bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLM_Sol: predicting protein solubility by benchmarking multiple protein language models with the updated Escherichia coli protein solubility dataset
Authors: Zhang Xuechun , Hu Xiaoxuan , Zhang Tongtong , Yang Ling , Liu Chunhong , Xu Ning , Wang Haoyi , Sun Wen 
Published: August 2024

Abstract
Protein solubility plays a crucial role in various biotechnological, industrial, and biomedical applications. With the reduction in sequencing and gene synthesis costs, the adoption of high-throughput experimental screening coupled with tailored bioinformatic prediction has witnessed a rapidly growing trend for the development of novel functional enzymes of interest (EOI). High protein solubility rates are essential in this process and accurate prediction of solubility is a challenging task. As deep learning technology continues to evolve, attention-based protein language models (PLMs) can extract intrinsic information from protein sequences to a greater extent. Leveraging these models along with the increasing availability of protein solubility data inferred from structural database like the Protein Data Bank holds great potential to enhance the prediction of protein solubility. In this study, we curated an Updated Escherichia coli protein Solubility DataSet (UESolDS) and employed a combination of multiple PLMs and classification layers to predict protein solubility. The resulting best-performing model, named Protein Language Model-based protein Solubility prediction model (PLM_Sol), demonstrated significant improvements over previous reported models, achieving a notable 6.4% increase in accuracy, 9.0% increase in F1_score, and 11.1% increase in Matthews correlation coefficient score on the independent test set. Moreover, additional evaluation utilizing our in-house synthesized protein resource as test data, encompassing diverse types of enzymes, also showcased the good performance of PLM_Sol. Overall, PLM_Sol exhibited consistent and promising performance across both independent test set and experimental set, thereby making it well suited for facilitating large-scale EOI studies. PLM_Sol is available as a standalone program and as an easy-to-use model at https://zenodo.org/doi/10.5281/zenodo.10675340.
An extension of latent unknown clustering integrating multi-omics data (LUCID) incorporating incomplete omics data
Authors: Zhao Yinqi , Jia Qiran , Goodrich Jesse , Darst Burcu , Conti David V 
Published: August 2024

Abstract

Motivation
Latent unknown clustering integrating multi-omics data is a novel statistical model designed for multi-omics data analysis. It integrates omics data with exposures and an outcome through a latent cluster, elucidating how exposures influence processes reflected in multi-omics measurements, ultimately affecting an outcome. A significant challenge in multi-omics analysis is the issue of list-wise missingness. To address this, we extend the model to incorporate list-wise missingness within an integrated imputation framework, which can also handle sporadic missingness when necessary.

Results
Simulation studies demonstrate that our integrated imputation approach produces consistent and less biased estimates, closely reflecting true underlying values. We applied this model to data from the ISGlobal/ATHLETE “Exposome Data Challenge Event” to explore the association between maternal exposure to hexachlorobenzene and childhood body mass index by integrating incomplete proteomics data from 1301 children. The model successfully estimated proteomics profiles for two clusters representing higher and lower body mass index, characterizing the potential profiles linking prenatal hexachlorobenzene levels and childhood body mass index.

Availability and implementation
The proposed methods have been implemented in the R package LUCIDus. The source code is available at https://github.com/USCbiostats/LUCIDus.
Adamts9 is required for the development of primary ovarian follicles and maintenance of female sex in zebrafish
Authors: Carver Jonathan J , Amato Ciro M , Hung-Chang Yao Humphrey , Zhu Yong 
Published: August 2024

Abstract
Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9 KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9 leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish.
A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels?
Authors: Chen Lixuan , Jin Chenyang , Chen Bo , Debora Asta , Su Weizeng , Zhou Qingwen , Zhou Shuai , Bian Jinyan , Yang Yunjun , Lan Li 
Published: August 2024

Abstract

Objective
CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients.

Methods
We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour’s region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram.

Results
Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort.

Conclusion
Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels.

Advances in knowledge
This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.
Diffusion tensor imaging in Behcet’s disease with and without neurological involvement patients: evaluation of microstructural white matter abnormality with a tract-based spatial statistical analysis
Authors: Aslan Kerim , Genç Barış , Bolat Necdet , Incesu Lutfi 
Published: August 2024

Abstract

Objective
This study aims to assess the microstructural abnormalities in white matter (WM) among Behcet’s disease (BD) patients, both with and without neurological involvement, utilising tract-based spatial statistics (TBSS) to elucidate the underlying causes of WM microstructural changes.

Methods
This prospective study comprised 43 BD patients without neurological involvement, 15 neuro-Behcet’s disease (NBD) patients with normal conventional MRI, and 54 healthy controls matched for age and sex. TBSS was applied in this diffusion tensor imaging study to conduct a whole-brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of WM.

Results
Compared to the control group, BD patients exhibited decreased FA and increased MD and RD in nearly all WM tracts, along with increased AD in the left corticospinal tract (CST), left inferior longitudinal fasciculus (ILF), and left superior longitudinal fasciculus (SLF). NBD patients also showed a widespread decrease in FA and increased MD and RD, similar to BD patients without neurological involvement. Additionally, NBD patients had increased AD in the left CST, left ILF, left SLF, left inferior fronto-occipital fasciculus (IFOF), and right CST. Compared to BD patients without neurological involvement, NBD patients exhibited a greater reduction in FA and an increase in MD and RD in WM tracts, with no significant differences in AD.

Conclusion
These results suggest that the main mechanism of microstructural changes in the WM of BD patients may be related to impaired fibre integrity, demyelination, and decreased myelin sheath integrity.

Advances in knowledge
This study demonstrated BD patients without neurological involvement and NBD patients a decrease in FA and an increase in MD and RD were observed in larger areas of major WM tracts, while an increase in AD values was observed in fewer tracts. Our findings may be useful in understanding the pathophysiology underlying subclinical parenchymal involvement and neurological dysfunction in BD patients and the management of BD patients.
Optical manipulation of graphene oxide nanosheets toward arbitrary hetero-stacking of graphene and niobate and titanate nanosheets
Authors: Suzuki Yasutaka , Ikeda Akira , Nakao Shuji , Nakato Teruyuki , Saito Kanji , Kawamata Jun 
Published: August 2024

Abstract
The study explores a novel method for constructing hetero-stacked bilayers of graphene and various inorganic oxide nanosheets by utilizing optical manipulation technique. A graphene oxide (GO) is trapped by a laser beam, and the GO nanosheet is converted to reduced graphene oxide (rGO). The rGO pressed against the substrate, forming a hetero-stacked rGO–GO bilayer. Precise control over the relative location of the nanosheets is achieved by optically manipulating the rGO nanosheet. The technique is demonstrated with rGO-niobate and rGO-titanate bilayers, highlighting its simplicity and versatility.
“We are just with each other, everything is going to be okay”—BlackQueer rural–urban migration, danger and digital sexual desires
Authors: Lupindo Esihle 
Published: August 2024

Abstract
Much research looking at Queer migration focuses on the movement of people between countries and continents, where countries of origin are deemed unsafe. However, literature shows that in South Africa there are more people migrating internally than those migrating into South Africa from other countries. In this article, I draw on 15 interviews with BlackQueers who moved from rural to urban areas in South Africa to explain their Queer-centric motivations for migrating internally, which enabled them to “confront what it means to be Queer” through physical and digital interactions. The digital world is important because it surpasses fixed geographies. Digital spaces offer a refuge that may not be available in offline spaces even when there are legal protections that state that this should not be the case. This article provokes transnational scholarship to pay equal attention to movements within countries and digital spaces as it does to cross-country flows.
A GC–MS Method for Determination of β-Propiolactone Residues in Inactivated Covid-19 Vaccines
Authors: Mirjalili Seyedeh Zohreh , Tamiji Zahra , Shirangi Mehrnoosh , Amini Mohsen 
Published: August 2024

Abstract
β-propiolactone is a common inactivator agent used in vaccines. Due to β-propiolactone carcinogenicity, complete hydrolysis of it is necessary to prevent cytotoxicity in mammalian cells. As a result, more attention should be paid to it at the clinic, and it is important to measure its trace amounts. β-propiolactone analysis is challenging due to its instability. A simple and fast gas chromatography–mass spectrometry method was developed for quantitation of residual β-propiolactone in inactivated coronavirus disease 2019 (Covid-19) vaccines. Caprolactone was used as an internal standard in sample solutions; the analysis was performed after extraction of analyte from vaccine media by ethyl acetate. The validity of the method was studied with a linearity of r2 &gt; 0.99 over the concentration range of 0.2–20 μg/mL with the limit of detection and the limit of quantification of 0.07 and 0.20 μg/mL, respectively. The target analyte β-propiolactone was not detected in the samples, demonstrating the test samples were qualified. The established method can be used for quality control of inactivated Covid-19 vaccines.
CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection
Authors: Donskey Curtis J , Dubberke Erik R , Klein Nicola P , Liles Elizabeth G , Szymkowiak Katarzyna , Wilcox Mark H , Lawrence Jody , Bouguermouh Salim , Zhang Haiying , Koury Kenneth , Bailey Ruth , Smith Helen M , Lockhart Stephen , Lamberth Erik , Kalina Warren V , Pride Michael W , Webber Chris , Anderson Annaliesa S , Jansen Kathrin U , Gruber William C , Kitchin Nicholas 
Published: August 2024

Abstract

Background
Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

Methods
This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed.

Results
The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], −38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, −28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P = .02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups.

Conclusions
Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden.

Clinical Trials Registration
NCT03090191.
Implementation of Single High-dose Liposomal Amphotericin B Based Induction Therapy for Treatment of HIV-associated Cryptococcal Meningitis in Uganda: A Comparative Prospective Cohort Study
Authors: Gakuru Jane , Kagimu Enock , Dai Biyue , Okurut Samuel , Nsangi Laura , Bahr Nathan C , Okirwoth Michael , Namuju Olivie C , Jarvis Joseph N , Lawrence David S , Ahimbisibwe Cynthia , Ellis Jayne , Tadeo Kizza Kandole , Boulware David R , Meya David B , Tugume Lillian 
Published: August 2024

Abstract

Background
In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.

Methods
We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022–2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.

Results
During 2022–2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%–76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%–78.8%; absolute risk difference = −3.1%; 95% CI: −13.1% to 6.9%; P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144).

Conclusions
The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.
Redundancy as a Legal Strategy to Combat Corruption: Exploring the Potential of Institutional Multiplicity to Create Fail-Safe Systems
Authors: Mota Prado Mariana 
Published: August 2024

Abstract
Engineering uses duplication to create fail-safe systems. The existence of two system components capable of performing the same function increases reliability, as the supposedly superfluous component can be turned on if the main one breaks down. Although redundancy ensures that many of our modern conveniences such as computers and planes do not crash, this solution has not been extensively explored in a legal context. This article will articulate some of the advantages of redundancy between different areas of the law (administrative, civil and criminal) and at an institutional level (among bodies performing monitoring, investigative, prosecutorial and adjudicative functions in the same and in distinct jurisdictions). Legal efforts to combat corruption around the world provide illustrative examples of the many advantages of this strategy, but also some of its risks and disadvantages. Far from providing a comprehensive empirical analysis of this subject, this article articulates hypotheses to be tested and proposes that the topic deserves more attention among legal scholars than it has received.
Heart–brain axis in health and disease: role of innate and adaptive immunity
Authors: Simats Alba , Sager Hendrik B , Liesz Arthur 
Published: August 2024

Abstract
The importance of the brain–heart interaction has been increasingly recognized as a critical physiological axis that is altered in disease. In this review, we explore the intricate relationship between the central nervous system and cardiovascular health, focusing particularly on immunological mechanisms that influence the course of both neurological and cardiovascular diseases. While previous studies have established a key role of the autonomic nervous system (ANS) in linking brain and the heart, more recent studies have expanded our understanding of the multifaceted inter-organ interactions. As such, circulating mediators include immune cells of the adaptive and innate immune system and their secreted immunogenic factors have come into the focus as mediators along this bidirectional communication. Hence, in this review we briefly discuss the contribution of the ANS and then focus on innate and adaptive immune mechanisms along the heart-to-brain and brain-to-heart axes, illustrating how cardiovascular diseases affect cognitive functions and how brain pathologies lead to cardiac complications.
Implementation of the kissing balloon technique using a perfusion balloon in acute myocardial infarction: a case report
Authors: Nakata Marohito , Tabata Tatsuya , Nago Chikashi , Abe Masami , Uehara Hiroki 
Published: August 2024

Abstract

Background
Prolonged antiplatelet-agent administration associated with stenting for acute myocardial infarction is not ideal in young patients. We successfully performed a perfusion balloon-based kissing balloon technique in the left anterior descending artery ostium in a young patient with acute myocardial infarction.

Case summary
A 34-year-old female presenting with recurrent chest pain was diagnosed with ST-segment elevation acute myocardial infarction. Emergency coronary angiography revealed 90% stenosis of the left anterior descending artery ostium. Considering her age, lesion dilation using a perfusion balloon was preferred. This inadvertently impinged the left circumflex artery, causing chest pain and ischaemia-related hypotension with only a 10 s perfusion dilation balloon. We transitioned to an alternative 7 Fr guiding catheter and performed the kissing balloon technique using a perfusion balloon. This allowed prolonged inflation for 120 s, without complications. Optical coherence tomography of the lesion revealed layered plaques. Based on the patient’s age and medical history, coronary spasm may be the aetiological factor underlying acute ST-segment elevation myocardial infarction. Coronary angiography 3 months post-discharge revealed no restenosis.

Discussion
Regarding acute myocardial infarction, prolonged inflation with a perfusion balloon had higher frequency of non-stent-related interventions than that of semi-compliant or non-compliant balloons. In this case, the perfusion balloon resulted in chest pain and hypotension. Perfusion balloon-based kissing balloon technique was useful in this setting. Optical coherence tomography revealing the responsible lesions can help determine the cause of acute myocardial infarction in young patients; in our case, a layered plaque was observed. Layered plaques are associated with coronary spasm; therefore, initiating treatment of coronary spasm was considered herein.