bluuebunny/crossref_metadata_2025 huggingface dataset:
From the tobacco industry's uses of science for public relations purposes to the alcohol industry: Tobacco industry documents study
Authors: Bartlett Andrew , Garry Jack , McCambridge Jim
Published: March 2023

Introduction

Associates for Research in Substances of Enjoyment (ARISE) was formed by tobacco companies in the late 1980s designed to counter public health policy development. This study examines the alcohol content of ARISE and the contribution of ARISE to alcohol industry activities in a key period in the globalisation of the alcohol industry, generating insights into the inter‐relationships between the tobacco and alcohol industries in their involvements in policy‐oriented science.

Methods

We systematically searched the UCSF Truth Tobacco Documents Library for information about ARISE, alcohol and the alcohol industry. This material was supplemented with an analysis of the contributions by ARISE associates to one volume in the International Center for Alcohol Policies (ICAP) book series on alcohol and pleasure.

Results

ARISE placed nicotine alongside caffeine, chocolate and other foods, and alcohol as treats which brought pleasure and other benefits. Alcohol was thus intrinsic to the ARISE project for the tobacco industry. This study shows that at a formative moment in the mid‐1990s the major alcohol companies took advantage of the intellectual inheritance and personnel provided by the tobacco industry when establishing ICAP. Key to this was an ICAP conference that resulted in Alcohol and pleasure: A health perspective (1999).

Discussion and Conclusions

Not only did ARISE use alcohol to play a supporting role in a sophisticated tobacco industry strategy, the alcohol industry engaged with ARISE as part of its own strategy. This shows the importance of careful attention to corporate activities on the fringes of peer‐reviewed science.
Access to legal cannabis market in Canada over the four years following non‐medical cannabis legalisation
Authors: Myran Daniel Thomas , Friesen Erik Loewen , Dickson Sarah , Konikoff Lauren , Arora Gaurav , Tanuseputro Peter
Published: March 2023

Introduction

An increasing number of countries are inthe process of legalising non‐medical cannabis. We described how the legal market has changed over the first 4 years following legalisation in Canada.

Methods

We collected longitudinal data on operating status and location of all legal cannabis stores in Canada for the first 4 years following legalisation. We examined per capita stores and sales, store closures, and the drive time between stores and each neighbourhood in Canada. We compared measures between public and private retail systems.

Results

Four years after legalisation, there were 3305 cannabis stores open in Canada (10.6 stores per 100,000 individuals aged 15+ years). Canadians spent $11.85CAD a month on cannabis per individual aged 15+ years, and 59% of neighbourhoods were within a 5‐minute drive of a cannabis store. Over 4 years, per capita stores and per capita sales increased each year by an average of 122.3% and 91.7%, respectively, with larger increases in private versus public systems (4.01 times greater for per capita stores and 2.46 times greater for per capita sales). The annual increase in per capita stores and sales during the first 3 years was 6.0 and 15.5 times greater, respectively, than the increase in the fourth year following legalisation. Over 4 years, 7% of retail store locations permanently closed.

Discussion and Conclusion

The legal cannabis market in Canada expanded enormously over the first 4 years following legalisation, with considerable variation in access between jurisdictions. The rapid retail expansion has implications for evaluation of health impacts of non‐medical legalisation.
Identification of patients with epilepsy using automated electronic health records phenotyping
Authors: Fernandes Marta , Cardall Aidan , Jing Jin , Ge Wendong , Moura Lidia M. V. R. , Jacobs Claire , McGraw Christopher , Zafar Sahar F. , Westover M. Brandon
Published: March 2023

Objective

Unstructured data present in electronic health records (EHR) are a rich source of medical information; however, their abstraction is labor intensive. Automated EHR phenotyping (AEP) can reduce the need for manual chart review. We present an AEP model that is designed to automatically identify patients diagnosed with epilepsy.

Methods

The ground truth for model training and evaluation was captured from a combination of structured questionnaires filled out by physicians for a subset of patients and manual chart review using customized software. Modeling features included indicators of the presence of keywords and phrases in unstructured clinical notes, prescriptions for antiseizure medications (ASMs), International Classification of Diseases (ICD) codes for seizures and epilepsy, number of ASMs and epilepsy‐related ICD codes, age, and sex. Data were randomly divided into training (70%) and hold‐out testing (30%) sets, with distinct patients in each set. We trained regularized logistic regression and an extreme gradient boosting models. Model performance was measured using area under the receiver operating curve (AUROC) and area under the precision–recall curve (AUPRC), with 95% confidence intervals (CI) estimated via bootstrapping.

Results

Our study cohort included 3903 adults drawn from outpatient departments of nine hospitals between February 2015 and June 2022 (mean age = 47 ± 18 years, 57% women, 82% White, 84% non‐Hispanic, 70% with epilepsy). The final models included 285 features, including 246 keywords and phrases captured from 8415 encounters. Both models achieved AUROC and AUPRC of 1 (95% CI = .99–1.00) in the hold‐out testing set.

Significance

A machine learning‐based AEP approach accurately identifies patients with epilepsy from notes, ICD codes, and ASMs. This model can enable large‐scale epilepsy research using EHR databases.
Baseline clinical, hormonal and molecular markers associated with clinical response to IL‐23 antagonism in hidradenitis suppurativa: A prospective cohort study
Authors: Flora A. , Kozera E. K. , Jepsen R. , Gill K. , Xu J. , Frew J. W.
Published: March 2023

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL‐23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL‐23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non‐responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL‐23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL‐17A and IL‐17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL‐23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.
Microbial necromass under global change and implications for soil organic matter
Authors: Hu Junxi , Du Meilin , Chen Jun , Tie Liehua , Zhou Shixing , Buckeridge Kate M. , Cornelissen J. Hans C. , Huang Congde , Kuzyakov Yakov
Published: March 2023

Microbial necromass is an important source and component of soil organic matter (SOM), especially within the most stable pools. Global change factors such as anthropogenic nitrogen (N), phosphorus (P), and potassium (K) inputs, climate warming, elevated atmospheric carbon dioxide (eCO2), and periodic precipitation reduction (drought) strongly affect soil microorganisms and consequently, influence microbial necromass formation. The impacts of these global change factors on microbial necromass are poorly understood despite their critical role in the cycling and sequestration of soil carbon (C) and nutrients. Here, we conducted a meta‐analysis to reveal general patterns of the effects of nutrient addition, warming, eCO2, and drought on amino sugars (biomarkers of microbial necromass) in soils under croplands, forests, and grasslands. Nitrogen addition combined with P and K increased the content of fungal (+21%), bacterial (+22%), and total amino sugars (+9%), consequently leading to increased SOM formation. Nitrogen addition alone increased solely bacterial necromass (+10%) because the decrease of N limitation stimulated bacterial more than fungal growth. Warming increased bacterial necromass, because bacteria have competitive advantages at high temperatures compared to fungi. Other global change factors (P and NP addition, eCO2, and drought) had minor effects on microbial necromass because of: (i) compensation of the impacts by opposite processes, and (ii) the short duration of experiments compared to the slow microbial necromass turnover. Future studies should focus on: (i) the stronger response of bacterial necromass to N addition and warming compared to that of fungi, and (ii) the increased microbial necromass contribution to SOM accumulation and stability under NPK fertilization, and thereby for negative feedback to climate warming.
Incidental left atrial appendage isolation after catheter ablation of persistent atrial fibrillation: Mechanisms and long‐term risk of thromboembolism
Authors: Ghannam Michael , Jongnarangsin Krit , Emami Hamed , Yokokawa Miki , Liang Jackson J. , Saeed Mohammed , Oral Hakan , Morady Fred , Chugh Aman
Published: March 2023

Introduction

Incidental left atrial appendage (LAA) isolation may occur during radiofrequency ablation of persistent atrial fibrillation (AF). The study aims to describe the mechanisms and long‐term thromboembolic risk related to incidental LAA isolation.

Methods

Patients who experienced incidental LAA isolation after AF ablation were included. Culprit sites where ablation resulted in LAA isolation were identified. Thromboembolic risk despite oral anticoagulation (OAC) was compared to that in a propensity‐matched control group without LAA isolation.

Results

Forty‐one patients with LAA isolation, and 82 matched patients without LAA isolation were included. The patient age, ejection fraction, LA diameter, and CHA2DS2‐VASc score were 64 ± 11 years, 55 ± 12%, 45.0 ± 7 mm and 2.62 ± 1.5, respectively. Culprit sites included the LAA base, mitral isthmus, inferior LA, Bachmann′s bundle, coronary sinus, and Marshall vein. After 4.2 ± 3.6 years follow‐up, thromboembolism occurred in 7 of 41 patients (17%) with LAA isolation versus 3 of 82 patients (4%) without isolation (log rank p < .009, HR 5.14, 95% CI [1.32–19.94], p = .02). Patients with and without thromboembolism had similar CHA2DS2‐VASc scores (2.65 ± 1.3 vs. 2.71 ± 0.76, p = .89). Thromboembolism occurred during noncompliance with or temporary discontinuation of OAC in four of the seven patients.

Conclusions

Incidental LAA isolation may occur during ablation of atrial arrhythmias in the vicinity of, or even at sites remote from the appendage. Patients with incidental LAA isolation had higher rates of thromboembolism compared to patients without isolation. Since thromboembolism may occur despite prescription for OAC, the risks of LAA isolation must be weighed against clinical benefit and appendage occlusion devices should be considered in vulnerable patients.
Atrial fibrillation ablation outcome prediction with a machine learning fusion framework incorporating cardiac computed tomography
Authors: Razeghi Orod , Kapoor Ridhima , Alhusseini Mahmood I. , Fazal Muhammad , Tang Siyi , Roney Caroline H. , Rogers Albert J. , Lee Anson , Wang Paul J. , Clopton Paul , Rubin Daniel L. , Narayan Sanjiv M. , Niederer Steven , Baykaner Tina
Published: March 2023

Background

Structural changes in the left atrium (LA) modestly predict outcomes in patients undergoing catheter ablation for atrial fibrillation (AF). Machine learning (ML) is a promising approach to personalize AF management strategies and improve predictive risk models after catheter ablation by integrating atrial geometry from cardiac computed tomography (CT) scans and patient‐specific clinical data. We hypothesized that ML approaches based on a patient's specific data can identify responders to AF ablation.

Methods

Consecutive patients undergoing AF ablation, who had preprocedural CT scans, demographics, and 1‐year follow‐up data, were included in the study for a retrospective analysis. The inputs of models were CT‐derived morphological features from left atrial segmentation (including the shape, volume of the LA, LA appendage, and pulmonary vein ostia) along with deep features learned directly from raw CT images, and clinical data. These were merged intelligently in a framework to learn their individual importance and produce the optimal classification.

Results

Three hundred twenty‐one patients (64.2 ± 10.6 years, 69% male, 40% paroxysmal AF) were analyzed. Post 10‐fold nested cross‐validation, the model trained to intelligently merge and learn appropriate weights for clinical, morphological, and imaging data (AUC 0.821) outperformed those trained solely on clinical data (AUC 0.626), morphological (AUC 0.659), or imaging data (AUC 0.764).

Conclusion

Our ML approach provides an end‐to‐end automated technique to predict AF ablation outcomes using deep learning from CT images, derived structural properties of LA, augmented by incorporation of clinical data in a merged ML framework. This can help develop personalized strategies for patient selection in invasive management of AF.
Associations of sleep quality with the skeletal muscle strength in patients with type 2 diabetes with poor glycemic control
Authors: Hayashi Takanori , Wada Nobuhiro , Kubota Tetsuya , Koizumi Chie , Sakurai Yoshitaka , Aihara Masakazu , Usami Satoshi , Yamauchi Toshimasa , Kubota Naoto
Published: March 2023

Aims/Introduction

Patients with type 2 diabetes mellitus are reported to be at a high risk for sarcopenia, and are known to have a poorer sleep quality. However, the association between sleep quality and skeletal muscle in patients with type 2 diabetes mellitus is not yet precisely understood.

Materials and Methods

A total of 110 inpatients with type 2 diabetes mellitus aged 40–90 years were enrolled. The sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Skeletal muscle mass was measured using bioelectrical impedance analysis. Muscle strength was evaluated by measuring the grip strength. We also performed dietary surveys and measurements of the plasma amino acid levels.

Results

A high total score on the PSQI was significantly associated with reduced muscle strength, and the association persisted even after adjustments for confounders. On the other hand, adjusted analysis did not reveal any significant associations between the PSQI total score and the skeletal muscle mass. In regard to the associations with subscores of the PSQI, the scores for sleep latency, sleep efficiency, and daytime dysfunction were significantly negatively associated with the muscle strength. Although poor sleep quality was associated with a high confectionery intake and low plasma arginine, citrulline, and ornithine levels, neither confectionery intake levels nor the plasma levels of these amino acids was associated with the muscle strength.

Conclusions

Our study revealed a significant association between the sleep quality and muscle strength in patients with type 2 diabetes mellitus. These results suggest that poor sleep quality is an important risk factor for sarcopenia in patients with type 2 diabetes mellitus.
Evaluation of an early flood warning system in Bamako (Mali): Lessons learned from the flood of May 2019
Authors: Chahinian Nanée , Alcoba Matias , Dembélé Ndji dit Jacques , Cazenave Fréderic , Bouvier Christophe
Published: March 2023

Devastating floods have plagued many West African cities in the past decades. In an attempt to reduce flood damage in Bamako (Mali), an early warning system (EWS) demonstrator (Raincell App) was developed for flash floods. On 16 May 2019, while the demonstrator was partially operational, an intense rainfall event led to devastating floods. We carried out an experience feedback on this flood event by comparing EWS simulations to the results of a field survey. Given the synoptic situation and the rapid development pattern of the storm, none of the global forecasting systems were able to foresee its occurrence and magnitude. The hydrological model developed as part of the demonstrator correctly identified most of the locations where overbank flow occurred. In the absence of data, the predicted discharge and volume values could not be validated. However, they are realistic based on the water levels reported in the Post‐Disaster Needs Assessment report. It would be advisable to couple it to a two‐dimensional hydraulic model and add discharge and water level monitoring to the already existing rainfall surveillance scheme to further improve the system's performance. Increasing the local population's awareness of the dangers of clogged waterways is also mandatory.
Orexin 2 receptor‐selective agonist danavorexton (TAK‐925) promotes wakefulness in non‐human primates and healthy individuals
Authors: Evans Rebecca , Kimura Haruhide , Nakashima Masato , Ishikawa Takashi , Yukitake Hiroshi , Suzuki Motohisa , Hazel James , Faessel Hélène , Wu Jingtao , Hang Yaming , Alexander Robert , Rosen Laura , Hartman Deborah S. , Ratti Emiliangelo
Published: March 2023

The orexin 2 receptor‐selective agonist danavorexton (TAK‐925) has been shown to produce wake‐promoting effects in wild‐type mice, narcolepsy‐model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake‐promoting effects of danavorexton in non‐human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (p < 0.05 at 0.1 mg kg−1, and p < 0.001 at 1 mg kg−1 and 10 mg kg−1) and cynomolgus monkeys (p ≤ 0.05 at 1 mg kg−1 and 3 mg kg−1). In a phase 1b crossover, randomized, double‐blind, placebo‐controlled and active‐controlled study in sleep‐deprived healthy participants (ClinicalTrials.gov identifier: NCT03522506), modafinil 300 mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44 mg and danavorexton 112 mg showed statistically superior wake‐promoting effects to placebo (n = 18). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44 mg, danavorexton 112 mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least‐squares mean difference from placebo in average sleep latency was 16.8 min with danavorexton 44 mg and 30.2 min with danavorexton 112 mg (both p < 0.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44 mg, p = 0.010; danavorexton 112 mg, p < 0.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non‐human primates and healthy individuals during their sleep phase.
Prediction of outcome after ligation or thin film banding of extrahepatic shunts, based on plasma albumin concentration and hematologic expression of 8 target genes in 85 dogs
Authors: van Blokland‐Post Krista , Weber Maarten F. , van Wolferen Monique E. , Penning Louis C. , van Sluijs Freek J. , Kummeling Anne
Published: March 2023

Background

In dogs with a congenital extrahepatic portosystemic shunt (EHPSS), outcome after surgical attenuation is difficult to predict.

Objectives

Develop a minimally invasive test to predict outcome after surgical EHPSS attenuation and establish risk factors for postattenuation seizures (PAS).

Animals

Eighty‐five client‐owned dogs referred for surgical attenuation of a single EHPSS.

Methods

mRNA expression of 8 genes was measured in preoperatively collected venous blood samples. Outcome was determined at a median of 92 days (range, 26‐208) postoperatively by evaluating clinical performance, blood test results and abdominal ultrasonography. Multivariable logistic regression was used to construct models predicting clinical and complete recovery. The associations between putative predictors and PAS were studied using univariable analyses.

Results

Five of 85 dogs developed PAS. Risk factors were age, white blood cell (WBC) count and expression of hepatocyte growth factor activator and LysM and putative peptidoglycan‐binding domain‐containing protein 2. Clinical recovery was observed in 72 of 85 dogs and complete recovery in 51 of 80 dogs (median follow‐up, 92 days). The model predicting clinical recovery included albumin, WBC count, and methionine adenosyltransferase 2 alpha (MAT2α) expression, whereas the model predicting complete recovery included albumin, and connective tissue growth factor precursor and MAT2α expression. The areas under the receiver operating characteristic curves were 0.886 (95% confidence interval [CI]: 0.783, 0.990) and 0.794 (95% CI: 0.686, 0.902), respectively.

Conclusions and Clinical Importance

Two models were constructed for predicting outcome after EHPSS attenuation using venous blood samples. The model predicting clinical recovery showed the best diagnostic properties. Clinical application requires further validation.
Widespread gene flow following range expansion in Anna's Hummingbird
Authors: Adams Nicole E. , Bandivadekar Ruta R. , Battey C. J. , Clark Michael W. , Epperly Kevin , Ruegg Kristen , Tell Lisa A. , Bay Rachael A.
Published: March 2023

Anthropogenic changes have altered the historical distributions of many North American taxa. As environments shift, ecological and evolutionary processes can combine in complex ways to either stimulate or inhibit range expansion. Here, we examined the role of evolution in a rapid range expansion whose ecological context has been well‐documented, Anna's Hummingbird (Calypte anna). Previous studies have suggested that theC. annarange expansion is the result of an ecological release facilitated by human‐mediated environmental changes, where access to new food sources have allowed further filling of the abiotic niche. We examined the role of gene flow and adaptation during range expansion from their native California breeding range, north into Canada and east into New Mexico and Texas, USA. Using low coverage whole genome sequencing we found high genetic diversity, low divergence, and little evidence of selection on the northern and eastern expansion fronts. Additionally, there are no clear barriers to gene flow across the native and expanded range. The lack of selective signals between core and expanded ranges could reflect (i) an absence of novel selection pressure in the expanded range (supporting the ecological release hypothesis), (ii) swamping of adaptive variation due to high gene flow, or (iii) limitations of genome scans for detecting small shifts in allele frequencies across many loci. Nevertheless, our results provide an example where strong selection is not apparent during a rapid, contemporary range shift.
Comparative phylogeography reveals the demographic patterns of neotropical ancient mountain species
Authors: Dantas‐Queiroz Marcos Vinicius , Hurbath Fernanda , de Russo Godoy Fernanda Maria , Lanna Flávia Mol , Versieux Leonardo M. , Palma‐Silva Clarisse
Published: March 2023

Mountains are renowned for their bountiful biodiversity. Explanations on the origin of such abundant life are usually regarded to their orogenic history. However, ancient mountain systems with geological stability also exhibit astounding levels of number of species and endemism, as illustrated by the Brazilian Quartzitic Mountains (BQM) in Eastern South America. Thus, cycles of climatic changes over the last couple million years are usually assumed to play an important role in the origin of mountainous biota. These climatic oscillations potentially isolated and reconnected adjacent populations, a phenomenon known as flickering connectivity, accelerating speciation events due to range fragmentation, dispersion, secondary contact, and hybridization. To evaluate the role of the climatic fluctuations on the diversification of the BQM biota, we estimated the ancient demography of distinct endemic species of animals and plants using hierarchical approximate Bayesian computation analysis and Ecological Niche Modelling. Additionally, we evaluated if climatic oscillations have driven a genetic spatial congruence in the genetic structure of codistributed species from the Espinhaço Range, one of the main BQM areas. Our results show that the majority of plant lineages underwent a synchronous expansion over the Last Glacial Maximum (LGM, c. 21 thousand years ago), although we could not obtain a clear demographic pattern for the animal lineages. We also obtained a signal of a congruent phylogeographic break between lineages endemic to the Espinhaço Range, suggesting how ancient climatic oscillations might have driven the evolutionary history of the Espinhaço's biota.
Mathematical pluralism
Authors: Zalta Edward N.
Published: March 2023

Mathematical pluralism can take one of three forms: (1) every consistent mathematical theory consists of truths about its own domain of individuals and relations; (2) every mathematical theory, consistent or inconsistent, consists of truths about its own (possibly uninteresting) domain of individuals and relations; and (3) the principal philosophies of mathematics are each based upon an insight or truth about the nature of mathematics that can be validated. (1) includes the multiverse approach to set theory. (2) helps us to understand the significance of the distinguished non‐logical individual and relation terms of even inconsistent theories. (3) is a metaphilosophical form of mathematical pluralism and hasn't been discussed in the literature. In what follows, I show how the analysis of theoretical mathematics in object theory exhibits all three forms of mathematical pluralism.
Tet methylcytosine dioxygenase 1 modulates Porphyromonas gingivalis–triggered pyroptosis by regulating glycolysis in cementoblasts
Authors: Peng Yan , Wang Huiyi , Huang Xin , Liu Heyu , Xiao Junhong , Wang Chuan , Ma Li , Wang Xiaoxuan , Cao Zhengguo
Published: March 2023

Porphyromonas gingivalis is involved in the pathogenesis of multiple polymicrobial biofilm–induced inflammatory diseases, including apical periodontitis, and it triggers pyroptosis accompanied by robust inflammatory responses. Tet methylcytosine dioxygenase 1 (TET1), an epigenetic modifier enzyme, has been is correlated with inflammation, though an association of TET1 and P. gingivalis–related pyroptosis in cementoblasts and the molecular mechanisms has not been shown. Our study here demonstrated that P. gingivalis downregulated Tet1 expression and elicited CASP11‐ and GSDMD‐dependent pyroptosis. Additionally, Tet1 mRNA silencing in cementoblasts appeared to result in a more severe pyroptotic phenotype, where levels of CASP11 and GSDMD cleavage, lactate dehydrogenase release, and IL‐1β and IL‐18 production were significantly increased. Moreover, Tet1 overexpression resulted in blockade of pyroptosis activation accompanied by inflammation moderation. Further analyses revealed that TET1 modulated glycolysis, confirmed by the application of the specific inhibitor 2‐deoxy‐d‐glucose (2‐DG). The pyroptosis phenotype enhanced by Tet1 silencing was moderated by 2‐DG upon P. gingivalis invasion. Taken together, these data show the effects and underlying mechanisms of TET1 on pyroptosis and inflammatory phenotype induced by P. gingivalis in cementoblasts, and provides insight into the involvement of P. gingivalis in apical periodontitis and, possibly, other inflammatory diseases.
Stenomitos terricola sp. nov. (Leptolyngbyaceae, Cyanobacteria) from the moist soil of Mt. Gwanggyo, Republic of Korea
Authors: Lee Nam‐Ju , Kim Do‐Hyun , Lee Ok‐Min
Published: March 2023

Stenomitos terricola FBCC‐A190 was collected from soils around the trees of Mt. Gwanggyo, located in Yeongtong‐gu, Suwon‐si, Gyeonggi‐do. S. terricola FBCC‐A190 is a thin and simple filament with a cell length that is longer than its width. It has a thin and firm sheath, exhibiting a blue‐green color. Species belonging to genus Stenomitos is semi‐cryptic species with slight morphological differences from each other. They were confirmed as Stenomitos species by analysis using 16S rRNA and 16S–23S ITS. A monophyletic cluster was formed with the previously reported genus Stenomitos, with 16S rRNA gene sequences sharing similarities of 95.9–97.9% except for S. pantisii TAU‐MAC 4318. In addition, 16S–23S ITS gene sequencing showed tRNAAla, tRNAIle and V2, similar to the previously reported genus Stenomitos. From these results, Stenomitos terricola sp. nov. was proposed as a new species belonging to genus Stenomitos.
The relationship between Th1/Th2 cytokine polarization and milk composition in the postnatal period in Kyrgyz mares and foals
Authors: Istanbullugil Fatih R. , Risvanli Ali , Salikov Ruslan , Bayraktar Metin , Kadiraliyeva Nariste , Zhunushova Aidai , Yilmaz Oznur , Yuksel Burak F. , Turanli Mert , Uz Muhammet , Asinbekovic Mirbek I.
Published: March 2023

Immune compatibility between mare and foal is one of the important topics of reproductive immunology. At this point, although there are many studies on antibodies, there are not many publications on the relationship between the cytokine levels of mare, foal and milk and the effects of milk composition on this relationship. Here we investigate the relationship between Th1/Th2 cytokine balance and milk composition in Kyrgyz mares and foals. Samples were taken soon after the foal was born and on days 5, 10 and 20 after birth. Th1 (IFN‐γ, IL‐2, TNF‐α) and Th2 (IL‐4, IL‐5, IL‐10) cytokine levels in blood samples were measured using a commercial ELISA kit. Dry matter, fat, protein and non‐fat dry matter ratios were determined in the mare's milk and colostrum. We detected no Th1/Th2 polarization in the mare's milk on the day of the foal's birth (day 0) and day 10, but there was Th1 polarization on day 5 and Th2 cytokine polarization on day 20. There was no polarization in the blood sera of the mares on days 0, 5, and 10, and Th1 cytokine polarization was also detected on day 20. We detected no Th1/Th2 cytokine polarization in the blood sera of the foals on any of the days. Dry matter (19.66 ± 0.39%), protein (16.56 ± 0.18%), fat (2.13 ± 0.17), and non‐fat dry matter (17.59 ± 0.44%) were higher in colostrum than the other days. When the correlations between cytokine levels in milk samples and milk composition were examined, there was a positive correlation between IL‐5 level and protein ratio on day 10. We detected a positive correlation between IL‐2 level and the fat rate on day 20. There was a positive correlation between the IL‐2 level and the non‐fat dry matter ratio on day 20. Further studies are now needed to determine the relationship between the changes in the composition of mare's milk in the postnatal period and Th1/Th2 cytokine polarization in mares and foals at the time of birth and in the postnatal period. Our finding that protein and fat ratios in mare's milk in the postnatal period are positively correlated with IL‐2 levels should be considered in terms of foal and human nutrition.
High preoperative bradykinin level is a risk factor for severe postoperative hypoxaemia in acute aortic dissection surgery
Authors: Guan XinLiang , Li Lei , Li JinZhang , Jiang WenJian , Li HaiYang , Wang XiaoLong , Han Lu , Liu YuYong , Gong Ming , Zhang HongJia
Published: March 2023

Severe hypoxaemia after cardiac surgery is associated with serious complications and a high risk of mortality. The purpose of this study is to investigate the independent risk factors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. We collected 77 patients with acute Stanford type A aortic dissection who underwent surgical treatment. The primary outcome was severe postoperative hypoxaemia (PaO2/FiO2 ≤ 100 mmHg), and a multivariate logistic regression analysis was performed to assess the independent predictors of risk for this. A mixed‐effects analysis of variance model and a receiver operating characteristic (ROC) curve were generated to evaluate the predictive probabilities of risk factors for severe postoperative hypoxaemia. A total of 36.4% of patients developed severe postoperative hypoxaemia. The multivariate logistic regression analysis identified high preoperative bradykinin level (odds ratio (OR) = 55.918, P < 0.001) and increased body mass index (BMI; OR = 1.292, P = 0.032) as independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. The mixed‐effect analysis of variance model and ROC curve indicated that high preoperative bradykinin level and BMI were significant predictors of severe postoperative hypoxaemia (area under the ROC curve = 0.834 and 0.764, respectively). High preoperative bradykinin levels and obesity were independent risk factors for severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high levels of bradykinin before surgery, clinicians should actively take measures to block bradykinin‐mediated inflammatory reactions.
Novel mutation causing Zellweger syndrome
Authors: Adiyapatham Sasidharan , Murugesan Ambalakkuthan
Published: March 2023

Genetic conditions have varied presentations, and one of them is the association with multiple malformation syndrome (MMS), which has a high mortality rate in the immediate postnatal period. Here, we describe a neonate born with multiple anomalies—wide anterior and posterior fontanelle, metopic suture, flat nasal bridge, hypertelorism, low set dysplastic ears, corneal cloudiness, micrognathia, webbed neck, simian crease, undescended testis, hypospadias, congenital talipes equinovarus, hypoplastic inferior cerebellar vermis, poor reflexes, hypotonia and ventricular septal defect. There was a history of sibling death with similar malformations, pointing towards a genetic aetiology. Clinical exome sequencing yielded the diagnosis of Zellweger syndrome with a rare mutation inPEX-19gene. Inherited metabolic syndromes frequently masquerade as malformations, but family history of an affected sibling and clinical suspicion aided diagnosis of the infant.
Femoral head osteochondritis dissecans in a child
Authors: Hernandez Sean G , McQueen Ryan G , Erickson John B
Published: March 2023

This case report describes an early-adolescent boy with an osteochondritis dissecans (OCD) lesion of the left femoral head secondary to significant acetabular dysplasia and coxa valga of the proximal femur. Patient underwent left proximal femur varus osteotomy. Follow-up imaging demonstrates healing and resolution of the OCD lesion. Future plan for left hip is periacetabular osteotomy, following triradiate cartilage closure, to correct acetabular dysplasia. The aim of this case report is to support clinicians in the assessment and treatment of this rare condition.
Systemic sclerosis following COVID-19 infection with recurrent corticosteroid-induced scleroderma renal crisis
Authors: Carroll Mitchell , Nagarajah Vanitha , Campbell Sian
Published: March 2023

Systemic sclerosis is a complex multisystem connective tissue disease resulting in fibrosis of the skin and internal organs. Exposure to corticosteroids can trigger scleroderma renal crisis, a life-threatening complication of the disease. Autoimmune disease following infection with COVID-19 is being increasingly recognised. The mechanisms of post-COVID-19 autoimmunity are likely multifactorial, involving immune dysregulation, molecular mimicry and the development of cross-reactive antibodies. There are currently only two reported cases of systemic sclerosis occurring post-COVID-19 infection.

We present the case of a female patient who developed systemic sclerosis post-COVID-19 infection. Following exposure to corticosteroids, the patient developed scleroderma renal crisis complicated by thrombotic microangiopathy, seizures and acute renal failure. Despite an antibody profile not typically associated with renal crisis (anti-topoisomerase positive, anti-RNA-polymerase III negative), the patient developed recurrent renal crisis with repeated exposure to corticosteroid therapy, highlighting the risk of steroid use in all patients with systemic sclerosis.
Type 2 hyper-IgM syndrome with a rare variant of AICDA gene mutation in a young woman
Authors: Prakash Prithivi Raaj , Gupta Gaurav , Aggarwal Mukul , Baitha Upendra
Published: March 2023

We report the case of a woman in her early 20s with a history of recurrent infection, atopic dermatitis, filariasis and bilateral purulent ear discharge since childhood with tonsillar enlargement on examination. She was started on supportive care and evaluated for primary immunodeficiency disease. Blood investigations revealed increased IgM levels with reduced IgG, IgA and IgE levels. Radiological imaging of the chest revealed bilateral bronchiectasis. Otoscopic examination showed features suggestive of chronic suppurative otitis media. Next-generation sequencing identified homozygous single base pair deletion in exon 2 of the activation-induced cytidine deaminase gene. Thus, a diagnosis of hyper-IgM syndrome type 2 was confirmed. The patient was started on monthly intravenous immunoglobulin replacement therapy and is currently symptomatically better, and she remains under regular follow-up.
Isolated renal mucormycosis masquerading as emphysematous pyelonephritis
Authors: Narayanaswamy Supradeep , Goradia Rajvi , Bellurkar Amit , Patwardhan Sujata
Published: March 2023

Mucormycosis is an acute, life-threatening infection and isolated renal involvement is rare. Due to the angioinvasive nature of the disease, it is rapidly progressive and can be lethal if not managed expeditiously. In patients with underlying conditions of immunosuppression, diabetes mellitus, transplantation, COVID-19, intravenous drug and substance use and pyelonephritis, which is unable to be controlled via regular antibiotics, mucormycosis must be considered on the differential and antifungals must be empirically started. Most cases are often diagnosed on histopathology, which causes delayed treatment and resolution. We present a case of emphysematous pyelonephritis diagnosed on imaging and was later found to have mucormycosis on histopathological examination.
Fundus topographical distribution patterns of ocular toxoplasmosis
Authors: Hasanreisoglu Murat , Halim Muhammad Sohail , Cakar Ozdal Pinar , Ormaechea Maria Soledad , Kesim Cem , Ozdemir Huseyin Baran , Uludag Gunay , Sredar Nripun , Cankurtaran Mahmut , Liu Xiaoxuan , Denniston Alastair Keith , Rudzinski Marcelo N. , Colombero Daniel N. , Schlaen Bernardo Ariel , Keane Pearse Andrew , Pavesio Carlos , Nguyen Quan Dong
Published: March 2023

Background

To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions.

Methods

In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed.

Results

984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola.

Conclusion

The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease.
Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma
Authors: Luo Yingxiu , Xu Mingpeng , Yang Ludi , Yao Yiran , Berry Jesse L , Xu Liya , Wen Xuyang , He Xiaoyu , Han Minglei , Fan Xianqun , Fan Jiayan , Jia Renbing
Published: March 2023

Background

This study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history.

Methods

Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors.

Results

Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043).

Discussion

Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically.

Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.
Association between tea consumption and glucose metabolism and insulin secretion in the Shanghai High-risk Diabetic Screen (SHiDS) study
Authors: Zhang Yinan , Bian Zhouliang , Lu Huijuan , Wang Lili , Xu Jinfang , Wang Congrong
Published: March 2023

Introduction

The relationship between tea consumption and glucose metabolism remains controversial. This study investigated the associations of tea consumption with impaired glucose regulation, insulin secretion and sensitivity in Shanghai High-risk Diabetic Screen project.

Research design and methods

A total of 2337 Chinese subjects were enrolled in the study from 2014 to 2019. Each participant conducted a 75 g oral glucose tolerance test (OGTT) with five-point glucose and insulin level examined. They also completed a nurse-administered standard questionnaire including tea, coffee, and alcohol consumption, smoking habit, physical activity, education, sleep quality, etc.

Results

The result showed that tea consumption was positively associated with plasma glucose levels during OGTT after adjusting for confounder (Ps <0.05) and was associated with worsening glucose tolerance (OR 1.21, 95% CI 1.01–1.44; p=0.034). Strong tea consumption or long-term tea intake (>10 years) had an increased risk of glucose intolerance (all p<0.05). These associations did not vary in participants drinking green tea. In addition, insulin secretion indexes were decreased 7.0%–13.0% in tea consumption group. Logistic regression analysis showed that tea consumption was independently associated with lower insulin secretion (homeostasis model assessment of β-cell function (HOMA-β) (OR 0.81, 95% CI 0.68–0.97; p=0.021); Stumvoll first-phase index (OR 0.81, 95% CI 0.68–0.97; p=0.020)) in a fully adjusted model. Green tea consumption showed a negative association with insulin secretion (HOMA-β (OR 0.77, 95% CI 0.62–0.96; p=0.019)).

Conclusions

Tea intake is associated with an increased risk of glucose intolerance in a large high-risk diabetic Chinese population. Habitual tea consumption subjects might have lower pancreatic β-cell function.
Primary placement of low-profile or ‘button’ versus traditional balloon-retention radiologically inserted gastrostomy catheters in adults: a retrospective review
Authors: Al-Balas Hassan , Metwalli Zeyad , Burney Iftikhar , Sada David
Published: March 2023

Objective

De novo percutaneous placement of radiologically inserted low-profile or ‘button-type’ gastrostomy catheters (LPG) is infrequently reported in adults. This study compares the safety and clinical outcomes of primary percutaneous placement of LPG catheters and traditional balloon-retention gastrostomy catheters (TG) using image guidance at a single institution.

Design

This was a retrospective, single-institution review comparing initial LPG and TG radiologically inserted catheter placements in a 36-month time period. The age, gender, indication, catheter type and method of anaesthesia of 139 consecutive initial gastrostomy placement procedures were recorded. Total catheter days without intervention, major and minor complications, reasons for reintervention, and procedure fluoroscopy times were compared.

Results

During the 36-month study period, 61 LPG and 78 TG catheters were placed. Mean total catheter days prior to intervention was 137 days in the LPG group and 128 days in the TG group (p=0.70). Minor complications including cellulitis, pericatheter leakage and early catheter occlusion occurred in 4.9% (3/61) in the LPG group and 9% (7/78) in the TG group (p=0.5). Major complications including early catheter dislodgement and bleeding requiring transfusion (in one patient) occurred in 4.9% (3/61) in the LPG group and 7.7% (6/78) in the TG group (p=0.4). Procedure fluoroscopy time was lower in the LPG group (2.56 min) compared with the TG group (4.21 min) (p<0.005).

Conclusion

Primary placement of low-profile or ‘button-type’ gastrostomy catheters is technically feasible with a low complication rate similar to that of traditional radiologically inserted gastrostomy catheters.