bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity-dependent test-seeking behaviors and test-negative designs: impact on estimated vaccine effectiveness and utility of analytic and design choices
Authors: Amin Avnika B , Hitchings Matt D T , Ranzani Otavio T , Andrews Jason R , Cummings Derek A T , Ko Albert I , Croda Julio , Dean Natalie E
Published: August 2024

Test-negative designs are increasingly used to evaluate vaccine effectiveness because of desirable properties like reduced confounding due to health care–seeking behaviors and lower cost than other study designs. An individual’s decision to seek care often depends on their disease severity, with severe disease more likely to be captured than mild disease. As many vaccines likely attenuate disease severity, this phenomenon generally results in an upward-biased estimate of vaccine effectiveness against symptomatic disease. To address the resulting bias, analytic solutions like adjusting for or matching on severity have been suggested. In this article, we examine the performance of the test-negative design under different vaccine effects on disease severity and the utility of adjusting or matching on severity. We further consider the implications of studies that focus only on milder disease by restricting recruitment to outpatient settings. Through an analytic framework and simulations accompanied by a real-world example, we demonstrate that when vaccination attenuates disease severity, the magnitude of bias is influenced by the degree of underascertainment of mild disease relative to severe disease. When vaccination does not attenuate disease severity, bias is not present. We further show that analytic fixes negligibly impact bias and that outpatient-only studies frequently produce downward-biased estimates.
NST3 induces ectopic transdifferentiation, forming secondary walls with diverse patterns and composition in Arabidopsis thaliana
Authors: Tamadaddi Chetana , Choi Juseok , Ghasemi Masoud , Kim Seong H , Gomez Enrique D , Gomez Esther W , Anderson Charles T
Published: August 2024

Background and Aims

The master transcription factor NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3), also known as SND1, plays a pivotal role in regulating secondary cell wall (SCW) development in interfascicular and xylary fibres in Arabidopsis thaliana. Despite progress in understanding SCW assembly in xylem vessel-like cells, the mechanisms behind its assembly across different cell types remain unclear. Overexpression of NST3 or its homologue NST1 leads to reduced fertility, posing challenges for studying their impact on secondary wall formation. This study aimed to develop a tightly regulated dexamethasone (DEX)-inducible expression system for NST3 and NST1 to elucidate the structure and assembly of diverse SCWs.

Methods

Using the DEX-inducible system, we characterized ectopically formed SCWs for their diverse patterns, mesoscale organization, cellulose microfibril orientation and molecular composition using spinning disc confocal microscopy, field emission scanning electron microscopy, vibrational sum-frequency generation spectroscopy, and histochemical staining and time-of-flight secondary ion mass spectrometry, respectively.

Key Results

Upon DEX treatment, NST3 and NST1 transgenic hypocotyls underwent time-dependent transdifferentiation, progressing from protoxylem-like to metaxylem-like cells. NST3-induced plants exhibited normal growth but had rough secondary wall surfaces with delaminating S2 and S3 layers. Mesoscale examination of induced SCWs in epidermal cells revealed that macrofibril thickness and orientation were comparable to xylem vessels, while wall thickness resembled that of interfascicular fibres. Additionally, induced epidermal cells formed SCWs with altered cellulose and lignin contents.

Conclusions

These findings suggest NST3 and/or NST1 induce SCWs with shared characteristics of both xylem and fibre-like cells forming loosely arranged cell wall layers and cellulose organized at multiple angles relative to the cell growth axis and with varied cellulose and lignin abundance. This inducible system opens avenues to explore ectopic SCWs for bioenergy and bioproducts, offering valuable insights into SCW patterning across diverse cell types and developmental stages.
Deep5hmC: predicting genome-wide 5-hydroxymethylcytosine landscape via a multimodal deep learning model
Authors: Ma Xin , Thela Sai Ritesh , Zhao Fengdi , Yao Bing , Wen Zhexing , Jin Peng , Zhao Jinying , Chen Li
Published: August 2024

Motivation

5-Hydroxymethylcytosine (5hmC), a crucial epigenetic mark with a significant role in regulating tissue-specific gene expression, is essential for understanding the dynamic functions of the human genome. Despite its importance, predicting 5hmC modification across the genome remains a challenging task, especially when considering the complex interplay between DNA sequences and various epigenetic factors such as histone modifications and chromatin accessibility.

Results

Using tissue-specific 5hmC sequencing data, we introduce Deep5hmC, a multimodal deep learning framework that integrates both the DNA sequence and epigenetic features such as histone modification and chromatin accessibility to predict genome-wide 5hmC modification. The multimodal design of Deep5hmC demonstrates remarkable improvement in predicting both qualitative and quantitative 5hmC modification compared to unimodal versions of Deep5hmC and state-of-the-art machine learning methods. This improvement is demonstrated through benchmarking on a comprehensive set of 5hmC sequencing data collected at four developmental stages during forebrain organoid development and across 17 human tissues. Compared to DeepSEA and random forest, Deep5hmC achieves close to 4% and 17% improvement of Area Under the Receiver Operating Characteristic (AUROC) across four forebrain developmental stages, and 6% and 27% across 17 human tissues for predicting binary 5hmC modification sites; and 8% and 22% improvement of Spearman correlation coefficient across four forebrain developmental stages, and 17% and 30% across 17 human tissues for predicting continuous 5hmC modification. Notably, Deep5hmC showcases its practical utility by accurately predicting gene expression and identifying differentially hydroxymethylated regions (DhMRs) in a case–control study of Alzheimer’s disease (AD). Deep5hmC significantly improves our understanding of tissue-specific gene regulation and facilitates the development of new biomarkers for complex diseases.

Availability and implementation

Deep5hmC is available via https://github.com/lichen-lab/Deep5hmC
New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy
Authors: Raasing Lisette R M , Vogels Oscar J M , Datema Mirjam , Ambarus Carmen A , Tannemaat Martijn R , Grutters Jan C , Veltkamp Marcel
Published: August 2024

Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40–86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, P = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing (R = 0.3; P = 0.02) and the small fiber neuropathy screening list (R = 0.3; P = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list (R = 0.3; P = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used.
Higher odds of squamous cell carcinoma in sexual minority males compared with heterosexual males is mediated by HIV status in a mediation analysis of 13 687 participants
Authors: Curtis Kaya L , Stubblefield Onajia , Goleva Slavina B , Denny Joshua C , Lipner Shari R
Published: August 2024

We evaluated skin cancer risk in sexual minority (SM) compared with heterosexual individuals and assessed the mediation effect of HIV status on the association between SM status and skin cancer using a national database.
Environmental pollutant 3-methyl-4-nitrophenol promotes the expression of oncostatin M to exacerbate airway allergic inflammation
Authors: Mo Lihua , Wang Xinxin , Liao Yun , Liu Yu , Tang Aifa , Li Jing , Yang Pingchang
Published: August 2024

Asthma exacerbation is a common clinical occurrence. The causal factors are not fully understood yet. Environmental pollution is linked to asthma exacerbation. The objective of this study is to elucidate the role of 3-methyl-4-nitrophenol (MNP), an environmental pollutant, in asthma exacerbation. In this study, an airway allergy mouse model was established with ovalbumin as a specific antigen with or without the presence of MNP. The results showed that, in a mouse model, the intensity of airway allergy was significantly increased by exposure to MNP. RNAseq results showed an increase in endoplasmic reticulum (ER) stress-associated molecules and the Osm expression in airway epithelial cells of mice with airway allergy. Exposure of epithelial cells to MNP in culture induced the expression of oncostatin M (OSM) and ER stress associated molecules. The OSM receptor was expressed by macrophages. OSM could drive macrophages to produce tumor necrosis factor-α (TNF-α). Inhibition of PERK, one of the key molecules of ER stress, or depletion of OSM receptor in macrophages, could effectively attenuate the MNP/ovalbumin protocol induced airway allergy. To sum up, by promoting ER stress, environmental pollutant MNP can cause airway epithelial cells to produce OSM. The latter induces macrophages to produce TNF-α, which can exacerbate airway allergy.
A real-world analysis of adherence, biochemical outcomes, and healthcare costs in patients treated with rosuvastatin/ezetimibe as single-pill combination vs. free combination in Italy
Authors: Zambon Alberto , Liberopoulos Evangelos , Dovizio Melania , Veronesi Chiara , Degli Esposti Luca , Pérez de Isla Leopoldo
Published: August 2024

Aims

To compare medication adherence, lipid goal attainment, and healthcare costs between patients receiving a single-pill combination (SPC) vs. a free combination treatment (FCT) of rosuvastatin/ezetimibe (ROS/EZE) in Italy.

Methods and results

Administrative databases of healthcare entities covering ∼7 million individuals were used to identify adults prescribed with ROS/EZE as SPC or FCT between January 2018 and June 2020. Adherence was calculated as the proportion of days covered (PDC) after cohort balancing by propensity score matching. Patients with available LDL cholesterol testing were assessed for the proportion of those who at baseline were above lipid targets recommended by ESC/EAS Guidelines for their cardiovascular risk category and reached the target during follow-up. Among 25 886 patients on SPC and 7309 on FCT, adherent patients were more represented in SPC than FCT cohort (56.8 vs. 44.5%, P < 0.001), and this difference remained significant (P < 0.001) after stratification by cardiovascular risk (very high, high, and other). The proportion of patients reaching LDL cholesterol target at 1 year follow-up was significantly (P < 0.001) higher in SPC vs. FCT cohort: 35.4 vs. 23.8% for very high cardiovascular risk, 46.9 vs. 23.1% for high risk and 71.6 vs. 49.5% for other risk. Total healthcare costs per patient at 1 year follow-up were lower in SPC vs. FCT users (2337€ vs. 1890€, P < 0.001). In both cohorts, costs were mainly driven by drug expenses and hospitalizations.

Conclusion

This real-world analysis in dyslipidaemic patients found that treatment with ROS/EZE as SPC resulted in better adherence, higher chances of reaching lipid goals, and cost savings over FCT, in all cardiovascular risk categories.
Accumulation of dually targeted StGPT1 in chloroplasts mediated by StRFP1, an E3 ubiquitin ligase, enhances plant immunity
Authors: Wu Xintong , Zhou Xiaoshuang , Lin Tianyu , Zhang Zhe , Wu Xinya , Zhang Yonglin , Liu Yanli , Tian Zhendong
Published: August 2024

Chloroplasts play a crucial role in essential processes, such as photosynthesis and the synthesis of primary and diverse secondary metabolites. Recent studies have also highlighted their significance linked to phytohormone production in plant immunity, especially SA and JA. Ubiquitination, a key posttranslational modification, usually leads to target protein degradation, which acts as a signal for remodeling the proteome via the induction of protein endocytosis or targeting to other membrane associated systems. Previously, the potato E3 ligase StRFP1 was shown to enhance resistance against Phytophthora infestans, but its mechanism remained unclear. Here, we demonstrate that StRFP1 interacted with the dually localized plastid glucose 6-phosphate transporter StGPT1 on the endoplasmic reticulum (ER). Transiently expressed StGPT1-GFP located on the chloroplast and ER in plant cells. Overexpression of StGPT1 enhances late blight resistance in potato and Nicotiana benthamiana, activates immune responses, including ROS bursts and up-regulation of PTI marker genes. The resistance function of StGPT1 seems to be related to its dual localization. Remarkably, StRFP1 ubiquitinates StGPT1 at the ER, possibly due to its merely transient function in peroxisomes, leading to apparent accumulation in chloroplasts. Our findings point to a novel mechanism by which a plant E3 ligase contributes to immunity via interacting with dually targeted GPT1 at the ER of plant cells.
First joint X-ray solar microflare observations with NuSTAR and Solar Orbiter/STIX
Authors: Bajnoková Natália , Hannah Iain G , Cooper Kristopher , Krucker Säm , Grefenstette Brian W , Smith David M , Jeffrey Natasha L S , Duncan Jessie
Published: August 2024

We present the first joint spectral and imaging analysis of hard X-ray (HXR) emission from three microflares observed by the Nuclear Spectroscopic Telescope ARray (NuSTAR) and Solar Orbiter/Spectrometer/Telescope for Imaging X-rays (STIX). We studied 5 joint spectra from GOES A7, B1, and B6 class microflares from active region AR12765 on 2020 June 6 and 7. As these events are very bright for NuSTAR, resulting in extremely low (<1 per cent) livetime, we introduce a pile-up correction method. All five joint spectra were fitted with an isothermal model finding temperatures in the 9–11 MK range. Furthermore, three joint spectra required an additional non-thermal thick-target model finding non-thermal powers of $10^{25}$–$10^{26}$ erg s$^{-1}$. All the fit parameters were within the ranges expected for HXR microflares. The fit results give a relative scaling of STIX and NuSTAR mostly between 6 and 28 per cent (one outlier at 52 per cent) suggesting each instrument are well calibrated. In addition to spectral analysis, we performed joint HXR imaging of the June 6 and one of the June 7 microflares. In NuSTAR’s field of view (FOV), we observed two separate non-thermal sources connected by an elongated thermal source during the June 6 microflares. In STIX’s FOV (44$^{\circ }$ W with respect to NuSTAR), we imaged thermal emission from the hot flare loops which when reprojected to an Earth viewpoint matches the thermal sources seen with NuSTAR and in the hotter EUV channels with the Solar Dynamic Observatory’s Atmospheric Imaging Assembly.
Clinical features of juvenile onset ankylosing spondylitis in Japanese patients
Authors: Kishimoto Kenji , Asai Shuji , Suzuki Mochihito , Sato Ryo , Hasegawa Junya , Terabe Kenya , Imagama Shiro
Published: August 2024

Objectives

This retrospective study aimed to examine the clinical features of juvenile onset ankylosing spondylitis (JoAS) in Japanese patients.

Methods

We examined clinical symptoms (including initial symptoms) and the progression to diagnosis of AS in 17 Japanese JoAS patients at Nagoya university hospital between January 2004 and May 2023. Initial symptoms considered were pain at axial joints and/or extra-axial joints.

Results

Mean ages (± standard deviation) at onset and diagnosis of AS were 12.9 (± 2.0) and 19.6 (± 9.6) years, respectively. The back was the most common site of initial symptoms (7 patients; 41.2%), followed by the hip (5 patients; 29.4%) and knees (5 patients; 29.4%). Initial symptoms were limited to extra-axial joints and axial joints in 9 (52.9%) and 7 (41.2%) patients, respectively. Nine patients (52.9%) were recognised as a musculoskeletal disease other than AS, such as oligoarticular juvenile idiopathic arthritis.

Conclusions

Sites of initial symptoms frequently were the back, hip, and knees, with 52.9% of patients having initial symptoms limited to extra-axial joints. More than half of the patients recognised musculoskeletal diseases other than AS.
Expanding super-resolution imaging versatility in organisms with multi-confocal image scanning microscopy
Authors: Ren Wei , Guan Meiling , Liang Qianxi , Li Meiqi , Jin Boya , Duan Guangxing , Zhang Liya , Ge Xichuan , Xu Hong , Hou Yiwei , Gao Baoxiang , Sodmergen  , Xi Peng
Published: August 2024

Resolving complex three-dimensional (3D) subcellular dynamics noninvasively in live tissues demands imaging tools that balance spatiotemporal resolution, field-of-view and phototoxicity. Image scanning microscopy (ISM), as an advancement of confocal laser scanning microscopy, provides a 2-fold 3D resolution enhancement. Nevertheless, the relatively low imaging speed has been the major obstacle for ISM to be further employed in in vivo imaging of biological tissues. Our proposed solution, multi-confocal image scanning microscopy (MC-ISM), aims to overcome the limitations of existing techniques in terms of spatiotemporal resolution balancing by optimizing pinhole diameter and pitch, eliminating out-of-focus signals, and introducing a frame reduction reconstruction algorithm. The imaging speed is increased by 16 times compared with multifocal structured illumination microscopy. We further propose a single-galvo scan, akin to the Archimedes spiral in spinning disk confocal systems, to ensure a high-speed and high-accuracy scan without the galvanometer's inertial motion. Benefitting from its high photon efficiency, MC-ISM allows continuous imaging of mitochondria dynamics in live cells for 1000 frames without apparent phototoxicity, reaching an imaging depth of 175 μm. Noteworthy, MC-ISM enables the observation of the inner membrane structure of living mitochondria in Arabidopsis hypocotyl for the first time, demonstrating its outstanding performance.
Direct propylene epoxidation with molecular oxygen over titanosilicate zeolites
Authors: Li Weijie , Qin Bin , Dong Zhuoya , Chai Yuchao , Wu Guangjun , Ma Yanhang , Wang Meng , Liu Xingwu , Ma Ding , Li Landong
Published: August 2024

The direct epoxidation of propylene with molecular oxygen represents a desired route for propylene oxide (PO) production with 100% theoretical atomic economy. However, this aerobic epoxidation reaction suffers from the apparent trade-off between propylene conversion and PO selectivity, and remains a key challenge in catalysis. We report that Ti-Beta zeolites containing isolated framework Ti species can efficiently catalyze the aerobic epoxidation of propylene. Stable propylene conversion of 25% and PO selectivity of up to 90% are achieved at the same time, matching the levels of industrial ethylene aerobic epoxidation processes. H-terminated pentacoordinated Ti species in Beta zeolite frameworks are identified as the preferred active sites for propylene aerobic epoxidation and the reaction is initiated by the participation of lattice oxygen in Ti-OH. These results are expected to spark new technology for the industrial production of PO toward more sustainable chemistry and chemical engineering.
Association of COVID-19 Vaccination With Risk of Medically Attended Postacute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras
Authors: Swift Melanie D , Breeher Laura E , Dierkhising Ross , Hickman Joel , Johnson Matthew G , Roellinger Daniel L , Virk Abinash
Published: August 2024

Background

Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings.

Methods

In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection.

Results

During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses.

Conclusions

We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.
Assessing the adoption and utilization of the Rwanda COVID-19 data analytics system: a mixed methods approach
Authors: Mugabo Hassan , Rukundo Gilbert , Ngabonziza Jean Claude S , Mazarati Jean-Baptiste , Aghatise Joseph , Akinwusi Olukunle
Published: August 2024

Introduction: Rwanda has been widely lauded for its exceptional response to the COVID-19 pandemic. However, although Rwanda established a national system for COVID-19 testing and vaccination data, concerns have been raised about data fragmentation which requires linkage of various data sources, access to data for real-time decision-making, and data completeness. Methods: We assessed the adoption of the Rwanda COVID-19 data Analytics System (RCAS) for public health staff that employ data from various platforms to generate evidence for policy- and decision-making. A random sample of 56 participants was drawn from the 98 who attended the 2022 RCAS training for data managers from the Rwanda Biomedical Center, technical partners, and health facilities. Of the selected participants, 42 completed the online self-administered questionnaire within the 14-day data collection period. Key informant interviews were then conducted with a subset of 14 respondents. Results: A strong positive relationship (χ2 = 9.1049, P < 0.05) emerged between respondents' decision-making regarding RCAS and their support for its sustainability. There was a marginal association (χ2 = 3.3358, P = 0.059) suggesting a link between users' ease of data exchange through RCAS and their support for its long-term sustainability, warranting further exploration. Conclusion: RCAS had a positive impact on improvements in data linkage, access to individual-level data for analyses, and progress toward harmonization of health data beyond COVID-19 in Rwanda. Users noted the usability, acceptability, and interoperability of the system. Recommendations for further improvement and scaling of the intervention are discussed.
It Takes a Movement: Lawyers, Litigation, and Legal Theory in the Attack on Campaign Finance Reform
Authors: Briffault Richard
Published: August 2024

Recent Supreme Court decisions have hobbled campaign finance regulation and placed significant constitutional constraints on possible future reforms. But the Supreme Court has not acted alone. Major constitutional changes often require a substantial legal and political infrastructure, an ecosystem of actors, ideas, strategies, and tactics to instantiate new constitutional doctrine into law. In Big Money Unleashed, Ann Southworth examines the composition, development, organization, and intellectual underpinning of the legal movement that has worked to cripple campaign finance regulation. She chronicles the raising and testing of the key legal theories; the sources of political and financial backing for the movement; the combination of disparate groups into an antireform coalition; and the organization of what has proven to be a very effective litigation strategy. The result, she explains, has been the ascendancy of a powerful constitutional discourse that treats money as speech, campaign spending as freedom, and government regulation as censorship. The antireform litigation campaign on its own would not have been enough to transform the law; key appointments to the Supreme Court were essential. But the movement provided the Court with the cases, the arguments, and broader political support that are part of constitutional change.
Using Neuromodulators for Salivary, Eccrine, and Apocrine Gland Disorders
Authors: Rajanala Susruthi , Salame Nicole , Dover Jeffrey S.
Published: August 2024

BACKGROUND

Sialorrhea, hyperhidrosis, bromhidrosis, and chromhidrosis are common glandular disorders that substantially impact patients' health and quality of life. Botulinum toxin can safely and temporarily decrease gland secretions by targeting the parasympathetic cholinergic neurons, resulting in diminished saliva and sweat production.

OBJECTIVE

The objective of this article is to describe the applications of neuromodulators for the treatment of salivary, eccrine, and apocrine glands.

METHODS

PubMed was searched from inception to February 1, 2024 using search terms “neurotoxin,” “botulinum toxin,” “sialorrhea,” “hyperhidrosis,” “bromhidrosis,” and “chromhidrosis.”

RESULTS

Incobotulinumtoxin A and Rimabotulinumtoxin B are approved by the FDA for the treatment of sialorrhea. Onabotulinumtoxin A is the only FDA-approved botulinum toxin for axillary hyperhidrosis and is used off-label for hyperhidrosis of nonaxillary sites, bromhidrosis, and chromhidrosis. Compared to botulinum toxin serotype A, serotype B has been associated with more immunogenicity, which may have implications for patients requiring long-term treatment for chronic glandular disorders.

CONCLUSION

Neuromodulators are safe and effective for the noninvasive treatment of excess gland activity and can improve patients' quality of life. While substantial literature supports botulinum toxin treatments for hyperhidrosis, further studies are needed to characterize standard dosing and administration techniques for sialorrhea, bromhidrosis, and chromhidrosis.
Serum protein responses to Dietary Approaches to Stop Hypertension (DASH) and DASH-Sodium trials and associations with blood pressure changes
Authors: Kim Hyunju , Lichtenstein Alice H. , Coresh Josef , Appel Lawrence J. , Rebholz Casey M.
Published: August 2024

Objectives:

The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure, but the mechanisms underlying DASH diet-blood pressure relations are not well understood. Proteomic measures may provide insights into the pathophysiological mechanisms through which the DASH diet reduces blood pressure.

Methods:

The DASH (1994–1996) and DASH-Sodium (1997–1999) trials were multicenter, randomized-controlled feeding trials. Proteomic profiling was conducted in serum collected at the end of the feeding period (DASH, N = 215; DASH-Sodium, N = 390). Multivariable linear regression models were used to identify interactions between 71 DASH diet-related proteins and changes in systolic and diastolic blood pressure. Estimates were meta-analyzed across both trials. Elastic net models were used to identify proteins that predict changes in blood pressure.

Results:

Ten significant interactions were identified [systolic blood pressure: seven proteins; diastolic blood pressure: three proteins], which represented nine unique proteins. A high level of renin at the end of the feeding period was associated with greater reductions in diastolic blood pressure in individuals consuming the control than DASH diets. A high level of procollagen c-endopeptidase enhancer 1 (PCOLCE) and collagen triple helix repeat-containing protein 1 (CTHRC1) were associated with greater reductions in systolic blood pressure in individuals consuming the DASH than control diets, and with elevations in systolic blood pressure in individuals consuming the control diets (P for interaction for all tests < 0.05). Elastic net models identified six additional proteins that predicted change in blood pressure.

Conclusions:

Several novel proteins were identified that may provide some insight into the relationship between the DASH diet and blood pressure.
Trajectory of Telework in a Brazilian Labor Court During the COVID-19 Pandemic
Authors: El Kadri Filho Fauzi , de Lucca Sérgio Roberto
Published: August 2024

Objective

This study aimed to compare ergonomic and psychosocial risks and the prevalence of musculoskeletal problems and common mental disorders during the coronavirus disease 2019 pandemic according to work modality.

Methods

A longitudinal study was carried out with 659 employees between 2021 and 2022. The data were collected via web with self-administered questionnaires. The Wilcoxon and repeated-measure analysis of variance tests were used.

Results

The participants who started teleworking during the pandemic showed significant improvements in their workstations and worsening of the risks associated with rest breaks after returning to face-to-face work. Employees in telework presented a significant reduction in the intensity of musculoskeletal complaints in the last 7 days compared to those who returned to face-to-face work.

Conclusions

Although there was a reduction in the ergonomic risk after returning to face-to-face work, telework was related to better working and health conditions.
Modern Oncologic Maxillary Reconstruction
Authors: Morrison Edwin J. , Matros Evan
Published: August 2024

Learning Objectives:

After studying this article, the participant should be able to: (1) Have a broad understanding of the oncological principles relating to cancers involving the maxilla. (2) Define anatomically the various types of maxillectomy defects and their associated morbidity. (3) Understand the goals and principles of maxillary reconstruction. (4) Demonstrate an understanding of the strengths, limitations, and alternative reconstructive options for the various types of maxillectomy defects.

Reconstruction of the maxilla following cancer resection has evolved over the past decade. Underpinned by advances in virtual surgery technology and an increased focus on dental rehabilitation, more sophisticated workflows using free bone flaps have become more commonplace. There are few reconstructions anywhere in the body that require the restoration of similarly intricate bone and soft-tissue relations with implications for both form and function, like the maxilla. Success demands careful anatomical definition of the defect, an understanding of the goals and principles of reconstruction, and the understanding of relative strengths and limitations of the various reconstructive options. Equally, as no one technique is without shortcomings and maxillary surgery can be associated with a significant complication profile, it is just as important to match the patient and oncologic context to the reconstruction. This article is intended to provide the reader with a broad overview of these core factors.
An Incidental Detection of Breast Cancer Osteolytic Bone Metastasis Using a 99mTc-TRODAT-1 SPECT Scan
Authors: Kuo Chun-Liang , Chang Yu-Hong , Yang Rong-Hsin
Published: August 2024

This report presents a case of suspected Parkinson disease in a 76-year-old woman with a history of slurred speech, general weakness, unstable gait, and bradykinesia for months. A 99mTc-TRODAT-1 SPECT scan revealed a symmetrically decreased bilateral nigrostriatal system, including bilateral putamen and caudate nuclei. The scintigraphic findings may reflect normal aging or atypical parkinsonism. The bilateral frontal bones and left temporal bone exhibited increased uptake of 99mTc-TRODAT-1, and previous 99mTc-MDP bone scan and CT images were reviewed. Osteolytic lesions at the corresponding site indicated bone metastasis from breast cancer.
Evaluation of Factors Influencing Postoperative Cognitive Dysfunction in Patients After Cranial Tumor Surgery
Authors: Cheng Fang , Lin Hua-Fu , Liang Xiao-Jie , Wu Shu-Yun , Wu Xu-Fang , Tu Wei-Feng
Published: August 2024

Background:

The authors retrospectively analyzed the perioperative data of 81 patients who underwent cranial tumor surgery to explore the factors influencing POCD in patients after the surgery.

Methods:

The authors evaluated preoperative cognitive dysfunction using the Mini-Mental State Examination (MMSE) score measured. For patients whose cognitive function was normal, the authors retrieved the MMSE score on the seventh day after surgery and compared it to determine whether the patients had POCD. The authors used a univariate logistic regression analysis to analyze the perioperative factors in patients, namely, age, gender, history of underlying diseases, tumor size, peritumoral edema, duration of surgery, blood loss, intraoperative fluid infusion, and type of anesthetic drugs. The authors then performed a multivariate logistic regression analysis for the statistically significant factors.

Results:

The authors found that 23 of 81 patients (28.4%) developed POCD. Univariate logistic analysis showed that a history of diabetes mellitus, peritumoral edema, intraoperative blood loss, and anesthetic drugs were the risk factors for patients developing POCD after cranial tumor surgery. Multivariate logistic regression analysis showed that a history of diabetes mellitus, peritumoral edema, and use of ciprofol as the anesthetic drug were independent risk factors for POCD after cranial tumor surgery.

Conclusions:

A history of diabetes mellitus, the degree of brain tumor edema, and the choice of anesthetic drugs significantly influence the occurrence of POCD in patients after cranial tumor surgery.
MECHANICAL LEFT VENTRICULAR UNLOADING IN CARDIOGENIC SHOCK TREATED WITH VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kotani Yuki , Yamamoto Taihei , Koroki Takatoshi , Yaguchi Takahiko , Nakamura Yuta , Tonai Mayuko , Karumai Toshiyuki , Nardelli Pasquale , Landoni Giovanni , Hayashi Yoshiro
Published: August 2024

Objective: To evaluate if mechanical left ventricular unloading could reduce mortality in patients with cardiogenic shock undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials and propensity score–matched studies published until December 20, 2023. The primary outcome was mortality at the longest follow-up. We used a Mantel-Haenszel random effects meta-analysis and reported the pooled results with a risk ratio (RR) and 95% confidence interval (CI). The review protocol was registered on PROSPERO International prospective register of systematic review (CRD42024498665). Results: We identified two randomized controlled trials and 11 propensity score–matched studies, totaling 9,858 patients. Mechanical left ventricular unloading was significantly associated with reduced mortality at the longest follow-up (RR, 0.89; 95% CI, 0.84–0.94; P = 0.0001; moderate certainty of evidence), which was confirmed in studies using intra-aortic balloon pump. Benefits of mechanical unloading were also observed in terms of successful VA-ECMO weaning (RR, 1.15; 95% CI, 1.02–1.29; P = 0.02; low certainty of evidence) and favorable neurological outcome (two studies; RR, 2.45; 95% CI, 1.62–3.69; P < 0.0001; low certainty of evidence), although we observed an increased incidence of major bleeding (RR, 1.27; 95% CI, 1.02–1.59; P = 0.03; low certainty of evidence) and hemolysis (RR, 1.49; 95% CI, 1.10–2.02; P = 0.01; moderate certainty of evidence). Conclusions: Among adult patients with cardiogenic shock treated with VA-ECMO, mechanical left ventricular unloading was associated with reduced mortality, which was confirmed in studies using intra-aortic balloon pump as an unloading device.
Freshwater fish and the Cretaceous/Palaeogene boundary: a critical assessment of survivorship patterns
Authors: Wilson Jacob D. , Huang E. J. , Lyson Tyler R. , Bever Gabriel S.
Published: August 2024

Mass extinctions are major influences on both the phylogenetic structure of the modern biota and our ability to reconstruct broad-based patterns of evolutionary history. The most recent mass extinction is also the most famous—that which implicates a bolide impact in defining the Cretaceous/Palaeogene boundary (K/Pg). Although the biotic effects of this event receive intensive scrutiny, certain ecologically important and diverse groups remain woefully understudied. One such group is the freshwater ray-finned fishes (Actinopterygii). These fish represent 25% of modern vertebrate diversity, yet the isolated and fragmentary nature of their K/Pg fossil record limits our understanding of their diversity dynamics across this event. Here, we address this problem using diversification analysis of molecular-based phylogenies alongside a morphotype analysis of fossils recovered from a unique site in the Denver Basin of western North America that provides unprecedented K/Pg resolution. Our results reveal previously unrecognized signals of post-K/Pg diversification in freshwater clades and suggest that the change was driven by localized and sporadic patterns of extinction. Supported inferences regarding the effects of the K/Pg event on freshwater fish also inform our expectations of how freshwater faunas might recover from the current biodiversity crisis.
FACS-based detection of extracellular ASC specks from NLRP3 inflammasomes in inflammatory diseases
Authors: Topping Joanne , Lara-Reyna Samuel , Ibbotson Alice , Jarosz-Griffiths Heledd , Chang Leon , Poulter James , Peckham Daniel , McDermott Michael F. , Savic Sinisa
Published: August 2024

The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is crucial for inflammasome assembly and activation of several inflammasomes, including NLRP3. ASC aggregates are detected in human sera post pyroptotic cell death, but their inflammasome origin remains unclear. This study aimed to develop a method to detect ASC aggregates originating from NLRP3 inflammasomes. Initially, human monocytes, macrophages, and THP-1 ASC reporter cells were employed to validate the detection of ASC/NLRP3-positive events through flow cytometry. The presence of ASC/NLRP3 specks was confirmed in cell supernatants from monocytes and macrophages treated with LPS and nigericin or ATP. Flow cytometry analysis identified double-positive specks in patient sera from inflammatory conditions when compared to healthy controls. Elevated ASC/NLRP3 specks were observed in conditions such as CAPS and Schnitzler’s syndrome. We validated FACS as a reliable method for detecting ASC/NLRP3 specks in human sera, with potential diagnostic and monitoring applications in certain systemic autoinflammatory diseases.
Inequalities in Mental Health: Age-related Trends Across Pandemic Phases in Singapore
Authors: Goh Nicole Shu En , Morgenstern Christian , Wei Yap Alex Jie , Yin Wong Stanford Chun , Subramaniam Mythily , Bin Abdin Edimansyah , Boon Lye David Chien , Tan Kelvin Bryan , Xuan Tan Sharon Hui
Published: August 2024

Background

In the sphere of mental health, little population wide-scale research has been done in Asia on the pandemic’s differential impacts on different sociodemographic groups over time.

Methods

This study evaluates symptoms of anxiety and depression within different age groups in Singapore across different pandemic phases. Symptoms of depression and anxiety were measured using the Patient Health Questionnaire-4 (PHQ-4), in which higher scores indicate more symptoms and lower scores indicate less. Cross-sectional data from 34,429 individuals aged 18 years and above in Singapore between 27 April 2020 and 27 September 2021 were analyzed. Multivariable logistic and linear regression were performed on PHQ-4 scores over pandemic phases and by age.

Findings

Overall symptoms of depression and anxiety did not vary significantly across pandemic phases in Singapore. However, compared to Circuit Breaker, younger age groups reported higher PHQ-4 scores as restrictions lifted (ages 18-29:beta (β)=0·59, 95% CI [0·22, 0·97]; ages 30-39: β=0·44, 95% CI [0·08, 0·80]), while older adults reported lower scores (ages 50-59: β=-0·45, 95% CI [-0·80, -0·10];ages 60 and above: β=-0·38, 95% CI [-0·73, -0·02]). This was associated with more symptoms of anxiety among younger adults, and less symptoms of depression and anxiety among older adults.

Interpretation

In Singapore, psychological responses to pandemic restrictions may be heterogenous across different age groups and across time. The study can inform policymakers’ decisions in distributing mental health resources during a crisis.

Funding

The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Adaptive Deep Brain Stimulation in Parkinson’s Disease: A Delphi Consensus Study
Authors: Guidetti M. , Bocci T. , De Pedro Del Álamo M. , Deuschl G. , Fasano A. , Fernandez R. Martinez , Gasca-Salas C. , Hamani C. , Krauss J.K. , Kühn A. A. , Limousin P. , Little S. , Lozano A.M. , Maiorana N.V. , Marceglia S. , Okun M.S. , Oliveri S. , Ostrem J. L. , Scelzo E. , Schnitzler A. , Starr P.A. , Temel Y. , Timmermann L. , Tinkhauser G. , Visser-Vandewalle V. , Volkmann J. , Priori A.
Published: August 2024

Importance

If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS.

Observations

We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson’s disease patients and for those with motor fluctuations and dyskinesias.

Conclusions and Relevance

Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.
Conditional Knockout of Striatal Gnal Produces Dystonia-like Motor Phenotypes
Authors: Chambers Nicole E. , Hall Dominic , Barsoum Stephanie , Miller Evan , Curry Tiffany , Kaplan Morgan , Garan Sarah , Gallardo Ignacio , Staab Rick , Nabert Douglas , Hutchinson Kevin , Millett Michael , Moehle Mark S.
Published: August 2024

Loss-of-function mutations inGNALhave been linked to an adult-onset, isolated dystonia that is largely indistinguishable from idiopathic dystonia.GNALencodes Gαolf, a heterotrimeric G-protein α subunit with a defined molecular function to increase the production of the second messenger cAMP. Gαolfis abundant in the striatum, and is the only stimulatory G-protein in many cell types of the striatum. Due to the defined molecular signaling pathway and expression pattern of Gαolf, the clear genetic link to dystonia makesGNALan exciting target to understand the pathological mechanisms of not only this genetic dystonia, but also the larger idiopathic disease. To better understandGNAL-linked dystonia, we generated a novel genetic mouse model that allows us to conditionally knock outGnalin a site and time-specific manner. In the current study we used genetic or AAV based approaches to express Cre to knockout striatalGnalin our novelGnal fl/flmodel. We then performed motor behavioral testing andex vivowhole-cell patch clamp electrophysiology of striatal spiny projection neurons to interrogate how loss ofGnalleads to dystonia. Mice with conditional striatal knockout ofGnalshow hindlimb clasping, other dystonia-like postures, less motor coordination, slowness, and torticollis as compared to age-matched controls. Furthermore, striatal spiny projection neurons show increased excitability inGnalknockout animals. These exciting data are the first to report uninduced, overt dystonia in a mouse model ofGNAL-linked dystonia, and directly correlate these with changes in spiny projection neuron electrophysiological properties. Our results show that adult loss ofGnalin the striatum leads to the development of dystonia, through homeostatic, paradoxical increases in spiny projection neuron excitability, and suggest that therapeutic strategies aimed at decreasing this hyperexcitable phenotype may provide symptomatic relief for patients with disease.

One Sentence Summary:WhenGnalis knocked out in the striatum of mice we observe overt behavioral symptoms and hyperexcitability in striatal spiny projection neurons.