bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic nomogram for overall survival in upper urinary tract urothelial carcinoma (UTUC) patients treated with chemotherapy: a SEER-based retrospective cohort study
Authors: Tian Cong , Liu Jun , An Lizhe , Hong Yang , Xu Qingquan
Published: January 2023

Objective

To establish a prognostic nomogram among UTUC patients who received chemotherapy.

Methods

1195 UTUC patients who received chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for the period between 2004 and 2015. Patients were randomly divided into a training and a validation set. Nomogram was constructed to predict 1-, 3-, and 5-year overall survival (OS) in those patients. Receiver-operating characteristic curves (ROCs), calibration plots, and Decision curve analysis (DCA) were applied to assess and compare the discrimination, accuracy, and practicability of the nomogram with 8th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system.

Results

Six clinical parameters were identified as independent prognostic factors for UTUC patients’ OS, including age, marital status, TNM stage, and surgical methods of the primary site. The ROC curves showed a satisfactory discrimination capacity of the nomogram, with 1-, 3-, and 5-year area under curve (AUC) values of 0.789, 0.772, and 0.763 in the training set and 0.772, 0.822, and 0.814 in the validation set, respectively. Calibration curves indicated a good agreement between actual observation and nomogram prediction. ROC and DCA curves showed our nomograms exhibited larger benefits than the 8th AJCC-TNM staging system.

Conclusions

A prognostic nomogram was established and validated to present individual predictions of OS among chemotherapeutic UTUC patients. This nomogram may assist clinicians in accurate survival prognostication, treatment decision-making, and design of future clinical trials.
Is aggressive care appropriate for patients with cancer complicated by pneumonia? A retrospective chart review in a tertiary hospital
Authors: Aramrat Chanchanok , Ratanasiri Thawalrat , Gomutbutra Patama
Published: January 2023

Background

Pneumonia in cancer patients is often problematic in order to decide whether to admit and administer antibiotics or pursue a comfort care pathway that may avoid in-hospital death. We aimed to identify factors which are easily assessed at admission in Thailand’s healthcare context that could serve as prognostic factors for in-hospital death.

Methods

Regression analysis was utilized to identify the prognostic factors from clinical factors collected at admission. The primary outcome was in-hospital death. Data was collected from the electronic medical records of Chiang Mai University Hospital, Thailand, from 2016 to 2017. Data on adult cancer patients admitted due to pneumonia were reviewed.

Results

In total, 245 patients were included, and 146 (59.6%) were male. The median age of the patients was 66 years (IQR: 57–75). A total of 72 (29.4%) patients died during admission. From multivariate logistic regression, prognostic factors for in-hospital death included: Palliative Performance Scale (PPS) ≤ 30 (OR: 8.47, 95% CI: 3.47–20.66), Palliative Performance Scale 40–50% (OR: 2.79, 95% CI: 1.34–5.81), percentage of lymphocytes ≤ 8.0% (OR: 2.10, 95% CI: 1.08–4.08), and pulse oximetry ≤ 90% (OR: 2.01, 95% CI: 1.04–3.87).

Conclusion

The in-hospital death rate of cancer patients admitted with pneumonia was approximately 30%. The PPS of 10–30%, PPS of 40–50%, percentage of lymphocytes ≤ 8%, and oxygen saturation < 90% could serve as prognostic factors for in-hospital death. Further prospective studies are needed to investigate the usefulness of these factors.
Assessment of health safety of pigs taking natural sorbents with feed
Authors: Wlazło Łukasz , Kwiecień Małgorzata , Bis-Wencel Hanna , Łopuszyński Wojciech , Buszewicz Grzegorz , Karpińska Katarzyna , Rodzyń Izabela , Kasela Martyna , Sobczak Paweł , Nowakowicz-Dębek Bożena
Published: January 2023

Background

The study assessed the effect of smectites (bentonite and zeolite) used as natural sorbents in the diet of pigs on feed digestibility, health parameters, the severity of anatomo-histological changes in organs, and the accumulation of volatile pollutants in organs.

Material and methods

The study was conducted using fattening pigs (crossbreds from multiple breeds) assigned to three groups – a control (C) and two experimental groups (A and B), with 240 pigs in each group (3 replicates × 80). The animals in group C received a standard complete diet, while groups A and B received diets with 1.5% composed smectite sorbents. The feed and faeces were analysed for content of dry matter, crude ash, crude protein, ether extract, and crude fibre. The content of P was determined using a Helios Alpha UV–VIS spectrophotometer. Whole blood was analysed for haematological parameters and serum for biochemical parameters. Tissue samples were collected for analysis of volatile substances and histological analysis. After slaughter, samples of the lungs, liver, kidneys and jejunum were collected for morphological evaluation, and samples of the perirenal fat, liver, kidneys, lungs and brain for headspace gas chromatography (GC) to determine the levels of volatile toxic substances.

Results

A statistical increase in the digestibility of crude fibre and an increase in that of P were observed in both experimental groups (A and B) in comparison to the control. The whole blood and serum of the pigs from the control group had statistically significantly higher levels of creatinine, urea, and Mg and a higher WBC count compared to both experimental groups (A and B).

Conclusions

The feed additives were not shown to have a negative effect on the health parameters analysed or on accumulation of pollutants in selected tissues. No significant effect on the digestibility of most nutrients was observed; only an increase in the digestibility of crude fibre and a decrease in P digestibility were noted in the experimental groups.
Enhanced production of d-pantothenic acid in Corynebacterium glutamicum using an efficient CRISPR–Cpf1 genome editing method
Authors: Su Rui , Wang Ting , Bo Taidong , Cai Ningyun , Yuan Meng , Wu Chen , Jiang Hao , Peng Huadong , Chen Ning , Li Yanjun
Published: January 2023

Background

Corynebacterium glutamicum has industrial track records for producing a variety of valuable products such as amino acids. Although CRISPR-based genome editing technologies have undergone immense developments in recent years, the suicide-plasmid-based approaches are still predominant for C. glutamicum genome manipulation. It is crucial to develop a simple and efficient CRISPR genome editing method for C. glutamicum.

Results

In this study, we developed a RecombinAtion Prior to Induced Double-strand-break (RAPID) genome editing technology for C. glutamicum, as Cpf1 cleavage was found to disrupt RecET-mediated homologous recombination (HR) of the donor template into the genome. The RAPID toolbox enabled highly efficient gene deletion and insertion, and notably, a linear DNA template was sufficient for gene deletion. Due to the simplified procedure and iterative operation ability, this methodology could be widely applied in C. glutamicum genetic manipulations. As a proof of concept, a high-yield D-pantothenic acid (vitamin B5)-producing strain was constructed, which, to the best of our knowledge, achieved the highest reported titer of 18.62 g/L from glucose only.

Conclusions

We developed a RecET-assisted CRISPR–Cpf1 genome editing technology for C. glutamicum that harnessed CRISPR-induced DSBs as a counterselection. This method is of great importance to C. glutamicum genome editing in terms of its practical applications, which also guides the development of CRISPR genome editing tools for other microorganisms.
Age-related attenuation of cortical synaptic tagging in the ACC is rescued by BDNF or a TrkB receptor agonist in both sex of mice
Authors: Zhou Si-Bo , Xue Man , Liu Weiqi , Chen Yu-Xin , Chen Qi-Yu , Lu Jing-Shan , Wang Jinjun , Ye Keqiang , Li Xu-Hui , Zhuo Min
Published: January 2023

Long-term potentiation (LTP) is a key cellular mechanism for learning and memory, and recent studies in the hippocampus found that LTP was impaired in aged animals. Previous studies of cortical LTP have focused primarily on the homosynaptic plasticity in adult mice, while fewer studies have looked at heterosynaptic plasticity—such as synaptic tagging in aged mice. In the present study, we investigated synaptic tagging in adult and middle-aged mice's anterior cingulate cortex (ACC) using the 64-channel multielectrode dish (MED64) recording system. We found that synaptic tagging was impaired in the ACC of middle-aged male mice as compared to adult mice. Both the network late-phase LTP (L-LTP) and the recruitment of inactive responses were reduced in the ACC of middle-aged male mice. Similar results were found in female middle-aged mice, indicating that there is no gender difference. Furthermore, bath application of brain-derived neurotrophic factor (BDNF) or systemic treatment with newly developed TrkB receptor agonists R13, was shown to rescue both synaptic tagging, and L-LTP, in middle-aged mice. To determine the distribution of synaptic LTP within the ACC, a new visualization method was developed to map the Spatio-temporal variation of LTP in the ACC. Our results provide strong evidence that cortical potentiation and synaptic tagging show an age-dependent reduction, and point to the TrkB receptor as a potential drug target for the treatment of memory decline.
“Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction”
Authors: Papaccio Federica , García-Mico Blanca , Gimeno-Valiente Francisco , Cabeza-Segura Manuel , Gambardella Valentina , Gutiérrez-Bravo María Fernanda , Alfaro-Cervelló Clara , Martinez-Ciarpaglini Carolina , Rentero-Garrido Pilar , Zúñiga-Trejos Sheila , Carbonell-Asins Juan Antonio , Fleitas Tania , Roselló Susana , Huerta Marisol , Sánchez del Pino Manuel M. , Sabater Luís , Roda Desamparados , Tarazona Noelia , Cervantes Andrés , Castillo Josefa
Published: January 2023

Background

Patient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics.

Methods

We generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization. We performed drug sensitivity assays with a panel of both standard and non-standard agents in five long-term cultures, and integrated drug response with a baseline proteomic and transcriptomic characterization by SWATH-MS and RNA-seq analysis, respectively.

Results

PDOs were successfully generated from heavily pre-treated patients, including a paired model of advanced MSI high CRC deriving from pre- and post-chemotherapy liver metastasis. Our PDOs faithfully reproduced genomic and phenotypic features of original tissue. Drug panel testing identified differential response among PDOs, particularly to oxaliplatin and palbociclib. Proteotranscriptomic analyses revealed that oxaliplatin non-responder PDOs present enrichment of the t-RNA aminoacylation process and showed a shift towards oxidative phosphorylation pathway dependence, while an exceptional response to palbociclib was detected in a PDO with activation of MYC and enrichment of chaperonin T-complex protein Ring Complex (TRiC), involved in proteome integrity. Proteotranscriptomic data fusion confirmed these results within a highly integrated network of functional processes involved in differential response to drugs.

Conclusions

Our strategy of integrating PDOs drug sensitivity with SWATH-mass spectrometry and RNA-seq allowed us to identify different baseline proteins and gene expression profiles with the potential to predict treatment response/resistance and to help in the development of effective and personalized cancer therapeutics.
MetaBinner: a high-performance and stand-alone ensemble binning method to recover individual genomes from complex microbial communities
Authors: Wang Ziye , Huang Pingqin , You Ronghui , Sun Fengzhu , Zhu Shanfeng
Published: January 2023

Binning aims to recover microbial genomes from metagenomic data. For complex metagenomic communities, the available binning methods are far from satisfactory, which usually do not fully use different types of features and important biological knowledge. We developed a novel ensemble binner, MetaBinner, which generates component results with multiple types of features by k-means and uses single-copy gene information for initialization. It then employs a two-stage ensemble strategy based on single-copy genes to integrate the component results efficiently and effectively. Extensive experimental results on three large-scale simulated datasets and one real-world dataset demonstrate that MetaBinner outperforms the state-of-the-art binners significantly.
Improving patient-centered communication in breast cancer: a study protocol for a multilevel intervention of a shared treatment deliberation system (SharES) within the NCI community oncology research program (NCORP) (Alliance A231901CD)
Authors: Hawley Sarah T. , Kidwell Kelley , Zahrieh David , McCarthy Anne , Wills Rachel , Rankin Aaron , Hofer Timothy , Chow Selina , Jagsi Reshma , Neuman Heather
Published: January 2023

Background

Advances in precision medicine have given oncologists new evaluative tools to better individualize treatments for patients with curable breast cancer. These innovations have revealed a need to improve patient understanding of novel, often complex information related to breast cancer treatment decisions. Ensuring patients have the emotional support to face consequential treatment decisions, as well as the opportunity to engage and discuss with their clinicians, is key to improving patient-centered communication and patient understanding.

Methods/design

This study will implement a multilevel intervention with patient and clinician components as a NCORP Cancer Care Delivery Research (CCDR) trial within the Alliance for Clinical Trials in Oncology Research Base (Alliance). The two interventions in this study, the Shared Decision Engagement System (SharES), include (1) two versions of an evidence-based patient-facing breast cancer treatment decision tool (iCanDecide +/− an emotional support module) and (2) a clinician-facing dashboard (Clinician Dashboard) that is reviewed by surgeons/clinicians and summarizes ongoing patient needs. The design is a near minimax, hybrid stepped wedge trial of SharES where both interventions are being evaluated in a crossed design over six 12-week time periods. The primary outcome (knowledge) and key secondary outcomes (i.e., self-efficacy and cancer worry) are assessed via patient report at 5 weeks after surgery. Secondary outcomes are also assessed at 5 weeks after surgery, as well as in a second survey 9 months after registration. We anticipate recruiting a total of 700 breast cancer patients (600 evaluable after attrition) from 25 surgical practices affiliated with Alliance.

Discussion

Upon study completion, we will have better understanding of the impact of a multilevel intervention on patient-centered communication in breast cancer with a specific focus on whether the intervention components improve knowledge and self-efficacy and reduce cancer worry.

Trial registration

ClinicalTrials.govNCT04549571. Registered on 16 September 2020.
Potential effects of teriparatide (PTH (1–34)) on osteoarthritis: a systematic review
Authors: Li Guoqing , Liu Su , Xu Huihui , Chen Yixiao , Deng Jiapeng , Xiong Ao , Wang Deli , Weng Jian , Yu Fei , Gao Liang , Ding Changhai , Zeng Hui
Published: January 2023

Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA drugs is approved currently. Teriparatide (PTH (1–34)) might stimulate chondrocyte proliferation and cartilage regeneration via some uncertain mechanisms. Relevant therapies of PTH (1–34) on OA with such effects have recently gained increasing interest, but have not become widespread practice. Thus, we launch this systematic review (SR) to update the latest evidence accordingly. A comprehensive literature search was conducted in PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase from their inception to February 2022. Studies investigating the effects of the PTH (1–34) on OA were obtained. The quality assessment and descriptive summary were made of all included studies. Overall, 307 records were identified, and 33 studies were included. In vivo studies (n = 22) concluded that PTH (1–34) slowed progression of OA by alleviating cartilage degeneration and aberrant remodeling of subchondral bone (SCB). Moreover, PTH (1–34) exhibited repair of cartilage and SCB, analgesic, and anti-inflammatory effects. In vitro studies (n = 11) concluded that PTH (1–34) was important for chondrocytes via increasing the proliferation and matrix synthesis but preventing apoptosis or hypertrophy. All included studies were assessed with low or unclear risk of bias in methodological quality. The SR demonstrated that PTH (1–34) could alleviate the progression of OA. Moreover, PTH (1–34) had beneficial effects on osteoporotic OA (OPOA) models, which might be a therapeutic option for OA and OPOA treatment.
Steady-state estradiol triggers a unique innate immune response to allergen resulting in increased airway resistance
Authors: Warren Kristi J. , Deering-Rice Cassandra , Huecksteadt Tom , Trivedi Shubhanshi , Venosa Alessandro , Reilly Christopher , Sanders Karl , Clayton Frederic , Wyatt Todd A. , Poole Jill A. , Heller Nicola M. , Leung Daniel , Paine Robert
Published: January 2023

Rationale

Asthma is a chronic airway condition that occurs more often in women than men during reproductive years. Population studies have collectively shown that long-term use of oral contraceptives decreased the onset of asthma in women of reproductive age. In the current study, we hypothesized that steady-state levels of estrogen would reduce airway inflammation and airway hyperresponsiveness to methacholine challenge.

Methods

Ovariectomized BALB/c mice (Ovx) were implanted with subcutaneous hormone pellets (estrogen, OVX-E2) that deliver consistent levels of estrogen [68 ± 2 pg/mL], or placebo pellets (OVX-Placebo), followed by ovalbumin sensitization and challenge. In conjunction with methacholine challenge, immune phenotyping was performed to correlate inflammatory proteins and immune populations with better or worse pulmonary outcomes measured by invasive pulmonary mechanics techniques.

Results

Histologic analysis showed an increase in total cell infiltration and mucus staining around the airways leading to an increased inflammatory score in ovarectomized (OVX) animals with steady-state estrogen pellets (OVX-E2-OVA) as compared to other groups including female-sham operated (F-INTACT-OVA) and OVX implanted with a placebo pellet (OVX-Pl-OVA). Airway resistance (Rrs) and lung elastance (Ers) were increased in OVX-E2-OVA in comparison to F-INTACT-OVA following aerosolized intratracheal methacholine challenges. Immune phenotyping revealed that steady-state estrogen reduced CD3+ T cells, CD19+ B cells, ILC2 and eosinophils in the BAL across all experiments. While these commonly described allergic cells were reduced in the BAL, or airways, we found no changes in neutrophils, CD3+ T cells or CD19+ B cells in the remaining lung tissue. Similarly, inflammatory cytokines (IL-5 and IL-13) were also decreased in OVX-E2-OVA-treated animals in comparison to Female-INTACT-OVA mice in the BAL, but in the lung tissue IL-5, IL-13 and IL-33 were comparable in OVX-E2-OVA and F-INTACT OVA mice. ILC2 were sorted from the lungs and stimulated with exogenous IL-33. These ILC2 had reduced cytokine and chemokine expression when they were isolated from OVX-E2-OVA animals, indicating that steady-state estrogen suppresses IL-33-mediated activation of ILC2.

Conclusions

Therapeutically targeting estrogen receptors may have a limiting effect on eosinophils, ILC2 and potentially other immune populations that may improve asthma symptoms in those females that experience perimenstrual worsening of asthma, with the caveat, that long-term use of estrogens or hormone receptor modulators may be detrimental to the lung microenvironment over time.
Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination
Authors: Guarraci Fay A. , Avendano Layla , Kelly Megan , Estoesta Cleriza , Sencherey Bernard , Valdivia Hannah S. , Gale Amanda , Yepez Lily , Belfield Jasmine B. , Carter Kristen M. , Williams Natalie , Gore Andrea C.
Published: January 2023

Background

GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot® (leuprolide acetate), have been used to suppress pubertal progression in adolescents who are questioning their gender identity. However, few preclinical studies have been conducted to investigate potential effects of using GnRH agonists in this context.

Methods

The present study tested the effects of daily leuprolide treatment (50 µg/kg, postnatal day (PD) 25–50) on pubertal onset in female (i.e., vaginal opening) and male (i.e., preputial separation) Long-Evans rats. The first estrous cycle immediately after vaginal opening was also measured. Sexual behavior and sexual motivation were tested using the partner-preference paradigm. Female rats were tested during the first behavioral estrus after treatment ended (between PD 51–64). Male rats were tested weekly for four consecutive weeks starting three days after treatment ended (PD 53).

Results

Consistent with previous findings, leuprolide significantly delayed pubertal onset in both female and male rats. In addition, the first estrous cycle during the treatment period was disrupted by leuprolide, as indicated by a failure to cycle into estrus after vaginal opening until treatment ended. However, leuprolide affected neither sexual motivation nor fertility when female rats were tested within 14 days of leuprolide treatment ending. In contrast, the development of copulatory behavior and sexual motivation was significantly delayed by leuprolide in male rats; however, mature reproductive behavior was observed by the fourth week post-treatment.

Conclusions

Taken together with previous findings, the present results indicate that male rats may be more sensitive to periadolescent leuprolide administration, taking longer to overcome the effects of leuprolide than female rats. Nevertheless, not long after leuprolide treatment is discontinued, sex-typical reproductive physiology and behavior emerge fully in female and male rats, indicating that the drug’s effects are not permanent. If translatable to humans, leuprolide may be a reversible option to give adolescents more time to consider their gender identity with minimal long-term effects on sexual development.
Transfer factor calculated using dermal exposure and dislodgeable foliar residue and exposure assessment for reentry worker after pesticide application in cucumber field
Authors: Choi Hoon
Published: January 2023

This study aimed to determine the transfer factor (TF) of methidathion for cucumber harvesters in greenhouses using the dermal exposure rates (DERs) and dislodgeable foliar residues (DFRs) measured simultaneously in my previous works. The DERs recalculated using the reference body surface area for the Korean adult males were 31.5–1281.1 μg/h, and the DFR values were 12.1–222.5 ng/cm2 over 7 d after application. A strong correlation between the DERs and DFRs was observed, with a regression coefficient of 0.9982. The TF for cucumber harvesters in greenhouses was determined to be 6020.4 cm2/h, which was five times higher than that proposed by the US Environmental Protection Agency (EPA). Additionally, based on TF value of methidathion, the reentry intervals (REIs) with or without personal protective equipment (PPE) were estimated for 82 pesticides registered on cucumber. The REIs with PPE, obtained from acceptable operator exposure levels and TF value, were less than 0 d, indicating the lowest risk possibility. However, REIs without PPE were estimated between 0.04 and 4.4 d for seven pesticides, including chlorothalonil, emamectin benzoate, flubendiamide, fluquinconazole, iminoctadine tris(albesilate), propineb, and pyridaben. In conclusion, cucumber harvesters should wear PPE for health safety when they reenter the greenhouse to harvest cucumbers following application of pesticides.
Radiomics based of deep medullary veins on susceptibility-weighted imaging in infants: predicting the severity of brain injury of neonates with perinatal asphyxia
Authors: Zhuang Xiamei , Lin Huashan , Li Junwei , Yin Yan , Dong Xiao , Jin Ke
Published: January 2023

Objective

This study aimed to apply radiomics analysis of the change of deep medullary veins (DMV) on susceptibility-weighted imaging (SWI), and to distinguish mild hypoxic-ischemic encephalopathy (HIE) from moderate-to-severe HIE in neonates.

Methods

A total of 190 neonates with HIE (24 mild HIE and 166 moderate-to-severe HIE) were included in this study. All of them were born at 37 gestational weeks or later. The DMVs were manually included in the regions of interest (ROI). For the purpose of identifying optimal radiomics features and to construct Rad-scores, 1316 features were extracted. LASSO regression was used to identify the optimal radiomics features. Using the Red-score and the clinical independent factor, a nomogram was constructed. In order to evaluate the performance of the different models, receiver operating characteristic (ROC) curve analysis was applied. Decision curve analysis (DCA) was implemented to evaluate the clinical utility.

Results

A total of 15 potential predictors were selected and contributed to Red-score construction. Compared with the radiomics model, the nomogram combined model incorporating Red-score and urea nitrogen did not better distinguish between the mild HIE and moderate-to-severe HIE group. For the training cohort, the AUC of the radiomics model and the combined nomogram model was 0.84 and 0.84. For the validation cohort, the AUC of the radiomics model and the combined nomogram model was 0.80 and 0.79, respectively. The addition of clinical characteristics to the nomogram failed to distinguish mild HIE from moderate-to-severe HIE group.

Conclusion

We developed a radiomics model and combined nomogram model as an indicator to distinguish mild HIE from moderate-to-severe HIE group.
ALKBH5 prevents hepatocellular carcinoma progression by post-transcriptional inhibition of PAQR4 in an m6A dependent manner
Authors: Wang Weijian , Huang Qibo , Liao Zhibin , Zhang Hongwei , Liu Yachong , Liu Furong , Chen Xiaoping , Zhang Bixiang , Chen Yan , Zhu Peng
Published: January 2023

Background

N6-methyladenosine (m6A) is a prevalent modification of mRNA and is known to play important roles in tumorigenesis in many types of cancer. The function of N6-methyladenosine (m6A) RNA methylation depends on a variety of methyltransferases and demethylases. AlkB homolog 5 (ALKBH5) is a demethylase, and its biological function has not been completely explored in HCC.

Results

ALKBH5 is downregulated and has antitumor effects in HCC cells. In addition, Progestin and AdipoQ Receptor 4 (PAQR4) was identified as a downstream target of ALKBH5 based on transcriptome sequencing and validation studies. We found that ALKBH5 decreases PAQR4 mRNA and protein expression in an N6-methyladenosine (m6A)-dependent manner. The study also showed that ALKBH5 changes PAQR4 expression via the m6A reader IGF2BP1. In both in vivo and in vitro experiments, PAQR4 showed a strong association with the development of HCC. Finally, we found that PAQR4 interacts with AKT and enhances PI3K/AKT pathway activation.

Conclusions

ALKBH5 inhibits HCC growth by downregulating PAQR4 expression in an m6A-dependent manner, therefore suppressing PI3K/AKT pathway activation.
Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer
Authors: Yu Haoli , Wang Yuesong , Chen Yan , Cui Mengyuan , Yang Fang , Wang Peng , Ji Min
Published: January 2023

Photothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9(RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9peptide endows the specifically targeting capacity for αvβ3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.
Hysterectomy and women’s health in India: evidence from a nationally representative, cross-sectional survey of older women
Authors: Desai Sapna , Singh Roopal Jyoti , Govil Dipti , Nambiar Devaki , Shukla Ankita , Sinha Hemali Heidi , Ved Rajani , Bhatla Neerja , Mishra Gita D.
Published: January 2023

Background

Hysterectomy, particularly when conducted in women younger than 45 years, has been associated with increased risk of non-communicable diseases. In India, research indicates that hysterectomy is a common procedure for women, but there have been no studies on its long-term effects. We examined patterns of hysterectomy amongst women in India and associations with their health and well-being in later life.

Methods

This analysis utilised the first wave of the Longitudinal Study on Aging in India, a nationally representative study of adults that included a module on health and well-being.

We analysed data on 35,083 women ≥45 years in India. We estimated prevalence of hysterectomy and performed multivariable logistic regression to identify associated risk factors and to examine the association between hysterectomy status and eight self-reported chronic conditions, hospitalisation and mobility.

Results

The prevalence of hysterectomy among women >=45 years was 11.4 (95% CI: 10.3, 12.6), with higher odds among urban women (aOR: 1.39; 1.17,1.64) and higher economic status (highest compared to lowest quintile: aOR: 1.95; 1.44, 2.63). Hysterectomy history was associated with four chronic conditions: hypertension (aOR: 1.51; 95% CI: 1.28, 1.79), high cholesterol (aOR: 1.43; 1.04, 1.97), diabetes (aOR: 1.69; 1.28, 2.24), and bone/joint disease (aOR: 1.54; 1.20, 1.97) and higher odds of any hospitalisation in the past year (aOR: 1.69; 1.36, 2.09).

Conclusions

In India, evidence suggests that hysterectomy is associated with major chronic conditions. The assessment for hysterectomy as a treatment option for gynaecological morbidity should consider potential health consequences in later life.
Work trajectories and status attainment process: a study using sequence analysis
Authors: Zhou Yang
Published: January 2023

Applying sequence analysis methods to work trajectories recorded in the 2012 China Labor Force Dynamics Survey, this study examines the types of work trajectories in China’s urban labor market in three dimensions: employment status, organizational type, and work position. The findings suggest that along with the market transition, China’s urban labor market is experiencing diverse and complex job mobility patterns. This study identifies four types of work trajectories: the merit-based work trajectory, the blue-collar’s work trajectory in the private sector, the blue-collar’s work trajectory in state-owned enterprises, and the self-employed trajectory. These four typical work trajectories have significantly different influences on individuals’ attainment of socioeconomic status and elite status. This study sheds light on the microprocesses in status attainment by examining the role of work trajectories from a longitudinal perspective.
The nature and sources of international variation in formal institutions related to initial coin offerings: preliminary findings and a research agenda
Authors: Kshetri Nir
Published: January 2023

As prior researchers have suggested, a firm’s success in an international market depends on how well its strategy fits the nonmarket environment, such as formal institutions. This paper examines the determinants of formal institutions around new areas of economic activities. Specifically, we propose a framework for understanding how the quality of formal institutions in promoting entrepreneurship drives the focus of such institutions concerning initial coin offering (ICO), which is emerging as a popular fundraising method. The paper uses inductive analysis to examine how nonmarket factors—such as a jurisdiction’s tax haven nature, regulators’ perceptions of ICOs as threats to national or political interests, and trade and industry associations—might moderate the relationship between the quality of institutions and the focus of such institutions regarding ICOs. One of this study’s key findings is that an economy’s quality of entrepreneurship-related institutions, perceived threats to national/political interests, and tax haven nature lead to different policy orientations. Consequently, regulators assign different importance when promoting crypto-entrepreneurship and dealing with associated risks. Regulators focusing mainly on promoting crypto-ventures have taken measures to enrich the blockchain ecosystem and provided tax and non-tax incentives to attract such ventures. Regulators focusing mainly on dealing with crypto-venture risks rely on a regulatory sandbox and close regulatory monitoring of such ventures.
Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling
Authors: Watanabe Hirofumi , Mokuda Sho , Tokunaga Tadahiro , Kohno Hiroki , Ishitoku Michinori , Araki Kei , Sugimoto Tomohiro , Yoshida Yusuke , Yamamoto Toshihiro , Matsumoto Mayuko , Masumoto Junya , Hirata Shintaro , Sugiyama Eiji
Published: January 2023

Background

Blood coagulation factor XIII (FXIII) promotes cross-linking between fibrin molecules at the final stage of the blood coagulation cascade. However, its expression in cells or tissues and function, particularly factor XIII subunit B (FXIII-B), remains controversial. Hemorrhagic FXIII deficiency following anti-interleukin-6 (IL-6) receptor antibody treatment has been reported in patients with rheumatoid arthritis (RA). Patients receiving this biologics have reduced FXIII activity when compared to the activity in those treated with other biologics. The relationship between pro-inflammatory cytokines and FXIII expression remains unknown.

Methods

To investigate the expression pattern of FXIII in synovial tissues, immunohistochemistry, RT-qPCR, and western blotting were performed. FXIII-A expressed monocyte-derived macrophages were treated with recombinant IL-6 and anti-IL-6 receptor antibody. RNA sequencing of FXIII-B-overexpressing cells was performed to clarify the function of FXIII-B.

Results

The immunohistochemical analysis of synovial tissues revealed that factor XIII subunit A (FXIII-A) was expressed in M2 macrophages, and FXIII-B was expressed in fibroblast-like synoviocytes. IL-6 stimulation upregulated FXIII-A expression in IL-4-induced monocyte-derived macrophages, and the anti-IL-6 receptor antibody suppressed FXIII-A expression. FXIII-B was more abundantly secreted in the supernatant of fibroblast-like synoviocytes compared with that of other cells. RNA sequencing showed that FXIII-B elevated the expression of genes associated with anti-apoptotic molecules and chemokines.

Conclusions

Our findings highlight that synovial tissue is one of the sources of FXIII production. We also have demonstrated IL-6-dependent FXIII-A expression and the novel potential functions of FXIII-B.
Etomidate-Induced Myoclonus in Sprague-Dawley Rats Involves Neocortical Glutamate Accumulation and N-Methyl-d-Aspartate Receptor Activity
Authors: Feng Yan , Chang Pan , Kang Yi , Liao Ping , Li Chen-yang , Liu Jin , Zhang Wen-sheng
Published: January 2023

BACKGROUND:

Etomidate-induced myoclonus, a seizure-like movement, is of interest to anesthetists. However, its origin in the brain and its underlying mechanism remain unclear.

METHODS:

Adult male Sprague-Dawley rats were anesthetized with etomidate, propofol, or lidocaine plus etomidate. We assessed the incidence of myoclonus, behavioral scores, and levels of glutamate and γ-aminobutyric acid (GABA) in the neocortex and hippocampus. To determine the origin and how N-methyl-d-aspartate receptors (NMDARs) modulate etomidate-induced neuroexcitability, the local field potential and muscular tension were monitored. Calcium imaging in vitro and immunoblotting in vivo were conducted to investigate the mechanisms underlying myoclonus.

RESULTS:

The incidence of etomidate (1.5 mg/kg in vivo)-induced myoclonus was higher than that of propofol (90% vs 10%, P = .0010) and lidocaine plus etomidate (90% vs 20%, P = .0050). Etomidate at doses of 3.75 and 6 mg/kg decreased the mean behavioral score at 1 (mean difference [MD]: 1.80, 95% confidence interval [CI], 0.58–3.02; P = .0058 for both), 2 (MD: 1.60, 95% CI, 0.43–2.77; P = .0084 and MD: 1.70, 95% CI, 0.54–2.86; P = .0060), 3 (MD: 1.60, 95% CI, 0.35–2.85; P = .0127 and MD: 1.70, 95% CI, 0.46–2.94; P = .0091) minutes after administration compared to etomidate at a dose of 1.5 mg/kg. In addition, 0.5 and 1 µM etomidate in vitro increased neocortical intracellular calcium signaling; this signaling decreased when the concentration increased to 5 and 10 μM. Etomidate increased the glutamate level compared to propofol (mean rank difference: 18.20; P = .003), and lidocaine plus etomidate (mean rank difference: 21.70; P = .0002). Etomidate in vivo activated neocortical ripple waves and was positively correlated with muscular tension amplitude (Spearman’s r = 0.785, P < .0001). Etomidate at 1.5 mg/kg decreased the K-Cl cotransporter isoform 2 (KCC2) level compared with propofol (MD: −1.15, 95% CI, −1.47 to −0.83; P < .0001) and lidocaine plus etomidate (MD: −0.64, 95% CI, −0.96 to −0.32; P = .0002), DL-2-amino-5-phosphopentanoic acid (AP5) suppressed these effects, while NMDA enhanced them.

CONCLUSIONS:

Etomidate-induced myoclonus or neuroexcitability is concentration dependent. Etomidate-induced myoclonus originates in the neocortex. The underlying mechanism involves neocortical glutamate accumulation and NMDAR modulation and myoclonus correlates with NMDAR-induced downregulation of KCC2 protein expression.
Socioeconomic Effects on Lumbar Fusion Outcomes
Authors: Touponse Gavin , Li Guan , Rangwalla Taiyeb , Beach Isidora , Zygourakis Corinna
Published: January 2023

BACKGROUND:

Recent studies suggest that socioeconomic status (SES) influences outcomes after spinal fusion. The influence of SES on postoperative outcomes is increasingly relevant as rates of lumbar fusion rise.

OBJECTIVE:

To determine the influence of SES variables including race, education, net worth, and homeownership on postoperative outcomes.

METHODS:

Optum's deidentified Clinformatics Data Mart Database was used to conduct a retrospective review of SES variables for patients undergoing first-time, inpatient lumbar fusion from 2003 to 2021. Primary outcomes included hospital length of stay (LOS) and 30-day reoperation, readmission, and postoperative complication rates. Secondary outcomes included postoperative emergency room visits, discharge status, and total hospital charges.

RESULTS:

In total, 217 204 patients were identified. On multivariate analysis, Asian, Black, and Hispanic races were associated with increased LOS (Coeff. [coefficient] 0.92, 95% CI 0.68-1.15; Coeff. 0.61, 95% CI 0.51-0.71; Coeff. 0.43, 95% CI 0.32-0.55). Less than 12th grade education (vs greater than a bachelor's degree) was associated with increased odds of reoperation (OR [odds ratio] 1.88, 95% CI 1.03-3.42). Decreased net worth was associated with increased odds of readmission (OR 1.32, 95% CI 1.25-1.40) and complication (OR 1.14, 95% CI 1.10-1.20). Renting a home (vs homeownership) was associated with increased LOS, readmissions, and total charges (Coeff. 0.30, 95% CI 0.17-0.43; OR 1.19, 95% CI 1.11-1.30; Coeff. 13 200, 95% CI 9000-17 000).

CONCLUSION:

Black race, less than 12th grade education, <$25K net worth, and lack of homeownership were associated with poorer postoperative outcomes and increased costs. Increasing perioperative support for patients with these sociodemographic risk factors may improve postoperative outcomes.
Incorporation of 53BP1 into phase-separated bodies in cancer cells during aberrant mitosis
Authors: Bleiler Marina , Cyr Aiyana , Wright Dennis L. , Giardina Charles
Published: January 2023

53BP1 (also known as TP53BP1) is a key mediator of the non-homologous end joining (NHEJ) DNA repair pathway, which is the primary repair pathway in interphase cells. However, the mitotic functions of 53BP1 are less well understood. Here, we describe 53BP1 mitotic stress bodies (MSBs) formed in cancer cell lines in response to delayed mitosis. These bodies displayed liquid–liquid phase separation characteristics, were close to centromeres, and included lamin A/C and the DNA repair protein RIF1. After release from mitotic arrest, 53BP1 MSBs decreased in number and moved away from the chromatin. Using GFP fusion constructs, we found that the 53BP1 oligomerization domain region was required for MSB formation, and that inclusion of the 53BP1 N terminus increased MSB size. Exogenous expression of 53BP1 did not increase MSB size or number but did increase levels of MSB-free 53BP1. This was associated with slower mitotic progression, elevated levels of DNA damage and increased apoptosis, which is consistent with MSBs suppressing a mitotic surveillance by 53BP1 through sequestration. The 53BP1 MSBs, which were also found spontaneously in a subset of normally dividing cancer cells but not in non-transformed cells (ARPE-19), might facilitate the survival of cancer cells following aberrant mitoses.

This article has an associated First Person interview with the first author of the paper.
Postconcussion Symptoms and Neuropsychological Performance in Athletes: A Literature Review
Authors: Ahmed By Zoubair , Benton Angela H. , Serra-Jovenich Michael , Toldi James P.
Published: January 2023

Neuropsychological assessment is a common part of concussion evaluation and plays an important role within the context of a comprehensive multidisciplinary approach to managing sports-related concussion. A literature review has shown an assortment of cognitive domains used for evaluation of PCS with their corresponding tests. This review focuses on the various cognitive domains following single or multiple TBIs in athletes. Decreases in memory, executive function, language, psychomotor function, and self-reported cognitive function reached statistical significance in concussed athletes versus controls. Length of time since onset of symptoms correlated with worse memory function in chronic concussion athletes and more headache symptoms correlated with a worse outcome as well. However, some treatments are shown to be beneficial for restoration of cognitive function. When analyzing these results, it is imperative to be cognizant of the bias in the current literature. Further well-designed studies are needed to replicate these findings in larger more diverse samples.
Training and Practice Settings of Physicians Dual-Certified in Emergency and Sports Medicine
Authors: Monseau Aaron J. , Balcik Brenden J. , Negaard Matthew , Lilly Christa , Hogrefe Christopher P. , Gould Sara , Odom Mitchell J. , Guyer Christopher , Davenport Moira , Chow Yvonne , Feden Jeffrey P. , Waterbrook Anna L.
Published: January 2023

Survey study of training and practice paradigms and job satisfaction of dual-boarded emergency medicine (EM) and sports medicine (SM) physicians. The REDCap survey was sent to 193 American Board of EM members who hold a Certificate of Added Qualification in SM. A total of 124 EM/SM physicians responded (67.5% male). More than 70% completed three-year residencies while only 28.5% had an EM/SM residency faculty. One-quarter delayed fellowship after residency 6.45 years on average. Regarding their first job after fellowship, 27.6% practiced only EM, 54.5% practiced both EM and SM, and 12.2% practiced only SM. Regarding their current job, 29.1% practice only EM. 47.3% practice both EM and SM, and 20.9% practice only SM. Only 13.9% and 9.9% indicated they are unhappy with their first job and current job, respectively. There is significant variability in practice settings for EM/SM physicians with the overwhelming majority being happy with their career choices.
Trends in the Sports Medicine Match: An Analysis of the National Resident Matching Program Data from 2010 to 2021
Authors: Zaremski Jason L. , Waterbrook Anna L. , Monseau Aaron J. , Kliethermes Stephanie A.
Published: January 2023

Sports medicine (SM) fellowship training has become popular among residents. Thus, an analysis was undertaken to assess data on matching rates from 2010 to 2021. The purpose of this study is to analyze trends in SM fellowship applications using National Resident Matching Program data. Retrospective study with analysis of applicants applying into accredited SM fellowships between 2010 and 2021. The number of accredited programs and fellowship positions have more than doubled from 2010 to 2021. There was a significant increase in match rates over time (P < 0.001); match rates were at 70% or below prior to 2015 and above 70% after 2015. The average number of applicants per position stayed consistent. The number of Doctor of Osteopathic Medicine applicants increased 110% whereas the number of U.S. born foreign and non-U.S. citizen applicants decreased 20.8%. SM fellowship training has increased since 2010. Acceptance rates and number of applicants have increased over time because of the growth in fellowship programs and accredited positions.