bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing expression system alters oligomerization and proinflammatory activity of recombinant human S100A9
Authors: Chisholm Lauren O. , Jeon Chae Kyung , Prell James S. , Harms Michael J.
Published: August 2024

S100A9 is a Damage Associated Molecular Pattern (DAMP) that activates the innate immune system via Toll-like receptor 4 (TLR4). Despite many years of study, the mechanism of activation remains unknown. To date, much of the biochemical characterization of S100A9 has been performed using recombinant S100A9 expressed inE. coli(S100A9ec). TLR4 is the canonical receptor for LPS, a molecule found in the outer membrane ofE. coli, raising the possibility of artifacts due to LPS contamination. Here we report characterization of LPS-free recombinant S100A9 expressed in insect cells (S100A9in). We show that S100A9indoes not activate TLR4. This difference does not appear to be due to LPS contamination, protein misfolding, purification artifacts, or differences in phosphorylation. We show instead that S100A9inadopts an altered oligomeric state compared to S100A9ec. Disrupting oligomer formation with theE. colidisaggregase SlyD restores activity to S100A9in. Our results also indicate that the oligomeric state of S100A9 is a major factor in its ability to activate TLR4 and that this can be altered in unexpected ways by the recombinant expression system used to produce the protein.
Benchmarking bulk and single-cell variant-calling approaches on Chromium scRNA-seq and scATAC-seq libraries
Authors: Wiens Matthew , Farahani Hossein , Scott R. Wilder , Underhill T. Michael , Bashashati Ali
Published: August 2024

Single-cell sequencing methodologies such as scRNA-seq and scATAC-seq have become widespread and effective tools to interrogate tissue composition. Increasingly, variant callers are being applied to these methodologies to resolve the genetic heterogeneity of a sample, especially in the case of detecting the clonal architecture of a tumor. Typically, traditional bulk DNA variant callers are applied to the pooled reads of a single-cell library to detect candidate mutations. Recently, multiple studies have applied such callers on reads from individual cells, with some citing the ability to detect rare variants with higher sensitivity. Many studies apply these two approaches to the Chromium (10x Genomics) scRNA-seq and scATAC-seq methodologies. However, Chromium-based libraries may offer additional challenges to variant calling compared with existing single-cell methodologies, raising questions regarding the validity of variants obtained from such a workflow. To determine the merits and challenges of various variant-calling approaches on Chromium scRNA-seq and scATAC-seq libraries, we use sample libraries with matched bulk whole-genome sequencing to evaluate the performance of callers. We review caller performance, finding that bulk callers applied on pooled reads significantly outperform individual-cell approaches. We also evaluate variants unique to scRNA-seq and scATAC-seq methodologies, finding patterns of noise but also potential capture of RNA-editing events. Finally, we review the notion that variant calling at the single-cell level can detect rare somatic variants, providing empirical results that suggest resolving such variants is infeasible in single-cell Chromium libraries.
Microscopic solutions for vortex clustering in two-band type-1.5 superconductors
Authors: Timoshuk Igor , Babaev Egor
Published: August 2024

Two-band superconductors exhibit a distinct phase characterized by two correlation lengths, one smaller and the other larger than the magnetic field penetration length. This regime was coined type-1.5 superconductivity, with several unconventional properties, such as vortex clustering. However, a fully microscopic solution for vortex clusters has remained challenging due to computational complexities beyond quasiclassical models. This work presents numerical solutions obtained in a fully self-consistent two-band Bogoliubov–de Gennes model. We show the presence of discrepant correlation lengths leading to vortex clustering in two-band superconductors.

Published by the American Physical Society
2024
Light tetraquark states with exotic quantum numbers
JPC=2+−
Authors: Wang Qi-Nan , Lian Ding-Kun , Chen Wei
Published: August 2024

We study the masses of light tetraquark states udu¯d¯, usu¯s¯, and sss¯s¯ with exotic quantum numbers JPC=2+− using the method of QCD sum rules. It is found that there is no tetraquark operator with two Lorentz indices coupling to the 2+− quantum numbers. To investigate such tetraquark states, we construct the interpolating tetraquark currents with three Lorentz indices and without a derivative operator. We calculate the correlation functions up to dimension-ten condensates and extract the 2+− invariant functions via the projector operator. Our results show that the masses of the udu¯d¯, usu¯s¯, and sss¯s¯ tetraquark states with JPC=2+− are about 3.3–3.5, 3.5–3.7, and 3.67 GeV, respectively. We further discuss the strong decays of these light tetraquarks into the two-meson and baryon-antibaryon final states and suggest to search for them in the ρπ, ωπ, ϕπ, b1π, h1π, KK¯*, KK¯1, ΔΔ¯, Σ*Σ¯*, Ξ*Ξ¯*, and ΩΩ¯ channels in the future.

Published by the American Physical Society
2024
Kinematic Hopf algebra and Bern-Carrasco-Johansson numerators at finite
α′
Authors: Chen Gang , Rodina Laurentiu , Wen Congkao
Published: August 2024

We significantly extend recent work on the kinematic Hopf algebra, a structure that was shown to underlie the color-kinematics duality in Yang-Mills (YM) theory coupled to two heavy scalars, known as the heavy-mass effective theory (HEFT) limit. First, staying in the HEFT limit, we show the same kinematic Hopf algebra can be used to obtain Bern-Carrasco-Johansson (BCJ) numerators in DF2+YM theory, a theory containing an infinite number of higher derivative corrections to YM, used to obtain string amplitudes via the double copy. Second, we exploit the intricate structure induced by the massive poles to obtain an efficient and direct expression for local BCJ numerators in pure YM based on the same kinematic Hopf algebra. This demonstrates that the kinematic Hopf algebra works even beyond the HEFT limit, strongly suggesting this structure universally underlies the color-kinematics duality.

Published by the American Physical Society
2024
Genomic stasis over millions of years in subseafloor sediment
Authors: Garber Arkadiy I. , Ramírez Gustavo A. , D'Hondt Steven
Published: August 2024

One of the significant challenges in microbiology is to understand the extent and mechanisms of evolution within life beneath the surface of the Earth. The population bottleneck that microbes in deep marine sediment experience implies that mutational and population genetic forces could lead to higher levels of relaxed selection and an increase in pseudogenes. To investigate this hypothesis, a group of Thalassospira strains were isolated from subseafloor sediment that is 3 to 6 million years old, as reported by Orsi and colleagues in 2021. These isolates, representing lineages that have been buried for millions of years, offer an excellent opportunity to study the evolution of life beneath the seafloor over a long period. The existence of closely related strains from environments on the surface of the Earth enabled us to examine the impact of selection within each group. We discovered that isolates from beneath the seafloor show lineage‐specific similarities to Thalassospira from the surface world, both in the overall intensity of selection on the genome and in the specific genes affected by mutation. We found no signs of increased relaxed selection or other notable genomic changes in the genomes of the Thalassospira isolates from beneath the seafloor, suggesting that these subseafloor isolates were awakened from a million‐year near‐stasis. The unique genomic characteristics of each Thalassospira lineage from beneath the seafloor must then reflect genetic changes that surface‐inhabiting decendants acquired in the past 3–6 million years. Remarkably, Thalassospira lineages beneath the surface appear to have stably maintained their genomes in the midst of metabolic dormancy and extremely long generation times.
Using Research to Improve Policing post Casey—and Why that Might not Happen
Authors: Sutherland Alex
Published: August 2024

Crime is a problem that extends beyond police and policing. As the saying goes, ‘you can't arrest your way out of crime’, nor can you police your way out of a recruitment crisis, or baton‐charge to improve trust. Policing faces some novel challenges, but not every policing problem is unique and there are ideas from outside policing that can help. This article makes suggestions on ways to resolve some of the issues raised in the Casey review using evidence from different disciplines and concludes with some reasons why research evidence is not routinely used in policing and what can be done to change this.
Identification of senescent cell subpopulations by CITE‐seq analysis
Authors: Abdelmohsen Kotb , Mazan‐Mamczarz Krystyna , Munk Rachel , Tsitsipatis Dimitrios , Meng Qiong , Rossi Martina , Pal Apala , Shin Chang Hoon , Martindale Jennifer L. , Piao Yulan , Fan Jinshui , Yanai Hagai , De Supriyo , Beerman Isabel , Gorospe Myriam
Published: August 2024

Cellular senescence, a state of persistent growth arrest, is closely associated with aging and age‐related diseases. Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence‐associated pathologies. In this study, proteins on the surface of cells rendered senescent by replicative exhaustion and by exposure to ionizing radiation (IR) were identified using mass spectrometry analysis, and a subset of them was further studied using single‐cell CITE‐seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis. Based on the presence of proteins on the cell surface, we identified two distinct IR‐induced senescent cell populations: one characterized by high levels of CD109 and CD112 (cluster 3), the other characterized by high levels of CD112, CD26, CD73, HLA‐ABC, CD54, CD49A, and CD44 (cluster 0). We further found that cluster 0 represented proliferating and senescent cells in the G1 phase of the division cycle, and CITE‐seq detection of cell surface proteins selectively discerned those in the senescence group. Our study highlights the heterogeneity of senescent cells and underscores the value of cell surface proteins as tools for distinguishing senescent cell programs and subclasses, paving the way for targeted therapeutic strategies in disorders exacerbated by senescence.
Dysregulation of choline metabolism and therapeutic potential of citicoline in Huntington's disease
Authors: Chang Kuo‐Hsuan , Cheng Mei‐Ling , Tang Hsiang‐Yu , Lin Chung‐Yin , Chen Chiung‐Mei
Published: August 2024

Huntington's disease (HD) is associated with dysregulated choline metabolism, but the underlying mechanisms remain unclear. This study investigated the expression of key enzymes in this pathway in R6/2 HD mice and human HD postmortem brain tissues. We further explored the therapeutic potential of modulating choline metabolism for HD. Both R6/2 mice and HD patients exhibited reduced expression of glycerophosphocholine phosphodiesterase 1 (GPCPD1), a key enzyme in choline metabolism, in the striatum and cortex. The striatum of R6/2 mice also showed decreased choline and phosphorylcholine, and increased glycerophosphocholine, suggesting disruption in choline metabolism due to GPCPD1 deficiency. Treatment with citicoline significantly improved motor performance, upregulated anti‐apoptotic Bcl2 expression, and reduced oxidative stress marker malondialdehyde in both brain regions. Metabolomic analysis revealed partial restoration of disrupted metabolic patterns in the striatum and cortex following citicoline treatment. These findings strongly suggest the role of GPCPD1 deficiency in choline metabolism dysregulation in HD. The therapeutic potential of citicoline in R6/2 mice highlights the choline metabolic pathway as a promising target for future HD therapies.
Age‐stratified risk of suicide in patients with schizophrenia
Authors: Lin Yueh‐Pin , Chen Wen‐Yin , Pan Chun‐Hung , Su Sheng‐Shiang , Tsai Shang‐Ying , Chen Chiao‐Chicy , Kuo Chian‐Jue
Published: August 2024

Objectives

Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size.

Methods

From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age‐stratified, nested case–control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age‐stratified risk profiles.

Results

The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug‐induced and alcohol‐induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65.

Conclusions

The risk factors for suicide differ by age. This study's findings can be used to optimize health‐care interventions for preventing suicide in patients with schizophrenia.
ChatGPT‐4: Alcohol use disorder responses
Authors: Russell Alex M. , Acuff Samuel F. , Kelly John F. , Allem Jon‐Patrick , Bergman Brandon G.
Published: August 2024

Background and aims

Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health‐related questions; web‐based results include a mix of high‐ and low‐quality information. Artificial intelligence may improve access to quality health information by providing concise, high‐quality responses to complex health‐related questions. This study evaluated the quality of ChatGPT‐4 responses to AUD‐related queries.

Method

A comprehensive list of 64 AUD‐related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT‐4 was prompted with each question, followed by a request to provide 3–5 peer‐reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence‐based, provided a referral and provided supporting documentation.

Results

ChatGPT‐4 responded to all AUD‐related queries, with 92.2% (59/64) of responses being fully evidence‐based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location‐specific (‘near me’) queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow‐up question provided supporting documentation.

Conclusions

ChatGPT‐4 responds to alcohol use disorder‐related questions with evidence‐based information and supporting documentation. ChatGPT‐4 could be promoted as a reasonable resource for those looking online for alcohol use disorder‐related information.
Anaplastic thyroid cancer: A review of recent evidence and summary of an Australian institutional protocol
Authors: Lawless Anna K , Kumar Shejil , Bindra Jessica , Sywak Mark , Chou Angela , Turchini John , Papachristos Alexander , Wijewardene Ayanthi , Sidhu Stanley , Ahadi Mahsa , Tacon Lyndal , Glover Anthony , Clark Katherine , Tsang Venessa , Pang Leo , Clifton‐Bligh Roderick J , Robinson Bruce , Gill Anthony J , Guminski Alexander , Eade Thomas , Gild Matti L
Published: August 2024

Anaplastic thyroid cancer (ATC), a rare and highly aggressive malignancy, is characterized by an exceptionally poor prognosis, where the majority of patients present with extensive local invasion and/or distant metastases. 20–30% of ATCs harbor the BRAF‐V600E mutation. Neoadjuvant BRAF‐targeted therapy may have the potential to downstage and facilitate surgical resection for patients with locally advanced and unresectable primary tumors with BRAF mutation and may convey a survival advantage in those with metastatic disease. There is emerging evidence to support the use of other targeted agents, including multikinase inhibitors, as well as the incorporation of immunotherapy into the treatment regimen. Rapid molecular and pathological diagnosis and expert multidisciplinary discussion at specialized treatment centers are critical to expedite investigations and initiate treatment for this complex and rapidly progressive disease.
Adherence to guidelines in curative treatment of venous thromboembolism in cancer patients: Insights from a retrospective Tunisian study
Authors: Fendri Sofiene , Latrous Alia , Meddeb Khedija , Ayadi Mouna , Mokrani Amina , Rais Henda Belhajali
Published: August 2024

Aim

To describe the management and treatment practices of venous thromboembolism (VTE) in cancer patients, assess compliance with the 2023 European Society for Medical Oncology recommendations, and identify factors that may limit or influence their application.

Methods

We conducted, in a Tunisian center, a retrospective study that included patients treated for cancer or hematologic malignancies and diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism between January 1, 2022, and August 1, 2023.

Results

The study involved 90 patients. DVTs were significantly predominant (81.1%). VTE mostly occurred within 3 months of the cancer diagnosis (41.1%). All patients received anticoagulant treatment. The most frequently prescribed class of anticoagulants was direct oral anticoagulants (42.2%), followed by low molecular weight heparin (36.7%), and finally vitamin K antagonists (21.1%). Financial constraints and/or refusal of social security to provide the treatment were the main cause for changes in the anticoagulant therapy (16.7%). Deaths (25.5%) and repermeabilization of the initially thrombosed venous network on imaging (11.1%) were the two primary reasons for treatment discontinuation. Bleeding complication was the cause of treatment modification or discontinuation in 7.7% and 5.5% of patients, respectively. Overall, guidelines were fully followed in 49 patients (54.4%) concerning the choice of pharmacological class, dose and duration of treatment. Financial constraints experienced by patients were significantly and independently associated with lower adherence to recommendations (p = 0.032).

Conclusion

Adherence to guidelines is insufficient. Measures must be implemented to enhance the management of VTE and to develop strategies for improving access to anticoagulants.
Risk of bias and problematic trials: characterising the research integrity of trials submitted to Anaesthesia
Authors: Bramley Paul , Hulman Joshua , Wanstall Helen
Published: August 2024

Background

There is some evidence for systematic biases and failures of research integrity in the anaesthesia literature. However, the features of problematic trials and effect of editorial selection on these issues have not been well quantified.

Methods

We analysed 209 randomised controlled trials submitted to Anaesthesia between 8 March 2019 and 31 March 2020. We evaluated the submitted manuscript, registry data and the results of investigations into the integrity of the trial undertaken at the time of submission. Trials were labelled ‘concerning’ if failures of research integrity were found, and ‘problematic’ if identified issues would have warranted retraction if they had been found after publication. We investigated how ‘problematic’ trials were detected, the distribution of p values and the risk of outcome reporting bias and p‐hacking. We also investigated whether there were any factors that differed in problematic trials.

Results

We found that false data was the most common reason for a trial to be labelled as ‘concerning’, which occurred in 51/62 (82%) cases. We also found that while 195/209 (93%) trials were preregistered, we found adequate registration for only 166/209 (79%) primary outcomes, 100/209 (48%) secondary outcomes and 11/209 (5%) analysis plans. We also found evidence for a step decrease in the frequency of p values > 0.05 compared with p values < 0.05. ‘Problematic’ trials were all single‐centre and appeared to have fewer authors (incident risk ratio (95%CI) 0.8 (0.7–0.9)), but could not otherwise be distinguished reliably from other trials.

Conclusions

Identification of ‘problematic’ trials is frequently dependent on individual patient data, which is often unavailable after publication. Additionally, there is evidence of a risk of outcome reporting bias and p‐hacking in submitted trials. Implementation of alternative research and editorial practices could reduce the risk of bias and make identification of problematic trials easier.
Healthcare Professionals' Perspectives on the Use of Standing Frames for Children Diagnosed With Cerebral Palsy: An Explanatory Mixed Methods Study
Authors: Andersen Michaela , Krarup Lærke Hartvig , Rolving Nanna , Holsgaard‐Larsen Anders , Pawlowski Charlotte , Rasmussen Helle Mätzke , Hubeishy Maja Husted
Published: August 2024

Background

Standing frames are commonly used by healthcare professionals in their practice with children with cerebral palsy (CP) who do not have an independent standing function. A better understanding of healthcare professionals' attitudes and experiences with standing frames may impact practice and rehabilitation. Therefore, this study aimed to investigate the standing frame practice among healthcare professionals and expand their attitude and experience with the use of standing frames for children with CP.

Methods

This is an explanatory sequential mixed methods study. A cross‐sectional survey was conducted, providing quantitative data on 210 healthcare professionals' use of standing frames. The quantitative data were descriptively analysed. Subsequently, the results from the survey were followed up with five focus group interviews of healthcare professionals (n = 14). The qualitative data were analysed using thematic analysis, enabling integration between the quantitative and qualitative data.

Results

When quantitative and qualitative data are integrated, expansion between the two datasets occurred. The quantitative dataset emphasised the use of GMFCS levels as a guideline for recommending standing frames, whereas the qualitative data showed that the healthcare professionals' recommendations were based on individual needs. Furthermore, the healthcare professionals expanded the quantitative data, showing that the healthcare professionals' considerations regarding age and dosage were based on clinical experience, and saw the standing frame as having many benefits.

Conclusion

The healthcare professionals had a child‐centred approach, where the child's need for using a standing frame was assessed based on the functional level, stage of development, cognitive level and clinical assessment. All of these considerations showed that the use of standing frames for children with CP was individualised, thereby making it difficult to make unified descriptions.
Religious Coping as Mediator of Sense of Competence and Post‐traumatic Growth in Mothers of Children With Cerebral Palsy
Authors: ul Ain Noor , Ali Anam , Bashir Nazia
Published: August 2024

Objectives

The present study aimed to determine whether religious coping mediates the relationship between parenting sense of competence (PSOC) and post‐traumatic growth (PTG).

Method

Cross‐sectional research design was used. A sample of 74 mothers (age range; 20–45 years) of CP children (age range; 2–9 years) was collected through purposive sampling from different physiotherapy centres and special education schools of Lahore. PSOC scale, brief RCOPE and PTG inventory were used.

Results

Positive religious coping partially mediated (β = 0.190, 95% CI [0.026, 0.374], p < 0.05) between PSOC and PTG. Partial mediation exists between PSOC and appreciation of life through pathway of positive religious coping (β = 0.040, 95% CI [0.007, 0.075], p < 05). Full mediation exists between PSOC and personal strength through pathway of positive religious coping (β = 0.041, 95% CI [0.001, 0.081], p < 0.05) and through negative religious coping (β = 0.034, 95% CI [0.002, 0.066], p < 0.05). Positive religious coping fully mediated (β = 0.029, 95% CI [0.007, 0.058], p < 0.05) between PSOC and spiritual change. Moreover, indirect effect of PSOC on relating to others and new possibilities through positive and negative religious coping was non‐significant, indicating no mediation.

Conclusion

Positive religious coping affected the association between PSOC and PTG, that is, mothers of CP children having high parenting competence are more likely to use positive religious coping strategies that results in more PTG.
Active spread of β‐thalassemia beyond the thalassemia belt: A study on a Russian population
Authors: Shchemeleva Ekaterina , Salomashkina Valentina V. , Selivanova Daria , Tsvetaeva Nina , Melikyan Anait , Doronina Liliya , Surin Vadim L.
Published: August 2024

β‐Thalassemia is a disease traditionally associated with thalassemia belt countries. Nonetheless, as global migration intensifies, β‐thalassemia–causing variants spread far from their origin. We investigated this process to detect some patterns underlying its course. We analyzed β‐thalassemia–causing variants and the origin of 676 unrelated participants in Moscow, the largest city of Russia, far away from the thalassemia belt. Our analyses revealed that modern Russia has one of the broadest spectra of thalassemia‐causing variants: 46 different variants, including two novel β0 variants. Only a small proportion of the reported pathogenic variants likely originated in the resident subpopulation. Almost half of the variants that supposedly had emerged outside the Russian borders have already been assimilated by (were found in) the resident subpopulation. The primary modern source of immigration transferring thalassemia to a nonthalassemic part of Russia is the Caucasus region. We also found traces of ancient migration flows from non‐Caucasus countries. Our data indicate that β‐thalassemia–causing variants are actively spilling over into resident populations of countries outside thalassemia belt regions. Therefore, viewing thalassemia as a disease exclusive to specific ethnic groups creates a mind trap that can complicate the diagnosis.
Periodontal tissue susceptibility to glycaemic control in type 2 diabetes
Authors: Inoue Moe , Sakanaka Akito , Katakami Naoto , Furuno Masahiro , Nishizawa Hitoshi , Omori Kazuo , Taya Naohiro , Ishikawa Asuka , Mayumi Shota , Tanaka Isomura Emiko , Takeuchi Hiroki , Amano Atsuo , Shimomura Iichiro , Fukusaki Eiichiro , Kuboniwa Masae
Published: August 2024

Aim

To assess the direct effect of intensive glycaemic control on periodontal tissues in patients with diabetes mellitus.

Materials and Methods

Twenty‐nine patients with type 2 diabetes were enrolled and hospitalized to receive a 2‐week intensive glycaemic control regimen. We observed and analysed the systemic and oral disease indicators before and after treatment and clarified the indicators related to periodontal inflammation.

Results

A significant reduction in glycaemic and periodontal parameters, including glycated albumin levels and periodontal inflamed surface area (PISA), was observed after treatment. The changes in PISA per tooth, indicative of periodontal healing, exhibited a bimodal distribution; the patients were divided into two groups on this basis. Correlations were observed between the changes in PISA per tooth and fasting plasma glucose, acetoacetic acid, and beta‐hydroxybutyrate levels in the PISA‐improved group. Significantly lower levels of C‐peptide, coefficient of variation of R‐R interval, and ankle‐brachial pressure index were observed before treatment in the PISA non‐improved group.

Conclusions

Glycaemic control treatment can effectively improve periodontitis in patients with type 2 diabetes, even in the absence of specific periodontal treatments. However, the periodontal responsiveness to glycaemic control treatment depends on the systemic condition of the patient.
Metformin in the Diabetes Prevention Program 3‐year trial: The cost‐effectiveness that never was
Authors: Rittenhouse Brian E. , Alolayan Sultan , Eguale Tewodros , Segal Alissa R. , Doucette Joanne
Published: August 2024

Aim

To highlight oversimplified quality‐adjusted life year (QALY) calculations and incremental cost‐effectiveness ratios (ICERs) regarding lifestyle metformin and placebo as flaws in the trial‐based (Diabetes Prevention Program) cost‐effectiveness analysis.

Materials and Methods

We revised the QALY calculations to conform to convention and calculated appropriate ICERs using both original and revised QALYs results. We used several additional health economics tools to present results, showing the consistency of each method and the added value of each. We presented net monetary benefits, assessed decision uncertainty and calculated net losses. We also used graphics, making correct interpretation clearer and allowing illustration and calculation of technical and economic inefficiencies of treatments that were not cost‐effective.

Results

ICERs with either QALY calculation indicated that metformin was technically and economically inefficient and not cost‐effective. There was virtually no decision uncertainty. All methods employed pointed to an identical conclusion.

Conclusions

In contrast to original claims, although lifestyle was cost‐effective in diabetes prevention, metformin was not, and acting otherwise imposes significant monetary and health costs. Various available tools of economic evaluation would probably have prevented the original misinterpretation by the authors had they been used. The varied tools implemented here illustrate with a common example their consistency and value to the field, showing how to depict the results in various ways.
Intra‐striatal infusion of the small molecule alpha‐synuclein aggregator, FN075, does not enhance parkinsonism in a subclinical AAV‐alpha‐synuclein rat model
Authors: Patton Tommy , Comini Giulia , Narasimhan Kaushik , Cairns Andrew G. , Ådén Jörgen , Almqvist Fredrik , Bemelmans Alexis , Brouillet Emmanuel , McKernan Declan P. , Dowd Eilís
Published: August 2024

Numerous challenges hinder the development of neuroprotective treatments for Parkinson's disease, with a regularly identified issue being the lack of clinically relevant animal models. Viral vector overexpression of α‐synuclein is widely considered the most relevant model; however, this has been limited by high variability and inconsistency. One potential method of optimisation is pairing it with a secondary insult such as FN075, a synthetic molecule demonstrated to accelerate α‐synucleinopathy. Thus, the aim of this study was to investigate if sequential infusion of adeno‐associated virus (AAV)‐α‐synuclein and FN075 into the rat brain can replicate α‐synucleinopathy, nigrostriatal pathology and motor dysfunction associated with Parkinson's disease. Rats received a unilateral injection of AAV‐α‐synuclein (or AAV‐green fluorescent protein) into two sites in the substantia nigra, followed 4 weeks later by unilateral injection of FN075 (or vehicle) into the striatum. Animals underwent behavioural testing every 4 weeks until sacrifice at 20 weeks, followed by immunohistochemistry assessment post‐mortem. As anticipated, AAV‐α‐synuclein led to extensive overexpression of human α‐synuclein throughout the nigrostriatal pathway, as well as elevated levels of phosphorylated and aggregated forms of the protein. However, the sequential administration of FN075 into the striatum did not exacerbate any of the α‐synuclein pathology. Furthermore, despite the extensive α‐synuclein pathology, neither administration of AAV‐α‐synuclein nor FN075, alone or in combination, was sufficient to induce dopaminergic degeneration or motor deficits. In conclusion, this approach did not replicate the key characteristics of Parkinson's disease, and further studies are required to create more representational models for testing of novel compounds and treatments for Parkinson's disease.
Paramedullary plasma cell myeloma originating from the first cervical vertebra (C1) in an 8‐month‐old Warmblood with tetraparesis: Clinical and pathological findings
Authors: Pelli Anna , Schiffbauer Vivien , Della Tommasa Simone , Ulrich Reiner , Reinert Anja , Gerlach Kerstin , Völker Iris
Published: August 2024

To the authors' knowledge there is only one report in the literature describing plasma cell paramedullary myeloma in horses as so‐called ‘break out lesions’, originating from vertebral bone marrow and invading the epidural space. This report describes clinical and pathomorphological findings of such. An 8‐month‐old Warmblood colt exhibited acute tetraparesis and a cervical column spinal cord lesion was suspected. Computed tomography revealed C1 osteolytic lesions by a heterogeneous mass. By pathomorphological examination including transmission electron microscopy, a plasma cell myeloma was identified, locally compressing the spinal cord. In tetraparetic young horses traumatic spinal cord injuries, cervical vertebral malformations, and central nervous system infectious diseases represent common differentials. However, osteolytic tumours such as paramedullary (plasma cell) myelomas, as space occupying lesion due to vertebral canal intrusion, should be considered as a cause for severe neurological deficits.
Comparison of radiography and computed tomography for identification of third metacarpal structural change and associated assessment of condylar stress fracture risk in Thoroughbred racehorses
Authors: Irandoust Soroush , O'Neil Linnea M. , Stevenson Christina M. , Franseen Faith M. , Ramzan Pieter H. L. , Powell Sarah E. , Brounts Sabrina H. , Loeber Samantha J. , Ergun David L. , Whitton R. Chris , Henak Corinne R. , Muir Peter
Published: August 2024

Background

Catastrophic injury has a low incidence but leads to the death of many Thoroughbred racehorses.

Objectives

To determine sensitivity, specificity, and reliability for third metacarpal condylar stress fracture risk assessment from digital radiographs (DR) and standing computed tomography (sCT).

Study design

Controlled ex vivo experiment.

Methods

A blinded set of metacarpophalangeal joint DR and sCT images were prepared from 31 Thoroughbreds. Four observers evaluated the condyles and parasagittal grooves (PSG) of the third metacarpal bone for the extent of dense bone and lucency/fissure and assigned a risk assessment grade for condylar stress fracture based on imaging features. Sensitivity and specificity for detection of subchondral structural changes in the condyles and PSG, and for risk assessment for condylar stress fracture were determined by comparison with a reference assessment based on sCT and joint surface examination. Agreement between observers and the reference assessment and reliability between observers were determined. Intra‐observer repeatability was also assessed.

Results

Sensitivity for detection of structural change was lower than specificity for both imaging methods and all observers. For agreement with the reference assessment of structural change, correlation coefficients were generally below 0.5 for DR and 0.49–0.82 for sCT. For horses categorised as normal risk on reference assessment, observer assessment often agreed with the reference. Sensitivity for risk assessment was lower than specificity for all observers. For horses with a reference assessment of high risk of injury, observers generally underestimated risk. Diagnostic sensitivity of risk assessment was improved with sCT imaging, particularly for horses categorised as having elevated risk of injury from the reference assessment. Assessment repeatability and reliability was better with sCT than DR.

Main limitations

The ex vivo study design influenced DR image sets.

Conclusions

Risk assessment through screening with diagnostic imaging is a promising approach to improve injury prevention in racing Thoroughbreds. Knowledge of sensitivity and specificity of fetlock lesion detection provides the critical guidance needed to improve racehorse screening programs. We found improved detection of MC3 subchondral structural change and risk assessment for condylar stress fracture with sCT ex vivo.
Mapping associations of polygenic scores with autistic and ADHD traits in a single city region
Authors: Reed Zoe E. , Thomas Richard , Boyd Andy , Griffith Gareth J. , Morris Tim T. , Rai Dheeraj , Manley David , Davey Smith George , Davis Oliver S.P.
Published: August 2024

Background

The genetic and environmental aetiology of autistic and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary spatially, but does this translate into variation in the association of specific common genetic variants?

Methods

We mapped associations between polygenic scores for autism and ADHD and their respective traits in the Avon Longitudinal Study of Parents and Children (N = 4,255–6,165) across the area surrounding Bristol, UK, and compared them to maps of environments associated with the prevalence of autism and ADHD.

Results

Our results suggest genetic associations vary spatially, with consistent patterns for autistic traits across polygenic scores constructed at different p‐value thresholds. Patterns for ADHD traits were more variable across thresholds. We found that the spatial distributions often correlated with known environmental influences.

Conclusions

These findings shed light on the factors that contribute to the complex interplay between the environment and genetic influences in autistic and ADHD traits.
The extended impact of the COVID‐19 pandemic on long‐term care residents in Medicare with frailty or dual Medicaid enrollment
Authors: Lin Sunny C. , Zheng Jie , Epstein Arnold , Orav E. John , Barnett Michael , Grabowski David C. , Joynt Maddox Karen E.
Published: August 2024

Background

Although many healthcare settings have since returned to pre‐pandemic levels of operation, long‐term care (LTC) facilities have experienced extended and significant changes to operations, including unprecedented levels of short staffing and facility closures, that may have a detrimental effect on resident outcomes. This study assessed the pandemic's extended effect on outcomes for LTC residents, comparing outcomes 1 and 2 years after the start of the pandemic to pre‐pandemic times, with special focus on residents with frailty and dually enrolled in Medicare and Medicaid.

Methods

Using Medicare claims data from January 1, 2018, through December 31, 2022, we ran over‐dispersed Poisson models to compare the monthly adjusted rates of emergency department use, hospitalization, and mortality among LTC residents, comparing residents with and without frailty and dually enrolled and non‐dually enrolled residents.

Results

Two years after the start of the pandemic, adjusted emergency department (ED) and hospitalization rates were lower and adjusted mortality rates were higher compared with pre‐pandemic years for all examined subgroups. For example, compared with 2018–2019, 2022 ED visit rates for dually enrolled residents were 0.89 times lower, hospitalization rates were 0.87 times lower, and mortality rates were 1.17 higher; 2022 ED visit rates for frail residents were 0.85 times lower, hospitalization rates were 0.83 times lower, and mortality rates were 1.21 higher.

Conclusions

In 2022, emergency department and hospital utilization rates among long‐term residents were lower than pre‐pandemic levels and mortality rates were higher than pre‐pandemic levels. These findings suggest that the pandemic has had an extended impact on outcomes for LTC residents.
“What choice do we have?” Reactive and proactive decision‐making for aging in place with dementia
Authors: Auriemma Catherine L. , Butt Maayra I. , McMillan Julia , Silvestri Jasmine A. , Chow Carolyn , Bahti Melanie , Klaiman Tamar , Harkins Kristin , Karlawish Jason , Halpern Scott D.
Published: August 2024

Background

Promoting options for aging in place (AIP) has broad appeal to policymakers and professionals providing services to persons living with dementia (PWD). However, the benefits or burdens of AIP likely vary among individuals and families. We sought to describe factors influencing decision‐making to age in place versus seek a higher level of residential care for PWD.

Methods

A qualitative study was undertaken as part of a larger mixed‐methods study utilizing semi‐structured interviews with PWD, family care partners, and dementia clinicians. Interview transcripts were analyzed using qualitative content analysis with constant comparison. Sample size was determined by thematic saturation within subgroups.

Results

We conducted 74 interviews among 14 PWD, 36 care partners, and 24 clinicians. Preferences for AIP were driven by (1) desire to preserve independence, (2) a sense that the “best care” is delivered by loved ones and in a familiar environment, (3) distrust and fear of care facilities, and (4) caregiver guilt. PWD and care partners frequently considered moving from home as a “last resort” and wanted to avoid planning for future care needs. Many decisions to move were reactive and triggered by patient safety events, physical dependency, or the loss of caregiver. Proactive decision‐making was facilitated by (1) prior experience witnessing the challenges of caring for a person with advanced dementia in the home; and (2) having substantial financial resources such that participants could seek major home adaptations or avoid “lower quality” institutions.

Conclusions

Decisions regarding care setting for PWD frequently do not feel like a choice and are made under imperfect conditions. Programs using AIP as an outcome measure should recognize the various patient‐centered and non‐patient‐centered factors that influence such choices, and interventions should be designed to promote more informed and equitable decision‐making for care setting in dementia.
Influence of collagen peptide supplementation on visible signs of skin and nail health and ‐aging in an East Asian population: A double blind, randomized, placebo‐controlled trial
Authors: Vleminckx Sara , Virgilio Nicolina , Asserin Jerome , Prawitt Janne , Silva Catarina I. F.
Published: August 2024

Background

A healthy skin provides protection against intrinsic and extrinsic factors. Skin aging is characterized by structural and morphological alterations affecting skin health, integrity, and functionality, resulting in visible aging signs.

Aim

The primary objective of this study was to assess the effect of a collagen peptide dietary supplement on skin aging in the East Asian population.

Methods

Eighty‐five healthy women, aged from 43 to 65 years old, were randomly assigned to the collagen supplement (CP, 5 g) or placebo (maltodextrin, 5 g) group. To standardize daily skin care, the volunteers in both groups used a specific face cream for 28 days prior to and throughout the supplementation period, creating an equal baseline for the assessment of the efficacy of CP on several skin parameters. At baseline, day 28 and day 84, the following hallmarks of skin and nail aging were assessed: dermis density, skin moisture and elasticity, wrinkle visibility, beauty perception, and nail color.

Results

After 84 days, a significant improvement of dermis density and skin moisture was observed in the collagen peptides group compared to the placebo group. Positive effects on skin elasticity, wrinkle visibility, nail color, and overall beauty perception were already observed within 28 days of supplementation in the CP group, while the same effects in the placebo group were only observed after 84 days.

Conclusion

Taken together, these results show that, in addition to a standardized skin care, daily supplementation with 5 g of collagen peptides positively affects visible signs of skin and nail aging in the East Asian population.
Investigating metabolic syndrome markers and body mass index changes in patients with acne vulgaris treated with isotretinoin: A prospective study
Authors: Bazargan Afsaneh Sadeghzadeh , Jafarzadeh Alireza , Danandeh Fatemeh , Salehi Sepideh
Published: August 2024

Background

Acne vulgaris is a common inflammatory skin disease that occurs during puberty, affecting approximately 85% of young adults and may persist into adulthood. The pathophysiology of acne is multifactorial, involving hormonal, inflammatory, and immune mechanisms. Isotretinoin is widely used for treating severe cystic acne or recurrent acne. This medication is considered a pharmacological option that significantly reduces sebum secretion, leading to a reduction in the size of sebaceous glands. It also induces a lack of differentiation in sebaceous cysts, resulting in a decrease in lipid accumulation.

Method

This research is a prospective study. Patient contact details were obtained directly from those visiting the dermatology clinic, and they were monitored for a duration of 3 months. Essential data was gathered through patient examinations and inquiries at the clinic, including the prescription of tests prior to initiating isotretinoin treatment. Furthermore, follow‐up tests and examinations were performed within the initial and third months post‐treatment commencement.

Results

Sixty‐two patients participated in the study, selected through non‐probability (convenience) sampling. The therapeutic dose taken by patients was 20 mg of isotretinoin daily (n = 49) or every other day (n = 13). Among the participants, six patients experienced a decrease of 3 units or more in HDL levels, while 16 patients saw an increase of 3 units or more in LDL levels, 3 months after beginning the treatment. Additionally, the triglyceride (TG) levels increased by 9 units or more in six individuals, and the blood sugar (BS) levels increased by 5 units or more in nine individuals, 3 months after treatment initiation. Moreover, one person's waist circumference increased by 1.5 cm 3 months after treatment began. The average weight of the individuals at the end of the treatment rose from 60.74 kg to 61.12 kg. However, this weight increase was not statistically significant. (p > 0.05).

Conclusion

In general, the results of our study show that the use of oral isotretinoin as a treatment option for the management of acne vulgaris can be effective when administered at the correct dosage, offering a safe and low‐complication option.
A digital workflow for full‐mouth rehabilitation using CAD‐CAM tooth reduction template
Authors: Liu Huanhuan , He Zijing , Xie Chenyang , Rao Sihan , Yu Haiyang
Published: August 2024

A digital workflow is presented for multiple transfers of targeted jaw relation and restorative spaces from interim to definitive restorations in patients with severe tooth wear. Following analysis of the targeted restorative space, segmented arch stereolithographic templates were digitally created and fabricated for precise control of reduction depth. Then, the jaw relation was transferred from the initially determined stabilization splint to the temporary fixed restoration and definitive restoration by using a digital articulator. This digital approach yielded a stabilized jaw relationship and restorative spaces transferring effect throughout successive stages of occlusal reconstruction resulting in satisfactory prosthetic outcomes.