bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting hepatotoxicity associated with low-dose methotrexate using machine learning
Authors: Hu Qiaozhi , Wang Hualing , Xu Ting
Published: November 2022

Purpose
An accurate prediction of the hepatotoxicity associated with low-dose methotrexate can provide evidence for a reasonable treatment choice. This study aimed to develop a machine learning-based prediction model to predict hepatotoxicity associated with low-dose methotrexate and explore the associated risk factors.
Methods
Eligible patients with immune system disorders, who received low-dose methotrexate at West China Hospital between January 1, 2018, and December 31, 2019, were enrolled. A retrospective review of the included patients was conducted. Risk factors were selected from multiple patient characteristics, including demographics, admissions, and treatments. Eight algorithms, including eXtreme Gradient Boosting (XGBoost), AdaBoost, CatBoost, Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LightGBM), Tree-based Pipeline Optimization Tool (TPOT), Random Forest (RF), and Artificial Neural Network (ANN), were used to establish the prediction model.
Results
A total of 782 patients were included, and hepatotoxicity was detected in 35.68% (279/782) of the patients. The Random Forest model with the best predictive capacity was chosen to establish the prediction model (receiver operating characteristic curve 0.97, accuracy 64.33%, precision 50.00%, recall 32.14%, and F1 39.13%). Among the 15 risk factors, the highest score was a body mass index of 0.237, followed by age (0.198), the number of drugs (0.151), and the number of comorbidities (0.144). These factors demonstrated their importance in predicting hepatotoxicity associated with low-dose methotrexate.
Conclusion
Using machine learning, this novel study established a predictive model for low-dose methotrexate-related hepatotoxicity. The model can improve medication safety in patients taking methotrexate in clinical practice.
Single center retrospective subgroup analysis of “primary aortic” (aneurysm, aortic dissection, PAU) and “secondary aortic” (iatrogenic, trauma and aortoesophageal fistula) indications for emergency TEVAR
Authors: Rebelo Artur , Partsakhashvili Jumber , Ronellenfitsch Ulrich , John Endres , Kleeff Jörg , Ukkat Jörg
Published: November 2022

Background
The aim of the study was to analyse the outcome of emergency thoracic endovascular aortic repair (TEVAR) in the treatment of “primary aortic” (aneurysm, aortic dissection, penetrating aortic ulcer [PAU]) and “secondary aortic” (iatrogenic, trauma and aortoesophageal fistula) pathologies.
Methods
Retrospective review of a cohort of patients treated at a single tertiary referral center from 2015 to 2021. Primary end point was postoperative in-hospital mortality. Secondary end points were the duration of the procedure, duration of postoperative intensive care treatment, length of hospital stay, and the nature and severity of postoperative complications according Dindo-Clavien Classification
Results
A total of 34 patients underwent TEVAR for emergency indications. 22 patients were treated for primary and 12 patients for secondary aortic pathologies. Concerning in-hospital mortality, no statistically significant difference could be observed between the primary and secondary aortic groups (27.3% vs 33.3%, p = 0.711). Patients with aortoesophageal fistula had a mortality rate of 66.7%. Postoperative morbidity (Dindo-Clavien > 3) was also not statistically significant different between the aortic and non-aortic groups (36.4% vs 33.3%, p = 0.86). Preoperative hemoglobin level (mmol/L) (p < 0.001), postoperative creatinine level (umol/L) (p = 0.009) and pre- and postoperative lactate levels (p < 0.001) were found to be independent factors associated with early mortality and morbidity (Dindo-Clavien > 3).
Conclusions
Morbidity and in-hospital mortality are still considerable after emergency TEVAR, for both aortic and non-aortic indications. Pre- and postoperative levels of hemoglobin, creatinine and lactate may be valuable to predict the patient outcomes.
Oral Manifestations of COVID-19: A Questionnaire-Based Survey of the Mild and Moderate Cases in the Turkish Population
Authors: Ünallı K. Esra , Gedik Ecem , Yazar Ezgi , Çandırlı Celal
Published: November 2022

BACKGROUND
A myriad of symptoms associated with COVID-19 have been reported in the literature. It's currently unclear if these symptoms are part of a normal clinical pattern directly induced by SARS-CoV-2 infection or are secondary to the patient's compromised systemic condition, given the probability of coinfections, immunosuppression, and treatment-related adverse effects (4). The aim of this research was to find answers to the question"What is the prevalence of oral symptoms in COVID-19 patients?“.
METHODS
A questionnaire was designed to detect and identify changes in the oral mucosa in patients with COVID-19 infection. During their follow-up at the Gölcük State Hospital COVID Outpatient Clinic, clinicians and an academic specialist performed a face-to-face survey of the patients. Participants were informed about the purpose of the study and their consent to participate in the study was obtained along with their signatures on the questionnaire form. The data was collected between April 12 and May 22, 2020, and it was analyzed, archived, and processed anonymously.
RESULTS
This survey included 306 COVID-19 patients in total. The results revealed that only 29.4% of respondents had complaints of oral aphthae and ulcers and 18.94% experienced oral pain; with the most commonly reported symptom being xerostomia (67,6%). There was a widespread distribution of reported symptoms with varying incidences and locations.
CONCLUSION
Analyzing the data this study procured, one still can’t conclusively determine whether the oral manifestations develop secondary to COVID-19.
On the non-linearity of radon-induced lung cancer
Authors: Rosenberger Albert , Bickeböller Heike , Christiani David C , Liu Geoffrey , Schabath Matthew B , Duarte Luisa F. , Marchand Loic Le , Haiman Christopher , Landi Teresa , Consonni Dario , Field John K , Davies Michael P.A. , Albanes Demetrios , Tardon Adonina , Fernández-Tardón Guillermo , Rennert Gad , Rennert Hedy , Amos Christopher I , Hung Rayjean J
Published: November 2022

Exposure to low doses of the radioactive gas radon, as found indoors in dwellings, has been consistently shown to be a risk factor for lung cancer (LC). The linear-no-threshold hypothesis (LNT) is often applied to estimate excess odds ratios or population attributable risks, albeit this LNT assumption remains debated. We investigate the profile of radon-induced LC-risk in a sample of 8,927 cases and 5,562 controls of the International Lung Cancer Consortium (ILCCO), contributed by studies with sufficient exposure heterogeneity. Spatial indoor-radon exposure in the residential area (sIR) obtained from the national surveys were linked to the participants’ residential geo-location. Parametric linear- and spline-functions were fitted within framework of logistic regression. We observed a U-shaped dose-risk relation, with the lowest risk exposure level (LRE) being 57.6 Bq/m³ (95%.CI: 56.1–59.2 Bq/m³). The risk of overall-LC at 25 Bq/m³ (OR = 1.31, 95%-CI: 1.01–1.59) was comparable to that at 100 Bq/m³ (OR = 1.34, 95%-CI: 1.20–1.45). Regarding histological subtypes, we observed the strongest risk for small-cell LC, and weak association for squamous-cell LC with no association below 58 Bq/m³. Our results showed a U-shaped risk-profile for radon-induced LC risk at very low exposure levels (sIR < 200 Bq/m³), lowest in areas of mean indoor radon levels of about 58 Bq/m³. Risk profiles differ between histological subtypes, and sex, age and smoking behaviour modify the lowest risk thresholds. sIR is a useful proxy for radon exposure, and the linearity-no-threshold assumption in this data seems not optimal for the dose-response relation of sIR less than 200 Bq/m³.
Data mining on identifying diagnosis and prognosis biomarkers in head and neck squamous carcinoma
Authors: Ju Guoyuan , Yao Zhangyu , Zhao Yanbin , Zhao Xiaotong , Liu Fangzhou
Published: November 2022

Head and neck squamous carcinoma (HNSC) induce high cancer-related death worldwide. The biomarker screening on diagnosis and prognosis is of great importance. This research is aimed to explore the specific diagnostic and prognostic biomarkers for HNSC through bioinformatics analysis. The mutation and dysregulation data were acquired from UCSC Xena and TCGA databases. The top ten genes with mutation frequency in HNSC were TP53 (66%), TTN (35%), FAT1 (21%), CDKN2A (20%), MUC16 (17%), CSMD3 (16%), PIK3CA (16%), NOTCH1 (16%), SYNE1 (15%), LRP1B (14%). A total of 1,060 DEGs were identified, with 396 up-regulated and 665 downregulated in HNSC patients. Patients with lower expression of ACTN2 (P = 0.039, HR = 1.3), MYH1 (P = 0.005, HR = 1.5), MYH2 (P = 0.035, HR = 1.3), MYH7 (P = 0.053, HR = 1.3), and NEB (P = 0.0043, HR = 1.5) exhibit longer overall survival time in HNSC patients. The main DEGs were further analyzed by pan-cancer expression and immune cell infiltration analyses. MYH1, MYH2, and MYH7 were dysregulated in the cancers. Compared with HNSC, their expression levels are lower in the other types of cancers. MYH1, MYH2, and MYH7 were expected to be the specific diagnostic and prognostic molecular biomarkers of HNSC. All the five DEGs have a significant positive correlation with CD4 + T cells and macrophages.
Metal-tolerance protein PCR2 enhances Cd tolerance by root efflux of Cd ions in poplar
Authors: Lyu Fuling , Shan Qinghua , Qiao Kun , Zhang Haizhen , Zhou Aimin
Published: November 2022

Cadmium (Cd) is a non-essential, toxic metal that affects plant growth. Plant cadmium-resistance (PCR) proteins play key roles in responding to heavy metal stress. In this study, we isolated the PCR gene PePCR2 from Populus euphratica. PePCR2 gene transcription was induced by Cd and peaked at 24 h after exposure; the PePCR2 protein was localized to the plasma membrane. Expressing PePCR2 in yeast enhanced the tolerance of yeast cells to Cd and decreased Cd content. Overexpression of PePCR2 in poplar conferred higher Cd resistance than in wild-type plants. Net Cd2+ efflux measurements showed increasing Cd2+ efflux in transgenic roots compared with wild-type plants. Furthermore, the overexpression of PePCR2 in poplar increased the transcription levels of ABCG29, HMA5, PDR2, YSL7, and ZIP1 and decreased that of NRAMP6 upon exposure to Cd. These data showed that PePCR2 increased Cd resistance by acting as a Cd extrusion pump or by regulating other Cd2+ transporters to decrease Cd toxicity in the cytosol. Our study provides an effective genetic resource for reducing Cd accumulation in plants.
Investigation on ratios of some common diseases and health risks relating to dioxin exposure in Da Nang, Vietnam
Authors: Sau Trinh Khac , Hung Dinh Viet , Le Quan Van , Quang Le Van
Published: November 2022

Analyze the current status of disease patterns and health risks of people in Thanh Khe district (TK group) residing near areas where Agent Orange (AO)/dioxin was stored in Da Nang airport compared with people in Son Tra district (ST group - control group), Da Nang city. A cross-sectional descriptive study. This is a survey of 402 families residing in the TK group and 400 ones residing in the ST group. Subjects in the age group 45–69 accounted for a high proportion, of which women accounted for the majority, the residence time was stable and long, mainly over 15 years in both groups. People in the TK group had direct and indirect exposure to AO/dioxin accounted for a higher proportion than in the ST group. The incidence of some diseases that are recommended to be related to AO/dioxin such as hypertension (33.6%), diabetes mellitus (8.96%), and other diseases: stomach (23.0%), joints (40.3%), ear-nose-throat (ENT, 11.2%), urinary system (7.21%) compared with the ST group. Exposure to AO/dioxin has changed the disease pattern and increased some diseases in people residing near areas where AO/dioxin was previously stored.
Optimal initiation of dialysis in end stage kidney disease patients: is it a resolved question? A Systematic Literature Review
Authors: Jia Xiaoyan , Tang Xueqing , Moreira Paulo , Li Yunfeng , Xu Dongmei
Published: November 2022

Is there a definite universally accepted optimal initiation of maintenance dialysis in end stage kidney disease patients (ESKD)? The decision on optimal initiation of maintenance dialysis is an ongoing common problem faced by nephrologists around he world. However, symptoms or signs of uremia are varied and complex, mainly depending on clinical judgment; what’s more, typical uremic symptoms such as pericarditis and encephalopathy in patients without volume overload often occur at a very low glomerular filtration rate (GFR) and these conditions are often combined with severe metabolic disorders and/or organ damages. The fact is that the exact optimal timing of dialysis for ESKD patients remains unknown. The study systematically reviewed the available evidence with regard to the optimal initiation of maintenance dialysis in ESKD patients, applying PRISMA and the Newcastle-Ottawa scale. The review identified approaches and methods for investigation of optimal dialysis initiation. Evidence suggests that GFR at dialysis initiation was not associated with mortality and that the timing of dialysis initiation should not be based on GFR. Assessments of volume load and patient’s tolerance to volume overload are prospective approaches recommended. The article updates and identifies approaches and methods for investigation of optimal dialysis initiation to support evidence-based clinical decision.
Effectiveness of eradication therapy for Helicobacter pylori infection in Africa: A systematic review and meta-analysis
Authors: Fekadu Sintayehu , Engiso Hizkel , Seyfe Sisay , Iizasa Hisashi , Godebo Ashebir , Deyno Serawit , Yoshiyama Hironori
Published: November 2022

Background
The effectiveness of Helicobacter pylori (H. pylori) eradication depends on the treatment protocol. This study aimed to investigate the H. pylori eradication effectiveness in Africa using the best available evidence from databases.
Methods
PubMed, Google Scholar, Hinari, Scopus, and the directory of Open Access Journals (DOAJ) were searched. The quality of each included study was assessed using Cochrane risk-of-bias tool for randomized trials (RoB2) and Risk of Bias in Non-Randomized Studies of Intervention (ROBINS-I) for observational studies. Heterogeneity between studies was assessed using I2 test statistics based on the random effect model. Stata version 13 (College Station, Texas 77845 USA) software was employed to compute the pooled eradication rate. Forest plots and tables were used to present the data.
Results
Twenty-two studies from 9 African countries with a total population of 2,163 met the inclusion criteria and were included in the analysis. The pooled eradication rate of H. pylori by standard therapy was 79% (95% CI: 75%, 82%), with heterogeneity (I2 = 93.02%). In the subgroup analysis by study design, a higher eradication rate was reported from observational studies (85%, 95% CI: 79%-90%), compared to randomized control trials (77%, 95% CI: 73%-82%); by the duration of therapy, higher eradication rate was reported in 10-days regimen (88%, 95% CI: 84–92), compared to 7-days regimen (66%, 95% CI: 55–77); by country, the highest eradication rate was found in Ethiopia (90%; 95% CI: 87%-93%) and the lowest eradication rate was reported in Ivory Coast (22.3%; 95% CI:15%-29%); by type of H. pylori test, the highest eradication rate was reported when rapid urease test coupled with histology (88%, 95% CI: 77–96), and the lowest eradication rate was reported using histology alone (22.3%; 95% CI:15%-29%).
Conclusions
Eradication therapy for H. pylori in Africa had eradication rates that could be considered effective even in the lowest reported cases. This study demonstrates the necessity to optimize current H. pylori treatment regimens in each country, taking into account the antibiotic susceptibility of the bacteria.
Phytoefficacy of Eicchornia crassipes (Mart.)Solms-Laub for aqua-remediation of hexavalent chromium – a novel in situ phytoremediation approach for abatement of chromium pollution in South Kaliapani chromite mine effluent of Odisha, India
Authors: Mohanty Monalisa , Pattnaik Mousumi , Mishra Aruna K. , Patra Hemanta K
Published: November 2022

A huge quantity of toxic hexavalent chromium (Cr-VI or Cr6+) was released into the environment through mine effluent at the South Kaliapani chromite mining area during different mining activities. The present in situ bioremediation approach was conducted to assess the remediation potential of a well-known aquatic weed water hyacinth (Eichhornia crassipes (Mart.) Solms-Laub) for attenuating Cr(VI) from mine wastewater. The study correlates the bio-concentration factors (BCF) of Cr with the reduction percentage. The percent reduction of Cr content in mine effluent was maximum (53.5%) at 100 days after treatment (DAT) followed by 40.7% at 75 DAT after passage through 2,000 sq. ft. area covering four water hyacinths populated (1350 plants) ponds. Reduction in Cr content if OMC discharged mine effluent varies with plant age as well as with the distance of passage. A constant increase in root biomass was recorded with increased passage distance and days of treatment of contaminated mine effluent. The plants could not survive after 125 days of treatment but could show an increasing trend in shoot biomass up to 100 DAT. After 75 days of treatment, it was noted that Cr concentration in roots decreased from 200 to 148 ppm and from 76 to 21 ppm in shoots after passage through the 2000 sq. ft area at 100 (DAT). Water hyacinth roots exhibit maximum Cr bioaccumulation at 75 DAT whereas this was highest in shoots at 100 DAT.
Rehabilitation for revision total knee replacement: Survey of current service provision and systematic review
Authors: Omar Ifrah , Kunutsor Setor , Bertram Wendy , Moore Andrew , Blom Ashley W , Lenguerrand Erik , Whitehouse Michael R , Wylde Vikki
Published: November 2022

Background
Approximately 6,000 revision total knee replacements are performed annually in the National Health Service. Revision total knee replacement is a major operation with a long recovery period and many patients report suboptimal outcomes. Rehabilitation has the potential to improve outcomes after revision total knee replacement. The aim of this study was to understand current provision of rehabilitation for revision total knee replacement in England and evaluate the existing evidence.
Methods
A national survey of education and rehabilitation provision for patients receiving revision total knee replacement was completed by physiotherapy staff at 22 hospitals across England. A systematic review was undertaken to identify studies evaluating rehabilitation programmes for revision joint replacement. Searches were conducted in MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane databases from inception to 15th June 2022. Studies were included if they evaluated post-operative rehabilitation interventions for adults undergoing revision joint replacement for any indication. Screening, data extraction and assessment of methodological quality were undertaken by two reviewers.
Results
Survey: Pre-operative education was provided in most hospitals, which predominately involved a single session delivered by a multidisciplinary team. Inpatient physiotherapy commonly commenced on post-operative day 1 and was provided twice daily, with most hospitals also providing occupational therapy. Rehabilitation was often provided in the first four weeks after hospital discharge, either in an outpatient, community or home setting. In most hospitals, the education and rehabilitation provided to patients receiving revision total knee replacement was the same as that provided to patients undergoing primary total knee replacement.
Systematic review: Of the 1,445 articles identified in the searches, three retrospective cohort studies based on hospital records review were eligible for inclusion. The studies evaluated intensive rehabilitation programmes delivered in an inpatient hospital setting, consisting of 2-3 hours of daily supervised group or individual physiotherapy, with additional occupational therapy in one study. All three studies reported improvement in functional outcomes for patients undergoing rehabilitation after revision total knee replacement.
Conclusion
This study identified the need for future research to develop and evaluate tailored rehabilitation to optimise patient outcomes following revision total knee replacement.
Ablation of SAMD1 in Mice Causes Failure of Embryonic Blood Vessel Maturation and Embryonic Lethality
Authors: Campbell Bruce , Weber Lisa Marie , Engle Sandra J. , Ozolinš Terence R.S. , Bourassa Patricia , Aiello Robert , Liefke Robert
Published: November 2022

SAM domain-containing protein 1 (SAMD1) has been implicated in atherosclerosis, as well as in chromatin and transcriptional regulation, suggesting a versatile and complex biological function. However, its role at an organismal level is currently unknown. Here, we generated SAMD1−/− and SAMD1+/− mice to explore the role of SAMD1 during mouse embryogenesis. Homozygous loss of SAMD1 was embryonic lethal with no living animals seen after embryonic day 18.5. At embryonic day 14.5, organs were degrading and/or incompletely developed and no functional blood vessels were observed. Sparse red blood cells were scattered and pooled, primarily near the embryo surface. Some embryos had malformed heads and brains at embryonic day 15.5. In vitro, SAMD1 absence impaired neuronal differentiation processes. Heterozygous SAMD1 knockout mice were born alive, but postnatal genotyping showed a reduced ability of these mice to thrive, possibly due to altered steroidogenesis. In summary, the characterization of SAMD1 knockout mice suggests a critical role of SAMD1 during developmental processes in multiple organs and tissues.
Effects of different sulfur compounds on the distribution characteristics of subcellular lead content in Arabis alpina L .var. parviflora Franch under lead stress
Authors: Xu Cui , Qin Li , Zu Yanqun , Li Yuan , Wang Jixiu
Published: November 2022

Sulfur plays a vital role in the phytoremediation of lead-contaminated soil. Effects of different sulfur forms (S0, Na2S, Na2SO4) on Pb absorption in hyperaccumulator Arabis alpina L. var. parviflora Franch were studied by soil culture pot experiment. The subcellular sulfur and lead enrichment characteristics in A. alpina were studied by adding sulfur in different forms and concentrations (0, 75, and 150 mg/kg) to Pb-contaminated soil. The results showed that the root and shoot biomass increased by 1.94 times under Na2S and Na2SO4 treatment, and the root-shoot ratio of A. alpine increased 1.62 times under three forms of sulfur treatments, compared with the control. Sulfur content in cell walls and soluble fractions of root and shoot of A. alpine significantly increased 3.35 ~ 5.75 times and decreased 5.85 and 9.28 times in the organelles under Na2SO4 treatment. Meanwhile, Pb content in the root and shoot cell walls of A. alpine significantly increased by 3.54 and 2.75 times, respectively. Pb content in the shoot soluble fraction significantly increased by 3.46 times, and the root organelle and soluble fraction significantly decreased by 2.72 and 2.46 times, respectively, while it significantly reduced by 3.78 times in the shoot organelle. Different forms and concentrations of sulfur had no regularity in the effect of Pb and sulfur content in the subcellular components of A. alpina, but the bioconcentration and translocation factors of A. alpina increased compared with the control. Under different concentrations of Na2SO4, there was a significant positive correlation between the contents of sulfur and Pb in the subcellular components of the root of A. alpina (P < 0.05). These results indicate that sulfur application can enhance the Pb resistance of A. alpina by strengthening the cell wall fixation and compartmentalization of vacuoles.
Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer
Authors: liu pengyu , Wang Wenxuan , Wang Fei , Fan Jiaqi , Guo Jinan , Wu Tao , Lu Dongliang , Zhou Qingchun , liu Zhuohao , Wang Yuliang , Shang Zhiqun , Chan Franky Leung , Yang Wei , li Xin , Zhao Shanchao , Zheng Qingyou , Wang Fei , Wu Dinglan
Published: November 2022

Background: Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. The functional role of some specific exosome biomarkers in the progression of CRPC were also investigated.
Methods: Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models.
Results: Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic [ROC] value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis.
Conclusion: Integration of proteomics and metabolomics data yielded proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression.
Using Phenotypic Data from the Electronic Health Record (EHR) to Predict Discharge Destination: A Predictive Model based on A Single-Center Retrospective Cohort
Authors: Bhatia Monisha C. , Wanderer Jonathan P. , Li Gen , Ehrenfeld Jesse M. , Vasilevskis Eduard
Published: November 2022

Background: Timely discharge to post-acute care (PAC) settings, such as skilled nursing facilities, requires early identification of eligible patients. We sought to develop and internally validate a model which predicts a patient’s likelihood of requiring PAC based on information obtained in the first 24 hours of hospitalization.
Methods: This was a retrospective observational cohort study. We collected clinical data and commonly used nursing assessments from the electronic health record (EHR) for all adult inpatient admissions at our academic tertiary care center from September 1, 2017 to August 1, 2018 We performed a multivariable logistic regression to derive the model from the derivation cohort of the available records. A secondary analysis was then conducted to evaluate the capability of the model to predict discharge destination on an internal validation cohort.
Results: Age (adjusted odds ratio (AOR), 1.04 [per year]; 95% Confidence Interval (CI), 1.03 to 1.04), admission to the intensive care unit (AOR, 1.51; 95% CI, 1.27 to 1.79), admission from the emergency department (AOR, 1.53; 95% CI, 1.31 to 1.78), taking more home medications (AOR, 1.06 [per medication count increase]; 95% CI 1.05 to 1.07), and higher Morse fall risk scores at admission (AOR, 1.03 [per unit increase]; 95% CI 1.02 to 1.03) were independently associated with higher likelihood of being discharged to PAC facility. The c-statistic of the model derived from the primary analysis was 0.875, and the model predicted the correct discharge destination in 81.2% of the validation cases.
Conclusions: A model that utilizes clinical factors and risk assessments has excellent model performance in predicting discharge to a PAC facility.
Multi-strategy approach towards optimization of maturation and germination in radiata pine somatic embryogenesis.
Authors: Castander-Olarieta Ander , Montalbán Itziar Aurora , Moncaleán Paloma
Published: November 2022

Somatic embryogenesis is a powerful technique for forestry improvement programs when implementing multi-varietal forestry. However, it still faces some bottlenecks to be efficient in many forestry species. In this work we have studied the effect of some physico-chemical modifications at proliferation, maturation and germination stages of Pinus radiata D. Don somatic embryogenesis, as well as the impact of this modifications on plant conversion, survival, and on the morphology and biochemical profile (carbohydrate and amino acid analysis) of the resulting plantlets. Given the long culture period needed for maturation and germination in radiata pine, an increase of the plant yield could be very beneficial for its commercial application. A preculture of 14 days without plant growth regulators before maturation seems to be beneficial for the development and germination of somatic embryos. Before germination, a cold storage at 4ºC had no detrimental effect and even increased plant conversion in some embryogenic cell lines. During germination, supplementation of the culture medium with glutamine and a reduction of the sucrose content can improve the greenhouse acclimatization of the plants. Similarly, germinants were demonstrated to be influenced by the light source: fluorescent light enhanced root formation, whereas blue LED light increased the shoot height of somatic plants. Moreover, the highest plants showed lower contents of arginine, asparagine and total carbohydrates.
Phage tRNAs evade tRNA-targeting host defenses through anticodon loop mutations
Authors: Berg Daan F. van den , Steen Baltus A. van der , Costa Ana Rita , Brouns Stan J. J.
Published: November 2022

tRNAs in bacteriophage genomes are widespread across bacterial genera, but their exact function has remained unclear for more than 50 years. Multiple hypotheses have been proposed, with the most established being codon compensation, where codons more rarely used by the host but necessary for the phage are supplemented by tRNAs encoded by the phage. Here, we combine several observations and propose a new hypothesis that phage-encoded tRNAs are a means to counteract the tRNA-depleting strategies of the host to defend from viral infection. Based on mutational patterns of tRNA anticodon loops, we predict that phage tRNAs are insensitive to the host tRNAses. For tRNAs targeted in the anticodon itself, we observe phage counter-selection of targeted isoacceptor tRNAs, further supporting the hypothesis that phage tRNAs are selected to be insensitive to host anticodon nucleases. Importance The presence of tRNAs in phages was discovered more than 50 years ago and their function has been debated ever since. Here, we propose that phage tRNAs counteract the tRNAse activities of the host, which may represent a depletion strategy of essential cellular components to stop translation and thereby phage infection.
Effectiveness and toxicity of re-irradiation after breast conserving surgery for recurrent or new primary breast cancer: a multi-institutional study
Authors: Abeloos Camille Hardy , Xiao Julie , Oh Cheongeun , Barbee David , Perez Carmen A , Oratz Ruth , Schnabel Freya , Axelrod Deborah , Guth Amber , Braunstein Lior , Khan Atif , Choi Isabelle , Gerber Naamit
Published: November 2022

Purpose:
Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This multi-institutional study reports safety and efficacy among women treated with repeat BCS and reRT.
Methods and Materials:
Patients who underwent repeat BCS followed by RT from 2015–2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan Meier estimates were used to evaluate overall survival (OS), distant metastasis free survival (DMFS) and locoregional recurrence-free survival (LR-RFS).
Results:
Sixty-six patients were reviewed with median follow-up of 16 months (range: 3–60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5Gy BID; 27% with 1.8Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%.
Conclusion:
In this multi-institutional series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens.
Molecular phylogeny of mega-diverse Carabus attests late Miocene evolution of alpine environments in the Himalayan-Tibetan Orogen
Authors: Schmidt Joachim , Opgenoorth Lars , Mao Kangshan , Baniya Chitra B. , Hofmann Sylvia
Published: November 2022

The timing, sequence, and scale of uplift of the Himalayan-Tibetan Orogen (HTO) are controversially debated. Many geoscientific studies assume paleoelevations close to present-day elevations and the existence of alpine environments across the HTO already in the late Paleogene, contradicting fossil data. Using molecular genetic data of ground beetles we reconstruct the paleoenvironmental history of the HTO, focusing on its southern margin (Himalayas, South Tibet). Based on a comprehensive sampling of extratropical Carabus, and ~ 10,000 bp of mitochondrial and nuclear DNA we applied Bayesian and Maximum likelihood phylogenetics. We show that Carabus arrived in the HTO at the Oligocene-Miocene boundary. During the early Miocene, five lineages diversified in different parts of the HTO, initially in its southern center and on its eastern margin. Evolution of subalpine-alpine taxa occurred during the late Miocene. There were apparently no habitats for Carabus before the late Oligocene. Until the Late Oligocene elevations must have been low throughout the HTO. Temperate forests emerged in South Tibet in the late Oligocene at the earliest. Alpine environments developed in the HTO from the late Miocene and, in large scale, during the Pliocene-Quaternary. Findings are consistent with fossil records but contrast with uplift models recovered from stable isotope paleoaltimetry.
Experimental Study on Impermeability of Loess Liner Mixed with Bentonite-HDTMA
Authors: Zhang Ming , Dongke Hu , Shaoyu Pan , Guozhou Chen
Published: November 2022

Permeability tests are performed by using the flexible wall permeameter to study the influence of bentonite-HDTMA on the permeability performance of loess as a lining material in landfills. Results show, the impermeability of compacted Malan loess in the middle and lower reaches of the Yellow River in China does not meet the code requirement as a landfill liner. The permeability of Malan loess mixed with more than 10% bentonite ratio is less than 1.0 ×10− 7 cm·s− 1. The permeability of modified loess increases slightly after mixing a small amount of HDTMA. The impermeability of loess mixed with some bentonite-HDTMA ratio still meet the requirement of China code. The SEMs show that the bentonite clay particle can fill the pores between loess coarse particles and improve the impermeability performance of the material. The HDTMA may destroy the soil aggregate structure and increase the soil permeate channel. The digital photos show that HDTMA can effectively resist the development of soil macro-cracks induced by wetting-drying cycles, better for liner to maintain good impermeability. On this basis, the relationship between the hydraulic conductivity of bentonite-HDTMA modified loess and dry density is constructed. From this study, loess can be used as a lining material for landfills, when mixed with bentonite/HDTMA at ratios of 10%/0% or 14%/2%.
Risk factors of pelvic organ prolapse: an ultrasound based retrospective study
Authors: Fang Jianqi , Zhang Ronghua , Weng Yilin , Lin Yang , Chen Yi , Wang Miao , Lu Yao , Lin Juan , Cai Shuhe
Published: November 2022

Objective: To analyse the risk factors of pelvic organ prolapse in postpartum period.
Methods: This retrospective study included 4965 participants who visited Fujian Maternity and Child Health Hospital from December 2019 to March 2022. All participants were assessed by medical professionals for general information and Pelvic floor 3D ultrasound.
Results: Logistic regression analysis showed that age and body mass index had a negative impact on cystocele, perineal hypermobility, hiatal ballooning, rectocele (BMI only), levator avulsion (age only). In contrast, education was a protective factor of uterine prolapse, perineal hypermobility, and hiatal ballooning. Multiparas were more likely to develop cystocele, while multiparas were less likely to get levator avulsion. Vaginal delivery was a risk factor of most of pelvic floor injury, including cystocele, uterine prolapse, perineal hypermobility, hiatal ballooning, and levator avulsion. Similarly, neonatal weight was also a negative factor of levator avulsion. No specific association was found between these factors and anterior, middle and posterior pelvic prolapse.
Conclusions: We found that age, body mass index, parity, vaginal delivery, and neonatal weight were the risk factors of pelvic organ prolapse or levator avulsion. But education and parity was the protective factor of pelvic organ prolapse and levator avulsion respectively.
Biomechanical investigation of long spinal fusion models using three-dimensional finite element analysis
Authors: Oku Norihiro , Demura Satoru , Tawara Daisuke , Kato Satoshi , Shinmura Kazuya , Yokogawa Noriaki , Yonezawa Noritaka , Shimizu Takaki , Kitagawa Ryo , Handa Makoto , Ryohei Annen , Tsuchiya Hiroyuki
Published: November 2022

Background: This study represents the first finite element (FE) analysis of long-instrumented spinal fusion from the thoracic vertebrae to the pelvis in the context of adult spinal deformity (ASD) with osteoporosis. We aimed to evaluate the mechanical stress in long spinal instrumentation for models that differ in terms of spinal balance, fusion length, and implant type.
Methods: In this three-dimensional FE analysis, FE models were developed based on computed tomography images from a patient with osteoporosis. Mechanical stress was compared for three different sagittal vertical axes (SVAs) (0, 50, and 100 mm), two different fusion lengths (from the pelvis to the second [T2-S2AI] or 10th thoracic vertebra [T10-S2AI]), and two different types of implants (pedicle screw or transverse hook) in the upper instrumented vertebra (UIV). We created 12 models based on combinations of these conditions.
Results: The overall mechanical stress was 3.1 times higher on the vertebrae and 3.9 times higher on implants for the 50-mm SVA models than that for the 0-mm SVA models. Similarly, the values were 5.0 times higher on the vertebrae and 6.9 times higher on implants for the 100-mm SVA models than that for the 0-mm SVA models. Higher SVA was associated with greater stress below the fourth lumbar vertebrae and implants. In the T2-S2AI models, the peaks of vertebral stress were observed at the UIV, at the apex of kyphosis, and below the lower lumbar spine. In the T10-S2AI models, the peaks of mechanical stress were observed at the UIV and below the lower lumbar region. Mechanical stress in the UIV was also higher for the screw models than for the hook models.
Conclusion: Higher SVA is associated with greater mechanical stress on the vertebrae and implants. Mechanical stress on the UIV is greater for the T10-S2AI models than for the T2-S2AI models. Using transverse hooks instead of screws at the UIV may reduce mechanical stress in patients with osteoporosis.
Highly Robust Electronic Skin based on Carbon Nanomaterials and SEBS for Object Recognition of Robot Hand: Proximity and Pressure Sensing Array
Authors: Sang Shengbo , Zhang Qiang , Zhang Rui , Lv Bohan , Chen Zhihong , Zhang Fan , Ji Chao , Zhang Chunyan , Fu Zhiyuan , Yang Kun
Published: November 2022

When robot hands work in a com plex environment, it not only needs to sense the objects in contact, but also needs to respond to remote events before physical contact. In this way, robot hands can make prediction, so as to better adapt to the complex environment. In this paper, we have designed a flexible sensor array, which integrates piezoresistive sensor and capacitive sensor for detecting pressure and proximity signals simultaneously. Piezoresistive sensors can detect pressure signals, and capacitive sensors detect pressure and proximity signals. The sensors are arranged in a patterned array and installed on the robot hand to help the robot hand detect the distance and direction of approaching objects, as well as the shape and size of the grasped objects. To avoid mechanical mismatch, piezoresistive sensors and capacitive sensors are fabricated by the same flexible materials. In addition, after extreme pressure tests, the sensors can still work normally, so as to ensure that the robot hands can work normally in complex environments. We also combined the detected signal with machine learning, so that the robot can accurately identify objects of different shapes. In the fruit recognition test, the recognition accuracy reached 90%.
Efficient Multi-Label Attribute Classification and Recognition of Vaginitis Bacteria Based on Deep Learning and model fine-tuning
Authors: Wu Duidi , Huang Haiqing , Zhang Shuo , Qi Jin , Wang Dong , Hu Jie
Published: November 2022

Bacterial vaginosis (BV) is the most common gynecological complaint affecting the health of a large percentage of women worldwide. Traditional manual microscopy methods are expensive and time-consuming, to improve accuracy and efficiency, automated bacterial identification devices with detection intelligence algorithms are urgently needed. We propose a Fine-tuned SmallerVGG (FTS-VGG) convolutional network model-based multi-label classification method for bacteria. Comparison experiments were deployed on several basic backbone networks, including transfer learning on pre-trained VGG19, demonstrating that the proposed method achieves the advantages of being lighter, faster, more accurate, and more efficient. Due to the high cost of time and expertise of experienced clinicians, we use random erasing for data augmentation to address the challenge of dataset collection and annotation, experiments demonstrate its robustness to occlusion. The proposed method has theoretical and practical implications and the potential to be widely extended to other microscopic imaging applications.
Generalized Impedance-Based Transient Analysis for Multi-branched Pipeline Systems
Authors: Kim Sanghyun
Published: November 2022

Transient analysis of multi-branched pipeline systems is generalized by the development of an impedance method. Both open and closed boundaries of branched pipeline elements were implemented in the analytical development of a reservoir pipeline multi-branched pipeline valve systems, in which the performances of the impedance and transient responses were compared with those of conventional approaches. To address realistic boundary conditions along the branched element, a partially-opened boundary condition was implemented in the impedance expression of the branched pipeline system. The performance of the generalized multi-branch impedance was tested on a large water supply system with 10 minor branches from an actual system. The impact of the designated branches was evaluated using the root-mean-square error (RMSE)of the pressure and the difference in the energy spectral density between the original and skeletonized systems. Combinations of multiple branches for certain flow conditions was identified based on the holistic response for both the frequency and time domains. The proposed method can be a useful alternative to effectively address the skeletonization issue for pipeline systems with multi-branched pipeline elements.
Comprehensive Analysis of PHGDH for Predicting Prognosis and Immunotherapy Response in Patients with Endometrial Carcinoma
Authors: Zhang He , Kong Weimin , Zhao Xiaoling , Xie Yunkai , Luo Dan , Chen Shuning
Published: November 2022

Background: PHGDH (Phosphoglycerate Dehydrogenase) is the first branch enzyme in the serine biosynthetic pathway and plays a vital role in several cancers. However, little is known about the clinical significance of PHGDH in endometrial cancer.
Methods: Clinicopathological data of endometrial cancer were downloaded from the Cancer Genome Atlas database (TCGA). First, the expression of PHGDH in pan-cancer was investigated, as well as the expression and prognostic value of PHGDH in endometrial cancer. The effect of PHGDH expression on the prognosis of endometrial cancer was analyzed by Kaplan-Meier plotter and Cox regression. The relationship between PHGDH expression and clinical characteristics of endometrial cancer was investigated by logistic regression. Receiver operating characteristic (ROC) curves and nomograms were developed. Possible cellular mechanisms were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the Gene Ontology (GO), and gene set enrichment analysis (GSEA). Finally, TIMER and CIBERSORT were used to analyze the relationship between PHGDH expression and immune infiltration. CellMinerTM was used to analyze the drug sensitivity of PHGDH.
Results: The results showed that PHGDH expression was significantly higher in endometrial cancer tissues than in normal tissues at mRNA and protein levels. Kaplan-Meier survival curves showed that patients in the high expression group had shorter overall survival (OS) and disease free survival (DFS) than patients in the low PHGDH expression group. Multifactorial COX regression analysis further supported that high PHGDH expression was an independent risk factor associated with prognosis in patients with endometrial cancer. The results showed estrogen response, mTOR, K-RAS, and epithelial mesenchymal transition (EMT) were differentially elevated in the high-expression group of the PHGDH group. CIBERSORT analysis showed that PHGDH expression is related to the infiltration of multiple immune cells. When PHGDH is highly expressed, the number of CD8+T cells decreases.
Conclusions: PHGDH plays a vital role in the development of endometrial cancer, which is related to tumor immune infiltration, and can be used as an independent diagnostic and prognostic marker for endometrial cancer.