bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication management in long-term care: using evidence generated from real-world data to effect policy change in the Australian setting
Authors: Sluggett Janet K , Inacio Maria C , Caughey Gillian E
Published: June 2024

Older individuals residing in long-term care facilities (LTCFs) are often living with multimorbidity and exposed to polypharmacy, and many experience medication-related problems. Because randomized controlled trials seldom include individuals in LTCFs, pharmacoepidemiological studies using real-world data are essential sources of new knowledge on the utilization, safety, and effectiveness of pharmacotherapies and related health outcomes in this population. In this commentary, we discuss recent pharmacoepidemiological research undertaken to support the investigations and recommendations of a landmark public inquiry into the quality and safety of care provided in the approximately 3000 Australian LTCFs that house more than 240 000 residents annually, which informed subsequent national medication-related policy reforms. Suitable sources of real-world data for pharmacoepidemiological studies in long-term care cohorts and methodological considerations are also discussed.

This article is part of a Special Collection on Pharmacoepidemiology.
A propensity score approach and a partitioned approach for the self-controlled case series design to evaluate safety of a 2-dose vaccine series: application to myocarditis/pericarditis following mRNA COVID-19 vaccination
Authors: Xu Stanley , Sy Lina S , Han Bing , Hong Vennis , Bruxvoort Katia J , Lewin Bruno , Holmquist Kimberly J , Qian Lei
Published: June 2024

The assumption that serious adverse events (SAEs) do not affect subsequent exposure might not hold when evaluating 2-dose vaccine safety through a self-controlled case series (SCCS) design. To address this, we developed: (1) propensity score SCCS (PS-SCCS) using a propensity score model involving SAEs during the risk interval after dose 1 (${R}_1$), and (2) partitioned SCCS (P-SCCS) estimating relative incidence (RI) separately for doses 1 and 2. In simulations, both provided unbiased RIs. Conversely, standard SCCS overestimated RI after dose 2. We applied these approaches to assess myocarditis/pericarditis risks after 2-dose mRNA coronavirus disease 2019 (COVID-19) vaccination in 12- to 39-year-olds. For BNT162b2, PS-SCCS yielded RIs of 1.85 (95% CI, 0.75-4.59) and 11.05 (95% CI, 6.53-18.68) 14 days after doses 1 and 2 respectively; standard SCCS provided similar RI after dose 1 and RI of 12.92 (95% CI, 7.56-22.09) after dose 2. For mRNA-1273, standard SCCS showed RIs of 1.96 (95% CI, 0.56-6.91) after dose 1 and 7.87 (95% CI, 3.33-18.57) after dose 2. As no mRNA-1273 recipients with SAEs during ${R}_1$ received dose 2, P-SCCS was used, yielding similar RI after dose 1 and RI of 6.48 (95% CI, 2.83-14.83) after dose 2. mRNA vaccines were associated with elevated myocarditis/pericarditis risks following dose 2 in 12- to 39-year-olds.
The impact of different strategies for modeling associations between medications at low doses and health outcomes: a simulation study and practical application to postpartum opioid use
Authors: Spieker Andrew J , Adgent Margaret A , Osmundson Sarah S , Phillips Sharon E , Mitchel Jr Ed , Leech Ashley A , Grijalva Carlos G , Wiese Andrew D
Published: June 2024

Pharmacoepidemiologic studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a nonlinear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose–response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose–response curves at low and infrequently used doses in the setting of no safe dose (“spike-at-zero” and “slab-and-spline”). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naive women with a vaginal delivery enrolled in Tennessee’s Medicaid program (United States, 2007-2014).
The AIA 1951 Lithographs: Contesting National Identity in Intermodern Prints
Authors: Clegg Michael
Published: June 2024

This essay examines the Artists’ International Association 1951 Lithographs, a series of prints produced to mark the Festival of Britain. It argues that these works, like others from the period, have received limited art-historical attention due to the dominance of a teleological narrative whose values are rooted in subsequent art movements. It proposes an alternative, ‘intermodern’ framing that emphasises continuity with pre-war ideals of democratising art ownership, and encourages historically informed analysis of the series’ images. In line with recent scholarship on the Festival of Britain, the interpretations offered show the series projecting an idea of Britain as harmonious, egalitarian and optimistic, in a way that supported the Labour government’s programme of social democratic reform. However, some images are also understood as manifesting ideological division and class conflict, as well as late imperial anxiety, in a way that ran counter to the Festival’s conceit of national harmony.
KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution
Authors: Reis de Andrade Joana , Scourfield Edward , Peswani-Sajnani Shilpa Lekhraj , Poulton Kate , ap Rees Thomas , Khooshemehri Paniz , Doherty George , Ong Stephanie , Ivan Iustina-Francisca , Goudarzi Negin , Gardiner Isaac , Caine Estelle , Maguire Thomas J A , Leightley Daniel , Torrico Luis , Gasulla Alex , Menendez-Vazquez Angel , Ortega-Prieto Ana Maria , Pickering Suzanne , Jimenez-Guardeño Jose M , Batra Rahul , Rubinchik Sona , Tan Aaron V F , Griffin Amy , Sherrin David , Papaioannou Stelios , Trouillet Celine , Mischo Hannah E , Giralt Victoriano , Wilson Samantha , Kirk Martin , Neil Stuart J D , Galao Rui Pedro , Martindale Jo , Curtis Charles , Zuckerman Mark , Razavi Reza , Malim Michael H , Martinez-Nunez Rocio T
Published: June 2024

Rapid and accessible testing was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. Here, we describe our learnings and provide our blueprint for launching diagnostic laboratories, particularly in low-resource settings. Between December 2020 and July 2022, we performed 158277 PCRs for our staff, students, and their household contacts, free of charge. Our average turnaround time was 16 h and 37 min from user registration to result delivery. KCL TEST combined open-source automation and in-house non-commercial reagents, which allows for rapid implementation and repurposing. Importantly, our data parallel those of the UK Office for National Statistics, though we detected a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing as an important measure for decreasing outbreaks and providing safe working spaces. Universities can therefore provide agile, resilient, and accurate testing that reflects the infection rate and trend of the general population. Our findings call for the early integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test, and accommodate efficient low-cost pipelines.
Plant–microbial fuel cell for electrical generation through living plants: an internal resistance insight into the plant species used
Authors: Martinez Raymond Daniel Rodriguez
Published: June 2024

Climate change is a global threat, the presence of which has encouraged the development and implementation of renewable energies, including plant–microbial fuel cells, which could generate 6 629 568–33 147 840 MWh per year due to their large-scale applicability. One of the main challenges associated with microbial cells is internal resistance—a parameter whose magnitude is influenced by several factors. In the case of plant–microbial fuel cells, adding a plant positively affects the mitigation of internal resistance. However, the species employed is expected to play an important role. In the present study, the objective was to determine as a general reference the internal resistance of cells using various plant species, among which were tomato (Solanum lycopersicum), black beans (Phaseolus vulgaris), aloe vera (Aloe vera), corn (Zea mays), and moss (Dicranidae). For this purpose, an experimental procedure was carried out to compare the manual voltage measurements with a free cell concerning the voltage obtained by adding an external resistor in series. The internal resistance values were determined as a function of the measured voltage, obtaining 177, 179, 175, 324, and 233 kΩ for aloe vera, corn, tomato, black beans, and moss, respectively. From this, it was shown that the roots of the plants represent an essential addition to the internal resistance of the cell in the short term. In contrast, plants with a C4 photosynthetic metabolism are more favourable, while C3 plants can also benefit from internal resistance during a more extended period of rhizodeposition.
Dapagliflozin treatment in patients with chronic kidney disease associated with autosomal dominant polycystic kidney disease
Authors: Yoshimoto Masatoshi , Sekine Akinari , Suwabe Tatsuya , Oba Yuki , Mizuno Hiroki , Yamanouchi Masayuki , Ubara Yoshifumi , Hoshino Junichi , Inoue Noriko , Tanaka Kiho , Hasegawa Eiko , Sawa Naoki , Wada Takehiko
Published: June 2024

Introduction

The DAPA-CKD study showed a protective effect of dapagliflozin on kidney function in chronic kidney disease (CKD) patients with and without diabetes mellitus. Although dapagliflozin is expected to be effective also in CKD patients with autosomal dominant polycystic kidney disease (ADPKD), its efficacy and safety in this population remain unknown because ADPKD was an exclusion criterion in the DAPA-CKD study. Therefore, we evaluated the effects of dapagliflozin in CKD patients with ADPKD.

Methods

We performed a retrospective observational study of seven patients with ADPKD treated with dapagliflozin at Toranomon Hospital, Tokyo, Japan. We analyzed changes in estimated glomerular filtration rate (eGFR) slope and annual height-corrected total kidney volume before and after starting dapagliflozin treatment.

Results

The median observation period after starting dapagliflozin was 20 months. Four patients received concomitant tolvaptan. The eGFR slope before and after initiation of dapagliflozin could be calculated in six patients and improved in all of them except the one who did not receive a renin-angiotensin system (RAS) inhibitor. Annual height-corrected total kidney volume increased in all patients. Concurrent tolvaptan treatment had no effect.

Conclusion

In CKD patients with ADPKD, dapagliflozin may increase kidney volume but may have a protective effect on kidney function when used concomitantly with RAS inhibitors.
Ethnic and seasonal variations in FGF-23 and markers of chronic kidney disease–mineral and bone disorder
Authors: Taskapan Hulya , Mahdavi Sara , Bellasi Antonio , Martin Salome , Kuvadia Saeeda , Patel Anfal , Taskapan Berkay , Tam Paul , Sikaneta Tabo
Published: June 2024

Background

Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease–mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions.

Methods

We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8 ± 14.3 mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons.

Results

Compared with other groups, White participants exhibited 8.0%–18.5% higher FGF-23 levels, Black participants had 0.17–0.32 mg/dL higher calcium levels, White participants had 10.0%–20.1% higher 25-OHD levels, South Asian participants had 7.3%–20.1% lower 25-OHD levels and Black participants had 22.1–73.8% higher iPTH levels, while East Asian participants had 10.7%–73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%–15.5% higher in summer compared with other seasons, while calcium levels were 0.03–0.06 mg/dL lower in summer. 25-OHD levels were 5.6%–10.6% higher in summer and autumn compared with other seasons.

Conclusions

This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings.
An improved DNN model for WLAN intrusion detection
Authors: Wang Haizhen , Cui Zhiqing , Lian Zuozheng , Yan Jinying
Published: June 2024

Intrusion detection represents an efficacious approach for addressing security concerns. However, given the substantial volume and high-dimensional nature of WLAN dataset features, existing methods exhibit limited effectiveness in feature extraction, thereby impacting classification performance. To address above problems, an improved deep neural network (DNN) model for WLAN intrusion detection was proposed. Firstly, the activation function and loss function of a single sparse autoencoders (SAE) were determined through experiments, followed by the addition of regularization terms to the autoencoder, to prevent the model from overfitting. Subsequently, multiple SAEs were employed for a stacked architecture. This configuration served the purpose of feature dimension reduction and facilitated the selection of suitable feature dimensions for training the dataset. The chosen features were then utilized as the input layer for a DNN, with a SoftMax classifier serving as the output layer. Secondly, to obtain better DNN model parameters, the grid search method was adopted to optimize the parameters of the DNN model, namely activation, epochs, batch_size, init_mode, and optimizer. The results were visualized for assessment and analysis. Finally, the receiver operating characteristic curves were generated to assess the performance of various models, the analysis results show that the model exhibited better classifier performance.
A Roman Urdu Corpus for sentiment analysis
Authors: Khan Marwa , Naseer Asma , Wali Aamir , Tamoor Maria
Published: June 2024

Sentiment analysis is a dynamic field focused on understanding and predicting emotional sentiments in text or images. With the prevalence of smartphones, e-commerce and social networks, individuals readily express opinions, aiding businesses, political analysts and organizations in decision-making. Despite extensive research in sentiment analysis for various languages, challenges persist in low-resource languages like Roman Urdu. Roman Urdu, the use of Roman script to write Urdu, has gained popularity, yet limited linguistic resources hinder sentiment analysis research. This study addresses this gap by developing a bidirectional long short-term memory network with FastText embeddings and additional layers. A large Roman Urdu corpus for sentiment analysis, consisting of over 51 000 reviews, is crated and the proposed model is trained and compared with 14 other models, demonstrating an accuracy of 0.854 and an F1-score of 0.84.
Age-related physiological dysregulation progresses slowly in semi-free-ranging chimpanzees
Authors: Cole Megan F , Barnes Paige , Monroe Isabelle G , Rukundo Joshua , Emery Thompson Melissa , Rosati Alexandra G
Published: June 2024

Background and objectives

Lifestyle has widespread effects on human health and aging. Prior results from chimpanzees (Pan troglodytes), one of humans’ closest evolutionary relatives, indicate that these lifestyle effects may also be shared with other species, as semi-free-ranging chimpanzees fed a naturalistic diet show healthier values in several specific health biomarkers, compared with their sedentary, captive counterparts. Here, we examined how lifestyle factors associated with different environments affect rates of physiological aging in closely related chimpanzees.

Methodology

We compared physiological dysregulation, an index of biological aging, in semi-free-ranging chimpanzees in an African sanctuary versus captive chimpanzees in US laboratories. If the rate of aging is accelerated by high-calorie diet and sedentism, we predicted greater age-related dysregulation in the laboratory populations. Conversely, if costs of a wild lifestyle accelerate aging, then semi-free-ranging chimpanzees at the sanctuary, whose environment better approximates the wild, should show greater age-related dysregulation. We further tested whether dysregulation differed based on sex or body system, as in humans.

Results

We found that semi-free-ranging chimpanzees showed lower overall dysregulation, as well as lower age-related change in dysregulation, than laboratory chimpanzees. Males experienced lower dysregulation than females in both contexts, and the two populations exhibited distinct aging patterns based on body system.

Conclusions and implications

Our results support the conclusion that naturalistic living conditions result in healthier aging in chimpanzees. These data provide support for the proposal that lifestyle effects on human health and aging are conserved from deeper into our evolutionary history.
Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT
Authors: Simonenko Maria , Hansen Dominique , Niebauer Josef , Volterrani Maurizio , Adamopoulos Stamatis , Amarelli Cristiano , Ambrosetti Marco , Anker Stefan D , Bayes-Genis Antonio , Gal Tuvia Ben , Bowen T Scott , Cacciatore Francesco , Caminiti Giuseppe , Cavarretta Elena , Chioncel Ovidiu , Coats Andrew J S , Cohen-Solal Alain , D’Ascenzi Flavio , de Pablo Zarzosa Carmen , Gevaert Andreas B , Gustafsson Finn , Kemps Hareld , Hill Loreena , Jaarsma Tiny , Jankowska Ewa , Joyce Emer , Krankel Nicolle , Lainscak Mitja , Lund Lars H , Moura Brenda , Nytrøen Kari , Osto Elena , Piepoli Massimo , Potena Luciano , Rakisheva Amina , Rosano Giuseppe , Savarese Gianluigi , Seferovic Petar M , Thompson David R , Thum Thomas , Van Craenenbroeck Emeline M
Published: June 2024

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients’ physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus
A qualitative assessment of using ChatGPT as large language model for scientific workflow development
Authors: Sänger Mario , De Mecquenem Ninon , Lewińska Katarzyna Ewa , Bountris Vasilis , Lehmann Fabian , Leser Ulf , Kosch Thomas
Published: June 2024

Background

Scientific workflow systems are increasingly popular for expressing and executing complex data analysis pipelines over large datasets, as they offer reproducibility, dependability, and scalability of analyses by automatic parallelization on large compute clusters. However, implementing workflows is difficult due to the involvement of many black-box tools and the deep infrastructure stack necessary for their execution. Simultaneously, user-supporting tools are rare, and the number of available examples is much lower than in classical programming languages.

Results

To address these challenges, we investigate the efficiency of large language models (LLMs), specifically ChatGPT, to support users when dealing with scientific workflows. We performed 3 user studies in 2 scientific domains to evaluate ChatGPT for comprehending, adapting, and extending workflows. Our results indicate that LLMs efficiently interpret workflows but achieve lower performance for exchanging components or purposeful workflow extensions. We characterize their limitations in these challenging scenarios and suggest future research directions.

Conclusions

Our results show a high accuracy for comprehending and explaining scientific workflows while achieving a reduced performance for modifying and extending workflow descriptions. These findings clearly illustrate the need for further research in this area.
Acoustic observations of walleye pollock (Gadus chalcogrammus) migration across the US-Russia boundary in the northwest Bering Sea
Authors: Levine Robert M , De Robertis Alex , Bassett Christopher , Levine Mike , Ianelli James N
Published: June 2024

The degree to which walleye pollock (Gadus chalcogrammus, hereafter pollock) move between the US and Russian zones of the Bering Sea is a key source of uncertainty for fisheries management. To study transboundary migrations across the US–Russia maritime boundary and explore how climate variability might influence these migrations, four seafloor-mounted echosounder moorings were deployed from July 2019 to August 2020 in the northwestern Bering Sea. The observations indicated that a substantial amount of pollock moves between the US and Russia seasonally, with a period of southeast movement into the US as winter as sea ice forms and northwest movement into Russia in early summer as waters warm. Over the deployment period, 2.3-times more pollock backscatter moved into the US zone in fall and winter than exited the subsequent spring and summer. We hypothesize that the difference in the net movement between regions was driven by pollock moving farther into Russia during the historically warm conditions at the start of deployment period and reduced northwest return migration the following summer when temperatures were relatively cooler. This supports the hypothesis that temperature affects pollock distribution, and that continued warming will lead to a larger proportion of the stock in Russian waters.
To Live or Not to Live With It? Examining the Cultivation Effect of State Media on Support for the Zero-COVID Policy
Authors: Wang Zituo , Kim Donggyu , Zhu Jiayi
Published: June 2024

This study delved into the influential role of state media in shaping public opinion and cultivating policy support. Focusing on the Chinese government’s insistence on the zero-COVID policy, we conducted a nationwide survey (N = 665) to examine the cultivation effect of state media on Chinese people’s support for the zero-COVID policy. We found that the more state media people were exposed to on social media, the more they supported the zero-COVID policy. State media exposure on social media was positively associated with trust in the government and fear of the virus among the audience, both of which mediated the effect of state media exposure on zero-COVID policy support. By applying the cultivation theory, this study contributed to our understanding of public opinion and information manipulation under authoritarian contexts in the digital age.
Nuclear Dimension of Subhomogeneous Twisted Groupoid C*-algebras and Dynamic Asymptotic Dimension
Authors: Bönicke Christian , Li Kang
Published: June 2024

We characterize subhomogeneity for twisted étale groupoid $\text{C}^{*}$-algebras and obtain an upper bound on their nuclear dimension. As an application, we remove the principality assumption in recent results on upper bounds on the nuclear dimension of a twisted étale groupoid $\text{C}^{*}$-algebra in terms of the dynamic asymptotic dimension of the groupoid and the covering dimension of its unit space. As a non-principal example, we show that the dynamic asymptotic dimension of any minimal (not necessarily free) action of the infinite dihedral group $D_{\infty }$ on an infinite compact Hausdorff space $X$ is always one. So if we further assume that $X$ is second-countable and has finite covering dimension, then $C(X)\rtimes _{r} D_{\infty }$ has finite nuclear dimension and is classifiable by its Elliott invariant.
Translation-Invariant Equations With at Least Four Variables
Authors: Schoen Tomasz
Published: June 2024

We prove that every subset of $\{1,\dots , N\}$ that does not contain any solutions to a translation invariant equation $a_{1}x_{1}+\dots +a_{k}x_{k}=0$ with $k\ge 4$ has at most $$ \begin{align*} & \exp\big(-c(\log N)^{1/5+o(1)}\big)N\end{align*} $$ elements, for some $c>0$. This theorem improves upon previous estimates. Additionally, our method has the potential to yield an optimal estimate for this problem that matches Behrend’s classical lower bound. Our approach relies on a new result on almost-periodicity of convolutions.
Dimension Growth for Affine Varieties
Authors: Vermeulen Floris
Published: June 2024

We prove uniform upper bounds on the number of integral points of bounded height on affine varieties. If $X$ is an irreducible affine variety of degree $d\geq 4$ in ${\mathbb{A}}^{n}$, which is not the preimage of a curve under a linear map ${\mathbb{A}}^{n}\to{\mathbb{A}}^{n-\dim X+1}$, then we prove that $X$ has at most $O_{d,n,\varepsilon }(B^{\dim X - 1 + \varepsilon })$ integral points up to height $B$. This is a strong analogue of dimension growth for projective varieties, and improves upon a theorem due to Pila, and a theorem due to Browning–Heath-Brown–Salberger. Our techniques follow the $p$-adic determinant method, in the spirit of Heath-Brown, but with improvements due to Salberger, Walsh, and Castryck–Cluckers–Dittmann–Nguyen. The main difficulty is to count integral points on lines on an affine surface in ${\mathbb{A}}^{3}$, for which we develop point-counting results for curves in ${\mathbb{P}}^{1}\times{\mathbb{P}}^{1}$. We also formulate and prove analogous results over global fields, following work by Paredes–Sasyk.
Intestinal persistence of Bifidobacterium infantis is determined by interaction of host genetics and antibiotic exposure
Authors: Wang Yiming , Choo Jocelyn M , Richard Alyson C , Papanicolas Lito E , Wesselingh Steve L , Taylor Steven L , Rogers Geraint B
Published: June 2024

Probiotics have gained significant attention as a potential strategy to improve health by modulating host–microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable interindividual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breve and B. bifidum, which cannot internalize α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.
Conditions for the spread of CRISPR-Cas immune systems into bacterial populations
Authors: Elliott Josie F K , McLeod David V , Taylor Tiffany B , Westra Edze R , Gandon Sylvain , Watson Bridget N J
Published: June 2024

Bacteria contain a wide variety of innate and adaptive immune systems which provide protection to the host against invading genetic material, including bacteriophages (phages). It is becoming increasingly clear that bacterial immune systems are frequently lost and gained through horizontal gene transfer. However, how and when new immune systems can become established in a bacterial population have remained largely unstudied. We developed a joint epidemiological and evolutionary model that predicts the conditions necessary for the spread of a CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated) immune system into a bacterial population lacking this system. We found that whether bacteria carrying CRISPR-Cas will spread (increase in frequency) into a bacterial population depends on the abundance of phages and the difference in the frequency of phage resistance mechanisms between bacteria carrying a CRISPR-Cas immune system and those not (denoted as ${f}_{\Delta }$). Specifically, the abundance of cells carrying CRISPR-Cas will increase if there is a higher proportion of phage resistance (either via CRISPR-Cas immunity or surface modification) in the CRISPR-Cas–possessing population than in the cells lacking CRISPR-Cas. We experimentally validated these predictions in a model using Pseudomonas aeruginosa PA14 and phage DMS3vir. Specifically, by varying the initial ratios of different strains of bacteria that carry alternative forms of phage resistance, we confirmed that the spread of cells carrying CRISPR-Cas through a population can be predicted based on phage density and the relative frequency of resistance phenotypes. Understanding which conditions promote the spread of CRISPR-Cas systems helps to predict when and where these defences can become established in bacterial populations after a horizontal gene transfer event, both in ecological and clinical contexts.
Impact of response bias in three surveys on primary care providers’ experiences with electronic health records
Authors: Hendrix Nathaniel , Maisel Natalya , Everson Jordan , Patel Vaishali , Bazemore Andrew , Rotenstein Lisa S , Holmgren A Jay , Krist Alex H , Adler-Milstein Julia , Phillips Robert L
Published: June 2024

Objective

To identify impacts of different survey methodologies assessing primary care physicians' (PCPs’) experiences with electronic health records (EHRs), we compared three surveys: the 2022 Continuous Certification Questionnaire (CCQ) from the American Board of Family Medicine, the 2022 University of California San Francisco (UCSF) Physician Health IT Survey, and the 2021 National Electronic Health Records Survey (NEHRS).

Materials and Methods

We evaluated differences between survey pairs using Rao-Scott corrected chi-square tests, which account for weighting.

Results

CCQ received 3991 responses from PCPs (100% response rate), UCSF received 1375 (3.6% response rate), and NEHRS received 858 (18.2% response rate). Substantial, statistically significant differences in demographics were detected across the surveys. CCQ respondents were younger and more likely to work in a health system; NEHRS respondents were more likely to work in private practice; and UCSF respondents disproportionately practiced in larger academic settings. Many EHR experience indicators were similar between CCQ and NEHRS, but CCQ respondents reported higher documentation burden.

Discussion

The UCSF approach is unlikely to supply reliable data. Significant demographic differences between CCQ and NEHRS raise response bias concerns, and while there were similarities in some reported EHR experiences, there were important, significant differences.

Conclusion

Federal EHR policy monitoring and maintenance require reliable data. This test of existing and alternative sources suggest that diversified data sources are necessary to understand physicians’ experiences with EHRs and interoperability. Comprehensive surveys administered by specialty boards have the potential to contribute to these efforts, since they are likely to be free of response bias.
Morphometric changes at terminal molt and reproductive capacity in the kelp crabPugettia feroxOhtsuchi & Kawamura, 2019 (Decapoda: Brachyura: Majoidea)
Authors: Fukasawa Aiko , Yasuda Chiaki I
Published: June 2024

It has been assumed that functional maturity and terminal molt occur simultaneously in majoid crabs. Although this assumption seems to be accurate in females, males of some majoids can mate with females even before their terminal molt. Here we describe the morphometric changes at terminal molt and test the reproductive capacity of pre-terminal molt males in the kelp crab Pugettia feroxOhtsuchi & Kawamura, 2019 (Majoidea, Epialtidae, Epialtinae). We measured the post-pseudorostral carapace length (PCL), claw length (CL), claw height (CH), and pleon (abdomen) width (AW) of crabs to estimate the morphological features distinguishing pre- and post-terminal molt individuals, namely relative claw length (CL/PCL) ≥ 0.660 in males and relative abdominal width (AW/PCL) ≥ 0.487 in females. Males with pre-terminal molt morphological features were observed for behavioral maturity through encounters with mature virgin females under laboratory conditions. More than half of the males copulated with a female and then underwent terminal molt. These females bred clutches, and larvae hatched. These results indicate that pre-terminal molt males of P. ferox can be functionally mature.
Revealing the potential role of hsa-miR-663a in modulating the PI3K-Akt signaling pathway via miRNA microarray in spinal muscular atrophy patient fibroblast-derived iPSCs
Authors: Gandhi Gayatri , Kodiappan Radha , Abdullah Syahril , Teoh Hoon Koon , Tai Lihui , Cheong Soon Keng , Yeo Wendy Wai Yeng
Published: June 2024

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder due to deletion or mutation of survival motor neuron 1 (SMN1) gene. Although survival motor neuron 2 (SMN2) gene is still present in SMA patients, the production of full-length survival motor neuron (SMN) protein is insufficient owing to missing or mutated SMN1. No current disease-modifying therapies can cure SMA. The aim of this study was to explore microRNA (miRNA)-based therapies that may serve as a potential target for therapeutic intervention in delaying SMA progression or as treatment. The study screened for potentially dysregulated miRNAs in SMA fibroblast-derived iPSCs using miRNA microarray. Results from the miRNA microarray were validated using quantitative reverse transcription polymerase chain reaction. Bioinformatics analysis using various databases was performed to predict the potential putative gene targeted by hsa-miR-663a. The findings showed differential expression of hsa-miR-663a in SMA patients in relation to a healthy control. Bioinformatics analysis identified GNG7, IGF2, and TNN genes that were targeted by hsa-miR-663a to be involved in the PI3K-AKT pathway, which may be associated with disease progression in SMA. Thus, this study suggests the potential role of hsa-miR-663a as therapeutic target for the treatment of SMA patients in the near future.
Restoration of thymic T-cell development by bone marrow transplantation in mouse radiation lymphomagenesis
Authors: Takeshima Tsuguhide , Hasegawa Sumitaka
Published: June 2024

Fractionated total body irradiation (TBI) with X-rays induces thymic lymphoma/leukemia (TL) in C57BL/6 mice. Radiation-induced mouse TL (RITL) can be prevented by bone marrow transplantation (BMT) of unirradiated BM cells. However, the mechanisms underlying the prevention of RITL with BMT remain unclear. Here, we show that BMT restores thymic T-cell differentiation in mice subjected to TBI. TBI (four times of 1.8 Gy X-rays weekly) was conducted with C57BL/6 mice. BMT was performed immediately after the last irradiation of TBI in mice by transplantation of BM cells isolated from enhanced green fluorescence protein (eGFP) transgenic mice. Thymic cell numbers were drastically decreased in TBI and TBI + BMT mice compared to those in non-irradiated mice. Flow cytometry showed a dramatic decrease in double negative (DN, CD4−CD8−) thymocytes, especially DN2 (CD25+CD44+) and DN3 (CD25+CD44−) subpopulations, in the TBI mice on Day 10 after the last irradiation. In contrast, the DN2 and DN3 populations were recovered in TBI + BMT mice. Interestingly, these restored DN2 and DN3 cells mainly differentiated from eGFP-negative recipient cells but not from eGFP-positive donor cells, suggesting that transplanted BM cells may interact with recipient cells to restore thymic T-cell development in the RITL model. Taken together, our findings highlight the significance of restoring thymic T-cell differentiation by BMT in RITL prevention.
Brain metastases of the mucoepidermoid lung carcinoma: a case report
Authors: Tomac Damir , Konstantinović Ivan , Tomasović-Lončarić Čedna , Maraković Jurica , Kaštelančić Anđelo , Orešković Darko , Romić Dominik , Marčinković Petar , Raguž Marina , Chudy Darko , Marinović Tonko
Published: June 2024

Mucoepidermoid carcinoma, a salivary gland tumor, rarely occurs in bronchial mucous glands. Brain metastases are rarely seen which makes for a challenging diagnosis and treatment approach. A 40-year-old woman presented with confusion, and ataxia, accompanied by a declining Glasgow Coma Score. Brain computerized tomography revealed two hyperdense, postcontrast-enhanced infra- and supratentorial lesions with perifocal edema. First causing obstructive hydrocephalus. The initial surgery involved external ventricular drainage system placement leading to the patient’s clinical improvement. After radiological diagnostics, both lesions were resected without complications. Histopathological analysis revealed solid clusters of atypical, polygonal epithelial cells exhibiting mucin production, classified as a poorly differentiated mucoepidermoid carcinoma metastasis which originated from the upper lobe’s apicoposterior segment and left lung. The correct treatment approach remains elusive due to the infrequent occurrence and challenging diagnosis. While new oncological and radiosurgery options promise improved overall survival rates, radical resection remains the preferred initial option.
Epicardial hematoma due to heart positioner device in minimally invasive coronary artery bypass
Authors: Mochizuki Nobuhiro , Ushioda Ryohei , Yoongtong Dit , Sakboon Boonsap , Cheewinmethasiri Jaroen , Kamiya Hiroyuki , Arayawudhikul Nuttapon
Published: June 2024

Minimally invasive cardiac surgery off-pump coronary artery bypass (MICSOPCAB) has become increasingly prevalent, with devices like the heart positioner aiding in surgical precision. However, rare complications such as epicardial hematoma can occur. Here, we present a case of a 75-year-old man undergoing MICSOPCAB who developed an epicardial hematoma due to the heart positioner. The hematoma was successfully repaired intraoperatively with direct suturing and large felts. Postoperative recovery was uneventful, highlighting the importance of vigilant monitoring and prompt management of such complications. This case underscores the need for careful attention during the use of cardiac positioners to minimize adverse events and ensure favorable patient outcomes.
Changes in the epidemiology of kidney replacement therapy across Europe in 2020 – the first year of the COVID-19 pandemic: an ERA Registry study
Authors: Kramer Anneke , Jager Kitty J , Chesnaye Nicholas C , Kerschbaum Julia , Hommel Kristine , Comas Farnés Jordi , Trujillo Alemán Sara , Santamaria Rafael , Finne Patrik , Hemmelder Marc H , Åsberg Anders , Nitsch Dorothea , Ambühl Patrice , Sørensen Søren S , Sánchez-Alvarez J Emilio , Segelmark Mårten , Resic Halima , Ots-Rosenberg Mai , Radunovic Danilo , Palsson Runolfur , Santiuste de Pablos Carmen , Rodríguez Arévalo Olga L , Legeai Camille , Lausevic Mirjana , Bakkaloglu Sevcan A , Ortiz Alberto , Stel Vianda S
Published: June 2024

Background

In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe.

Methods

Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017–2019. Changes occurring during the first and second waves of the pandemic were also explored.

Results

The incidence of KRT was 6.2% lower in 2020 compared with 2017–2019, with the lowest point (−22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (−5.2%) than in females (−8.2%) and was moderate for peritoneal dialysis (−3.7%) and haemodialysis (−5.4%) but substantial for pre-emptive kidney transplantation (−23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of −80.1% during the first wave, and was greatest for living donor kidney transplants (−30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65–74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N = 317 787) resembled that of 2019 (N = 317 077).

Conclusion

The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries.
From bench to bedside: Advancing towards therapeutic treatment of vestibular schwannomas
Authors: Guo Shaolei , Zheng Xuan , Chen Wenli , Raza Umar , Zeng Ailiang , Akter Farhana , Huang Quan , Yao Shun
Published: June 2024

Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration–approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.
Identifying research priorities and essential elements of palliative care services for people facing malignant brain tumors: A participatory co-design approach
Authors: Salmi Liz , Otis-Green Shirley , Hayden Adam , Taylor Lynne P , Reblin Maija , Kwan Bethany M
Published: June 2024

Background

Primary malignant brain tumors (ie, brain cancer) impact the quality of life (QoL) for patients and care partners in disease-specific ways involving cognition and communication. Palliative care (PC) addresses patient/care partner QoL, but it is not known how PC may address the unique needs of brain cancer patients. The purpose of this project was to identify brain cancer PC research priorities using participatory co-design methods.

Methods

Participatory co-design included the formation of a longitudinal, collaborative advisory group, engagement frameworks, design-thinking processes, and social media-based engagement over a 1-year period. Community-identified brain cancer QoL needs and research priorities were mapped to proposed “essential elements” of brain cancer PC services.

Results

We engaged an estimated 500 patients, care partners, healthcare professionals, and others with an interest in QoL and PC services for people with malignant brain tumors. Research priorities included testing the early introduction of PC services designed to address the unique QoL needs of brain cancer patients and care partners. Essential elements of brain cancer PC include: (1) addressing brain cancer patients’ unique range of QoL needs and concerns, which change over time, (2) tailoring existing services and approaches to patient needs and concerns, (3) enhancing the involvement of interprofessional care team members, and (4) optimizing timing for PC services. This was the first participatory research effort exploring brain cancer patient and care partner QoL needs and PC services.

Conclusions

The brain tumor community calls for research testing PC service models for patients that incorporate the “essential elements” of palliative care.