bluuebunny/crossref_metadata_2025_split huggingface dataset:
A future of data-rich pharmacoepidemiology studies: transitioning to large-scale linked electronic health record + claims data
Authors: Schneeweiss Sebastian , Desai Rishi J , Ball Robert 
Published: July 2024

Abstract
Electronic health record (EHR) data are seen as an important source for pharmacoepidemiology studies. In the US health-care system, EHR systems often identify only fragments of patients’ health information across the care continuum, including primary care, specialist care, hospitalizations, and pharmacy dispensing. This leads to unobservable information in longitudinal evaluations of medication effects, causing unmeasured confounding, misclassification, and truncated follow-up times. A remedy is to link EHR data with longitudinal health insurance claims data, which record all encounters during a defined enrollment period across all care settings. Here we evaluate EHR and claims data sources in 3 aspects relevant to etiological studies of medical products: data continuity, data granularity, and data chronology. Reflecting on the strengths and limitations of EHR and insurance claims data, it becomes obvious that they complement each other. The combination of both will improve the validity of etiological studies and expand the range of questions that can be answered. As the research community transitions towards a future state with access to large-scale combined EHR + claims data, we outline analytical templates to improve the validity and broaden the scope of pharmacoepidemiology studies in the current environment where EHR data are available only for a subset of patients with claims data.
This article is part of a Special Collection on Pharmacoepidemiology.
Worker perspectives on improving occupational health and safety using wearable sensors: a cross-sectional survey
Authors: Mueller William , Smith Alice , Kuijpers Eelco , Pronk Anjoeka , Loh Miranda 
Published: July 2024

Abstract
Workplace exposure is an important source of ill health. The use of wearable sensors and sensing technologies may help improve and maintain worker health, safety, and wellbeing. Input from workers should inform the integration of these sensors into workplaces. We developed an online survey to understand the acceptability of wearable sensor technologies for occupational health and safety (OSH) management. The survey was disseminated to members of OSH-related organizations, mainly in the United Kingdom and the Netherlands. There were 158 respondents, with over half (n = 91, 58%) reporting current use of wearable sensors, including physical hazards (n = 57, 36%), air quality (n = 53, 34%), and location tracking (n = 36, 23%), although this prevalence likely also captures traditional monitoring equipment. There were no clear distinctions in wearable sensor use between the reported demographic and occupational characteristics, with the exception that hygienists were more likely than non-hygienists (e.g. safety professionals) to use wearable sensors (66% versus 34%). Overall, there was an interest in how sensors can help OSH professionals understand patterns of exposure and improve exposure management practices. Some wariness was expressed primarily around environmental and physical constraints, the quality of the data, and privacy concerns. This survey identified a need to better identify occupational situations that would benefit from wearable sensors and to evaluate existing devices that could be used for occupational hygiene. Further, this work underscores the importance of clearly defining “sensor” according to the occupational setting and context.
Mandibular Ligament and the Prejowl Sulcus Explained
Authors: Talei Benjamin , Ziai Hedyeh 
Published: July 2024

Abstract

The exact relationship between the jowl and the mandibular ligament and causes for jowling remain unclear in the literature. The anatomic basis for the jowl is multifactorial and disparities in descriptions of the mandibular ligament and prejowl sulcus have resulted in variations in its management. The aim of this paper was to clarify the anatomy and aging around the prejowl sulcus and the mandibular ligament and review our experience with its management in facial rejuvenation. We performed a retrospective blinded review of patients in a high-volume private practice comparing patients who underwent mandibular ligament release in a subdermal plane during facelift with those who solely underwent fat grafting of the prejowl sulcus with facelift. Blinded surgeons graded 25 patients who had undergone mandibular ligament release and 25 patients who did not. Patient photographs were scored on a 1 to 4 graded scale of correction on the degree of jowling and prejowl sulcus depth and color. We also performed a literature review to describe the anatomy of the mandibular ligament and its implications for jowls, and techniques to address it in facial rejuvenation. Patients who had fat grafting with minimal or no release of the skin around the prejowl sulcus or mandibular ligament had a greater degree of correction of their jowls in their postoperative photographs than those who had a mandibular ligament release without fat grafting (P = .046). Adverse sequelae were also lower in the group with less skin dissection around the mandibular ligament. Our findings support the theory that the appearance of tethering and depression in the prejowl sulcus is more likely the cause of atrophy in the subdermal soft tissues than a consequence of ligamentous contracture. Volumetric replenishment with fat grafting provides a more direct solution to the cause of the issue, providing more universal improvements with less risk. Surgeons should consider volumetric fat grafting with or without subsequent subdermal release if needed.

Level of Evidence: 4
Mating preferences act independently on different elements of visual signals in Heliconius butterflies
Authors: Smith Sophie Helen , Queste Lucie M , Wright Daniel Shane , Bacquet Caroline Nicole , Merrill Richard M 
Published: July 2024

Abstract
Mating cues are often comprised of several elements, which can act independently, or in concert to attract a suitable partner. Individual elements may also function in other contexts, such as anti-predator defense or camouflage. In Heliconius butterflies, wing patterns comprise several individual color pattern elements, which advertise the butterflies’ toxicity to predators. These wing patterns are also mating cues and males predominantly court females that possess the same wing pattern as their own. However, it is not known whether male preference is based on the full wing pattern or only individual pattern elements. We compared preferences of male H. erato lativitta between female models with the full wing pattern and those with some pattern elements removed. We found no differences in preference between the full wing pattern model and a model with pattern elements removed, indicating that the complete composition of all elements is not essential to the mating signal. Wing pattern preferences also contribute to pre-mating isolation between two other Heliconius taxa, H. erato cyrbia, and H. himera; therefore, we next compared preferences for the same models in these species. H. erato cyrbia and H. himera strongly differed in preferences for the models, potentially providing a mechanism for how pre-mating isolation acts between these species. These findings suggest that contrasting levels of selective constraint act on elements across the wing pattern.
Molecular identification of polymorphic transposable elements in populations of the invasive ant Cardiocondyla obscurior
Authors: van den Bos Esther , Gadau Jürgen , Schrader Lukas 
Published: July 2024

Abstract
Transposable elements (TEs) are found in virtually every eukaryotic genome and are important for generating de novo genetic variation. However, outside of costly and time-consuming whole-genome sequencing approaches, the set of available methods to study TE polymorphisms in non-model species is very limited. The Transposon Display (TD) is a simple yet effective technique to characterize polymorphisms across samples by identifying amplified fragment length polymorphisms using primers targeting specific TE families. So far, this technique has almost exclusively been used in plants. Here, we present an optimized TD protocol for insect species with small genomes such as ants (ca. 200–600 Mb). We characterized TE polymorphisms between two distinct genetic lineages of the invasive ant Cardiocondyla obscurior, as well as between neighboring populations of the New World lineage. We found active LTR/Ty3 retrotransposons, that contributed to the genetic diversification of populations in this species.
Model-based multifacet clustering with high-dimensional omics applications
Authors: Zong Wei , Li Danyang , Seney Marianne L , Mcclung Colleen A , Tseng George C 
Published: July 2024

Summary
High-dimensional omics data often contain intricate and multifaceted information, resulting in the coexistence of multiple plausible sample partitions based on different subsets of selected features. Conventional clustering methods typically yield only one clustering solution, limiting their capacity to fully capture all facets of cluster structures in high-dimensional data. To address this challenge, we propose a model-based multifacet clustering (MFClust) method based on a mixture of Gaussian mixture models, where the former mixture achieves facet assignment for gene features and the latter mixture determines cluster assignment of samples. We demonstrate superior facet and cluster assignment accuracy of MFClust through simulation studies. The proposed method is applied to three transcriptomic applications from postmortem brain and lung disease studies. The result captures multifacet clustering structures associated with critical clinical variables and provides intriguing biological insights for further hypothesis generation and discovery.
Establishing minimal clinically important differences for the Pemphigus Disease Area Index
Authors: Tseng Henry , Stone Corey , Shulruf Boaz , Murrell Dédée F 
Published: July 2024

Abstract

Background
Pemphigus is a rare autoimmune blistering disease with potentially life-threatening consequences. Establishing minimal clinically important differences (MCIDs) for disease severity scores like the Pemphigus Disease Area Index (PDAI) is crucial for assessing treatment efficacy.

Objectives
To calculate MCIDs for both improvement and deterioration in PDAI scores in patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), using the anchor-based method.

Methods
A total of 41 patients with pemphigus were recruited, with 35 meeting the MCID analysis criteria. The anchor-based method was used to calculate MCIDs for PDAI scores against the 15-point Likert scale and the Physician Global Assessment visual analogue scale (PGA-VAS) anchors. Receiver operating characteristic curves were employed to determine optimal MCID cutpoints with the highest Youden Index (J). The 15-point Likert scale scores the change in disease severity spanning from –7 to +7, designed to quantify the extent of disease improvement/deterioration since the preceding visit.

Results
The MCID for improvement in PDAI activity scores was 2.65 points using the 15-point Likert scale (78.7% correct classification; sensitivity 75.9%; specificity 73.5%) and 2.5 points using the PGA-VAS as the anchor (78.0% correct classification; sensitivity 84.4%; specificity 68.2%). Given the slightly higher correct classification rate using the 15-point Likert scale anchor, the MCID of 2.65 points was selected for PDAI activity score improvement. In contrast, the MCID for deterioration consistently remained at 2.5 points for the 15-point Likert scale anchor (81.0% correct classification; sensitivity 72.7%; specificity 81.0%) and 2.5 points for the PGA-VAS anchor (70.9% correct classification; sensitivity 69.6%; specificity 76.9%).

Conclusions
This study marks the inaugural attempt at MCID determination for PDAI scores in pemphigus, filling a critical knowledge gap. The study’s calculated MCIDs provide essential benchmarks for clinical trials, treatment evaluation and research design optimization. Future studies should explore international collaborations, to examine potential cross-cultural variations in MCIDs.
Variation in root functional traits of Neotropical epiphytic and terrestrial orchids along an elevational gradient
Authors: De Bock Katrijn , Jacquemyn Hans , Ospina-Calderón Nhora H , Flanagan Nicola S , Ventre-Lespiaucq Agustina 
Published: July 2024

Abstract
Assessing variation in root functional traits may offer novel insights into plant adaptations to changing environmental conditions. However, such studies, particularly on epiphytic species in tropical ecosystems, are still limited. Previous research has suggested that precipitation has a major impact on epiphyte survival and thus can be considered a candidate driver of epiphytic root trait variation, though compelling evidence is lacking. In this study, we investigated variation in 19 root functional traits in 43 epiphytic (36 species) and 14 terrestrial (7 species) orchids along an elevational gradient in Colombia and examined whether this variation is associated with differences in abiotic conditions. Contrary to previous studies, our findings did not associate trait variation with precipitation but revealed strong correlations with solar radiation, temperature, and water vapour pressure. The variation was particularly pronounced in traits related to the velamen radicum. Epiphytic and terrestrial orchids showed similar responses despite their different growth habits. Overall, these patterns suggest that higher sunlight and temperature conditions lead both orchid types to allocate more resources to root structures that mitigate abiotic stress, and highlight the role of other environmental factors in driving root trait variability.
Inflammation-induced mast cell-derived nerve growth factor: a key player in chronic vulvar pain?
Authors: Awad-Igbaria Yaseen , Edelman Doron , Ianshin Elvira , Abu-Ata Saher , Shamir Alon , Bornstein Jacob , Palzur Eilam 
Published: July 2024

Abstract
Provoked vulvodynia (PV) is characterized by localized chronic vulvar pain. It is associated with a history of recurrent inflammation, mast cell (MC) accumulation and neuronal sprouting in the vulva. However, the mechanism of how vulvar-inflammation promotes neuronal sprouting and gene-expression adaptation in the spinal cord, leading to hypersensitivity and painful sensations, is unknown.
Here, we found that vulvar tissue from women with PV (n = 8) is characterized by MC accumulation and neuronal sprouting compared to women without PV (n = 4). In addition, we observed these changes in an animal study of PV. Thus, we found that repeated vulvar zymosan-inflammation challenges lead to long-lasting mechanical and thermal vulvar hypersensitivity, which is mediated by MC accumulation, neuronal sprouting, overexpression of the pain channels (TRPV1 and TRPA1) in vulvar neurons, as well as a long-term increase of gene expression related to neuroplasticity, neuroinflammation and nerve growth factor (NGF) in the spinal cord/dorsal root ganglia (DRG) (L6–S3). However, regulation of the NGF pathway by stabilization of MC activity with ketotifen fumarate (KF) during vulvar inflammation attenuates the local increase of NGF and histamine, as well as the elevated transcription of pro-inflammatory cytokines and NGF pathway in the spinal cord. Additionally, KF treatment during inflammation modulates MC accumulation, neuronal hyperinnervation and overexpression of the TRPV1 and TRPA1 channels in the vulvar neurons, consequently preventing the development of vulvar pain.
A thorough examination of the NGF pathway during inflammation revealed that blocking NGF activity by using an NGF-non-peptide-inhibitor (Ro08-2750) regulates the upregulation of genes related to neuroplasticity and the NGF pathway in the spinal cord, as well as modulating neuronal sprouting and overexpression of the pain channels, resulting in a reduced level of vulvar hypersensitivity. On the other hand, stimulation of the NGF pathway in the vulvar promotes neuronal sprouting, overexpression of pain channels and increase of gene expression related to neuroplasticity, neuroinflammation and NGF in the spinal cord, resulting in long-lasting vulvar hypersensitivity.
In conclusion, our findings suggest that vulvar allodynia induced by inflammation is mediated by MC accumulation, neuronal sprouting and neuromodulation in the vulvar. Additionally, chronic vulvar pain may involve a long-term adaptation in gene expression in the spinal cord, which probably plays a critical role in central sensitization and pain maintenance. Strikingly, regulating the NGF pathway during the critical period of inflammation prevents vulvar pain development via modulating the neuronal changes in the vestibule and spinal cord, suggesting a fundamental role for the NGF pathway in PV development.
Synaptic mitochondria glycation contributes to mitochondrial stress and cognitive dysfunction
Authors: Samanta Sourav , Akhter Firoz , Xue Renhao , Sosunov Alexandre A , Wu Long , Chen Doris , Arancio Ottavio , Yan Shi Fang , Yan Shirley ShiDu 
Published: July 2024

Abstract
Mitochondrial and synaptic dysfunction are pathological features of brain ageing and cognitive decline. Synaptic mitochondria are vital for meeting the high energy demands of synaptic transmission. However, little is known about the link between age-related metabolic changes and the integrity of synaptic mitochondria.
To this end, we investigated the mechanisms of advanced glycation end product (AGE)-mediated mitochondrial and synaptic stress and evaluated the strategies to eliminate these toxic metabolites. Using aged brain and novel transgenic mice overexpressing neuronal glyoxalase 1 (GLO1), we comprehensively analysed alterations in accumulation/build-up of AGEs and related metabolites in synaptic mitochondria and the association of AGE levels with mitochondrial function.
We demonstrated for the first time that synaptic mitochondria are an early and major target of AGEs and the related toxic metabolite methylglyoxal (MG), a precursor of AGEs. MG/AGE-insulted synaptic mitochondria exhibit deterioration of mitochondrial and synaptic function. Such accumulation of MG/AGEs positively correlated with mitochondrial perturbation and oxidative stress in ageing brain. Importantly, clearance of AGE-related metabolites by enhancing neuronal GLO1, a key enzyme for detoxification of AGEs, reduces synaptic mitochondrial AGE accumulation and improves mitochondrial and cognitive function in ageing and AGE-challenged mice. Furthermore, we evaluated the direct effect of AGEs on synaptic function in hippocampal neurons in live brain slices as an ex vivo model and in vitro cultured hippocampal neurons by recording long-term potentiation (LTP) and measuring spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs). Neuronal GLO1 rescues deficits in AGE-induced synaptic plasticity and transmission by full recovery of decline in LTP or frequency of mEPSC.
These studies explored crosstalk between synaptic mitochondrial dysfunction and age-related metabolic changes relevant to brain ageing and cognitive decline. Synaptic mitochondria are particularly susceptible to AGE-induced damage, highlighting the central importance of synaptic mitochondrial dysfunction in synaptic degeneration in age-related cognitive decline. Thus, augmenting GLO1 function to scavenge toxic metabolites represents a therapeutic approach to reduce age-related AGE accumulation and improve mitochondrial function and learning and memory.
Generative whole-brain dynamics models from healthy subjects predict functional alterations in stroke at the level of individual patients
Authors: Idesis Sebastian , Allegra Michele , Vohryzek Jakub , Perl Yonatan Sanz , Metcalf Nicholas V , Griffis Joseph C , Corbetta Maurizio , Shulman Gordon L , Deco Gustavo 
Published: July 2024

Abstract
Computational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterations in inter-regional functional interactions. These interactions are typically measured by correlating the time series of the activity between two brain regions in a process, called resting functional connectivity. We show that adding information about the structural disconnections produced by a patient’s lesion to a whole-brain model previously trained on structural and functional data from a large cohort of healthy subjects enables the prediction of the resting functional connectivity of the patient and fits the model directly to the patient’s data (Pearson correlation = 0.37; mean square error = 0.005). Furthermore, the model dynamics reproduce functional connectivity-based measures that are typically abnormal in stroke patients and measures that specifically isolate these abnormalities. Therefore, although whole-brain models typically involve a large number of free parameters, the results show that, even after fixing those parameters, the model reproduces results from a population very different than that on which the model was trained. In addition to validating the model, these results show that the model mechanistically captures the relationships between the anatomical structure and the functional activity of the human brain.
Genetic deletion or pharmacologic inhibition of histone deacetylase 6 protects the heart against ischaemia/reperfusion injury by limiting tumour necrosis factor alpha–induced mitochondrial injury in experimental diabetes
Authors: Baumgardt Shelley L , Fang Juan , Fu Xuebin , Liu Yanan , Xia Zhengyuan , Zhao Ming , Chen Ling , Mishra Rachana , Gunasekaran Muthukumar , Saha Progyaparamita , Forbess Joseph M , Bosnjak Zeljko J , Camara Amadou K S , Kersten Judy R , Thorp Edward B , Kaushal Sunjay , Ge Zhi-Dong 
Published: July 2024

Abstract

Aims
The histone deacetylase 6 (HDAC6) inhibitor, tubastatin A (TubA), reduces myocardial ischaemia/reperfusion injury (MIRI) in type 1 diabetic rats. It remains unclear whether HDAC6 regulates MIRI in type 2 diabetic animals. Diabetes augments the activity of HDAC6 and the generation of tumour necrosis factor alpha (TNF-α) and impairs mitochondrial complex I (mCI). Here, we examined how HDAC6 regulates TNF-α production, mCI activity, mitochondria, and cardiac function in type 1 and type 2 diabetic mice undergoing MIRI.

Methods and results
HDAC6 knockout, streptozotocin-induced type 1 diabetic, and obese type 2 diabetic db/db mice underwent MIRI in vivo or ex vivo in a Langendorff-perfused system. We found that MIRI and diabetes additively augmented myocardial HDAC6 activity and generation of TNF-α, along with cardiac mitochondrial fission, low bioactivity of mCI, and low production of adenosine triphosphate. Importantly, genetic disruption of HDAC6 or TubA decreased TNF-α levels, mitochondrial fission, and myocardial mitochondrial nicotinamide adenine dinucleotide levels in ischaemic/reperfused diabetic mice, concomitant with augmented mCI activity, decreased infarct size, and improved cardiac function. Moreover, HDAC6 knockout or TubA treatment decreased left ventricular dilation and improved cardiac systolic function 28 days after MIRI. H9c2 cardiomyocytes with and without HDAC6 knockdown were subjected to hypoxia/reoxygenation injury in the presence of high glucose. Hypoxia/reoxygenation augmented HDAC6 activity and TNF-α levels and decreased mCI activity. These negative effects were blocked by HDAC6 knockdown.

Conclusion
HDAC6 is an essential negative regulator of MIRI in diabetes. Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart from MIRI by limiting TNF-α–induced mitochondrial injury in experimental diabetes.