bluuebunny/crossref_metadata_2025 huggingface dataset:
l-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study
Authors: Zhao Jie V. , Burgess Stephen , Fan Bohan , Schooling C. Mary
Published: September 2022

Background

l-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety ofl-carnitine, we assessed how genetically different levels ofl-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence andl-carnitine in men, we also examined sex-specific associations.

Methods

We used Mendelian randomization to obtain unconfounded estimates. Specifically, we used genetic variants to predictl-carnitine, and obtained their associations with coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation, as well as CVD risk factors (type 2 diabetes, glucose, HbA1c, insulin, lipid profile, blood pressure and body mass index) in large consortia and established cohorts, as well as sex-specific association in the UK Biobank. We obtained the Wald estimates (genetic association with CVD and its risk factors divided by the genetic association withl-carnitine) and combined them using inverse variance weighting. In sensitivity analysis, we used different analysis methods robust to pleiotropy and replicated using anl-carnitine isoform, acetyl-carnitine.

Results

Genetically predictedl-carnitine was nominally associated with higher risk of CAD overall (OR 1.07 per standard deviation (SD) increase inl-carnitine, 95% CI 1.02 to 1.11) and in men (OR 1.09, 95% CI 1.02 to 1.16) but had a null association in women (OR 1.00, 95% CI 0.92 to 1.09). These associations were also robust to different methods and evident for acetyl-carnitine.

Conclusions

Our findings do not support a beneficial association ofl-carnitine with CVD and its risk factors but suggest potential harm.l-carnitine may also exert a sex-specific role in CAD. Consideration of the possible sex disparity and exploration of the underlying pathways would be worthwhile.
Combination treatment with hENT1 and miR-143 reverses gemcitabine resistance in triple-negative breast cancer
Authors: Xi Yue , Li Ting , Xi Yun , Zeng Xinyi , Miao Ying , Guo Rui , Zhang Min , Li Biao
Published: September 2022

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and is susceptible to develop gemcitabine (GEM) resistance. Decreased expression of human equilibrative nucleoside transporter 1 (hENT1) accompanied by compensatory increase of glycolysis is strongly associated with GEM resistance in TNBC. In this study, we investigated the treatment feasibility of combined hENT1 upregulation and miR-143-mediated inhibition of glycolysis for reversing GEM resistance in TNBC.

Methods

Experiments were performed in vitro and in vivo to compare the efficacy of GEM therapies. In this study, we established stable drug-resistant cell line, GEM-R cells, from parental cells (MDA-MB-231) through exposure to GEM following a stepwise incremental dosing strategy. Then GEM-R cells were transfected by lentiviral plasmids and GEM-R cells overexpressing hENT1 (GEM-R-hENT1) were established. The viability and apoptosis of wild-type (MDA-MB-231), GEM-R, and GEM-R-hENT1 cells treated with GEM or GEM + miR-143 were analyzed by CCK8 assay and flow cytometry. The RNA expression and protein expression were measured by RT-PCR and western blotting respectively. GEM uptake was determined by multiple reaction monitoring (MRM) analysis. Glycolysis was measured by glucose assay and18F-FDG uptake. The antitumor effect was assessed in vivo in a tumor xenograft model by evaluating toxicity, tumor volume, and maximum standardized uptake value in18F-FDG PET. Immunohistochemistry and fluorescence photography were taken in tumor samples. Pairwise comparisons were performed using Student’s t-test.

Results

Our results represented that overexpression of hENT1 reversed GEM resistance in GEM-R cells by showing lower IC50and higher rate of apoptosis. MiR-143 suppressed glycolysis in GEM-R cells and enhanced the effect of reversing GEM resistance in GEM-R-hENT1 cells. The therapeutic efficacy was validated using a xenograft mouse model. Combination treatment decreased tumor growth rate and maximum standardized uptake value in18F-FDG PET more effectively.

Conclusions

Combined therapy of exogenous upregulation of hENT1 expression and miR-143 mimic administration was effective in reversing GEM resistance, providing a promising strategy for treating GEM-resistant TNBC.
Burden of malaria infection among individuals of varied blood groups in Kenya
Authors: Yeda Redemptah , Okudo Charles , Owiti Eunice , Biwot Gladys , Momanyi Cliff , Korir Winnie , Mitsanze Thoya , Tegerei Caroline , Juma Dennis , Opot Benjamin , Mwakio Edwin , Chemwor Gladys , Okoth Raphael , Ochora Douglas O. , Cheruiyot Agnes C. , Roth Amanda , Akala Hoseah M. , Andagalu Ben
Published: September 2022

Background

The ABO blood groups consist of A, B, and H carbohydrate antigens, which regulate protein activities during malaria infection in humans. Understanding the interplay between the malaria parasite and blood group antigens is essential in understanding new interventions to reduce the global burden of malaria. This study assessed the burden of malaria infection among individuals with varying blood groups seeking treatment at selected hospitals in Kenya.

Methods

A total of 366 samples from an ongoing malaria surveillance study were diagnosed for malaria by microscopy and further typed for blood group using ABO blood grouping. Age and sex were recorded in a data sheet, and analysed using R software version 4. Groups’ proportions (blood group, malaria infection, age and sex) were compared using Pearson’s Chi-square and Fischer exact tests. Wilcoxon and Kruskal-Wallis tests were performed and P-value < 0.05 was considered significant after Bonferroni correction for multiple comparisons. To understand the effect of each blood group on parasitaemia, multivariate logistic regression was used to model ABO blood group in relation to parasitaemia.

Results

Of the 366 samples analysed, 312 were malaria positive, mean age was 9.83 years (< 5 years n = 152 (48.41%), 6 to 17 years n = 101 (32.16%) and > 18 years n = 61 (19.43%)). Malaria prevalence was higher among females than males, 54.46% and 45.54%, respectively. Kisumu enrolled the highest number 109 (35%)) of malaria cases, Kombewa 108 (35%), Malindi 32 (10%), Kisii 28 (9%), Marigat 23 (7%), and Kericho 12 (4%). Blood group O+ was the most prevalent among the enrolled individuals (46.50%), A+ (27.71%), B+ (21.02%) and AB+ (4.78%) respectively. Compared to blood group O+, blood group B+ individuals were (14%) were more likely to habour Plasmodium falciparum infection as opposed to A+ and AB+ individuals, that were 7% and 20%, respectively,. Those living in malaria-endemic zones presented with higher parasite densities compared to those living in malaria-epidemic (p = 0.0061). Individuals bearing B + blood group are more likely to habour high parasitaemia compared to O + blood group bearers (OR = 4.47, CI = 1.53–13.05, p = 0.006).

Conclusion

Individuals of blood group B harbour high parasitaemia compared with the blood group O, Additionally, blood group A and B present with symptoms at lower parasitaemia than blood group O. Regardles of malaria transmission zones, individuals from endemic zones showed up with high parasitaemia and among them were more individuals of blood groups A and B than individuals of blood group O. Implying that these individuals were more at risk and require additional attention and effective case management.

Garphical Abstract
Potential application of the haematology analyser XN-31 prototype for field malaria surveillance in Kenya
Authors: Kagaya Wataru , Takehara Ikki , Kurihara Kyoko , Maina Michael , Chan Chim W. , Okomo Gordon , Kongere James , Gitaka Jesse , Kaneko Akira
Published: September 2022

Background

Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results.

Methods

Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15–25 °C) or chilled temperatures (2–8 °C).

Results

Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p.

Conclusion

These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model.
Does the level of inferior mesenteric artery ligation affect short-term and long-term outcomes of patients with sigmoid colon cancer or rectal cancer? A single-center retrospective study
Authors: Wang Yawei , Wang Yan , Zou Liaonan , Deng Lingna , Wu Tianchong , Liu Linsen , Jiang Jiling , An Tailai
Published: September 2022

Background

For sigmoid colon or rectal cancer, a definite consensus regarding the optimal level ligating the inferior mesenteric artery (IMA) has not been reached. We performed this study to determine whether the ligation level significantly affected short-term and long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.

Methods

Medical records of patients with sigmoid colon or rectal cancer who had undergone curative laparoscopic surgery between January 2008 and December 2014 at the Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine were reviewed. Then, the high tie group (HTG) was compared with the low tie group (LTG) in terms of short-term and long-term outcomes.

Results

Five-hundred ninety patients were included. No significant differences between two groups regarding baseline characteristics existed. HTG had a significantly higher risk of anastomotic fistula than LTG (21/283 vs 11/307, P = 0.040). Additionally, high ligation was proven by multivariate logistic regression analysis to be an independent factor for anastomotic fistula (P = 0.038, OR = 2.232, 95% CI: 1.047–4.758). Furthermore, LT resulted in better preserved urinary function. However, LTG was not significantly different from HTG regarding operative time (P = 0.075), blood transfusion (P = 1.000), estimated blood loss (P = 0.239), 30-day mortality (P = 1.000), ICU stay (P = 0.674), postoperative hospital stay (days) (P = 0.636), bowel obstruction (P = 0.659), ileus (P = 0.637), surgical site infection (SSI) (P = 0.121), number of retrieved lymph nodes (P = 0.501), and number of metastatic lymph nodes (P = 0.131). Subsequently, it was revealed that level of IMA ligation did not significantly influence overall survival (OS) (P = 0.474) and relapse-free survival (RFS) (P = 0.722). Additionally, it was revealed that ligation level did not significantly affect OS (P = 0.460) and RFS (P = 0.979) of patients with stage 1 cancer, which was also observed among patients with stage 2 or stage 3 cancer. Ultimately, ligation level was not an independent predictive factor for either OS or RFS.

Conclusions

HT resulted in a significantly higher incidence of anastomotic fistula and worse preservation of urinary function. Level of IMA ligation did not significantly affect long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.
Development, validation and item reduction of a food literacy questionnaire (IFLQ-19) with Australian adults
Authors: Thompson Courtney , Byrne Rebecca , Adams Jean , Vidgen Helen Anna
Published: September 2022

Background

Food literacy is theorised to improve diet quality, nutrition behaviours, social connectedness and food security. The definition and conceptualisation by Vidgen & Gallegos, consisting of 11 theoretical components within the four domains of planning and managing, selecting, preparing and eating, is currently the most highly cited framework. However, a valid and reliable questionnaire is needed to comprehensively measure this conceptualisation. Therefore, this study draws on existing item pools to develop a comprehensive food literacy questionnaire using item response theory.

Methods

Five hundred Australian adults were recruited in Study 1 to refine a food literacy item pool using principal component analysis (PCA) and item response theory (IRT) which involved detailed item analysis on targeting, responsiveness, validity and reliability. Another 500 participants were recruited in Study 2 to replicate item analysis on validity and reliability on the refined item pool, and 250 of these participants re-completed the food literacy questionnaire to determine its test–retest reliability.

Results

The PCA saw the 171-item pool reduced to 100-items across 19 statistical components of food literacy. After the thresholds of 26 items were combined, responses to the food literacy questionnaire had ordered thresholds (targeting), acceptable item locations (< -0.01 to + 1.53) and appropriateness of the measurement model (n = 92% expected responses) (responsiveness), met outfit mean-squares MSQ (0.48—1.42) (validity) and had high person, item separation (> 0.99) and test–retest (ICC 2,1 0.55–0.88) scores (reliability).

Conclusions

We developed a 100-item food literacy questionnaire, the IFLQ-19 to comprehensively address the Vidgen & Gallegos theoretical domains and components with good targeting, responsiveness, reliability and validity in a diverse sample of Australian adults.
Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway
Authors: Yao Chongjie , Ren Jun , Huang Ruixin , Tang Cheng , Cheng Yanbin , Lv Zhizhen , Kong Lingjun , Fang Sitong , Tao Jiming , Fu Yangyang , Zhu Qingguang , Fang Min
Published: September 2022

Background

Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT.

Methods

We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats.

Results

Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects.

Conclusions

In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.
IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes
Authors: Lemaître Florent , Farzam-kia Negar , Carmena Moratalla Ana , Carpentier Solorio Yves , Clenet Marie-Laure , Tastet Olivier , Cleret-Buhot Aurélie , Guimond Jean Victor , Haddad Elie , Duquette Pierre , Girard J. Marc , Prat Alexandre , Larochelle Catherine , Arbour Nathalie
Published: September 2022

Background

Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor for IL-27, we sought to determine how these glial cells respond to this cytokine and whether such exposure alters their interactions with infiltrating activated T lymphocytes. To determine whether inflammation shapes the impact of IL-27, we compared the effects of this cytokine in non-inflamed and inflamed conditions induced by an IL-1β exposure.

Main body

Transcriptomic analysis of IL-27-exposed human astrocytes showed an upregulation of multiple immune genes. Human astrocytes increased the secretion of chemokines (CXCL9, CXCL10, and CXCL11) and the surface expression of proteins (PD-L1, HLA-E, and ICAM-1) following IL-27 exposure. To assess whether exposure of astrocytes to IL-27 influences the profile of activated T lymphocytes infiltrating the CNS, we used an astrocyte/T lymphocyte co-culture model. Activated human CD4+ or CD8+ T lymphocytes were co-cultured with astrocytes that have been either untreated or pre-exposed to IL‑27 or IL-1β. After 24 h, we analyzed T lymphocytes by flow cytometry for transcription factors and immune molecules. The contact with IL-27-exposed astrocytes increased the percentages of T-bet, Eomes, CD95, IL-18Rα, ICAM-1, and PD-L1 expressing CD4+ and CD8+ T lymphocytes and reduced the proportion of CXCR3-positive CD8+ T lymphocytes. Human CD8+ T lymphocytes co-cultured with human IL-27-treated astrocytes exhibited higher motility than when in contact with untreated astrocytes. These results suggested a preponderance of kinapse-like over synapse-like interactions between CD8+ T lymphocytes and IL-27-treated astrocytes. Finally, CD8+ T lymphocytes from MS patients showed higher motility in contact with IL-27-exposed astrocytes compared to healthy donors’ cells.

Conclusion

Our results establish that IL-27 alters the immune functions of human astrocytes and shapes the profile and motility of encountered T lymphocytes, especially CD8+ T lymphocytes from MS patients.
Women’s experience of unintended pregnancy and changes in contraceptive methods: evidence from a nationally representative survey
Authors: Khan Md Nuruzzaman , Islam M. Mofizul
Published: September 2022

Background

Ineffective or no use of contraception following an unintended pregnancy contributes to a subsequent unintended pregnancy. This study aimed to determine whether women’s experiences of unintended pregnancies affect changing their contraceptive using patterns.

Methods

We analysed the 2017/2018 Bangladesh Demographic and Health Survey data. The contraceptive switching pattern was computed by comparing women’s contraceptives using data before and after pregnancy. Women were categorised into the following three groups, depending on their patterns of contraceptive use before and after pregnancy: no change, if there were no change in contraceptive using pattern; switched to higher effective contraceptives, if changed from pre-pregnancy less effective contraceptives to post-pregnancy more effective contraceptives; switched to less effective contraceptives, if changed from pre-pregnancy more effective contraceptives to post-pregnancy less effective contraceptives. Women’s intention in the most recent pregnancy was our primary explanatory variable, classified as wanted, mistimed and unwanted. Multinomial multilevel logistics regression was used to determine the association between women’s intention in the most recent pregnancy and women’s contraceptive methods switching patterns from before to after pregnancy.

Results

Around 20% of the most recent pregnancies that ended with a live birth were unintended at conception. No contraceptive use was reported by 37% of women before their pregnancies which decreased to 24% after pregnancies. Overall, around 54% of women who reported no contraceptive use before pregnancy used modern contraceptives after pregnancy. The rate was higher among women who experienced unwanted pregnancy (73.4%) than mistimed (58.8%) and wanted (53.4%) pregnancy. Experience of mistimed pregnancy was associated with a higher likelihood of no contraceptive change (aOR, 1.84, 95% CI 1.41–2.39) and switching to less effective contraceptives (aOR, 1.58, 95% CI 1.10–2.26) than switching to more effective contraceptives. However, unwanted pregnancy was not associated with any significant change in contraceptives use from before to after pregnancy.

Conclusion

Experience of unintended pregnancy did not change women’s contraception using patterns, which indicates the risk of repeat unintended pregnancies and associated adverse consequences, including maternal and child morbidity and mortality. Policies to ensure access to and use of modern contraceptives among women facing unwanted or mistimed pregnancies are recommended.
The underlying mechanism of Guillain-Barré syndrome in a young patient suffered from Japanese encephalitis virus infection: a case report
Authors: Liu Sheng , Wang Jinyong , Yang Jun , Wen Ying
Published: September 2022

Background

The presentation of Guillain–Barré syndrome (GBS) caused by Japanese encephalitis virus (JEV) is uncommon, although clusters of GBS cases were observed in China in 2018. The underlying mechanism is unclear, particularly in individuals vaccinated against Japanese encephalitis in childhood.

Case presentation

We report a patient with acute flaccid paralysis involving four extremities and respiratory muscles, while magnetic resonance imaging of the brain and spine were standard. Electrophysiological examination displayed slowed motor nerve conduction speed and reduced evoked velocity amplitude. GBS was finally considered which was related to JEV infection verified by positive anti-JEV immunoglobulin M antibody and positive immunoglobulin G antibody in the serum. Unfortunately, the patient refused intravenous immunoglobulin and declined the use of mechanical ventilation again. He voluntarily withdrew from the hospital and died on the 36th day after the onset of illness. We also performed a review of previously reported related cases and discussed the underlying mechanism.

Conclusion

JEV infection-associated GBS is unusual. We should pay attention to the atypical manifestations of JEV infection and explore possible pathogenesis in particular individuals.
Eight-year operation status and data analysis of the first human milk bank in East China
Authors: Xiaoshan Hu , Xue Chu , Jun Zhang , Feng Liu , Xiaohui Chen , Zhangbin Yu , Shuping Han
Published: September 2022

Background

Human milk banks (HMBs) are essential facilities for the selection, collection, testing, transportation,storage, and distribution of DHM for special medical needs. The aim of this analysis was to analyze the operation status and data over the last 8 years of operation of the first human milk bank (HMB) in East China.

Methods

Data related to the costs, donors, donation, pasteurization, and recipients were extracted from the web-based electronic monitoring system of the HMB for the period August 1, 2013 to July 31, 2021.

Results

Over the 8 years of operation, 1,555 qualified donors donated 7,396.5L of qualified milk at a cost of ¥1.94 million($306,051), with the average cost per liter of donor human milk being ¥262.3($41.4). The donors were between 25 and 30 years of age, and the majority (80.1%) were primipara. All the donated milk was pasteurized and subjected to bacteriological tests before and after pasteurization: 95.4% passed the pre-pasteurization tests, and 96.3% passed the post-pasteurization tests. A total of 9,207 newborns received 5,775.2L of pasteurized donor milk. The main reason for the prescription of donor human milk was preterm birth. As a result of continuous quality improvements, January 2016 witnessed a significant increase in the volume of qualified DHM and the number of qualified donors. However, in 2020, as a result of the restrictions related to the COVID-19 pandemic, the volume of qualified DHM and the number of qualified donors decreased.

Conclusions

Over its 8 years of operation, our HMB has made steady quality improvements in its screening and information processes. Continuous quality improvement is on ongoing need, along with recruiting more qualified donors and collecting donor human milk for vulnerable newborns.
A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism
Authors: Xia Sheng-li , Ma Zi-yuan , Wang Bin , Gao Feng , Guo Sheng-yang , Chen Xu-han
Published: September 2022

Background

Osteoporosis (OP) patients complicated with type II diabetes mellitus (T2DM) has a higher fracture risk than the non-diabetic patients, and mesenchymal stem cells (MSCs) from T2DM patients also show a weaker osteogenic potent. The present study aimed to provide a gene expression profile in MSCs from diabetic OP and investigated the potential mechanism.

Methods

The bone-derived MSC (BMSC) was isolated from OP patients complicated with or without T2DM (CON-BMSC, T2DM-BMSC). Osteogenic differentiation was evaluated by qPCR analysis of the expression levels of osteogenic markers, ALP activity and mineralization level. The differentially expressed genes (DEGs) in T2DM-BMSC was identified by RNA-sequence, and the biological roles of DEGs was annotated by bioinformatics analyses. The role of silencing the transcription factor (TF), Forkhead box Q1 (FOXQ1), on the osteogenic differentiation of BMSC was also investigated.

Results

T2DM-BMSC showed a significantly reduced osteogenic potent compare to the CON-BMSC. A total of 448 DEGs was screened in T2DM-BMSC, and bioinformatics analyses showed that many TFs and the target genes were enriched in various OP- and diabetes-related biological processes and pathways. FOXQ1 had the highest verified fold change (abs) among the top 8 TFs, and silence of FOXQ1 inhibited the osteogenic differentiation of CON-BMSC.

Conclusions

Our study provided a comprehensive gene expression profile of BMSC in diabetic OP, and found that downregulated FOXQ1 was responsible for the reduced osteogenic potent of T2DM-BSMC. This is of great importance for the special mechanism researches and the treatment of diabetic OP.
Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study
Authors: Luther Tomas , Eckerbom Per , Cox Eleanor , Lipcsey Miklos , Bülow Sara , Hultström Michael , Torrente Francisco Martinez , Weis Jan , Palm Fredrik , Francis Susan , Frithiof Robert , Liss Per
Published: September 2022

Background

Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI.

Methods

A prospective case–control study where patients without prior kidney disease treated in intensive care for respiratory failure due to COVID-19 were examined. Kidney Disease: Improving Global Outcomes Creatinine criteria were used for group allocation. Main comparisons were tested using Mann–Whitney U test.

Results

Nineteen patients were examined, ten with AKI and nine without AKI. Patients with AKI were examined in median 1 [0–2] day after criteria fulfillment. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423–753] vs. 859 [746–920] ml/min, p = 0.037). Regional perfusion was reduced in both cortex (76 [51–112] vs. 146 [123–169] ml/100 g/min, p = 0.015) and medulla (28 [18–47] vs. 47 [38–73] ml/100 g/min, p = 0.03). Renal venous saturation was similar in both groups (72% [64–75] vs. 72% [63–84], ns.), as was regional oxygenation (R2*) in cortex (17 [16–19] vs. 17 [16–18] 1/s, ns.) and medulla (29 [24–39] vs. 27 [23–29] 1/s, ns.).

Conclusions

In critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flows were reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting.

Trial registration ClinicalTrials ID: NCT02765191, registered May 6 2014 and updated May 7 2020.

Graphic Abstract
Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock
Authors: Watchorn James , Huang Dean , Bramham Kate , Hutchings Sam
Published: September 2022

Background

Reduced renal perfusion has been implicated in the development of septic AKI. However, the relative contributions of macro- and microcirculatory blood flow and the extent to which impaired perfusion is an intrinsic renal phenomenon or part of a wider systemic shock state remains unclear.

Methods

Single-centre prospective longitudinal observational study was carried out. Assessments were made at Day 0, 1, 2 and 4 after ICU admission of renal cortical perfusion in 50 patients with septic shock and ten healthy volunteers using contrast-enhanced ultrasound (CEUS). Contemporaneous measurements were made using transthoracic echocardiography of cardiac output. Renal artery blood flow was calculated using velocity time integral and vessel diameter. Assessment of the sublingual microcirculation was made using handheld video microscopy. Patients were classified based on the degree of AKI: severe = KDIGO 3 v non-severe = KDIGO 0–2.

Results

At study enrolment, patients with severe AKI (37/50) had prolonged CEUS mean transit time (mTT) (10.2 vs. 5.5 s, p < 0.05), and reduced wash-in rate (WiR) (409 vs. 1203 au, p < 0.05) and perfusion index (PI) (485 vs. 1758 au, p < 0.05); differences persisted throughout the entire study. Conversely, there were no differences in either cardiac index, renal blood flow or renal resistive index. Sublingual microcirculatory variables were not significantly different between groups at study enrolment or at any subsequent time point. Although lactate was higher in the severe AKI group at study enrolment, these differences did not persist, and there were no differences in either ScvO2 or ScvCO2-SaCO2 between groups. Patients with severe AKI received higher doses of noradrenaline (0.34 vs. 0.21mcg/kg/min, p < 0.05). Linear regression analysis showed no correlation between mTT and cardiac index (R-0.18) or microcirculatory flow index (R-0.16).

Conclusion

Renal cortical hypoperfusion is a persistent feature in critically ill septic patients who develop AKI and does not appear to be caused by reductions in macrovascular renal blood flow or cardiac output. Cortical hypoperfusion appears not be associated with changes in the sublingual microcirculation, raising the possibility of a specific renal pathogenesis that may be amenable to therapeutic intervention.

Trial Registration Clinical Trials.gov NCT03713307, 19 Oct 2018.
MIRTH: Metabolite Imputation via Rank-Transformation and Harmonization
Authors: Freeman Benjamin A. , Jaro Sophie , Park Tricia , Keene Sam , Tansey Wesley , Reznik Ed
Published: September 2022

Out of the thousands of metabolites in a given specimen, most metabolomics experiments measure only hundreds, with poor overlap across experimental platforms. Here, we describe Metabolite Imputation via Rank-Transformation and Harmonization (MIRTH), a method to impute unmeasured metabolite abundances by jointly modeling metabolite covariation across datasets which have heterogeneous coverage of metabolite features. MIRTH successfully recovers masked metabolite abundances both within single datasets and across multiple, independently-profiled datasets. MIRTH demonstrates that latent information about otherwise unmeasured metabolites is embedded within existing metabolomics data, and can be used to generate novel hypotheses and simplify existing metabolomic workflows.
Prediction of evolutionary constraint by genomic annotations improves functional prioritization of genomic variants in maize
Authors: Ramstein Guillaume P. , Buckler Edward S.
Published: September 2022

Background

Crop improvement through cross-population genomic prediction and genome editing requires identification of causal variants at high resolution, within fewer than hundreds of base pairs. Most genetic mapping studies have generally lacked such resolution. In contrast, evolutionary approaches can detect genetic effects at high resolution, but they are limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Here we use genomic annotations to accurately predict nucleotide conservation across angiosperms, as a proxy for fitness effect of mutations.

Results

Using only sequence analysis, we annotate nonsynonymous mutations in 25,824 maize gene models, with information from bioinformatics and deep learning. Our predictions are validated by experimental information: within-species conservation, chromatin accessibility, and gene expression. According to gene ontology and pathway enrichment analyses, predicted nucleotide conservation points to genes in central carbon metabolism. Importantly, it improves genomic prediction for fitness-related traits such as grain yield, in elite maize panels, by stringent prioritization of fewer than 1% of single-site variants.

Conclusions

Our results suggest that predicting nucleotide conservation across angiosperms may effectively prioritize sites most likely to impact fitness-related traits in crops, without being limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Our approach—Prediction of mutation Impact by Calibrated Nucleotide Conservation (PICNC)—could be useful to select polymorphisms for accurate genomic prediction, and candidate mutations for efficient base editing. The trained PICNC models and predicted nucleotide conservation at protein-coding SNPs in maize are publicly available in CyVerse (https://doi.org/10.25739/hybz-2957).
Yogurt and molasses can alter microbial-digestive and nutritional characteristics of pomegranate leaves silage
Authors: Kazemi Mohsen , Valizadeh Reza , Ibrahimi Khoram Abadi Elias
Published: September 2022

Fewer studies in recent years have been conducted on the nutritional potential and fermentation quality of silage prepared from pomegranate leaves (PL). So, we investigated the nutritional-fermentation quality of PL before and after ensiling with or without yogurt containing mainly lactic acid-producing bacteria (Lactobacillus bulgaricusandStreptococcus thermophiles) and molasses (at two levels of 2 and 4% of dry matter) in the polyethylene microsilos for 60 days. A range of dry matter (29.1–39.1%), crude protein (3.85–4.83%), ash (5.33–8.60%), and non-fiber carbohydrates (53.2%–58.6%) contents were observed among the treatments. A significant increase in calcium, potassium, magnesium, manganese, iron, and zinc was observed in PL after ensiling compared to before ensiling (p < 0.05). The PL ensiled with 4% yogurt exhibited the highest ammonia nitrogen, lactic and acetic acids, but the lowest butyric acid among the ensiled PL (p < 0.05). The ensiling of PL without additive (control) significantly decreased potential gas production, dry matter digestibility, organic matter digestibility, total volatile fatty acids, metabolizable energy, net energy for lactation, base-buffering capacity, titratable alkalinity, and acid–base buffering capacity compared to before ensiling (p < 0.05). According to the present results, the nutritional value of PL before ensiling was higher than after ensiling. The addition of yogurt and molasses to PL at the ensiling process especially at 4% of dry matter, improved the fermentation and nutritional characteristics. In general, the addition of yogurt or molasses as two cheap and available additives is recommended to improve the digestive-fermentation parameters of PL in silo and ruminal environments.
Acupuncture for pain control after degenerative lumbar spine surgery
Authors: Chen Bo-An , Deng Wen-Chun , Chen Mao-Yu
Published: September 2022

Background

Wound pain after surgery for lumbar spine disease may interfere with patients’ recovery. Acupuncture is commonly used for pain management, but its efficacy for postoperative pain control is unclear. This study aimed to evaluate the effectiveness of acupuncture for adjuvant pain control after surgery for degenerative lumbar spine disease.

Methods

We retrospectively reviewed the records of consecutive patients who received surgery for degenerative lumbar spine disease at our institution from 2013 to 2014. Surgical procedures included open laminectomy, discectomy, and trans-pedicle screw instrumentation with posterior-lateral fusion. Patients were grouped by pain control methods, including routine analgesia, patient-controlled analgesia (PCA), and acupuncture. The routine analgesia group received oral acetaminophen/non-steroidal anti-inflammatory drugs with meperidine as needed for immediate pain control. The PCA group received a basal dose of morphine and subsequent user-demand doses. The acupuncture group received acupuncture every other day after surgery.

Results

Ninety-six patients were included, of whom 37 received acupuncture, 27 received PCA, and 32 received routine analgesics for pain control. Visual analog scale (VAS) pain scores in all 3 groups decreased significantly, and to the same degree, from the first postoperative day to the second day. No significant differences were found in VAS scores over the next 6 postoperative days; however, the scores of patients treated with PCA were slightly but still significantly higher (p = 0.026) on postoperative day 4 than scores of patients treated with acupuncture and traditional analgesia, a difference likely due to PCA being discontinued on postoperative day 3. No major complications were noted in the acupuncture group, but 2 patients dropped out because of fear of needle insertion.

Conclusions

Acupuncture may be as effective as traditional analgesia and PCA for adjuvant pain control after surgery for degenerative lumbar spine disease.
The effect of prior exposure on the lightfastness of early synthetic dyes on textiles
Authors: Hagan Eric , Poulin Jennifer
Published: September 2022

Many studies have investigated light-induced damage to colourants in heritage collections using prepared samples of materials such as artist paints and dyed textiles. The body of research focuses primarily on the response of virgin materials, where colour change is assessed with respect to the original colour as light dose increases. From a practical perspective, most objects in museum collections have accumulated a significant light dose from illumination before acquisition, and subsequent years of exhibit lighting. When considering the risk of further degradation, it is often stated by heritage professionals that fugitive colourants with past light exposure are no longer as sensitive due to the slowing rate of visual damage. This is evident by studying ‘fading curves’, where the rate of colour change typically diminishes with increasing light dose. It remains unclear, however, to what degree the lightfastness of remaining colour changes with ongoing exposure. To address the issue, the light sensitivity of residual colour was investigated as a function of prior dose using a published dataset of colour measurements from textiles dyed with early synthetic colourants in the period of 1874–1905. The CIELAB colour values (D65/2°) for each material and dose increment were used to determine the future dose that causes a just-noticeable difference (JND), ΔE
00 = 1.7, starting at different amounts of past exposure. This involved resetting the reference CIELAB values to that of the residual colour after each prior dose. The analysis provides an extension of our earlier work, where only the initial lightfastness was reported. A summary of the findings illustrates the shifting distribution of lightfastness, toward higher Blue Wool (BW) ratings with increasing exposure. As the dose progresses, dyes that start at BW1 sensitivity progress to BW2, then BW3 and so on. The findings from this work may assist with boundary approximations of object sensitivity when prior light exposure is known, or a reasonable estimate is available. An analysis of experimental data is summarised as a tool for this type of decision-making process.
Research on mechanical characteristics and energy dissipation of traditional ramming technology
Authors: Pei Qiangqiang , Liu Xiaoying , Hou Zhichun , Zhao Guojing , Zhang Bo , Guo Qinglin
Published: September 2022

The ramming technique is a traditional method used to improve the compactness of soil with impact and vibration energy. Based on the measured data of ramming force transmission and dissipation, this study reveals the mechanism of energy transfer and dissipation of single-layer ramming as well as the law of variation with ramming quality, laying thickness, and ramming times. It also establishes the ramming model and empirical formula of ramming quality, laying thickness, and ramming times, introduces the ramming layer changes associated with the constitutive relationship (elastic to elastoplastic parts) as a function of ramming times, and determines the influence depth and horizontal range based on real-time data monitoring. It was found that as the mass of the rammer increases, the range of influence of the impact stress inside the earth also increases proportionally, and this effect is more pronounced vertically. However, the dissipation rate of energy in horizontal direction is much greater than in the vertical direction. The traditional stacked ramming technique of “chong hai wo, hang yin ding” can effectively eliminate the defects of horizontal reversal upwelling impact and unevenness of the ramming layer during the ramming process. The research results provide a theoretical basis for evaluating the quality of the traditional ramming technique.
Controlling skin microbiome as a new bacteriotherapy for inflammatory skin diseases
Authors: Ito Yoshihiro , Amagai Masayuki
Published: September 2022

The skin serves as the interface between the human body and the environment and interacts with the microbial community. The skin microbiota consists of microorganisms, such as bacteria, fungi, mites, and viruses, and they fluctuate depending on the microenvironment defined by anatomical location and physiological function. The balance of interactions between the host and microbiota plays a pivotal role in the orchestration of skin homeostasis; however, the disturbance of the balance due to an alteration in the microbial communities, namely, dysbiosis, leads to various skin disorders. Recent developments in sequencing technology have provided new insights into the structure and function of skin microbial communities. Based on high-throughput sequencing analysis, a growing body of evidence indicates that a new treatment using live bacteria, termed bacteriotherapy, is a feasible therapeutic option for cutaneous diseases caused by dysbiosis. In particular, the administration of specific bacterial strains has been investigated as an exclusionary treatment strategy against pathogens associated with chronic skin disorders, whereas the safety, efficacy, and sustainability of this therapeutic approach using isolated live bacteria need to be further explored. In this review, we summarize our current understanding of the skin microbiota, as well as therapeutic strategies using characterized strains of live bacteria for skin inflammatory diseases. The ecosystem formed by interactions between the host and skin microbial consortium is still largely unexplored; however, advances in our understanding of the function of the skin microbiota at the strain level will lead to the development of new therapeutic methods.