography, whereas the rest of the LVs were enhanced. To answer this question, one must examine the concept of the lymphosome, first described by Suami, defined as a particular region drained by LVs into the same subgroup of regional lymph nodes (LNs) (eg, superficial groin LNs). Suami’s lymphosome concept represents “LN-based lymphosomes.” In addition, Shinaoka identified four distinct lymphatic groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limbs after ICG injection. This represents the concept “group-based lymphosomes.” Nevertheless, neither the LN- nor group-based lymphosome concepts offer an appropriate explanation for the clinical findings described above. In addition to the aforementioned lymphosome concepts, the author proposes a novel hypothesis called “lymphatic-based lymphosome,” which considers each LV as a single lymphosome. Therefore, the normal-type LV remained unenhanced when ICG was not injected into the draining territory. To enhance post-LVA outcomes, an even distribution of anastomoses to different group-based lymphosomes is important, as is avoiding performing all anastomoses onto a single LV or within the same group-based lymphosome.
Evaluation of Retinal Layers in Individuals With Pseudoexfoliation Syndrome and Ocular Hypertension
Authors: Koç Alpaslan , Özcura Fatih , Gültekin Irgat Saadet , Arik Özlem
Published: December 2023

Précis:

This study investigated the retinal segmental thicknesses in individuals with pseudoexfoliation syndrome and ocular hypertension. Maximum thinning was found at 6 mm inferior to the inner plexiform layer. This layer is very important for the early diagnosis of glaucoma.

Purpose:

To analyze the thickness of the peripapillary retinal nerve fiber layer and 8 macular layers using optical coherence tomography in eyes with ocular hypertension (OHT) and pseudoexfoliation syndrome (PXS) and healthy eyes and to evaluate between-group differences.

Materials and Methods:

In a prospective study, the macular segmentation of retinal layers in 120 eyes of 120 participants was performed automatically using current Heidelberg Spectralis optical coherence tomography software, which provides measurements for 8 retinal layers. Thickness maps divided into nine subfields (ie, 1, 3, and 6 mm) were extracted from the software for each retinal layer and compared between groups.

Results:

The thinnest macular layers appeared in the ocular hypertensive PXS, normotensive PXS, and OHT groups in that order. In the inner retinal layers (macular retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer), statistically significant differences emerged between the PXS and control groups in all quadrants of the 3 and 6 mm areas. No significant difference between the OHT group and control group appeared except in the 6 mm temporal quadrant of the inner plexiform layer (IPL). Receiving operating characteristic analysis revealed quadrants with high area-under-the-curve values at 3 and 6 mm in macular segments in all 3 groups compared with the control group.

Conclusion:

In macular segment analysis, the inner retinal layers showed the most thinning in patients with ocular hypertensive PXS. According to receiving operating characteristic curve analysis, examinations performed 6 mm inferior to the IPL, as the quadrant with the highest area under the curve in all 3 groups, are critical for the early diagnosis of glaucoma.
Long-Term Results of Transscleral Diode Laser Cyclophotocoagulation in Glaucoma: A Real-Life Study
Authors: Sari Cem , Alagoz Nese , Omeroglu Asena , Cakir Ihsan , Pasaoglu Isil , Altan Cigdem , Yasar Tekin
Published: December 2023

Précis:

Transscleral diode laser cyclophotocoagulation (TDLC) is effective and safe in a large population and different types of glaucoma but is least effective in the neovascular glaucoma (NVG) group.

Objective:

We aimed to investigate the clinical outcomes of TDLC in a large cohort of patients with different types of refractory glaucoma.

Patients and Methods:

Using patient charts, we retrospectively analyzed the success and complications of TDLC performed on eyes categorized into 6 groups: primary glaucoma (116 eyes), trauma (41 eyes), NVG (84 eyes), post-vitreoretinal surgery (post-VRS, 79 eyes), penetrating keratoplasty (47 eyes), and miscellaneous (40 eyes). Failure was defined as intraocular pressure (IOP) >22 mm Hg or <5 mm Hg, the need for further glaucoma surgery, and the loss of light perception during follow-up.

Results:

Overall, the mean follow-up time was 33.4 ± 17.4 months, the mean total energy delivered was 109.2 ± 56.5 J, and the mean IOP reduction rate was 41.8%. Total energy delivered and IOP reduction rates were similar between the groups (all P > 0.05). The probability of success at 36 months was 71.5%, 70.7%, 55.9%, 77.2%, 72.3%, and 72.5% in primary glaucoma, trauma, NVG, post-VRS, penetrating keratoplasty, and miscellaneous groups, respectively. The NVG group showed a significantly lower success rate (P = 0.009) than the other groups. Significant complications consisted of phthisis bulbi in 1 eye (0.2%) in the NVG group and chronic hypotony in 7 eyes (1.7%) in the NVG (3 eyes), trauma (2 eyes), post-VRS (1 eye), and primary glaucoma (1 eye) groups.

Conclusions:

Although TDLC was found to be a safe, effective method in the long term, it was least effective in eyes with NVG.
Comparison of Patterns of Structural Progression in Primary Open Angle Glaucoma and Pseudoexfoliation Glaucoma
Authors: Wy Seoyoung , Lee Yun Jeong , Sun Sukkyu , Bak Eunoo , Kim Young Kook , Park Ki Ho , Kim Hee Chan , Jeoung Jin Wook
Published: December 2023

Précis:

Primary open angle glaucoma and pseudoexfoliation glaucoma showed different progression patterns of the retinal nerve fiber layer and ganglion cell-inner plexiform layer thinning in OCT-guided progression analysis.

Purpose:

To compare the patterns of progression of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning by guided progression analysis (GPA) of optical coherence tomography (OCT) in primary open angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG).

Materials and Methods:

The progression of RNFL and GCIPL thinning was assessed by the GPA of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). By overlaying the acquired images of the RNFL and GCIPL thickness-change maps, the topographic patterns of progressive RNFL and GCIPL thinning were evaluated. The rates of progression of RNFL and GCIPL thinning were analyzed and compared between patients with POAG and those with PXG.

Results:

Of the 248 eyes of 248 patients with POAG (175 eyes of 175 patients) or PXG (73 eyes of 73 patients) enrolled, 156 POAG eyes and 48 PXG eyes were included. Progressive RNFL thinning was significantly more common in PXG than in POAG (P=0.005). According to the RNFL progression-frequency maps, progression appeared mainly in the superotemporal and inferotemporal areas in POAG, whereas it had invaded more into the temporal area in PXG. According to the GCIPL maps, progression was most common in the inferotemporal area in both POAG and PXG. The average progression rate of GCIPL thinning was faster in PXG than in POAG (P=0.013), and when analyzed in 2 halves (superior/inferior), the progression rate of the inferior half was faster in PXG than in POAG (P=0.011).

Conclusions:

OCT GPA showed progression patterns of RNFL and GCIPL thinning in POAG and PXG. Understanding the specific patterns of progressive RNFL and GCIPL thinning according to glaucoma type may prove helpful to glaucoma-patient treatment and monitoring.
Anterior Segment Optical Coherence Tomography for Cases of High Intraocular Pressure Following XEN Implant for Glaucoma
Authors: Tatti Filippo , Lixi Filippo , Demarinis Giuseppe , Napoli Pietro , Fossarello Maurizio
Published: December 2023

Précis:

This study showed that the XEN patency should be verified by OCT imaging in cases of encapsulated blebs. Although fibrosis plays the principal role, humor aqueous flow reduction could affect the “spacer” effect that inhibits the fibroblast attachments.

Purpose:

To evaluate the application of the anterior segment optical coherence tomography (AS-OCT) imaging in studying the relationship between a low flow rate through the XEN63 and the development of a cystic bleb.

Methods:

Retrospective case series of 3 eyes presenting a cystic bleb after an XEN63 implantation for uncontrolled intraocular pressure (IOP). Demographic and clinical data were obtained from medical records. The imaging findings, complications, and managements following the surgery were evaluated.

Results:

Three patients, with an average age of 67.3 years, initially showed a patent stent lumen and a functional bleb after surgery. The IOP of all eyes increased on average at 28.3 days from the surgery, with a mean value of 39.66 mm Hg. The slit lamp examination showed a cystic bleb. The AS-OCT imaging confirmed the previous finding and revealed either a partial or total occlusion of the stent internal ostium. A Nd:YAG laser, in proximity to the ostium, was performed to resolve the obstruction. Although the AS-OCT imaging showed the device patency and the IOP immediately decreased, the latter became elevated again. Consequently, in all the cases, a further needling procedure was needed to achieve an adequate IOP reduction. Six months after the two-step procedure, the IOP averaged 13.33 mm Hg, the XEN63 lumens appeared cleared, and the blebs showed a functional morphology. No adverse events were observed.

Conclusion:

The development of a cystic bleb may result from an altered balance between the flow rate through the XEN63 and the fibrosis development in the postoperative healing process. A proper follow-up based on slit lamp biomicroscopy, IOP measurement, and AS-OCT imaging is advisable to estimate and manage a cystic bleb following XEN63 implantation.
Single-Use Lens Compromise During Selective Laser Trabeculoplasty
Authors: Liu Alice S. , Lyons Lance J. , Khanna Cheryl L. , Roddy Gavin W. , Hodge David O. , Sit Arthur J.
Published: December 2023

Précis:

Damage to disposable selective laser trabeculoplasty (SLT) lenses correlated with the amount of total laser energy. Furthermore, greater lens damage was associated with diminished patient treatment response.

Purpose:

Disposable SLT lenses have been observed to be damaged during use by laser, potentially affecting therapeutic response. This study sought to identify factors associated with the magnitude of lens damage and its effect on treatment outcomes.

Patient and Methods:

We analyzed 113 eyes from 82 patients who underwent SLT between 2020 and 2021 at an American academic medical center. For each procedure, we recorded baseline patient characteristics, procedure settings, physician age (as a possible factor causing laser defocus due to accommodation), and area of lens damage. Treatment response was calculated as the difference between preoperative and postoperative intraocular pressure (IOP).

Results:

Area of lens damage was associated with greater total laser energy (r=0.34, P<0.001) and greater mean energy per application (r=0.37, P<0.001). IOP reduction decreased with increasing lens damage (r=−0.19, P=0.022). Lens damage was not associated with patient characteristics indicative of glaucoma severity or user settings (physician age and slit lamp used). Greater IOP reduction was associated with higher preop IOP (r=0.46, P<0.001) and a smaller cup-to-disc ratio (r=0.22, P=0.036). IOP reduction was not associated with retinal nerve fiber layer thickness, patient age, or the number of glaucoma medications.

Conclusions:

Increased laser damage to disposable SLT lenses was associated with diminished treatment effect. The amount of damage was correlated with total and average laser energy, but not patient or physician factors. Overall, these findings call for reconsideration of using disposable SLT lenses as part of routine practice.
Lessons From The Glaucoma Foundation Think Tank 2023: A Patient-Centric Approach to Glaucoma
Authors: Harris Alon , Verticchio Vercellin Alice , Weinreb Robert N. , Khawaja Anthony , MacGregor Stuart , Pasquale Louis R.
Published: December 2023

Précis:

The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.

Purpose:

To summarize the main topics discussed during the 28th Annual Glaucoma Foundation Think Tank Meeting “A Patient-Centric Approach to Glaucoma” held in New York on June 9 and 10, 2023.

Methods:

The highlights of the sessions on BIG DATA, genetics, modifiable lifestyle risk factors, female sex hormones, and neuroprotection in the field of primary open angle glaucoma (POAG) were summarized.

Results:

The researchers discussed the importance of BIG DATA repositories available at national and international levels for POAG research, including the United Kingdom Biobank. Combining genotyped large cohorts worldwide, facilitated by artificial intelligence (AI) and machine-learning approaches, led to the milestone discovery of 312 genome-wide significant disease loci for POAG. While these loci could be combined into a polygenic risk score with clinical utility, Think Tank meeting participants also provided analytical epidemiological evidence that behavioral risk factors modify POAG polygenetic risk, citing specific examples related to caffeine and alcohol use. The impact of female sex hormones on POAG pathophysiology was discussed, as was neuroprotection and the potential use of AI to help mitigate specific challenges faced in clinical trials and speed approval of neuroprotective agents.

Conclusions:

The experts agreed on the importance of genetics in defining individual POAG risk and highlighted the additional crucial role of lifestyle, gender, blood pressure, and vascular risk factors. The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.
Clinical Usefulness of T-Cell Receptor Vβ Repertoire Analysis for Differentiating Multisystem Inflammatory Syndrome in Japanese Children From Toxic Shock Syndrome and Kawasaki Disease
Authors: Kaneko Shuya , Noguchi Yusuke , Hatano Maho , Shimbo Asami , Irabu Hitoshi , Furuno Kenji , Iwata Naomi , Fujimura Junya , Akamine Keiji , Kobayashi Anna , Endo Takuya , Morio Tomohiro , Shimizu Masaki
Published: December 2023

The specific expansion of T-cell receptor β chain variable region (TCR-Vβ21.3+) CD4+ and CD8+ T cells was observed in Japanese patients with multisystem inflammatory syndrome in children. In contrast, these findings were not observed in patients with toxic shock syndrome and Kawasaki disease. T-cell receptor β chain variable region repertoire analysis to detect specific expansion of Vβ21.3+ T cells might be useful for differentiating multisystem inflammatory syndrome in children from toxic shock syndrome and Kawasaki disease.