bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Size on the Stability of Narrow Foundation Pits
Authors: He Caihao , Lu Yi , Yang Yanlu
Published: December 2022

The traditional design method for narrow foundation pits ignores size effects. Engineering practice shows that this is too conservative and causes large‐scale waste. In this study, with the help of ABAQUS finite element software, retaining‐structure models in semi‐infinite and infinite elastic space are used to simulate the mechanical performances of pile‐supported structures under different combinations of excavation depth, retaining pile‐embedded depth, and excavation width. Furthermore, based on antioverturning stability theory and circular slip theory, the intrinsic relationship among these variables and their effects on the stability of excavation is analysed. Finally, based on the restraint effect of retaining structures on the soil below the pit bottom under actual working conditions, critical width is determined and used to classify foundation pits. Moreover, the applicability of existing codes is discussed. These results can improve the design and construction of narrow excavations, benefitting the construction industry and society in general.
Rare Proteus mirabilis Aortic Valve Infective Endocarditis without a Urinary Tract Infection
Authors: Gorn Sarah , Talley Nicholas , Mitchell Austin , Pineda Alejandro
Published: January 2023

Proteus mirabilis infective endocarditis is a rare disease with only 17 reported cases. It is typically associated with urinary tract infections (UTIs), staghorn calculi, and/or asymptomatic bacteriuria. We present a case of a 73-year-old male who presented with positive blood cultures for Proteus mirabilis but with a negative urinalysis and urine culture. He presented with acute renal failure and required hemodialysis. TTE was remarkable for a 30% ejection fraction, and no vegetations were visualized. TEE demonstrated a small vegetation on the left aortic valve. The initial urine culture remained negative throughout his hospitalization. He was treated with IV antibiotics and discharged without hemodialysis.
Selection of Semiconductor Packaging Materials by Combined Fuzzy AHP-Entropy and Proximity Index Value Method
Authors: Bingol Sedat
Published: January 2023

The residue of no-clean flux (NCF) on the printed circuit board assembly has been one of the major reasons for corrosion reliability failure of electronic devices. The source of aggressive contamination is the carboxylic acid activator as the main cleaning agent for soldering surfaces. Selecting the suitable activator has always been one of the concerns due to its conflicting properties, for example, suberic acid has a lower boiling point that will help in minimizing the residue; however, its dissociation constant is low which will increase the aggressive residue. The selection of a suitable activator based on the conflicting criteria is a multicriteria decision-making (MCDM) problem. In this study, thirty-one carboxylic acids (mono, di, tri, and hydroxyl) were ranked based on the six different criteria, i.e., melting point, molecular weight, boiling point, acid dissociation constant (pKaa value), solubility, and number of carboxylic acids using combined fuzzy AHP-entropy and the proximity index value method. Weight of the criterion was calculated using combined fuzzy AHP-entropy; whereas, ranking of the alternative carboxylic acid was done by the proximity index value method. First, the ranking was done based on the overall carboxylic acid; consequently, the groupwise ranking was also evaluated. As a result of this study, margaric acid occupied rank 1 out of all the thirty-one carboxylic acids and monocarboxylic acids; whereas, malonic acid acquired the lowest rank. In addition, out of 9 dicarboxylic acids, sebacic acid was the most suitable alternative. In the case of tricarboxylic acids, trimesic acid was a suitable alternative. Sensitivity analysis was performed to verify the reliability and consistency of the result obtained through applied MCDM.
The Oxidative Drug Combination for Suppressing KRAS G12D Inducible Tumour Growth
Authors: Begimbetova Dinara , Kukanova Assiya , Fazyl Fatima , Manekenova Kenzhekyz , Omarov Talgat , Burska Agata N. , Khamijan Medina , Gulyayev Alexandr , Yermekbayeva Bakytgul , Makishev Abay , Saliev Timur , Batyrbekov Kanat , Aitbayev Chokan , Spatayev Zhanat , Sarbassov Dos
Published: December 2022

Background. Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective. To determine how effective is the ATO/D‐VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D‐ascorbic acid isomer (D‐VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods. In this study, we examined the effectiveness of ATO and D‐VC on xenograft models—AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results. The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D‐VC is a promising approach to overcome the limitation of drug selectivity and efficacy.
Practical Philosophy West and East
Authors: Forster Michael N.
Published: December 2022

This article offers a broad-ranging comparison of practical philosophy in the West and in China with a view to enabling not only better mutual understanding between the two sides but also better self-understanding on each side. Contrary to widespread Western conceptions that Chinese practical philosophy may have contributed some important principles in first-order morality but has contributed little in the area of meta-ethics as compared to the West, it is argued here that Chinese practical philosophy did indeed make important contributions in first-order morality, but that in addition it is generally superior to Western practical philosophy in the area of meta-ethics. There are, however, certain exceptions to this rule on both sides. In the end, therefore, a comparison of the two traditions can contribute not only to a better mutual understanding, but also to a better self-understanding and improvement on each side.
Between and beyond Consequentialism and Deontology: Reflections on Mencius’ Moral Philosophy
Authors: Bai Tongdong
Published: December 2022

Mencius’s account of the yi-li (righteousness-benefit) distinction is important in his moral philosophy, and is often compared with consequentialism or deontology in Western moral philosophy. After showing the problems with a naïve deontological reading and a sophisticated consequentialist reading of Mencius, I will argue that both a really sophisticated consequentialist reading and a non-Kantian deontological reading are more defensible. But they couldn’t address the inequality hidden in Mencius’s moral philosophy, making a Nietzschean reading possible. However, Mencius embraced compassion as a key virtue, which Nietzsche would reject. Mencius’s moral philosophy is doubly bifurcated and different from consequentialism, deontology, and also Nietzsche’s philosophy.
Unexceptional Moral Knowledge
Authors: Williamson Timothy
Published: December 2022

The article defends moral realism against epistemological objections by arguing that if there are moral truths, some of them are known. The claim that moral properties are unknowable because causally inert is shown to be ineffective: none of the main current theories of knowledge requires a causal connection, and anyway moral properties have not been shown to be causally inert. It is explained why a posteriori moral knowledge need not derive from combining a priori moral knowledge with a posteriori non-moral knowledge. The possibility of moral knowledge by perception and by testimony is briefly defended. The role of recognitional capacities for instances of moral properties is emphasized.
“How to Make Athens Closer to Jerusalem”
Authors: Sidharta (戴永富) Leonard
Published: December 2022

Theology and philosophy are strange bedfellows: although they share many similar interests and constantly influence each other, their relationship is fraught with suspicion or even enmity. This problem is especially acute for those who want to harmonize their commitment to sola Scriptura with the use of philosophy in their theology. Drawing insights from Herman Bavinck’s Neo-Calvinist worldview, I argue that this apparent competition is mainly caused by the failure to recognize the organic unity between both disciplines. Without theology, all disciplines would be meaningless, but without philosophy, all disciplines would be unintelligible. Portraying the harmony between theology and philosophy depends on the success of locating the difference and relationship between the universality of theology and that of philosophy. Further, the organicity that suffuses all things and affirms the primacy of special revelation reflects the Neo-Calvinist belief in both sola Scriptura and the sacredness of all vocations.
Short-Term Comparison Between Unilateral Versus Bilateral Percutaneous Pedicle Screw Fixation in Short-Level Lateral Lumbar Interbody Fusion–A Prospective Randomized Study
Authors: Hiyama Akihiko , Katoh Hiroyuki , Sakai Daisuke , Sato Masato , Watanabe Masahiko
Published: December 2022

Study Design

Prospective randomized controlled trial.

Objectives

No prospective studies have directly compared clinical and radiographic outcomes of unilateral vs bilateral instrumented lateral lumbar interbody fusion (LLIF) for lumbar degenerative disease (LDD). We compared the short-term radiographic, clinical outcomes, and some complications of the unilateral percutaneous pedicle screw (PPS) (UPS) vs bilateral PPS (BPS) fixation in short-level spinal fusion with LLIF for LDD.

Methods

This was a prospective randomized controlled study of 33 patients who underwent UPS or BPS fixation after LLIF for LDD; 18 patients were assigned to the UPS group and 15 patients to the BPS group. Clinical outcomes, complication rates, and fusion rates were assessed.

Results

The two groups were similar in age, sex, preoperative diagnosis, and level of surgery. Blood loss, length of hospital stay, and numeric rating scale score one year after surgery did not differ between groups. The operative time was longer in the BPS than UPS group (120.2 vs 88.8 min, respectively; P = .029). Both groups showed improvement in disc height and dural sac in the immediate postoperative computed tomography and magnetic resonance imaging, which did not differ significantly between groups. The subsidence grade and fusion rate did not differ, but cage subsidence was more severe in the UPS than BPS group.

Conclusion

Unilateral and bilateral PPS fixation after LLIF yielded similar short-term clinical and radiological outcomes. However, severe cage subsidence was more common in the UPS group, which suggests that BPS fixation after LLIF may be a better choice over the long term.
The exhaustion of lymphocytes is the main factor that decreases the sensitivity of QFT-GIT detection in silicosis
Authors: Yu Xin , Huang Li-Na , Xu Jun-Chi , Song Yi-Yan , Chen Hui , Shi Cui-Lin , Tang Pei-Jun , Tao Tao , Zhu Ye-Han
Published: December 2022

Background

Tuberculosis infection is a major complication of silicosis, but there is no study on whether silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analyze the relationship between silicosis and QFT-GIT, determine the main factor of the QFT-GIT sensitivity decrease in silicosis and explore the methods to increase the sensitivity.

Methods

Silicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used.

Results

The sensitivity of QFT-GIT in silicosis patients (58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients and silicosis only patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis.

Conclusions

This is the first study to analyze the relationship between immune exhaustion and QFT-GIT in silicosis and found that the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provided a new method to improve the sensitivity of QFT in silicosis. The study also found that silicosis can increase PD-1 expression. As PD-1 functions in infectious diseases, it will promote immune exhaustion in silicosis and lead to tuberculosis from latent to active infection. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.
Molecular mechanisms involved in the IL-6-mediated upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) expression in the chorionic villi and decidua of women in early pregnancy
Authors: Wang Rui , Zhao Shuyun , Chen Xiaojuan , Xiao Ziwen , Wen Xinghui , Zhong Xingming , Li Shixiang , Cheng Hui , Huang Guanyou
Published: December 2022

Background

IL-6 induces the upregulation of indoleamine 2,3-dioxygenase (IDO1) at the maternal-foetal interface, but the regulation mechanisms of IDO1 by IL-6 at this interface have not been fully understood.

Methods

Western blotting, qRT–PCR and/or immunohistochemistry were employed to measure the expression of IDO1, IL-6, SHP-1/2, SOCS3 and STAT3/p (STAT3 and pSTAT3) in tissues of chorionic villi and decidua (TCVD) in vivo and in cultured TCVD that were treated with IL-6 in the presence or absence of an IL-6 inhibitor.

Results

Mutually positive relationships among the protein levels of IL-6, IDO1, SHP-1/2 and STAT3/p was observed, and the expression of IDO1, SHP-1/2 and STAT3/p was increased in a dose-dependent manner in TCVD in vivo and in cultured TCVD treated with IL-6 at increasing concentrations (0–100 ng/ml). The level of IL-6 was negatively related to SOCS3 level in TCVD. The expression of SOCS3 was increased in a dose-dependent manner, and SOCS3 level was positively correlated with SHP-1, SHP-2 and STAT3/p level in cultured TCVD treated with 0–2 ng/ml IL-6; however, opposite results were observed after treatment with 2–100 ng/ml IL-6. The IL-6-induced upregulation of IDO1, SHP-1, SHP-2 and STAT3/p expression could be reversed, while the IL-6-induced upregulation of SOCS3 expression was exacerbated by Corylifol A.

Conclusions

In normal pregnancy, IL-6 upregulates the expression of IDO1 by promoting SHP-1/2 expression via STAT3/p and simultaneously negatively regulates the expression of SOCS3. High expression of IL-6 causes the upregulation of IDO1 expression and the downregulation of SOCS-3 expression, which may be beneficial for maintaining immunological tolerance.
Clinical features of cancer with unknown primary site (clinical features, treatment, prognosis of cancer with unknown primary site)
Authors: Yang HongLiang , He Feng , Xu Wen , Cao Zeng
Published: December 2022

Cancer of unknown primary site(CUPs) is a metastatic syndrome with an unidentifiable primary tumor, even after extensive workup to seek the primary site. CUPs accounts for about 3%-5% of the total number of all cancer diagnoses worldwide. The current precision medicine era has reclassified patients with CUPs into the favorable and unfavorable prognostic subset. In this study clinical characteristics and treatment of patients of CUPs were retropactively analysed. Thirty-two patients treated from July 2016 to October 2021 were included in the Affiliated Tumor Hospital of Tianjin Medical University(Tianjin, China).Common symptoms were anemia, fever, enlarged lymph nodes, abdominal pain, edema/multiple serous cavity effusion. Patients with good prognostic factors achieved good outcomes with treatment, conversely, patients with poor prognosis were generally treated empirically and had poorer outcomes. After anti-tumor treatment, the total effective rate was 41 percent(41% was the percentage of patients who achievedtumour respons). To the end of follow-up, after anti-tumor treatment, the median Overall Survival(OS) of patients was 5.4 months.
Evaluation of strategies for the prevention of mother-to-child transmission of HIV in Cameroon: a mixed qualitative and quantitative cross-sectional analysis from the Adamawa region of Cameroon
Authors: Kameni Bibiane Siaheu , Nansseu Jobert Richie , Bigna Jean Joel , Tatah Sandra Ayuk , Seyler Catherine
Published: December 2022

Background

To accelerate the fight against HIV/AIDS and eliminate the mother-to-child transmission (MTCT) of the virus, Cameroon has implemented and intensified several strategies despite which numerous children continue to be born infected with HIV. This study aimed to evaluate these strategies put in place for the prevention of MTCT (PMTCT) in Cameroon.

Methods

A qualitative and quantitative cross-sectional analysis was conducted in seven PMTCT care units situated in the Adamawa region of the country. The qualitative analysis included 16 individual interviews of key informants and observations of attitudes and practices being implemented in each unit. On the other hand, the quantitative analysis targeted 106 known HIV-positive breastfeeding women being followed-up at the unit.

Results

Task-shifting and sharing was effective, but majority of staffs had not received any specific training on PMTCT. Moreover, the integration of PMTCT within the maternal, neonatal and child health services remained ineffective, especially in health facilities of heavy workload. The coordination of PMTCT services was led by a well-designated focal person; however, his/her roles and responsibilities had not clearly been defined. Of the 106 women enrolled, 59.4% had a level of knowledge on PMTCT less than 80%. Similarly, their attitudes and practices towards PMTCT were inadequate or inaccurate in more than 60% of cases.

Conclusion

PMTCT strategies are globally well known and accepted by healthcare professionals. However, weaknesses have been figured out regarding service integration, task shifting and sharing, and coordination. In addition, beneficiaries’ attitudes and practices are insufficient, and their level of knowledge does not guarantee to lessen the risk of MTCT of HIV.
A New Zealand regional work-related sprains and strains surveillance, management and prevention programme: study protocol
Authors: Laird Ian , McIntyre Justine , Borman Barry , Adank Rod , Ashby Liz
Published: December 2022

Background

The impact and costs associated with work-related sprains and strains in New Zealand and globally are substantial and a major occupational and public health burden. In New Zealand around one-third of all sprains and strains workers compensation (ACC) claims (2019) are for back injuries, but shoulder and arm injuries are increasing at a faster rate than other sprain and strain injuries (ACC, 2020). A need exists for a change to current approaches to sprains and strains prevention, to more effectively manage this significant and persistent problem in workplaces. Designing out hazards is one of the most effective means of preventing occupational injuries and illnesses. This paper outlines the study protocol of the surveillance, management and prevention programme and describes the utilisation of prevention through design principles in the prevention of work-related sprains and strains in agriculture/horticulture/food production in the Hawkes Bay region of New Zealand.

Methods

This is a prospective mixed methods study incorporating the collection of quantitative data to describe the epidemiology of work related sprains and strains injuries presenting to the regional health centre (Hastings Health Centre) over a period of 24 months and qualitative data from participants presenting at the health centre to identify high risk industry sectors/ occupations/ workplaces and tasks and design, develop and apply prevention through design principles/ solutions/interventions to critical features of the work and work environment and undertake an outcome evaluation during the last 6 months of the project.

Discussion

The purpose of this project is to establish an epidemiological surveillance programme to assess the incidence and prevalence of work-related sprains and strains according to age, sex, industry sector and occupation to target efforts to prevent work-related sprains and strains, by applying prevention through design (PtD) principles in selected workplaces in agriculture. The collection of more detailed case, occupational and work history data from a sample of patients presenting at the HHC clinic will identify high risk industry sectors/occupations/workplaces and tasks. Assessment techniques will include comprehensive design, design thinking and human factors/ergonomics methodologies through co-design and participatory ergonomics techniques. The PtD solutions/ interventions implemented will be evaluated using a quasi-experimental design consisting of a pre-test/ post-test with-in subjects design with control groups that do not receive the intervention.
Antibiotic artificial bone implantation for the treatment of infection after internal fixation of tibial plateau fractures
Authors: Hua Haotian , Zhang Lei , Guo Zairan , Zhong Wenlong , Chen Jiangfei , Guo Jiangang , Zhang Yang , Tong Peijian , Wang Xinwei
Published: December 2022

Objective

To explore the clinical effect of antibiotic artificial bone (Calcium phosphate) in the treatment of infection after internal fixation of tibial plateau fractures.

Methods

We retrospectively reviewed the clinical data of 32 patients with infection after internal fixation of tibial plateau fractures treating from March 2010 to October 2021. There were 18 males and 14 females, aged from 23 to 70 (average 49.66 ± 10.49), 19 cases of the left side and 13 cases of the right side. Among them, 7 cases were open fractures with initial injury and 25 cases were closed fractures. On the basis of thorough debridement and implanting antibiotic artificial bone, the internal fixation of 18 patients were tried to be preserved and the internal fixation of 14 patients were removed completely. In order to provide effective fixation, 14 patients also received external fixation. Postoperative wound healing, infection control, Hospital for Special Surgery knee scores (HSS), related inflammatory indicators and bone healing time were recorded and followed up.

Results

Thirty-two patients were followed up for 12 ~ 82 months (average 36.09 ± 19.47 months). The redness, swelling and pain of pin site occurred in 2 patients, which returned to normal after applying antibiotics and continuous dressing change. One patient retained the internal fixation during the first-stage operation. Redness and swelling of incision, subcutaneous undulation occurred after two months. In order to avoid the recurrence of infection, the internal fixation was removed completely and antibiotic artificial bone was filled again. The infection was controlled and fracture healed. Four patients’ wounds could not be closed directly due to soft tissue defect and was covered with skin flap. After the first-stage operation, 12 patients received second-stage autologous iliac bone grafting due to residual bone defects and poor healing of the fracture end. The bone healing time was 4 ~ 16 months (average 7.31 ± 2.79 months). Inflammatory indicators including CRP, ESR, and WBC returned to normal levels within 2 ~ 10 weeks (average 4.97 ± 2.58 weeks). The HSS of all patients were 54 ~ 86 points (average 73.06 ± 8.44 points) at the last follow-up.

Conclusion

Implantation of antibiotic artificial bone, retention or removal of internal fixation according to infection and fracture healing, application of external fixation timely is an effective method to treat infection after internal fixation of tibial plateau fractures, which can control infection effectively and promote functional recovery.
Association between PPARγ, PPARGC1A, and PPARGC1B genetic variants and susceptibility of gastric cancer in an Eastern Chinese population
Authors: Chen Boyang , Wang Yafeng , Tang Weifeng , Chen Yu , Liu Chao , Kang Mingqiang , Xie Jinbiao
Published: December 2022

Purpose

Previous studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC).

Patients and methods

We performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit.

Results

The PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42–0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42–0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2.

Conclusion

This study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.
Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients
Authors: Charpentier Etienne , Redheuil Alban , Bourron Olivier , Boussouar Samia , Lucidarme Olivier , Zarai Mohamed , Kachenoura Nadjia , Bouazizi Khaoula , Salem Joe-Elie , Hekimian Guillaume , Kerneis Matthieu , Amoura Zahir , Allenbach Yves , Hatem Stephane , Jeannin Anne-Caroline , Andreelli Fabrizio , Phan Franck ,   COVID-19 APHP. SU Group, Tilmont Romain , Chenu Romain , Meyfroit Louise , Pasi Nicoletta , Larbi-Messaoud Schahrazed , Laroche Suzanne , Ciangura Cécile , Popelier Marc , Jacqueminet Sophie , Halbron Marine , Hartemann Agnès
Published: December 2022

Background

Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D.

Methods

Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined.

Results

One hundred and eight controls [median age: 76(IQR:59–83), 61% male, median BMI: 24(22–27)] and ninety-four T2D patients [median age: 70(IQR:61–77), 70% male, median BMI: 27(24–31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was  > 100 mL/m2 with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death.

Conclusions

Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution.
Modular co-culture engineering of Yarrowia lipolytica for amorphadiene biosynthesis
Authors: Marsafari Monireh , Azi Fidelis , Dou Shaohua , Xu Peng
Published: December 2022

Amorphadiene is the precursor to synthesize the antimalarial drug artemisinin. The production of amorphadiene and artemisinin from metabolically engineered microbes may provide an alternate to plant secondary metabolite extraction. Microbial consortia can offer division of labor, and microbial co-culture system can be leveraged to achieve cost-efficient production of natural products. Using a co-culture system of Y. lipolytica Po1f and Po1g strains, subcellular localization of ADS gene (encoding amorphadiene synthase) into the endoplasmic reticulum, co-utilization of mixed carbon source, and enlargement of the endoplasmic reticulum (ER) surface area, we were able to significantly improve amorphadiene production in this work. Using Po1g/PPtM and Po1f/AaADSERx3/iGFMPDU strains and co-utilization of 5 µM sodium acetate with 20 g/L glucose in YPD media, amorphadiene titer were increased to 65.094 mg/L. The enlargement of the ER surface area caused by the deletion of the PAH1 gene provided more subcellular ER space for the action of the ADS-tagged gene. It further increased the amorphadiene production to 71.74 mg/L. The results demonstrated that the importance of the spatial localization of critical enzymes, and manipulating metabolic flux in the co-culture of Y. lipolytica can be efficient over a single culture for the bioproduction of isoprenoid-related secondary metabolites in a modular manner.

Graphical Abstract
Assessing the inequality in out-of-pocket health expenditure among the chronically and non-chronically ill in Saudi Arabia: a Blinder-Oaxaca decomposition analysis
Authors: Al-Hanawi Mohammed Khaled , Njagi Purity
Published: December 2022

Background

Many high-income countries have made significant progress towards achieving universal health coverage. Nevertheless, out-of-pocket (OOP) health expenditure continues to undermine the effectiveness of the universal healthcare system. In Saudi Arabia, due to the overburdened free public health services, many people opt for alternative healthcare services, risking high OOP payments. The presence of chronic illness further exacerbates this situation. However, there is limited evidence on the extent of the gap in OOP health expenditure between the chronically and non-chronically ill and the associated drivers contributing to this gap. The aim of this study was to assess inequalities in relative OOP health expenditure, estimated as the percentage of income spent on healthcare, between the chronically and non-chronically ill in Saudi Arabia and their associated drivers.

Methods

Data from 10,785 respondents were obtained from a national cross-sectional survey conducted in Saudi Arabia as part of the 2018 Family Health Survey. Inequalities in relative OOP health expenditure were measured using concentration indices and curves. A Blinder-Oaxaca decomposition analysis was used to assess the differences in relative OOP health expenditure between the chronically and non-chronically ill.

Results

The results showed that the chronically ill experience a higher financial burden due to healthcare services in absolute costs and relative to their income compared to the non-chronically ill. In addition, there was higher pro-poor inequality (–0.1985) in relative OOP health expenditure among the chronically ill compared to that (–0.1195) among the non-chronically ill. There was a 2.6% gap in relative OOP health expenditure among the chronically and non-chronically ill, of which 53.8% was attributable to unexplained factors, with explained factors accounting for the 46.2% difference. Factors that significantly contributed to the overall gap (i.e. both explained and non-explained factors) included employment status, insurance status, self-rated health, and periodic check-ups.

Conclusion

This study underscores the high financial burden due to OOP payments among the chronically ill and the existence of pro-poor inequalities. In addition, there is a significant gap in relative OOP health expenditure between the chronically and non-chronically ill, which is mainly attributable to differences in socio-economic characteristics. This indicates that the existing financial mechanisms have not been sufficient in cushioning the chronically ill and less well off in Saudi Arabia. This situation calls for health policymakers to integrate a social safety net into the health financing system and to prioritize the disadvantaged population, thereby ensuring access to health services without experiencing financial hardship.
Metabolic pathway analysis of hyperuricaemia patients with hyperlipidaemia based on high-throughput mass spectrometry: a case‒control study
Authors: Wei Xue , Jia Xiaodong , Liu Rui , Zhang Sha , Liu Shixuan , An Jing , Zhou Lei , Zhang Yushi , Mo Yuanning , Li Xiao
Published: December 2022

Background

Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics.

Methods

This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software.

Results

The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway.

Conclusions

Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.
Adverse effects of low serum lipoprotein cholesterol on the immune microenvironment in gastric cancer: a case‒control study
Authors: Zou Yi , Yu Xiaoyan , Zhou Chenqi , Zhu Chunpeng , Yuan Ying
Published: December 2022

Background

Cholesterol is crucial for tumor immune microenvironment (TIME) remodeling. Serum lipoprotein cholesterol is closely associated with gastric cancer (GC) progression, but whether it affects TIME remodeling is unknown.

Methods

GC patients with differential serum high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol levels were collected. After balancing the baseline, immunohistochemical staining was performed on serial whole-tissue sections to detect B-cell and T-cell subsets, macrophages, and PD-L1. Features of tertiary lymphoid structures (TLSs) and the extra-TLS zone, including TLS distribution and maturation, immune cell density, and PD-L1 expression, were measured by annotating TLSs or regions of interest (ROIs) in the extra-TLS zone.

Results

A total of 9,192 TLSs and over 300 ROIs from 61 patients were measured. Compared to HDL-normal patients, HDL-low patients had a decreased secondary-TLS fraction or density but an elevated NK-cell density in the extra-TLS zone. Compared to LDL-normal patients, LDL-low patients had a higher ratio of PD-1 + T follicular helper cells to CD20 + B cells in TLSs, a higher ratio of PD-1 + T cells to CD8 + T cells and increased PD-1 + T-cell density in the extra-TLS zone. Different correlations were found in groups with differential HDL or LDL levels. Cell dynamics in the immune response were weaker in patients with low lipoprotein cholesterol. TLS parameters reached their peak earlier than those of the extra-TLS zone along with tumor progression.

Conclusion

Low serum lipoprotein cholesterol caused adverse effects on antitumor immunity in GC. Lipid management or immunometabolic drugs deserve more attention.
Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study
Authors: Arrestier Romain , Bastard Paul , Belmondo Thibaut , Voiriot Guillaume , Urbina Tomas , Luyt Charles-Edouard , Gervais Adrian , Bizien Lucy , Segaux Lauriane , Ben Ahmed Mariem , Bellaïche Raphaël , Pham Taï , Ait-Hamou Zakaria , Roux Damien , Clere-Jehl Raphael , Azoulay Elie , Gaudry Stéphane , Mayaux Julien , Fage Nicolas , Ait-Oufella Hafid , Moncomble Elsa , Parfait Mélodie , Dorgham Karim , Gorochov Guy , Mekontso-Dessap Armand , Canoui-Poitrine Florence , Casanova Jean-Laurent , Hue Sophie , de Prost Nicolas
Published: December 2022

Background

Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs.

Results

We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12–1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1–3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38–1.26], p = 0.23).

Conclusions

In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.
Frailty is a stronger predictor of death in younger intensive care patients than in older patients: a prospective observational study
Authors: De Geer Lina , Fredrikson Mats , Chew Michelle S.
Published: December 2022

Background

While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages.

Methods

Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups.

Results

Patients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8–11.4), P < 0.05; 8.0 (4.0–16.2), P < 0.05; 4.1 (2.2–6.6), P < 0.05; 2.4 (1.1–5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P < 0.05).

Conclusions

Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.
Nuclear Receptor Imaging In Vivo—Clinical and Research Advances
Authors: Parent Ephraim E , Fowler Amy M
Published: December 2022

Nuclear receptors are transcription factors that function in normal physiology and play important roles in diseases such as cancer, inflammation, and diabetes. Noninvasive imaging of nuclear receptors can be achieved using radiolabeled ligands and positron emission tomography (PET). This quantitative imaging approach can be viewed as an in vivo equivalent of the classic radioligand binding assay. A main clinical application of nuclear receptor imaging in oncology is to identify metastatic sites expressing nuclear receptors that are targets for approved drug therapies and are capable of binding ligands to improve treatment decision-making. Research applications of nuclear receptor imaging include novel synthetic ligand and drug development by quantifying target drug engagement with the receptor for optimal therapeutic drug dosing and for fundamental research into nuclear receptor function in cells and animal models. This mini-review provides an overview of PET imaging of nuclear receptors with a focus on radioligands for estrogen receptor, progesterone receptor, and androgen receptor and their use in breast and prostate cancer.
The potential usage of thyroid hormones as sport doping - a mini-review
Authors: Gałązka Jakub
Published: January 2023

A thyroid gland is one of the most important organs of a human body. Thyroid hormones, at least in physiological concentration, have anabolic features. The aid of this review is to summarize knowledge on potential usage of thyroid hormones in sport doping.

            Thyroid hormones play a crucial role in skeletal muscles physiology. The exposition to T3 and T4 may improve myogenesis, muscles regeneration and muscles blood blow. In a long-time perspective, those hormones may help in reducing body weight.

            According to those mechanisms, thyroid hormones may be considered as a plausible agent in sport doping. However WADA guidelines does not include T3 or T4 in a list o sport doping substances, the debate on their inclusion is on-going, and the physicians should be aware of thyroid hormones effects on human metabolism from sports medicine perspective.
Wilms Tumor - Pathogenesis, diagnosis, treatment and prognosis
Authors: Milczek Maria , Warzyszak Paweł , Żołyniak Wojciech , Tomasik Mikołaj , Hawranik Izabela , Żaba Ziemowit , Niski Szymon , Małek Róża , Lisowska Aleksandra , Skrzypek Mateusz
Published: January 2023

Introduction: Wilms tumor is the most common occuring malignant tumor of kidney among children. Mostly appears in infants and young children. The main symptom is enlargement od the abdomen. It is often diagnosed incidentally during USG examination.

Aim of the study: Summary of current knowledge on the pathogenesis, diagnosis, treatment and prognosis of Wilms Tumor.

Methods and matherials: A review of  the literaturę available in the PubMed data base, using the following keywords: :„Wilms Tumor”,„Wilms tumor genetics”

State of knowledge: Wilms tumor appears more often among people with certain genetic syndromes. There are two to treat WT depending on the world region (SIOP, COG). According to SIOP, the diagnosis is made based on imaging. This is followed by neoadiuvant chemotherapy, and then it is surgically removed. According to COG, the first stage of treatment is surgical removal of the tumor, then chemotherapy. During chemotherapy, vincristine, actinomycin, doxodubicin are used in both schemes. Although both strategies differ in their pretreatment approach, they lead to similar overall survival rates.

Conclusions:Despite already advanced treatment techniques for the tumor, and extensive knowledge about it, its pathogenesis still remains somewhat unknown. Increased understanding of the aberrant molecular pathways active in Wilms tumorigenesis has identified many potential targeted therapeutic approaches that could be applied in a clinical setting