bluuebunny/crossref_metadata_2025 huggingface dataset:
TAWFN: a deep learning framework for protein function prediction
Authors: Meng Lu , Wang Xiaoran
Published: September 2024

Motivation

Proteins play pivotal roles in biological systems, and precise prediction of their functions is indispensable for practical applications. Despite the surge in protein sequence data facilitated by high-throughput techniques, unraveling the exact functionalities of proteins still demands considerable time and resources. Currently, numerous methods rely on protein sequences for prediction, while methods targeting protein structures are scarce, often employing convolutional neural networks (CNN) or graph convolutional networks (GCNs) individually.

Results

To address these challenges, our approach starts from protein structures and proposes a method that combines CNN and GCN into a unified framework called the two-model adaptive weight fusion network (TAWFN) for protein function prediction. First, amino acid contact maps and sequences are extracted from the protein structure. Then, the sequence is used to generate one-hot encoded features and deep semantic features. These features, along with the constructed graph, are fed into the adaptive graph convolutional networks (AGCN) module and the multi-layer convolutional neural network (MCNN) module as needed, resulting in preliminary classification outcomes. Finally, the preliminary classification results are inputted into the adaptive weight computation network, where adaptive weights are calculated to fuse the initial predictions from both networks, yielding the final prediction result. To evaluate the effectiveness of our method, experiments were conducted on the PDBset and AFset datasets. For molecular function, biological process, and cellular component tasks, TAWFN achieved area under the precision-recall curve (AUPR) values of 0.718, 0.385, and 0.488 respectively, with corresponding Fmax scores of 0.762, 0.628, and 0.693, and Smin scores of 0.326, 0.483, and 0.454. The experimental results demonstrate that TAWFN exhibits promising performance, outperforming existing methods.

Availability and implementation

The TAWFN source code can be found at: https://github.com/ss0830/TAWFN.
Treatment of neurological pathology and inflammation in Machado–Joseph disease through in vivo self-assembled siRNA
Authors: Li Zhizong , Du Xinghu , Yang Yixuan , Zhang Li , Chen Penglu , Kan Yansheng , Pan Jinmeng , Lin Lishan , Liu Ding , Jiang Xiaohong , Zhang Chen-Yu , Pei Zhong , Chen Xi
Published: September 2024

Machado–Joseph disease, also known as spinocerebellar ataxia type 3 (MJD/SCA3), is a fatal autosomal dominant hereditary ataxia characterized by cerebellar ataxia resulting from the abnormal expansion of CAG repeats in exon 10 of the ATXN3 gene. At present, there is no effective treatment for SCA3. Small interfering RNAs (siRNAs) are emerging as potential therapeutic strategies to target the disease-causing mutant ATXN3 (mATXN3) protein specifically. However, the efficiency of delivery of siRNAs remains a major obstacle for clinical application, particularly in brain disorders.

The aim of this study was to develop a synthetic biology strategy to reprogram the host liver as a tissue chassis to induce and deliver in vivo self-assembled siRNAs to target the ATXN3 gene. A synthetic construct directed by a cytomegalovirus promoter was designed to encode a neuron-targeting rabies virus glycoprotein tag and mATXN3-siRNA. After intravenous injection, the synthetic construct was taken up by mouse livers, which were then reprogrammed to enable the self-assembly, production and secretion of small extracellular vesicles encapsulating mATXN3-siRNA. The small extracellular vesicle-encapsulated mATXN3-siRNA was transported through the endogenous circulating system of small extracellular vesicles, crossing the blood–brain barrier and reaching the cerebellar cortex and spinal cerebellar tract, where they silenced the ATXN3 gene.

Treatment with the synthetic construct for 8 or 12 weeks led to significant improvements in motor balance ability and reduction of cerebellar atrophy in YACMJD84.2 transgenic mice. The number of Purkinje cells in the cerebellar cortex was significantly increased, and the loss of myelin basic protein was reduced. Moreover, the quantity of neurotoxic nuclear inclusion bodies and the expression of glial fibrillary acidic protein, which promotes neuroinflammation in activated astrocytes, were decreased significantly.

The synthetic construct facilitated the generation and delivery of in vivo self-assembled siRNA to the cerebellar cortex and spinal cerebellar tract, thereby inhibiting the expression of mATXN3 protein. This treatment successfully addressed motor impairments, alleviated neuropathological phenotypes and mitigated neuroinflammation in YACMJD84.2 transgenic mice. Our strategy effectively overcomes the primary challenges associated with siRNA therapy for cerebellar ataxia, offering a promising avenue for future clinical treatments.
Transdiagnostic depression severity and its relationship to global and prefrontal-amygdala structural properties in people with major depression and post-traumatic stress disorder
Authors: Li Lei , Jiang Jing , Zhong Shitong , Lin Jinping , Yao Yuhao , Kemp Graham J , Chen Ying , Gong Qiyong
Published: September 2024

While some studies have used a transdiagnostic approach to relate depression to metabolic or functional brain alterations, the structural substrate of depression across clinical diagnostic categories is underexplored. In a cross-sectional study of 52 patients with major depressive disorder and 51 with post-traumatic stress disorder, drug-naïve, and spanning mild to severe depression severity, we examined transdiagnostic depressive correlates with regional gray matter volume and the topological properties of gray matter-based networks. Locally, transdiagnostic depression severity correlated positively with gray matter volume in the right middle frontal gyrus and negatively with nodal topological properties of gray matter-based networks in the right amygdala. Globally, transdiagnostic depression severity correlated positively with normalized characteristic path length, a measure implying brain integration ability. Compared with 62 healthy control participants, both major depressive disorder and post-traumatic stress disorder patients showed altered nodal properties in regions of the fronto–limbic–striatal circuit, and global topological organization in major depressive disorder in particular was characterized by decreased integration and segregation. These findings provide evidence for a gray matter-based structural substrate underpinning depression, with the prefrontal–amygdala circuit a potential predictive marker for depressive symptoms across clinical diagnostic categories.
Transcatheter mitral valve implantation using TENDYNE valve for the treatment of residual severe mitral regurgitation post-transcatheter mitral valve edge-to-edge repair: a case report
Authors: Abunab Mohammed Ali , Alamri Bandar Naim , Shah Muhammad Azam , Alshehri Halia Zain
Published: September 2024

Background

Functional mitral regurgitation (MR) in patients with heart failure can be treated medically or by transcatheter edge-to-edge repair (TEER) if medical therapy fails. Patients who are not suitable for TEER or surgical intervention might benefit from transcatheter mitral valve implantation using the TENDYNE valve.

Case summary

A 58-year-old male with a history of heart failure was admitted frequently with acute heart failure and functional MR, treated medically without significant improvement. He underwent mitral TEER therapy using MitraClip. A few months later, he was admitted with acute decompensated heart failure. Echocardiography showed severe MR with a detached clip from the posterior leaflet. He underwent redo mitral TEER using MitraClip as an option for treating single leaflet device detachment. He was readmitted with the same symptoms and his echocardiography showed detachment of both clips from the posterior leaflet. The patient underwent TMVI using the TENDYNE valve being not suitable for another attempt of mitral TEER. On follow-up, he was asymptomatic and echocardiography showed normal functioning mitral bioprosthesis with a mean gradient of 4 mm/Hg and no paravalvular leak.

Discussion

Transcatheter mitral valve implantation using TENDYNE valve is an option for treating patients with functional MR and detached MitraClips.
Physiologic pacing in congenitally corrected transposition of the great arteries with electroanatomic mapping guidance: a case report
Authors: Brem Ofir , Buturlin Kirill , Kolker Shimon , Schamroth Pravda Nili
Published: September 2024

Background

This case report details the application of left bundle branch pacing in a patient with congenitally corrected transposition of the great arteries (cc-TGA), a rare congenital heart defect characterized by anatomical complexities that pose unique challenges in the management of device-related complications and heart failure. The patient’s history is notable for complex anatomical considerations, cardiovascular implantable electronic device (CIED) infection, and heart failure.

Case summary

The patient underwent a series of interventions, including treatment for pocket-site infections, abandonment of epicardial leads, and an unsuccessful attempt at trans-catheter leadless pacemaker implantation. Given the patient’s complex anatomy and prior CIED infection, traditional pacing methods were deemed unsuitable, leading to the selection of left bundle branch pacing. The lead implantation was guided using 3D electro-anatomical mapping to ensure synchronous physiologic pacing in a patient with heart failure.

Discussion

The case underscores the heightened risks faced by cc-TGA patients, with a focus on systemic right ventricular dysfunction and pacing-induced ventricular dysfunction. In these patients, ventricular synchrony is critical and can be achieved with biventricular pacing. Physiologic pacing emerges as a promising alternative to cardiac resynchronization therapy (CRT), especially in cases where endovascular CRT is unfeasible. This case demonstrates the utilization of 3D electro-anatomical mapping for achieving successful physiologic pacing in complex congenital heart lesions. At the 12-month follow-up, the patient presented with stable clinical status and a narrow QRS complex. Echocardiography indicated improvement in the right systemic ventricular function.
CardiacField: computational echocardiography for automated heart function estimation using two-dimensional echocardiography probes
Authors: Shen Chengkang , Zhu Hao , Zhou You , Liu Yu , Yi Si , Dong Lili , Zhao Weipeng , Brady David J , Cao Xun , Ma Zhan , Lin Yi
Published: September 2024

Aims

Accurate heart function estimation is vital for detecting and monitoring cardiovascular diseases. While two-dimensional echocardiography (2DE) is widely accessible and used, it requires specialized training, is prone to inter-observer variability, and lacks comprehensive three-dimensional (3D) information. We introduce CardiacField, a computational echocardiography system using a 2DE probe for precise, automated left ventricular (LV) and right ventricular (RV) ejection fraction (EF) estimations, which is especially easy to use for non-cardiovascular healthcare practitioners. We assess the system’s usability among novice users and evaluate its performance against expert interpretations and advanced deep learning (DL) tools.

Methods and results

We developed an implicit neural representation network to reconstruct a 3D cardiac volume from sequential multi-view 2DE images, followed by automatic segmentation of LV and RV areas to calculate volume sizes and EF values. Our study involved 127 patients to assess EF estimation accuracy against expert readings and two-dimensional (2D) video-based DL models. A subset of 56 patients was utilized to evaluate image quality and 3D accuracy and another 50 to test usability by novice users and across various ultrasound machines. CardiacField generated a 3D heart from 2D echocardiograms with <2 min processing time. The LVEF predicted by our method had a mean absolute error (MAE) of 2.48%, while the RVEF had an MAE of 2.65%.

Conclusion

Employing a straightforward apical ring scan with a cost-effective 2DE probe, our method achieves a level of EF accuracy for assessing LV and RV function that is comparable to that of three-dimensional echocardiography probes.
Sex-specific differences in alive hospital discharge following infrarenal abdominal aortic aneurysm repair
Authors: Pouncey Anna Louise , Sweeting Michael J , Bicknell Colin , Powell Janet T , Lübcke Jenny , Gunnarsson Kim , Wanhainen Anders , Mani Kevin
Published: September 2024

Background and Aims

A longer time to alive hospital discharge following infrarenal abdominal aortic aneurysm (AAA) repair is associated with reduced patient satisfaction and increased length of stay, hospital-acquired deconditioning, infection, and costs. This study investigated sex-specific differences in, and drivers of, the rate of alive hospital discharge.

Methods

Examination of UK National Vascular Registry (UK NVR), 2014–19, and Swedish National Patient Registry (SE NPR) elective AAA patients, 2010–18, for endovascular (EVAR) or open aneurysm repair (OAR). Cox models assessed sex-specific difference in the rate of alive hospital discharge, adjusting for co-morbidity, anatomy, standard of care, post-operative complications, and year, with in-hospital death as the competing risk.

Results

A total of 29 751 AAA repairs (UK NVR: EVAR 12 518:1532; OAR 6803:837; SE NPR: EVAR 4234:792; OAR 2638:497, men:women) were assessed. For EVAR, the unadjusted rate of alive hospital discharge was ∼25% lower for women [UK NVR: hazard ratio (HR) 0.75 (0.71–0.80), P < .001; SE NPR: HR 0.75 (0.69–0.81), P < .001]. Following adjustment, the sex-specific HR narrowed but remained significant [UK NVR: HR 0.83 (0.79–0.88), P < .001; SE NPR: HR 0.83 (0.76–0.89), P < .001]. For OAR, the rate of alive hospital discharge was 23%–27% lower for women [UK NVR: HR 0.73 (0.67–0.78), P < .001; SE NPR: HR 0.77 (0.70–0.85), P < .001]. Following adjustment, the sex-specific HR narrowed [UK NVR: HR 0.82 (0.76–0.88), P < .001; SE NPR: HR 0.79 (0.72–0.88), P < .001] but remained significant.

Conclusions

Women have a 25% lower rate of alive discharge after aortic surgery, despite adjustment for pre/peri- and post-operative parameters. Efforts to increase the rate of alive hospital discharge for women should be sought.
Point-of-care ultrasonography for cardiovascular conditions in family practice: between risk and opportunity
Authors: Magro Valerio Massimo
Published: September 2024

Several articles have appeared in the medical literature on the use of ultrasound in primary care. Point-of-care ultrasound refers to ultrasound protocols performed at the bedside to evaluate many conditions such as aortic aneurysm or assessment of left ventricular function by estimation of ejection fraction. Primary care physicians can play a key role in evaluating such conditions for their patients. It should be considered that the use of ultrasound in general practice can not only be an aid to diagnosis but also an active screening tool, accessible even to those with basic training in ultrasound; the left ventricle and large abdominal vessels are indeed clearly visible with this technique, which with little training can become accessible to many. In a working organization, so few trained physicians would be sufficient to screen the target population of the entire group and extend the assessment to a large number of participants.
The tectonic development of the Central African Plateau: evidence from shear-wave splitting
Authors: Kounoudis R , Kendall J -M , Ogden C S , Fishwick S , Chifwepa C , Daly M C
Published: September 2024

The Central African Plateau comprises a mosaic of numerous Archean terranes—the Congo, Bangweulu and Kalahari Cratons—sutured in a series of Proterozoic to early Cambrian orogenic events. Major upper-crustal deformation and complex craton margin fault zones reflect the region’s diverse tectonic history: rifting during the Neoproterozoic, collision during the Pan-African orogeny, and more recently, Permo-Triassic Karoo rifting and the Pliocene development of the Southwestern branch of the East African Rift. The tectonic evolution and extent to which the lithospheric mantle has been re-worked by each tectonic event is poorly understood. New seismograph networks across the Plateau provide fresh opportunity to place constraints on the plate-scale Precambrian-to-Phanerozoic processes that have acted across the region. Utilizing data from seismograph deployments across the Central African Plateau, including the new Copper Basin Exploration Science network—a NW–SE-trending, 750-km-long profile of 35 broad-band stations—we explore lithospheric deformation fabrics associated with past and present tectonic events via a shear-wave splitting study of mantle seismic anisotropy. Results reveal short length-scale variations in splitting parameters (fast direction: $\phi$, delay time: $\delta$t), suggestive of a fossil lithospheric fabric cause for the observed anisotropy. A lack of fault-parallel $\phi$ across the Mwembeshi shear zone, suggests it may be too narrow at mantle depths, a thin-skinned, crustal-scale feature, and/or did not experience sufficient fault parallel shear-strain during its last active phase to form a lithospheric deformation fabric discernible via teleseismic shear-wave splitting. In the heart of the Lufilian Arc, we observe abrupt changes in splitting parameters with NE–SW, N–S and NW–SE $\phi$ and 0.5 s $< $$\delta$t$< $ 1.2 s evident at short length-scales: no single, uniform, anisotropic lattice preferred orientation (LPO) fabric defines the entire region. This is consistent with the view that multiple episodes of deformation shaped the Lufilian Arc, or perhaps that pre-existing fabrics, relating to Neoproterozoic Katangan Basin development, have failed to be completely overprinted by the Pan-African orogeny. Near the Domes, where most intense crustal re-working is thought to have taken place during the Pan-African orogeny, there is a cluster of null and low $\delta$t splits which likely reflects the lack of organized LPO fabrics, perhaps due to the presence of depth-dependent anisotropy. The neighbouring Congo Craton margin is marked by consistently weak anisotropy ($\delta$t$\lt $ 0.7 s) indicating a weak horizontal alignment of olivine at mantle lithospheric depths, typical of several Archean terranes worldwide.
On the v-Picard Group of Stein Spaces
Authors: Ertl Veronika , Gilles Sally , Nizioł Wiesława
Published: September 2024

We study the image of the Hodge–Tate logarithm map (in any cohomological degree), defined by Heuer, in the case of smooth Stein varieties. Heuer, motivated by the computations for the affine space of any dimension, raised the question whether this image is always equal to the group of closed differential forms. We show that it indeed always contains such forms but the quotient can be non-trivial: it contains a slightly mysterious $\mathbf{Z}_{p}$-module that maps, via the Bloch–Kato exponential map, to integral classes in the pro-étale cohomology. This quotient is already non-trivial for open unit disks of dimension strictly greater than $1$.
Clinical Characteristics of Tick-Borne Encephalitis in Adult Patients: A 10-year Retrospective Study in Stockholm, Sweden
Authors: Bartholdsson Sofia , Hergens Maria-Pia , Hansson Karin E , Ragnarsson Josef , Hodosi Peter , Kus Ismail , Insulander Mona , Vene Sirkka , Lindquist Lars , Askling Helena H , Gredmark-Russ Sara
Published: September 2024

Background

The incidence of tick-borne encephalitis (TBE) has increased during the last decades in Europe. Our aim was to assess the clinical characteristics and outcome of patients with TBE in Region Stockholm, as a high-risk area in Sweden.

Methods

The notification database at the regional Department of Communicable Disease Control and Prevention was used to identify TBE cases during 2006–2015. Clinical data were retrieved from the included patients’ medical records. The associations of specific variables to predefined outcomes of disease severity were evaluated with multivariate logistic regression models.

Results

Of 1004 identified TBE cases, 703 adult patients were included. Sixty-one percent were men, and the median age was 50 years (range, 18–94 years). The majority of patients were nonvaccinated. Comorbidity was present in 34%, and 4% were receiving immunomodulatory therapy. Seventy-five percent were hospitalized, and 11% had severe disease. More than 70% of the 79 patients followed up for >6 months had persisting symptoms. The case fatality rate was 1.4%, 15% in the group with immunomodulatory treatment. In the multivariate analysis, severe disease was associated with underlying comorbid conditions, age ≥50 years, and previous complete TBE vaccination.

Conclusions

This is the largest cohort of patients with TBE in Scandinavia. Our findings of a more severe course of disease in older patients, those receiving immunomodulatory therapy, those with comorbid conditions, and those with vaccination breakthrough infections must be interpreted in the context of hospitalized patients. Optimized prevention is needed for patients receiving immunomodulatory therapy, given the considerable case fatality rate. Follow-up visits and rehabilitation should be better standardized.
Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection
Authors: Ke Shanlin , Gálvez Javier A Villafuerte , Sun Zheng , Cao Yangchun , Pollock Nira R , Chen Xinhua , Kelly Ciarán P , Liu Yang-Yu
Published: September 2024

Clostridioides difficile infection (CDI) is a major cause of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) shows promise for recurrent CDI, its mechanisms and long-term safety are not fully understood. Live biotherapeutic products (LBPs) using predefined bacterial consortia offer an alternative option, but the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three metagenomic datasets to identify microbial strains for LBPs targeting CDI. We constructed the CDI-related microbial genome catalog, comprising 3741 nonredundant metagenome-assembled genomes (nrMAGs), and identified multiple potential protective nrMAGs, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these protective nrMAGs were found to play an important role in FMT success, and most top protective nrMAGs can be validated by various previous findings. Our results demonstrate a framework for selecting microbial strains targeting CDI, paving the way for the computational design of LBPs against other enteric infections.
Challenges to Meaningful Youth E-Participation in Political Decision-Making in Finland
Authors: Spurava Guna , Varsaluoma Jari , Väänänen Kaisa
Published: September 2024

This article explores the factors that make youth e-participation in political decision-making meaningful and identifies the challenges associated with it from the perspectives of government officials. Empirical data for the research are collected by conducting in-depth interviews with Finland’s government officials from nine ministries who possess experience working with young people. The results reveal that there is a lack of inclusion and understanding of existing digital tools and governmental processes. Furthermore, officials perceive feedback to young people as an essential component of meaningful participation, emphasising the importance of dialogue in this process and the necessity for innovative digital solutions to support it. The study contributes to developing the evidence base necessary for designing e-participation services that would bridge the gap between the needs of young people and the realities of the political environment.
A chromosome phased diploid genome assembly of African hunting dog (Lycaon pictus)
Authors: Kliver Sergei , Kovacic Iva , Mak Sarah , Sinding Mikkel-Holger S , Stagegaard Julia , Petersen Bent , Nesme Joseph , Gilbert Marcus Thomas Pius
Published: September 2024

The African hunting dog (Lycaon pictus, 2n = 78) once ranged over most sub-Saharan ecosystems except its deserts and rainforests. However, as a result of (still ongoing) population declines, today they remain only as small fragmented populations. Furthermore, the future of the species remains unclear, due to both anthropogenic pressure and interactions with domestic dogs, thus their preservation is a conservation priority. On the tree of life, the hunting dog is basal to Canis and Cuon and forms a crown group with them, making it a useful species for comparative genomic studies. Here, we present a diploid chromosome-level assembly of an African hunting dog. Assembled according to Vertebrate Genomes Project guidelines from a combination of PacBio HiFi reads and HiC data, it is phased at the level of individual chromosomes. The maternal (pseudo)haplotype (mat) of our assembly has a length of 2.38 Gbp, and 99.36% of the sequence is encompassed by 39 chromosomal scaffolds. The rest is included in only 36 unplaced short scaffolds. At the contig level, the mat consists of only 166 contigs with an N50 of 39 Mbp. BUSCO (Benchmarking Universal Single-Copy Orthologue) analysis showed 95.4% completeness based on Carnivora conservative genes (carnivora_odb10). When compared with other available genomes from subtribe Canina, the quality of the assembly is excellent, typically between the first and third depending on the parameter used, and a significant improvement on previously published genomes for the species. We hope this assembly will play an important role in future conservation efforts and comparative studies of canid genomes.
The Geopolitics of Global Infrastructure Projects: Challenges and Opportunities for Health and Wellbeing
Authors: Khan Abdul Moiz
Published: September 2024

Global infrastructure projects have emerged as pivotal instruments in shaping economic growth and geopolitical dynamics in the contemporary world. Infrastructure, traditionally associated with physical structures like roads, bridges and utilities, now extends to include services vital for societal standards and economic progress. This evolution reflects a broader recognition of infrastructure’s role in fostering development, with distinctions drawn between physical infrastructure such as transport and energy networks, and services-oriented infrastructures encompassing health and education. Scholarly discourse on the correlation between infrastructure development and economic growth varies significantly. While some researchers assert a positive relationship, citing infrastructure’s stimulative effects on economies, others argue that this link is not universally conclusive, highlighting nuances in variables and methodologies used in studies. Nevertheless, the consensus underscores the critical role of infrastructure in enhancing economic activities, particularly in developing countries where the infrastructure gap remains stark. Central to contemporary infrastructure dynamics is China’s Belt and Road Initiative (BRI), a global development policy launched in 2013 aimed at enhancing connectivity and economic integration across Asia, Europe and beyond. The USA and its allies have also initiated the Partnership for Global Infrastructure and Investment (PGII), to promote sustainable infrastructure development aligned with Western values and global governance standards. As these global powers focus on infrastructure development, the implications for health and well-being emerge as critical considerations. Infrastructure projects not only promise economic benefits but also present opportunities to address public health challenges, enhance connectivity and promote sustainable development goals. However, they also pose challenges such as environmental impact, debt sustainability and geopolitical tensions, underscoring the complex interplay between infrastructure development, global governance and human welfare. This paper explores the multifaceted dimensions of global infrastructure projects, examining their implications for health and well-being amidst evolving geopolitical competition. By analyzing key initiatives like BRI and PGII, it aims to provide insights into how infrastructure investments can be leveraged to foster equitable socio-economic development while navigating the challenges posed by climate change, governance issues and geopolitical rivalries. Understanding these dynamics is crucial for harnessing the transformative potential of global infrastructure projects to promote health and well-being on a global scale.
Transcription factor VRT2 reinitiates vernalization when interrupted by warm temperatures in a temperate grass model
Authors: Kennedy Alice , Li Meixia , Vandeperre Anja , Hameed Muhammad Usama , Van Dyck Michelle , Engelen Sarah , Preston Jill C , Geuten Koen
Published: September 2024

Vernalization-responsive plants use cold weather, or low temperature, as a cue to monitoring the passing of winter. Winter cereals can remember the extent of coldness they have experienced, even when winter is punctuated by warm days. However, in a seemingly unnatural process called “devernalization,” hot temperatures can erase winter memory. Previous studies in bread wheat (Triticum aestivum) have implicated the MADS-box transcription factor VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT2) in vernalization based on transcriptional behavior and ectopic expression. Here, we characterized 3 BdVRT2 loss-of-function alleles in the temperate model grass Brachypodium distachyon. In addition to extended vernalization requirements, mutants showed delayed flowering relative to wild-type plants when exposed only briefly to warm temperatures after partial vernalization, with flowering being unaffected when vernalization was saturating. Together, these data suggest a role for BdVRT2 in both vernalization and in its reinitiation when interrupted by warm temperatures. In controlled constant conditions, BdVRT2 transcription was not strongly affected by vernalization or devernalization. Yet, by monitoring BdVRT2 expression in seasonally varying and fluctuating conditions in an unheated greenhouse, we observed strong upregulation, suggesting that its transcription is regulated by fluctuating vernalizing–devernalizing conditions. Our data suggest that devernalization by hot temperatures is not a peculiarity of domesticated cereal crops but is the extreme of the reversibility of vernalization by warm temperatures and has broader biological relevance across temperate grasses.
A breath-based in vitro diagnostic assay for the detection of lower respiratory tract infections
Authors: Chen Dapeng , Mirski Marek A , Chen Shuo , Bryden Wayne A , McLoughlin Michael , Kiser Kiana M , Caton Emily R , Haddaway Caroline R , Cetta Maximilian S , Pan Yezhi
Published: September 2024

An accurate diagnosis is critical to reducing mortality in people with lower respiratory tract infections (LRTIs). Current microbiological culture is time-consuming, and nucleic acid amplification-based molecular technologies cannot distinguish between colonization and infection. Previously, we described developing a sampling system for effectively capturing biomolecules from human breath. We identified a new class of proteoform markers of protease activation, termed proteolytic products of infection, for detecting LRTIs in people with mechanical ventilation. Here, we further developed an in vitro assay by designing a specific substrate sensor for human neutrophil elastase (HNE) to detect LRTIs in breath samples. In the proof-of-concept study, we then applied this in vitro assay to breath samples collected from intubated patients and healthy volunteers. The findings revealed that the LRTI group demonstrated a significant mean differential, showing a 9.8-fold elevation in measured HNE activity compared with the non-LRTI group and a 9.2-fold compared with healthy volunteers. The in vitro assay's diagnostic potential was assessed by constructing a receiver operating characteristic curve, resulting in an area under the curve of 0.987. Using an optimal threshold for HNE at 0.2 pM, the sensitivity was determined to be 1.0 and the specificity to be 0.867. Further correlation analysis revealed a strong positive relationship between the measured HNE activity and the protein concentration in the breath samples. Our results demonstrate that this breath-based in vitro assay provides high diagnostic performance for LRTIs, suggesting that the technology may be useful in the near term for the accurate diagnosis of LRTIs.
Who Is The Rural Voter? A Review Article and Appraisal of the Field of Rural Politics
Authors: Shepherd Michael E
Published: September 2024

Who is this rural voter pundits and politicians are so captivated by? In their important new book, Nicholas Jacobs and Daniel Shea shed light on this important question, offering many new and nuanced insights on The Rural Voter in America. Providing novel and rich survey data on rural Americans from across the entire U.S. Jacobs and Shea dispel harmful stereotypes of rural people and clarify misperceptions often held by those unfamiliar with rural communities, all while providing the most in-depth exploration of rural public opinion to date. The Rural Voter is an essential read for any one wishing to wrestle with the politics of rural communities.
Class experiences and the long-term evolution of economic values
Authors: Helgason Agnar Freyr , Rehm Philipp
Published: September 2024

While there is a strong cross-sectional association between social class and political attitudes, recent research—based on longitudinal data—finds that changes in class are, at most, weakly related to changes in such attitudes. One common explanation for this finding is that early life socialization affects both social class and political attitudes and that class has little, if any, direct effect on them. In this manuscript, we explore an alternative explanation that centers on the importance of cumulative class experiences for the long-term evolution of attitudes. To evaluate this perspective, we leverage data from the British Household Panel Survey, which contains measures of economic values that span up to 16 years, as well as complete work-life histories of respondents that allow us to track individual class experiences over people’s life span. Our findings show that cumulative class experiences are strongly associated with the development of economic values.
Urinary kallikrein reverses neuropathic pain by inhibiting ectopic neural discharges, neural inflammation and oxidative stress
Authors: Chen Mingsheng , Wu Jinze , Gao Yafei , Li Yunlei , He Shiming , Jin Jungong
Published: September 2024

Background

Neuropathic pain is a refractory disease and badly impacts the lives of patients. Urinary kallikrein (UK) acted as a glycoprotein has been discovered to play a pivotal role in neuroprotection. However, the regulatory impacts and correlative pathways of UK in the progression of neuropathic pain remain dimness.

Methods

The chronic constriction injury (CCI) rat model was firstly established to mimic neuropathic pain. The withdrawal threshold was measured through the Von Frey test. The levels of TNF-α, IL-1β and IL-6 were determined through ELISA. The levels of ROS, GSH, SOD and GSH-Px were examined through the commercial kits. The ectopic discharges were assessed. The protein expressions were inspected through western blot.

Results

It was demonstrated that withdrawal threshold was reduced in CCI rat model, but this change was reversed after UK treatment, indicating that UK relieved mechanical allodynia. Moreover, UK alleviated the inflammatory response through reducing TNF-α, IL-1β and IL-6 levels. It was uncovered that oxidative stress was strengthened in CCI rat model, but this impact was restrained after UK treatment. Additionally, UK suppressed ectopic discharge. At last, it was proved that UK triggered the Nrf2/ARE signaling pathway in CCI rat model.

Conclusion

This study manifested that UK reversed neuropathic pain by inhibiting ectopic neural pathways, neural pathways and oxidation via the Nrf2/ARE pathway. This study may offer useful proofs the regulatory functions of UK in the cure of neuropathic pain.
Alternaria Species on Convolvulus arvensis Revealed as a Potential Inoculum Source for Solanaceous Crops in Serbia
Authors: Blagojević Jovana , Andjelković Ana , Vučurović Ivan , Trkulja Nenad , Ristić Danijela
Published: September 2024

Alternaria pathogens are a global agronomic challenge affecting the health of Solanaceae crops. Crop debris, seeds, and perennial weeds are potential inoculum reservoirs, but knowledge on their relative importance remains limited. Plants of Convolvulus arvensis showing early blight and brown leaf spot symptoms were collected from in and around potato and tomato fields in Serbia, grown both in open conditions and in tunnels, in the late season of 2021 to 2022. Morphological characterization and multilocus sequence analysis were performed on collected samples, using three genes (GPD, CAL, and RPB2) for large-spored species and six genes (Alt a1, ATP, HIS3, endoPG, TEF-1, and OPA10-2) for small-spored species of Alternaria. A total of 58 strains were identified: four large-spored species (A. grandis, A. solani, A. protenta, and A. linariae) and two small-spored species (A. alternata and A. arborescens). Phylogenetic analyses of concatenated loci and haplotype network for every investigated locus revealed that large-spored isolates from C. arvensis exhibit a low genetic variability, suggesting common haplotypes in a broad solanaceous host range. Meanwhile, small-spored Alternaria isolates displayed high genetic diversity in all examined gene regions, indicating potential geographical haplotype distribution per HIS3 locus. Pathogenicity tests confirmed the virulence of all isolates on original hosts, with crop plants of potato and tomato also showing high susceptibility. Notably, this research documents six Alternaria species on C. arvensis in Serbia for the first time, significantly broadening our understanding of the pathogen’s diversity and suggesting new sources of inoculum in solanaceous crops.
Comparison of Intercostal Nerve Block and Serratus Anterior Plane Block for Perioperative Pain Management and Impact on Chronic Pain in Thoracoscopic Surgery
Authors: Jin Jiahui , Sun Huanan , Zhang Xinyue , Wu Xinyi , Pan Xue , Lv Danni , He Yi , Cao Xuezhao
Published: September 2024

Objectives:

The intent of this study was to compare the analgesic efficacy of intercostal nerve block (ICNB) under direct thoracoscopic visualization and serratus anterior plane block (SAPB) with ultrasound guidance during thoracoscopic surgery’s perioperative period. Furthermore, it examined their impact on chronic pain and identifies potential risk factors associated with its development.

Materials and Methods:

In this prospective randomized controlled study, 74 thoracoscopic surgery patients were randomly assigned to ICNB or SAPB groups. Attending surgeons administered ICNB, while anesthesiologists performed SAPB, both using 20 mL of 0.5% ropivacaine. Primary outcomes included Visual Analog Scale (VAS) scores for resting and coughing pain at 6, 12, 24, and 48 hours postoperatively, perioperative opioid and NSAID consumption, and chronic pain incidence at 3 months postoperatively. Secondary outcomes aimed to identify independent risk factors for chronic pain.

Results:

The primary results reveal that the SAPB group exhibited significantly lower VAS scores than the ICNB group for postoperative coughing at 24 hours (P<0.001, 95% CI=0.5, 1) and for resting pain at 48 hours (P=0.001, 95% CI=0.2, 1). Conversely, the ICNB group demonstrated a reduced VAS score for resting pain at 6 hours compared with the SAPB group (P=0.014, 95% CI=−0.5, 0.5). SAPB group required significantly less intraoperative sulfentanil (P<0.001, 95% CI=2.5, 5), remifentanil (P=0.005, 95% CI=−0.4, −0.1), and flurbiprofen ester (P=0.003, 95% CI=0, 50) than ICNB group. Chronic pain incidence was similar (P=0.572, 95% CI=0.412, 1.279), with mild pain in both ICNB and SAPB groups. Secondary findings indicate that resting VAS score at 12 hours (OR=7.59, P=0.048, 95% CI=1.02, 56.46), chest tube duration (OR=3.35, P=0.029, 95% CI=1.13, 9.97), and surgical duration (OR=1.02, P=0.049, 95% CI=1.00, 1.03) were significant predictors of chronic pain occurrence.

Discussion:

ICNB and SAPB demonstrated comparable analgesic effects, with similar rates of chronic pain occurrence. Chronic pain independent risk factors included resting VAS score at 12 hours, chest tube duration, and surgical duration.
Using Limited Trial Evidence to Credibly Choose Treatment Dosage when Efficacy and Adverse Effects Weakly Increase with Dose
Authors: Manski Charles F.
Published: September 2024

It has become standard in medical treatment to base dosage on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has been to compare some dose of a new drug with an established therapy or placebo. Standard trial analysis views each trial arm as qualitatively different, but it may be credible to assume that efficacy and adverse effects weakly increase with dosage. Optimization of patient care requires joint attention to both, as well as to treatment cost. This article develops a methodology to use limited trial evidence to choose dosage when efficacy and adverse effects weakly increase with dose. I suppose that dosage is an integer t ∊ (0,1,...,T), T being a specified maximum dose. I study dosage choice when trial evidence on outcomes is available for only K dose levels, where K < T + 1. Then the population distribution of dose response is partially identified. I show that the identification region is a convex polygon. I characterize clinical and population decision-making using the minimax regret criterion. A simple analytical solution exists when T = 2. Computation is tractable when T is larger.
Exploring the Promising Impact of Pulmonary Rehabilitation on Gait and Balance in Patients With COPD
Authors: Khosravi Mobina , Naimi Sedigheh Sadat , Shokouhyan Seyed Mohammadreza , Nemati Aysan , Abedi Mohsen
Published: September 2024

Purpose:

Chronic obstructive pulmonary disease (COPD) is commonly associated with respiratory difficulties, but it also presents with musculoskeletal problems. The objective of this systematic review and meta-analysis was to evaluate the effects of pulmonary rehabilitation (PR) on balance and gait in patients with COPD.

Review Methods:

We conducted a comprehensive search of 4 databases, including PubMed, Google Scholar, Science Direct, and Web of Science, from inception to November 2023. The review included studies reporting the association between COPD status and balance and gait using PR. Two independent reviewers examined the titles and abstracts, extracted the data using a standardized form, and assessed the risk of bias of the included articles.

A total of 14 studies with 320 patients in the study groups and 188 controls were included in the analysis. The risk of bias in the included studies was medium to high. The results showed that PR non-statistically significantly improved balance, as demonstrated by moderate effect sizes in the Timed Up and Go (standardized mean difference [SMD] = 0.1: 95% CI, −1.41 to 1.69) and Berg Balance Scale (SMD = −0.39: 95% CI, −1.30 to 0.53). However, the impact of PR on gait function was less clear, with mixed results. The study findings highlight the positive but non-significant effects of PR on balance in individuals with COPD. The results suggest that PR programs could include exercises that target balance improvement to enhance the overall quality of patients. However, further research is needed to determine the optimal duration and intensity of these exercises to achieve maximum benefits for patients with COPD.
Relationship between systolic blood pressure and renal function on clinical outcomes in patients with atrial fibrillation: a report from the prospective AF-GEN-UK Registry
Authors: Shantsila Alena , Lip Gregory Y.H. , Lane Deirdre A.
Published: September 2024

Background:

Blood pressure (BP) extremes and renal (dys)function contribute to poor outcomes in patients with atrial fibrillation (AF). Using data from the prospective AF-GEN-UK study, we investigated the effect of systolic BP and interaction with renal function for prognostication.

Methods:

Baseline systolic BP (SBP) values were recorded for 1580 patients (mean [SD] age 71 [11] years, 60% male) and categorized as follows: 120–129 mmHg (n = 289, reference group) <110 mmHg (n = 165), 110–119 mmHg, (n = 254), 130–139 mmHg (n = 321), 140–159 mmHg (n = 385) and ≥160 mmHg (n = 166). Cox regression analysis, adjusted for age, oral anticoagulation (OAC) and CHA2DS2-VASc score established the impact of SBP, renal function and their interaction on 1-year outcomes. SBP groups were compared using ANOVA and chi-square tests.

Results:

OAC use was 84% and similar across SBP groups. Renal dysfunction [estimated baseline glomerular filtration rate (eGFR) < 60 ml/min] was present in 24%, with significantly lower eGFR values in the SBP 110–119 mmHg group. History of heart failure was significantly higher in those with SBP <110 mmHg. SBP <110 mmHg was predictive of all cause-death on univariate [hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.20–4.64] and adjusted (aHR 9.71, 95% CI 1.73–54.5) regression. There was no statistically significant interaction between SBP and eGFR, no associations of SBP with haemorrhagic or thromboembolic events.

Conclusions:

In people with AF, SBP <110 mmHg was independently predictive of all-cause death, with no significant interaction between SBP and renal (dys)function. This may reflect general poor health and/or excessive antihypertensive therapy, which should be avoided.
A Comparative Study of Ocular Surface Disease in Childhood Glaucoma
Authors: Elhusseiny Abdelrahman M. , Haseeb Abid , Eleiwa Taher K. , Elfattah Dina Abd , Sadik Nashwa , Solyman Omar , Chauhan Muhammad Z. , Shaikh Zain , Elsaadani Ibrahim , Elwehidy Ahmed S. , Saeed Hajirah N.
Published: September 2024

Purpose:

To evaluate ocular surface disease (OSD) in patients with childhood glaucoma (CG).

Methods:

A multicenter, comparative, cross-sectional study of 41 eyes of 27 patients with CG and 42 eyes of 42 healthy age- and sex-matched controls was conducted between 2021 and 2022. Developmentally delayed children and those having a coexisting systemic illness that might affect the ocular surface were not enrolled. Data collected included glaucoma type, glaucoma medications and surgeries, anterior segment examination, symptom frequency and severity, and tear break-up time (TBUT). Dry eye disease (DED) symptoms were evaluated using an Arabic-language SPEED questionnaire.

Results:

The average number of glaucoma medications and surgeries among the 27 patients with CG was 1.17 and 1.4, respectively. TBUT was shorter in patients with CG compared with controls and even shorter when glaucoma medication usage was accounted for. Punctate epithelial erosions were more prevalent in patients with CG and of a higher grade. The severity of all DED parameters, and the prevalence of all DED parameters except for eye fatigue, were greater in patients with CG on the day of questionnaire intake. In addition, each additional glaucoma drop was associated with worse TBUT and ocular surface dryness. All analyses mentioned above were statistically significant (P < 0.05).

Conclusions:

In this first study to comprehensively evaluate OSD in patients with CG, a significantly greater incidence of OSD signs and symptoms was found in patients with CG compared with a healthy population. Additional study by CG subtype is needed.