bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Esophageal Reconstruction: Indications, Techniques, and Outcomes
Authors: Treffalls John A. , Jacobsen Christian P. , Das Nitin A. , Medina Rebecca A. , Koch Marc , DeArmond Daniel T. , Johnson Scott B.
Published: November 2023

Objective:

The purpose of this study was to evaluate indications, techniques, and outcomes of patients who underwent delayed esophageal reconstruction.

Methods:

A retrospective chart review was performed for all esophagectomy patients who underwent delayed esophageal reconstruction from 2006 to 2020. Demographics, surgical indication, type of esophageal discontinuity procedure performed, duration between esophagectomy and reconstruction, type and technique of reconstruction performed, follow-up duration, change in body mass index, and overall outcome were assessed.

Results:

Fifteen patients (8 women, 53.3%) with a median age of 57.6 years (IQR 50.5-66.7 years) were included. Etiology necessitating foregut discontinuity included: delayed postoperative complications in 6 (40.0%), iatrogenic injury in 3 (20.0%), strangulated bowel in 3 (20.0%), trauma in 2 (13.3%), and esophageal cancer in 1 (6.7%). Median duration of esophageal discontinuity was 277 days (range 105-1045). Eleven patients (73%) underwent a substernal colon interposition; 2 (13%) substernal gastric advancement; and 2 (13%) small bowel advancement in the posterior mediastinum with jejunum via Roux-en-Y. Complications were noted in 7 (47%) patients. Median decrease in BMI was 4.7 (IQR 1.4-12.4). Overall, 11 (73.3%) patients had a good outcome, 3 (20.0%) patients had a fair outcome, and 1 poor outcome (6.7%). The median follow-up duration since reconstruction was 4.2 (IQR 2.8-5.4) years.

Conclusion:

Delayed esophageal reconstruction can be performed with acceptable outcomes with careful preparation and often require lengthy recoveries.
A Scoping Review of Adjuvant Perioperative Therapies for Primary Cleft Lip Repair
Authors: Lem Melinda , T Pham Jason , Arora Jagmeet , Trivedi Shivang , Arowojolu Omotayo , Castro Ruben , Mocharnuk Joseph , Vyas Raj , Pfaff Miles J.
Published: November 2023

Background:To date, there is little guidance regarding current adjuvant therapies for primary surgical repair of cleft lip. There are studies on the effect of botulinum toxin type A, revision fat grafting, silicone gel and sheeting, intense pulsed light, and carbon dioxide lasers to ameliorate contracture and hypertrophic scar formation, but a comprehensive review of these options is lacking. The aim of this scoping review is to examine adjuvant techniques and therapies that modulate scar outcomes for primary cleft lip repair outcomes in the perioperative period. Methods: PROSPERO, PubMed/MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrial.gov were searched for studies that evaluated adjuvant therapies for primary cleft lip repair. Results: The initial search resulted in 688 studies, with 48 studies including relevant key terms in the title and abstract screening. After the full-text screening, 11 studies were included in the final scoping review. These included 3 studies about use of botulinum toxin injection, 2 studies about fat grafting, 2 studies about nasal stents, and 4 studies about various topical treatments. In the Jadad quality index evaluation and MINORS assessment of the methodological quality of the included papers, there was a strong level of agreement among the 2 raters respectively (weighted κ = 1, κ = 0.817, both P-value < .0001). Conclusion: From this scoping review, adjuvant therapies such as utilizing botulinum toxin and immediate fat grafting intraoperatively and nasal stents and topical treatments including antibiotic ointment, lidocaine, hydrogen peroxide, and silicone gels postoperatively are worthwhile to consider as a combination of adjuvant treatments to prevent adverse scar formation in patients undergoing primary cleft lip repair. The most robust evidence lies with botulinum toxin use.
Sustainable agriculture
Authors: Datta Subhojit , Hamim Islam , Jaiswal Durgesh Kumar , Sungthong Rungroch
Published: November 2023

Developing sustainable agricultural practices is currently becoming an increasingly relevant challenge. As the worldwide population rises and climate change affects agriculture globally, new and sustainable approaches must be adopted to ensure food security. In this editorial, we invite contributions to a BMC Plant Biology collection on ‘Sustainable agriculture,’ covering research on the environmental and socioeconomic factors that affect sustainable agricultural practices and their management.
Comparison of the hemodynamic changes between preeclamptic and normotensive parturients who underwent cesarean section under spinal anesthesia at North Showa zone public hospitals, Oromia region, Ethiopia, 2022: a prospective cohort study
Authors: Belachew Bizuwork Girma , Kasahun Blen , Demissie Birhanu Wondimeneh , Sintayhu Ashagrie , Dendir Getahun , Ali Abas , Awol Redi , Angasa Dugo , Tasew Asaminew , Eshatu Oliyad , Desta Aschalew Besha , Girma Derara , Debalke Getachew
Published: November 2023

Background

Spinal anaesthesia complicates maternal hemodynamic and may expose the parturient to dangerous cardiovascular problems. Up to 7% to 89.2% of pregnant women can suffer from spinal anaesthesia-related hypotension. The aim of this study to compare the hemodynamic changes between preeclamptic and normotensive parturients who underwent caesarean section under spinal anaesthesia at North Showa Zone Public Hospitals, Oromia Region, from February 15 to May 15, 2022.

Methods

A prospective cohort study was conducted on a total of 140 parturients (70 in each group) who underwent cesarean delivery under spinal anesthesia. The study participants were chosen using a consecutive sampling technique. Data were collected from patient charts and intraoperative observations and entered into the Epi Data software version 4.6 and exported to the Statistical Package for the Social Sciences version 25 software. Hemodynamic change = (baseline value-current value/baseline value) * 100. The independent t-test, Mann–Whitney U test, two ways mixed ANOVA, chi-square, and Fisher's exact test was used to analyze the data as appropriate. A P < 0.05 was statistically significant.

Results

The mean percentage change in SBP, DBP, and MAP after spinal anaesthesia was a statistically significant difference between the normotensive and preeclamptic groups, except MAP at 15 min was comparable between the two groups with p = 0.638. The proportion of preeclamptic parturients who develop hypotension was 47%, compared to 74% of normotensive parturients, and the RR of developing hypotension, if participants were preeclamptic, was 0.63, with a 95% confidence interval of 0.412 to 0.978 and a p = 0.039. The mean change in heart rate during the first 15 min was comparable between the groups.

Conclusion

In contrast to normotensive parturients undergoing caesarean section under spinal anaesthesia, our study found that the hemodynamic change was lower in preeclamptic parturients. The proportion of preeclamptic women who develop hypotension was 47%, compared to 74% of normotensive parturients.
The ED50 and ED95 of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy: a prospective, double-blinded trial
Authors: Xu Zhongling , Lang Yantao , Xu Xiaolei , Deng Linjuan , Song Hengya , Yin Dekun
Published: November 2023

Background

This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy.

Methods

54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon’s up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions.

Results

The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05).

Conclusions

In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively.

Trial registration

ChiCTR2200066663, 13/12/2022.
Patient perspective on task shifting from general practitioners to medical practice assistants – a quantitative survey in Germany
Authors: Kuschick Doreen , Dierks Marius Tibor , Grittner Ulrike , Heintze Christoph , Kümpel Lisa , Riens Burgi , Rost Liliana , Schmidt Konrad , Schulze Daniel , Toutaoui Kahina , Wolf Florian , Döpfmer Susanne
Published: November 2023

Introduction

Various developments result in increasing workloads in general practices. New models of care and a restructuring of the division of tasks could provide relief. One approach is to extend the delegation of medical tasks from general practitioners (GPs) to medical practice assistants (MPAs). So far, there has been a lack of information about specific situations in which patients are willing to be treated exclusively by MPAs.

Methods

In three German federal states, patients who visited a general practice were surveyed exploratively and cross-sectionally with a self-designed, paper-based questionnaire. The data were analysed descriptively and multivariate. A mixed binary logistic regression model was calculated to account for cluster effects at practice level (random intercept model). The dependent variable was patients' acceptance of task delegation.

Results

A total of 1861 questionnaires from 61 general practices were included in the analysis. Regarding the current problem/request, a total of 30% of respondents could imagine being treated only by MPAs. Regarding theoretical reasons for consultation, more than half of the patients agreed to be treated by MPAs. According to the regression model, MPAs were preferred when patients were younger (10-year OR = 0.84, 95%-CI [0.75, 0.93]) or had a less complicated issue (OR = 0.44, 95%-CI [0.26, 0.8]). For four current problems/requests (“acute complaints” OR = 0.27, 95%-CI [0.17, 0.45], “routine health check” OR = 0.48, 95%-CI [0.3, 0.79], “new problem” OR = 0.13, 95%-CI [0.06, 0.28], “known problem” OR = 0.16, 95%-CI [0.1, 0.27]) patients prefer to be treated by GPs instead of MPAs.

Discussion

For the first time, statements could be made on patients’ acceptance of task delegation in relation to current and theoretical reasons for treatment in general practices in Germany. The discrepancy in response behaviour on a theoretical and individual level could be explained by different contexts of questions and differences at practice level. Overall, patients seem to be open to increased delegation of medical tasks, depending on the reason for treatment. Selection and response biases should be considered in the interpretation.

Conclusion

The results are not completely opposed to an extension of task delegation. Further interventional studies could provide information on the possible effects of expansion of delegable tasks.
COVID 19 infection clinical features in pediatric patients in Southwestern Iran: a cross-sectional, multi-center study
Authors: Jamalidoust Marzieh , Jalil Mohsen , Ashkan Zahra , Sharifi Moslem , Hemmati Rouhollah , Dashti Anahita Sanaei , Kadivar Mohammad Rahim , Pouladfar Gholamreza , Amanati Ali , Hamzavi Seyeheh Sedigheh , Asaie Sadaf , Eskandari Maryam , Aliabadi Nasrin , Ziyaeyan Mazyar
Published: November 2023

With the SARS-CoV-2 pandemic, the impact of recent coronavirus, especially in children, cannot be ignored. In this study, we evaluated the SARS-CoV-2 infection rates and associated features in children less than 18 years of age in “Fars” and “Kohgiluyeh and Boyer Ahmad”, provinces, Iran. 5943 children who were suspected cases to SARS-CoV-2 infection were enrolled in this study. Demographic and clinical data of SARS-CoV-2 patients were collected from 16 February 2020 to 20 June 2021. Underlying conditions were considered in this study as well. Among 5943 patients suspected COVID 19 cases, 13.51% were confirmed by real-time PCR assay. The female/male ratio was 1:1.3 with a mean age of 5.71 years. 11.2% of confirmed patients were transferred and admitted in Pediatric ICU. COVID 19 was significantly higher in children with malignancy and diabetes rather than those with other underlying diseases. Children of all ages were susceptible to COVID 19, and there is no significant difference between both sexes. Most of the COVID 19 cases were in 10–18 years old group. Among a number of children with different underlying diseases, children with malignancy had the highest rate of SARS-CoV-2 infection, followed by those with diabetes.
Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data
Authors: Zou Yanzheng , Yue Ming , Jia Linna , Wang Yifan , Chen Hongbo , Zhang Amei , Xia Xueshan , Liu Wei , Yu Rongbin , Yang Sheng , Huang Peng
Published: November 2023

Background

Most existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model.

Methods

A total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison.

Results

During a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838–0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively).

Conclusions

Our longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.
Finite element analysis of the angle range in trans-inferior alveolar nerve implantation at the mandibular second molar
Authors: Wu Wenli , Song Liangyue , Liu Jinming , Du Lingyi , Zhang Yuhang , Chen Yingying , Tang Zichun , Shen Ming
Published: November 2023

Background

Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle.

Methods

Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height < 9 mm in the edentulous area were selected. The distances from the mandibular nerve canal to the buccal cortex, the lingual cortex and the alveolar ridge crest were measured by using a combination of software. The angular ranges of the buccal-lingual inclination of simulated trans-IAN implants were measured and three-dimensional finite element models were constructed in the mandibular second molar area according to the differences of the inclination angles. A vertical load (200N) was then applied to analyze the biomechanical conditions of the implant-bone interface during median occlusion.

Results

The distance at the second molar from the nerve canal to the buccal cortex, lingual cortex and alveolar crest were 6.861 ± 1.194 mm, 2.843 ± 0.933 mm and 7.944 ± 0.77 mm. Trans-IAN implantation was feasible in 73.33% of patients. The minimum angle and maximum angles of the buccal-lingual inclination of the simulated implant were 19.135 ± 6.721° and 39.282 ± 6.581°. When a vertical static load of 200N was applied, the tensile stress in cortical bone gradually increased with the increase of the implant tilt angle. When the inclination angle reached 30°, the tensile stress (105.9 MPa) exceeded the yield strength (104 MPa) of cortical bone. Compared with the conventional implants, the stress peak value of the vertical ultra-short implant in cortical bone was greater than the stress peak value of the conventional implants at 10°(79.81 MPa) and 20°(82.83 MPa) and was smaller than the stress of the implant at 30°(105.9 MPa) and 40°(107.8 MPa). Therefore, when the bone mass allows, conventional-length implants should be selected whenever possible, and an operative range of the trans-IAN implantation in the mandibular second molar could be retained with an inclination angle of < 30°.

Conclusions

The mandibular nerve canal at the mandibular second molar was obviously biased to the lingual side, which ensured sufficient bone mass at the buccal side. In most patients with severe mandibular atrophy, it was possible to maintain a safe distance from the nerve canal with conventional-length implants via the trans-IAN implantation technique.
Time to complete contemporary dental procedures – estimates from a cross-sectional survey of the dental team
Authors: Bannister Christian , Cope Anwen Louise , Karki Anup , Harper Paul , Peddle Sarah , Walters Brenda , Allen Michael , Chestnutt Ivor Gordon
Published: November 2023

Background

There are few contemporary studies on the time taken to complete dental procedures, those most heavily relied on in the United Kingdom date back to 1999.

Objectives

This work aimed to establish how long members of the dental team took to complete specific dental procedures, relevant to their scope of practice.

Methods

Data were collected via a purposive sample of 96 dentists, dental hygienists/therapists and dental nurses. Via an online survey, participants were asked to state the mean, minimum and maximum time they estimated that they took to complete individual dental procedures.

Results

The mean time taken to complete procedures common to both dentists and dental hygienists/therapists ranged from 3.7 to 4 min respectively for clinical note reading prior to seeing patients to 30.1 and 28 min to undertake root surface debridement. There were no significant differences between the time taken by dentists and dental hygienists/therapists to treat adult patients. However, in all but one procedure, dental hygienists/therapists reported taking longer (p = 0.04) to treat child patients.

Conclusions

The data provided here represent an up to date assessment of the time taken to complete specific tasks by different members of the dental team. These data will be of value to service planners and commissioners interested in evolving a dental care system that employs a greater degree of skill-mix and preventively oriented care.
Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer
Authors: Wang Ganggang , Zhang Hao , Shen Xiaowei , Jin Wenzhi , Wang Xiaoliang , Zhou Zhijie
Published: November 2023

Triple-negative breast Cancer (TNBC) is a highly malignant cancer with unclear pathogenesis. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) vitally influence tumor onset and progression. Thus, this research aimed to identify distinct subgroups of CAF using single-cell and TNBC-related information from the GEO and TCGA databases, respectively. The primary aim was to establish a novel predictive model based on the CAF features and their clinical relevance. Moreover, the CAFs were analyzed for their immune characteristics, response to immunotherapy, and sensitivity to different drugs. The developed predictive model demonstrated significant effectiveness in determining the prognosis of patients with TNBC, TME, and the immune landscape of the tumor. Of note, the expression of GPR34 was significantly higher in TNBC tissues compared to that in other breast cancer (non-TNBC) tissues, indicating that GPR34 plays a crucial role in the onset and progression of TNBC. In summary, this research has yielded a novel predictive model for TNBC that holds promise for the accurate prediction of prognosis and response to immunotherapy in patients with TNBC.
Role of arachidonic acid metabolism in intervertebral disc degeneration: identification of potential biomarkers and therapeutic targets via multi-omics analysis and artificial intelligence strategies
Authors: Tan Jianye , Shi Meiling , Li Bin , Liu Yuan , Luo Shengzhong , Cheng Xigao
Published: November 2023

Background

Intervertebral disc degeneration (IVDD) is widely recognized as the primary etiological factor underlying low back pain, often necessitating surgical intervention as the sole recourse in severe cases. The metabolic pathway of arachidonic acid (AA), a pivotal regulator of inflammatory responses, influences the development and progression of IVDD.

Methods

Initially, a comparative analysis was conducted to investigate the relationship between AA expression patterns and different stages of IVDD using single-cell sequencing (scRNA-seq) data. Additionally, three machine learning methods (LASSO, random forest, and support vector machine recursive feature elimination) were employed to identify hub genes associated with IVDD. Subsequently, a novel artificial intelligence prediction model was developed for IVDD based on an artificial neural network algorithm and validated using an independent dataset. The identified hub genes were further subjected to functional enrichment, immune infiltration, and Connectivity Map analysis. Moreover, external validation was performed using flow cytometry and real-time reverse transcription polymerase chain reaction analysis.

Results

Both scRNA-seq and bulk RNA-seq data revealed a positive correlation between the severity of IVDD and the AA metabolic pathway. They also revealed increased AA metabolic activity in macrophages and neutrophils, as well as enhanced intercellular communication with nucleus pulposus cells. Utilizing advanced machine learning algorithms, five hub genes (AKR1C3, ALOX5, CYP2B6, EPHX2, and PLB1) were identified, and an incipient diagnostic model was developed with an AUC of 0.961 in the training cohort and 0.72 in the validation cohort. An in-depth exploration of the functionality of these hub genes revealed their notable association with inflammatory responses and immune cell infiltration. Lastly, AH6809 was found to delay IVDD by inhibiting AKR1C3.

Conclusions

This study offers comprehensive insights into potential biomarkers and small molecules associated with the early pathogenesis of IVDD. The identified biomarkers and the developed integrated diagnostic model hold great promise in predicting the onset of early IVDD. AH6809 was established as a therapeutic target for AKR1C3 in the treatment of IVDD, as evidenced by computer simulations and biological experiments.
Fluorescence-enhanced dual signal lateral flow immunoassay for flexible and ultrasensitive detection of monkeypox virus
Authors: Yang Xingsheng , Cheng Xiaodan , Wei Hongjuan , Tu Zhijie , Rong Zhen , Wang Chongwen , Wang Shengqi
Published: November 2023

The outbreak of the monkeypox virus (MPXV) worldwide in 2022 highlights the need for a rapid and low-cost MPXV detection tool for effectively monitoring and controlling monkeypox disease. In this study, we developed a flexible lateral flow immunoassay (LFIA) with strong colorimetric and enhanced fluorescence dual-signal output for the rapid, on-site, and highly sensitive detection of the MPXV antigen in different scenarios. A multilayered SiO2-Au core dual-quantum dot (QD) shell nanocomposite (named SiO2-Au/DQD), which consists of a large SiO2 core (~ 200 nm), one layer of density-controlled gold nanoparticles (AuNPs, 20 nm), and thousands of small QDs, was fabricated instead of a traditional colorimetric nanotag (i.e., AuNPs) and a fluorescent nanotag (QD nanobead) to simultaneously provide good stability, strong colorimetric ability and superior fluorescence intensity. With the dual-signal output LFIA, we achieved the specific screening of the MPXV antigen (A29L) in 15 min, with detection limits of 0.5 and 0.0021 ng/mL for the colorimetric and fluorometric modes, respectively. Moreover, the colorimetric mode of SiO2-Au/DQD-LFIA exhibits the same sensitivity as the traditional AuNP- LFIA, whereas the overall sensitivity of this method on the basis of the fluorescent signal can achieve 238- and 3.3-fold improvements in sensitivity for MPXV compared with the AuNP-based LFIA and ELISA methods, respectively, indicating the powerful performance and good versatility of the dual-signal method in the point-of-care testing of the MPXV.
Zn-Shik-PEG nanoparticles alleviate inflammation and multi-organ damage in sepsis
Authors: Guo Jie , Miao Yuqing , Nie Fayi , Gao Fei , Li Hua , Wang Yuan , Liu Qi , Zhang Tingbin , Yang Xiaohang , Liu Li , Fan Haiming , Wang Qiang , Qiao Haifa
Published: November 2023

Sepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn2+-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.
Role of hypermethylated SLC5A8 in follicular thyroid cancer diagnosis and prognosis prediction
Authors: Yang Yan , Liao Chenjin , Yang Qian , Li Yuxia , Tang Yunxiang , Xu Bin
Published: November 2023

Objective

Thyroid cancer is one of the most frequently reported endocrine system malignancies. It is difficult to distinguish follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) during pathological diagnosis in patients without lymph nodes or distant metastases. Therefore, we conducted a retrospective study to investigate the significance of SLC5A8 methylation and expression in the diagnosis and prognosis of FTC.

Methods

We used 165 tissue samples, including FTC (n = 58), thyroid tumors of uncertain malignant potential (TT-UMP, n = 40), and FTA (n = 67), to explore the differences in SLC5A8 methylation and mRNA transcription in different pathological types. Survival analysis was conducted to evaluate the recurrence rate at a 5-year follow-up.

Results

The SLC5A8 methylation positive rate was higher in patients with thyroglobulin ≥ 40 μg/l and Chol ≥ 5.17 mmol/l, and it was higher in patients with FTC (n = 42, 72.4%) than those with FTA (n = 27, 40.3%) and TT-UMP (n = 23, 57.5%). The relative concentration of SLC5A8 mRNA was lower in patients with FTC than in those with FTA (p < 0.05). At 5-year follow-ups, patients who were SLC5A8 methylation-positive had a higher recurrence rate than those who were methylation-negative.

Conclusions

Our current study indicates that SLC5A8 gene methylation occurs more commonly in patients with FTC than in those with FTA. The differences in SLC5A8 methylation and expression among FTA, FTC, and TT-UMP provide an important basis for further exploration of epigenetic changes in the occurrence, development, and prognosis of thyroid cancer. Our findings need to be further validated in larger populations with long-term follow-up in the future.
Comprehensive clinicopathological significance and putative transcriptional mechanisms of Forkhead box M1 factor in hepatocellular carcinoma
Authors: Wu Hua-Yu , Luo Li-Feng , Wei Fang , Jiang Hong-Mian
Published: November 2023

Background

The Forkhead box M1 factor (FOXM1) is a crucial activator for cancer cell proliferation. While FOXM1 has been shown to promote hepatocellular carcinoma (HCC) progression, its transcriptional mechanisms remain incompletely understood.

Methods

We performed an in-house tissue microarray on 313 HCC and 37 non-HCC tissue samples, followed by immunohistochemical staining. Gene chips and high throughput sequencing data were used to assess FOXM1 expression and prognosis. To identify candidate targets of FOXM1, we comprehensively reanalyzed 41 chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets. We predicted FOXM1 transcriptional targets in HCC by intersecting candidate FOXM1 targets with HCC overexpressed genes and FOXM1 correlation genes. Enrichment analysis was employed to address the potential mechanisms of FOXM1 underlying HCC. Finally, single-cell RNA sequencing analysis was performed to confirm the transcriptional activity of FOXM1 on its predicted targets.

Results

This study, based on 4235 HCC tissue samples and 3461 non-HCC tissue samples, confirmed the upregulation of FOXM1 in HCC at mRNA and protein levels (standardized mean difference = 1.70 [1.42, 1.98]), making it the largest multi-centered study to do so. Among HCC patients, FOXM1 was increased in Asian and advanced subgroups, and high expression of FOXM1 had a strong ability to differentiate HCC tissue from non-HCC tissue (area under the curve = 0.94, sensitivity = 88.72%, specificity = 87.24%). FOXM1 was also shown to be an independent exposure risk factor for HCC, with a pooled hazard ratio of 2.00 [1.77, 2.26]. The predicted transcriptional targets of FOXM1 in HCC were predominantly enriched in nuclear division, chromosomal region, and catalytic activity acting on DNA. A gene cluster encoding nine transcriptional factors was predicted to be positively regulated by FOXM1, promoting the cell cycle signaling pathway in HCC. Finally, the transcriptional activity of FOXM1 and its targets was supported by single-cell analysis of HCC cells.

Conclusions

This study not only confirmed the upregulation of FOXM1 in HCC but also identified it as an independent risk factor. Moreover, our findings enriched our understanding of the complex transcriptional mechanisms underlying HCC pathogenesis, with FOXM1 potentially promoting HCC progression by activating other transcription factors within the cell cycle pathway.
Clinical application of calcium silicate-based bioceramics in endodontics
Authors: Wang Xinyuan , Xiao Yizhi , Song Wencheng , Ye Lanxiang , Yang Chen , Xing Yuzhen , Yuan Zhenglin
Published: November 2023

Pulp treatment is extremely common in endodontics, with the main purpose of eliminating clinical symptoms and preserving tooth physiological function. However, the effect of dental pulp treatment is closely related to the methods and materials used in the process of treatment. Plenty of studies about calcium silicate-based bioceramics which are widely applied in various endodontic operations have been reported because of their significant biocompatibility and bioactivity. Although most of these materials have superior physical and chemical properties, the differences between them can also have an impact on the success rate of different clinical practices. Therefore, this review is focused on the applications of several common calcium silicate-based bioceramics, including Mineral trioxide aggregate (MTA), Biodentine, Bioaggregate, iRoot BP Plus in usual endodontic treatment, such as dental pulp capping, root perforation repair, regenerative endodontic procedures (REPs), apexification, root-end filling and root canal treatment (RCT). Besides, the efficacy of these bioceramics mentioned above in human trials is also compared, which aims to provide clinical guidance for their clinical application in endodontics.
Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product
Authors: Wiercinska E. , Quade-Lyssy P. , Hümmer C. , Beifuß J. , Akarkach K. , Poppe C. , Olevska V. , Dzionek J. , Lahnor H. , Bosio A. , Papanikolaou E. , Bonig Halvard
Published: November 2023

Introduction

In vitro or in vivo depletion of alloreactive T cells can facilitate haplo-identical hematopoietic stem cell transplantation (HSCT). Very satisfactory transplant outcomes were thus reported for TCRαβ/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current semi-automatic manufacturing process on the CliniMACS Plus, although robust, still requires a significant amount of manual labor to be completed. Towards advancing and further facilitating large scale cell processing, a new TCRαβ/CD19 depletion module combined with the previously described CD45RA depletion module (to serve as allo-reactivity attenuated donor lymphocyte infusion) was established on the CliniMACS Prodigy.

Methods

We evaluated six apheresis products from G-CSF-mobilized volunteer donors which were split automatically by the Prodigy, one portion each depleted of CD45RA+ or of TCRαβ+ and CD19+ cells. We investigated critical quality attributes for both products. Products were assessed for recovery of HSPCs and mature subsets, as well as depletion efficiency of targeted cells using flow cytometry. Effects of apheresis and product age post 48 h storage at 2–6 °C as well as freeze-thawing on product viability and recovery of WBC and HPSCs were assessed by flow cytometry.

Results

Ten sequential automatic processes were completed with minimal hands-on time beyond tubing set installation. Depletion efficiency of CD45RA+ resp. TCRαβ+ and CD19+ cells was equivalent to previous reports, achieving mean depletions of 4 log of targeted cells for both products. HSPC products retained TCRγδ+ and NK cells. 48 h storage of apheresis product was associated with the expected modest loss of HSPCs, but depletions remained efficient. Depleted products were stable until at least 72 h after apheresis with stem cell viabilities > 90%. Freeze-thawing resulted in loss of NK cells; post-thaw recovery of viable CD45+ and HSPCs was > 70% and in line with expectation.

Conclusion

The closed, GMP-compatible process generates two separate medicinal products from the same mobilized apheresis product. The CD45RA-depleted products contained functional memory T cells, whereas the TCRαβ/CD19-depleted products included HSPCs, TCRγδ+ and NK cells. Both products are predicted to be effectively depleted of GVH-reactivity while providing immunological surveillance, in support of haplo-identical HSCT.

Graphical Abstract
Paneth cell-derived iNOS is required to maintain homeostasis in the intestinal stem cell niche
Authors: Huang Lingxiao , Xu Zhenni , Lei Xudan , Huang Yujun , Tu Siyu , Xu Lu , Xia Jieying , Liu Dengqun
Published: November 2023

Background

Mammalian intestinal epithelium constantly undergoes rapid self-renewal and regeneration sustained by intestinal stem cells (ISCs) within crypts. Inducible nitric oxide synthase (iNOS) is an important regulator in tissue homeostasis and inflammation. However, the functions of iNOS on ISCs have not been clarified. Here, we aimed to investigate the expression pattern of inducible nitric oxide synthase (iNOS) within crypts and explore its function in the homeostatic maintenance of the ISC niche.

Methods

Expression of iNOS was determined by tissue staining and qPCR. iNOS−/− and Lgr5 transgenic mice were used to explore the influence of iNOS ablation on ISC proliferation and differentiation. Enteroids were cultured to study the effect of iNOS on ISCs in vitro. Ileum samples from wild-type and iNOS−/− mice were collected for RNA-Seq to explore the molecular mechanisms by which iNOS regulates ISCs.

Results

iNOS was physiologically expressed in Paneth cells. Knockout of iNOS led to apparent morphological changes in the intestine, including a decrease in the small intestine length and in the heights of both villi and crypts. Knockout of iNOS decreased the number of Ki67+ or BrdU+ proliferative cells in crypts. Loss of iNOS increased the number of Olfm4+ ISCs but inhibited the differentiation and migration of Lgr5+ ISCs in vivo. iNOS depletion also inhibited enteroid formation and the budding efficiency of crypts in vitro. Moreover, iNOS deficiency altered gluconeogenesis and the adaptive immune response in the ileum transcriptome.

Conclusion

Paneth cell-derived iNOS is required to maintain a healthy ISC niche, and Knockout of iNOS hinders ISC function in mice. Therefore, iNOS represents a potential target for the development of new drugs and other therapeutic interventions for intestinal disorders.
Radiogenomic analysis of cellular tumor-stroma heterogeneity as a prognostic predictor in breast cancer
Authors: Fan Ming , Wang Kailang , Zhang You , Ge Yuanyuan , Lü Zhong , Li Lihua
Published: November 2023

Background

The tumor microenvironment and intercellular communication between solid tumors and the surrounding stroma play crucial roles in cancer initiation, progression, and prognosis. Radiomics provides clinically relevant information from radiological images; however, its biological implications in uncovering tumor pathophysiology driven by cellular heterogeneity between the tumor and stroma are largely unknown. We aimed to identify radiogenomic signatures of cellular tumor-stroma heterogeneity (TSH) to improve breast cancer management and prognosis analysis.

Methods

This retrospective multicohort study included five datasets. Cell subpopulations were estimated using bulk gene expression data, and the relative difference in cell subpopulations between the tumor and stroma was used as a biomarker to categorize patients into good- and poor-survival groups. A radiogenomic signature-based model utilizing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was developed to target TSH, and its clinical significance in relation to survival outcomes was independently validated.

Results

The final cohorts of 1330 women were included for cellular TSH biomarker identification (n = 112, mean age, 57.3 years ± 14.6) and validation (n = 886, mean age, 58.9 years ± 13.1), radiogenomic signature of TSH identification (n = 91, mean age, 55.5 years ± 11.4), and prognostic (n = 241) assessments. The cytotoxic lymphocyte biomarker differentiated patients into good- and poor-survival groups (p < 0.0001) and was independently validated (p = 0.014). The good survival group exhibited denser cell interconnections. The radiogenomic signature of TSH was identified and showed a positive association with overall survival (p = 0.038) and recurrence-free survival (p = 3 × 10–4).

Conclusion

Radiogenomic signatures provide insights into prognostic factors that reflect the imbalanced tumor-stroma environment, thereby presenting breast cancer-specific biological implications and prognostic significance.
Acute phase protein concentration in pharyngeal swabs from clinically healthy commercial dairy calves
Authors: Petersen Mette Bisgaard , Capion Nynne
Published: November 2023

Background

Early diagnosis of disease in calves is crucial for fast recovery and prudent use of antibiotics. The serum concentration of acute phase proteins (APPs) is up- or downregulated in response to tissue injury and has been studied widely in human medicine. There is growing interest in using APPs as biomarkers for different diseases and as a tool to initiate and monitor treatment in veterinary medicine as well. The concentration of APPs in saliva in healthy calves has not been established and the use of pharyngeal swabs offers a non-invasive alternative to blood sampling. Pharyngeal swabs, tracheal aspirate (TA) and blood samples were collected from 84 clinically healthy commercial dairy calves and analyzed for the APPs serum amyloid A (SAA), haptoglobin (Hp) and lipopolysaccharide binding protein (LBP).

Results

We found detectable concentrations of SAA, Hp and LBP in pharyngeal swabs from calves, as well as in TA and serum. There were no biologically interesting correlations between the SAA concentrations in serum and TA or pharyngeal swabs. This also applied to Hp and LBP concentrations in serum and TA or pharyngeal swabs.

Conclusions

SAA, Hp and LBP can be measured in saliva and TA from calves, but there was no correlation between the specific APP concentration in serum and pharyngeal swab or TA. There was a considerable technical variation in the sampling method for both pharyngeal swab and TA, and further validation of the methods is needed.
Endoscopy-based IBD identification by a quantized deep learning pipeline
Authors: Datres Massimiliano , Paolazzi Elisa , Chierici Marco , Pozzi Matteo , Colangelo Antonio , Dorian Donzella Marcello , Jurman Giuseppe
Published: November 2023

Background

Discrimination between patients affected by inflammatory bowel diseases and healthy controls on the basis of endoscopic imaging is an challenging problem for machine learning models. Such task is used here as the testbed for a novel deep learning classification pipeline, powered by a set of solutions enhancing characterising elements such as reproducibility, interpretability, reduced computational workload, bias-free modeling and careful image preprocessing.

Results

First, an automatic preprocessing procedure is devised, aimed to remove artifacts from clinical data, feeding then the resulting images to an aggregated per-patient model to mimic the clinicians decision process. The predictions are based on multiple snapshots obtained through resampling, reducing the risk of misleading outcomes by removing the low confidence predictions. Each patient’s outcome is explained by returning the images the prediction is based upon, supporting clinicians in verifying diagnoses without the need for evaluating the full set of endoscopic images. As a major theoretical contribution, quantization is employed to reduce the complexity and the computational cost of the model, allowing its deployment on small power devices with an almost negligible 3% performance degradation. Such quantization procedure holds relevance not only in the context of per-patient models but also for assessing its feasibility in providing real-time support to clinicians even in low-resources environments. The pipeline is demonstrated on a private dataset of endoscopic images of 758 IBD patients and 601 healthy controls, achieving Matthews Correlation Coefficient 0.9 as top performance on test set.

Conclusion

We highlighted how a comprehensive pre-processing pipeline plays a crucial role in identifying and removing artifacts from data, solving one of the principal challenges encountered when working with clinical data. Furthermore, we constructively showed how it is possible to emulate clinicians decision process and how it offers significant advantages, particularly in terms of explainability and trust within the healthcare context. Last but not least, we proved that quantization can be a useful tool to reduce the time and resources consumption with an acceptable degradation of the model performs. The quantization study proposed in this work points up the potential development of real-time quantized algorithms as valuable tools to support clinicians during endoscopy procedures.
IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis
Authors: Zheng Hui , Guan Xiaolin , Meng Xin , Tong Ying , Wang Yanchun , Xie Suhong , Guo Lin , Lu Renquan
Published: November 2023

Background

Inflammation and immunity are two main characteristics of tumor microenvironment (TME). Interferon-gamma (IFN-γ) is generally considered as a pro-inflammatory cytokine which mediates anti-tumor immune response. Recently, IFN-γ was also reported to play a protumorigenic role. However, the mechanisms of tumor-promoting effect induced by IFN-γ remain unclear.

Methods

The expression of leukocyte antigen-E (HLA-E), IFN-γ, CD3 and CD56 in clinical samples of ovarian cancer was detected by mutiplexed immunohistochemistry. The mechanism to induce HLA-E overexpression by IFN-γ was explored using human ovarian cancer cell lines through western blot and flow cytometry. We further clarify the role of overexpressed-HLA-E on natural killer (NK)-mediated cell lysis.

Results

We found that IFN-γ could upregulate HLA-E protein expression through activating of JAK/STAT1 signaling pathway, and increase cell surface HLA-E level through enhancing proteasome activity. We also observed that only high levels of membrane HLA-E expression contributed to the inhibition of NK-mediated cytotoxicity. We showed that progression-free survival (PFS) of ovarian cancer patients was negatively correlated with IFN-γ expression in their tumor tissues, due to more tumor infiltrating NK cells compared with T lymphocytes.

Conclusions

Our study revealed the protumorigenic role of IFN-γ by upregulation of HLA-E expression and rendering tumors less susceptible to immune attack. We also provided a novel insight into the relationship between tumor microenvironment and immune evasion.
Progress of the application clinical prediction model in polycystic ovary syndrome
Authors: Guixue Guan , Yifu Pu , Yuan Gao , Xialei Liu , Fan Shi , Qian Sun , Jinjin Xu , Linna Zhang , Xiaozuo Zhang , Wen Feng , Wen Yang
Published: November 2023

Clinical prediction models play an important role in the field of medicine. These can help predict the probability of an individual suffering from disease, complications, and treatment outcomes by applying specific methodologies. Polycystic ovary syndrome (PCOS) is a common disease with a high incidence rate, huge heterogeneity, short- and long-term complications, and complex treatments. In this systematic review study, we reviewed the progress of clinical prediction models in PCOS patients, including diagnosis and prediction models for PCOS complications and treatment outcomes. We aimed to provide ideas for medical researchers and clues for the management of PCOS. In the future, models with poor accuracy can be greatly improved by adding well-known parameters and validations, which will further expand our understanding of PCOS in terms of precision medicine. By developing a series of predictive models, we can make the definition of PCOS more accurate, which can improve the diagnosis of PCOS and reduce the likelihood of false positives and false negatives. It will also help discover complications earlier and treatment outcomes being known earlier, which can result in better outcomes for women with PCOS.