bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling Population Protein Dynamics Through Bayesian Modeling
Authors: Lehmann Sylvain , Vialaret Jérôme , Gabelle Audrey , Bauchet Luc , Villemin Jean-Philippe , Hirtz Christophe , Colinge Jacques
Published: July 2024

Motivation

The knowledge of protein dynamics, or turnover, in patients provides invaluable information related to certain diseases, drug efficacy, or biological processes. A great corpus of experimental and computational methods has been developed, including by us, in the case of human patients followed in vivo. Moving one step further, we propose a novel modeling approach to capture population protein dynamics using Bayesian methods.

Results

Using two datasets, we demonstrate that models inspired by population pharmacokinetics can accurately capture protein turnover within a cohort and account for inter-individual variability. Such models pave the way for comparative studies searching for altered dynamics or biomarkers in diseases.

Availability

R code and preprocessed data are available from zenodo.org. Raw data are available from panoramaweb.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Genome-wide detection of somatic mosaicism at short tandem repeats
Authors: Sehgal Aarushi , Ziaei Jam Helyaneh , Shen Andrew , Gymrek Melissa
Published: July 2024

Motivation

Somatic mosaicism has been implicated in several developmental disorders, cancers, and other diseases. Short tandem repeats (STRs) consist of repeated sequences of 1–6 bp and comprise >1 million loci in the human genome. Somatic mosaicism at STRs is known to play a key role in the pathogenicity of loci implicated in repeat expansion disorders and is highly prevalent in cancers exhibiting microsatellite instability. While a variety of tools have been developed to genotype germline variation at STRs, a method for systematically identifying mosaic STRs is lacking.

Results

We introduce prancSTR, a novel method for detecting mosaic STRs from individual high-throughput sequencing datasets. prancSTR is designed to detect loci characterized by a single high-frequency mosaic allele, but can also detect loci with multiple mosaic alleles. Unlike many existing mosaicism detection methods for other variant types, prancSTR does not require a matched control sample as input. We show that prancSTR accurately identifies mosaic STRs in simulated data, demonstrate its feasibility by identifying candidate mosaic STRs in Illumina whole genome sequencing data derived from lymphoblastoid cell lines for individuals sequenced by the 1000 Genomes Project, and evaluate the use of prancSTR on Element and PacBio data. In addition to prancSTR, we present simTR, a novel simulation framework which simulates raw sequencing reads with realistic error profiles at STRs.

Availability and implementation

prancSTR and simTR are freely available at https://github.com/gymrek-lab/trtools. Detailed documentation is available at https://trtools.readthedocs.io/.
Harmonizing immune cell sequences for computational analysis with large language models
Authors: Alsaafin Areej , Tizhoosh Hamid R
Published: July 2024

We present SEQuence Weighted Alignment for Sorting and Harmonization (Seqwash), an algorithm designed to process sequencing profiles utilizing large language models. Seqwash harmonizes immune cell sequences into a unified representation, empowering LLMs to embed meaningful patterns while eliminating irrelevant information. Evaluations using immune cell sequencing data showcase Seqwash’s efficacy in standardizing profiles, leading to improved feature quality and enhanced performance in both supervised and unsupervised downstream tasks for sequencing data.
Contesting Neoliberal Reform of Statutory Social Work in Switzerland and England: Discretionary Spaces, Collective Resistance and Ethico-Political Professionalism
Authors: Moth Rich , Schilling Sigrid , Neuhaus Lukas , Lavalette Michael , Mürner Beat
Published: July 2024

This article reports findings from a qualitative study of the impacts of, and practitioner responses to, neoliberal social work reforms in Switzerland and England. The article highlights commonalities, and contrasts, in how neoliberalism has restructured social work across the two jurisdictions. Social workers responded to neoliberalisation in a variety of ways, often through adaptation but sometimes by challenging reforms. This resistance primarily involved individualised forms of agency promoting social justice in practice, such as carving out discretionary spaces within casework. However, in Switzerland, collective agency also emerged in the form of anti-cuts campaigning alongside service users. The literature tends to counterpose these micro and macro levels of agency, theorising discretion and resistance to the contradictions and value tensions generated by neoliberal reform as largely a product of practitioners’ individual ethical dispositions. However, we argue that enduring legacies of social justice values and relationship-based practices within social work institutions are also relevant in shaping how social workers navigate reforms. These enduring features offer institutional and normative resources of solidarity which can strengthen the possibilities for practitioner agency, at both individual and collective levels, to resist neoliberal reconfigurations and promote more liberatory and transformative forms of practice. We call this orientation ‘ethico-political professionalism’.
Multiple cognition associated multimodal brain networks in major depressive disorder
Authors: Yang Xiao , Wang Min , Liao Qimeng , Zhao Liansheng , Wei Jinxue , Wang Qiang , Sui Jing , Qi Shile , Ma Xiaohong
Published: July 2024

Major depressive disorder frequently leads to cognitive impairments, significantly affecting patients’ quality of life. However, the neurobiological mechanisms underlying cognitive deficits remain unclear. This study aimed to explore multimodal imaging biomarkers associated with cognitive function in major depressive disorder. Five cognitive scores (sustained attention, visual recognition memory, pattern recognition memory, executive function, and working memory) were used as references to guide the fusion of gray matter volume and amplitude of the low frequency fluctuation. Social function was assessed after 2 yr. Linear regression analysis was performed to identify brain features that were associated with social function of patients with major depressive disorder. Finally, we included 131 major depressive disorder and 145 healthy controls. A multimodal frontal-insula-occipital network associated with sustained attention was found to be associated with social functioning in major depressive disorders. Analysis across different cognitive domains revealed that gray matter volume exhibited greater sensitivity to differences, while amplitude of the low frequency fluctuation consistently decreased in the right temporal-occipital-hippocampus circuit. The consistent functional changes across the 5 cognitive domains were related to symptom severity. Overall, these findings provide insights into biomarkers associated with multiple cognitive domains in major depressive disorder. These results may contribute to the development of effective treatment targeting cognitive deficits and social function.
Elucidating trauma-related and disease-related regional cortical activity in post-traumatic stress disorder
Authors: Zhong Ruihan , Zhang Lianqing , Li Hailong , Wang Yingying , Cao Lingxiao , Bao Weijie , Gao Yingxue , Gong Qiyong , Huang Xiaoqi
Published: July 2024

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder–related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.
Fluctuation in cortical excitation/inhibition modulates capability of attention across time scales ranging from hours to seconds
Authors: Yang Binghao , Liu Hao , Jiang Tianzi , Yu Shan
Published: July 2024

Sustained attention, as the basis of general cognitive ability, naturally varies across different time scales, spanning from hours, e.g. from wakefulness to drowsiness state, to seconds, e.g. trial-by-trail fluctuation in a task session. Whether there is a unified mechanism underneath such trans-scale variability remains unclear. Here we show that fluctuation of cortical excitation/inhibition (E/I) is a strong modulator to sustained attention in humans across time scales. First, we observed the ability to attend varied across different brain states (wakefulness, postprandial somnolence, sleep deprived), as well as within any single state with larger swings. Second, regardless of the time scale involved, we found highly attentive state was always linked to more balanced cortical E/I characterized by electroencephalography (EEG) features, while deviations from the balanced state led to temporal decline in attention, suggesting the fluctuation of cortical E/I as a common mechanism underneath trans-scale attentional variability. Furthermore, we found the variations of both sustained attention and cortical E/I indices exhibited fractal structure in the temporal domain, exhibiting features of self-similarity. Taken together, these results demonstrate that sustained attention naturally varies across different time scales in a more complex way than previously appreciated, with the cortical E/I as a shared neurophysiological modulator.
Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients
Authors: Chen Ya , Hou Xinle , Zhou Huijuan , Han RuiChen , Lv Tingyu , Yang Zhiyuan , Zheng Wenao , Bai Feng
Published: July 2024

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer’s disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4 weeks, 20 Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.
Antibiotic Prescribing for Respiratory Tract Infections in Urgent Care: A Comparison of In-Person and Virtual Settings
Authors: Martinez Kathryn A , Deshpande Abhishek , Stanley Elizabeth , Rothberg Michael B
Published: July 2024

Background

Little is known about antibiotic prescribing for respiratory tract infections (RTIs) in virtual versus in-person urgent care.

Methods

In this retrospective study, we used electronic health record data from Cleveland Clinic Health System. We identified RTI patients via International Classification of Diseases, Tenth Revision, Clinical Modification, codes and assessed whether the visit resulted in an antibiotic. We described differences in diagnoses and prescribing by setting (virtual versus in-person). We used mixed effects logistic regression to model the odds of antibiotic receipt by urgent care setting. We applied the model first to all physicians and second only to those who saw patients in both settings.

Results

There were 69 189 in-person and 19 003 virtual visits. Fifty-eight percent of virtual visits resulted in an antibiotic compared with 43% of in-person visits. Sinusitis diagnoses were more than twice as common in virtual versus in-person care (36% vs 14%) and were associated with high rates of prescribing in both settings (95% in-person, 91% virtual). Compared with in-person care, virtual urgent care was positively associated with a prescription (odds ratio, 1.64; 95% confidence interval [CI]: 1.53–1.75). Among visits conducted by 39 physicians who saw patients in both settings, odds of antibiotic prescription in virtual care were 1.71 times higher than in in-person care (95% CI: 1.53–1.90).

Conclusions

Antibiotic prescriptions were more common in virtual versus in-person urgent care, including among physicians who provided care in both platforms. This appears to be related to the high rate of sinusitis diagnosis in virtual urgent care.
Experience with tafamidis in peritoneal dialysis for a patient diagnosed with transthyretin cardiac amyloidosis
Authors: Fazlic Diego López , García Samuel Abrante , Gerard Micaela , Izquierdo Edduin Martín , Bethencourt Alejandro Alonso , Vannini Luca , García Celestino Hernández , Heras Manuel Macía
Published: July 2024

Cardiac amyloidosis is a cardiomyopathy resulting from the extracellular deposition of proteins such as transthyretin (TTR). We present the case of a 72-year-old male with hereditary cardiac amyloidosis. After confirming the diagnosis, tafamidis, a TTR stabilizer, was administered. Remarkably, tafamidis, when coupled with peritoneal dialysis for chronic kidney disease, maintained stability in both cardiac and renal functions. Previous studies have demonstrated the efficacy of tafamidis in reducing all-cause mortality and cardiovascular hospitalizations, although its use in severe renal failure lacks specific evaluation. This case suggests a potential application of tafamidis in moderate–severe kidney disease, emphasizing the need for further research in this population.
Practical and secure policy-based chameleon hash for redactable blockchains
Authors: Li Nan , Li Yingjiu , Manulis Mark , Tian Yangguang , Yang Guomin
Published: July 2024

Policy-based chameleon hash functions have been widely proposed for its use in blockchain rewriting systems. They allow anyone to create a mutable transaction associated with an access policy, while an authorized user who possesses sufficient rewriting privileges from a trusted authority satisfying the access policy can rewrite the mutable transaction. However, existing chameleon hash functions lack certain fundamental security guarantees, including forward security and backward security. In this paper, we introduce a new primitive called forward/backward-secure policy-based chameleon hash (FB-PCH for short). We present a practical instantiation. We prove that the proposed scheme achieves forward/backward-secure collision-resistance, and show its practicality through implementation and evaluation analysis.
‘There was a bit of PTSD every time I walked through the office door’: Ransomware harms and the factors that influence the victim organization’s experience
Authors: Mott Gareth , Turner Sarah , Nurse Jason R C , Pattnaik Nandita , MacColl Jamie , Huesch Pia , Sullivan James
Published: July 2024

Ransomware is a pernicious contemporary cyber threat for organizations, with ransomware operators intentionally leveraging a range of harms against their victims in order to solicit increasingly significant ransom payments. This article advances current research by engaging in a topical analysis into the depth and breadth of harms experienced by victim organizations and their members of staff. We, therefore, enhance the understanding of the negative experiences from ransomware attacks, particularly looking beyond the financial impact which dominates current narratives. Having conducted an interview or workshop with 83 professionals including ransomware victims, incident responders, ransom negotiators, law enforcement, and government, we identify a wide array of severe harms. For organizations, the risk of business interruption and/or data exposure presents potentially highly impactful financial and reputational harm(s). The victim organization’s staff can also experience a range of under-reported harms, which include physiological and physical harms that may be acute. We also identify factors that can either alleviate or aggravate the experiencing of harms at the organizational and employee level; including ransomware preparedness, leadership culture, and crisis communication. Given the scale and scope of the identified harms, the paper provides significant new empirical evidence to emphasize ransomware’s positioning as a whole-of-organization crisis phenomenon, as opposed to an ‘IT problem’. We argue that the wider discourse surrounding ransomware harms and impacts should be reflective of the nature of the real-term experience(s) of victims. This, in turn, could help guide efforts to alleviate ransomware harms, through improved organizational ransomware preparedness and tailored post-ransomware mitigation.
Misconception of ‘malignant’ and ‘scissor-like compression’ of interarterial course in anomalous aortic origin of a coronary artery: a case series
Authors: Schütze Jonathan , Stark Anselm W , Bigler Marius R , Räber Lorenz , Gräni Christoph
Published: July 2024

Background

The notion that the ‘interarterial’ segment of anomalous aortic origin of a coronary artery (AAOCA) is ‘malignant’ and ‘scissor-like’ compressed between the aorta and pulmonary artery (PA) is debated, owing to the lower pressure in the pulmonary system compared with that in the coronary system. However, data supporting or refuting this belief under stress conditions are lacking.

Case summary

Three cases of right AAOCA with interarterial/intramural courses (52, 66, and 51 years old) were assessed. Invasively measured fractional flow reserve (FFR) under dobutamine was 0.85, 0.82, and 0.81, respectively. Intravascular ultrasound illustrated lateral vessel compression of the intramural course with a decrease of minimal lumen area (MLA) (i.e. 5.71–3.47 mm2, 5.88–4.00 mm2, and 5.85–4.06 mm2) under stress conditions with heart rates of 130, 140, and 150 b.p.m., respectively. Pulmonary artery pressure (PAP) increased from rest {s/d (m) [systolic/diastolic (mean)] 22/11 (15), 15/2 (5), and 24/6 (14) mmHg} to stress [s/d (m) 47/24 (36), 30/3 (11), and 36/22 (24) mmHg] and remained below aortic peak pressure (blood pressure, BP) rest [s/d (m) 116/64 (91), 94/48 (71), 99/53 and (62) mmHg]; BP stress [s/d (m) 142/63 (80), 123/63 (88), and 86/46 (62) mmHg]; coronary pressure (CoP) rest [s/d (m) 100/59 (80), 80/45 (62), and 83/47 (63) mmHg]; and CoP stress [s/d (m) 95/60 (69),101/54 (72), and 70/32 (50) mmHg].

Conclusion

This case series challenges the assumption that the interarterial segment of AAOCA is scissor-like compressed by both the aorta and PA. The decrease in MLA and FFR under stress is due to the aorta’s unidirectional lateral compression on the intramural segment. Additionally, the term ‘malignant’ should not be universally applied to all AAOCA cases with an interarterial course, as not all result in haemodynamic significance.
The effect of post-traumatic chondropathy on the functional state of knee joints in athletes while playing basketball
Authors: Cui Wenpeng , Bezmilov Mykola
Published: July 2024

The widespread occurrence of knee injuries in athletes when playing basketball, in particular, damage to the cartilage system of the knee joint is reviewed. Basketball players may develop post-traumatic chondropathy with a subsequent change in the functional state of knee joints, which is inextricably linked with a decrease in the quality of life, the occurrence of pain syndrome, shortening of career duration, an increased risk of surgical interventions, and possible disability, from a long-term perspective. This review was conducted to explore modern ideas about the impact of post-traumatic chondropathy on the functional state of knee joints in athletes during basketball games. Literature databases were searched for relevant studies. Given the character of the basketball game, knee injuries, both acute and chronic, are widespread among athletes of this sport, including cartilaginous defects of the knee joint. The findings of this study are of practical value for sports medicine doctors, physiotherapists, and traumatologists because they present the main mechanisms of knee injuries in athletes when playing basketball and the possible consequences of these injuries in the long term.
NaV1.5 autoantibodies in Brugada syndrome: pathogenetic implications
Authors: Tarantino Adriana , Ciconte Giuseppe , Melgari Dario , Frosio Anthony , Ghiroldi Andrea , Piccoli Marco , Villa Marco , Creo Pasquale , Calamaio Serena , Castoldi Valerio , Coviello Simona , Micaglio Emanuele , Cirillo Federica , Locati Emanuela Teresina , Negro Gabriele , Boccellino Antonio , Mastrocinque Flavio , Ćalović Žarko , Ricagno Stefano , Leocani Letizia , Vicedomini Gabriele , Santinelli Vincenzo , Rivolta Ilaria , Anastasia Luigi , Pappone Carlo
Published: July 2024

Background and Aims

Patients suffering from Brugada syndrome (BrS) are predisposed to life-threatening cardiac arrhythmias. Diagnosis is challenging due to the elusive electrocardiographic (ECG) signature that often requires unconventional ECG lead placement and drug challenges to be detected. Although NaV1.5 sodium channel dysfunction is a recognized pathophysiological mechanism in BrS, only 25% of patients have detectable SCN5A variants. Given the emerging role of autoimmunity in cardiac ion channel function, this study explores the presence and potential impact of anti-NaV1.5 autoantibodies in BrS patients.

Methods

Using engineered HEK293A cells expressing recombinant NaV1.5 protein, plasma from 50 BrS patients and 50 controls was screened for anti-NaV1.5 autoantibodies via western blot, with specificity confirmed by immunoprecipitation and immunofluorescence. The impact of these autoantibodies on sodium current density and their pathophysiological effects were assessed in cellular models and through plasma injection in wild-type mice.

Results

Anti-NaV1.5 autoantibodies were detected in 90% of BrS patients vs. 6% of controls, yielding a diagnostic area under the curve of .92, with 94% specificity and 90% sensitivity. These findings were consistent across varying patient demographics and independent of SCN5A mutation status. Electrophysiological studies demonstrated a significant reduction specifically in sodium current density. Notably, mice injected with BrS plasma showed Brugada-like ECG abnormalities, supporting the pathogenic role of these autoantibodies.

Conclusions

The study demonstrates the presence of anti-NaV1.5 autoantibodies in the majority of BrS patients, suggesting an immunopathogenic component of the syndrome beyond genetic predispositions. These autoantibodies, which could serve as additional diagnostic markers, also prompt reconsideration of the underlying mechanisms of BrS, as evidenced by their role in inducing the ECG signature of the syndrome in wild-type mice. These findings encourage a more comprehensive diagnostic approach and point to new avenues for therapeutic research.
The Erasmus+ EUMOVE project—a school-based promotion of healthy lifestyles to prevent obesity in European children and adolescents
Authors: Ruiz-Hermosa Abel , Sánchez-López Mairena , Castro-Piñero José , Grao-Cruces Alberto , Camiletti-Moirón Daniel , Martins João , Mota Jorge , Ceciliani Andrea , Murphy Marie , Vuillemin Anne , Sánchez-Oliva David ,   EUMOVE Consortium, Calvo Tomás García , Ponce Inmaculada González , González Juan José Pulido , Marcos Francisco Miguel Leo , Miguel Pedro Antonio Sánchez , Marín Diego Muñoz , Serrano Javier Sevil , Serrano Miguel Ángel Tapia , Gómez Rocío Izquierdo , Caveda Julio Conde , Moledo Carmen Padilla , Martínez-Vizcaíno Vicente , Morcillo Carlos González , Garzón Palma Chillón , Onofre Marcos , Marques Adilson , Ribeiro Tiago , Silva Paula , Santos Paula , Pizarro Andreia , Corrion Karine , Garbarino Jean-Marie , Dallolio Laura , Masini Alice , Marini Sofia , Carlin Angela , Connolly Sinead , Ferro Nuno , Bolaños Felix , Costa João , Pjevac Dusan , Fournier Marion , Mulato Raffaela , Riegger Stephan
Published: July 2024

The aim of this study was to describe the goals, activities, and methods of EUMOVE project in developing a set of resources targeting both primary and secondary schools that allow the entire educational community to promote healthy lifestyles (HL). The EUMOVE project is an Erasmus+ program based in the Creating Active Schools (CAS) framework. The project lasted 3 years and was developed by 14 academic and non-governmental institutions from Spain, Portugal, France, Italy, and the UK. EUMOVE was divided into three phases. In the first phase, several work packages were carried out aimed to ensure the coordination/management of the project activities. In the second phase, seven educational resources strengthened by rigorous scientific research were developed to promote HL from schools. During the last phase, all the resources were disseminated through scientific seminars, workshops with families and teachers, and the online promotion by the non-governmental institutions of each country. The EUMOVE project developed and promoted a smartphone APP, video/activity repository of physically active lessons, active break virtual platform, learning units, and parent/teachers/school-leaders’ guidelines to promote physical activity, active commuting, active school playgrounds, healthy diet, and sleep habits. To our knowledge, EUMOVE is the first European project to provide a set of practical tools based on scientific evidence to help schools or future school-wide interventions implement a paradigm shift based on the CAS framework for the promotion of HL. Future research will need to investigate the implementation, effectiveness, and scalability of this proposal.
Development and validation of the Environmental Health Literacy Index: a new tool to assess the environmental health literacy among university students
Authors: Fiore Maria , Lorini Chiara , Bonaccorsi Guglielmo , Paoli Sonia , Vaccaro Gabriele , Verani Marco , Federigi Ileana , Ferrante Margherita , Carducci Annalaura
Published: July 2024

Environmental health literacy (EHL) is a rather recent concept that applies health literacy skills to environmental issues. Research in this field is still at the beginning, and there is currently no existing tool in the literature designed to comprehensively assess individual general EHL among university students. The aim of our study is to fill this gap through the validation of the Environmental Health Literacy Index (EHLI) in such a target group. We adapted a previously administered survey, originally completed by 4778 university students from various Italian universities. Starting from the original questionnaire, our methodology involved a three-round item selection process, followed by a comprehensive evaluation of the instrument’s psychometric properties. The EHLI consists of 13 Likert-type items, covering three primary domains of health literacy: functional (six items), interactive (three items), and critical (four items). The Cronbach’s alpha coefficient is 0.808 for the global scale, while it stands at 0.888 for the functional, 0.795 for the critical, and 0.471 for the interactive components. The area under the receiver operating characteristic curve reached a value of 0.643. Spearman correlation analysis revealed a significant yet slight correlation between EHLI and both functional health literacy score and the extent of pro-environmental behaviors adoption. Our study serves as an important initial step in developing a tool able to evaluate the EHL of university-aged individuals. Further research efforts may improve the questionnaire’s validity and completeness, as well as to explore its applicability to different age groups.
ETV4/NSUN2 Axis modulates aerobic glycolysis and malignancy in HSCC
Authors: Ding Xiaoxu , Zhang Xueyan , Fang Panxia , Bai Weiliang
Published: July 2024

This study delves into the molecular intricacies of hypopharyngeal squamous cell carcinoma (HSCC), specifically focusing on the pivotal role played by ETS translocation variant 4 (ETV4) in aerobic glycolysis. The objective is to uncover new targets for early diagnosis and treatment of HSCC. ETV4 expression in HSCC tissues was rigorously examined, revealing its association with patient survival. Through comprehensive experimentation, we demonstrated that ETV4 activation promotes HSCC cell proliferation and invasion while inhibiting apoptosis. Furthermore, in vivo experiments confirmed the tumor-promoting effect of ETV4 activation. The study elucidated the binding of ETV4 to the NSUN2 promoter and its influence on PKM2 expression, thereby regulating glycolysis and cellular functions in HSCC.
Transcription factors LvBBX24 and LvbZIP44 coordinated anthocyanin accumulation in response to light in lily petals
Authors: Gao Zhenhua , Sun Yibo , Zhu Ziman , Ni Na , Sun Shaokun , Nie Mengyao , Du Weifeng , Irfan Muhammad , Chen Lijing , Zhang Li
Published: July 2024

Lily (Lilium spp.), a horticultural crop serving both ornamental and edible functions, derives its coloration primarily from anthocyanins. However, limited studies have been conducted on the accumulation of anthocyanins within lilies. In this study, we cloned a light-induced transcription factor named as LvBBX24 in lilies. Through genetic and biochemical analysis, we determined that LvBBX24 could upregulate the transcription of LvMYB5 and facilitate anthocyanin synthesis. Moreover, we identified that darkness promoted the degradation of LvBBX24 protein. Through screening a yeast library, we identified LvbZIP44 acts as its interacting partner. Genetic testing confirmed that LvbZIP44 also plays a role in promoting lily anthocyanin synthesis. This indicates a potential synergistic regulatory effect between LvBBX24 and LvbZIP44. Our study indicates that LvBBX24 and LvbZIP44 cooperate to regulate anthocyanin accumulation in lily petals. These findings provide compelling evidence supporting the idea that LvBBX24 and LvbZIP44 may form a looped helix surrounding the LvMYB5 promoter region to regulate anthocyanin biosynthesis.
The ECHR and the Positive Obligation to Criminalise Domestic Psychological Violence
Authors: Hedlund Niels
Published: July 2024

This article explores the scope of the positive obligation deriving from the case law of the European Court of Human Rights (ECtHR) to criminalise forms of domestic psychological violence. This is primarily done by examining the implications of Volodina v Russia (No. 1), Volodina v Russia (No. 2) and Tunikova and Others v Russia regarding the obligation in question. Additionally, this article addresses different legislative approaches towards the criminalisation of domestic violence that have been distinguished by the ECtHR and discusses whether they adequately criminalise domestic psychological violence. Some approaches appear ill-suited as they concern national offences that focus on serious incidents. Domestic psychological violence, on the other hand, can involve a course of conduct consisting of seemingly minor incidents. It is concluded that State Parties should review to what extent such forms of psychological violence are criminalised under their national criminal laws.
A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events
Authors: Sekiguchi William Kazunori , de Oliveira Vítor Falcão , Cavassin Francelise Bridi , Taborda Mariane , Gonçalves Kono Magri Adriana Satie , da Cruz Isabela Carvalho Leme Vieira , Vidal Jose Ernesto , Falci Diego Rodrigues , Silva de Miranda Godoy Cássia , de Bastos Ascenço Soares Renata , de Oliveira Carla Sakuma , Mendes Ana Verena Almeida , Breda Giovanni Luís , Rego Caroline Martins , Félix Maíra Araujo , Katopodis Paula Pacheco , da Silva do Ó Julia Raquel , Abrão Mirela Pereira Lima , Baú-Carneiro João Luiz , Pereira Talita Teles Teixeira , Queiroz-Telles Flávio , Mihailenko Chaves Magri Marcello
Published: July 2024

Background

Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates.

Objectives

Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality.

Methods

This multicentre retrospective cohort study (January 2014–December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses.

Results

The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment.

Conclusions

We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.
Returning value from the All of Us Research Program to PhD-level nursing students using ChatGPT as programming support: results from a mixed-methods experimental feasibility study
Authors: Reading Turchioe Meghan , Kisselev Sergey , Fan Ruilin , Bakken Suzanne
Published: July 2024

Objective

We aimed to evaluate the feasibility of using ChatGPT as programming support for nursing PhD students conducting analyses using the All of Us Researcher Workbench.

Materials and Methods

9 students in a PhD-level nursing course were prospectively randomized into 2 groups who used ChatGPT for programming support on alternating assignments in the workbench. Students reported completion time, confidence, and qualitative reflections on barriers, resources used, and the learning process.

Results

The median completion time was shorter for novices and certain assignments using ChatGPT. In qualitative reflections, students reported ChatGPT helped generate and troubleshoot code and facilitated learning but was occasionally inaccurate.

Discussion

ChatGPT provided cognitive scaffolding that enabled students to move toward complex programming tasks using the All of Us Researcher Workbench but should be used in combination with other resources.

Conclusion

Our findings support the feasibility of using ChatGPT to help PhD nursing students use the All of Us Researcher Workbench to pursue novel research directions.
Automated pipe design in 3D using a multi-objective toolchain for efficient decision-making
Authors: Neumaier Moritz , Kranemann Stefan , Kazmeier Bernd , Rudolph Stephan
Published: July 2024

Pipe design in 3D is typically characterized by competing objectives, since the different design objectives, such as the reduction of length, weight, number of bends, manufacturing cost, and overall angle sum, are examples for such competing design goals, where one goal is often at the expense of the other. The origin of these competing design goals lies in the highly coupled problems of finding a permissible and collision-free pipe path in a complex 3D geometry and the physical properties of the path found. Because of the complex physics and geometry, these couplings are highly non-linear and mostly accessible via simulation only. The underlying pipe design optimization problem can thus not be solved explicitly and is tackled instead with a multi-disciplinary search procedure. Since the trade-offs between different competing evaluation objectives are often not known in advance, an automated design space exploration can be performed to generate different pipe designs, leading to well-informed design decisions by human experts. Such a design space exploration is shown and discussed using the pipework in a mounting rack in an Airbus A320 main landing gear bay. A total of 144 valid designs are generated, out of which the best in each criteria and the pareto-optimal solutions are automatically selected. Compared to the manually created Airbus A320 series solution, up to $10.4\%$ of the pipe length or up to $16.9\%$ of the bends can be saved using the same fixings and connection points, demonstrating both the feasibility and the industrial applicability of the automated toolchain.
Therapeutic efficacy and safety of biweekly administration of enfortumab vedotin for urothelial carcinoma
Authors: Nakagawa Ryunosuke , Izumi Kouji , Toriumi Ren , Aoyama Shuhei , Kamijima Taiki , Kano Hiroshi , Makino Tomoyuki , Naito Renato , Iwamoto Hiroaki , Yaegashi Hiroshi , Kawaguchi Shohei , Shigehara Kazuyoshi , Nohara Takahiro , Mizokami Atsushi
Published: July 2024

Objectives

Enfortumab vedotin (EV) is an established pharmacotherapy for metastatic urothelial carcinoma (mUC); however, its adverse events (AEs) cannot be overlooked. The study investigated the efficacy and safety of biweekly EV administration.

Methods

Patients with mUC who received EV at our institution were included in the study. Eligible patients were classified into two groups as follows: those who received EV on a standard schedule (standard group) and those who received EV on a biweekly schedule (biweekly group); the treatment outcomes and AEs between the two groups were compared.

Results

Nine and 19 patients were in the standard group and biweekly groups, respectively. The progression-free survival, overall survival, and overall response rate were not significantly different between the two groups. AEs following EV administration, such as decreased appetite (P < .01), pruritus (P < .01), rash maculopapular (P < .01), anemia (P = .04), and liver dysfunction (P = .04), were significantly more frequent in the standard group. Grade 3 or higher AEs, such as pruritus (P = .03) and rash maculopapular (P < .01), were significantly more frequent in the standard group. Furthermore, significantly more patients in the standard group had to be given a reduced dose due to adverse events (P = .02).

Conclusions

Biweekly administration of EV may be safer without compromising therapeutic efficacy than the standard schedule.
How black hole activity may influence exoplanetary evolution in our Galaxy
Authors: Ishibashi W
Published: July 2024

An increasing number of exoplanets have been discovered in the Milky Way galaxy, which is also known to harbour a super-massive black hole (Sagittarius A*) at its centre. Here, we investigate how the central black hole (BH) activity may affect the evolution of exoplanets in our Galaxy. Accreting BHs emit high-energy radiation – extreme ultraviolet and X-rays – which can lead to XUV photoevaporation of the planetary atmospheres. We evaluate the atmospheric mass-loss using both theoretical estimates of the BH radiative output and observational constraints on the past activity history of Sgr A*. The resulting mass-loss is analysed as a function of the galactocentric distance. For the first time, we compute the exoplanet atmospheric evolution under BH irradiation by explicitly including the temporal evolution of the central luminosity output (i.e. the BH activity history). We obtain that Sgr A* could have a major impact on exoplanets located in the inner region of the Galaxy (e.g. Galactic bulge); a significant fraction of the atmospheric mass can be removed by BH irradiation; and in extreme cases, the initial atmosphere may be completely stripped away. Such mass-loss can have important consequences on the atmospheric chemistry and potential biological evolution. We discuss the physical implications for planetary habitability, and we also briefly consider the case of stellar-mass BHs. Overall, accreting black holes may play a significant role in the evolution of exoplanets in our Galaxy across cosmic time.
Understanding the relationship between sequences and kinetics of DNA strand displacements
Authors: Long Da , Shi Peichen , Xu Xin , Ren Jiayi , Chen Yuqing , Guo Shihui , Wang Xinchang , Cao Xiaoyu , Yang Liulin , Tian Zhongqun
Published: July 2024

Precisely modulating the kinetics of toehold-mediated DNA strand displacements (TMSD) is essential for its application in DNA nanotechnology. The sequence in the toehold region significantly influences the kinetics of TMSD. However, due to the large sample space resulting from various arrangements of base sequences and the resulted complex secondary structures, such a correlation is not intuitive. Herein, machine learning was employed to reveal the relationship between the kinetics of TMSD and the toehold sequence as well as the correlated secondary structure of invader strands. Key factors that influence the rate constant of TMSD were identified, such as the number of free hydrogen bonding sites in the invader, the number of free bases in the toehold, and the number of hydrogen bonds in intermediates. Moreover, a predictive model was constructed, which successfully achieved semi-quantitative prediction of rate constants of TMSD even with subtle distinctions in toehold sequence.
Structural insights into the assembly of type IIA topoisomerase DNA cleavage-religation center
Authors: Liu Ko-Ting , Chen Shin-Fu , Chan Nei-Li
Published: July 2024

The ability to catalyze reversible DNA cleavage and religation is central to topoisomerases' role in regulating DNA topology. In type IIA topoisomerases (Top2), the formation of its DNA cleavage-religation center is driven by DNA-binding-induced structural rearrangements. These changes optimally position key catalytic modules, such as the active site tyrosine of the WHD domain and metal ion(s) chelated by the TOPRIM domain, around the scissile phosphodiester bond to perform reversible transesterification. To understand this assembly process in detail, we report the catalytic core structures of human Top2α and Top2β in an on-pathway conformational state. This state features an in trans formation of an interface between the Tower and opposing TOPRIM domain, revealing a groove for accommodating incoming G-segment DNA. Structural superimposition further unveils how subsequent DNA-binding-induced disengagement of the TOPRIM and Tower domains allows a firm grasp of the bound DNA for cleavage/religation. Notably, we identified a previously undocumented protein-DNA interaction, formed between an arginine-capped C-terminus of an α-helix in the TOPRIM domain and the DNA backbone, significantly contributing to Top2 function. This work uncovers a previously unrecognized role of the Tower domain, highlighting its involvement in anchoring and releasing the TOPRIM domain, thus priming Top2 for DNA binding and cleavage.
Definition of the effector landscape across 13 phytoplasma proteomes with LEAPH and EffectorComb
Authors: Calia Giulia , Cestaro Alessandro , Schuler Hannes , Janik Katrin , Donati Claudio , Moser Mirko , Bottini Silvia
Published: July 2024

‘Candidatus Phytoplasma’ genus, a group of fastidious phloem-restricted bacteria, can infect a wide variety of both ornamental and agro-economically important plants. Phytoplasmas secrete effector proteins responsible for the symptoms associated with the disease. Identifying and characterizing these proteins is of prime importance for expanding our knowledge of the molecular bases of the disease. We faced the challenge of identifying phytoplasma's effectors by developing LEAPH, a machine learning ensemble predictor composed of four models. LEAPH was trained on 479 proteins from 53 phytoplasma species, described by 30 features. LEAPH achieved 97.49% accuracy, 95.26% precision and 98.37% recall, ensuring a low false-positive rate and outperforming available state-of-the-art methods. The application of LEAPH to 13 phytoplasma proteomes yields a comprehensive landscape of 2089 putative pathogenicity proteins. We identified three classes according to different secretion models: ‘classical’, ‘classical-like’ and ‘non-classical’. Importantly, LEAPH identified 15 out of 17 known experimentally validated effectors belonging to the three classes. Furthermore, to help the selection of novel candidates for biological validation, we applied the Self-Organizing Maps algorithm and developed a Shiny app called EffectorComb. LEAPH and the EffectorComb app can be used to boost the characterization of putative effectors at both computational and experimental levels, and can be employed in other phytopathological models.