bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of SCB Specimen Size, Temperature, Loading Rate, and Loading Mode on Fracture Behavior of Asphalt Mixture Using Response Surface Method
Authors: Vaseghi Zahra , Pirmohammad Sadjad , Momeni Ramin
Published: October 2024

This study aimed to investigate the influence of semicircular bend (SCB) specimen size (R), loading mode (Me), and loading rate (Lr) on fracture resistance indicators, namely, fracture work (Wf), fracture energy (Gf), and fracture strength (Kf), of asphalt concrete at three different temperatures (−30°C, −20°C, and 10°C). Using Minitab software, response surface methodology (RSM) under central composite design (CCD) was employed to design experiments and develop predictive models for Wf, Gf, and Kf in terms of R, Me, and Lr at each temperature. The results demonstrated that the RSM models accurately predicted the fracture test data for all temperatures. The analysis of variance (ANOVA) revealed that R, Me, and Lr significantly influenced Wf, Gf, and Kf at each temperature, whereas the square terms R2, Me2, and Lr2 were not significant. The significance of two‐way interaction terms varied across different responses and temperatures. Overall, the experiments conducted at −30°C, −20°C, and 10°C indicated that varying R, Lr, and Me had notable effects on Wf, Gf, and Kf. Increasing R and Me while decreasing Lr resulted in an increase in Wf and Gf. Furthermore, Kf exhibited a direct relationship with R and Lr but an inverse relationship with Me.
Clinicopathologic features and outcomes of hepatic inflammatory pseudotumour (IPT) and hepatic IPT‐like lesions
Authors: Nguyen Eric D , Wen Kwun Wah , Kakar Sanjay , Balitzer Dana J
Published: October 2024

Aims

Hepatic inflammatory pseudotumours (IPTs) are nonneoplastic hepatic masses characterized by variably fibroblastic stroma and inflammatory infiltrate, hypothesized to arise as part of a response to infection or prior surgery. The aim of this study was to evaluate the clinicopathologic features and outcomes of biopsy‐proven hepatic IPT as well as other cases with IPT‐like histologic features.

Methods and Results

A database search at our institution identified cases with a pathologic diagnosis of hepatic IPT (n = 80) between 2000 and 2023. Histologic features (stromal quality, inflammatory cell components, granulomas, and necrosis) were evaluated. Past medical and surgical history, microbiologic studies, and outcomes were reviewed retrospectively. Patients frequently had a past medical history of malignancy (34%), biliary disease (15%), or prior intraabdominal surgery (24%), and often presented with multifocal hepatic lesions (36%). Variable inflammatory backgrounds were present, including histiocytic (36%), lymphoplasmacytic (34%), or neutrophilic (24%). Specific organisms were identified in 15% of cases, most commonly Klebsiella and Staphylococcus species. Most patients with available clinical follow‐up demonstrated radiologic resolution and/or had repeat negative biopsy; a minority of patients (8%) were subsequently diagnosed with neoplastic hepatic lesions. No significant association was seen between histologic features and the subsequent clinical or pathologic diagnosis of hepatic neoplastic lesions.

Conclusions

Hepatic IPT is a heterogeneous entity that can present in a variety of clinical scenarios and show a wide morphologic spectrum. These lesions often regress spontaneously or with antibiotics. A subset of cases with hepatic IPT‐like histologic features were subsequently diagnosed with malignancy, emphasizing the need for continued follow‐up and repeat biopsy depending on clinical and radiologic features.
Consumer Perspectives on Food Traceability—A Systematic Literature Review and Future Research Agenda
Authors: Chaudhary Anam , Sharma Rajat , Vemireddy Vidya
Published: October 2024

Food traceability is a critical approach that ensures the safety and quality of food. It has garnered significant attention, particularly in the aftermath of multiple food safety incidents reported in various countries. While there is extant literature available on consumer perspectives on food traceability, the findings are not consistent across studies. This systematic literature review aims to provide a comprehensive understanding by integrating findings from past studies. It includes 61 articles sourced from two databases, namely Scopus and Web of Science. This review outlines various stages of a consumer's decision for food traceability, starting from exposure, awareness, understanding, liking and disliking, attitudes and preferences, purchase intentions and willingness to pay, to the final purchase. It also identifies the determinants of consumer responses to food traceability, categorising them as factors internal to the consumers, determinants due to the perception of external factors and contextual factors. Moreover, it identifies gaps in the existing research and proposes research questions to expand the knowledge in this area.
Digital Approach Provides Predictability in Increasing the VDO in Erosive Wear: Clinical Technique and 9‐Year Follow‐Up
Authors: Ibrahim Fady , Plaster Udo , Gierthmuehlen Petra C.
Published: October 2024

Objective

This clinical case describes a digital workflow using face scans and CAD/CAM technology for a full‐mouth rehabilitation with increased vertical dimension of occlusion (VDO) with adhesive lithium disilicate restorations after 9 years.

Clinical Considerations

A healthy, 46‐year‐old man displaying severe tooth wear, underwent an extensive full‐mouth rehabilitation involving an increase of the VDO through laminate veneers and adhesive partial coverage lithium disilicate restorations. Anatomical landmarks of the face and reference planes were captured using a digital face scanning system. The anatomical position of the maxilla was registered with a transfer device. Digital data sets of the intraoral situation combined with a facial scan enabled precise virtual planning, guiding minimally invasive preparations. Long‐term provisional restorations, milled from high‐performance polycarbonate, were used to test the novel VDO before the final lithium disilicate restorations were fabricated. This approach provided a time‐ and cost‐efficient treatment solution. No failures were observed at the 9‐year follow‐up.

Conclusions

Utilizing face scans and design software enable a virtual visualization and comprehensive quality control for patients with dental wear, resulting in significant time savings and increased predictability for the dental technician, dentist and patient.

Clinical Significance

The described digital workflow optimizes the planning and implementation of a comprehensive adhesive full‐arch rehabilitation with an increase of the VDO. The clinical long‐term follow up result of CAD/CAM assisted minimally invasive lithium disilicate restorations after 9 years demonstrates to clinicians a reliable treatment concept for patients with dental wear.
Therapeutic targets for hepatocellular carcinoma identified using proteomics and Mendelian randomization
Authors: Zhu Weixiong , Fan Chuanlei , Liu Bo , Qin Jianqi , Fan Aodong , Yang Zengxi , Zhang Hui , Zhou Wence
Published: October 2024

Background and Aim

Hepatocellular carcinoma (HCC) emerges as a formidable malignancy marked by elevated morbidity and mortality rates, coupled with a dismal prognosis. The revelation of gene–protein associations has presented an avenue for the exploration of novel therapeutic targets.

Methods

Pooling plasma proteomic data (seven published GWAS) and HCC data (DeCODE cohort), we applied MR to identify potential drug targets, which were further validated in the FinnGen cohort and UK Biobank. Subsequent colocalization and summary‐data‐based Mendelian randomization analyses were performed for potential associations of this set of proteins. In addition, enrichment information pathways were investigated in depth by KEGG pathway analysis, single‐cell sequencing, PPI and DGIdb, ChEMBL, and DrugBank database analyses, specific cell types enriched for expression were identified, interacting proteins were identified, and finally, druggability was assessed.

Results

In summary, the levels of 10 proteins are linked to HCC risk. Elevated levels of TFPI2 as well as decreased levels of ALDH1A1, KRT18, ADAMTS13, TIMD4, SCLY, HRSP12, TNFAIP6, FTCD, and DDC are associated with increased HCC risk. Notably, HRSP12 show the strongest evidence. These genes are primarily expressed in specific cell types within the HCC TME. Moreover, intricate protein–protein interactions, involving key players like ALDH1A1 and RIDA, ALDH1A1 and DDC, and ALDH1A1 and KRT18, contribute significantly to the amino acid metabolism and dopaminergic neurogenesis pathway. Proteins such as ALDH1A1, KRT18, TFPI2, and DDC are promising targets for HCC therapy and broader cancer drug development. Targeting these proteins offers substantial potential in advancing HCC treatment strategies.

Conclusions

This research delineates 10 protein biomarkers linked to HCC risk and offers novel perspectives on its etiology, as well as promising avenues for the screening of HCC protein markers and therapeutic agents.
Feasibility of endoscopic resection for superficial laryngopharyngeal cancer after radiotherapy
Authors: Ashizawa Hiroshi , Yamamoto Yoichi , Mukaigawa Takashi , Kawata Noboru , Maeda Yuki , Yoshida Masao , Minamide Tatsunori , Hotta Kinichi , Imai Kenichiro , Ito Sayo , Takada Kazunori , Sato Junya , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki
Published: October 2024

Background and Aim

We aimed to elucidate the feasibility of endoscopic resection (ER) for salvage and metachronous lesions following chemoradiotherapy (CRT) and radiotherapy (RT) for laryngopharyngeal cancer.

Methods

Consecutive patients who underwent ER for superficial laryngopharyngeal cancer between March 2005 and September 2022 were retrospectively reviewed and stratified into salvage (16 patients, 16 lesions), metachronous (18 patients, 27 lesions), and naïve RT (217 patients, 306 lesions) groups. Salvage lesions were residual or local recurrent after CRT, and metachronous lesions were second primary lesions in the irradiated field following complete response. Short‐term outcomes were evaluated, including R0 resection, en bloc resection, procedure time, adverse events, local recurrence rate, and clinical course.

Results

The en bloc resection rates were 88%, 93%, and 88%; R0 resection rates were 50%, 52%, and 56%; procedure times were 25, 27, and 25 min, in the salvage, metachronous, and naïve RT groups, none of which were significantly different among the three groups. Although adverse event rates tended to be higher in the salvage and metachronous groups than in the naïve RT group, the differences were not significant (18%, 15%, and 8%). The cumulative local recurrence rates at 2 years were 21%, 13%, and 6%, significantly higher in the salvage group than in the naïve RT group. The local control rates with ER alone were 94%, 93%, and 97%; none were significantly different among the three groups.

Conclusion

ER for salvage and metachronous superficial lesions can be safely performed, suggesting its acceptability as a minimally invasive treatment.
Risk of colorectal cancer among fecal immunochemical test‐positive individuals by timing of previous colonoscopy: A multicenter analysis
Authors: Kawamura Takuji , Oda Yasushi , Toyoizumi Hirobumi , Kato Masayuki , Sekiguchi Masau , Takamaru Hiroyuki , Mizuguchi Yasuhiko , Horiguchi Go , Kobayashi Kiyonori , Sada Miwa , Yokoyama Akira , Utsumi Takahiro , Tsuji Yosuke , Ohki Daisuke , Takeuchi Yoji , Shichijo Satoki , Ikematsu Hiroaki , Matsuda Koji , Teramukai Satoshi , Kobayashi Nozomu , Matsuda Takahisa , Saito Yutaka , Tanaka Kiyohito
Published: October 2024

Background and Aim

The risk of colorectal cancer among fecal immunochemistry test‐positive individuals who had undergone previous colonoscopies remains unclear. Therefore, this study aimed to determine the differences in the risk of colorectal cancer among fecal immunochemistry test‐positive individuals according to the timing of their previous colonoscopies.

Methods

This multicenter, retrospective, observational study was conducted in Japan as a subgroup analysis of the J‐SCOUT study (UMIN000040690), which integrated and analyzed a database comprising all colonoscopies performed at participating Japanese institutions between 2010 and 2020. This study used colonoscopy data of fecal immunochemistry test‐positive individuals aged ≥ 20 years from three facilities that entered the timing of previous colonoscopies into the endoscopy database. Histologically confirmed advanced neoplasia was the study's primary outcome. Multivariate logistic regression analysis was used to calculate the odds ratios for each variable.

Results

In total, 11,143 fecal immunochemistry test‐positive patients underwent colonoscopy during the study period. Of these, 10,160 patients were included in the analysis after excluding those who met the exclusion criteria. The overall advanced neoplasia detection rate was 9.38% (953/10,160; 95% confidence interval: 8.82–9.96%). Compared with the first colonoscopy, the odds ratios for advanced neoplasia in individuals who underwent colonoscopies 1, 2, 3, 4, 5, > 5, and ≥ 10 years previously were 0.27, 0.15, 0.06, 0.10, 0.29, 0.31, and 0.31, respectively.

Conclusions

The detection rates of advanced neoplasia were low among the fecal immunochemistry test‐positive individuals who had undergone colonoscopy, particularly in the past 5 years.
Understanding the clinical management of co‐occurring sleep‐related bruxism and obstructive sleep apnea in adults: A narrative and critical review
Authors: Dal Fabbro Cibele , Bornhardt‐Suazo Thomas , Landry Schönbeck Anaïs , de Meyer Micheline , Lavigne Gilles J.
Published: October 2024

Sleep‐related bruxism (SRB) is a motor oral behavior characterized by tooth grinding and jaw clenching activity, reported by 8%–12% of the adult general population and 3% of older individuals. The frequency of one of its biomarkers, rhythmic masticatory muscle activity (RMMA), remains elevated across ages. Obstructive sleep apnea (OSA) is associated with the brief and repetitive pause of breathing (apnea) and with transient reduction in oxygen (hypoxia). OSA is observed at all ages and in about 50% of older individuals with a male preponderance. SRB clinical assessment is based on self‐reporting of tooth grinding sound, awareness of clenching, jaw pain or headache, and clinical observation of tooth damage. OSA clinical assessment is based on sleepiness and fatigue, snoring, sleep quality, and awareness of breathing cessation, plus clinical examination of anatomical factors (e.g., obesity, retrognathia, large tonsil, macroglossia), age, gender, and body mass. Although the literature does not support association or causality between these two conditions, the co‐occurrence is reported in about 30%–50% of adults. To confirm a diagnosis of co‐occurring SRB and OSA, home sleep testing (HST) may be indicated. A sleep test is performed using electromyography (EMG) of jaw muscle (masseter or temporalis) and cardio‐respiratory variables (e.g., air flow, respiratory effort, oxygen level, heart rate). The management of co‐occurring SRB and OSA for individuals with prosthodontic needs is challenging to prevent compromising the oro‐pharyngeal space and breathing efficiency. OSA treatment in the presence of SRB includes continuous positive airway pressure (CPAP) use alone or with an occlusal splint or mandibular advancement device (MAD). In addition, the following may be considered: supine sleep correction device, myofuncional therapy, medications, and surgeries. All have limitations and risks. Individual variability suggests that phenotyping is mandatory to select the most efficient and personalized treatment.
Pathological study of progressive supranuclear palsy the cases with mutations in Bassoon
Authors: Wakita Masahiro , Yaguchi Hiroaki , Otuski Mika , Tanikawa Satoshi , Miki Yasuo , Aiba Ikuko , Yoshida Mari , Nomura Taichi , Uwatoko Hisashi , Mito Yasunori , Sinpo Kazuyoshi , Ikeuchi Takeshi , Tanaka Shinya , Wakabayashi Koichi , Yabe Ichiro
Published: October 2024

Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.Pro3866Ala in the Bassoon (BSN) gene in a Japanese family with PSP‐like syndrome. We newly detected BSN mutations in two autopsied PSP cases carrying p.Thr2542Met and p.Glu2759Gly, respectively. The case with p.Thr2542Met mutation showed neurological symptoms including behavioral abnormalities, cognitive dysfunction, and parkinsonism. Brain magnetic resonance imaging (MRI) showed atrophy of the midbrain tegmentum and hippocampus. Pathologically, moderate to severe loss of neurons with gliosis was also found in the substantia nigra, and there was an almost complete loss of neurons with gliosis in the transitional zone of the cornu ammonis (CA) 1 region to the subiculum. NFTs were observed in the globus pallidus, subthalamic nucleus, substantia nigra, and CA1. 4R tau‐dominant tauopathy was detected. The case with p.Glu2759Gly mutation showed neurological symptoms, including right‐dominant motor impairment, right limping gait, postural instability, and cognitive dysfunction. Brain MRI showed mild atrophy of the midbrain tegmentum and left‐dominant parietal lobe atrophy. Pathologically, NFTs were detected in the globus pallidus, subthalamic nucleus, substantia nigra, thalamus, putamen, and brainstem tegmentum. Most neurons were immunopositive for four‐repeat tau, whereas only a few of them harbored three‐repeat tau‐positive NFTs in the hippocampus. We showed the results of a pathological study of PSP cases with BSN mutations; these were two new cases. The clinical phenotypes were similar to the first case in the point of neurological symptoms. Accumulation of four‐repeat tau was dominant. Further autopsies of BSN mutation cases and further elucidation of the molecular biological mechanism are desirable.
Molecular mechanisms of the obesity associated with Bardet‐Biedl syndrome: An update
Authors: Zhong Bang‐Hua , Nie Ning , Dong Ming
Published: October 2024

Obesity is a prominent feature of Bardet‐Biedl syndrome (BBS), which represents a major and growing public health problem. More than half of BBS patients carry mutations in one of eight genes that encode subunits of a protein complex known as the BBSome, which has emerged as a key regulator of energy and glucose homeostasis. However, the mechanisms underlying obesity in BBS are complex. Numerous studies have identified a high prevalence of insulin resistance and metabolic syndrome among individuals with BBS. However, the exact mechanisms are not fully understood. This review summarized evidence from experiments using mouse and cell models, focusing on the energy imbalance that leads to obesity in patients with BBS. The studies discussed in this review contribute to understanding the functional role of the BBSome in the obesity associated with BBS, laying the foundation for developing new preventive or therapeutic strategies for obese patients.
Exploring the Shift in Pro‐American Attitudes and Influencing Factors: An Analysis Using a Quasi‐experimental Design of Taiwanese Students
Authors: Wang Chia‐chou
Published: October 2024

How can pro‐American attitudes be measured? What factors influence shifts in these attitudes? Anchored in institutional identity theory, this study constructs a pro‐American attitude scale and posits three hypotheses concerning Taiwanese consciousness, the evaluation of interdependent benefits, and political learning to elucidate the shift in pro‐American attitudes. Targeting Taiwanese students, this study employs a quasi‐experimental design for data collection and linear regression for hypothesis testing. The findings indicate that from February to June 2023, 37.68% of participants demonstrated a decrease in pro‐American attitudes, 36.24% demonstrated an increase, and 26.09% remained unchanged. Participants in the political learning experimental group displayed a shift in pro‐American attitudes in contrast to the control group. The regression model developed in this study accounted for 25.07% of the variance in the shift in Taiwanese students' pro‐American attitudes, and all hypotheses were empirically supported. An increase in Taiwanese consciousness or frequency of political learning corresponds to a decrease in pro‐American attitudes. Conversely, an elevated evaluation of Taiwan–America interdependent benefits correlates with an increase in pro‐American attitudes. This study demonstrates that political learning can mitigate the enhancing effect of political communication on pro‐American attitudes, thus offering a unique contribution to academic and practical fields.
CRISPR/Cas9‐Mediated Genome Editing for Trait Improvement and Stress Tolerance in Leguminosae (Legume Family)
Authors: Singh Sadhana , Mishra Vigya , Riyazuddin Riyazuddin , Chugh Vishal , Upadhyay Santosh Kumar
Published: October 2024

Legumes represent a significant source of protein, roughage, minerals and carbohydrates in global diets. They are cultivated primarily for human consumption, forage and as a green manure. However, the growth and productivity of legumes are often hindered by a range of biological and environmental factors. The most prevalent diseases afflicting legumes include downy mildew, fusarium root rot, southern blight and common leaf spot. Additionally, environmental stresses such as salinity and drought represents significant challenges. Over time, the development of cultivars with enhanced tolerance has emerged as a sustainable approach to combat the impact of these stresses. Although environmentally friendly, traditional breeding methods entail lengthy screening and cross‐breeding protocols, which constrain their efficacy in addressing climate challenges and ensuring global food security. Furthermore, these approaches rely on the natural availability of genetic variation, which may not always be exist for specific traits, particularly in the context of rapidly changing environmental conditions. Additionally, the traditional breeding method is not sufficiently precise, which can result in the unintended introduction of undesirable traits. Furthermore, the genetic intricacy of legumes presents an additional challenge making it difficult to isolate and enhance desired traits. These constrain impede the capacity to expeditiously develop cultivars that can withstand emerging stresses, such as climate change. Genome editing has emerged as a powerful tool to overcome the limitations of traditional breeding methods. By enabling precise and targeted genetic manipulation, genome editing can enhance desired traits or introduce new ones, thereby facilitating the development of climate‐resilient agronomic varieties. In particular, clustered regularly interspaced short palindromic repeat/CRISPR associated protein (CRISPR/Cas9)‐mediated editing has demonstrated considerable potential in enhancing legume adaptability to diverse stress conditions and increasing crop yield. This study highlights the advancements in genome editing, with a specific focus on CRISPR/Cas9 technology, as a means to improve legume crops' resilience and productivity in response to environmental pressures.
Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway
Authors: Mi Lei , Jin Jie , Zhang Yingying , Chen Ming , Cui JianLi , Chen Rui , Zheng Xiao , Jing Changqing
Published: October 2024

Intestinal ischaemia–reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3‐like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia–reoxygenation (H/R) IEC‐6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC‐6 cells. The H/R‐induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R‐induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3‐kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF‐κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF‐κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R‐induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC‐6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury.
Nanofabrication of high transition temperature superconductive electronics with focused helium ion irradiation
Authors: LeFebvre Jay C. , Parachikunnumal Adhilsha , Cybart Shane A.
Published: October 2024

Superconductive electronics from Josephson junctions are governed by quantum mechanical tunneling through sub-10 nm scale insulating tunnel barriers. The electrical properties are exponentially sensitive to this dimension, which necessitates fabrication with nanoscale precision and uniformity. For circuits in high-transition temperature YBa2Cu3O7−δ (YBCO) thin films, direct writing of the material with a focused helium ion beam has shown promise in the creation of uniform nanoscale insulators for YBCO Josephson junctions and other circuit regions. In this paper, we report on the procedures and variables associated with this process and discuss the potential for scaling up the number of junctions for quantum sensing and complex energy efficient digital circuits.
Proteome profiling of polyomavirus nuclear replication centers using iPOND
Authors: Erickson Kimberly D. , Langsfeld Erika S. , Holland Alexandra , Ebmeier Christopher C. , Garcea Robert L.
Published: October 2024

Polyomaviruses (PyVs) cause diverse diseases in a variety of mammalian hosts. During the life cycle, PyVs recruit nuclear host factors to viral genomes to facilitate replication and transcription. While host factors involved in DNA replication, DNA damage sensing and repair, and cell cycle regulation have been observed to bind PyV DNA, the complete set of viral and host proteins comprising the PyV replisome remains incompletely characterized. Here, the iPOND-MS technique (Isolation of Proteins on Nascent DNA coupled with Mass Spectrometry) was used to identify the proteome bound to murine PyV (MuPyV) DNA immediately following synthesis and 2 hours post-synthesis. Several novel MuPyV DNA interactors were identified on newly synthesized viral DNA (vDNA), including MCM complex members, DNA primase, DNA polymerase alpha, DNA ligase, and replication factor C. Though displaying partial overlap, the host and viral proteins bound to MuPyV DNA 2 hours post-synthesis lacked many of the replication proteins found on newly synthesized vDNA. These data help distinguish between the host factors critical for MuPyV DNA replication and those involved in downstream processing.

IMPORTANCE

Polyomaviruses are the causative agents of serious diseases in humans, including progressive multifocal leukoencephalopathy (PML), BK virus nephropathy, and Merkel cell carcinoma. The exact mechanisms by which the virus replicates, and which host cell proteins are required, are incompletely characterized. Identifying the host proteins necessary for efficient viral replication in the cell may reveal targets for downstream targets that may suppress viral replication
in vivo
.
Performance of rapid antigen tests to detect SARS-CoV-2 variant diversity and correlation with viral culture positivity: implication for diagnostic development and future public health strategies
Authors: Goux Heather , Green Jennetta , Wilson Andrew , Sozhamannan Shanmuga , Richard Stephanie A. , Colombo Rhonda , Lindholm David A. , Jones Milissa U. , Agan Brian K. , Larson Derek , Saunders David L. , Mody Rupal , Cox Jason , Deans Robert , Walish Joseph , Fries Anthony , Simons Mark P. , Pollett Simon D. , Smith Darci R.
Published: October 2024

Antigen-based rapid diagnostic tests (Ag-RDTs) provide timely results, are simple to use, and are less expensive than molecular assays. Recent studies suggest that antigen-based testing aligns with virus culture-based results (a proxy of contagiousness at the peak viral phase of illness); however, the performance of Ag-RDTs for newer SARS-CoV-2 variants is unclear. In this study, we (i) assessed the performance of Ag-RDTs and diagnostic antibodies to detect a range of SARS-CoV-2 variants and (ii) determined whether Ag-RDT results correlated with culture positivity. We noted only minor differences in the limit of detection by variant for all assays, and we demonstrated consistent antibody affinity to the N protein among the different variants. We observed moderate to high sensitivity (46.8%–83.9%) for Ag-RDTs when compared to PCR positivity (100%), and all variants were assessed on each assay. Ag-RDT sensitivity and PCR Ct showed an inverse correlation with the detection of viable virus. Collectively, our results demonstrate that commercially available Ag-RDTs offer variable sensitivity compared to PCR, show similar diagnostic validity across variants, and may predict the risk of transmissibility. These findings may be used to support more tailored SARS-CoV-2 isolation strategies, particularly if other studies clarify the direct association between Ag-RDT positivity and transmission risk. The apparent trade-off between sensitivity in the detection of any PCR-positive infection and concordance with infectious virus positivity may also inform new RDT diagnostic development strategies for SARS-CoV-2 and other epidemic respiratory pathogens.

IMPORTANCE

Despite the availability of vaccines, COVID-19 continues to be a major health concern, and antigen-based rapid diagnostic tests (Ag-RDTs) are commonly used as point-of-care or at-home diagnostic tests. In this study, we evaluated the performance of two commercially available Ag-RDTs and a research Ag-RDT to detect multiple SARS-CoV-2 variants using upper respiratory tract swab samples from clinical COVID-19 cases. Furthermore, we determined whether Ag-RDT results correlated with culture positivity, a potential proxy of viral transmissibility. Our results have important implications to inform future testing and response strategies during periods of high COVID-19 transmission with new variants.
Cryo-EM structure of the
Mycobacterium smegmatis
MmpL5-AcpM complex
Authors: Maharjan Rakesh , Zhang Zhemin , Klenotic Philip A. , Gregor William D. , Purdy Georgiana E. , Yu Edward W.
Published: October 2024

Mycobacterium tuberculosis
, the causative agent of the airborne infection tuberculosis (TB), contains 13 mycobacterial membrane protein large (MmpL) transporters that can be divided into two distinct subclasses. These MmpL proteins play important functional roles within the mycobacterium and subsequently are considered attractive drug targets to combat TB infection. Previously, we reported both X-ray and cryo-electron microscopy (cryo-EM) structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Thus far, there is no structural information available for the other subclass, which includes MmpL5, an inner membrane transporter that plays a critical role in iron hemostasis. Here, we report the first cryo-EM structure of the
Mycobacterium smegmatis
MmpL5 transporter bound with the meromycolate extension acyl carrier protein M (AcpM) to a resolution of 2.81 Å. Our structural data reveals that MmpL5 and AcpM interact in the cytoplasm to form a complex, and this allows us to propose that MmpL5 may also associate with the mycobactin L (MbtL) protein in a similar fashion to form a heterocomplex important for iron acquisition, which enables the survival and replication of the mycobacterium.

IMPORTANCE

The emergence and spread of multidrug-resistant tuberculosis (TB) present enormous challenges to the global public health. The causative agent,
Mycobacterium tuberculosis
, has now infected more than one-third of the world's population. Here, we report the first structure of the mycobacterial membrane protein large 5 (MmpL5), an essential transporter for iron acquisition, bound with the meromycolate extension acyl carrier protein M (AcpM), indicating a plausible pathway for mycobactin translocation. Our studies will ultimately inform an era in structure-guided drug design to combat TB infection.
The promiscuous biotin ligase TurboID reveals the proxisome of the T3SS chaperone IpgC in
Shigella flexneri
Authors: Haidar-Ahmad Nathaline , Tomaro Kyle , Lavallée-Adam Mathieu , Campbell-Valois François-Xavier
Published: October 2024

Promiscuous biotin ligases derived from the bacterial enzyme BirA are used to identify proteins vicinal to a bait protein, thereby defining its proxisome. Despite the popularity of this approach, surprisingly little is known about its use in prokaryotes. Here, we compared the activity of four widely used promiscuous biotin ligases in the cytoplasm of
Shigella flexneri
, a pathogenic subgroup of
Escherichia coli
. Our data indicate that the kinetics of TurboID’s biotinylating activity is the highest of those tested. In addition, TurboID showed reduced interaction with the natural BirA binding partners, BccP and the biotin operator, when compared to its ancestor BioID. We therefore evaluated the ability of TurboID to probe the proxisome of the type III secretion system (T3SS) chaperone IpgC and the transcriptional activator MxiE. When the T3SS is inactive (off-state), these proteins are inhibited by forming complexes with the T3SS substrates OspD1 and IpaBC, respectively. In contrast, when the T3SS is active (on-state), OspD1 and IpaBC are secreted allowing MxiE and IpgC to interact together and activate their target genes. The results obtained with the IpgC and TurboID fusions capture a good fraction of these known interactions. It also suggests that the availability of IpgC increases in the on-state, resulting in a greater number of proteins detected in its vicinity. Among these is the T3SS ATPase SpaL (also known as Spa47 or SctN), further supporting the notion that chaperones escort their substrate to the T3SS. Interestingly, a specific subset of proteins conserved in
E. coli
completes the IpgC proxisome in the on-state.

IMPORTANCE

Promiscuous biotin ligases are widely used to study protein function in eukaryotes. Strikingly, their use in prokaryotes has been rare. Indeed, the small volume and the cytoplasmic location of the biotin ligase’s natural binding partners in these organisms pose unique challenges that can interfere with the study of the proxisome of proteins of interest. Here, we evaluated four of the most common promiscuous biotin ligases and found TurboID was best suited for use in the cytoplasm of
Shigella flexneri
. Using this method, we extended the proxisome of IpgC beyond its known direct binding partners involved in the regulation of the type III secretion system (T3SS) signaling cascade. Of particular interest for further study are transcription factors and housekeeping proteins that are enriched around IpgC when the T3SS is active. We propose a model in which the increased availability of IpgC in the on-state may allow cross-talk of the T3SS with other cellular processes.
Magnetic resonance imaging changes in spinal arteriovenous fistulae treated by endovascular means: are they reliable to predict complete cure of the fistula?
Authors: Allard Julien , Chiaroni Pierre-Marie , Elhorany Mahmoud , Coudert Romain , Parat Damien , Bensemain Mehdi , Ghazanfari Sam , Boch Anne-Laure , Premat Kevin , Lenck Stephanie , Sourour Nader-Antoine , Shotar Eimad , Clarençon Frédéric
Published: October 2024

Background

Regression or disappearance of MRI abnormalities is usually observed after treatment of spinal dural arteriovenous fistulae (sDAVF).

Objective

To assess the correlation between spinal MRI (sMRI) changes with sDAVF exclusion and clinical outcome.

Methods

Imaging data of patients treated with endovascular embolization for sDAVF between 2007 and 2023 were retrospectively analyzed. Spinal cord edema and perimedullary flow voids at baseline and 3-months' follow-up were compared between patients with and without sDAVF persistent occlusion and clinical improvement on the Aminoff and Logue Scale.

Results

Twenty-five patients were included in this study. At 3-months' follow-up, regression of spinal cord edema was significantly associated with sDAVF persistent occlusion (P=0.038). The combination of edema and flow voids regression was significantly associated with higher odds of a cured sDAVF (P<0.001) and clinical improvement (P<0.01). Improvement in the combination of the above-mentioned sMRI signs presented high sensitivity (100% (95% CI 78.20%–100%)) and negative predictive value (100% (95% CI 47.82%–100%)) for the detection of sDAVF cure compared with the criterion standard (digital subtraction angiography (DSA)).

Conclusions

Patients with both spinal cord edema and flow voids regression at 3 months were more likely to present with a persistent occlusion of sDAVF and clinical improvement after endovascular embolization. Patients without sMRI improvement should be referred for DSA to seek recurrence of sDAVF.
Predictors of distal embolization during thrombectomy for anterior circulation large vessel bifurcation occlusion stroke
Authors: Tan Yanping , Mao Zhenlin , Li Zhenhui , Fan Hongxing
Published: October 2024

Background

Distal embolization is a frequent complication of mechanical thrombectomy (MT) for acute ischemic stroke, often leading to poor clinical outcomes. The vascular bifurcations represent a specialized anatomical location, thereby augmenting the complexity of MT. The specific factors contributing to distal embolization in this context have not been thoroughly explored. This study seeks to identify the factors associated with distal embolization during MT in patients with anterior circulation large vessel bifurcation occlusion stroke.

Methods

A retrospective analysis was conducted on patients who underwent MT for acute anterior circulation bifurcation occlusion stroke between January 2015 and December 2023. Baseline characteristics, procedural details, and clinical outcomes were assessed. Univariate and multivariable analyses were performed to identify predictors of distal embolization during MT.

Results

The study included 119 patients. Univariate analysis revealed significant associations between distal embolization and occlusion location, internal carotid artery (ICA) tortuosity, first-line thrombectomy strategy, and the number of device passes. Multivariate analysis identified ICA bifurcation occlusions (odds ratio (OR) 3.21, 95% confidence interval (CI) 1.188 to 8.672, P=0.021), stent retriever thrombectomy (SRT) (OR 6.177, 95% CI 1.77 to 21.555, P=0.004), and a higher number of device passes (OR 1.778, 95% CI 1.132 to 2.792, P=0.013) as independent predictors of distal embolization.

Conclusions

ICA bifurcation occlusion, the use of SRT, and an increased number of device passes are significant predictors of distal embolization during MT in patients with anterior circulation large vessel bifurcation occlusion strokes.
Not All Carcinogens Are Directly Mutagenic: A Holistic View of the Environmental Exposure–Cancer Connection
Authors: Okwan-Duodu Derick , Pandiri Arun R. , Adams David J.
Published: October 2024

Cancers, a leading cause of morbidity and mortality worldwide, are undergoing notable shifts in incidence patterns. Cancer subtypes generally associated with advancing age are now increasingly being diagnosed in younger populations, while gender disparities in cancer susceptibility have fluctuated across various malignancies. Some cancer subtypes previously confined to specific geographical populations are now globally prevalent. Remarkably, these changing patterns of cancer incidence have occurred despite relatively stable mutational landscapes specific to each cancer type, highlighting the role of environmental exposures (exposomes) as potential drivers of these trends. Intriguingly, evidence suggests that the exposome may exert some of its influence through nonmutagenic mechanisms, although the precise ways in which environmental carcinogens trigger or promote cancer development remain poorly understood. This review summarizes the current understanding of the mutagenic and nonmutagenic mechanisms through which carcinogens, including tobacco smoke, air pollutants, metals, diet, and alcohol, impact cancer development, as this may help inform precision prevention and public health policy.
Electrochemical Properties of CeCl3 by Fitting Cyclic Voltammetry Data to a Kinetic Model Accounting for Adsorption and Nucleation
Authors: Zhang Xinyu , Yi Feng , Zhou Wentao , Wang Dezhong
Published: October 2024

Due to the co-deposition phenomenon of actinides and rare Earth elements in the electrorefining process, understanding the electrochemical properties of rare Earth elements is crucial for element separation in spent nuclear fuel reprocessing. In this paper, a kinetic model for electrorefining is established to cover the adsorption and nucleation mechanisms occurring on the electrode surface. The study simulates the cyclic voltammetry of cerium (Ce) in molten LiCl-KCl at a temperature of 773 K, with varying scan rates and concentrations, using the model. The electrochemical properties of Ce are deduced by fitting the experimental voltammetry data. The model is validated by comparing derived properties with those from experimental data. Notably, the diffusion coefficient and apparent potential obtained from the model agree well with those obtained experimentally. Finally, the effects of adsorption and nucleation parameters on the behaviors of Ce were explored.
Experimental and Computational Insights into the Effects of -NH2 and -Cl Functional Groups on the Copper Corrosion Inhibition by Benzotriazole
Authors: Pham Thanh Hai , Chihaia Viorel , Le Phung K. , Son Do Ngoc
Published: October 2024

The influences of -NH2 and -Cl groups on the copper corrosion inhibition in 0.5 M H2SO4 solution by benzotriazole were studied using experimental methods and density functional theory calculations. Mass loss tests, potentiodynamic polarization, and surface morphology analyses revealed notable differences: while unmodified benzotriazole showed an inhibition efficiency of 76.6%, the -Cl derivative increased this to 87.6%, whereas the -NH2 derivative dropped it to 61.0% at the concentration of 5 × 10−4 M. Density functional theory calculations indicated these differences are not due to electronic properties or inhibitor-copper interaction energies but rather to the inhibitor’s influence on the oxygen reduction reaction, especially O2 and H2O adsorption. The -NH2 group formed strong hydrogen bonds with O2 and H2O, reducing oxygen reduction inhibition, while the -Cl group repelled O2, resulting in enhanced inhibition. Free energy analysis of the oxygen reduction reaction supported these findings. These new insights into benzotriazole derivatives’ copper corrosion inhibition mechanisms offer valuable guidance for developing next-generation corrosion inhibitors.
Supplementary Table S19 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

Table S19. Variable Importance for predicting BCLM PD-L1+ using primary tumor clusters.
Supplementary Table S16 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

Supplementary Table S16. Variable Importance for predicting BCLM HIF1α+ using primary tumor clusters.
Supplementary Table S15 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

Table S15. Variable Importance for predicting BCLM E-cad+ using primary tumor clusters.
Supplementary Table S14 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

Table S14. Variable Importance for predicting BCLM Collagen+ using primary tumor clusters.
Supplementary Figure S9 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

S9. Variable importance for prediction of BCLM CD68+CD163+CD206+, CD68+MMP9+, CD8a+PD1-, and CD8a+PD1+ using ML models.
Supplementary Figure S7 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

S7. Variable importance for prediction of BCLM CD14+, CD163+, CD163+MMP9+, and CD206+ using ML models.
Figure 6 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

Primary tumor IMC clusters sorted by average relative rank across the ML models (lowest number denotes the highest rank) based on their importance for classification of the BCLM IMC clusters. Each box denotes the relative rank of a cluster in a particular model (with lowest rank as most important), whereas a checked box highlights the relative rank of a cluster when included by a model for prediction of BCLM cluster densities.
Figure 3 from Characterization of the Breast Cancer Liver Metastasis Microenvironment via Machine Learning Analysis of the Primary Tumor Microenvironment
Authors: Goodin Dylan A. , Chau Eric , Zheng Junjun , O’Connell Cailin , Tiwari Anjana , Xu Yitian , Niravath Polly , Chen Shu-Hsia , Godin Biana , Frieboes Hermann B.
Published: October 2024

IMC raw data. A, UMAP representation of 20 identified clusters from breast primary and metastatic liver tumors. B, Heatmap of corresponding cluster and marker intensities from the IMC assay. UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction.