bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ repair or reconstruction of the abdominal aorta-iliac artery by autologous fascia-peritoneum with posterior rectus sheath for the treatment of the infected abdominal aortic and iliac artery aneurysms: A case series and literature review
Authors: Li Lubin , Liu Guolong , Yu Benxiang , Niu Wenqiang , Pei Zhigang , Zhang Juwen , Che Haijie , Song Fubo , Yang Mu
Published: November 2022

Background

Infected abdominal aortic and iliac artery aneurysms are considered acute and severe diseases with insidious onset, rapid development, and high mortality in vascular surgery. Currently, there is no better treatment, either anatomic or extra-anatomical repair.

Case presentation

From February 2018 to April 2022, 7 patients with infected abdominal aortic and iliac artery aneurysms did not have sufficient autologous venous material for repair. With the consent of the Ethics Committee of the hospital, it uses the autologous peritoneal fascial tissue with rectus sheath to repair or reconstruct the infected vessels in situ. There were 5 cases of infected abdominal aortic aneurysm, 1 case of an infected common iliac aneurysm, and 1 case of the infected internal iliac aneurysm. Aortoduodenal fistula was found in 3 cases, all of them were given duodenal fistula repair and gastrojejunostomy and cholecystostomy. Three cases of infected abdominal aortic aneurysms were repaired with the autologous peritoneal fascial tissue patch, and 2 cases of infected abdominal aortic aneurysms were reconstructed by the autologous peritoneal fascial tissue suture to bifurcate graft in situ, the autologous peritoneal fascial tissue suture reconstructed the rest 2 cases of infected iliac aneurysm to tubular graft in situ. It was essential that Careful debridement of all infected tissue and adequate postoperative irrigation and drainage. Antibiotics were administered perioperatively, and all patients were subsequently treated with long-term antibiotics based on bacterial culture and susceptibility results of infected tissues and blood. All 7 patients had underwent surgery successfully. But there were 2 cases died of anastomotic infection or massive hemorrhage after the operation, the other 5 cases survived. The follow-up time was 2–19 months. The enhanced CT of postoperation showed that the reconstructed arteries were smooth without obvious stenosis or expansion, and no abdominal wall hernia occurred.

Conclusion

In situ repair or reconstruction with autologous peritoneal fascial tissue with rectus sheath is a feasible treatment for the infected aneurysm patients without adequate autologous venous substitute, but it still needs long-term follow-up and a large sample to be further confirmed.
Analysis of blood lipid changes and influencing factors in physical examination population of a city in central China
Authors: Zhu Boya , Wang Wenjing , Li Mengying , Peng Shuzhen , Tan Xiaodong
Published: November 2022

Purpose

The prevalence of cardiovascular diseases (CVDs) associated with lipid levels is increasing worldwide. Our purpose is to analyze the distribution level and influencing factors of lipid in the whole population and to put forward suggestions for preventing abnormal lipid levels.

Methods

The study was based on a sample of 91,480 Chinese who participated in a nationwide physical examination program in Wuhan, a midland city in China, in 2018. The distribution of blood lipid in the population was observed using average, and the relationship between the influencing factors and blood lipid level was observed by quantile regression (QR).

Results

A total of 91,480 people were evaluated in this study, among which 59,165 (64.68%) were female with a mean age of 51.71 ± 10.82 years. QR results showed that different physical examination indexes had different effects on lipid levels. Fasting plasma glucose (FBG) has the largest QR coefficient and BMI had positive effects on total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). In males, age has a positive influence on TC, LDL-C, and high-density lipoprotein cholesterol (HDL-C), while in females, age has a positive influence on all four indexes.

Conclusion

We found that the TC and LDL-C levels of females were more susceptible to age than males, and the lipid levels of older females were higher than males. BMI has a greater effect on lipid levels in males than in females. Regardless of gender should pay attention to dyslipidemia caused by diabetes and abnormal liver function.
Unsupervised mobile app-based cognitive testing in a population-based study of older adults born 1944
Authors: Öhman Fredrik , Berron David , Papp Kathryn V. , Kern Silke , Skoog Johan , Hadarsson Bodin Timothy , Zettergren Anna , Skoog Ingmar , Schöll Michael
Published: November 2022

Background

Mobile app-based tools have the potential to yield rapid, cost-effective, and sensitive measures for detecting dementia-related cognitive impairment in clinical and research settings. At the same time, there is a substantial need to validate these tools in real-life settings. The primary aim of this study was thus to evaluate the feasibility, validity, and reliability of mobile app-based tasks for assessing cognitive function in a population-based sample of older adults.

Method

A total of 172 non-demented (Clinical Dementia Rating 0 and 0.5) older participants (aged 76–77) completed two mobile app-based memory tasks—the Mnemonic Discrimination Task for Objects and Scenes (MDT-OS) and the long-term (24 h) delayed Object-In-Room Recall Task (ORR-LDR). To determine the validity of the tasks for measuring relevant cognitive functions in this population, we assessed relationships with conventional cognitive tests. In addition, psychometric properties, including test-retest reliability, and the participants’ self-rated experience with mobile app-based cognitive tasks were assessed.

Result

MDT-OS and ORR-LDR were weakly-to-moderately correlated with the Preclinical Alzheimer's Cognitive Composite (PACC5) (r = 0.3–0.44, p < .001) and with several other measures of episodic memory, processing speed, and executive function. Test-retest reliability was poor–to-moderate for one single session but improved to moderate–to-good when using the average of two sessions. We observed no significant floor or ceiling effects nor effects of education or gender on task performance. Contextual factors such as distractions and screen size did not significantly affect task performance. Most participants deemed the tasks interesting, but many rated them as highly challenging. While several participants reported distractions during tasks, most could concentrate well. However, there were difficulties in completing delayed recall tasks on time in this unsupervised and remote setting.

Conclusion

Our study proves the feasibility of mobile app-based cognitive assessments in a community sample of older adults, demonstrating its validity in relation to conventional cognitive measures and its reliability for repeated measurements over time. To further strengthen study adherence, future studies should implement additional measures to improve task completion on time.
“Screwed from the start”: How women perceive opportunities and barriers for building a successful research career
Authors: Berggren Åsa , Almlöv Cecilia , D’Urso Alexandra , Grubbström Ann
Published: November 2022

After finishing the PhD, the researcher enters a stage in their early research career where more independence is expected. Within a relatively short time period, the researcher needs to gather research experience and support in the form of tangible resources as funding, and intangible resources like access to research networks, close collaborations, and mentorship to support their next career stage. How resources are allocated are therefore important determinants for the success of researchers. However, research shows that the resource allocation decisions in academia are biased in favor of men, with many of these gender biases that influence the success of research careers increasing. In this study, we asked women employed as early-career researchers (WECRs) about how they view their opportunities and potential for long-term success within academia, and how this relates to the resources that they have access to. We found that the WECRs were given few resources and support, and that they perceived that finding resources important for their career was up to themselves. The noticeable male dominance in who receives resources and positions within the university and the lack of women as role-models signals to WECRs that they are not wanted in academia. The WECRs suggest several ways to improve the possibilities for a successful research career for women on more equal terms as their male collegues: these include transparent processes for resource allocations, equal opportunity officers in all hiring processes, and mandatory gender training for all senior research and administrative staff. All the actions suggested are within the control of the university.
Maternal diabetes and the role of neonatal reticulocyte hemoglobin content as a biomarker of iron status in the perinatal period
Authors: Babacheva Evgeniya , Rallis Dimitrios , Christou Helen , Mitsiakos George , Mikos Themistoklis , Dampala Kalliopi , Tsakalidis Christos , Kioumi Anna , Goulis Dimitrios G. , Soubasi Vasiliki
Published: November 2022

Aims

We aimed to evaluate the effects of maternal diabetes on neonatal iron status, measuring erythrocyte indices including hemoglobin, hematocrit, reticulocytes, mean corpuscular volume (MCV), percent (%) hypochromia, ferritin, and additionally mean reticulocyte hemoglobin content (MCHr) as an early marker of iron deficiency, and examine the association between neonatal MCHr, red cell indices, and ferritin.

Materials and Methods

We conducted a hospital-based prospective cohort study in a tertiary neonatal unit of a University Hospital from 2018 to 2020. We enrolled 126 maternal-infant pairs of mothers whose pregnancy was associated with diabetes and 74 maternal-infant pairs from uncomplicated pregnancies. Erythrocyte indices were analyzed within the first twelve hours after birth. Erythrocyte parameters were compared between infants of the diabetes and the non-diabetic group. We examined the correlation of the neonatal MCHr with perinatal characteristics, including gestation, birth weight, maternal body mass index, the erythrocytic indices, maternal diabetes, maternal obesity, prematurity, small-for-gestational-age status, maternal preeclampsia, and maternal anemia. Finally, we evaluated the discordance between neonatal MCHr and neonatal ferritin.

Results

Infants of the diabetes group had a significantly lower MCHr (32.6 pg vs. 34.2 pg, p=0.003) compared with infants of uncomplicated pregnancies. Neonatal MCHr was significantly correlated with maternal hypochromia (r=-0.237, p=0.004) and neonatal MCV (r=0.674, p<0.001). Neonatal MCHr was significantly associated with maternal diabetes [standardized coefficients 0.21, 95% confidence interval (CI) 0.05-0.58, p=0.003) and maternal preeclampsia (standardized coefficients 0.17, 95% CI 0.02-0.92, p=0.019), after adjusting for maternal anemia, maternal obesity, prematurity, and small-for-gestational-age status. Those results were consistent also when analyzing maternal-infant pairs with pre-existing diabetes, and maternal-infant pairs with gestational diabetes. There was significant discordance between neonatal MCHr and neonatal ferritin (p=0.001).

Conclusions

MCHr was significantly lower in infants of mothers whose pregnancy was associated with diabetes compared with infants of non-diabetic mothers and correlated with neonatal and maternal red cell indices of iron deficiency. Since there was significant discordance between neonatal MCHr and ferritin during the first postnatal day, it is possible that MCHr could be used as a screening test for iron deficiency, especially in infants.
Comparison of four tools to identify painful new osteoporotic vertebral fractures in the postmenopausal population in Beijing
Authors: Guo SiJia , An Ning , Lin JiSheng , Fan ZiHan , Meng Hai , Yang Yong , Fei Qi
Published: November 2022

Objectives

To validate and compare four tools, the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD), Beijing Friendship Hospital Osteoporosis Screening Tool (BFH-OST), Osteoporosis Self-Assessment Tool for Asians (OSTA), and BMD, to identify painful new osteoporotic vertebral fractures (PNOVFs).

Methods

A total of 2874 postmenopausal women treated from June 2013 to June 2022 were enrolled and divided into two groups: patients with PNOVFs who underwent percutaneous vertebroplasty (PNOVFs group, n = 644) and community-enrolled females (control group, n = 2230). Magnetic resonance and X-ray imaging were used to confirm the presence of PNOVFs. Dual-energy X-ray absorptiometry was performed to calculate the BMD T-scores. Osteoporosis was diagnosed according to WHO Health Organization criteria. Data on the clinical and demographic risk factors were self-reported using a questionnaire. The ability to identify PNOVFs using FRAX, BFH-OST, OSTA, and BMD scores was evaluated using receiver operating characteristic (ROC) curves. For this evaluation, we calculated the areas under the ROC curves (AUCs), sensitivity, specificity, and optimal cut-off points.

Results

There were significant differences in FRAX (without BMD), BFH-OST, OSTA, and BMD T-scores (total hip, femoral neck, and lumbar spine) between the PNOVFs and control groups. Compared with BFH-OST, OSTA, and BMD, the FRAX score had the best identifying value for PNOVFs; the AUC of the FRAX score (optimal cutoff =3.6%) was 0.825, while the sensitivity and specificity were 82.92% and 67.09%, respectively.

Conclusion

FRAX may be the preferable tool for identifying PNOVFs in postmenopausal women, while BFH-OST and OSTA can be applied as more simple screening tools for PNOVFs.
Ceritinib (LDK378) prevents bone loss via suppressing Akt and NF-κB-induced osteoclast formation
Authors: He Wenxin , Cao Xiankun , Kong Keyu , Rong Kewei , Han Shuai , Qin An
Published: November 2022

Background

Ceritinib is used for the treatment of patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), who are at the risk of developing bone metastasis. During bone metastasis, tumor cells release factors that induce osteoclast formation, resulting in osteolysis. However, the effect of ceritinib on osteoclast formation remains unclear.

Methods

Osteoclastogenesis was induced to assess the effect of ceritinib on osteoclast formation and osteoclast-specific gene expression. Western blotting was used to examine the molecular mechanisms underlying the effect of ceritinib on osteoclast differentiation. An in vivo ovariectomized mouse model was established to validate the effect of ceritinib in suppressing osteoclast formation and preventing bone loss.

Results

The differentiation of osteoclasts and the expression of osteoclast-specific genes were inhibited upon ceritinib stimulation. Ceritinib suppressed Akt and p65 phosphorylation during the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis. The administration of ceritinib to ovariectomized mice ameliorated trabecular bone loss by inhibiting osteoclast formation.

Conclusions

Ceritinib is beneficial in preventing bone loss by suppressing osteoclastic Akt and nuclear factor κB (NF-κB) signaling.
Research and analysis of the effect between the power level and economy on the lead-based modular nuclear power reactor
Authors: Lei Lou , Lianjie Wang , Bingyan Zhou , Chen Zhao , Bin Zhang , Mingyu Yan , Ce Zhang , Hongzhi Xiang , Yun Cai , Xingbo Wang , Zifan Zhao , Nan Zhou , Jiayi Liu
Published: November 2022

The fast reactor is gradually being paid attention to in nuclear power due to a better breeding effect, and its economy is also directly followed. Due to the restriction of the core power density, the core power level is directly related to the volume of the core active area. When the power level and the volume of the core gradually increase, the mass of uranium and 235U in the core at the beginning of life will gradually increase on the basis of a critical uranium inventory. At the same time, due to the gradual increase in the breeding effect, the utilization rate of uranium resources at the end of life will gradually increase. Due to the characteristics of the large critical uranium mass and high breeding effect, the mass of uranium and 235U in the low power level core at the beginning of life cannot be further reduced because of the critical uranium inventory. The lifetime of the high power level core should be extended to use the wealthy reactivity of the core because of the improvement in the breeding effect. However, due to the requirements of the nuclear power refuel time and the limitation to fuel consumption, the breeding effect brought by the improvement in the core power level and the size of the active zone may be less effective. In this article, the power level and economy of lead-based modular nuclear power are analyzed, and the economy of different power level fast reactors with 2,000 EFPD lifetime such as 100 MWt, 300 MWt, 500 MWt, 700 MWt, and 1000 MWt thermal power is designed and analyzed. By analyzing the invention of uranium and 235U and the fuel utilization of different core schemes, the best economic analysis of the single reactor power of the current lead-based modular reactor is proposed and the foundation of the lead-based modular nuclear power is provided.
Multifactor dimensionality reduction reveals the effect of interaction between ERAP1 and IFIH1 polymorphisms in psoriasis susceptibility genes
Authors: Zhang Chang , Qin Qin , Li Yuanyuan , Zheng Xiaodong , Chen Weiwei , Zhen Qi , Li Bao , Wang Wenjun , Sun Liangdan
Published: November 2022

Background: Psoriasis is a common immune-mediated hyperproliferative skin dysfunction with known genetic predisposition. Gene–gene interaction (e.g., between HLA-C and ERAP1) in the psoriasis context has been reported in various populations. As ERAP1 has been recognized as a psoriasis susceptibility gene and plays a critical role in antigen presentation, we performed this study to identify interactions between ERAP1 and other psoriasis susceptibility gene variants.

Methods: We validated psoriasis susceptibility gene variants in an independent cohort of 5,414 patients with psoriasis and 5,556 controls. Multifactor dimensionality reduction (MDR) analysis was performed to identify the interaction between variants significantly associated with psoriasis in the validation cohort and ERAP1 variants. We then conducted a meta-analysis of those variants with datasets from exome sequencing, target sequencing, and validation analyses and used MDR to identify the best gene–gene interaction model, including variants that were significant in the meta-analysis and ERAP1 variants.

Results: We found that 19 of the replicated variants were identified with p < 0.05 and detected six single-nucleotide polymorphisms of psoriasis susceptibility genes in the meta-analysis. MDR analysis revealed that the best predictive model was that between the rs27044 polymorphism of ERAP1 and the rs7590692 polymorphism of IFIH1 (cross-validation consistency = 9/10, test accuracy = 0.53, odds ratio = 1.32 (95% CI, 1.09–1.59), p < 0.01).

Conclusion: Our findings suggest that the interaction between ERAP1 and IFIH1 affects the development of psoriasis. This hypothesis needs to be tested in basic biological studies.
The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016–2021
Authors: Roht Laura , Tooming Mikk , Rekker Kadri , Roomere Hanno , Toome Kadri , Murumets Ülle , Šamarina Ustina , Õunap Katrin , Kahre Tiina
Published: November 2022

Background: Colorectal cancer (CRC) is the third most common cancer in Estonia in both women and men. According to the Estonian National Institute for Health Development, in 2017, there were 357 new colon cancer only cases in women and 282 in men. For colorectal cancer, the number for men and women altogether was 1040 in the same year. In 2018, there were over 1.8 million new cases worldwide. The Mayo Clinic found in a prospective, two-year multi-site study of CRC patients that 15.5% of patients carried pathogenic germline variants (PGV), using an >80 gene Next Generation Sequencing (NGS) panel.

Material and methods: This retrospective study aimed to analyse the estimated prevalence of pathogenic/likely pathogenic germline variants in Estonian colorectal cancer patients using NGS in a routine clinical setting. We gathered five-year data (July 2016-July 2021) of colorectal cancer patients (mostly not selected for age or family history) tested with either Illumina TruSight Cancer (94 genes) or TruSight Hereditary Cancer (113 genes) NGS panels.

Results: Three hundred and fourteen NGS analyses were performed due to either CRC or polyposis in anamnesis and/or family anamnesis, including 126 CRC cases and 44 colorectal polyposis cases, while 144 were either healthy family members or had other types of cancers. While a known disease-causing variant was identified in 16.4% of all cancer patients tested, we found that 21.4% of CRC patients had such a variant. Among the 44 colorectal polyps cases MLH1, gene was the most affected one (25%), the second and third most affected genes were MSH2 and CHEK2. Other genes with disease-causing variants found in CRC patients included APC, BLM, BMPR1A, BRCA1, FANCM, MSH6, MUTYH, PMS2, SMAD4, SPINK1 and VHL.

Conclusion: Our result give an overview of genetic testing of CRC patients, the prevalence of disease-causing variants and their landscape in Estonia. According to Estonian data, only 2.7–6.1% of CRC patients are genetically tested, which is around ten times less frequently than breast cancer patients and their family members. The diagnostic yield of CRC patients is 21.4%, suggesting that genetic testing will likely improve timely diagnosis and outcomes.
Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value
Authors: Wang Danke , Dai Jiacheng , Suo Chen , Wang Shangzi , Zhang Yuting , Chen Xingdong
Published: November 2022

The tumor heterogeneity of the transcriptional profiles is independent of genetic variation. Several studies have successfully identified esophageal squamous cell carcinoma (ESCC) subtypes based on the somatic mutation profile and copy number variations on the genome. However, transcriptome-based classification is limited. In this study, we classified 141 patients with ESCC into three subtypes (Subtype 1, Subtype 2, and Subtype 3) via tumor sample gene expression profiling. Differential gene expression (DGE) analysis of paired tumor and normal samples for each subtype revealed significant difference among subtypes. Moreover, the degree of change in the expression levels of most genes gradually increased from Subtype 1 to Subtype 3. Gene set enrichment analysis (GSEA) identified the representative pathways in each subtype: Subtype 1, abnormal Wnt signaling pathway activation; Subtype 2, inhibition of glycogen metabolism; and Subtype 3, downregulation of neutrophil degranulation process. Weighted gene co-expression network analysis (WGCNA) was used to elucidate the finer regulation of biological pathways and discover hub genes. Subsequently, nine hub genes (CORO1A, CD180, SASH3, CD52, CD300A, CD14, DUSP1, KIF14, and MCM2) were validated to be associated with survival in ESCC based on the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database. The clustering analysis of ESCC granted better understanding of the molecular characteristics of ESCC and led to the discover of new potential therapeutic targets that may contribute to the clinical treatment of ESCC.
Genomic approaches for improving grain zinc and iron content in wheat
Authors: Roy Chandan , Kumar Sudhir , Ranjan Rakesh Deo , Kumhar Sita Ram , Govindan Velu
Published: November 2022

More than three billion people worldwide suffer from iron deficiency associated anemia and an equal number people suffer from zinc deficiency. These conditions are more prevalent in Sub-Saharan Africa and South Asia. In developing countries, children under the age of five with stunted growth and pregnant or lactating women were found to be at high risk of zinc and iron deficiencies. Biofortification, defined as breeding to develop varieties of staple food crops whose grain contains higher levels of micronutrients such as iron and zinc, are one of the most promising, cost-effective and sustainable ways to improve the health in resource-poor households, particularly in rural areas where families consume some part of what they grow. Biofortification through conventional breeding in wheat, particularly for grain zinc and iron, have made significant contributions, transferring important genes and quantitative trait loci (QTLs) from wild and related species into cultivated wheat. Nonetheless, the quantitative, genetically complex nature of iron and zinc levels in wheat grain limits progress through conventional breeding, making it difficult to attain genetic gain both for yield and grain mineral concentrations. Wheat biofortification can be achieved by enhancing mineral uptake, source-to-sink translocation of minerals and their deposition into grains, and the bioavailability of the minerals. A number of QTLs with major and minor effects for those traits have been detected in wheat; introducing the most effective into breeding lines will increase grain zinc and iron concentrations. New approaches to achieve this include marker assisted selection and genomic selection. Faster breeding approaches need to be combined to simultaneously increase grain mineral content and yield in wheat breeding lines.
Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy
Authors: Hu Fang , Li Huan , Li Lei , Gale Robert Peter , Song Yuanbin , Chen Shuiqin , Liang Yang
Published: November 2022

Some cells within a diffuse large B-cell lymphoma (DLBCL) have the genotype of a stem cell, the proportion of which is termed degree of stemness. We interrogated correlations between the degree of stemness with immune and stromal cell scores and clinical outcomes in persons with DLBCL. We evaluated gene expression data on 1,398 subjects from Gene Expression Omnibus to calculate the degree of stemness. Subjects were classified into low- and high-stemness cohorts based on restricted cubic spline plots. Weighted gene co-expression network analysis (WGCNA) was used to screen for stemness-related genes. Immune and stromal scores correlated with the degree of stemness (both P < 0.001). A high degree of stemness correlated with a shorter progression-free survival (PFS; Hazard Ratio [HR; 95% Confidence Interval [CI] =1.90 (1.37, 2.64; P < 0.001) and a shorter survival (HR = 2.29 (1.53, 3.44; P < 0.001). CDC7 expression correlated with the degree of stemness, and CDC7-inhibitors significantly increased apoptosis (P < 0.01), the proportion of cells in G1 phase (P < 0.01), and inhibited lymphoma growth in a mice xenograft model (P = 0.04). Our data indicate correlations between the degree of stemness, immune and stromal scores, PFS, and survival. These data will improve the prediction of therapy outcomes in DLBCL and suggest potential new therapies.
Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial
Authors: He Cong , Xie Yong , Zhu Yin , Zhuang Kun , Huo Lijuan , Yu Yong , Guo Qiang , Shu Xu , Xiong Zhijuan , Zhang Zhenyu , Lyu Bin , Lu Nonghua
Published: November 2022

Background

Helicobacter pylori (H. pylori) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure.

Objectives

To evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy.

Methods

This was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori-positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing.

Results

The incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus. The expansion of some pathogenic genera, including Porphyromonas, Leptotrichia, in the mouth was suppressed by probiotics.

Conclusion

This study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics.
A single birth dose of Hepatitis B vaccine induces polyfunctional CD4+ T helper cells
Authors: Strandmark Julia , Darboe Alansana , Diray-Arce Joann , Ben-Othman Rym , Vignolo Sofia M. , Rao Shun , Smolen Kinga K. , Leroux-Roels Geert , Idoko Olubukola T. , Sanchez-Schmitz Guzmán , Ozonoff Al , Levy Ofer , Kollmann Tobias R. , Marchant Arnaud , Kampmann Beate
Published: November 2022

A single birth-dose of Hepatitis B vaccine (HepB) can protect newborns from acquiring Hepatitis B infection through vertical transmission, though several follow-up doses are required to induce long-lived protection. In addition to stimulating antibodies, a birth-dose of HepB might also induce polyfunctional CD4+T-cells, which may contribute to initial protection. We investigated whether vaccination with HepB in the first week of life induced detectable antigen-specific CD4+T-cells after only a single dose and following completion of the entire HepB vaccine schedule (3 doses). Using HBsAg- stimulated peripheral blood mononuclear cells from 344 infants, we detected increased populations of antigen-specific polyfunctional CD154+IL-2+TNFα+CD4+T-cells following a single birth-dose of HepB in a proportion of infants. Frequencies of polyfunctional T-cells increased following the completion of the HepB schedule but increases in the proportion of responders as compared to following only one dose was marginal. Polyfunctional T-cells correlated positively with serum antibody titres following the birth dose (day30) and completion of the 3-dose primary HepB vaccine series (day 128). These data indicate that a single birth dose of HepB provides immune priming for both antigen-specific B- and T cells
Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients
Authors: Qiao Min , Li Shanshan , Yuan Jinfeng , Ren Weicong , Shang Yuanyuan , Wang Wei , Liu Rongmei , Zhang Fuzhen , Li Qing , Wu Xiao , Lu Jie , Gao Mengqiu , Pang Yu
Published: November 2022

Background

Apart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.

Methods

Based on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.

Results

A total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.

Conclusion

Our data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.
Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions
Authors: Thuesen Nikolas Hallberg , Klausen Michael Schantz , Gopalakrishnan Shyam , Trolle Thomas , Renaud Gabriel
Published: November 2022

Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower depth of coverage (DOC) was evaluated by subsampling and HLA typing 230 WES samples at DOC ranging from 1X to 100X. The HLA typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions (P group and pseudo-sequence), which specifically focus on the peptide binding region. On average, across the five HLA loci examined, HLA*LA was found to have the highest typing accuracy. For the individual loci, HLA-A, -B and -C, Optitype’s typing accuracy was the highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1. The tools’ robustness to lower DOC data varied widely and further depended on the specific HLA locus. For all Class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the HLA molecule) at 50X, but increasing the DOC beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA loci as well as HLA*LA’s typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which is often based on sequencing data with lower quality and DOC. Interestingly, we found that Optitype’s typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the DOC is sufficiently high.
Assessing bias in aerial surveys for cetaceans: Results from experiments conducted with the franciscana dolphin
Authors: Sucunza Federico , Danilewicz Daniel , Andriolo Artur , de Castro Franciele R. , Cremer Marta , Denuncio Pablo , Ferreira Emanuel , Flores Paulo A. C. , Ott Paulo H. , Perez Martin S. , Pretto Dan , Sartori Camila M. , Secchi Eduardo R. , Zerbini Alexandre N.
Published: November 2022

Line transect aerial surveys are widely used for estimating abundance of biological populations, including threatened species. However, estimates obtained with data collected from aircraft are often underestimated because of visibility bias and bias in estimating group sizes from a fast-moving platform. An assessment of multiple sources of bias in aerial surveys were carried out in Brazilian coastal waters by experiments on multiple survey platforms (i.e., boat, airplane and helicopter). These studies focused on evaluating visibility bias (perception and availability bias) and potential differences in the estimation of group sizes from different types of platforms used in franciscana (Pontoporia blainvillei) abundance surveys. The ultimate goal was to develop correction factors to improve accuracy of estimates of density and population size for this threatened dolphin. Estimates of density and group sizes computed from boats were assumed to be unbiased and were compared to estimates of these quantities obtained from an airplane in the same area and period. In addition, helicopter surveys were conducted in two areas where water turbidity differed (clear vs. murky waters) to determine surfacing-diving intervals of franciscana groups and to estimate availability for aerial platforms. Abundance computed from the aerial survey data underestimated the true abundance by about 4-5 times, with ~70% of the total bias resulting from visibility bias (~80% from availability bias and ~20% from perception bias) and ~30% from bias in estimates of group size. The use of multiple survey platforms in contrasting habitats provided the opportunity to compute correction factors that can be used to refine range wide abundance estimates of the threatened franciscana given certain assumptions are met. Visibility bias and group size bias were substantial and clearly indicate the importance for accounting for such correction factors to produce unequivocal population assessment based on aerial survey data.
The importance of the dissolved organic matter pool for the carbon sequestration potential of artificial upwelling
Authors: Gómez-Letona Markel , Sebastián Marta , Baños Isabel , Montero María Fernanda , Barrancos Clàudia Pérez , Baumann Moritz , Riebesell Ulf , Arístegui Javier
Published: November 2022

In the face of climate change there is a need to reduce atmospheric CO2 concentrations. Artificial upwelling of nutrient-rich deep waters has been proposed as a method to enhance the biological carbon pump in oligotrophic oceanic regions in order to increase carbon sequestration. Here we examine the effect of different artificial upwelling intensities and modes (single pulse versus recurring pulses) on the dynamics of the dissolved organic matter pool (DOM). We introduced nutrient-rich deep water to large scale mesocosms (~44 m3) in the oligotrophic subtropical North Atlantic and found that artificial upwelling strongly increased DOM concentrations and changed its characteristics. The magnitude of the observed changes was related to the upwelling intensity: more intense treatments led to higher accumulation of dissolved organic carbon (>70 μM of excess DOC over ambient waters for the most intense) and to comparatively stronger changes in DOM characteristics (increased proportions of chromophoric DOM (CDOM) and humic-like fluorescent DOM), suggesting a transformation of the DOM pool at the molecular level. Moreover, the single upwelling pulse resulted in higher CDOM quantities with higher molecular weight than the recurring upwelling mode. Together, our results indicate that under artificial upwelling, large DOM pools may accumulate in the surface ocean without being remineralized in the short-term. Possible reasons for this persistence could be a combination of the molecular diversification of DOM due to microbial reworking, nutrient limitation and reduced metabolic capabilities of the prokaryotic communities within the mesocosms. Our study demonstrates the importance of the DOC pool when assessing the carbon sequestration potential of artificial upwelling.
Case report: Hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma: A rare case and minireview of the literature
Authors: Ding Fan , Wang Chao , Xu Chi , Tang Hui
Published: November 2022

Inflammatory pseudotumor (IPT)-like follicular dendritic cell sarcoma (FDCS) is a rare neoplasm referred to as the FDCS variant. Here we report a 66-year-old female patient suffering from hepatic IPT-like FDCS and summarize IPT-like FDCS reported in the literature. The patient presented with obvious abdominal pain without significant laboratory abnormalities and subsequently underwent surgical resection of a hepatic lesion. Postoperative pathological results demonstrated a vascular tissue-rich neoplasm (7.0-cm maximum diameter). The tumor cells expressed CD21 and CD35, and in situ hybridization detected Epstein–Barr virus-encoded RNA (EBER). Metastasis or recurrence was not detected during the 7-year follow-up.
Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study
Authors: Mena-Vázquez Natalia , Lisbona-Montañez Jose Manuel , Redondo-Rodriguez Rocío , Mucientes Arkaitz , Manrique-Arija Sara , Rioja José , Garcia-Studer Aimara , Ortiz-Márquez Fernando , Cano-García Laura , Fernández-Nebro Antonio
Published: November 2022

Objectives

To describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden.

Methods

We performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity.

Results

A total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%);p= 0.018] and high values for CRP (p= 0.039) and IL-6 (p= 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49–10.71);p= 0.008], smoking [OR (95% CI) 2.07 (1.13–3.78);p= 0.017], anti–citrullinated peptide antibody [OR (95% CI) 3.24 (1.15–9.13);p= 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03–14.23);p= 0.034], and physical activity [OR (95% CI) 0.99 (0.99–0.99);p= 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA.

Conclusion

Control of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.
Patients with inflammatory bowel disease have a higher chance of developing periodontitis: A systematic review and meta-analysis
Authors: Domokos Zsuzsanna , Uhrin Eszter , Szabó Bence , Czumbel Márk László , Dembrovszky Fanni , Kerémi Beáta , Varga Gábor , Hegyi Péter , Hermann Péter , Németh Orsolya
Published: November 2022

Background and objective

Periodontitis affects up to one billion people worldwide, and has been proven to be associated with several systemic inflammatory conditions. This study investigates the specific relationship between two multifactorial diseases: Inflammatory bowel disease (IBD) and periodontitis. To thoroughly explore this issue, we investigated separately whether IBD patients have a higher chance of developing periodontitis, and equally, whether patients with periodontitis have a higher chance of developing IBD.

Methods

The systematic search was performed in three databases: MEDLINE, Cochrane Trials, and Embase, up to 26 October 2021. The protocol was registered in PROSPERO. All eligible studies investigating the association between IBD and periodontitis from either direction were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. As a primary outcome, we investigated the prevalence of IBD and periodontitis, and calculated the odds ratio (OR). Our secondary outcomes involved comparing the clinical periodontal outcomes of IBD patients to those of IBD-free patients.

Results

The systematic search resulted in 1,715 records, 14 of which were eligible for qualitative synthesis and 8 for quantitative synthesis. On the basis of the results of the primary outcome, IBD diagnosis was associated with significantly higher odds of periodontitis: OR = 2.65 (CI: 2.09-3.36, I2 = 0 (CI: 0-0.75)). For subgroup analysis, we investigated separately the odds in Crohn’s disease (CD) patients: OR = 2.22 (CI: 1.49-3.31, I2 = 0.05 (CI: 0-0.76)) and in ulcerative colitis (UC) patients: OR = 3.52 (CI: 2.56 to 4.83, I2 = 0 (CI: 0-0.75)); the odds were significantly higher in all cases. Two studies investigated whether patients with periodontitis were more susceptible to IBD, and both found that periodontitis was significantly associated with the risk of subsequent UC, but not with subsequent CD. However, more studies are needed to prove an association.

Conclusion

Our analysis confirmed that IBD patients have a higher chance of developing periodontitis, and are a higher risk population in dentistry. Both dentists and gastroenterologists should be aware of this relationship and should emphasize the importance of prevention even more than in the healthy population.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021286161].
Mathematical appraisal of SARS-CoV-2 Omicron epidemic outbreak in unprecedented Shanghai lockdown
Authors: Jiang Minghao , Yin Hongxin , Zhang Shiyan , Meng Guoyu , Wu Geng
Published: November 2022

The SARS-CoV-2 Omicron outbreak is ongoing in Shanghai, home to 25 million population. Here, we presented a novel mathematical model to evaluate the Omicron spread and Zero-COVID strategy. Our model provided important parameters, the average quarantine ratio, the detection interval from being infected to being tested positive, and the spreading coefficient to understand the epidemic progression better. Moreover, we found that the key to a relatively accurate long-term forecast was to take the variation/relaxation of the parameters into consideration based on the flexible execution of the quarantine policy. This allowed us to propose the criteria for estimating the parameters and outcome for the ending stage that is likely to take place in late May. Altogether, this model helped to give a correct mathematical appraisal of the SARS-CoV-2 Omicron outbreak under the strict Zero-COVID policy in China.