bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Functioning and the Quality of Survey Responses: An Individual Participant Data Meta-Analysis of 10 Epidemiological Studies of Aging
Authors: Schneider Stefan , Lee Pey-Jiuan , Hernandez Raymond , Junghaenel Doerte U , Stone Arthur A , Meijer Erik , Jin Haomiao , Kapteyn Arie , Orriens Bart , Zelinski Elizabeth M
Published: March 2024

Objectives

Self-reported survey data are essential for monitoring the health and well-being of the population as it ages. For studies of aging to provide precise and unbiased results, it is necessary that the self-reported information meets high psychometric standards. In this study, we examined whether the quality of survey responses in panel studies of aging depends on respondents’ cognitive abilities.

Methods

Over 17 million survey responses from 157,844 participants aged 50 years and older in 10 epidemiological studies of aging were analyzed. We derived 6 common statistical indicators of response quality from each participant’s data and estimated the correlations with participants’ cognitive test scores at each study wave. Effect sizes (correlations) were synthesized across studies, cognitive tests, and waves using individual participant data meta-analysis methods.

Results

Respondents with lower cognitive scores showed significantly more missing item responses (overall effect size ρ^ = −0.144), random measurement error (ρ^ = −0.192), Guttman errors (ρ^ = −0.233), multivariate outliers (ρ^ = −0.254), and acquiescent responses (ρ^ = −0.078); the overall effect for extreme responses (ρ^ = −0.045) was not significant. Effect sizes were consistent across studies, modes of survey administsration, and different cognitive functioning domains, although some cognitive domain specificity was also observed.

Discussion

Lower-quality responses among respondents with lower cognitive abilities add random and systematic errors to survey measures, reducing the reliability, validity, and reproducibility of survey study results in aging research.
Heterogeneous Effects of Volunteering on Frailty in Later Life: A Panel Quantile Regression Approach
Authors: Han Sae Hwang , Park Narae
Published: March 2024

Objectives

Decades of research indicate that volunteering is associated with better health for the volunteer beyond the selection effects based on health. However, little is known about potential heterogeneity in health outcomes associated with volunteering in the context of good or poor health. This study addresses this gap by focusing on the frailty index (FI) to investigate the volunteering–health nexus across the population frailty distribution ranging from fit to frail.

Methods

Using nationally representative data from the Health and Retirement Study (person N = 34,986; 198,218 person-wave observations), we estimated unconditional quantile regression models with panel fixed effects to estimate changes in FI associated with changes in the share of volunteers in the population across the frailty distribution observed across the study period (1998–2020).

Results

Our findings demonstrated that the volunteering–FI association was heterogeneous across the frailty distribution. The association was the most potent at the higher end of the frailty distribution, suggesting that efforts to promote volunteering may yield greater benefits for older adults experiencing high levels of frailty.

Discussion

The current study findings provide unique and compelling evidence in support of earlier calls for considering volunteering as a public health intervention. The study findings are discussed in the context of population health outcomes and health disparities.
Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study
Authors: Sands Bruce E , D’Haens Geert , Clemow David B , Irving Peter M , Johns Jordan T , Hunter Gibble Theresa , Abreu Maria T , Lee Scott , Hisamatsu Tadakazu , Kobayashi Taku , Dubinsky Marla C , Vermeire Severine , Siegel Corey A , Peyrin-Biroulet Laurent , Moses Richard E , Milata Joe , Arora Vipin , Panaccione Remo , Dignass Axel
Published: March 2024

Background

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104.

Methods

Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC).

Results

Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 54.0%, 62.8%, and 70.1% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 76.6%, 89.0%, and 98.3% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events.

Conclusions

Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.
Instituting coronavirus disease 2019 testing: opportunities and challenges of molecular laboratory diagnosis in a Southern Nigerian teaching hospital
Authors: Osaigbovo Iriagbonse I , Igbarumah Isaac O , Obaseki Darlington E
Published: March 2024

The coronavirus disease 2019 pandemic emphasised the importance of laboratory preparedness, including molecular diagnostic capacity, in the control of infectious disease outbreaks. This article reflects on diagnostic capacity-building opportunities presented by the pandemic, the challenges experienced along the way and the lessons learned from the perspective of a university teaching hospital in Southern Nigeria. We advocate for these lessons to inform strategic planning for laboratory preparedness at subnational, national and continental levels.
What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review
Authors: Assefa Getnet M , Roberts Jason A , Mohammed Solomon A , Sime Fekade B
Published: March 2024

Background

Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of β-lactam/β-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs.

Objectives

This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with β-lactam antibiotics.

Methods

Literature was searched online through PubMed, Embase, Web of Science, Scopus and Cochrane Library databases up to 5 June 2023. Studies that report the PK/PD index and threshold concentration of BLIs approved for clinical use were included. Narrative data synthesis was carried out to assimilate the available evidence.

Results

Twenty-three studies were included. The PK/PD index that described the efficacy of BLIs was fT>CT for tazobactam, avibactam and clavulanic acid and fAUC0–24/MIC for relebactam and vaborbactam. The optimal magnitude of the PK/PD index is variable for each BLI based on the companion β-lactam antibiotics, type of bacteria and β-lactamase enzyme gene transcription levels.

Conclusions

The PK/PD index that describes the efficacy of BLIs and the exposure measure required for their efficacy is variable among inhibitors; as a result, it is difficult to make clear inference on what the optimum index is. Further PK/PD profiling of BLI, using preclinical infection models that simulate the anticipated mode(s) of clinical use, is warranted to streamline the exposure targets for use in the optimization of dosing regimens.
Genetic parameters for yearling male reproduction traits in tropical composite cattle population
Authors: Facy Madeliene L , Hebart Michelle L , Oakey Helena , McEwin Rudi A , Pitchford Wayne S
Published: March 2024

Fertility is economically important but is hard to quantify and measure in breeding programs which has led extensive breeding programs to ignore fertility in their selection criteria. While female fertility traits have been extensively researched, male fertility traits have been largely ignored. It is estimated that 20% to 40% of bulls have sub-fertility, reducing the number of calves born and profits, highlighting the importance of investigating bull fertility. The most practical measure of male fertility is a bull breeding soundness evaluation (BBSE) which assesses structure as well as semen quality and quantity. Generally, traits recorded in a BBSE are neither genetically evaluated nor used for selection in breeding programs. All traits recorded during a BBSE were analyzed through a series of univariate and bivariate linear mixed models using a genomic relationship matrix to estimate genetic parameters. All genotype and phenotype data were obtained from a tropical composite commercial cattle population and imputed to 27,638 single-nucleotide polymorphisms (SNPs) with a total of 2,613 genotyped animals with BBSE records ranging from 616 to 826 animals depending on the trait. The heritabilities of the 27 traits recorded during a BBSE ranged from 0.02 to 0.49. Seven of the male fertility traits were recommended to be included in a breeding program based on their heritability and their phenotypic and genetic correlations. These traits are scrotal circumference, percent normal sperm, proximal droplets, distal midpiece reflex, knobbed acrosomes, vacuoles/teratoids, and sheath score. Using these seven traits in a breeding program would result in higher calving rates, increasing production and profitability.
Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen
Authors: Lin-Hui Li , Yuan-Yuan Zha , Ming-Yu Liu , Xu-Dong Hong , Yin-Jia Ding , Yue Zhou , Yang-Hong-Hong Fei , Ai-Fen Chen , Xu-Dong Zhang , Zheng-Li Chen , Jian Jin
Published: March 2024

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography–tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2ʹ-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis—especially that of type III—thereby reducing the type I/III ratio and improving hypertrophic scarring.
PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti–PD-1 immunotherapy
Authors: Zhang Dong , Wang Min , Wang Wenying , Ma Shiya , Yu Wenwen , Ren Xiubao , Sun Qian
Published: March 2024

Triple-negative breast cancer is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in triple-negative breast cancer is affected by immunocyte infiltration in the tumor microenvironment. PGAM1 is a key enzyme involved in cancer metabolism; however, its role in the tumor microenvironment remains unclear. In this study, we aimed to investigate the role of PGAM1 in triple-negative breast cancer and determine the potential of PGAM1 inhibition in combination with anti–PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in triple-negative breast cancer and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti–PD-1 immunotherapy, significantly remodeling the tumor microenvironment and leading to an increase in antitumor immunocytes, such as CD8+ T cells and M1 macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti–PD-1 immunotherapy, providing a novel treatment strategy for triple-negative breast cancer.
Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis
Authors: Agrawal Pranjal , Singh Sajya M , Hsueh Jessica , Grutman Aurora , An Clemens , Able Corey , Choi Una , Kohn Jaden , Clifton Marisa , Kohn Taylor P
Published: March 2024

Background

Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results.

Aim

To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database.

Methods

The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years).

Outcomes

We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh.

Results

When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls.

Clinical Implications

Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women.

Strengths and Limitations

The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors.

Conclusions

We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.
Predictors of Positive Airway Pressure Therapy Adherence Among U.S. Active Duty Military Personnel With Obstructive Sleep Apnea
Authors: Shaha David P , Ee Juliana S , Pham Christopher K , Choi Lea S , Dogbey Godwin Y , Pogorzelski Nina
Published: March 2024

Introduction

Obstructive sleep apnea (OSA) is prevalent among U.S. military personnel, but adherence to positive airway pressure (PAP) treatment is suboptimal. This study sought to identify factors that predict the adherence to PAP therapy of active duty military patients newly diagnosed with OSA.

Materials and Methods

The study was a retrospective cross-sectional analysis of 239 active duty military patients (94% men, mean age 40.0 ± 7.8 years), who were admitted into PAP therapy and participated in a single 90-minute behavioral intervention session. The session included a self-assessment of sleep trouble, sleep distress, impact of sleep on functioning, emotional difficulty from sleep, stress appraisal, and beliefs about OSA and PAP. PAP usage data of the patients were analyzed at 30-, 60-, and 180 days post-intervention using descriptive statistics and multivariable linear regression analysis.

Results

Positive airway pressure adherence of at least 4 hours nightly usage decreased slightly over the course of the study; mean number of days used over a 30-day timeframe at the 30-, 60-, and 180-day mark were 15.6, 14.9, and 14.1 days, respectively. On nights used, PAP usage remained consistent at 4.8 to 5.0 hours over the 30-, 60-, and 180-day mark. Age, apnea-hypopnea index, readiness, self-efficacy or confidence in treatment implementation, and worries about sleep were statistically significant predictors of adherence. Furthermore, worries about sleep negatively affected PAP usage hours on nights used, regardless of meeting adherence criterion, in the early phase of treatment and in the long run at the 180-day mark.

Conclusions

Readiness for therapy, self-efficacy, confidence in putting into action the treatment plan, and worries about sleep are modifiable variables that may be targeted in programs to boost PAP adherence and usage among the military population. Future studies should explore the predictive aspects of each of these variables and identify interventions to improve them.
Analysis, classification and identification of gastropod locomotive mucus by Fourier transform infrared spectroscopy
Authors: Ledesma Edgar Barajas , Holland Chris
Published: March 2024

Mucus is a defining feature of many gastropod phenotypes. Its material properties are a product of selection acting on the relationship between mucus composition, structure and performance; however, to date, there are very few studies addressing this. Here, we introduce attenuated total reflection Fourier transform infrared (FTIR) spectroscopy as an accessible analytical technique to record, identify and classify gastropod locomotive mucus, as deposited, with practically no intervention. Advancing the field beyond previous spectroscopic studies, we also probe mucus response to a temperature increase, determining its propensity to remain hydrated (i.e. resist denaturation) and serving as the basis for building cladograms based on spectral similarities. Specifically, the relative content of proteins, their secondary structures, protein-carbohydrate interactions, and thermal stability were investigated and shown to have significant variation between species. Collating and comparing over 648 spectra across 12 species and 7 superfamilies, we report that it is even possible to classify gastropods based solely on their secreted pedal mucus. This was further compared to previously published phylogenetic data and taxonomies enabling a 100% hit rate of genus assignment, implying that mucus FTIR may also be a powerful tool for field-based biodiversity studies.
Baseline total brain volume predicts changes in quality of life and overall survival after cranial radiotherapy in older patients with glioblastoma: Results from the prospective BRITER study
Authors: Lorimer Cressida , Mills Samantha , Chalmers Anthony , Coombes Isobelle , Thompson Gerard , Glendenning Jennifer , Radon Mark , Jones Christopher , Williamson Aoife , Brock Juliet
Published: March 2024

Background

Short-course partial brain radiotherapy ± chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy-related side effects.

Methods

This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL).

Results

126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The median OS was 10.7 months. After accounting for age, sex, treatment, and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI −3.24 to −0.19 P = .027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow-up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P < .001).

Conclusions

This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.
Patterns of care and survival in patients with multifocal glioblastoma: A Danish cohort study
Authors: Trip Anouk Kirsten , Hedegaard Dahlrot Rikke , Aaquist Haslund Charlotte , Muhic Aida , Rosendal Korshøj Anders , Laursen René Johannes , Rom Poulsen Frantz , Skjøth-Rasmussen Jane , Lukacova Slavka
Published: March 2024

Background

This Danish cohort study aims to (1) compare patterns of care (POC) and survival of patients with multifocal glioblastoma (mGBM) to those with unifocal glioblastoma (uGBM), and (2) explore the association of patient-related factors with treatment assignment and prognosis, respectively, in the subgroup of mGBM patients.

Methods

Data on all adults with newly diagnosed, pathology-confirmed GBM between 2015 and 2019 were extracted from the Danish Neuro-Oncology Registry. To compare POC and survival of mGBM to uGBM, we applied multivariable logistic and Cox regression analysis, respectively. To analyze the association of patient-related factors with treatment assignment and prognosis, we established multivariable logistic and Cox regression models, respectively.

Results

In this cohort of 1343 patients, 231 had mGBM. Of those, 42% underwent tumor resection and 41% were assigned to long-course chemoradiotherapy. Compared to uGBM, mGBM patients less often underwent a partial (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.6), near-total (OR 0.1, 95% CI 0.07–0.2), and complete resection (OR 0.1, 95% CI 0.07–0.2) versus biopsy. mGBM patients were furthermore less often assigned to long-course chemoradiotherapy (OR 0.6, 95% CI 0.4–0.97). Median overall survival was 7.0 (95% CI 5.7–8.3) months for mGBM patients, and multifocality was an independent poor prognostic factor for survival (hazard ratio 1.3, 95% CI 1.1–1.5). In mGBM patients, initial performance, O[6]-methylguanine-DNA methyltransferase promotor methylation status, and extent of resection were significantly associated with survival.

Conclusions

Patients with mGBM were treated with an overall less intensive approach. Multifocality was a poor prognostic factor for survival with a moderate effect. Prognostic factors for patients with mGBM were identified.
Ultrasound guided quadro-iliac plane block: another novel fascial plane block
Authors: Tulgar Serkan , Ciftci Bahadir , Ahiskalioglu Ali , Bilal Bora , Sakul Bayram Ufuk , Girit Melike , Akin Tugce , Narayanan Madan , Alici Haci Ahmet
Published: March 2024

Study objective

We report a novel block technique aimed to provide lumbosacral, abdominal, and hip analgesia: The quadro-iliac plane (QIP) block.

Design

A cadaveric examination that evaluates the spread of QIP block.

Setting

Cadaver laboratory.

Patients

One unembalmed cadaver.

Interventions

Bilateral ultrasound-guided QIP blocks on cadavers with 40 mL of methylene blue %0.5 each side.

Measurements

Dye spread in cadaver.

Main results

There was staining in the deep interfascial plane of the erector spinae muscles. Extensive staining of the interfascial plane corresponding to the posterior aspect of the quadratus lumborum muscle (QLM) was observed. There was extensive staining on the anterior surface of the QLM. There was spread of dye traversing along the transversalis fascia and significantly infiltrating retroperitoneal fat tissue. Bilateral staining of the ilioinguinal and iliohypogastric nerves was observed. On the right, there was minimal staining over the subcostal nerve. There was dye present bilaterally within the deep regions of the transverse processes. The lumbar plexus was stained on both sides.

Conclusion

The local anesthetic applied from a place where the QLM reaches its largest volume and the fascial plane creates a closed gap in the caudal area may exhibit a more rounded and extensive spread.

Quadro-iliac plane block, involves the administration of local anesthetic to the posterior aspect of the QLM at its origin from the iliac crest. According to our cadaver study, this technique may be a promising option for alleviating acute and chronic pain in the lumbosacral, lower abdominal, and hip regions.
Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish SLE patients
Authors: Elbagir Sahwa , Mohammed NasrEldeen A , Oke Vilija , Larsson Anders , Nilsson Jan , Elshafie Amir , Elagib Elnour M , Nur Musa A M , Gunnarsson Iva , Svenungsson Elisabet , Rönnelid Johan
Published: March 2024

Objectives

In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured ANA sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines.

Methods

We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192). Autoantibodies targeting ANA sub-specificities: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with the Proximity Extension Assay technique or ELISA.

Results

Among Sudanese patients, the investigated antibodies were significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies were associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.

Among Swedish patients, MCP-1, CXCL10, and SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared with anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant.

Conclusion

In two cohorts of different ethnical origins, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be the main drivers of type-1 interferon activity in SLE.
Documenting Decentralization: Empirical Evidence on Administrative Unit Proliferation from Uganda
Authors: Cohen Isabelle
Published: March 2024

Decentralization is an important and commonplace type of reform, yet our understanding of its effects remains limited. This paper documents the effects of the 2009–10 wave of district creation in Uganda, which increased the country’s districts by 42 percent, using rich data on subdistrict units to assess the effects of district creation on a broad range of post-decentralization outcomes in a difference-in-differences framework. The effects of decentralization are concentrated in newly split off—rather than split from—districts, and are heterogeneous across outcome types. Newly split-off districts have more per capita frontline workers, but appear to have worse quality infrastructure and lower economic development. The study also presents suggestive evidence that administrative capacity decreases for newly formed districts post-split. These findings demonstrate the importance of considering a broad range of outcomes when thinking about decentralization.
m6A reader IGF2BP1 reduces the sensitivity of nasopharyngeal carcinoma cells to Taxol by upregulation of AKT2
Authors: Zhao Chong , Zhang Fang , Tian Yang , Tang Bingjie , Luo Jing , Zhang Jianhui
Published: March 2024

Taxol is widely used in the treatment of nasopharyngeal carcinoma (NPC); nevertheless, the acquired resistance of NPC to Taxol remains one of the major obstacles in clinical treatment. In this study, we aimed to investigate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in Taxol resistance of NPC. Taxol-resistant NPC cell lines were established by exposing to gradually increased concentration of Taxol. Relative mRNA and protein levels were tested using qRT-PCR and western blot, respectively. NPC cell viability and apoptosis were assessed by cell counting kit-8 and flow cytometry analysis, respectively. Cell migration and invasion capacities were measured using transwell assay. Interaction between IGF2BP1 and AKT2 was examined by RNA immunoprecipitation assay. The N6-methyladenosine level of AKT2 was tested using methylated RNA immunoprecipitation-qPCR. IGF2BP1 expression was enhanced in Taxol-resistant NPC cell lines. Knockdown of IGF2BP1 strikingly enhanced the sensitivity of NPC cells to Taxol and repressed the migration and invasion of NPC cells. Mechanistically, IGF2BP1 elevated the expression of AKT2 by increasing its mRNA stability. Furthermore, overexpression of AKT2 reversed the inhibitory roles of IGF2BP1 silence on Taxol resistance and metastasis. Our results indicated that IGF2BP1 knockdown enhanced the sensitivity of NPC cells to Taxol by decreasing the expression of AKT2, implying that IGF2BP1 might be promising candidate target for NPC treatment.
Using Initial Biopsies and Vertical Sections to Improve Trainees' Confidence in Performing Mohs Surgery
Authors: Lee Jennifer , Bae Edward , Yang Eric J. , Iwamoto Satori
Published: March 2024

BACKGROUND

Tissue preservation and tumor clearance are hallmarks of Mohs micrographic surgery, but no standardized method currently exists to guide trainees on how to balance the two.

OBJECTIVE

The authors provided residents and fellows with additional histologic information to enhance their surgical decision-making without changing the standard methodology of Mohs surgery.

METHODS AND MATERIALS

Trainees were provided initial biopsy slides (IS) and frozen vertical sections (VS) of the first Mohs layer. All Mohs layers were excised in standard fashion, and vertically oriented sections were taken from the layer without disturbing the surgical margins to obtain VS. Surveys were used to assess trainees' confidence in performing Mohs surgery with and without these tools.

RESULTS

Trainees reported increased confidence in performing Mohs surgery when they reviewed IS before surgery and viewed VS of the first layer.

CONCLUSION

Reviewing IS and VS improved trainees' confidence in performing Mohs surgery. This additional histological information was obtained while maintaining the usual steps of Mohs surgery. Objective information obtained from IS and VS may explain why trainees' confidence increased using this technique. Both IS and VS can be valuable teaching tools that may enhance trainees' ability to perform Mohs surgery.
An Analysis of Dermatology-Related Red-Light Therapy Patient Questions on Reddit
Authors: Wang Jennifer Y. , Patel Paras , Bitterman David , Jagdeo Jared
Published: March 2024

BACKGROUND

Reddit is one of the world's most popular social media platforms and is increasingly used as a health information resource for patients on topics such as red-light (RL) therapy.

OBJECTIVE

In this article, the authors present an analysis of prevalent patient questions and concerns regarding RL therapy.

METHODS

All posts on the “Hot” page of the r/redlighttherapy subreddit were analyzed and categorized.

RESULTS

A total of 930 questions from 664 posts were analyzed. The most commonly asked question category was related to product recommendations or feedback (29.7%), followed by usage instructions (15.3%), safety and side effects (12.6%), and indications and efficacy (12.3%).

CONCLUSION

Understanding patient concerns and questions about RL, as expressed on online platforms like Reddit, can help clinicians improve patient satisfaction, education, and clinical outcomes. The study offers an innovative approach by using social media to uncover valuable patient insights that might not be easily observable within clinical settings.
Cosmetic Contact Lenses in the United Kingdom: Assessment of Online Regulation and Quality of Consumer Health Information
Authors: Ng Benjamin , Azzopardi Matthew , Ditchfield Alice , Zi Jin , Logeswaran Abison , Hawthorne Imogen , Ting Darren S. J. , Chong Yu Jeat
Published: March 2024

Objectives:

To determine the compliance of online vendors to the UK Opticians Act 1989 Section 27 requirements and safety regulations for cosmetic contact lens (CCL) sales and the quality of online CCL health information.

Methods:

The top 50 websites selling CCLs on each three search engines, namely Google, Yahoo, and Bing, were selected. Duplicates were removed, and the remaining websites were systematically analyzed in February 2023. UK legal authorization for CCL sales was assessed using the Opticians Act Section 27 and safety regulations determined by the presence of Conformité Européene (CE) marking. The quality and reliability of online information was graded using the DISCERN (16–80) and JAMA (0–4) scores by two independent reviewers.

Results:

Forty-seven eligible websites were analyzed. Only six (12.7%) met the UK legal authorization for CCL sales. Forty-nine different brands of CCLs were sold on these websites, of which 13 (26.5%) had no CE marking. The mean DISCERN and JAMA benchmark scores were 26 ± 12.2 and 1.3 ± 0.6, respectively (intraclass correlation scores: 0.99 for both).

Conclusions:

A significant number of websites provide consumers with easy, unsafe, and unregulated access to CCLs. Most online stores do not meet the requirements set out in the Opticians Act for CCL sales in the United Kingdom. A significant number of CCLs lack CE marking, while the average quality of information on websites selling CCLs is poor. Together, these pose a risk to consumers purchasing CCLs from unregulated websites, and therefore, further stringent regulations on the online sales of these products are needed.
“Window of Opportunity” in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports
Authors: Surenkhuu Bayasgalan , Mun Christine S. , Kim Christian , Atassi Nour Yanna , Mun Jessica , Dhall Nikhil , Abdel-Hadi Sarah , Sheth Tanya , Dondeti Priyanka , Bernal Alexandria , Pradeep Anubhav , Rondelli Damiano , Jain Sandeep
Published: March 2024

Objective:

To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the “window of opportunity” concept in oGVHD treatment.

Methods:

Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels.

Results:

In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the “window of opportunity” was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation.

Conclusions:

A “window of opportunity” exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.
Frequency, clinical, and laboratory findings of platelet secretion disorders in patients referred to the specialized coagulation laboratory of the Iranian Blood Transfusion Organization
Authors: Shahbazi Massoumeh , Ahmadinejad Minoo , Mahabadi Vahid Pirhajati , Teimourpour Amir , Golzadeh Khadijeh
Published: March 2024

Objectives

Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO).

Methods

The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 109 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs.

Results

Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD).

Conclusions

The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.
Levodopa–Carbidopa–Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience
Authors: Szász József Attila , Dulamea Adriana Octaviana , Constantin Viorelia Adelina , Mureşanu Dafin Fior , Dumbravă Lăcrămioara Perju , Tiu Cristina , Jianu Dragoş Cătălin , Simu Mihaela , Ene Amalia , Axelerad Any , Falup-Pecurariu Cristian , Lungu Mihaela , Danci Adina Gabriela , Sabau Monica , Strilciuc ştefan , Popescu Bogdan Ovidiu
Published: March 2024

Background:

For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa–entacapone–carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021.

Study Question:

What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD?

Study Design:

A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania.

Measures and Outcomes:

Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted.

Results:

At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day (P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications.

Conclusions:

These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.
Applying Lessons From Ars Moriendi to Foster Dying Well in Acute Care Settings
Authors: Forte Kathy , Larkin Danielle
Published: March 2024

Medical and technological advances have made it possible to keep people alive well beyond what was once possible, leading health care providers to focus on life-sustaining measures rather than questioning the futility of such measures and considering quality of life. In the midst of the struggle to foster dying well in a medicalized environment, acute care nurses may be challenged with shifting the focus to providing optimal end-of-life care because of lack of training, time, and resources. A remedy for the current western societal approach to medicalized dying is to look back in history to a time during the late Middle Ages, when death was an accepted part of medieval life. A literary genre called Ars Moriendi (translated “the art of dying”) was written and illustrated to provide instruction on how to die well and how to care for the dying. Nurses can apply lessons from this text to fulfill the ethical obligation to practice with dignity and provide compassionate end-of-life care. These lessons include helping patients and families identify goals of care and accept finitude, encouraging the participation of loved ones at the bedside, and fostering reconciliation at the end of life.
Improved Short-Term Prognosis of Pediatric Partial-Thickness Burns
Authors: Liu Hailiang , Li Dongjie , Yuan Huageng , Sun Tianjun , Li PengCheng , Cai Zhiwei , Shen Chuan'an
Published: March 2024

Objectives

Early wound management for pediatric patients with partial-thickness burns in the emergency department remains debatable. This study aims to evaluate the value of emergency conservative debridement under topical anesthesia in improving short-term prognosis of pediatric partial-thickness burns.

Methods

This retrospective cohort study enrolled children with partial-thickness thermal burns presenting to the emergency department within 6 hours postburn. All the enrolled patients were divided into 2 groups: the debridement group and the dressing group. The associations between emergency conservative debridement and time to reepithelialization was analyzed by using Kaplan-Meier curves with log rank test and multivariate Cox regression analysis. Moreover, the associations between emergency conservative debridement and in-hospital cost and length of stay were also evaluated.

Results

All baseline characteristics between groups were comparable (allP> 0.05). Emergency conservative debridement under topical anesthesia significantly decreased the median value of time to reepithelialization (13 vs 14 days,P= 0.02). Cox regression analysis showed that emergency conservative debridement significantly improved wound reepithelialization after adjusting for burn size (odds ratio, 4.07; 95% confidence interval, 1.64–10.11;P< 0.01). The mean length of stay of patients receiving conservative wound debridement was lower than that of patients in the wound dressing group (14.3 ± 7.3 vs 18.8 ± 10.4 days,P< 0.01), but not in terms of mean in-hospital cost per 1% total body surface area (2.8 ± 1.9 vs 3.0 ± 2.1 × 103 RMB per 1% total body surface area,P= 0.58).

Conclusions

Emergency conservative debridement of pediatric partial-thickness burns under topical anesthesia significantly improves the wound healing outcomes without increasing health care burden.