bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of topography and transport history on the composition of clastic deposits from the Jurassic Tlaxiaco basin, southern Mexico: limitations on the use of mineral and chemical indices as proxies for paleoclimate
Authors: Martini Michelangelo , Zepeda-Martínez Mildred , Mori Laura , Núñez-Useche Fernando , Velasco de León Maria Patricia , Solari Luigi
Published: January 2024

The mineral and chemical composition of clastic deposits is commonly used as a proxy for reconstructing the climatic history of the Earth. A mineralogical and chemical study of clastic deposits from the Jurassic Tlaxiaco basin of southern Mexico illustrates that the entire sedimentary system in which detritus is generated, subaerially transported, and deposited exerts a major control on the composition of sedimentary rocks, placing some constraints on the use of mineral and chemical indices as paleoclimatic proxies. Since clastic deposits of the Tlaxiaco basin were formed under similar humid climatic conditions, but in sedimentary systems with different topography and transport histories, they represent a natural laboratory for testing the control that these parameters exert on the composition of clastic rocks. Our petrographic and chemical results show that, in sedimentary systems associated with low relief and in which detritus had the possibility of being temporarily stored in floodplains and meandering bars, parent rocks and the derivative detritus interacted with weathering fluids over a long time, producing clastic deposits with composition that is representative of the weathering conditions and climate of the region. On the other hand, in environments associated with steep and tectonically active relief, the rates of sediment transport and burial exceed the rate at which weathering can generate detritus, producing sedimentary deposits with composition that largely underestimates potential weathering and provide unreliable information on climate. Mineral and chemical indices should be considered as reliable paleoclimate proxies only when sedimentological data indicate that the sedimentary system allowed sediment interaction with weathering fluids over a long time.
Asynchronous Quantum Random Walks
Authors: Harringer Manfred
Published: January 2024

I build random walks on finite graphs Γ(V,E) with vertices V and directed edges E by sequences of randomly selected edges. I obtain quantum canonical ensembles with vacuum. Single steps of these walks are acceptions and rejections, corresponding to stimulated and spontaneous emission. Split into small steps, such random walks are asynchronous versions of time evolution in quantum mechanics. As a result, for a fixed weight function of edges I obtain a family of quantum canonical ensembles, where the members are parametrized by the number of elements N, with a common balance condition, fulfilled by the first eigenvector of the weight matrix. The family connects a Markov chain with a quantum grand canonical ensemble by a passage from N = 1 to large N-values.
Diversity and Distributional Pattern of Grasshoppers Fauna in Agroforest and Vegetative Lands of Tehsil Havelian, Pakistan
Authors: Waqar Zainab , Ahmed Shabir , Mehmood Sardar Azhar , Panhwar Waheed Ali , Ahmad Bilal , Khan Salman
Published: January 2024

Grasshoppers are one of the most varied group of insects. They belong to phylum Arthropoda, class Insecta and order Orthoptera. Ensifera and Caelifera are two common suborders of the order Orthoptera. The current study was carried out to explore the diversity and distribution of grasshoppers in Tehsil Havelian, District Abbottabad, KPK. Field survey was conducted in 19 localities of Tehsil Havelian from August 2022 to October 2022. Environmental parameters like Temperature and Humidity were also measured. Total 400 specimens were collected from Tehsil Havelian by using Sweep Netting method and Handpicking method and were preserved in the Zoological Museum of Hazara University Mansehra. This study revealed 18 species, 14 genera and 3 families belonging to 2 sub-orders of Orthoptera. Species identified during present research includes: Acrida cinerea, Acrida exaltata, Aiolopus thalassinus, Hieroglyphus nigrorepletus, Oedaleus decorus, Oedaleus senegalensis, Oxya hyla, Oxya japonica, Oxya velox, Patanga succincta, Spathosternum prasiniferum, Trilophidiini annulate, Atractomorpha crenulate, Chrotogonus trachypterus, Conocephalus maculatus, Himertula kinneari, Mecopoda elongate and Phaneroptera gracilis. The most common species recorded in Tehsil Havelian was Spathosternum prasiniferum. Moreover, Acrididae was the most common family and Pyrogomorphidae was recorded as least common family in Tehsil Havelian.
Mechanism of BRCA1-BARD1 function in DNA end resection and DNA protection
Authors: Cejka Petr , Ceppi Ilaria , Stritto Maria Rosaria Dello , Braunshier Stefan , Mutze Martin , Reginato Giordano , Sanchez Aurore , Halder Swagata , Howard Sean , Mengoli Valentina , Seidel Ralf
Published: January 2024

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by DNA end resection, a process involving the controlled degradation of the 5'-terminated strands at DSB sites 1,2. The breast cancer suppressor BRCA1-BARD1 not only promotes resection and HR, but it also protects DNA upon replication stress 1,3-9. While BRCA1-BARD1 counteracts the anti-resection and pro-non-homologous end-joining factor 53BP1, its direct role in resection has been unclear, particularly due to complex phenotypes associated with the depletion of this essential and multi-functional complex 10-18. Using purified recombinant proteins, we show here that BRCA1-BARD1 directly promotes long-range DNA end resection pathways catalyzed by the EXO1 or DNA2 nucleases. In the DNA2-dependent pathway, BRCA1-BARD1 stimulates DNA unwinding by the WRN/BLM RecQ family helicase. Together with MRE11-RAD50-NBS1 (MRN) and phosphorylated CtIP, BRCA1-BARD1 forms the BRCA1-C complex 19,20, which stimulates resection synergistically to even a greater extent. A mutation in phosphorylated CtIP (S327A), which disrupts its binding to the BRCT repeats of BRCA1 and hence the integrity of the BRCA1-C complex 21-23, inhibits resection, showing that BRCA1-C is a functionally integrated ensemble directly promoting long-range resection. While BRCA1-BARD1 stimulates resection in DSB repair, it paradoxically also protects replication forks from unscheduled degradation upon stress, which involves an HR-independent function of the recombinase RAD51 4-6,8. We show that in the presence of RAD51, BRCA1-BARD1 instead inhibits DNA degradation. Based on our data, the presence and local concentration of RAD51 might determine the balance between the pro-nuclease and the DNA protection functions of BRCA1-BARD1 in the various physiological contexts.
Effects of different concentrations of corn stover on microbial community structure during rumen fluid pretreatment and the biogas production by anaerobic digestion
Authors: Yu Qing , Sun Chen , Cao Weixing , Liu Ronghou , Abd-Alla Mohamed Hemida , Rasmey Abdel-Hamied M.
Published: January 2024

In this work, the corn stover (CS) with concentration of 3%, 6% and 9% (w/v) were pretreated by rumen fluid and then used for batched mesophilic biogas production. The results showed that after a 6-day pretreatment, VFAs production of 3.78, 8.27, and 10.4 g/L could be found in 3%, 6% and 9%, respectively. When concerning with biogas production, the highest accumulative methane production of 149.1 mL CH4/g VS was achieved by 6% pretreated CS, which was 22% and 45% higher than 3% and 9%, respectively. Also, it was 3.6 times higher than the same concentration of unpretreated CS. The results of microbial community structure revealed highest relative abundance of Firmicutes (45%) and Euryarchaeota (3.9%) in 6% CS, which was beneficial to its high VFAs and methane production. These findings provide scientific reference for the utilization of CS and support the development of agricultural waste resource utilization and environmental protection.
Simulation-Based, Peer-to-Peer Learning of a Technical Skill for Pre-Clinical Medical Students
Authors: Bederson Maria , McNicholas Meagan , Jamison Shandra , Ryals Athena , Ledersnaider Max , Brown Carlos
Published: January 2024

Background
Simulation is a promising tool for medical education of technical skills without the risk of harm to patients. The aim of this project was to design, implement, and assess the impact of an hour-long, student-led, point-of-care ultrasound (POCUS) workshop for first-year medical students, which included novel learning methods. The primary goal was to increase confidence, comfort, and competence in a technical skill.
Methods
Students’ baseline understanding of POCUS was assessed with pre- and post-workshop surveys, which included a Likert scale for rating confidence, and multiple-choice answer questions. The workshop itself consisted of a ten-minute didactics’ session, which emphasized the principles of echogenicity using light-logic, and three hands-on stations for the practice of skills including: probe handling, object identification and ultrasound-guided needle aspiration of a simulated soft-tissue abscess. Molds were made on site with a mixture of Jell-O and Psyllium using previously published methods. Pre- and post-workshop survey entries were collected and analyzed for statistical significance.
Results
Every student from the first-year medical class at the researchers’ institution participated in this workshop (N = 57), with 55 surveys included for analysis. Surveys were performed anonymously. Results showed a significant improvement in self-assessed comfort and confidence with newly learned ultrasound skills and clinical applications. In total, 87.3% of students reported an improved understanding of POCUS, 93% endorsed a benefit from the experience to their learning, and 89% endorsed improvement of their clinical skills. Free responses for feedback highlighted a desire for more practice, more time, and more frequent activities similar to the one described herein.
Conclusions
The described activity resulted in overwhelmingly positive feedback from students and measured substantial improvement in subjective and objective understanding of POCUS. Further work is needed to assess the effectiveness of the individual components of the activity and long-term retention of knowledge learned.
Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer’s disease
Authors: Gudmundsdottir Valborg , Frick Elisabet , Emilsson Valur , Jonmundsson Thorarinn , Steindorsdottir Anna , Johnson Erik C.B. , Puerta Raquel , Dammer Eric , Shantaraman Anantharaman , Cano Amanda , Boada Merce , Valero Sergi , Garcia-Gonzalez Pablo , Gudmundsson Elias , Gudjonsson Alexander , Pitts Rebecca , Qiu Xiazi , Finkel Nancy , Loureiro Joseph , Orth Anthony , Seyfried Nicholas , Levey Allan , Ruiz Agustín , Aspelund Thor , Jennings Lori , Launer Lenore , Gudnason Vilmundur
Published: January 2024

The current demand for early intervention, prevention, and treatment of late onset Alzheimer’s disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older adults (n = 5,294), we identified 303 unique proteins associated with incident LOAD (median follow-up 12.8 years). Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status. These proteins were implicated in neuronal processes and overlapped with protein signatures of LOAD in brain and cerebrospinal fluid. We found 17 proteins which LOAD-association was strongly dependent on APOE-ε4 carrier status. Most of them showed consistent associations with LOAD in cerebrospinal fluid and a third had brain-specific gene expression. Remarkably, four proteins in this group (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated as a consequence of LOAD as determined in a bi-directional Mendelian randomization analysis, reflecting a potential response to the disease onset. Accordingly, the direct association of these proteins to LOAD was reversed upon APOE-ε4 genotype adjustment, a finding which we replicate in an external cohort (n = 719). Our findings provide an insight into the dysregulated pathways that may lead to the development and early detection of LOAD, including those both independent and dependent on APOE-ε4. Importantly, many of the LOAD-associated proteins we find in the circulation have been found to be expressed - and have a direct link with AD - in brain tissue. Thus, the proteins identified here, and their upstream modulating pathways, provide a new source of circulating biomarker and therapeutic target candidates for LOAD.
Neutralizing Antibodies Reveal Cryptic Vulnerabilities and Interdomain Crosstalk in the Porcine Deltacoronavirus Spike
Authors: Bosch Berend-Jan , Du Wenjuan , Debski-Antoniak Oliver , Drabek Dubravka , Haperen Rien van , Dortmondt Melissa van , Lee Joline van der , Drulyte Ieva , Kuppeveld Frank van , Grosveld Frank , Hurdiss Daniel
Published: January 2024

Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen in pigs that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here we generated and characterized a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to the APN receptor. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide critical structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.
The Best Timing of IVF-ET after Laparoscopic Tubal Ligation for Patients with Hydrosalpinx
Authors: Li Jie , Zhou Li , Mo Fuhua , Lin Zhong , Mo Sien , Shi Qiuling
Published: January 2024

Purpose
The purpose of this study was to investigate the effect of in vitro fertilization-embryo transfer (IVF-ET) at different time intervals after laparoscopic tubal ligation on pregnancy outcomes.
Methods
The main outcome measures included: ovarian response index, laboratory index and clinical pregnancy outcome. The indicators were analyzed by univariate and multivariate-Logistic regression. Our study was a retrospective cohort study and 976 patients were included (Group 1: 0–3 months after ligation, N = 186, Group 2: 3–6 months after ligation, N = 438, Group 3: 6–12 months after ligation, N = 352).
Results
The clinical pregnancy rate (CPR), live birth rate (LBR) and cumulative live birth rate (CLBR) in group 1 were higher than those in group 2 and group 3 (61.36% vs. 52.89% vs. 56.61% for CPR, 53.79% vs. 43.93% vs. 47.93% for LBR, 76.34% vs. 69.41% vs. 65.91% for CLBR, P < 0.05). In addition, the biochemical pregnancy abortion rate in group 1 was significantly lower (1.52% vs. 5.20% vs. 6.20%, P < 0.05). In linear regression analysis, with the delay of IVF-ET treatment after ligation, the number of available D3 embryos, the rates of available blastocyst and high-quality blastocyst tended to decrease (P < 0.05). In logistic regression analysis, the CPR and LBR in group 1 were significantly higher than those in group 3 (OR: 578, 95%CI: 0.384, 0.870 for CPR, OR: 643, 95%CI: 0.436, 0.950 for LBR, P < 0.05). For elderly patients, the different time intervals did not affect pregnancy outcomes. For patients with DOR, the LBR in group 1 was higher than that in group 2 and group 3 (69.23% vs. 32.43% vs. 60.0%, P < 0.05). Biochemical pregnancy rate, CPR and CLBR in group 1 were higher than other groups, but no statistical difference (P > 0.05).
Conclusions
For patients with hydrosalpinx, IVF-ET treatment within 3 months after laparoscopic tubal ligation would result in more potential embryos and better pregnancy outcomes.
Characterisation and Modelling of Potassium-ion Batteries
Authors: Dhir Shobhan , Cattermull John , Jagger Ben , Schart Maximilian , Olbrich Lorenz , Chen Yifan , Zhao Junyi , Sada Krishnakanth , Goodwin Andrew , Pasta Mauro
Published: January 2024

Potassium-ion batteries (KIBs) are emerging as a promising alternative technology to lithium-ion batteries (LIBs) due to their significantly reduced dependency on critical minerals. KIBs may also present an opportunity for superior fast-charging compared to LIBs, with significantly faster K-ion electrolyte transport properties already demonstrated. In the absence of a viable K-ion electrolyte, a full-cell KIB rate model in commercial cell formats is required to determine the fast-charging potential for KIBs. However, a thorough and accurate characterisation of the critical electrode material properties determining rate performance---the solid state diffusivity and exchange current density---has not yet been conducted for the leading KIB electrode materials. Here, for the first time, we accurately characterise the effective solid state diffusivities and exchange current densities of the graphite anode and potassium manganese hexacyanoferrate KMn[Fe(CN)6] (KMF) cathode, through a combination of optimised material design and state-of-the-art analysis. Finally, we present the first Doyle-Fuller-Newman model of a KIB full cell in a hypothetical commercial cylindrical cell format, identifying the critical materials properties that limit their rate capability.
The potential value of pre-delivery hematologic index in patients with placental abruption and perinatal outcomes
Authors: LI HUA , li Wenxia , Xu Ting , Chen Qiu ling , Cai Min , Hu Ke , Shi Jun , LI meiyi , Peng Jing
Published: January 2024

Objective
This study aimed to clarify the risk factors, clinical features, diagnosis, and management of placental abruption(PA), as well as explore the relationship between the severity of placental abruption and maternal and fetal outcomes. Another purpose of the study was to evaluate changes in hematological biomarkers before delivery in PA and whether their use in predicting the severity of PA.
Methods
A total of 310 cases of placental abruption among 56,895 women who delivered at our tertiary maternity center between December 2015 and February 2021 were retrospectively analyzed. Patients were classified into four groups based on abruption severity of grade 0, I, II or III, then clinical variables and in hematological biomarkers before delivery were compared among the four groups. The clinic data and pre-delivery hematological biomarkers of placental abruption of different severities were analyzed.
Results
The incidence of placental abruption in our sample was 0.54%. Primary symptoms of placental abruption included abdominal pain (49.6%), vaginal bleeding (39%), bloody amniotic fluid (24%), abnormal fetal heart rate (16.4%), or no symptoms at all (4.5%). Grade III abruption was significantly more likely to occur than abruption of other grades in patients with preterm delivery, hypertensive disorders in pregnancy, and anemia (P < 0.05). As the severity of placental abruption increased, birth weight and Apgar scores at 1 and 5 min decreased significantly, while the risk of neonatal asphyxia increased significantly. Overall, 0.64% of fetuses had cerebral palsy and 0.96% died. Among mothers, the risk of blood transfusion or cesarean section increased with abruption severity. Pre-delivery hematologic index, the lymphocytes, hemoglobin and fibrinogen decreased significantly(P < 0.05), while the neutrophils, neutrophil to lymphocyte ratio(NLR), prothrombin time(PT) and D-dimer increased significantly with abruption severity(P < 0.05). The variation in the level of coagulation indicators was corresponded to the amount of blood loss during postpartum hemorrhage.
Conclusions
With increasing severity of placental abruption was associated with adverse maternal and neonatal outcomes. The pre-delivery hematologic index, especially NLR, PT and D-dimer were associated with disease severity, further research should focus on the changes in the hematologic index in PA is critical to reveal the underlying pathophysiologic mechanisms.
Impact of opsin kinetics on high-rate stimulation of the auditory nerve in mice
Authors: Ajay Elise A. , Thompson Alex C. , Azees Ajmal A. , Wise Andrew , Grayden David B. , Fallon James B. , Richardson Rachael T.
Published: January 2024

Optogenetic stimulation improves spectral resolution compared to electrical stimulation in preclinical cochlear implant studies but remains unreliable at the high stimulation rates needed for precise temporal resolution. Combined optogenetic-electrical stimulation has been shown to improve temporal resolution while maintaining good spectral resolution. However, the reliability of combined stimulation at clinically relevant stimulation rates (> 400 pulses per second (pps)) is yet to be tested, nor whether altering opsin channel kinetics impacts these findings. We investigated responses of the auditory nerve and inferior colliculus to electrical, optogenetic, and combined stimulation in mice virally transduced with one of three opsin variants with different opsin kinetics: ChR2-H134R, ChIEF, or ChR2-C128A. Robust optogenetic responses were elicited in ChR2-H134R and ChIEF mice but extended periods of stimulation led to severe and non-recoverable deterioration of optogenetic responses. Unlike previous studies, there was no consistent facilitation of electrical responses in combined stimulation trials. Although ChIEF responses outperformed ChR2-H134R at 100 pps, the temporal characteristics were similar at higher rates. Combined stimulation significantly improved response characteristics at 400 pps, shown here for the first time in mice virally transduced with the ChR2-H134R and ChIEF opsins. These results have significant implications for the translation of optogenetic-only and combined stimulation techniques for hearing loss.
Instruments for Patient Safety Assessment: a scoping review
Authors: Nunes Elisabete Maria Garcia Teles , Sirtoli Fernanda , Lima Eliane , Minarini Greyce , Gaspar Filomena , Lucas Pedro , Primo Cândida
Published: January 2024

Objective: To perform a systematic review of the existing literature to map instruments/scales for assessing patient safety in healthcare services.
Method: scoping review. The protocol was registered on the Open Science Framework (https://osf.io/p329w). Eligibility criteria were defined based on the mnemonic P (patients), C (instruments/scales for assessing safety), C (healthcare services), in any language, and without temporal restriction. The study search was conducted in the MEDLINE, EMBASE, LILACS, and Scopus databases, and the repository of the Brazilian Digital Library of Theses and Dissertations. Two independent reviewers performed selection and data extraction.
Results: 63 articles were selected, identifying 48 instruments/scales and 71 dimensions for patient safety assessment, with a predominance of dimensions such as teamwork, professional satisfaction, safety climate, communication, and working conditions.
Conclusion: The diversity of instruments and dimensions for patient safety assessment characterizes the multidimensionality and scope of patient safety. However, it hinders benchmarking between institutions and healthcare units.
SKP alleviates the ferroptosis in diabetic kidney disease through suppression of HIF-1α/HO-1 pathway based on network pharmacology analysis and experimental validation.
Authors: Yan Yangtian , Yuan Ningning , Chen Yuchi , Ma Yun , Chen Ali , Wang Fujing , Yan Shihua , He Zhuo’en , He Jinyue , Zhang Chi , Wang Hao , Wang Mingqing , Diao Jianxin , Xiao Wei
Published: January 2024

Backgroud
Diabetic kidney disease (DKD) represents a microvascular complication of diabetes mellitus. Shenkang Pills (SKP), a traditional Chinese medicine formula, has been widely used in the treatment of DKD and has obvious antioxidant effect. Ferroptosis, a novel mode of cell death due to iron overload, has been shown to be associated with DKD. Nevertheless, the precise effects and underlying mechanisms of SKP on ferroptosis in diabetic kidney disease remain unclear.
Methods
The active components of SKP were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database.Targets related to DKD and ferroptosis were collected from the GeneCards database. Protein-protein interaction (PPI) network and Herb-ingredient-targets gene network were constructed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted utilizing the Metascape system database. Additionally, an in vivo model of DKD induced by Streptozotocin (STZ) was established to further investigate and validate the possible mechanisms underlying the effectiveness of SKP.
Results
We retrieved 56 compounds and identified 223 targets of SKP through the TCMSP database. Key targets were identified by PPI. Using Herb-ingredient-Targets gene network, the primary active ingredients in SKP to alleviate ferroptosis in diabetic kidney disease were obtained. KEGG pathway enrichment analysis suggested that SKP has the potential to alleviate ferroptosis through HIF signaling pathway, thereby mitigating renal injury in DKD. In animal experiments, fasting blood glucose, 24h urine protein, urea nitrogen and serum creatine were measured. The results showed that SKP could improve DKD. Results from animal experiments were also confirmed the efficacy of SKP in alleviating renal fibrosis, oxidative stress and ferroptosis in DKD mice.These effects were accompanied by the significant reductions in renal tissue expression of HIF-1α and HO-1 proteins. The mRNA and immunohistochemistry results were the same as above.
Conclusions
SKP potentially mitigating renal injury in DKD by subduing ferroptosis through the intricacies of the HIF-1α/HO-1 signaling pathway.
Proteinase-Activated Receptor 1 Inhibition Alleviates Intestinal Fibrosis in Mice with Chronic Colitis
Authors: Song Jia , Guo Jinbo , Sun Donglei , Luo Yuxin , Zhan Rongrong , Li Chenyang , Liang Xiaonan , Yin Fengrong , Zhang Xiaolan
Published: January 2024

Intestinal fibrosis is a serious complication of inflammatory bowel disease (IBD). Proteinase-activated receptor (PAR) 1 is a highly conserved G protein-coupled receptor that is relevant to IBD. We investigated the expression of PAR1 in the progression of intestinal fibrosis in human tissues and mice with chronic enteritis. We acquired intestinal biopsy samples from 6 patients with stenotic UC, 6 patients with stenotic CD, and 6 patients without IBD (control individuals). Biopsy samples were analyzed through histology to test for fibrosis and through immunohistochemistry and RT‒qPCR to measure the levels of PAR1. We studied inflammation and fibrosis severity in intestinal tissues from PAR1–/– mice, and mice were given injections of the PAR1 antagonist; chronic colitis and fibrosis were induced by repetitive administration of DSS. Human intestinal fibroblasts were incubated with thrombin, a PAR1 antagonist, SB-431542 or control medium. The proliferation, activation, migration and collagen synthesis of fibroblasts were detected by CCK8 assay, immunofluorescence cytochemistry, scratch test, transwell assay, western blot, RT‒qPCR and ELISA. Compared with those in mucosal and submucosal biopsy tissue from control individuals, obviously greater levels of collagen deposition were noted in bowel biopsy tissue from patients with fibrostenotic UC or CD. Tissues from patients with fibrostenotic UC or CD had significantly greater levels of PAR1. Mice given injections of a PAR1 antagonist and of PAR1–/– mice exhibited significantly less established fibrosis than mice with chronic colitis. PAR1 inhibition of human intestinal fibroblasts reduced proliferation, differentiation, migration and collagen synthesis. Mechanistically, PAR1 antagonism effectively inhibited the phosphorylation of the Smad2 and Smad3 proteins and the Smad2/3 protein. Compared with those in control individuals, we found enhanced levels of PAR1 in fibrotic bowel tissues from patients with IBD. PAR1 promoted fibrogenesis in fibroblasts. Inhibition or knockout of the PAR1 gene in mice decreases chronic intestinal inflammation and intestinal fibrosis. This research may offer new ideas for the treatment of intestinal fibrosis complicated with chronic intestinal inflammation.
Simple mathematical model for predicting COVID-19 outbreaks in Japan based on epidemic waves with a cyclical trend
Authors: Manabe Hiroki , Manabe Toshie , Honda Yuki , Kawade Yoshihiro , Kambayashi Dan , Manabe Yoshiki , Kudo Koichiro
Published: January 2024

Background
Several models have been used to predict outbreaks during the COVID-19 pandemic, with limited success. We developed a simple mathematical model to accurately predict future epidemic waves.
Methods
We used data from the Ministry of Health, Labour and Welfare - Japan for newly confirmed COVID-19 cases. COVID-19 case data were summarized as weekly data; then, epidemic waves were visualized and identified. The periodicity of COVID-19 in each prefecture of Japan was confirmed using time-series analysis and the autocorrelation coefficient, which was used to investigate the longer-term pattern of COVID-19 cases. Outcomes using the autocorrelation coefficient were visualized via a correlogram to capture the periodicity of the data. An algorithm for a simple prediction model of the seventh COVID-19 wave in Japan comprised three steps. Step 1: machine learning techniques was used to depict the regression lines for each epidemic wave, denoted the “rising trend line”; Step 2: an exponential function with good fit was identified from data of rising straight lines up to the sixth wave and the timing of the rise of the seventh wave and speed of its spread were calculated; Step 3: a logistic function was created using the values calculated in Step 2 as coefficients to predict the seventh wave. The accuracy of the model in predicting the seventh wave was confirmed using data up to the sixth wave.
Results
Up to March 31, 2023, the correlation coefficient value was approximately 0.5, indicating significant periodicity. The spread of COVID-19 in Japan was repeated in a cycle of approximately 140 days. In the predicted seventh wave, although the starting time and peak time of the epidemic were slightly behind, our developed prediction model had a fairly high degree of accuracy.
Conclusion
Our newly developed prediction model based on the rising trend line could predict COVID-19 outbreaks up to a few months in advance with high accuracy. The findings of the present study warrant further investigation regarding application to emerging infectious diseases other than COVID-19 when an epidemic wave has high periodicity.
A Prognostic Signature of Cuproptosis-Related LncRNAs to Predict Survival and Immune Response in Esophageal Cancer
Authors: Wang Xiaofeng , Huang Yiheng , Jing Hui , Yu Zhenjia , Su Liping , Li Hecheng
Published: January 2024

Cuproptosis is a novel copper ion-dependent mode of programmed cell death. Aberrantly expressed lncRNAs are closely associated with the development of esophageal cancer (ESCA), yet the role played by cuproptosis and lncRNAs in ESCA remains unknown. The purpose of the study was to identify a prognostic signature of cuproptosis-related lncRNAs for predicting prognosis and immune response in ESCA. In this study, the transcriptomic and clinical data of ESCA patients were obtained from the TCGA and cuproptosis-related genes were obtained from previously published literatures, from which cuproptosis-related differentially expressed lncRNAs were identified by co-expression analysis. Selected lncRNAs were analyzed with univariate and lasso regression to construct the prognostic signature, of which we assessed the predictive power in terms of overall survival, clinical features, immune infiltration, mutational profiles, efficacy of immunotherapy, and drug sensitivity. We ultimately screened 6 cuproptosis-related prognostic lncRNAs (AC110611.2, AC125437.1, C2orf27A, EWSAT1, GK-IT1 and PRANCR) to construct a novel prognostic signature (CupRLSig) and divided the ESCA patient samples into high- and low- risk groups using the median risk score as a threshold. We demonstrated that the high- and low-risk groups differed in overall survival, clinical parameters, immune infiltration, and drug sensitivity, with the high-risk group having lower survival, more aggressive disease (tumor infiltration depth, lymph node metastasis), immunosuppressive microenvironment (M2 macrophage), and higher tumor immune dysfunction and exclusion (TIDE).The low-risk group was characterized by more antitumor immune cells (neutrophils, T cells) and enhanced immune function (T cell co − stimulation, inflammation promoting), higher tumor mutational load (TMB) and increased drug sensitivity. Gene set enrichment analysis (GSEA) results showed that tumor and immune-related pathways were obviously enriched in the low-risk group. The novel prognostic signature of cuproptosis-related lncRNAs has the potential to predict survival, immune response and drug sensitivity in ESCA, contributing to personalized clinical prediction and treatment.
Pragmatic Nationwide Master Observational Trial Based on Genomic Alterations in Advanced Solid Tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II Study Protocol KCSG AL-22-09
Authors: Kim Sun Young , Kim Jee Hyun , Kim Tae-Yong , Park Sook Ryun , Yoon Shinkyo , Lee Soohyeon , Lee Se-Hoon , Kim Tae Min , Han Sae-Won , Kim Hye Ryun , Yun Hongseok , Lee Sejoon , Kim Jihun , Choi Yoon-La , Choi Kui Son , Chae Heejung , Ryu Hyewon , Lee Gyeong-Won , Zang Dae Young , Ahn Joong Bae
Published: January 2024

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform.
Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50%±3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment.
Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers.
Trial Registration:NCT05525858
Identification, Heterologous Expression and Characterization of a New Unspecific Peroxygenase from Marasmius fiardii PR-910
Authors: Li Aitao , Fu Xin , Lin Kexin , Zhang Xiaodong , Guo Zhiyong , Kang Lixin
Published: January 2024

Unspecific peroxygenases (UPOs) are glycosylated enzymes that provide an efficient method for oxyfunctionalizing a variety of substrates using only hydrogen peroxide (H2O2) as the oxygen donor. However, their poor heterologous expression has hindered their practical application. Here, a novel UPO from Marasmius fiardii PR910 (MfiUPO) was identified and heterologously expressed in Pichia pastoris. By employing a two-copy expression cassette, the protein titer reached 1.18 g L− 1 in a 5-L bioreactor, marking the highest record. The glycoprotein rMfiUPO exhibited a smeared band in the 40 to 55 kDa range and demonstrated hydroxylation, epoxidation and alcohol oxidation. Moreover, the peroxidative activity was enhanced by 150% after exposure to 50% (v/v) acetone for 40 h. A semi-preparative production of 4-OH-β-ionone on a 100 mL scale resulted in a 54.2% isolated yield with 95% purity. With its high expression level, rMfiUPO is a promising candidate as an excellent parental template for enhancing desirable traits such as increased stability and selectivity through directed evolution, thereby meeting the necessary criteria for practical application.
Ultrasmall Silica Nanoparticles: Synthesis, Functionalization and Biomedical Application
Authors: Cui Feihu , Qu Lishuo , Gong Yao , Xie Yijun , Chang Qing , Celia Christian , Deng Xiaoyong
Published: January 2024

Ultrasmall silica nanoparticles (USNPs) with a size ＜20 nm exhibit unique advantages such as low toxicity, surface modification, and efficient renal clearance, making them highly promising in the fields of bioimaging, disease detection, gene delivery, and drug delivery. In this short review, synthesis, functionalization, and biomedical applications of USNPs are discussed. First, the different synthetic methods for fabricating hollow USNPs and solid USNPs. Then, surface modification methods are described in detail. Finally, the biomedical application progress and toxicity of USNPs encapsulated with fluorescent and drug molecule are discussed.
An ensemble method based on weight voting method for improved prediction of slope stability
Authors: Chen Yumin , Fu Zhongling , Yao Xiaofei , Han Yi , Li Zhenxiong
Published: January 2024

This study proposes a novel ensemble method based on weighted majority voting to evaluate the stability of slope. The ensemble classifier is composed of 5 base classifiers including random forest (namely RF), logistic regression (namely LR), naive Bayes (namely NB), support vector machine (namely SVC) and backpropagation (BP). An integrated approach was developed using 213 slope cases collected from the literature and the performance of the proposed approach was validated. Selection of training parameters was carried out by the definition of safety factor (FS) and the correlation analysis of parameters. Then, a search for the optimal hyperparameters of the base classifiers is performed using a grid search algorithm combined with a five-fold cross-validation. Weights to each base classifier is obtained by the AUC value of the training dataset. To the end, the ensemble method based on weights is established to predict the stability of slopes in this paper. It is demonstrated that the ensemble algorithm is superior to the base classifier with regard to accuracy (ACC), Kappa(K), Precision (P), recall (R), F1 score (F1), and the receiver's operating characteristic curve area under the curve (AUC). Also, the importance scores of training parameters are obtained by the random forest theory.
Tests to Confirm Inherently Safe Commercial Nuclear Reactors
Authors: Dong Zhe , Zhang Zuoyi , Dong Yujie , Li Fu , Huang Xiaojin , Zheng Yanhua , Zhang Han , Chen Zhipeng , Li Xiaowei
Published: January 2024

Nuclear fission energy is one of the firm low-carbon resources containing the cost of deep decar-bonization. Safety is the basis of deploying nuclear power plants near load centers in a large-scale. The safety of inherently safe nuclear reactors is defined to depends solely on the laws of nature. The world’s first demonstration plant of High Temperature Reactor with Pebble-Bed Module (HTR-PM) entered its commercial operation since December 6, 2023. To confirm the existence of inherent safety in a commercial scale, two safety tests were conducted on the two reactor modules of HTR-PM plant, each at a power of 200MWt. During the test, the active power supply was total-ly switched off to see if the decay heat can be removed passively. The responses of nuclear power and temperatures within different reactor structures show that the reactors can be naturally cooled down without active intervention. The results manifest the existence of commercial-scale inherent safety for the first time.
Assessment of genetic diversity of Camellia yuhsienensis based on leaf structure and ISSR markers
Authors: Zou Yuling , Ge Xiaoning , Yan Chao , Zhong Qiuping , Chen Danyang , Chen Zexin , Yuan Yaqi , Guo Hongyan , Zhou Youcheng , Wang Jinfeng , Cao Linqing
Published: January 2024

Genetic diversity of Camellia yuhsienensis was analyzed according to leaf structure and molecular markers to determine genetic relationships and genetic differentiation characteristics among various strains. Leaf structural traits and ISSR molecular markers were selected to study the genetic diversity and cluster analysis of C. yuhsienensis. Twenty-one leaf traits varied to different degrees, and variation coefficients ranged from 6.91–20.45%. They all reached significant or extremely significant levels. Through principal component analysis, the cumulative contribution rate of the first four principal components reached 85.57%, and eight typical leaf characteristics were screened out. Molecular markers revealed that 201 loci were amplified by 10 ISSR primers, and 175 were polymorphic loci with an average polymorphism rate of 87.06%. Nei's Diversity Index and the Shannon diversity index values were 0.2613 and 0.4013, respectively. An ISSR identification card drawn using primer 826 was used to identify 13 C. yuhsienensis. Cluster analysis demonstrated that the clustering results based on leaf structure and molecular markers were generally consistent. Only CL1 and CL2 differed between the two methods, and the ISSR molecular markers detected small variations at the molecular level. Therefore, the clustering was more detailed than that of leaf structural traits. In the two clustering methods, germplasms with higher phloem thickness and main vein bulge and a short diameter of the vascular bundle were clustered into one category, and the specific germplasm LY2 was clustered into another category. Our results provide a theoretical basis for the diversity, germplasm identification, and rational utilization of C. yuhsienensis.
Accelerating the discovery of biodiversity by detecting “new” species based on machine learning method
Authors: Lu Yuanyuan , Li Jing , Zhao Zhengyu , Zhang Yongchao , Tong Yijie , Teng Bei , Liu Ning , Shaw Josh Jenkins , Bai Ming
Published: January 2024

Background
Recently, machine learning (ML) has been widely used in species auto-identification systems for multi-scene applications in biodiversity, while most of the existing ML systems relying on images are limited to identifying the species on which they are trained, and unknown species out of the system are normally incorrectly identified.
Results
Here, we propose a new workflow system based on the ML system and PERMANOVA analysis, named Taichi for the detection and confirmation of unknown species status, stimulated by the traditional biodiversity discovery process. First, we developed a series of high-throughput photography devices that could efficiently obtain aligned multiangle images for ML system training. Then the new analysis workflow was integrated in Python codes based on the convolutional neural networks: MobileNetV2 (selected from four available networks) and further PERMANOVA analysis of euclidean distances to detect 'new' species. Two newly established beetle datasets: Melanopopillia (4 species, 55 specimens, 42 450 images) and Hong Kong beetles (21 species, 206 specimens, 35 450 images) were constructed in this work to demonstrate the Taichi system. The diagnostic information for species is generated from the output results of the ML system (top-1 accuracy rate reached 97.76% and 96.22% respectively) naming as the artificial intelligence (AI) barcode, and extra analysis of AI barcodes could help visualization the diagnostic characters from multiangle images.
Conclusions
By comparing AI barcodes of different specimens outside the system, it is proved that the Taichi workflow can rapidly detect whether the input sample is a known species or possible 'new' species. This workflow provides a newly possible self-extensibility solution for the acceleration of biodiversity discovery. Additionally, it can also drive the development of data mining from the digitization of natural history collections around the world and has great potential to advance the field of biodiversity science.
The relationship between modifiable risk factors and depression in age-specific cancer survivors: Evidence from NHANES
Authors: Qiu Minhao
Published: January 2024

Background: There is limited and inconsistent evidence on whether the modifiable risk factors linked to depression in cancer survivors remain the same across different age groups. We aimed to identify modifiable risk factors that are associated with depression in cancer survivors and determine whether this association varies with age.
Methods: This cross-sectional study analyzed 3,368 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), categorized into adults (20-64 years) and seniors (65 years and above). Cancer survivors were defined as individuals who self-reported having been diagnosed with cancer. Depression was defined as a score of 10 or higher on The Patient Health Questionnaire (PHQ-9). Logistic regression models were used to assess the relationship between modifiable factors and depression.
Results: This analysis included 3,368 participants, 1,332 (39.6%) were aged 20-64, with 205 (15.39%) having depression, and 2,036 (60.4%) were 65 and above, with 121 (5.94%) experiencing depression. Healthcare access (OR: 1.834, 95% CI: 1.145 to 2.937) and insurance (OR: 2.058, 95% CI: 1.393 to 3.039) significantly influenced depression, while mental healthcare (OR: 0.235, 95% CI: 0.176 to 0.314), smoking (OR: 1.694, 95% CI: 1.321 to 2.171), physical activity (OR: 1.588, 95% CI: 1.252 to 2.014), and dietary quality (OR: 1.691, 95% CI: 1.177 to 2.43) were also notable factors. After stratification by age, younger adults (20-64) were more influenced by smoking (OR: 0.709, 95% CI: 0.382 to 1.036) and physical activity (OR: 0.788, 95% CI: 0.468 to 1.108), while older adults (65+) were more affected by insurance (OR: 1.128, 95% CI: 0.159 to 2.096).
Conclusion: The impact of modifiable factors like insurance, smoking, and physical activity varies across age groups, while healthcare access, mental healthcare, and dietary quality remain consistent. The research emphasizes the importance of age-specific mental health support and lifestyle adjustments for cancer survivors.