bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring bovine dairy calf health and related risk factors in the first three months of rearing
Authors: Otten Nina Dam , Skarbye Alice Puk , Krogh Mogens Agerbo , Michelsen Anne Marie , Nielsen Liza Rosenbaum
Published: June 2023

Background
Rearing replacement heifers is pivotal for the dairy industry and is also associated with high input costs for the preweaned calves, due to their higher susceptibility to diseases. Ensuring calf health and viability calls for systematic approaches in order to mitigate the costs induced by managing sick calves and to ensure animal welfare. The objective of this study was to develop a systematic and feasible health-monitoring tool for bovine dairy calves based on repeated clinical observations and diagnostic results of calves at three time points; the first (T0), the third (T1) and the 12th (T3) week of age. The study included observations from 77 dairy heifer calves in nine Danish commercial dairy herds. Clinical scoring included gastrointestinal disease (GD) and respiratory disease (RD). The average daily weight gain (ADWG) was estimated from heart-girth measurements. Pathogen detection from nasal swabs and faecal samples were analysed for 16 respiratory and enteric pathogens by means of high-throughput rt-PCR. Immunisation status was assessed by serum Brix% at T0. All measures obtained in each herd were visualised in a panel to follow the health status of each calf over time.
Results:
The individual clinical observations combined with diagnostic information from immunisation and pathogen detection form each enrolled calf are presented in a herd dashboard illustrating the health status over the study period. This monitoring revealed failure of passive transfer (Brix%<8.1) in 31% of the 77 enrolled calves, signs of severe GD peaked at T0 with 20% affected calves, while signs of severe RD peaked at T2 with 42% affected calves. ADWG over the first eight weeks was estimated to be 760 g (± 190 g). Pathogen profiles varied between herds.
Conclusions:
Combining the different sources of information in one visualisation panel allows calf caretakers to detect emerging infections and initiate timely interventions as well as to evaluate the effect of given interventions. It can also provide quality assurance of calf rearing and management practices.
Therapeutic obstinacy and futile treatments in end-of- life care - the perceptions of health-care professionals
Authors: Bacoanu Gema , Poroch Vladimir , Lazar Diana Elena , Postolica Roxana , Hanganu Bianca , Poroch Mihaela , Ioan Beatrice Gabriela
Published: June 2023

The treatment of terminally ill patients raises many dilemmas that make it difficult to draw a line between treatment of uncertain benefits and therapeutic utility. Aim: To synthesize the qualitative and quantitative evidence on the views, experiences and perceptions of doctors and nurses from different specialties involved in the care of people nearing the end of life in relation to therapeutic obstinacy and futility. Design: Systematic review and narrative synthesis of qualitative and quantitative studies. Data sources: PubMed, PsycINFO, the International Association for Hospice and Palliative Care/Cumulative Index of Nursing and Allied Health Literature [IAHPC/CINAHL], and Communication & Mass Media Complete [CMMC] databases. Review methods: Databases were searched for studies from May 2016 to November 2021. Pediatric studies, family/relative viewpoints, advance care directives, and euthanasia studies were excluded. Results were synthesized using a narrative synthesis approach with thematic analysis. Results: 8 studies were included. Conclusion: Despite different perceptions among health professionals, the complexity of supporting therapy obstinacy and futile therapies lead to burnout, professional dissatisfaction and impaired communication skills among health professionals. Impact: This review will be of interest to palliative care, oncology and critical care practitioners and those planning to train and practice in these fields and will also provide inputs to debates on ethical issues in end-of-life care.
Invasive Group A Streptococcal Infections: are we facing a new outbreak? a case series with the experience of a Single Tertiary Center
Authors: Garancini Nicolò , Ricci Giulia , Ghezzi Michele , Tommasi Paola , Zunica Fiammetta , Mandelli Anna , Zoia Elena , D'Auria Enza , Zuccotti Gian Vincenzo
Published: June 2023

Background
In pediatric age, Group A Streptococcus (GAS) is responsible for a wide spectrum of clinical manifestations, from mild localized infections to life-threatening invasive diseases. In December 2022, the World Health Organization reported an increased incidence of scarlet fever and invasive GAS infections (iGAS) cases in Europe and the United States. In line with these observations, surveillance has been strengthened in our Region, allowing the identification of certified or highly suspected forms of iGAS.
Case presentation:
We report here 4 emblematic cases of iGAS admitted to our Intensive Care Unit (ICU) in the short time span from mid-February to mid-March 2023. Particularly, we describe a case of pleuropneumonia (4 year old boy) and a case of respiratory failure (2 year old boy), who necessitated Non-Invasive Ventilation support, a case of Streptococcal Toxic Shock Syndrome (6 year old girl), presenting with multi-organ failure, who needed Invasive Ventilation, and a case of meningitis (5 year old girl). All these patients needed intensive care support.
Conclusions
Accurate differential diagnosis and early treatment both could help to reduce the transmission of GAS and consequently the risk of severe iGAS. These cases confirmed the need for close monitoring and appropriate notification, in order to verify their actual increased incidence.
Simplified and Highly-reliable automated production of [18F]FSPG for clinical studies
Authors: Lin Mai , Ta Robert T. , Manning H. Charles
Published: June 2023

Background
(S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of ([18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [18F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use.
Results
Starting with activity levels of 60–85 GBq, the fully-automated process to produce [18F]FSPG took less than 45 minutes with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [18F]FSPG solution was determined to be sterile and colorless with the pH of 6.5–7.5. No radiolysis of the product was observed up to 8 hours after final batch formulation.
Conclusions
In summary, cGMP-compliant radiosyntheses and quality control of [18F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [18F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [18F]FSPG.
Lessons learned from the experiences and perspectives of frontline healthcare workers on the COVID-19 response
Authors: Orhierhor Marian , Pringle Wendy , Halperin Donna , Parsons Janet , Halperin Scott A. , Bettinger Julie A.
Published: June 2023

Background
During the COVID-19 pandemic, healthcare systems and healthcare workers (HCWs) faced significant demands and unique challenges. In this qualitative study, we explore the effects of the COVID-19 public health policies on British Columbia’s frontline HCWs, describe what worked in the management of the pandemic, and elucidate the lessons learned that could be applied to future pandemic preparedness, recovery and response.
Methods
This qualitative descriptive study is part of a larger, national multi-case study on pandemic policy communication and uptake. Semi-structured interviews were conducted from November 2020- June 2021 with fourteen HCWs working in long-term care (LTC), acute care and public health settings. Data were inductively coded, and analyzed following a resilience framework for public health emergency preparedness, which emphasizes the essential elements of a public health system, vital to all phases of health emergency management, readiness, response and recovery.
Results
HCWs experienced confusion, frustration, uncertainty, anxiety, fatigue and stress, during the pandemic and detailed challenges that affected policy implementation. This included communication and coordination inconsistencies between the province and regional health authorities; lack of involvement of frontline staff in pandemic planning; inadequate training and support; inadequate personal protective equipment resource capacity and mobilization; and staffing shortages. HCWs recommended increased collaboration between frontline staff and policy makers, investment in preparing and practicing pandemic plans, and the need for training in emergency management and infection prevention and control.
Conclusions
Pandemic planning, response and recovery should include inputs from actors/key stakeholders at the provincial, regional and local levels, to facilitate better coordination, communication and outcomes. Also, given the critical roles of frontline HCWs in policy implementation, they should be adequately supported and consideration must be given to how they interpret and act on policies. Bi-directional communication channels should be incorporated between policymakers and frontline HCWs to verify the appropriate adoption of policies, reflective learning, and to ensure policy limitations are being communicated and acted upon by policy makers.
Biomimetic anisotropic macroporous cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche via down-regulating the ROMO1
Authors: Liu Hai , Pan Weilun , Liu Honglin , Xie Denghui , Liao Liqiong
Published: June 2023

Background Osteoporosis is a systemic bone disease prone to fractures due to decreased bone density and bone quality. The pathological environment of osteoporosis interferes with the normal process of fracture healing. The clinical regenerative repair materials specifically used for osteoporotic bone defects are not satisfactory, and the study of the mechanism of bone defect regeneration in the pathological environment of osteoporosis is helpful for the design of related materials.Methods In this study, the cryogels were prepared from decellularized extracellular matrix (dECM), methacrylate gelatin (GelMA), and carboxymethyl chitosan (CMCS) via unidirectional freezing, photocrosslinking, and genipin crosslinking. dECM extracted from normal or osteoporotic rats was applied for the preparation of the cryogels, named as GelMA-CMCS@Normal or GelMA-CMCS@OVX, respectively. The effects of different cryogels on BMSCs isolated from osteoporotic rats (OVX-BMSCs) were observed in vitro and in vivo.Results It was verified that the cryogels had excellent in vitro and in vivo biocompatibility. Furthermore, the GelMA-CMCS@Normal could effectively improve the proliferation of OVX-BMSCs, and promote the differentiation of OVX-BMSCs into osteoblasts in vitro and in vivo. RNA sequencing found that the OVX-BMSCs co-cultured with GelMA-CMCS@Normal cryogel exhibited down-regulated expression of reactive oxygen species modulator 1 (Romo1), which could activate the expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2, NRF2). Further evidence showed that the reactive oxygen species (ROS) of the OVX-BMSCs were scavenged effectively after co-cultured with the GelMA-CMCS@Normal cryogel.Conclusions The results indicated that GelMA-CMCS@Normal cryogel was expected to be a clinical candidate for the repair of osteoporotic bone defects by regulating the ROS niche of OVX-BMSCs.Trial registration: Not applicable.
A prognostic model of clear cell renal cell carcinoma based on telomere-related lncRNAs
Authors: Chen Hao , Li Li , Mao Longkun , Zeng Jianfeng
Published: June 2023

Background
Telomeres have been demonstrated to be critical in the development of multiple tumors. However, the association of telomere-related lncRNAs with clear cell renal cell carcinoma (ccRCC) and their prognostic roles in ccRCC patients remain unknown.
METHODS
Expression matrix and clinicopathological data of ccRCC patients were extracted from The Cancer Genome Altas and UCSC Xena browser. The differentially expressed genes were identified and intersected with the telomere-related genes downloaded from the Telnet database. Telomere-related lncRNAs were screened by the univariate Cox regression analysis. Each patient's risk score was calculated to establish a nomogram based on eight telomere-related lncRNAs screened by the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The correlation between telomere-related lncRNAs and immune cells was assessed by the CIBEERSORT algorithm. The immune and stromal infiltrations were quantified by the ESTIMATE algorithm. Gene set enrichment analysis (GSEA) was performed to explore the selected lncRNA functions.
Result
We screened eight telomere-related lncRNAs and established a risk score model for predicting survival in ccRCC patients. A nomogram was developed to predict the survival outcomes of postoperative patients by integrating several clinical factors, and a well-predictive effect was observed. The correlation between selected lncRNAs and immune function was explored by the CIBEERSORT and ESTIMATE algorithms. Besides, GSEA showed that telomere-related lncRNAs could affect ccRCC prognosis through multiple pathways.
Tensile strength of polyester fiber estimated by molecular-chain extension prior to structure formation
Authors: Ohkoshi Yutaka , Tomisawa Ren , Nagata Mutsuya , Otsuka Yumu , Ikaga Toshifumi , Kim KyoungHou , Okada Kazuyuki , Kanaya Toshiji , Katsuta Hiroo
Published: June 2023

The combination of laser irradiation heating and synchrotron X-ray sources has made it possible to observe the fiber-structure development that occurs at sub-millisecond timescales after necking during continuous drawing. Through wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) analysis of poly(ethylene terephthalate) fibers of three different molecular weights drawn under equivalent stresses, a good correlation was observed between the d-spacing of smectic (001') diffraction extrapolated to the necking point and the strength of the drawn fiber. This indicates that the molecular chains that bear the drawing stress also bear most of the applied stress during tensile testing of the resultant fiber. In addition, considering the drawing-stress dependence of the d-spacing and the molecular weight distribution of the fiber revealed that molecular chains with molecular weights over 23,000 g/mol bear the majority of tensile force applied to the fiber.
FOXO1：An Indicator for Prognosis of Lung Adenocarcinoma and Squamous Carcinoma from a Comprehensive Analysis of Bioinformatics
Authors: Zhang Hui , Zong Ming , Cheng Kai , Fu Yan , Yu Xueying , Man Qiuhong
Published: June 2023

Background
Patients diagnosed with lung adenocarcinoma and lung squamous carcinoma typically face a poor clinical prognosis. There is an urgent need to identify biomarkers that can enhance the potential clinical prognoses and guide lung cancer treatment. FOXO1, a tumour suppressor, is frequently inactivated in various human cancers and may be correlated with patients' prognosis.
Methods
In this study, we utilised comprehensive online databases, including Oncomine, Kaplan-Meierplotter, and PrognoScan, to investigate the expression of FOXO1 and its relationship with patients' prognosis. To generate informative plots, we employed sophisticated analytical tools such as R-language and the Xiantao academic platform.
Results
Our findings revealed downregulation of FOXO1 expression in both lung adenocarcinoma and lung squamous carcinoma, which exhibited a significant positive correlation with overall survival and recurrence-free survival. Notably, in lung adenocarcinoma, the anti-tumour activity of FOXO1 appeared to be predominantly associated with central memory T cells, mast cells, T helper cells, and helper T cells 2. Conversely, in lung squamous carcinoma, the anti-tumour effect seemed to be related to central memory T cells, mast cells, macrophages, and gamma delta T cells.
Conclusions
Based on our results, FOXO1 shows potential as a prognostic marker for predicting the survival outcomes of patients with lung adenocarcinoma and lung squamous carcinoma. Further validation and exploration of FOXO1's role in these cancer types are warranted to advance our understanding and potentially improve clinical management strategies.
Clinical features and prognostic factors of acute glufosinate ammonium
Authors: Huang Changbao , Xie Donghui , Shen Yulan , Xue Xiang
Published: June 2023

This retrospective study was conducted on 67 patients who suffered from acute oral glufosinate ammonium poisoning to summarize a comprehensive overview of the clinical characteristics. General clinical data and laboratory test results were collected from the time of admission to hospital discharge. The most common clinical symptom of GA poisoning were nausea and vomiting, The incidence of unfavorable outcomes and the mortality of GA poisoning were 41.8% and 13.4%. The unfavorable outcomes group had a higher initial serum ammonia level (75.7±17.3umol/L vs 47.5±12.8umol/L), more ingestion amount of GA (103.6±63.4ml vs 72.3±37.7ml) and higher-level CK-MB (43.5 U/L vs 16.0 U/L) compared to favorable outcomes groups. The area under the curve in the ROC analysis for the predictive variables, initial ammonia and CK-MB, were 0.873 and 0.680.The patients with GA poisoning may exhibit clinical symptoms of gastrointestinal and neurological toxicity, as well as respiratory failure which experience different latent period that we need to pay special attention to. Initial serum and CK-MB might be the most accurate prognostic factors for predicting the unfavorable outcomes.
Association between PM10 and respiratory diseases admission in Peninsular Malaysia during the haze
Authors: Zulkifli Siti Wafiah Hanin Mohd , Samsudin Humaida Banu , Majid Noriza
Published: June 2023

Numerous studies have been conducted in other countries on the health effects of exposure to particulate matter with a diameter of 10 microns or less PM10 , but little research has been conducted in Malaysia, particularly during the haze season. This study intends to investigate how exposure of PM10 influenced hospital admissions for respiratory diseases during the haze period in peninsular Malaysia and it was further stratified by age group, gender and respiratory diseases categories. The study includes data from all patients with respiratory diseases in government hospitals, as well as PM10 concentration and meteorological data from all monitoring stations in peninsular Malaysia starting from 1st January 2000 to 31st December 2019. A quasi-poison time series regression with distributed lag nonlinear model (DLNM) was employed in this study to examine the relationship between exposure of PM10 and hospital admissions for respiratory diseases during the haze period. According to the findings of this study, PM10 was positively associated with respiratory disease admissions within 30 lag days under various lag patterns, with lag 25 showing the strongest association (RR = 1.001742,CI : 1.001029,1.002456). Using median as a reference, it was discovered that females were more likely than males to be hospitalized for PM10 exposure. Working age group will be the most affected by the increase in PM10 exposure with a significant cumulative RR from lag 010 to lag 030. The study found that PM10 had a significant influence on respiratory hospitalisation in peninsular Malaysia, particularly for lung diseases caused by external agents(CD5). Therefore, it is important to implement effective intervention measures to control PM10 and reduce the burden of respiratory disease admissions
COVID-19 Distress, Parenting Stress, Maladaptive Parenting and Children’s Problematic Media Use in China: Evidence from 2022 Spring in Shanghai
Authors: Wang Jingyao , Wang Shumin , Xiao Bowen , Li Juan , Feng Yuemin , Li Yan
Published: June 2023

The COVID-19 lockdowns have forced young children to spend more time in front of the media and significantly impacted their mothers' mental health. This study explored how mothers' individual distress influences children's problematic media use during the Shanghai citywide lockdown caused by COVID-19. Data were collected from 1889 Chinese mothers (Mage= 34.69 years,SD = 3.94 years) with preschoolers aged 3–6 years (Mage= 4.38 years,SD = 1.06 years; 49.0% boys) via an online survey. The statistical analyses relied on SPSS Statistics version 26.0 and macro-program PROCESS 3.3. to investigate the associations and mediation analysis among all the study variables. The results indicated that: (1) significant associations between individual maternal distress with children's problematic media use; (2) maternal parenting stress and maladaptive parenting serial mediated the relationship between mothers' individual distress and children's problematic media use. The findings imply that parents need to enhance their ability to manage risk and promote mental health during periods of significant stress and routine disruption to reduce children's problematic media use.
Utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions
Authors: Wang Gaozhe , Jin Yan , Xiong Kunlong , Jin Xiaoyan , Cao Chao
Published: June 2023

Background: Bronchoscopy is currently the most common technique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients withbronchial mucosal lesions.
Methods: We conducted a retrospective studyin a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions.
Results: A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3% (95% confidence interval [CI]: 53.1%-67.1%), which was higher than that of patients with WLB alone (45.2%, 95% CI: 38.2-52.4%) (P= 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100%, 95% CI: 95.5-100% versus 69.6%, 95% CI: 59.6-78.1%), positive predictive value (100%, 95% CI: 96.1-100% versus 74.3%, 95% CI: 65.5-81.7%) and negative predictive value (56.3%, 95% CI: 48.8-63.6% versus 39.4%, 95% CI: 32.3-47.0%).
Conclusion: Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.
How Perfectionism Determines Success or Failure: A Dual Pathway Mechanism Study on the Influence of Perfectionistic Climate on Performance of Elite Female Basketball Players in CUBAL
Authors: Meng Meng , Su Rong-Hai , Kogiso Kohei , Zheng Rong-Rong , Chen Lin , Wei Li , Hsu Mao-Chou
Published: June 2023

This study, based on the cognitive appraisal theory of stress, constructs a dual-pathway theoretical model called the Perfectionism-Performance Theory to examine the influence of perfectionistic climate on athletes' performance. The study empirically tests the relationships among the constructs in the model using a sample of 125 core players from the top-level women's basketball teams in the 24th CUBA L24 tournament in 2022. The findings reveal a double-edged effect of perfectionistic climate on athletes' performance. In the positive pathway, perfectionistic climate positively influences athletes' performance through challenge stressors and positive coping strategies. In the negative pathway, perfectionistic climate negatively affects athletes' performance through hindrance stressors and negative coping strategies. This study aims to enhance athletes' adaptation to perfectionistic climate and further improve individual and team performance.
Mitochondrial-derived Peptides: Are They Actually Important?
Authors: Gruschus James M. , Morris Daniel L. , Tjandra Nico
Published: June 2023

Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have various effects in cell culture and animal models, affecting neuroprotection, insulin sensitivity, and apoptosis, and some are secreted, potentially having extracellular signaling roles. However, except for humanin, their importance in normal cell function is unknown. To gauge their importance, their coding sequences in vertebrates have been analyzed for synonymous codon bias. Because they lie in RNA genes, such bias should only occur if their amino acids have been conserved to maintain biological function. Humanin and SHLP6 show strong synonymous codon bias and sequence conservation. In contrast, SHLP1, SHLP2, SHLP3, and SHLP5 show no significant bias and are poorly conserved. MOTS-c, SHLP4 also lack significant bias, but contain highly conserved N-terminal regions, and their biological importance cannot be ruled out. An additional potential mitochondrial-derived peptide sequence was discovered preceding SHLP2, named SHLP2b, which also contains a highly conserved N-terminal region with synonymous codon bias.
Chlorfenapyr metabolism by mosquito P450s associated with pyrethroid resistance: identification of potential activation markers.
Authors: Yunta Cristina , Ooi Jocelyn , Oladepo Folasade , Grafanaki Sofia , Pergantis Spiros , Tsakireli Dmitra , Ismail Hanafy , Paine Mark
Published: June 2023

Chlorfenapyr is a pro-insecticide increasingly used in combination with pyrethroids such as a-cypermethrin or deltamethrin in insecticide treated bednets (ITNs) to control malaria transmitted by pyrethroid-resistant mosquito populations. Chlorfenapyr requires P450 activation to produce tralopyril and other bioactive metabolites. Pyrethroid resistance is often associated with elevated levels of chemoprotective P450s with broad substrate specificity, which could influence chlorfenapyr activity. Here, we have investigated chlorfenapyr metabolism by a panel of eight P450s commonly associated with pyrethroid resistance in An. gambiae and Ae. aegypti, the major vectors of malaria and arboviruses. Chlorfenapyr was activated to tralopyril by An. gambiae CYP6P3, CYP9J5, CYP9K1 and Ae. aegypti, CYP9J32. Kcat/ KM value of 0.66 µM-1 min-1, 6.7 fold higher than CYP6P3 and CYP9J32 (both 0.1 µM-1 min-1) and 22-fold higher than CYP9J5 (0.03 µM-1 min-1). Further investigation of the effect of a-cypermethrin equivalent to the ratios used with chlorfenapyr in bed nets (~ 1:2 molar ratio) resulted in a reduction in chlorfenapyr metabolism by CYP6P3 and CYP6K1 and of 76.8% and 56.8% respectively. This research provides valuable insights into the metabolism of chlorfenapyr by mosquito P450s and highlights the need for continued investigation into effective vector control strategies.
Establishing a one-step marker-free CRISPR/Cas9 system for industrial Aspergillus niger using counter-selectable marker Ang-ace2
Authors: Liu Jiao , Zhu Jie , Zhang Qian , Lv Ruitong , Liu Hao
Published: June 2023

Objectives
To develop a one-step, marker-free CRISPR/Cas9 system for highly efficient genome editing in industrial Aspergillus niger, with a short genetic operation cycle.
Results
Firstly, evaluation of different promoters for sgRNA expression revealed tRNAGly15 as the most efficient, achieving a remarkable 100% gene editing efficiency. Furthermore, a counter-selectable marker, Ang-ace2, was identified for A. niger. Subsequently, a CRISPR/Cas9 plasmid was developed, utilizing a truncated AMA1 element and the Ang-ace2 conditional expression cassette driven by a Tet-on promoter. In the presence of doxycycline, the plasmid demonstrated a 33% loss efficiency in the progeny of A. niger spores after a single generation, resulting in a shortened genetic operation cycle of 16 days for CRISPR/Cas9.
Conclusions
The one-step marker-free CRISPR/Cas9 system was successfully developed in industrial A. niger, allowing for efficient gene editing while simultaneously reducing the editing time.
Risk factors for metachronous colorectal cancer and advanced neoplasia following primary colorectal cancer: A systematic review and meta-analysis
Authors: Zhang Ye , Karahalios Amalia , Aung Ye Kyaw , Win Aung Ko , Boussioutas Alex , Jenkins Mark A.
Published: June 2023

Background
Identifying risk factors for metachronous colorectal cancer (CRC) and metachronous advanced neoplasia could be useful for guiding surveillance and cancer prevention. We conducted a systematic review and meta-analysis to investigate the risk factors for metachronous CRC and advanced neoplasia.
Methods
Searches were conducted in MEDLINE, Embase, Web of Science and Cochrane Central Registry of Controlled Trials. Random effects models were fitted to estimate the association between the investigated risk factors and metachronous CRC or advanced neoplasia.
Results
22 articles were included in the systematic review. The risks of metachronous CRC or advanced neoplasia were higher if the first CRC was diagnosed in the presence of a synchronous advanced lesion (pooled risk ratio (RR) from 3 studies: 3.61, 95% confidence interval (CI): 1.44–9.05; and pooled RR from 8 studies: 2.77, 95% CI: 2.23–3.43, respectively). The risk of metachronous CRC was lower, but the risk of metachronous advanced neoplasia was higher if the first CRC was distal (compared with proximal) (pooled RR from 3 studies: 0.48, 95% CI: 0.23–0.98; and pooled RR from 2 studies: 2.99, 95% CI: 1.60–5.58 respectively). The risk of metachronous advanced neoplasia increased with age (pooled RR from 3 studies: 1.07 per year of age, 95% CI: 1.03–1.11). There was no evidence that any lifestyle risk factors studied were associated with the risk of metachronous CRC or advanced neoplasia.
Conclusions
Identified risk factors for metachronous CRC and advanced neoplasia might be useful to tailor the existing surveillance guidelines after the first CRC.
Integrating cfDNA Liquid Biopsy and Organoid-Based Drug Screening Reveals PI3K Signaling as a Promising Therapeutic Target in Colorectal Cancer
Authors: YANG HUAN , Xiao Xing , Zeng Leli , Zeng Haiteng , Wang Jingshu , Li Guanghua , Dai Weigang , He Yulong , Wang Suihai , Peng Jianjun , Chen Wei
Published: June 2023

Background The current model of precision medicine relay on biomarkers, which are mainly obtained through next generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. The current study tried to combine liquid biopsy with functional drug test through organoid models to find potential drugs for cancer patients.Methods CRC patients were prospectively enrolled and blood samples were collected from patients start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models.Results A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients.Conclusion Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.
Exploratory biological coordinate analysis on 2,4-epi-brassinolide-induced the size change of leaf angle in tobacco seedlings
Authors: He Hui , Xiao Junchen , Zhang Yang , Dai Huawei , Dong Xiaowei , Ma Ruhui , Shi Yi , Sun Yanguo , Zhang Yan
Published: June 2023

Leaf angle (LA) is one of the most important agronomic trait of plant architecture for crop yield. 2,4-epibrassinolide (EBR) is a bioactive form of brassinosteroids (BRs) and plays a significant role in influencing plant architecture, including the regulation of LA. To investigate the effect of EBR on the size of LA in tobacco seedlings, we performed a histochemical and molecular characterization of LA by spraying differential concentrations of EBR, T1(1×10− 8mol/L), T2 (1×10− 5 mol/L) and CK (0 mol/L). The results showed that compared with CK, EBR could significantly enlarge the size of LA in T1 and T2, respectively (increased 38.6% and 37.3%), especially by promoting cell area (increased 95.2% and 185%) and inhibiting cell division (cell number in per unit area reduced 16.4% and 41.8%). The relative expression levels of NtBIN2, NtEXPA28, and NtCYCD1 was consistent correlation with the size of LA. Through detection the representative genes of IAA, GA, BR biosynthesis and signaling pathway, the coordinate relationship of these hormones were evaluated. It showed a positive correlation of EBR concentration with the genes of IAA biosynthesis (NtYUCCA8), GA biosynthesis (NtGA20), BR signaling pathway (NtBRI1, NtBES1), IAA signaling pathway (NtGH3.2 and NtLC3), and a negative correlation with cell cycle (NtCYCD2, NtCYCD3, and NtCYCD5). In conclusion, exogenously application of EBR enlarge the size of LA in tobacco seeding via increasing the cell area by modulating the IAA, GA biosynthesis and IAA, BR signaling and restraining the cell division by cell cycle regulation.
Lattice dynamics and carrier recombination in GaAs/GaAsBi nanowires
Authors: Jansson M. , Nosenko V. V. , Rudko G. Yu. , Ishikawa F. , Chen W. M. , Buyanova I. A.
Published: June 2023

GaAsBi nanowires represent a novel and promising material platform for future nano-photonics. However, the growth of high-quality GaAsBi nanowires and GaAsBi alloy is still a challenge due to a large miscibility gap between GaAs and GaBi. In this work we investigate effects of Bi incorporation on lattice dynamics and carrier recombination processes in GaAs/GaAsBi core/shell nanowires grown by molecular-beam epitaxy. By employing photoluminescence (PL), PL excitation, and Raman scattering spectroscopies complemented by scanning electron microscopy, we show that increasing Bi-beam equivalent pressure (BEP) during the growth does not necessarily result in a higher alloy composition but largely affects the carrier localization in GaAsBi. Specifically, it is found that under high BEP, bismuth tends either to be expelled from a nanowire shell towards its surface or to form larger clusters within the GaAsBi shell. Due to these two processes the bandgap of the Bi-containing shell remains practically independent of the Bi BEP, while the emission spectra of the NWs experience a significant red shift under increased Bi supply as a result of the localization effect.
Some like it burnt: species differences in small mammal assemblage in a Mediterranean-basin nearly 3 years after a major fire
Authors: Tomassini Orlando , Aghemo Anna , Baldeschi Benedetta , Bedini Gianni , Petroni Giulio , Giunchi Dimitri , Massolo Alessandro
Published: June 2023

The Habitat Accommodation Model (HAM) predicts wildlife community recovery based on vegetation structure. However, studies on HAM in the Mediterranean basin are scarce. Here, we described the assemblage of small mammals in a Mediterranean area ~ 3 years after a fire, specifically examining three functional small mammalian categories: ground-foraging insectivorous, ground-foraging herbivorous/granivorous and arboreal-foraging species. The study was conducted in Monte Pisano (Italy), where a September 2018 fire burned ~ 12 km2. A stratified random sampling was adopted, basing on burnt status and forest type. In each site, during late spring-summer 2021, hair-tube sampling was conducted, and collected hair were species-attributed. Distance-based redundancy analysis (db-RDA) explored assemblage composition, and single-species occupancy models tested hypotheses for the identified species.Crociduraspp. andApodemusspp. abundances were not significantly associated with any factor tested. Abundances of house mouseMus domesticusand Savi’s pine voleMicrotus saviiwere higher in the burnt area. Garden dormouseEliomys quercinushad higher abundance in pine forest, whereas red squirrelSciurus vulgariswas more abundant in chestnut forest. The overall greater abundance of ground-foraging herbivorous/granivorous in the burnt area, characterised by a dense undergrowth, could be related to anti-predatory strategies and food opportunities. Insectivorous could be in a recolonisation phase that would hide their earlier absence. Arboreal-foraging species were associated with forest type, regardless of burnt status. The HAM was overall confirmed also in Mediterranean basin ecosystems, probably due to their temperate climate. This may facilitate predictions about post-fire animal successions, which will be even more crucial in future.
Three-dimensional printed titanium mesh combined with iliac cancellous bone in the reconstruction of mandibular defects secondary to ameloblastoma resection
Authors: Zhao Zhiyang , Shen Shunyao , Yu Hongbo , Shen Guofang , Li Meng , Ding Guanrong
Published: June 2023

Background
The reconstruction of large mandibular defects is a challenge, and the free vascularized bone flaps are most commonly used. However, the precision and symmetry of this repair are deficient, and patients have a risk of vascular embolism, flap necrosis and donor site complications. Therefore, to explore an ideal alternative in mandibular reconstruction with high surgical accuracy and low complications is indispensable.
Methods
Seven patients with recurrent or large-scope ameloblastoma were enrolled in this study. All patients were provided with a fully digital treatment plan, including the design of osteotomy lines, surgical guides, and three-dimensional printed titanium mesh for implantation. With the assistance of a surgical guide, ameloblastomas were resected, and custom 3D printed titanium mesh combined with posterior iliac bone harvest was used in mandibular reconstruction. The surgical discrepancy between the surgical plan and the real result was compared. At the same time, the resorption rate of the implanted bone was evaluated.
Results
All patients completed the fully digital treatment process successfully without severe complications. Image fusion showed that the postoperative contour of the mandible was basically consistent with surgical planning, except for a slight increase in the inferior border of the affected side. The mean error between the intraoperative bone volume and the digital planning bone volume was 2.44%±2.10%. Furthermore, the bone resorption rates of the harvested graft 6 months later were 32.15%±6.95%.
Conclusions
The use of digital surgical planning and 3D-printed templates can assist surgeons in performing precise surgery, and the 3D-printed titanium mesh implant can improve the patient's facial symmetry. 3D printed titanium combined with posterior iliac cancellous bone graft can be regarded as an ideal alternative in extensive mandibular reconstruction.
Association between chronic obstructive pulmonary disease and 28-day mortality in patients with sepsis: a retrospective study based on the MIMIC-III database
Authors: Chen Yubiao , Lu Lifei , Li Xicong , Liu Baiyun , Zhang Yu , Zheng Yongxin , Zeng Yuan , Wang Ke , Pan Yaru , Liang Xiangning , Wu Zhongji , Fu Yutian , Huang Yongbo , Li Yimin
Published: June 2023

Background: Along with a variety of chronic co-morbid medical conditions, sepsis is a common cause of mortality in critically ill patients, and chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in septic patients. However, the impact of COPD on patients with sepsis is still unclear. Therefore, the purpose of this study was aimed to assess the effect of COPD on the prognosis of sepsis patients based on MIMIC-III database.
Methods: In this retrospective study based on the Medical Information Mart for Intensive Care (MIMIC)-III database version 1.4 (v1.4), we collected clinical data and 28-day all-cause mortality from sepsis patients in intensive care unit (ICU) who met the diagnostic criteria of Sepsis 3 on ICU admission between 2008 and 2012. ICD-9 code was used to identified COPD. We applied Kaplan-Meier analysis to compare difference between 28-day all-cause mortality of COPD and non-COPD patients. Univariate and multivariate cox proportional-hazards model was applied to explore the risk factor associated with 28-day all-cause mortality in patients with sepsis.
Results: 6257 patients with sepsis were included in this study, including 955 (15.3%) with COPD and 5302 without COPD (84.7%). Compared with sepsis patients without COPD, sepsis patients with COPD were older (median: 73.5 vs 65.8, P<0.001), had a higher simplified acute physiology score II (SAPSII) (median: 40.0 vs 38.0, P<0.001) and greater proportion of mechanical ventilatory support (MV) (55.0% vs 48.9%, P=0.001). In our study, patients with COPD had higher 28-day all-cause mortality (23.6% vs 16.4%, P < 0.001) than non-COPD patients. After adjusting the confounding factors, the results showed that COPD was an independent risk factor for the 28-day all-cause mortality in septic patients (HR 1.30, 95%CI: 1.12-1.51, P=0.001).
Conclusions: The comorbidity of COPD was an independent predictor of 28-day all-cause mortality in critical septic patients. Clinically, sepsis patients with COPD should be given additional care.
Prediction of metachronous gastric neoplasms after curative endoscopic submucosal dissection for early gastric cancer
Authors: Chen Na , Ge Jian , Shi Lei , Jia Ruzhen , Jiang Junmei
Published: June 2023

Background: As more early gastric cancer (EGC) patients are being treated with endoscopic submucosal dissection (ESD), it is important to find the risk factors which contribute to the occurrence of metachronous gastric neoplasms (MGN). This study aimed to analyze the characteristics of MGN and to generate useful tools for the prediction of MGN following ESD.
Methods: A total of 819 patients were retrospectively enrolled. The risk factors for MGN were analyzed using Cox hazard proportional model. Moreover, RStudiosoftware is used to build nomogram models, and evaluate the discrimination, consistency and decision curves.
Results: A total of 5.0% (41/819) of patients had MGN after ESD for EGC. The median interval between the discovery of MGN and the initial EGC was 23 months. Cox multivariable analysis found that history of drinking [HR:2.486(1.082-5.710), p=0.032], location of lesion (middle 1/3) [HR: 2.613(1.192-5.725), p=0.016], node metastasis [HR: 3.152(1.046-9.502), p=0.041] and whole lesion removal(not) [HR: 2.526(1.029-6.200), p=0.043] were independent risk factors for the development of MGN. In addition, we were developed and internally validated nomogram to predict the 3-, 5-, and 7-year probability of developing MGN after ESD for EGC (C index= 0.665). The calibration chart showed that the predicted probability of MGN after ESD for EGC was the similar to the actual observed result and the DCA decision curve analysis showed strong clinical practicability.
Conclusions: We constructed a nomogram for predicting the incidence of MGN after ESD in EGC patients and the performance of the model is excellent.
Falls, hospitalizations, and poor self-rated health in older people with diabetes and frailty: A secondary analysis of SABE-Colombia
Authors: Morros-González Elly , Chacón-Valenzuela Estephania , Vargas-Beltrán María Paula , Gómez Ana María , Chavarro-Carvajal Diego , Cano-Gutiérrez Carlos Alberto , Venegas-Sanabria Luis Carlos
Published: June 2023

Background
Diabetes and frailty, together, have been related to adverse events such as increased risk of hypoglycemia, functional decline, disability, hospital admissions, and worsening quality of life. We estimated the prevalence of diabetes and frailty and their association with hospitalization, poor self-rated health, recurrent falls, and fear of falling.
Methods
Data came from the “Salud, Bienestar y Envejecimiento” (SABE) Colombia Survey 2015, a cross-sectional study of 23694 community-dwelling adults aged 60 years or older living in rural or urban areas, a representative sample from the total population. A modified version created of the frailty phenotype proposed by Fried, was used to measure frailty. Diabetes prevalence was considered by self-report.
Results
3873 older people were analyzed, 16.2% had diabetes, were more likely to be women, younger age (≤ 69 years), lived in urban areas and had lower economic income. Geriatric syndromes, chronic illnesses, hospitalization in the last year and poor self-rated health were also significantly associated with diabetes. The prevalence of older adults having diabetes and frailty was 22.4%. Diabetes and frailty were associated with hospitalization in the last year, poor self-rated health, recurrent falls, and fear of falling, associations that were higher than analysis with diabetes or frailty.
Conclusions
Findings of our study provide additional evidence supporting association between older people with diabetes and frailty and unfavorable outcomes.
A possible expansion of the VISTA enhancer database
Authors: Ni Pengyu , Wu Siwen , Su Zhengchang
Published: June 2023

The VISTA enhancer database is a valuable resource for evaluating predicted enhancers in humans and mice. In addition to thousands of validated positive regions (VPRs) in the human and mouse genomes, the database also contains similar numbers of validated negative regions (VNRs). We have previously shown that the VPRs are on average half as long as predicted overlapping enhancers that are highly conserved, and hypothesize that the VPRs might be truncated forms of long bona fide enhancers. Here, we show that like the VPRs, the VNRs also are under strongly evolutionary constraints and overlap predicted enhancers in the genomes. Moreover, the VNRs are also on average half as long as predicted overlapping enhancers that are highly conserved. Thus, we hypothesize that like the VPRs, the VPRs might also be truncated forms of long bona fide enhancers.