bluuebunny/crossref_metadata_2025 huggingface dataset:
The gut microbiome modulates the susceptibility to traumatic stress in a sex‐dependent manner
Authors: Shen Dan , Chang Liang , Su Feng , Huang Shihao , Xu Hubo , Si Yue , Wang Feng , Xue Yanxue
Published: March 2024

Post‐traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats. Here, we utilized the single prolonged stress animal model and employed unsupervised machine learning to classify stressed animals into stress‐susceptible subgroups and stress‐resilient subgroups. Subsequently, using 16S V3‐V4 rDNA sequencing, we investigated the differential gut microbiota alterations between susceptible and resilient individuals in male and female rats. Our findings revealed distinct changes in gut microbiota composition between the sexes at different taxonomic levels. Furthermore, the abundance of Parabacteroides was lower in rats that underwent SPS modeling compared to the control group. In addition, the abundance of Tenericutes in the stress‐susceptible subgroup was higher than that in the control group and stress‐resilient subgroup, suggesting that Tenericutes may be able to characterize stress susceptibility. What is particularly interesting here is that Cyanobacteria may be particularly associated with anti‐anxiety effects in male rats. This study underscores sex‐specific variations in gut microbiota composition in response to stress and sex differences should be taken into account when using macrobiotics for neuropsychiatric treatment, highlighting potential targets for PTSD therapeutic interventions.
Ex vivo storage of human osteochondral allografts: Long‐term analysis over 300 days using a Ringer‐based solution
Authors: Jiang Zhida , Clausen Jan‐Dierk , Jahn Denise , Wulsten Dag , Gladitz Luisa M. , Bundkirchen Katrin , Krettek Christian , Neunaber Claudia
Published: March 2024

Large osteochondral defects are a major challenge in orthopedics, for which osteochondral allograft (OCA) transplantation is nowadays considered as an option, especially in young patients. However, a major issue with OCA is the need for graft storage, which ensures adequate cartilage integrity over time. The aim of this study was to test how long a Ringer‐based storage solution can provide good graft quality after explantation and thus meet the requirements for OCA. For this purpose, human osteochondral allografts of the knee and ankle were analyzed. Live/Dead analysis was performed and glycosaminoglycan, as well as hydroxyproline content, were measured as crucial chondrocyte integrity factors. Furthermore, biomechanical tests focusing on stress relaxation and elastic compression modulus were performed. The critical value of 70% living chondrocytes, which corresponds to a number of 300 cells/mm², was reached after an average of 16 weeks of storage. In addition, a constant cell shrinkage was observed over time. The amount of glycosaminoglycan and hydroxyroline showed a slight and constant decrease over time, but no significant differences when compared from Day 0 to the values at Weeks 40–43. Biomechanical testing also revealed no significant differences at the different time points. Therefore, the results show that the Ringer‐based storage solution at 4°C is able to provide a chondrocyte survival of 70% until Week 16. This is comparable to previously published storage solutions. Therefore, the study contributes to the establishment of a Ringer‐based osteochondral allograft transplantation system for countries where medium‐based storage solution cannot be approved.
Increased Wnt5a/ROR2 signaling is associated with chondrogenesis in meniscal degeneration
Authors: Inoue Yusuke , Kumagai Ken , Ishikawa Kimi , Kato Ikuma , Kusaba Youhei , Naka Takuma , Nagashima Kiyotaka , Choe Hyonmin , Ike Hiroyuki , Kobayashi Naomi , Inaba Yutaka
Published: March 2024

The aim of the present study was to investigate the association between chondrogenic differentiation and Wnt signal expression in the degenerative process of the human meniscus. Menisci were obtained from patients with and without knee osteoarthritis (OA), and degeneration was histologically assessed using a grading system. Immunohistochemistry, real‐time polymerase chain reaction (PCR), and Western blot analysis were performed to examine the expressions of chondrogenic markers and of the components of Wnt signaling. Histological analyses showed that meniscal degeneration involved a transition from a fibroblastic to a chondrogenic phenotype with the upregulation of SOX9, collagen type II, collagen type XI, and aggrecan, which were associated with increased Wnt5a and ROR2 and decreased TCF7 expressions. OA menisci showed significantly higher expressions of Wnt5a and ROR2 and significantly lower expressions of AXIN2 and TCF7 than non‐OA menisci on real‐time PCR and Western blot analysis. These results potentially demonstrated that increased expression of Wnt5a/ROR2 signaling promoted chondrogenesis with decreased expression in downstream Wnt/β‐catenin signaling. This study provides insights into the role of Wnt signaling in the process of meniscal degeneration, shifting to a chondrogenic phenotype. The findings suggested that the increased expression of Wnt5a/ROR2 and decreased expression of the downstream target of Wnt/β‐catenin signaling are associated with chondrogenesis in meniscal degeneration.
Factors associated with an increased risk of vitamin B12 deficiency in patients with type 2 diabetes mellitus on metformin
Authors: Wagner Ross , Mahashabde Ruchira , Painter Jacob , Boehmer Kaci
Published: March 2024

Background

Metformin is used to treat type 2 diabetes mellitus, but prolonged use has been associated with vitamin B12 deficiency. Many other factors have also been associated with vitamin B12 deficiency. Studies on the possible additive effect of risk factors for developing a vitamin B12 deficiency are lacking.

Aim

The objective of this study was to assess the correlation between other known risk factors for vitamin B12 deficiency among patients with type 2 diabetes mellitus prescribed metformin who had a vitamin B12 deficiency.

Method

For inclusion in this single‐centre, retrospective cohort study, patients needed to be at least 18 years old, diagnosed with type 2 diabetes, taking metformin for at least 2 years and actively taking metformin during the study period. The primary outcome was the rate of low B12 levels with metformin. Secondary outcomes were risk factors associated with B12 deficiency. The patient and clinical characteristics were compared between the two study groups using Student's t‐test for continuous variables and chi‐squared tests for categorical variables. This project was exempt due to the local policy requirements that constitute research by the University of Arkansas for Medical Sciences Institutional Review Board (IRB) (IRB Program Manager, 11 August 2021). The justification for this ethics exemption was as follows: the project was determined to be of minimal risk to privacy of subjects because the research team had mechanisms to protect the personal health identifiers from improper use or disclosure; to destroy the identifiers at the earliest opportunity consistent with the conduct of research, and provided assurance that the identifiers will not be re‐used or disclosed to any other person or entity, except as required by law, for authorised oversight of the research project, or for other research as permitted by the HIPAA regulations.

Results

A total of 387 patients were included in this study, from which 364 patients had a vitamin B12 deficiency. The cohort was an average 69‐years‐old and predominantly female (66%). No risk factors were associated with a higher incidence of B12 deficiency. Patient age (p = 0.0063) and time on metformin (p = 0.0144) were significantly and negatively correlated with B12 deficiency.

Conclusion

Younger age and shorter duration of metformin use may increase the risk of vitamin B12 deficiency. Although guidelines recommend occasional checks, only 21% of patients had vitamin B12 levels assessed during the study period.
Clinical report and genetic analysis of rare premature infant nephronophthisis caused by biallelic TTC21B variants
Authors: Li Yingying , Dai Liying , Xu Hong , Huang Jin , Zhang Jinqiu , Mei Zhenzhu , Zhang Rui
Published: March 2024

Background

Nephronophthisis (NPHP) is a genetically heterogeneous disease that can lead to end‐stage renal disease (ESRD) in children. The TTC21B variant is associated with NPHP12 and mainly characterized by cystic kidney disease, skeletal malformation, liver fibrosis, and retinopathy. Affected patients range from children to adults. Some patients experience ESRD in infancy or early childhood, but clinical reports on neonatal patients are rare. We report a case of NPHP12 in a premature infant and analyze its genetic etiology.

Methods

Trio‐whole exome sequencing analysis was performed on the patient and her parents; bioinformatics software was used to predict and analyze the hazards of the variants. Sanger sequencing was performed to verify variants. We calculated the free energy between mutant IFT139 and the IFT121‐IFT122‐IFT43 complex structure using molecular dynamics (MD). Finally, the clinical and genetic characteristics of patients with hotspot variant Cys518Arg were reviewed.

Results

Genetic analysis revealed compound‐heterozyous TTC21B variants in the patient, c.497delA (p.Lys166fs*36) and c.1552T>C (p.Cys518Arg). Her father and mother had heterozygous c.497delA (p.Lys166fs*36) and heterozygous c.1552T>C (p.Cys518Arg), respectively. Cys518Arg represents a hotspot variant, and the MD calculation results show that this can reduce the structural stability of the IFT121‐IFT122‐IFT139‐IFT43 complex structure. A literature review showed that Cys518Arg might lead to the early occurrence of ESRD.

Conclusions

Compound‐heterozygous TTC21B variants underlie the phenotype in this patient. Thus, Cys518Arg may be a hotspot variant in the Chinese population. Genetic testing should be recommended for NPHP in neonates and early infants.
A theoretical framework to investigate the effect of high permittivity materials in MRI using anatomy‐mimicking cylinders
Authors: Miranda Vincenzo , Ruello Giuseppe , Lattanzi Riccardo
Published: March 2024

Purpose

Recent numerical and empirical results proved that high permittivity materials (HPM) used in pads placed near the subject or directly integrated with coils can increase the SNR and reduce the specific absorption rate (SAR) in MRI. In this paper, we propose an analytical investigation of the effect on the magnetic field distribution of a layer of HPM surrounding an anatomy‐mimicking cylindrical sample.

Methods

The study is based on a reformulation of the Mie scattering for cylindrical geometry, following an approach recently introduced for spherical samples. The total field in each medium is decomposed in terms of inward and outward electromagnetic waves, and the fields are expressed as series of cylindrical harmonics, whose coefficients can be interpreted as classical reflection and transmission coefficients.

Results

Our new formulation allows a quantitative evaluation of the effect of the HPM layer for varying permittivity and thickness, and it provides an intuitive understanding of such effect in terms of propagation and scattering of the RF field.

Conclusion

We show how HPM can filter out the modes that only contribute to the noise or RF power deposition, resulting in higher SNR or lower SAR, respectively. Our proposed framework provides physical insight on how to properly design HPM for MRI applications.
Submillimeter balanced SSFP BOLD–functional MRI accelerated with 3D stack‐of‐spirals at 9.4 T
Authors: Iyyappan Valsala Praveen , Veldmann Marten , Bosch Dario , Scheffler Klaus , Ehses Philipp
Published: March 2024

Purpose

This work aims to improve the speed of balanced SSFP (bSSFP) acquisition with segmented 3D stack‐of‐spirals for functional brain studies at ultrahigh field.

Methods

Functional experiments were performed with an accelerated 3D stack‐of‐spirals sequence with water excitation for fat suppression. The resulting data were reconstructed using an iterative algorithm with corrections for system imperfections such as trajectory deviations and B0 inhomogeneity. In the first set of experiments, we evaluated the signal change and stability with respect to echo and TR for a full‐field checkerboard stimulus. To demonstrate the high spatio‐temporal resolution of the developed method, the results of three optimized protocols at submillimeter resolution (0.6‐mm isotropic and 0.8‐mm isotropic) and at 1.2 mm isotropic resolution for whole‐brain coverage were shown.

Results

Water excitation and the model‐based iterative reconstruction improved image quality. The BOLD‐related signal changes increased with longer TE and longer TR. We observed an increase in thermal noise performance at lower TE and higher TR. However, signal stability deteriorates at higher TE and TR. Therefore, optimized protocols used shorter TE and moderately long TR to maximize the sensitivity and speed. Reproducible activations were detected along the gray‐matter gyri in the submillimeter protocols with a median signal change of approximately 4% across subjects.

Conclusions

Three‐dimensional stack‐of‐spirals enables passband balanced SSFP functional imaging at a much higher spatial and temporal scale, compared with conventional spoiled gradient‐echo train sequences.
Prospectively accelerated dynamic speech magnetic resonance imaging at 3 T using a self‐navigated spiral‐based manifold regularized scheme
Authors: Rusho Rushdi Zahid , Ahmed Abdul Haseeb , Kruger Stanley , Alam Wahidul , Meyer David , Howard David , Story Brad , Jacob Mathews , Lingala Sajan Goud
Published: March 2024

This work develops and evaluates a self‐navigated variable density spiral (VDS)‐based manifold regularization scheme to prospectively improve dynamic speech magnetic resonance imaging (MRI) at 3 T. Short readout duration spirals (1.3‐ms long) were used to minimize sensitivity to off‐resonance. A custom 16‐channel speech coil was used for improved parallel imaging of vocal tract structures. The manifold model leveraged similarities between frames sharing similar vocal tract postures without explicit motion binning. The self‐navigating capability of VDS was leveraged to learn the Laplacian structure of the manifold. Reconstruction was posed as a sensitivity‐encoding–based nonlocal soft‐weighted temporal regularization scheme. Our approach was compared with view‐sharing, low‐rank, temporal finite difference, extra dimension‐based sparsity reconstruction constraints. Undersampling experiments were conducted on five volunteers performing repetitive and arbitrary speaking tasks at different speaking rates. Quantitative evaluation in terms of mean square error over moving edges was performed in a retrospective undersampling experiment on one volunteer. For prospective undersampling, blinded image quality evaluation in the categories of alias artifacts, spatial blurring, and temporal blurring was performed by three experts in voice research. Region of interest analysis at articulator boundaries was performed in both experiments to assess articulatory motion. Improved performance with manifold reconstruction constraints was observed over existing constraints. With prospective undersampling, a spatial resolution of 2.4 × 2.4 mm2/pixel and a temporal resolution of 17.4 ms/frame for single‐slice imaging, and 52.2 ms/frame for concurrent three‐slice imaging, were achieved. We demonstrated implicit motion binning by analyzing the mechanics of the Laplacian matrix. Manifold regularization demonstrated superior image quality scores in reducing spatial and temporal blurring compared with all other reconstruction constraints. While it exhibited faint (nonsignificant) alias artifacts that were similar to temporal finite difference, it provided statistically significant improvements compared with the other constraints. In conclusion, the self‐navigated manifold regularized scheme enabled robust high spatiotemporal resolution dynamic speech MRI at 3 T.
The publicness of private foundations: Online accountability and Internet presence
Authors: Park Gowun , Suárez David
Published: March 2024

Private foundations face persistent charges of plutocracy and secrecy, undermining their legitimacy as philanthropic organizations that contribute to the public good, yet they can respond to the criticism proactively through online accountability and Internet presence. To what extent do foundations use web‐based tools to demonstrate public accountability, how are these tools used for this purpose, and what explains foundation participation in this form of self‐regulation? We argue that managerialism, organizational fields, and stakeholder relationships will matter for online accountability and Internet presence because they capture or reflect the “publicness” of private foundations. We test our conceptual framework on two online tools—websites and social media—using a dataset of private foundations located in Washington state. We find that few private foundations have a website or a social media account, and our analysis of those tools suggests that substantive accountability is not a high priority for those that do. Our empirical models nevertheless reveal that several components of our conceptual framework are associated with multiple forms of disclosure (operational, financial, and performance) and dialogic communication, a contribution to research on nonprofit accountability that also advances the literature on the organizational behavior of foundations.
Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity
Authors: Fordham Talyia M. , Morelli Nazeen S. , Garcia‐Reyes Yesenia , Ware Meredith A. , Rahat Haseeb , Sundararajan Divya , Fuller Kelly N. Z. , Severn Cameron , Pyle Laura , Malloy Craig R. , Jin Eunsook S. , Parks Elizabeth J. , Wolfe Robert R. , Cree Melanie G.
Published: March 2024

Objective

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS.

Methods

A randomized, double‐blind, crossover, placebo‐controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 ± 6.5 kg/m2, age 15.6 ± 1.3 years). Liver fat, very low‐density lipoprotein (VLDL) lipogenesis, and triacylglycerol (TG) metabolism were measured following each 28‐day phase of placebo or EAA.

Results

Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (−0.8% absolute, −7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (−8%, p = 0.004). Plasma TG (−9%, p = 0.015) and VLDL‐TG (−21%, p = 0.031) were reduced as well. VLDL‐TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046).

Conclusions

Similar to studies in older adults, short‐term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.
Plasma proteomic profile of abdominal obesity in older adults
Authors: Sathyan Sanish , Milman Sofiya , Ayers Emmeline , Gao Tina , Verghese Joe , Barzilai Nir
Published: March 2024

Objective

This study examines the plasma proteomic profile of abdominal obesity in older adults.

Methods

The association of abdominal obesity (waist circumference [WC]) with 4265 plasma proteins identified using the SomaScan Assay was examined in 969 Ashkenazi Jewish participants (LonGenity cohort), aged 65 years and older (mean [SD] age 75.7 [6.7] years, 55.4% women), using regression models. Pathway analysis, as well as weighted correlation network analysis, was performed. WC was determined from the proteome using elastic net regression.

Results

A total of 480 out of 4265 proteins were associated with WC in the linear regression model. Leptin (β [SE] = 12.363 [0.490]), inhibin β C chain (INHBC; β [SE] = 24.324 [1.448]), insulin‐like growth factor‐binding protein 2 (IGFBP‐2; β [SE] = −12.782 [0.841]), heparan‐sulfate 6‐O‐sulfotransferase 3 (H6ST3; β [SE] = −39.995 [2.729]), and matrix‐remodeling‐associated protein 8 (MXRA8; β [SE] = −27.101 [1.850]) were the top proteins associated with WC. Cell adhesion, extracellular matrix remodeling, and IGF transport pathways were the top enriched pathways associated with WC. WC signature determined from plasma proteins was highly correlated with measured WC (r = 0.80) and was associated with various metabolic and physical traits.

Conclusions

The study unveiled a multifaceted plasma proteomic profile of abdominal obesity in older adults, offering insights into its wide‐ranging impact on the proteome. It also elucidated novel proteins, clusters of correlated proteins, and pathways that are intricately associated with abdominal obesity.
First‐Principles Studies on Transition Metal Doped Mo2B2 as Anode Material for Li‐Ion Batteries
Authors: Shi Jianjian , Yu Chaojie , Kang Wei , Xiao Xiuchan , Sun Xiaoli
Published: March 2024

New two‐dimensional (2D) transition‐metal borides have attracted considerable interest in research on electrode materials for Li‐ion batteries (LIBs) owing to their promising properties. In this study, 2D molybdenum boride (Mo2B2) with and without transition metal (TM, TM=Mn, Fe, Co, Ni, Ru, and Pt) atom doping was investigated. Our results indicated that all TM‐doped Mo2B2 samples exhibited excellent electronic conductivity, similar to the intrinsic 2D Mo2B2 metal behavior, which is highly beneficial for application in LIBs. Moreover, we found that the diffusion energy barriers of Li along paths 1 and 2 for all TM‐doped Mo2B2 samples are smaller than 0.30 and 0.24 eV of the pristine Mo2B2. In particular, for 2D Co‐doped Mo2B2, the diffusion energy barriers of Li along paths 1 and 2 are reduced to 0.14 and 0.11 eV, respectively, making them the lowest Li diffusion barriers in both paths 1 and 2. This indicates that TM doping can improve the electrochemical performance of 2D Mo2B2 and that Co‐doped Mo2B2 is a promising electrode material for LIBs. Our work not only identifies electrode materials with promising electrochemical performance but also provides guidance for the design of high‐performance electrode materials for LIBs.
Superior heat‐resistant polylactide/poly(butylene succinate) blend fibers via in‐situ reactive compatibilization
Authors: Huang Wei , Zhang Guiju , Zhou Yuxiang , Joziasse Cornelis A. P. , Wang Ruyin , du Sart Gerrit Gobius , Chen Peng
Published: March 2024

Blending poly(butylene succinate) (PBS) with polylactide (PLLA) has proven effective in improving heat resistance of PLLA fibers. Unfortunately, it remains challenging to maintain good spinnability for PLLA/PBS blends with high content of PBS with which further improved heat resistance could be anticipated. In this study, reactive melt‐extrusion was devised to in‐situ generate PLLA‐PBS copolymers by introducing zinc acetate as a transesterification catalyst into PLLA/PBS blends. The compatibility between the PLLA and PBS phases was greatly improved by the formation of PLLA‐PBS copolymers, resulting in excellent melt‐spinnability even for the PLLA/PBS blends with high PBS content up to 20 wt%. In addition, an increase in crystallinity of PLLA was achieved in PLLA/PBS blend fibers, thanks to the enhanced compatibility. More importantly, the presence of PBS nuclei retarded the molecular orientation of the amorphous PLLA phase, consistent with the effective results from the relaxation heat‐setting treatment. These led to an exceptionally improved heat resistance of the PLLA/PBS blend fibers. As an encouraging result, the boiling water shrinkage was significantly reduced from ca. 20% for neat PLLA fibers to 3.7% for the PLLA/PBS blend fibers with 20 wt% PBS content. These findings may open up a facile and effective route to develop PLLA/PBS blend fibers showing sound spinnability, greatly improved heat resistance and softness.
Computational tools and algorithms for ion mobility spectrometry‐mass spectrometry
Authors: Ross Dylan H. , Bhotika Harsh , Zheng Xueyun , Smith Richard D. , Burnum‐Johnson Kristin E. , Bilbao Aivett
Published: March 2024

Ion mobility spectrometry‐mass spectrometry (IMS‐MS or IM‐MS) is a powerful analytical technique that combines the gas‐phase separation capabilities of IM with the identification and quantification capabilities of MS. IM‐MS can differentiate molecules with indistinguishable masses but different structures (e.g., isomers, isobars, molecular classes, and contaminant ions). The importance of this analytical technique is reflected by a staged increase in the number of applications for molecular characterization across a variety of fields, from different MS‐based omics (proteomics, metabolomics, lipidomics, etc.) to the structural characterization of glycans, organic matter, proteins, and macromolecular complexes. With the increasing application of IM‐MS there is a pressing need for effective and accessible computational tools. This article presents an overview of the most recent free and open‐source software tools specifically tailored for the analysis and interpretation of data derived from IM‐MS instrumentation. This review enumerates these tools and outlines their main algorithmic approaches, while highlighting representative applications across different fields. Finally, a discussion of current limitations and expectable improvements is presented.
Biodegradable zwitterionic polymers as PEG alternatives for drug delivery
Authors: Zhang Ziwen , Sun Haotian , Giannino Justin , Wu Yun , Cheng Chong
Published: March 2024

Poly(ethylene glycol) (PEG) is a highly biocompatible and water‐soluble polymer that is widely utilized for biomedical applications. Unfortunately, the immunogenicity and antigenicity of PEG severely restrict the biomedical efficacy of pegylated therapeutics. As emerging PEG alternatives, biodegradable zwitterionic polymers (ZPs) have attracted significant interest in recent years. Biodegradable ZPs generally are not only water‐soluble and immunologically inert, but also possess a range of favorable biomedically relevant properties, without causing long‐term side effects for in vivo biomedical applications. This review presents a systematic overview of recent studies on biodegradable ZPs. Their structural designs and synthetic strategies by integrating biodegradable base polymers with zwitterions are addressed. Their applications in the delivery of small molecule drugs (as mono‐drugs or multi‐drugs) and proteins are highlighted.
AbDPP: Target‐oriented antibody design with pretraining and prior biological structure knowledge
Authors: Yu Chenglei , Lin Xiangtian , Cheng Yuxuan , Xu Jiahong , Wang Hao , Yan Yuyao , Huang Yanting , Liu Lanxuan , Zhao Wei , Zhao Qin , Wang John , Zhang Lei
Published: March 2024

Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target‐oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning‐based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP.
Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit
Authors: Liu Lu , Wang Kun , Sun Zhongyi , Yan Pangke , Hu Mengyue , Liu Xiao , Chen Meixia , Wu Nan , Xiang Xiaoqiang
Published: March 2024

Ciprofol (HSK3486) is a newly developed, highly selective γ‐aminobutyric acid‐A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis. Exposure–safety relationship for hypotension was evaluated based on the data gathered from 112 subjects in two clinical trials of mechanically ventilated patients in the ICU. Ciprofol pharmacokinetics (PKs) was adequately described by a three‐compartment linear disposition model with first‐order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long‐term infusion vs. short‐term infusion), and patient population (ICU vs. non‐ICU) were identified as statistically significant covariates on the PKs of ciprofol. Within the exposure range of the mechanically ventilated ICU patient population, no meaningful association was observed between ciprofol exposure and the incidence of hypotension. These results support the dosing regimen currently used in mechanically ventilated patients in the ICU.
Electric, Dielectric, and Phonon Properties of Cu2OCl2
Authors: Apostolova Iliana N. , Apostolov Angel T. , Wesselinowa Julia M.
Published: March 2024

Investigating the multiferroic properties of , their temperature and magnetic‐field dependencies around the magnetic and ferroelectric phase transition temperatures and are analyzed using a microscopic model and Green's function technique. Near the Neel temperature , a kink in the specific heat and also in the phonon energy and damping due to strong anharmonic spin–phonon interaction is observed. The kink in disappears with increasing magnetic field h. The polarization shows also a small anomaly at and decreases with increasing magnetic field h. This behavior strongly suggests that exhibits multiferroic characteristics. A kink at can be seen in the real part of the dielectric constant , too. It should be noted that demonstrates a significant increase with increasing field strength h below , which is a pronounced magneto‐dielectric effect. These findings qualitatively agree with the experimental data.
Impact of end‐capped engineering on the optoelectronic characteristics of pyrene‐based non‐fullerene acceptors for organic photovoltaics
Authors: Qundeel  , Adnan Muhammad , Hussain Riaz , Shehzad Rao Aqil , Muhammad Shabbir , Mustafa Ghulam , Irshad Zobia
Published: March 2024

Pyrene‐based molecules are being explored as prospective fullerene‐free acceptors for organic solar cells (OSCs), due to their easy accessibility, structural planarity, and excellent electron delocalization. In this work, we successfully designed and analyzed pyrene‐based acceptor materials (QL1–QL8) to investigate their photophysical and electro‐optical parameters. Various geometric parameters were computed at the MPW1PW91/6‐31G(d,p). Advanced quantum chemical approaches were employed to characterize the molecules. All the tailored molecules (QL1–QL8) exhibit a lower bandgap than the reference (R), signifying their superiority. Among these, QL8 was found to have a maximum absorption (λmax) at 791.37 nm and an optical bandgap (ELUMO − EHOMO) minimum of 2.11 eV. Redshifted absorption spectra are observed in both gaseous and solvent phases for all the designed (QL1–QL8) molecules in contrast to R. Among these, QL4 exhibits the highest light harvesting efficiency (0.9826), and open‐circuit voltage. A detailed donor–acceptor investigation of QL8/PBDB‐T revealed the marvelous charge switching at the donor–acceptor interface. The approach used in this study is anticipated to facilitate the manufacturing of highly efficient OSC molecules.
Error‐controlled feature selection for ultrahigh‐dimensional and highly correlated feature space using deep learning
Authors: Ganguli Arkaprabha , Maiti Tapabrata , Todem David
Published: March 2024

Deep learning has been at the center of analytics in recent years due to its impressive empirical success in analyzing complex data objects. Despite this success, most existing tools behave like black‐box machines, thus the increasing interest in interpretable, reliable, and robust deep learning models applicable to a broad class of applications. Feature‐selected deep learning has emerged as a promising tool in this realm. However, the recent developments do not accommodate ultrahigh‐dimensional and highly correlated features or high noise levels. In this article, we propose a novel screening and cleaning method with the aid of deep learning for a data‐adaptive multi‐resolutional discovery of highly correlated predictors with a controlled error rate. Extensive empirical evaluations over a wide range of simulated scenarios and several real datasets demonstrate the effectiveness of the proposed method in achieving high power while keeping the false discovery rate at a minimum.
Estimation and reduction of bias in self‐controlled case series with non‐rare event dependent outcomes and heterogeneous populations
Authors: Lee Kenneth Menglin , Cheung Yin Bun
Published: March 2024

The self‐controlled case series (SCCS) is a commonly adopted study design in the assessment of vaccine and drug safety. Recurrent event data collected from SCCS studies are typically analyzed using the conditional Poisson model which assumes event times are independent within‐cases. This assumption is violated in the presence of event dependence, where the occurrence of an event influences the probability and timing of subsequent events. When event dependence is suspected in an SCCS study, the standard recommendation is to include only the first event from each case in the analysis. However, first event analysis can still yield biased estimates of the exposure relative incidence if the outcome event is not rare. We first demonstrate that the bias in first event analysis can be even higher than previously assumed when subpopulations with different baseline incidence rates are present and describe an improved method for estimating this bias. Subsequently, we propose a novel partitioned analysis method and demonstrate how it can reduce this bias. We provide a recommendation to guide the number of partitions to use with the partitioned analysis, illustrate this recommendation with an example SCCS study of the association between beta‐blockers and acute myocardial infarction, and compare the partitioned analysis against other SCCS analysis methods by simulation.
Solution‐Processed Metal Oxide Thin‐Film Transistor at Low Temperature via A Combination Strategy of H2O2‐Inducement Technique and Infrared Irradiation Annealing
Authors: Yang Jingze , Lin Dong , Chen Yushan , Li Tiejun , Liu Jing
Published: March 2024

Solution processing has emerged as a promising technique for the fabrication of oxide thin‐film transistors (TFTs), offering advantages such as low cost, high throughput, and exceptional compositional control. However, achieving reasonable electrical properties typically demands high annealing temperatures in the fabrication process. In addressing this challenge, a novel combination strategy is proposed that involves integrating the H2O2 inducement technique with infrared (IR) irradiation annealing. The study investigates the effects of precursors and IR irradiation annealing temperatures on the electrical properties of In2O3 TFTs. It is found that H2O2 can help accelerate the decomposition of organic residues, while IR irradiation annealing could enhance the film densification. By employing the proposed strategy, metal oxide TFTs consisting of a Zr‐Al‐O dielectric fabricated at 230 °C and an In2O3 channel layer fabricated at 185 °C demonstrated high performance with field‐effect mobility = 31.7 cm2 V−1·s−1, threshold voltage = 1.3 V, subthreshold swing = 0.13 V per decade, and on‐to‐off current ratio = 1.1 × 105. This work demonstrates the proposed combinational strategy is a general method to fabricate not only metal oxide semiconductors but also dielectrics.
D$$ D $$‐optimal designs for multi‐response linear models with two groups
Authors: Liu Xin , He Lei , Yue Rong‐Xian
Published: March 2024

In recent years, multi‐response linear models have gained significant popularity in various statistical applications. However, the design aspects of multi‐response linear models with group‐wise considerations have received limited attention in the literature. This paper aims to thoroughly investigate ‐optimal designs for such models. Specifically, we focus on scenarios involving two groups, where the proportions of observations for each group can be arbitrarily selected or not. Two equivalence theorems are presented to elaborate the characterization of ‐optimal designs. Additionally, we delve into the admissibility of approximate designs and establish necessary conditions for a design to be deemed admissible. Several illustrative examples are addressed to demonstrate the application of the derived theoretical results.
Vision‐based robust missing and loosened bolt detection for splice plate joints
Authors: Yao Zhidong , Chen Zhihua , Liu Hongbo , Lu Jiaqi
Published: March 2024

Vision‐based bolt defect detection methods based on feature changes have been reported. However, the robustness of key feature extraction and bolt detection requires improvement. This paper proposes a robust missing and loose bolt defect detection approach. The key features—reference points for perspective correction and the straight lines of the bolt edges—are extracted from the masks obtained by semantic segmentation models. The true and false bolt discrimination approach based on the mask shape can help improve bolt object detection accuracy. Overlapping between the bolt bounding boxes in the reference and detection images indicates missing bolts. The rotation angles reveal loosened bolts. The proposed approach was tested on fabricated bolted joint specimens and a steel railway bridge. The results suggest that these improvements ensure defect detection accuracy, with a miss rate of only 1% for missing bolt detection. Moreover, a loosened bolt with only 3° rotation is successfully detected. This approach has promising potential applicability in automatically detecting bolt defects in large steel structures.
Elucidating the molecular mechanisms of sepsis: Identifying key aging‐related biomarkers and potential therapeutic targets in the treatment of sepsis
Authors: Zhou Jie , Liu Jiao , Zhang Chuanwu , Zhou Yihua , Zheng Zemao , Li Haoguang
Published: March 2024

Background

Sepsis remains a crucial global health issue characterized by high mortality rates and a lack of specific treatments. This study aimed to elucidate the molecular mechanisms underlying sepsis and to identify potential therapeutic targets and compounds.

Methods

High‐throughput sequencing data from the GEO database (GSE26440 as the training set and GSE13904 and GSE32707 as the validation sets), weighted gene co‐expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, alongside a combination of PPI and machine learning methods (LASSO and SVM) were utilized.

Results

WGCNA identified the black module as positively correlated, and the green module as negatively correlated with sepsis. Further intersections of these module genes with age‐related genes yielded 57 sepsis‐related genes. GO and KEGG pathway enrichment analysis, PPI, LASSO, and SVM selected six hub aging‐related genes: BCL6, FOS, ETS1, ETS2, MAPK14, and MYC. A diagnostic model was constructed based on these six core genes, presenting commendable performance in both the training and validation sets. Notably, ETS1 demonstrated significant differential expression between mild and severe sepsis, indicating its potential as a biomarker of severity. Furthermore, immune infiltration analysis of these six core genes revealed their correlation with most immune cells and immune‐related pathways. Additionally, compounds were identified in the traditional Chinese medicine Danshen, which upon further analysis, revealed 354 potential target proteins. GO and KEGG enrichment analysis of these targets indicated a primary enrichment in inflammation and immune‐related pathways. A Venn diagram intersects these target proteins, and our aforementioned six core genes yielded three common genes, suggesting the potential efficacy of Danshen in sepsis treatment through these genes.

Conclusions

This study highlights the pivotal roles of age‐related genes in the molecular mechanisms of sepsis, offers potential biomarkers, and identifies promising therapeutic compounds, laying a robust foundation for future studies on the treatment of sepsis.
Telephonic follow‐up after day case pediatric surgery in an upper middle income country: A pilot study
Authors: Patel Nirav , Loveland Jerome , Scribante Juan
Published: March 2024

Background

One third of South African children live in households with no employed adult. Telemedicine may save patients and the strained public health sector significant resources. We aimed to determine the safety and benefits of telephonic post‐operative follow‐up of patients who presented for day case surgery at CHBAH from 1 January–31 March 2023.

Methods

A prospective descriptive study on patients undergoing day case surgery was performed. Healthy patients greater than 6 years old whose caregivers spoke English and had access to a smartphone were included. Data on the total number of telephonic follow‐ups, operative complications, need for in person review, satisfaction with telephonic follow‐up, and savings in transport costs and time by avoiding in person follow‐up were collected.

Results

A total of 38 telephonic follow‐ups were performed. Six (15.8%) patients presented for in person review due to the detection of major complications (2, 5.3%), minor complications (2, 5.3%), and parental concern (2, 5.3%) during telephonic follow‐up. All caregivers reported being satisfied with telephonic follow‐up. Total savings in transport costs were R4452 (US $ 248.45). The majority of patients (29, 76.3%) had at least one unemployed parent. Seven caregivers (18.4%) avoided taking paid leave and 2 (5.3%) unpaid leave from work due to follow‐up being performed telephonically.

Conclusions

Innovation is necessary in order to expand access to safe, affordable, and timely care. In this selected group, telephonic follow‐up was a safe, acceptable, and cost‐effective intervention. The expansion of such a program has the potential for significant savings for patients and the healthcare system.
The landscape of composite Higgs models
Authors: Chala Mikael , Fonseca Renato
Published: March 2024

Abstract

We classify all different composite Higgs models (CHMs) characterised by the coset space $$ \mathcal{G} $$
G
/$$ \mathcal{H} $$
H
of compact semi-simple Lie groups $$ \mathcal{G} $$
G
and $$ \mathcal{H} $$
H
involving up to 13 Nambu-Goldstone bosons (NGBs), together with mild phenomenological constraints. As a byproduct of this work, we prove several simple yet, to the best of our knowledge, mostly unknown results: (1) under certain conditions, a given set of massless scalars can be UV completed into a CHM in which they arise as NGBs; (2) the set of all CHMs with a fixed number of NGBs is finite, and in particular there are 642 of them with up to 13 massless scalars (factoring out models that differ by extra U(1)’s); (3) any scalar representation of the Standard Model group can be realised within a CHM; (4) Certain symmetries of the scalar sector allowed from the IR perspective are never realised within CHMs. On top of this, we make a simple statistical analysis of the landscape of CHMs, determining the frequency of models with scalar singlets, doublets, triplets and other multiplets of the custodial group as well as their multiplicity. We also count the number of models with a symmetric coset.
Optimizing exposure data collection for plant protection products: identifying ideal collectors with the fluorescent dye pyranine
Authors: Ehmke Annika , Wegener Jens Karl , Melfsen Andreas , Hartung Eberhard
Published: March 2024

When approving plant protection products, exposure data are required for risk analysis. Exposure data can be collected for various exposure pathways, such as dermal, inhalation or ground sediment. For measuring exposures, pyranine, a fluorescent dye, and a collector can be used. However, the choice of collector material depends on the specific exposure pathway. This study aims to determine the most suitable collector, in combination with the tracer pyranine, for recording exposure through different pathways in practical trials.

Seven different collectors (Tyvek®, labels, plastic patches, paper patches, nylon filters, fibreglass filters, petri dishes) were subjected to laboratory and field tests to assess various quality parameters. Blank values, recovery rates, storability, and fluorescence degradation under UV-radiation were measured. Based on the results, a matrix was created summarizing which collector might be best suited to capture each exposure pathway. Almost all collectors demonstrated high recovery rates (Tyvek® 100%; labels 100%; plastic patches 100%; paper patches 100%; nylon filters 95%; fiberglass filters 60.9%) as well as good storability. Furthermore, all plastic-based collectors (labels, Tyvek®, plastic patches, petri dishes) showed a very good recovery rate above 95% when exposed to UV-radiation. However, nylon filters were not suitable for utilization under field conditions due to the rapid degradation of fluorescence under UV-radiation (recovery rate: 20–56%). Nevertheless, nylon filters showed stable recoveries under protected conditions and can be used to assess inhalation exposures under these conditions. Fibreglass filters, with recovery rates of 84–86%, were well-suited for testing inhalative exposures outdoors when a correction factor was applied. Tyvek® was the most suitable material for detecting total dermal exposure under field conditions. This is due to its quality characteristics and availability in a variety of sizes. Finally, petri dishes were ideal for collecting ground sediments.