bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of succinate with two CO2 fixation reactions from fatty acids in Cupriavidus necator H16
Authors: Li Linqing , Zhou Xiuyuan , Gao Zhuoao , Xiong Peng , Liu Xiutao
Published: July 2024

Background

Biotransformation of CO2 into high-value-added carbon-based products is a promising process for reducing greenhouse gas emissions. To realize the green transformation of CO2, we use fatty acids as carbon source to drive CO2 fixation to produce succinate through a portion of the 3-hydroxypropionate (3HP) cycle in Cupriavidus necator H16.

Results

This work can achieve the production of a single succinate molecule from one acetyl-CoA molecule and two CO2 molecules. It was verified using an isotope labeling experiment utilizing NaH13CO3. This implies that 50% of the carbon atoms present in succinate are derived from CO2, resulting in a twofold increase in efficiency compared to prior methods of succinate biosynthesis that relied on the carboxylation of phosphoenolpyruvate or pyruvate. Meanwhile, using fatty acid as a carbon source has a higher theoretical yield than other feedstocks and also avoids carbon loss during acetyl-CoA and succinate production. To further optimize succinate production, different approaches including the optimization of ATP and NADPH supply, optimization of metabolic burden, and optimization of carbon sources were used. The resulting strain was capable of producing succinate to a level of 3.6 g/L, an increase of 159% from the starting strain.

Conclusions

This investigation established a new method for the production of succinate by the implementation of two CO2 fixation reactions and demonstrated the feasibility of ATP, NADPH, and metabolic burden regulation strategies in biological carbon fixation.
Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy
Authors: Tang Bufu , Zhu Jinyu , Shi Yueli , Wang Yajie , Zhang Xiaojie , Chen Biao , Fang Shiji , Yang Yang , Zheng Liyun , Qiu Rongfang , Weng Qiaoyou , Xu Min , Zhao Zhongwei , Tu Jianfei , Chen Minjiang , Ji Jiansong
Published: July 2024

Background

The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks.

Methods

Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification–mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC.

Results

We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT).

Conclusions

Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.
Associations between different triglyceride glucose index-related obesity indices and periodontitis: results from NHANES 2009–2014
Authors: Yang Liyuan , Fang Shiyan , Zhang Runzhen , Xia Rong
Published: July 2024

Background

This study aimed to explore the associations between triglyceride glucose (TyG) index-related obesity indices and periodontitis within the American population.

Methods

This cross-sectional investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) for 2009–2014. The association between the TyG–waist-to-height ratio (TyG-WHtR), TyG–weight-adjusted-waist index (TyG-WWI), TyG–waist circumference (TyG-WC), or TyG–body mass index (TyG-BMI) and periodontitis was investigated utilizing multivariable logistic regression model, subgroup, and dose-response curve analyses.

Results

This study enrolled 4,808 adult participants. Except for TyG-BMI, which did not exhibit a relationship with periodontitis, TyG-WHtR, [odds ratio (OR) (95% confidence interval (CI))] = 2.83 [1.58–5.10], P = 0.002], TyG-WWI [OR (95% CI) = 7.50 (3.06–18.34), P < 0.001], and TyG-WC [OR (95% CI) = 2.12 (1.23–3.64), P = 0.011] were all associated with periodontitis. Participants in the highest quartile displayed an elevated risk of periodontitis relative to their counterparts in the lowest quartile, as evidenced for TyG-WWI [OR (95% CI) = 1.72 (1.26–2.33), P = 0.001] and TyG-WC [OR (95% CI) = 1.50 (1.13–1.99), P = 0.009] in the full adjustment model. Subgroup analyses suggested more pronounced positive associations between these indices and periodontitis in participants who were < 60 years old, had a BMI ≥ 25, and did not have diabetes. The dose-response curve indicated linear responses in these associations.

Conclusions

This investigation identified a significant and stable association between TyG-WHtR, TyG-WWI, or TyG-WC and periodontitis, which implies a robust correlation between high insulin resistance and susceptibility to periodontitis in the American population.
Genetic variability of human papillomavirus type 18 based on E6, E7 and L1 genes in central China
Authors: Li Ting , Yang Zhiping , Luo Ping , Yang Yang , Lin Zicong , Mei Bing
Published: July 2024

Background

High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16.

Methods

In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively.

Results

A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes.

Conclusion

The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.
Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China
Authors: Wang Jin-feng , Li Chen , Yang Jing-yi , Wang Yue-ling , Ji Jing
Published: July 2024

Background

Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients.

Methods

In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi’an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis.

Results

The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS.

Conclusion

In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.
Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
Authors: Uramoto Hidetaka , Motono Nozomu , Iwai Shun
Published: July 2024

Background

Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC.

Methods

We conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions).

Results

The clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3).

Conclusion

The therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.
Calcium supplementation during trauma resuscitation: a propensity score-matched analysis from the TraumaRegister DGU®
Authors: Helsloot Dries , Fitzgerald Mark , Lefering Rolf , Groombridge Christopher , Becaus Nathalie , Verelst Sandra , Missant Carlo ,   The TraumaRegister DGU
Published: July 2024

Background

In major trauma patients, hypocalcemia is associated with increased mortality. Despite the absence of strong evidence on causality, early calcium supplementation has been recommended. This study investigates whether calcium supplementation during trauma resuscitation provides a survival benefit.

Methods

We conducted a retrospective analysis using data from the TraumaRegister DGU® (2015–2019), applying propensity score matching to balance demographics, injury severity, and management between major trauma patients with and without calcium supplementation. 6 h mortality, 24 h mortality, and in-hospital mortality were considered as primary outcome parameters.

Results

Within a cohort of 28,323 directly admitted adult major trauma patients at a European trauma center, 1593 (5.6%) received calcium supplementation. Using multivariable logistic regression to generate propensity scores, two comparable groups of 1447 patients could be matched. No significant difference in early mortality (6 h and 24 h) was observed, while in-hospital mortality appeared higher in those with calcium supplementation (28.3% vs. 24.5%, P = 0.020), although this was not significant when adjusted for predicted mortality (P = 0.244).

Conclusion

In this matched cohort, no evidence was found for or against a survival benefit from calcium supplementation during trauma resuscitation. Further research should focus on understanding the dynamics and kinetics of ionized calcium levels in major trauma patients and identify if specific conditions or subgroups could benefit from calcium supplementation.
Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis
Authors: Orso Daniele , Fonda Federico , Brussa Alessandro , Comisso Irene , Auci Elisabetta , Sartori Marco , Bove Tiziana
Published: July 2024

Background

There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events.

Methods

A systematic review and meta-analysis was performed.

Results

Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37–1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69–1.01) for the common effects model and 0.82 (95% CI 0.63–1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09–2.77), and 1.71 (95% CI 1.01–2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87–1.69) for the common effects model and 1.18 (95% CI 0.86–1.62) for the random effects model (I2 = 0%).

Conclusion

Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events.

Clinical trial registration

PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.
Predicting progression from subjective cognitive decline to mild cognitive impairment or dementia based on brain atrophy patterns
Authors: Lerch Ondrej , Ferreira Daniel , Stomrud Erik , van Westen Danielle , Tideman Pontus , Palmqvist Sebastian , Mattsson-Carlgren Niklas , Hort Jakub , Hansson Oskar , Westman Eric
Published: July 2024

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the ‘severity index’ generated using a standard classification model trained on patients with AD dementia versus a new model trained on β-amyloid (Aβ) positive patients with amnestic mild cognitive impairment (aMCI).

Methods

We used structural MRI data of 504 patients from the Swedish BioFINDER-1 study cohort (cognitively normal (CN), Aβ-negative = 220; SCD, Aβ positive and negative = 139; aMCI, Aβ-positive = 106; AD dementia = 39). We applied multivariate data analysis to create two predictive models trained to discriminate CN individuals from either individuals with Aβ positive aMCI or AD dementia. Models were applied to individuals with SCD to classify their atrophy patterns as either high-risk “disease-like” or low-risk “CN-like”. Clinical trajectory and model accuracy were evaluated using 8 years of longitudinal data.

Results

In predicting progression from SCD to MCI or dementia, the standard, dementia-based model, reached 100% specificity but only 10.6% sensitivity, while the new, aMCI-based model, reached 72.3% sensitivity and 60.9% specificity. The aMCI-based model was superior in predicting progression from SCD to MCI or dementia, reaching a higher receiver operating characteristic area under curve (AUC = 0.72; P = 0.037) in comparison with the dementia-based model (AUC = 0.57).

Conclusion

When predicting conversion from SCD to MCI or dementia using structural MRI data, prediction models based on individuals with milder levels of atrophy (i.e. aMCI) may offer superior clinical value compared to standard dementia-based models.
Breathlessness assessment, management and impact in the intensive care unit: a rapid review and narrative synthesis
Authors: Richardson Ben R. , Decavèle Maxens , Demoule Alexandre , Murtagh Fliss E. M. , Johnson Miriam J.
Published: July 2024

Background

Adults in the intensive care unit (ICU) commonly experience distressing symptoms and other concerns such as pain, delirium, and breathlessness. Breathlessness management is not supported by any ICU guidelines, unlike other symptoms.

Aim

To review the literature relating to (i) prevalence, intensity, assessment, and management of breathlessness in critically ill adults in the ICU receiving invasive and non-invasive mechanical ventilation (NIV) and high-flow oxygen therapy, (HFOT), (ii) the impact of breathlessness on ICU patients with regard to engagement with rehabilitation.

Methods

A rapid review and narrative synthesis using the Cochrane Methods Group Recommendations was conducted and reported in accordance with PRISMA. All study designs investigating breathlessness in adult ICU patients receiving either invasive mechanical ventilation (IMV), NIV or HFOT were eligible. PubMed, MEDLINE, The Cochrane Library and CINAHL databased were searched from June 2013 to June 2023. Studies were quality appraised.

Results

19 studies representing 2822 ICU patients were included (participants mean age 48 years to 71 years; proportion of males 43–100%). The weighted mean prevalence of breathlessness in ICU patients receiving IMV was 49% (range 34–66%). The proportion of patients receiving NIV self-reporting moderate to severe dyspnoea was 55% prior to initiation. Breathlessness assessment tools included visual analogue scale, (VAS), numerical rating scale, (NRS) and modified BORG scale, (mBORG). In patients receiving NIV the highest reported median (interquartile range [IQR]) VAS, NRS and mBORG scores were 6.2cm (0–10 cm), 5 (2–7) and 6 (2.3–7) respectively (moderate to severe breathlessness). In patients receiving either NIV or HFOT the highest reported median (IQR) VAS, NRS and mBORG scores were 3 cm (0–6 cm), 8 (5–10) and 4 (3–5) respectively.

Conclusion

Breathlessness in adults receiving IMV, NIV or HFOT in the ICU is prevalent and clinically important with median intensity ratings indicating the presence of moderate to severe symptoms.
Effect of suckler cow breed type and parity on the development of the cow-calf bond post-partum and calf passive immunity
Authors: Brereton Noeleen , McGee Mark , Beltman Marijke , Byrne Colin J. , Meredith David , Earley Bernadette
Published: July 2024

Background

Development of the cow-calf bond post-partum and passive immunity of calves from spring-calving beef × beef (B×B) and beef × dairy (B×D) cow genotypes was determined using primiparous and multiparous (Experiment 1), and primiparous and second-parity (Experiment 2) animals. In Experiment 1, calves either suckled colostrum naturally (‘natural-suckling’) (n = 126), or were fed colostrum, using an oesophageal-tube (‘artificially-fed’) (n = 26), from their dam within 1-h post-partum. In Experiment 2, all calves (n = 60) were artificially-fed colostrum from their dam. Prior to colostrum suckling/feeding, colostrum was sampled for IgG analysis. The cow-calf bond was assessed using CCTV recordings during the first 4-h post-partum. Calves were blood sampled at 48-h post-partum to determine IgG and total protein (TP) concentrations, and zinc sulphate turbidity (ZST) units.

Results

There was no difference (P > 0.05) in cow licking behaviours and calf standing and suckling behaviours between the genotypes, except in Experiment 2 where B×D calves had more attempts to suckle before suckling occurred (P ≤ 0.05) compared to B×B calves. In Experiment 1, multiparous cows licked their calves sooner (P ≤ 0.05) and for longer (P < 0.01), and their calves had fewer attempts to stand (P < 0.001), stood for longer (P = 0.05), and had fewer attempts to suckle before suckling occurred (P < 0.001) than primiparous cows; there was no parity effect on cow-calf behaviour in Experiment 2. Colostrum IgG concentrations and measures of calf passive immunity did not differ (P > 0.05) between the genotypes in either Experiment. In Experiment 1, colostrum IgG concentrations were greater (P ≤ 0.05) in multiparous compared to primiparous cows and their calves had superior (P ≤ 0.05) passive immunity; no effect of parity was found in Experiment 2. Passive immunity did not differ (P > 0.05) between suckled and artificially-fed calves in Experiment 1.

Conclusions

Cow genotype had little effect on cow-calf behaviours, but under ‘natural-suckling’ conditions primiparous cows expressed maternal inexperience and their calves were less vigorous than multiparous cows. Colostrum IgG concentration and calf passive immunity measures were unaffected by genotype, but under ‘natural-suckling’ conditions calves from primiparous cows had lower passive immunity.
Establishment of an ovarian cancer exhausted CD8+T cells-related genes model by integrated analysis of scRNA-seq and bulk RNA-seq
Authors: Hua Tian , Liu Deng-xiang , Zhang Xiao-chong , Li Shao-teng , Wu Jian-lei , Zhao Qun , Chen Shu-bo
Published: July 2024

Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan–Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.
Exploring AI-driven approaches for unstructured document analysis and future horizons
Authors: Mahadevkar Supriya V. , Patil Shruti , Kotecha Ketan , Soong Lim Way , Choudhury Tanupriya
Published: July 2024

In the current industrial landscape, a significant number of sectors are grappling with the challenges posed by unstructured data, which incurs financial losses amounting to millions annually. If harnessed effectively, this data has the potential to substantially boost operational efficiency. Traditional methods for extracting information have their limitations; however, solutions powered by artificial intelligence (AI) could provide a more fitting alternative. There is an evident gap in scholarly research concerning a comprehensive evaluation of AI-driven techniques for the extraction of information from unstructured content. This systematic literature review aims to identify, assess, and deliberate on prospective research directions within the field of unstructured document information extraction. It has been observed that prevailing extraction methods primarily depend on static patterns or rules, often proving inadequate when faced with complex document structures typically encountered in real-world scenarios, such as medical records. Datasets currently available to the public suffer from low quality and are tailored for specific tasks only. This underscores an urgent need for developing new datasets that accurately reflect complex issues encountered in practical settings. The review reveals that AI-based techniques show promise in autonomously extracting information from diverse unstructured documents, encompassing both printed and handwritten text. Challenges arise, however, when dealing with varied document layouts. Proposing a framework through hybrid AI-based approaches, this review envisions processing a high-quality dataset for automatic information extraction from unstructured documents. Additionally, it emphasizes the importance of collaborative efforts between organizations and researchers to address the diverse challenges associated with unstructured data analysis.
Practical use of transanal decompression tube following the repair of fourth-degree perineal tears associated with vaginal delivery
Authors: Miki Hisanori , Toshinori Kobayashi , Masahiko Hatta , Yagyu Takuki , Sekimoto Mitsugu
Published: July 2024

Background

Fourth-degree perineal tears associated with vaginal delivery (PTAVD) occur in approximately 0.25 to 6% of vaginal deliveries. A persistent challenge in treating fourth-degree PTAVD is the high incidence of anastomotic leakage, leading to impaired quality of life, marked by incontinence, rectovaginal fistula, and painful sexual intercourse. Thus, effective interventions are necessary. Herein, we report our successful approach in repairing a fourth-degree PTAVD, involving the placement of a transanal decompression tube (TDT) during the early postoperative period.

Case presentation

Five patients underwent the repair of fourth-degree PTAVD by suturing the mucosal and muscular layers of the rectum, and the vaginal wall in layers. Subsequently, a TDT was placed in the rectum, positioned 10–15 cm from the anal verge. The TDT was allowed to drain spontaneously without suction. Gastrografin enema examination was performed through a TDT, followed by a computed tomographic scan on postoperative days 3–4. After unfavorable complications were ruled out, the TDT was removed and the patients were transitioned to a normal diet.

Result

All patients showed favorable outcomes with no occurrence of vaginal fistula or incontinence.

Conclusion

This simple intervention demonstrates potential efficacy in reducing anastomotic leakage following the repair of fourth-degree PTAVD.
Effectiveness of registered dietitian-led management of early nutritional support in the emergency intensive care unit: a retrospective observational study
Authors: Hayashi Mamoru , Nishikido Yuki , Banno Hiroyuki , Michitaka Tsuzuki , Tachibana Eiko , Tsukahara Takayoshi
Published: July 2024

Background

Appropriate nutritional management in critically ill patients positively impacts prognosis. This study evaluated the effectiveness of a dietitian-led early enteral nutrition protocol in an intensive care unit (ICU).

Methods

This retrospective analysis of prospectively collected data included patients who stayed in the emergency ICU (EICU) for at least 5 days between April 2021 and May 2022. Patients were divided into control and early support groups based on the implementation of the early enteral nutrition protocol in November 2021.

Results

The time to start enteral nutrition after admission was significantly shorter in the early support group (41.9 h) than in the control group (59.8 h). The early support group (n = 58) also had higher nutritional sufficiency rates than the control group (n = 56) and a lower incidence of diarrhea (10% vs. 37.5%).

Conclusions

The dietitian-led early nutritional support system effectively reduced the time to enteral nutrition initiation, improved nutritional sufficiency rates, and decreased the incidence of diarrhea in the EICU.
Association between the adherence to Mediterranean diet and depression in rheumatoid arthritis patients: a cross-sectional study from the NHANES database
Authors: Ma Liya , Yuan Jingman , Yang Xichao , Yan Meixi , Li Ying , Niu Min
Published: July 2024

Background

Rheumatoid arthritis (RA) is a systemic autoimmune disease, and depression is a most frequent comorbid condition associated with RA. Studies have shown that inflammation plays a vital role in the pathophysiology of depression and RA. Mediterranean diet (MED) has been proved to be a healthy anti-inflammatory dietary pattern. This study aims to explore the association between the adherence to Mediterranean diet (aMED) and depression in RA patients.

Methods

In this study, RA patients aged ≥ 20 years old were extracted from the National Health and Nutrition Examination Survey (NAHNES) database. Dietary intake information was obtained from 24-h dietary recall interview. Covariates included sociodemographic information, lifestyles, laboratory parameters, and the history of diseases and medications were included. The weighted univariable and multivariable logistic regression models were used to assess the association between aMED and depression. Subgroup analysis was conducted to further explore the association between MED components and depression.

Results

Totally 1,148 patients were included, of whom 290 (25.26%) had depression. After adjusted all covariates, high aMED was associated with the lower odds of depression in RA patients (OR = 0.53, 95%CI: 0.29–0.97). Among MED components, higher consumption of vegetables (OR = 0.54, 95%CI: 0.34–0.84) and cereals (OR = 0.63, 95%CI: 0.39–0.99) contributed more to decrease the odds of depression.

Conclusion

Greater aMED may have potential benefits for improving mental health in RA patients. Future large-scale cohort studies are needed to explore the association between aMED and depression in RA patients.
Human α-glucosidase inhibition and phytochemical profile of natural and shinzuke treated olives: implications from the processing method
Authors: Yonekura Lina , Hisada Haruka , Intravichakul Jittipon
Published: July 2024

Olive (Olea europaea) phytochemicals are associated with a reduced risk of type 2 diabetes. Table olives typically have higher phytochemical concentrations than olive oil, but their impact on human intestinal α-glucosidase is largely unknown. Shinzuke, the most common trade preparation in Japan, are alkali-treated non-fermented green olives. In contrast, natural olives are debittered by brining, which may enhance phytochemical retention. We evaluated the α-glucosidase inhibitory effect of Shinzuke and natural green olives produced in-house and compared them with commercial table olives. Eight types of table olives were tested against human intestinal α-glucosidase. Shinzuke Mission was the least effective (IC50 0.710 ± 0.058 mg/mL), while Natural green olives showed double to triple activity, with a non-competitive mechanism. Natural table olives retained more phytochemicals than shinzuke and other treated olives, and are good inhibitors of human α-glucosidase in vitro, exhibiting potential as a functional food for the management of postprandial glycaemia.

Graphical Abstract
Evaluating the performance of two different chemiluminescence analyzers systems in screening donors’ samples for HCV infection
Authors: Salem Dalia Diaa ElDine , ElSayed Heba-TAllah Nader
Published: July 2024

Background

The approved screening test for HCV infection among blood donors is the HCV antibody test. The diagnostic performances of the available immunoassays in the market that target different HCV antigens have not yet been thoroughly analyzed. Our study aimed to assess the diagnostic performances of two different chemiluminescence immunoassay (CLIA) assays.

Methods

We analyzed 1909 samples using two assay systems (COBAS e601 ROCHE® & Vitros 3600 ORTHO®) and evaluated the agreement of each with the gold standard method ELISA, as well as studying their diagnostic performances.

Results

The Cohen’s Kappa statistics revealed excellent agreement between ELISA and both CLIA methods performed on Cobas e 601 ROCHE and Vitrous 3600 ORTHO (0.81 & 0.994 respectively). The sensitivities and positive predictive values were 95.05% and 73.85% for Cobas e 601 ROCHE, 100.00%, and 98.97% for Vitrous 3600 ORTHO, respectively.

Conclusions

Excellent diagnostic performance was detected by both assays; however, Vitros 3600 ORTHO outperformed Cobas e 601 ROCHE in terms of sensitivity and specificity.
The association of adherence to 24-hour movement guidelines with frailty and mortality: cross-sectional and longitudinal analyses of NHANES data
Authors: Meister Daniel J. , Kehler D. Scott , Bouchard Danielle R. , Thomson Amy M. , Sénéchal Martin
Published: July 2024

Background

Adherence to the Canadian 24-Hour Movement Guidelines (24 H-MG) has been associated with a reduced risk of developing various chronic conditions. However, its association with frailty and all-cause mortality has not been investigated. Therefore, our primary and secondary objective was to investigate the association between adherence to the 24 H-MG and frailty and mortality, respectively.

Methods

This study included 2739 individuals (age = 50.6 ± 18.1 years; male = 1370 (50.0%)) from the 2005–2006 cycle of the National Health and Nutrition Examination Survey (NHANES). Frailty was quantified with a 46-item frailty index and analyzed cross-sectionally using linear regression. All-cause mortality data were obtained from the National Death Index and was analyzed prospectively over 10 years using Cox regression. The primary exposure variable was six individual and combined 24 H-MG components including the moderated-to-vigorous physical activity, light physical activity, sedentary time, recreational screen time, sleep, and strength training guidelines. All analyses were stratified into two age groups (younger: 20–64 and older adults 65 + years).

Results

Our cross-sectional analyses demonstrated an inverse dose-response relationship between the number of individual 24 H-MG components met and frailty level in adults aged 20–64 (β = -0.439 (95% C.I. = -0.551:-0.328)) and 65+ (β = -0.322 (95% C.I. = -0.490:-0.154)). Of the individual guideline components, following the moderate-to-vigorous physical activity (MVPA) guideline in individuals aged 20–64 and the recreational screen time guideline in adults aged 65 + was associated with lower frailty (p < 0.001). There was no clear prospective relationship between adherence to the combined 24 H-MG and mortality. Of the individual guideline components, only meeting the MVPA guideline component in the 65 + group was prospectively associated with reduced mortality risk (HR = 0.48 (95% C.I. = 0.25–0.93)).

Conclusion

Adherence to the Canadian 24 H-MG may be protective against frailty. Increasing MVPA and decreasing recreational screen time may be important behaviors to consider for frailty prevention and should be investigated further.
Analytical solutions of ray-tracing equations in generalized elliptical anisotropy
Authors: Diner Çağrı , Beyaz Ahmet
Published: July 2024

Ray-tracing in anisotropic media is pivotal for interpreting observed seismic data and creating high-resolution images of subsurface structures, which are crucial in exploration geophysics. Elliptical anisotropy, a simplified model that approximates a transversely isotropic medium, is particularly relevant for geologic settings such as shale formations or stressed sedimentary layers where directional dependencies of seismic velocities are pronounced. We develop an analytical solution of the ray-tracing equations for a 2D inhomogeneous and anisotropic medium, where velocities depend elliptically on direction and increase linearly with depth — a scenario frequently encountered in stratified geologic formations. Unlike previous studies that assume constant ellipticity throughout the medium, our approach allows for variations in ellipticity, providing a more flexible and realistic representation of subsurface anisotropy. The phase velocities along the x- and z-axes are not necessarily multiples of each other at every point, offering a generalized version of the elliptical anisotropy. This enhancement may enable more accurate predictions and interpretations of observed seismic data, particularly in complex exploration scenarios. The analytical solution yields expressions for the ray paths and the wavefront normals. By setting the normals of the wavefront at the seismic source point and the location of the seismic source as the initial conditions in phase space, we explore the evolution of these wavefront normal curves across different types of the elliptical anisotropy. Our innovative approach includes plotting the evolution of wavefront normal curves on the generalized momentum coordinate plane of the phase space — that commonly overlooked in traditional models focused only on position coordinates.
Pooled safety analysis of sacituzumab govitecan (SG) in multiple solid tumor types.
Authors: Rugo Hope S. , Tolaney Sara M. , Bardia Aditya , Cortes Javier , Marmé Frederik , Schmid Peter , Carey Lisa A. , Loibl Sibylle , Kalinsky Kevin , O'Shaughnessy Joyce , Hurvitz Sara A. , Valdez Theresa , Meng Ya , Verret Wendy , Tagawa Scott T.
Published: July 2024

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Background: SG is an antibody-drug conjugate targeted to Trop-2 that received approval for treatment of previously treated metastatic triple negative breast cancer (mTNBC) and HR+/HER2- mBC in multiple countries and accelerated approval for previously treated metastatic urothelial cancer (mUC) in the US. In multiple clinical trials, SG has demonstrated significantly improved efficacy compared to standard of care therapies and a consistent, manageable safety profile with limited treatment discontinuations from adverse events (AEs). We present an analysis of pooled safety data from patients (pts) treated with SG in clinical trials, including differences by UGT1A1 polymorphisms. Methods: Safety data for pts treated with SG (10 mg/kg, days 1 and 8 every 21-day cycle) were pooled from 4 clinical trials of multiple solid tumors, including mTNBC, HR+/HER2- mBC, and mUC: ASCENT (NCT02574455), TROPiCS-02 (NCT03901339), TROPHY-U-01 (NCT03547973), and IMMU-132-01 (NCT01631552). Treatment-emergent AEs (TEAEs) were defined as any AE that started on or after first dose date until ≤ 30 days after last dose date. Results: The pooled analysis included 1063 pts; > 99% experienced any-grade TEAEs, and 76% experienced grade ≥ 3 TEAEs (Table). The most common any-grade TEAEs were nausea (64%), diarrhea (64%), neutropenia (61%), and fatigue (51%). The most common grade ≥ 3 TEAEs were neutropenia (46%), anemia (12%), leukopenia (11%), and diarrhea (11%). Febrile neutropenia occurred in 6% of pts (both any-grade and grade ≥ 3). TEAEs led to SG dose reduction in 31% and SG discontinuation in 7% of pts. The most common TEAEs that led to discontinuation were neutropenia, diarrhea, pneumonia, and fatigue (1% each). In pts with available UGT1A1 genotypes, *28/*28 was associated with a higher rate of grade ≥ 3 TEAEs and TEAEs leading to dose reduction and SG interruption compared to *1/*1 and *1/*28 (Table). Conclusions: The results of the pooled safety analysis of pts treated with SG were consistent with previous clinical trials, with neutropenia remaining the most common grade ≥ 3 TEAE. Neutropenia and diarrhea were generally manageable, and the rate of TEAEs leading to discontinuation was low. The *28/*28 UGT1A1 genotype was associated with higher rates of grade ≥ 3 TEAEs, as previously observed. This is the largest SG safety analysis published to date, providing further support for SG as a treatment with a consistent and manageable safety profile. Clinical trial information: NCT02574455 , NCT03901339 , NCT03547973 , NCT01631552 . [Table: see text]
Efficacy and safety of fruquintinib in patients with metastatic colorectal cancer according to prior treatment sequence in the refractory setting: Results from FRESCO and FRESCO-2.
Authors: Bekaii-Saab Tanios S. , Dasari Arvind , Eng Cathy , Lonardi Sara , Yoshino Takayuki , Sobrero Alberto F. , Yao James C. , Garcia-Alfonso Pilar , Sartore-Bianchi Andrea , Hochster Howard S. , Hubbard Joleen M. , Price Timothy Jay , Tougeron David , Qin Shukui , Li Jin , Schelman William R. , Fan Songhua , Yu Ziji , Chen Lucy F. , Tabernero Josep
Published: July 2024

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Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 VEGF receptors. Based on FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) data, F was approved by the US FDA for previously treatedmetastatic colorectal cancer (mCRC). Efficacy and safety of F + best supportive care (BSC) vs placebo (P) + BSC were analyzed according to prior treatment (tx) sequence using FRESCO and FRESCO-2 data. Methods: In FRESCO and FRESCO-2, patients (pts) were randomized 2:1 to receive F 5 mg or matching P, PO daily x 21 days every 28 days. In FRESCO, eligible pts had received ≥2 prior chemotherapy regimens and were permitted to have received prior anti-VEGF and/or anti-EGFR therapies, whereas in FRESCO-2, in addition to standard chemotherapies, anti-VEGF, and anti-EGFR therapies if indicated, prior exposure to trifluridine/tipiracil (TAS) and/or regorafenib (rego) was required. FRESCO-2 pts must have also received a BRAF inhibitor and/or immunotherapy, if indicated and available in their country. Results: In FRESCO (F n=278 vs P n=138), no pts had received rego and 16/416 pts (4%) had received TAS. InFRESCO-2, prior therapies were balanced between F vs P arms; pts had received prior TAS or rego in these sequences: prior TAS only (n=240 vs n=121); prior rego only (n=40 vs n=18); prior rego then TAS (n=84 vs n=45); prior TAS then rego (n=95 vs n=44). Improvements in OS and PFS were seen with F vs P regardless of prior tx sequence (Table), with similar magnitudes of benefit for OS (HRs 0.53–0.77) and PFS (HRs 0.25–0.37). F safety profile was consistent regardless of prior tx sequence (Table). Conclusions: F is effective in mCRC with a manageable safety profile regardless of prior TAS or rego tx and sequence. Improvement with F was similar for OS and PFS despite the number and sequence of prior regimens. F provides a new tx option for pts with previously treated mCRC regardless of prior TAS or rego exposure. Clinical trial information: NCT04322539 . [Table: see text]