bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort
Authors: Bonney Asha , Brodersen John , Siersma Volkert , See Katharine , Marshall Henry M. , Steinfort Daniel , Irving Louis , Lin Linda , Li Jiashi , Pang Siyuan , Fogarty Paul , Brims Fraser , McWilliams Annette , Stone Emily , Lam Stephen , Fong Kwun M. , Manser Renee
Published: January 2024

Background

Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST).

Methods

The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results.

Results

Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results.

Conclusion

COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program.

Trial registration

NCT02871856.
Targeting the macrophage immunocheckpoint: a novel insight into solid tumor immunotherapy
Authors: Zhou Bei , Yang Yan , Kang Yan , Hou Jingjing , Yang Yun
Published: January 2024

Tumor immunotherapy, which targets immune checkpoints, presents a promising strategy for the treatment of various cancer types. However, current clinical data indicate challenges in its application to solid tumors. Recent studies have revealed a significant correlation between the degree of immune response in immunotherapy and the tumor microenvironment, particularly with regard to tumor-infiltrating immune cells. Among these immune cells, macrophages, a critical component, are playing an increasingly vital role in tumor immunotherapy. This review focuses on elucidating the role of macrophages within solid tumors and provides an overview of the progress in immunotherapy approaches centered around modulating macrophage responses through various immune factors.
Non-bone-derived exosomes: a new perspective on regulators of bone homeostasis
Authors: Wang Ping , Shao Wenkai , Li Zilin , Wang Bo , Lv Xiao , Huang Yiyao , Feng Yong
Published: January 2024

Accumulating evidence indicates that exosomes help to regulate bone homeostasis. The roles of bone-derived exosomes have been well-described; however, recent studies have shown that some non-bone-derived exosomes have better bone targeting ability than bone-derived exosomes and that their performance as a drug delivery vehicle for regulating bone homeostasis may be better than that of bone-derived exosomes, and the sources of non-bone-derived exosomes are more extensive and can thus be better for clinical needs. Here, we sort non-bone-derived exosomes and describe their composition and biogenesis. Their roles and specific mechanisms in bone homeostasis and bone-related diseases are also discussed. Furthermore, we reveal obstacles to current research and future challenges in the practical application of exosomes, and we provide potential strategies for more effective application of exosomes for the regulation of bone homeostasis and the treatment of bone-related diseases.
Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes
Authors: Gutiérrez-Ruíz Stephany Celeste , Cortes Hernán , González-Torres Maykel , Almarhoon Zainab M. , Gürer Eda Sönmez , Sharifi-Rad Javad , Leyva-Gómez Gerardo
Published: January 2024

Background

Polymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration.

Results

Chitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8–56.2 mV values, while the dialyzed samples led to smaller particle sizes (152–184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process.

Conclusions

In Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis.
Antibody selection strategies and their impact in predicting clinical malaria based on multi-sera data
Authors: Fonseca André , Spytek Mikolaj , Biecek Przemysław , Cordeiro Clara , Sepúlveda Nuno
Published: January 2024

Background

Nowadays, the chance of discovering the best antibody candidates for predicting clinical malaria has notably increased due to the availability of multi-sera data. The analysis of these data is typically divided into a feature selection phase followed by a predictive one where several models are constructed for predicting the outcome of interest. A key question in the analysis is to determine which antibodies  should be included in the predictive stage and whether they should be included in the original or a transformed scale (i.e. binary/dichotomized).

Methods

To answer this question, we developed three approaches for antibody selection in the context of predicting clinical malaria: (i) a basic and simple approach based on selecting antibodies via the nonparametric Mann–Whitney-Wilcoxon test; (ii) an optimal dychotomizationdichotomization approach where each antibody was selected according to the optimal cut-off via maximization of the chi-squared (χ2) statistic for two-way tables; (iii) a hybrid parametric/non-parametric approach that integrates Box-Cox transformation followed by a t-test, together with the use of finite mixture models and the Mann–Whitney-Wilcoxon test as a last resort. We illustrated the application of these three approaches with published serological data of 36 Plasmodium falciparum antigens for predicting clinical malaria in 121 Kenyan children. The predictive analysis was based on a Super Learner where predictions from multiple classifiers including the Random Forest were pooled together.

Results

Our results led to almost similar areas under the Receiver Operating Characteristic curves of 0.72 (95% CI = [0.62, 0.82]), 0.80 (95% CI = [0.71, 0.89]), 0.79 (95% CI = [0.7, 0.88]) for the simple, dichotomization and hybrid approaches, respectively. These approaches were based on 6, 20, and 16 antibodies, respectively.

Conclusions

The three feature selection strategies provided a better predictive performance of the outcome when compared to the previous results relying on Random Forest including all the 36 antibodies (AUC = 0.68, 95% CI = [0.57;0.79]). Given the similar predictive performance, we recommended that the three strategies should be used in conjunction in the same data set and selected according to their complexity.
Gene panel selection for targeted spatial transcriptomics
Authors: Zhang Yida , Petukhov Viktor , Biederstedt Evan , Que Richard , Zhang Kun , Kharchenko Peter V.
Published: January 2024

Targeted spatial transcriptomics hold particular promise in analyzing complex tissues. Most such methods, however, measure only a limited panel of transcripts, which need to be selected in advance to inform on the cell types or processes being studied. A limitation of existing gene selection methods is their reliance on scRNA-seq data, ignoring platform effects between technologies. Here we describe gpsFISH, a computational method performing gene selection through optimizing detection of known cell types. By modeling and adjusting for platform effects, gpsFISH outperforms other methods. Furthermore, gpsFISH can incorporate cell type hierarchies and custom gene preferences to accommodate diverse design requirements.
An intricate vagina penetrating injury with a 22 cm cassava stick in situ for 6 months: a case report
Authors: Irumba Charles , Baragaine Justus , Obore Susan , Mwanje Haruna , Nteziyaremye Julius
Published: January 2024

Background

Trauma remains one of the major causes of morbidity and mortality and a threat to attainment of sustainable development goal 11. Genital urinary trauma is reported in about 10% of patients presenting with trauma worldwide, and in about 6.6% of patients in Sub-Saharan Africa. If not careful enough, one may miss the foreign body in the vagina and this may be associated with morbidity, and although  rare, mortality.

Case presentation

We report a case of a 7-year-old Black Ugandan that had suffered vagina trauma 6 months prior to presentation at our facility and presented with chronic vagina pus discharge for 6 months. Prior examinations had failed to recognize the foreign body and so did the two abdominal pelvic ultrasound scans. During examination under anesthesia, we were able to locate the cassava stick that had caused penetrating vagina injury and we were able to dislodge it. It was a blunt cassava stick with length of 22 cm and diameter of 2 cm. Although it had gone through the peritoneal cavity, we did not do a laparotomy.

Conclusion

This case emphasizes the need for a thorough vaginal exam including the need to do it under anesthesia with good lighting even when ultrasound scan findings are normal. It presents an opportunity for one to manage penetrating peritoneal injury without a laparotomy in highly selected cases. Gynecologists should be keen as well to rule out child molestation.
Bias-free estimation of the covariance function and the power spectral density from data with missing samples including extended data gaps
Authors: Damaschke Nils , Kühn Volker , Nobach Holger
Published: January 2024

Nonparametric estimation of the covariance function and the power spectral density of uniformly spaced data from stationary stochastic processes with missing samples is investigated. Several common methods are tested for their systematic and random errors under the condition of variations in the distribution of the missing samples. In addition to random and independent outliers, the influence of longer and hence correlated data gaps on the performance of the various estimators is also investigated. The aim is to construct a bias-free estimation routine for the covariance function and the power spectral density from stationary stochastic processes under the condition of missing samples with an optimum use of the available information in terms of low estimation variance and mean square error, and that independent of the spectral composition of the data gaps. The proposed procedure is a combination of three methods that allow bias-free estimation of the desired statistical functions with efficient use of the available information: weighted averaging over valid samples, derivation of the covariance estimate for the entire data set and restriction of the domain of the covariance function in a post-processing step, and appropriate correction of the covariance estimate after removal of the estimated mean value. The procedures abstain from interpolation of missing samples as well as block subdivision. Spectral estimates are obtained from covariance functions and vice versa using Wiener–Khinchin’s theorem.
Prognostic impact of oral microbiome on survival of malignancies: a systematic review and meta-analysis
Authors: Li Shuluan , Wang Tianyu , Ren Ya , Liu Zhou , Gao Jidong , Guo Zhi
Published: January 2024

Background

Recent studies have shown that there exists a significant correlation between oral microbiome and the occurrence of malignancies. However, the prognostic significance of oral microbiome for cancer patients remains unclear. The purpose of this meta-analysis is to evaluate the impact of oral microbiome on the survival of patients with malignant neoplasms.

Methods

We conducted a thorough literature search of PubMed, Embase, and Cochrane Library databases until September 2022. The hazard ratio (HR) with a corresponding 95% confidence interval (CI) was analyzed using Review Manager 5.4 software for survival outcomes, including overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and disease-free survival (DFS).

Results

A total of 15 studies, covering 5191 samples with various types of cancers, were selected based on specified inclusion and exclusion criteria. In both univariate and multivariate analysis, patients with low diversity of the oral microbiome, or those with Fusobacterium-high/positive, or P. gingivalis positive in cancer tissue displayed poorer OS (univariate HR = 1.74; 95% CI 1.15–2.62; P = 0.009; multivariate HR = 1.56; 95% CI 1.07–2.27; P = 0.02), DSS (univariate HR = 2.06; 95% CI 1.50–2.84; P < 0.00001; multivariate HR = 1.80; 95% CI 1.48–2.20; P < 0.00001), and PFS/DFS (univariate HR = 2.00; 95% CI 1.12–3.58; P = 0.002; multivariate HR = 1.78; 95% CI 1.05–3.02; P = 0.003). Subgroup analysis revealed that Fusobacterium positive or high abundance in cancer tissues was associated with poor OS in multivariate analysis but had no statistical differences in PFS or DFS in univariate and multivariate analysis. Additionally, P. gingivalis positive in cancer tissue was also associated with worse OS.

Conclusions

Our meta-analysis suggests that the composition of the oral microbiome may play a significant role in predicting survival outcomes for cancer patients.
Weighted estimates for fractional bilinear Hardy operators on variable exponent Morrey–Herz space
Authors: Asim Muhammad , Ayoob Irshad , Hussain Amjad , Mlaiki Nabil
Published: January 2024

In this article, we analyze the boundedness for the fractional bilinear Hardy operators on variable exponent weighted Morrey–Herz spaces ${M\dot{K}^{\alpha (\cdot ),\lambda}_{q,p(\cdot)}(w)}$
M

K
˙

q
,
p
(
⋅
)

α
(
⋅
)
,
λ

(
w
)
. Similar estimates are obtained for their commutators when the symbol functions belong to BMO space with variable exponents.
Informal sale of antibiotics in Guatemalan convenience stores before and after implementation of federal antibiotic dispensing legislation
Authors: Rojop N. , Moreno P. , Grajeda L. , Romero J. , Reynoso L. , Muñoz E. , Palmer G. H. , Cordón-Rosales C. , Call D. R. , Ramay B. M.
Published: January 2024

Background

Convenience stores in Guatemala provide essential consumer goods in communities, but many dispense antibiotics illegally. Federal legislation, passed in August of 2019, requires prescriptions for antibiotic purchase at pharmacies but it is unclear if this legislation is enforced or if it has any impact on unlawful sales of antibiotics.

Methods

To determine if antibiotic availability changed in convenience stores, we carried out a repeated measures study collecting antibiotic availability data before and after implementation of the dispensing regulation.

Results

There was no statistical difference in the proportion of convenience stores that sold antibiotics before and after antibiotic regulations [66.6% (295/443) and 66.7% (323/484), respectively, P>0.96], nor in the number of stores selling amoxicillin [55.5% (246/443) and 52.3% (253/484), respectively, P>0.96], but fewer stores (20%) sold tetracycline capsules after regulation was passed (P<0.05). For stores visited both before and after passage of legislation (n=157), 15% stopped selling antibiotics while 25% started selling antibiotics. Antibiotics from convenience stores were reportedly sold for use in people and animals.

Conclusions

Antibiotics remain widely available in convenience stores consistent with no significant change in the informal sector after implementation of prescription requirements for pharmacies. Importantly, effects from regulatory change could have been masked by potential changes in antibiotic use during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic.
Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling
Authors: Tan Ximin , Kong Deguang , Tao Zhuoli , Cheng Fangling , Zhang Baoyuan , Wang Zaiqi , Mei Qi , Chen Chuang , Wu Kongming
Published: January 2024

Background

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking effective targeted therapies, necessitating innovative treatment approaches. While targeting ROS proto-oncogene 1 (ROS1) with crizotinib has shown promise, resistance remains a limitation. Recent evidence links focal adhesion kinase (FAK) to drug resistance, prompting our study to assess the combined impact of FAK inhibitor IN10018 and crizotinib in TNBC and elucidate the underlying mechanisms.

Methods

We employed the Timer database to analyze FAK and ROS1 mRNA levels in TNBC and adjacent normal tissues. Furthermore, we investigated the correlation between FAK, ROS1, and TNBC clinical prognosis using the GSE database. We conducted various in vitro assays, including cell viability, colony formation, flow cytometry, EdU assays, and western blotting. Additionally, TNBC xenograft and human TNBC organoid models were established to assess the combined therapy’s efficacy. To comprehensively understand the synergistic anti-tumor mechanisms, we utilized multiple techniques, such as RNA sequencing, immunofluorescence, cell flow cytometry, C11-BODIPY staining, MDA assay, and GSH assay.

Results

The Timer database revealed higher levels of FAK and ROS1 in TNBC tissues compared to normal tissues. Analysis of GEO databases indicated that patients with high FAK and ROS1 expression had the poorest prognosis. Western blotting confirmed increased p-FAK expression in crizotinib-resistant TNBC cells. In vitro experiments showed that the combination therapy down-regulated cyclin B1, p-Cdc2, and Bcl2 while up-regulating BAX, cleaved-Caspase-3, cleaved-Caspase-9, and cleaved PARP. In TNBC xenograft models, the tumor volume in the combination therapy group was 73% smaller compared to the control group (p < 0.0001). Additionally, the combination therapy resulted in a 70% reduction in cell viability in human TNBC organoid models (p < 0.0001). RNA sequencing analysis of TNBC cells and xenograft tumor tissues highlighted enrichment in oxidative stress, glutathione metabolism, and p53 pathways. The combined group displayed a fivefold rise in the reactive oxygen species level, a 69% decrease in the GSH/GSSG ratio, and a sixfold increase in the lipid peroxidation in comparison to the control group. Western blotting demonstrated p53 upregulation and SCL7A11 and GPX4 downregulation in the combination group. The addition of a p53 inhibitor reversed these effects.

Conclusion

Our study demonstrates that the combination of IN10018 and crizotinib shows synergistic antitumor effects in TNBC. Mechanistically, this combination inhibits cell proliferation, enhances apoptosis, and induces ferroptosis, which is associated with increased p53 levels.
Exploring non-invasive precision treatment in non-small cell lung cancer patients through deep learning radiomics across imaging features and molecular phenotypes
Authors: Zhang Xingping , Zhang Guijuan , Qiu Xingting , Yin Jiao , Tan Wenjun , Yin Xiaoxia , Yang Hong , Wang Hua , Zhang Yanchun
Published: January 2024

Background

Accurate prediction of tumor molecular alterations is vital for optimizing cancer treatment. Traditional tissue-based approaches encounter limitations due to invasiveness, heterogeneity, and molecular dynamic changes. We aim to develop and validate a deep learning radiomics framework to obtain imaging features that reflect various molecular changes, aiding first-line treatment decisions for cancer patients.

Methods

We conducted a retrospective study involving 508 NSCLC patients from three institutions, incorporating CT images and clinicopathologic data. Two radiomic scores and a deep network feature were constructed on three data sources in the 3D tumor region. Using these features, we developed and validated the ‘Deep-RadScore,’ a deep learning radiomics model to predict prognostic factors, gene mutations, and immune molecule expression levels.

Findings

The Deep-RadScore exhibits strong discrimination for tumor molecular features. In the independent test cohort, it achieved impressive AUCs: 0.889 for lymphovascular invasion, 0.903 for pleural invasion, 0.894 for T staging; 0.884 for EGFR and ALK, 0.896 for KRAS and PIK3CA, 0.889 for TP53, 0.895 for ROS1; and 0.893 for PD-1/PD-L1. Fusing features yielded optimal predictive power, surpassing any single imaging feature. Correlation and interpretability analyses confirmed the effectiveness of customized deep network features in capturing additional imaging phenotypes beyond known radiomic features.

Interpretation

This proof-of-concept framework demonstrates that new biomarkers across imaging features and molecular phenotypes can be provided by fusing radiomic features and deep network features from multiple data sources. This holds the potential to offer valuable insights for radiological phenotyping in characterizing diverse tumor molecular alterations, thereby advancing the pursuit of non-invasive personalized treatment for NSCLC patients.
Nutrition of host plants influence the infectivity of nucleopolyhedrovirus to polyphagous caterpillar, Hyphantria cunea
Authors: Zhao Xudong , Geng Yishu , Qiao Heng , Liu Yu , Hu Tianyi , Xu Wenxuan , Hao Dejun
Published: January 2024

Plants play an important role in interactions between insect herbivores and their pathogens. The ability of host plants to modify the infectivity of entomopathogens in herbivorous insects has been widely documented. However, the plants’ nutrients have always been neglected as a factor contributing to variation in the susceptibility of insect herbivores to entomopathogens. The fall-webworm (FWW), Hyphantria cunea Drury, is a typical polyphagous caterpillar, and the Hyphantria cunea nucleopolyhedrovirus (HycuNPV) is a distinctly specialized baculovirus for the FWW, which is safe for other organisms and has been effectively used as a biological insecticide against H. cunea in China. In this study, we investigated the nutrient components of four host plant species, i.e., Prunus serrulate, Cerasus serrulate, Camptotheca acuminata, and Populus deltoides, and their effects on the susceptibility of H. cunea larvae to HycuNPV. The HycuNPV-infected larvae fed on P. deltoides leaves exhibited higher survival rates, longer survival times, more food intake, and gained larger body size. These biological parameters were positively correlated with the nitrogen components of host plant leaves. Moreover, the larval antioxidant enzymes exhibited different responses to HycuNPV. HycuNPV infection significantly triggered the catalase (CAT) and prophenoloxidase (PPO) enzyme activity levels of H. cunea larvae. The uninfected larvae fed on poplar leaves induced a robust increase in the POD activity, which could scavenge extra reactive oxygen species and provide a protective effect against the HycuNPV. In conclusion, the plant-mediated effects of HycuNPV on the FWW have been investigated in this study. The nitrogen content in dietary was an essential factor in determining the insect herbivore susceptibility to entomopathogenic viruses, and it helped explain variations in the susceptibility of pests to the entomopathogenic viruses and aid in developing more robust tolerance monitoring assays in the lab that reflect the performance of pests in the field.

Graphical Abstract
Elimination of Curtobacterium sp. strain A7_M15, a contaminant in Prunus rootstock tissue culture production, using reduced graphene oxide–silver–copper and silver–selenium nanocomposites
Authors: Tekielska Dorota , Pečenka Jakub , Hakalová Eliška , Čechová Jana , Bytešníková Zuzana , Richtera Lukáš , Kiss Tomáš , Eichmeier Aleš , Baránek Miroslav
Published: January 2024

Background

Bacterial contamination poses a high risk to the successful establishment and maintenance of plant tissue cultures. The aim of this study was to identify the isolates representing the frequent bacterial contaminants of Prunus rootstock tissue cultures and to determine the most effective concentration of nanomaterials for Curtobacterium sp. strain A7_M15 elimination without a negative impact on explants.

Results

Six Curtobacterium sp. strains were isolated and identified, and the whole-genome sequence was obtained for strain A7_M15. Two nanocomposites, reduced graphene oxide–copper–silver and silver–selenium, with the highest bactericidal activity were selected for elimination of Curtobacterium sp. contamination in Gisela 5 rootstock tissue cultures. Both nanocomposites showed 100% inhibition of bacterial plaque formation on culture medium at concentrations of 100, 200 and 400 mg L-1 Ag (2 ×–8 × MBC). The quantity of Curtobacterium sp. on culture medium assessed using cfu enumeration was reduced by 92% and 74% in comparison to the positive control after treatment with reduced graphene oxide–silver–copper and silver–selenium at a concentration of 200 mg L-1 Ag, respectively. None of the tested concentrations resulted in a decrease in Curtobacterium sp. quantity in explants. Curtobacterium sp. was detected in donor Gisela 5 plants, indicating an endophytic character of this bacterium. The dry weight of explants was not negatively affected by the application of nanocomposites regardless of concentration, and no detrimental effect of either nanocomposite at 100 or 200 mg L-1 Ag on the surface covered by plants was observed.

Conclusions

Reduced graphene oxide–silver–copper and silver–selenium nanocomposites at 200 mg L-1 Ag effectively limited the Curtobacterium sp. presence in micropropagated Prunus rootstock without causing phytotoxicity; therefore, those treatments could be offered as prevention with a high activity against bacterial contamination in plant tissue cultures.

Graphical Abstract
Validation of an alternative technique for RQ estimation in anesthetized pigs
Authors: Karlsson Jacob , Svedmyr Anders , Wallin Mats , Hallbäck Magnus , Lönnqvist Per-Arne
Published: January 2024

Background

Respiratory quotient (RQ) is an important variable when assessing metabolic status in intensive care patients. However, analysis of RQ requires cumbersome technical equipment. The aim of the current study was to examine a simplified blood gas-based method of RQ assessment, using Douglas bag measurement of RQ (Douglas-RQ) as reference in a laboratory porcine model under metabolic steady state. In addition, we aimed at establishing reference values for RQ in the same population, thereby generating data to facilitate further research.

Methods

RQ was measured in 11 mechanically ventilated pigs under metabolic steady state using Douglas-RQ and CO-oximetry blood gas analysis of pulmonary artery and systemic carbon dioxide and oxygen content. The CO-oximetry data were used to calculate RQ (blood gas RQ). Paired recordings with both methods were made once in the morning and once in the afternoon and values obtained were analyzed for potential significant differences.

Results

The average Douglas-RQ, for all data points over the whole day, was 0.97 (95%CI 0.95–0.99). The corresponding blood gas RQ was 0.95 (95%CI 0.87–1.02). There was no statistically significant difference in RQ values obtained using Douglas-RQ or blood gas RQ for all data over the whole day (P = 0.43). Bias was − 0.02 (95% limits of agreement ± 0.3). Douglas-RQ decreased during the day 1.00 (95%CI 0.97–1.03) vs 0.95 (95%CI 0.92–0.98) P < 0.001, whereas the decrease was not significant for blood gas RQ 1.02 (95%CI 0.89–1.16 vs 0.87 (0.80–0.94) P = 0.11.

Conclusion

RQ values obtained with blood gas analysis did not differ statistically, compared to gold standard Douglas bag RQ measurement, showing low bias but relatively large limits of agreement, when analyzed for the whole day. This indicates that a simplified blood gas-based method for RQ estimations may be used as an alternative to gold standard expired gas analysis on a group level, even if individual values may differ. In addition, RQ estimated with Douglas bag analysis of exhaled air, was 0.97 in anesthetized non-fasted pigs and decreased during prolonged anesthesia.
Ultrasound microflow patterns help in distinguishing malignant from benign thyroid nodules
Authors: Li Wanying , Gao Luying , Du Yiyan , Wang Ying , Yang Xiao , Wang Hongyan , Li Jianchu
Published: January 2024

Background

Vascular features are not commonly used to evaluate thyroid nodules by conventional ultrasound due to the low sensitivity. Superb Microvascular Imaging (SMI) is a new ultrasonic Doppler technology that specializes in depicting microvessels and low-speed flow. The objective of this study was to explore the value of microflow features on SMI in differentiating malignant from benign thyroid nodules.

Methods

One hundred and seventy-seven adult patients with thyroid nodules in our center from October 2021 to June 2022 with available histopathological results were recruited, including 125 malignant nodules and 123 benign nodules. Preoperative ultrasound was performed using greyscale, Color Doppler Flow Imaging (CDFI), monochrome SMI (mSMI) and color SMI (cSMI). Vascular features such as flow richness, microflow distribution and microflow patterns of malignant thyroid nodules were compared with those of benign nodules.

Results

Penetrating vessel ≥ 1 (82.4% in the malignant group vs. 30.9% in the benign group, P < 0.001), the crab claw-like pattern (64.0% vs. 10.6%, P < 0.001) and the root hair-like pattern (8.0% vs. 2.4%, P = 0.049) were common in malignant thyroid nodules, among which the crab claw-like pattern was an independent risk factor for malignant thyroid nodules. The wheel-like pattern (1.6% in the malignant group vs. 33.3% in the benign group, P < 0.001) and the arborescent pattern (0 vs. 19.5%, P < 0.001) were more likely to appear in benign nodules. The diagnostic specificities of the crab claw-like pattern and the root hair-like pattern for malignant thyroid nodules were 0.894, 0.976, and the positive predictive values were 0.860, 0.769. The diagnostic specificities of the wheel-like pattern and the arborescent pattern for benign thyroid nodules were 0.984, 1.000, and the positive predictive values were 0.953, 1.000.

Conclusions

The crab claw-like pattern and the root hair-like pattern were microflow characteristics of malignant thyroid nodules. The wheel-like pattern and the arborescent pattern could help exclude the diagnosis of thyroid cancer.
Mobile immobility: an exploratory study of rural women’s engagement with e-commerce livestreaming in China
Authors: Huang Yanning , Yang Zi , Chang Kuan
Published: January 2024

Based on our fieldwork in Yunnan Province and Ningxia Hui Autonomous Region, this paper explores the different ways in which Chinese rural women engage with the rising industry of e-commerce livestreaming related to agricultural products and villages. Our analytical framework is informed by feminist political economy, which pays heed to the gendered social settings, operation of power, and entanglement between women’s domesticity and productivity that underpin people’s economic activities. We argue that Chinese rural women’s simultaneous empowerment and disempowerment by e-commerce livestreaming are characterized by “mobile immobility”, a term inspired by Wallis’s (2013) research on rural women’s technological empowerment by mobile phones a decade ago. On the one hand, this latest form of e-commerce has created an apparently accessible path for rural women, who tend to be geographically immobile, to achieve social mobility by becoming professional webcasters and/or vloggers. On the other hand, this enablement is in fact classed, aged, and preconditioned on in-laws’ support and willingness to share these women’s domestic duties, which are not guaranteed. The urban-oriented digital economy of e-commerce livestreaming capitalizes on rural young women’s femininity, docile bodies and labor as well as the reproductive labor performed by their family members at the microlevel, reinforcing the urban–rural disparity at the macrolevel. The paper ends with reflections on the role of information and communication technologies and e-commerce in the development of rural China.
A descriptive study on spatial and temporal distributions of genetic clusters of porcine reproductive and respiratory syndrome virus infecting pig sites in Quebec, Canada, between 2010 and 2019
Authors: Lambert Marie-Ève , Arsenault Julie , Côté Jean-Charles , D’Allaire Sylvie
Published: January 2024

Background

The wide diversity of porcine reproductive and respiratory syndrome virus (PRRSV) strains combined with incomplete heterologous cross-protection complicates the management of the disease at both the herd and the regional levels. The objectives of this study were to describe the spatial and temporal distribution of various PRRSV genetic clusters infecting pig sites in Quebec, Canada, and to compare PRRSV regional diversity of wild-type sequences over the years.

Materials and methods

A retrospective surveillance-based study was conducted on all pig sites which had PRRSV ORF5 sequences from field submissions transferred into the Laboratoire d'épidémiologie et de médecine porcine database from January 1, 2010 to December 31, 2019. A maximum likelihood phylogenetic tree inferred from multiple sequence alignment was used to identify genetic clusters. For each wild-type cluster gathering ≥ 15 sequences, the number of pig sites in which the cluster was detected per administrative region and per year were displayed on bubble charts and the spatiotemporal distribution of pig sites was illustrated using pie chart maps. A molecular analysis of variance was performed to compare PRRSV wild-type sequence diversity according to the administrative region for each year.

Results

A total of 32 wild-type clusters gathering 1653 PRRSV2 sequences from 693 pig sites were described. Each cluster was detected on up to 132 pig sites and 7 administrative regions over the 10-year period. Annually, the mean (min–max) number of wild-type clusters detected in at least one pig site reached 24 (17–29). Some clusters remained localized on a few sites over time whereas others were widespread over the territory during a few or many years. For each year, regional differences were also observed in PRRSV diversity of wild-type sequences.

Conclusions

The differences observed in both the spatiotemporal distributions of PRRSV clusters and in the regional diversity of wild-type sequences highlight the importance of ongoing provincial surveillance to improve collective PRRS management strategies.
Enhanced detection of obfuscated malware in memory dumps: a machine learning approach for advanced cybersecurity
Authors: Hossain Md. Alamgir , Islam Md. Saiful
Published: January 2024

In the realm of cybersecurity, the detection and analysis of obfuscated malware remain a critical challenge, especially in the context of memory dumps. This research paper presents a novel machine learning-based framework designed to enhance the detection and analytical capabilities against such elusive threats for binary and multi type’s malware. Our approach leverages a comprehensive dataset comprising benign and malicious memory dumps, encompassing a wide array of obfuscated malware types including Spyware, Ransomware, and Trojan Horses with their sub-categories. We begin by employing rigorous data preprocessing methods, including the normalization of memory dumps and encoding of categorical data. To tackle the issue of class imbalance, a Synthetic Minority Over-sampling Technique is utilized, ensuring a balanced representation of various malware types. Feature selection is meticulously conducted through Chi-Square tests, mutual information, and correlation analyses, refining the model’s focus on the most indicative attributes of obfuscated malware. The heart of our framework lies in the deployment of an Ensemble-based Classifier, chosen for its robustness and effectiveness in handling complex data structures. The model’s performance is rigorously evaluated using a suite of metrics, including accuracy, precision, recall, F1-score, and the area under the ROC curve (AUC) with other evaluation metrics to assess the model’s efficiency. The proposed model demonstrates a detection accuracy exceeding 99% across all cases, surpassing the performance of all existing models in the realm of malware detection.
Essays on Partial Derangement of the Mind in Supposed Connexion with Religion by John Cheyne
Authors: Cook Christopher C.H.
Published: January 2024

Essays on Partial Derangement of the Mind in Supposed Connection with Religion, written amidst the illness of its author almost two centuries ago, was the little-known work of a distinguished physician. Seeking to rebut the argument that religion is causative of ‘derangement of the mind’ it takes a surprisingly biological view of such conditions while, at the same time, affirming the importance of faith, hope and love in human well-being. Despite its limitations, it makes observations that remain relevant to debates about religion and psychiatry today.
Heavy Metals and Trajectories of Anti-Müllerian Hormone During the Menopausal Transition
Authors: Ding Ning , Wang Xin , Harlow Siobán D , Randolph John F , Gold Ellen B , Park Sung Kyun
Published: January 2024

Background

Experimental and epidemiological studies have linked metals with women's reproductive aging, but the mechanisms are not well understood. Disrupted ovarian folliculogenesis and diminished ovarian reserve could be a pathway through which metals impact reproductive hormones and outcomes.

Objective

The study aimed to evaluate the associations of heavy metals with anti-Müllerian hormone (AMH), a marker of ovarian reserve.

Methods

The study included 549 women from the Study of Women's Health Across the Nation with 2252 repeated AMH measurements from 10 to 0 years before the final menstrual period (FMP). Serum AMH concentrations were measured using picoAMH ELISA. Urinary concentrations of arsenic, cadmium, mercury, and lead were measured using high-resolution inductively coupled plasma mass spectrometry. Multivariable linear mixed regressions modeled AMH as a function of time before the FMP interaction terms between metals and time to the FMP were also included.

Results

Adjusting for confounders, compared with those in the lowest tertile, women in the highest tertile of urinary arsenic or mercury concentrations had lower AMH concentrations at the FMP (percent change: −32.1%; 95% CI, −52.9 to −2.2, P-trend = .03 for arsenic; percent change: −40.7%; 95% CI, −58.9 to −14.5, P-trend = .005 for mercury). Higher cadmium and mercury were also associated with accelerated rates of decline in AMH over time (percent change per year: −9.0%; 95% CI, −15.5 to −1.9, P-trend = .01 for cadmium; −7.3%; 95% CI, −14.0 to −0.1, P-trend = .04 for mercury).

Conclusion

Heavy metals including arsenic, cadmium, and mercury may act as ovarian toxicants by diminishing ovarian reserve in women approaching the FMP.
Long-term Recordings of Arcuate Nucleus Kisspeptin Neurons Across the Mouse Estrous Cycle
Authors: Vas Szilvia , Wall Ellen , Zhou Ziyue , Kalmar Lajos , Han Su Young , Herbison Allan E
Published: January 2024

The arcuate nucleus kisspeptin (ARNKISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved GCaMP fiber photometry system enabling long-term continuous recordings, we aimed to establish a definitive profile of ARNKISS neuronal activity across the murine estrous cycle. As noted previously, a substantial reduction in the frequency of ARNKISS neuron synchronization events (SEs) occurs on late proestrus and extends into estrus. The SE amplitude remains constant throughout the cycle. During metestrus, we unexpectedly detected many multipeak SEs where many SEs occurred rapidly, within 160 seconds of each other. By applying a machine learning-based, k-means clustering analysis, we were further able to detect substantial within-stage variability in the patterns of pulse generator activity. Estrous cycle-dependent changes in SE activity occurred around the time of lights on and off. We also find that a mild stressor such as vaginal lavage reduces ARNKISS neuron SE frequency for up to 3 hours. These observations provide a comprehensive account of ARNKISS neuron activity across the estrous cycle, highlight a new pattern of multipeak SE activity, and introduce a new k-means clustering approach for analyzing ARNKISS neuron population behavior.
The Mediterranean mussel Mytilus galloprovincialis: a novel model for developmental studies in mollusks
Authors: Miglioli Angelica , Tredez Marion , Boosten Manon , Sant Camille , Carvalho João E. , Dru Philippe , Canesi Laura , Schubert Michael , Dumollard Rémi
Published: January 2024

A model organism in developmental biology is defined by its experimental amenability and by resources created for the model system by the scientific community. For the most powerful invertebrate models, the combination of both has already yielded a thorough understanding of developmental processes. However, the number of developmental model systems is still limited, and their phylogenetic distribution heavily biased. Members of one of the largest animal lineages, the Spiralia, for example, have long been neglected. In order to remedy this shortcoming, we have produced a detailed developmental transcriptome for the bivalve mollusk Mytilus galloprovincialis, and have expanded the list of experimental protocols available for this species. Our high-quality transcriptome allowed us to identify transcriptomic signatures of developmental progression and to perform a first comparison with another bivalve mollusk: the Pacific oyster Crassostrea gigas. To allow co-labelling studies, we optimized and combined protocols for immunohistochemistry and hybridization chain reaction to create high-resolution co-expression maps of developmental genes. The resources and protocols described here represent an enormous boost for the establishment of Mytilus galloprovincialis as an alternative model system in developmental biology.
Tree-ring formation dynamics in Fagus sylvatica and Quercus petraea in a dry and a wet year
Authors: Puchałka Radosław , Prislan Peter , Klisz Marcin , Koprowski Marcin , Gričar Jožica
Published: January 2024

European beech Fagus sylvatica and Sessile oak Quercus petraea are reaching the north-eastern limits of their natural ranges in northern Poland. According to the projected changes in potential ranges in this region, climatic conditions for both species until 2080 will remain stable. On the other hand, a decrease in the vitality of mature trees and a reduction in their radial growth are currently observed. To understand these contradictory findings, we monitored the cambial activity in both species during two vegetation seasons. 2015 was characterized by a negative water balance, while 2017 was wet. This provided an opportunity to compare how the xylogenesis proceeds in diffuse-porous beech and ring-porous oak during contrasting in the summer precipitation seasons. The forming annual increments were sampled with Presler borer at variable time intervals depending on the leaf phenological phases. The cores were prepared using a sledge microtome and double-stained with safranin and astra blue. Observations of the phases of wood formation and measurements of the width of the forming increments were analysed on the microslide digital images. Differences in the dates of the phenological phases were analysed using Two-Way ANOVA, while the dynamics of the formation of annual increments were fitted to the Single and Double Gompertz function for beech and oak, respectively. The beginning of vessel formation started earlier in both seasons compared to previous studies. Inter-seasonal differences in the duration of spring phenological phases were insignificant for both species, while inter-species differences were significant due to physiological diversity between diffuse-porous beech and ring-porous oak. In dry 2015, cambial activity ceased sooner in both species than in 2017. Differences between oak and beech were insignificant in both years, but statistically significant disparities existed within each species due to varying in precipitation seasons. Rainfall significantly elongated the duration of cambial activity and caused wider tree-rings. According to our study, despite predicted maintaining their climatic niche, both species, situated at the north-eastern cooler range boundary, are expected to produce wood at a lower rate due to the projected warmer central European climate with increased heatwaves and summer droughts.