bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic scores for low lung function and the future risk of adverse health outcomes
Authors: Zaigham Suneela , Gonçalves Isabel , Center Regeneron Genetics , Engström Gunnar , Sun Jiangming
Published: November 2022

Aims

Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes.

Methods

We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS.

Results

FEV1-PGS and FVC-PGS were significantly associated with mean sBP at baseline after adjustments (FEV1-PGS Q1 (highest PGS = highest lung function): 140.7mmHg vs. Q4: 141.5mmHg, p-value 0.008). A low FVC-PGS was significantly associated with the risk of future diabetic events after adjustments (Q4 vs. Q1 HR: 1.22 (CI 1.12–1.32), p-trend < 0.001) and had added value to risk prediction models for diabetes. Low FEV1-PGS was significantly associated with future coronary events (Q4 vs. Q1 HR: 1.13 (CI: 1.04–1.22), p-trend 0.008). No significant association was found between PGS and sudden cardiac death, chronic kidney disease or all-cause mortality. Results remained largely unchanged in a subgroup of subjects when further adjusted for apolipoproteins.

Conclusion

Genetic susceptibility for reduced lung function is associated with higher sBP, increased risk of diabetes and to a lesser extent, future coronary events, suggesting etiological roles of lung function on these outcomes. Using PGS, high-risk groups could be early detected to implement early lifestyle changes to mitigate the risk.
Segregationally stabilised plasmids improve production of commodity chemicals in glucose-limited continuous fermentation
Authors: Allen James R. , Torres-Acosta Mario A. , Mohan Naresh , Lye Gary J. , Ward John M.
Published: November 2022

Background

The production of chemicals via bio-based routes is held back by limited easy-to-use stabilisation systems. A wide range of plasmid stabilisation mechanisms can be found in the literature, however, how these mechanisms effect genetic stability and how host strains still revert to non-productive variants is poorly understood at the single-cell level. This phenomenon can generate difficulties in production-scale bioreactors as different populations of productive and non-productive cells can arise. To understand how to prevent non-productive strains from arising, it is vital to understand strain behaviour at a single-cell level.

The persistence of genes located on plasmid vectors is dependent on numerous factors but can be broadly separated into structural stability and segregational stability. While structural stability refers to the capability of a cell to resist genetic mutations that bring about a loss of gene function in a production pathway, segregational stability refers to the capability of a cell to correctly distribute plasmids into daughter cells to maintain copy number. A lack of segregational stability can rapidly generate plasmid-free variants during replication, which compromises productivity.

Results

Citramalate synthase expression was linked in an operon to the expression of a fluorescent reporter to enable rapid screening of the retention of a model chemical synthesis pathway in a continuous fermentation of E. coli. Cells without additional plasmid stabilisation started to lose productivity immediately after entering the continuous phase. Inclusion of a multimer resolution site, cer, enabled a steady-state production period of 58 h before a drop in productivity was detected. Single-cell fluorescence measurements showed that plasmid-free variants arose rapidly without cer stabilisation and that this was likely due to unequal distribution of plasmid into daughter cells during cell division. The addition of cer increased total chemical yield by more than 50%.

Conclusions

This study shows the potential remains high for plasmids to be used as pathway vectors in industrial bio-based chemicals production, providing they are correctly stabilised. We demonstrate the need for accessible bacterial ‘toolkits’ to enable rapid production of known, stabilised bacterial production strains to enable continuous fermentation at scale for the chemicals industry.
Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages
Authors: Jin Yu , Zhang Qing , Qin Xing , Liu Zhen , Li Zhenxia , Zhong Xiaoxia , Xia Lunguo , He Jie , Fang Bing
Published: November 2022

Background

Osteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target.

Results

A kind of carbon dots (CDs) with excellent biocompatibility was fabricated from folic acid via hydrothermal method and could effectively attenuate osteoarthritis. It was demonstrated that CDs treatment could rescue IL1β-induced proinflammatory responses, oxidative stress, cartilage degeneration and extracellular matrix degradation. Moreover, CDs reprogrammed lipopolysaccharide (LPS)-induced macrophage inflammation and polarization. Conditioned medium (CM) from CDs-treated macrophages could attenuate IL1β-induced chondrocyte injury. Also, CM from CDs-treated chondrocytes had immunoregulatory functions on macrophages. Mechanistically, CDs inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in IL1β-stimulated chondrocytes. In vivo, anterior cruciate ligament transection (ACLT) mice model was adopted and it was indicated that intra-articular injection of CDs effectively delays OA pathogenesis.

Conclusions

Taken together, these findings indicated CDs could mediate OA via promoting cartilage repair and immunomodulating macrophages within local microenvironment, which may provide evidences for utilizing CDs as a novel nanomaterial for OA treatment.
Primary squamous cell carcinoma of thyroid gland: 11 case reports and a population-based study
Authors: Yan Wanyun , Chen Huiying , Li Jiangmiao , Zhou Ruifa , Su Jiping
Published: November 2022

Background

Primary squamous cell carcinoma of thyroid gland (PSCCT) is a highly aggressive malignant tumor associated with a poor prognosis. Due to the rare case, there is a knowledge gap on the features of PSCCT. There is limited understanding of the treatment and molecular biology of this tumor. More genomic work and relevant perspective work need to be done.

Methods

We retrospectively reviewed the medical information of patients with PSCCT diagnosed from December 2009 to December 2020 at The First Affiliated Hospital of Guangxi Medical University. In addition, we conducted an electronic search of the paper in CNKI, Wanfang, VIP, PubMed, Embase, Web of Science, and ProQuest databases by recently updated articles. Survival analysis was conducted using the Kaplan–Meier method.

Results

There were only 11 patients met the study’s inclusion criteria in our institution. The patients ranged in age from 25 to 68 years old and female preponderance (M:F = 1:1.7). The median survival time was 6 months, and 1-year survival rate was 33.3%. Fifty-three patients’ individual data from 45 articles were selected for analysis. The median age at diagnosis was 63 years and female preponderance (M:F = 1:2.5). The commonest complaint was the anterior neck mass (77.3%), followed by hoarseness (32.1%). The median survival time was 9 months, and the overall 1-, 2-, and 5-year survival rate was 39.8%, 33.7%, and 26.9%, respectively. The log-rank method shows that age, tumor size, lymph node status, M stage, surgical range, and tracheal status were the relevant factors affecting the prognosis. In contrast, gender, treatment modality, and resection margin were not prognostic factors. On multivariable analysis, age and M stage were associated with overall survival.

Conclusion

The median overall survival was 6–9 months of PSCCT. Age and M stage are predictors of PSSCT.
Neuron matters: neuromodulation with electromagnetic stimulation must consider neurons as dynamic identities
Authors: Ye Hui , Hendee Jenna , Ruan Joyce , Zhirova Alena , Ye Jayden , Dima Maria
Published: November 2022

Neuromodulation with electromagnetic stimulation is widely used for the control of abnormal neural activity, and has been proven to be a valuable alternative to pharmacological tools for the treatment of many neurological diseases. Tremendous efforts have been focused on the design of the stimulation apparatus (i.e., electrodes and magnetic coils) that delivers the electric current to the neural tissue, and the optimization of the stimulation parameters. Less attention has been given to the complicated, dynamic properties of the neurons, and their context-dependent impact on the stimulation effects. This review focuses on the neuronal factors that influence the outcomes of electromagnetic stimulation in neuromodulation. Evidence from multiple levels (tissue, cellular, and single ion channel) are reviewed. Properties of the neural elements and their dynamic changes play a significant role in the outcome of electromagnetic stimulation. This angle of understanding yields a comprehensive perspective of neural activity during electrical neuromodulation, and provides insights in the design and development of novel stimulation technology.
Age-related radiographic parameters difference between the degenerative lumbar spinal stenosis patients and healthy people and correlation analysis
Authors: Li Donglai , Wang Lianlei , Wang Zheng , Li Chao , Yuan Suomao , Tian Yonghao , Yu Xuguang , Liu Xinyu
Published: November 2022

Objectives

To identify age-related radiographic risk factors for degenerative lumbar spinal stenosis (DLSS) and analyze correlations among them.

Methods

A total of 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray was examined. And following parameters were measured and evaluated: intervertebral disk height (IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disk degeneration (DD), cartilaginous endplate failure (CEF), Modic changes, the thickness of ligamentum flavum (LF), range of intervertebral motion (ROM), facet joint opening (FJO), facet joint angle (FJA), the standard cross-sectional area (SCSA) of the multifidus, erector spinae, and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed.

Results

Compared with the control group, the DLSS group had higher IDH except for L4-5 and larger iIDHL4-5 (P < 0.05). Significant differences were shown in CEF and the thickness of LF at L1-S1 and DD at L4-5 (P < 0.05). The DLSS group had smaller SCSA of multifidus, erector spinae, and psoas major muscles but greater FJA, FJO (P < 0.05). And the risk of DLSS increased when iIDHL4-5 ≥ 10.73 mm, FJA ≥ 52.03° , or FJO ≥ 3.75 mm. IDH positively correlated with SCSA of multifidus and psoas major muscles and ROM at L1-S1 (P < 0.05). DD showed negative linear relations with SCSA of multifidus and psoas muscle and positive linear relation with CEF at L1-2, L2-3, and L5-S1 (P < 0.05).

Conclusion

Larger initial disk height and excessive CEF may induce DLSS by increasing intervertebral mobility to promote DD, and atrophied paravertebral muscles by weakening the stability of lumbar spine.
A new proof of evidence of cysteamine quantification for therapeutic drug monitoring in patients with cystinosis
Authors: Franzin Martina , Rossetto Silvia , Ruoso Rachele , Del Savio Rossella , Stocco Gabriele , Decorti Giuliana , Addobbati Riccardo
Published: November 2022

Background

To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine.

Results

The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported.

Conclusion

The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples.
Whole blood methylome-derived features to discriminate endocrine hypertension
Authors: Armignacco Roberta , Reel Parminder S. , Reel Smarti , Jouinot Anne , Septier Amandine , Gaspar Cassandra , Perlemoine Karine , Larsen Casper K. , Bouys Lucas , Braun Leah , Riester Anna , Kroiss Matthias , Bonnet-Serrano Fidéline , Amar Laurence , Blanchard Anne , Gimenez-Roqueplo Anne-Paule , Prejbisz Aleksander , Januszewicz Andrzej , Dobrowolski Piotr , Davies Eleanor , MacKenzie Scott M. , Rossi Gian Paolo , Lenzini Livia , Ceccato Filippo , Scaroni Carla , Mulatero Paolo , Williams Tracy A. , Pecori Alessio , Monticone Silvia , Beuschlein Felix , Reincke Martin , Zennaro Maria-Christina , Bertherat Jérôme , Jefferson Emily , Assié Guillaume
Published: November 2022

Background

Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches.

Results

Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL.

Conclusions

The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder.
Rare presentation of Waldenström’s macroglobulinaemia requiring bilateral above-knee amputations: a case report
Authors: Deen Raeed , Austin Calyb , Bowden Alexander , Bullen Andrew
Published: November 2022

Background

Waldenström’s macroglobulinaemia is a rarely encountered B-lymphocytic malignancy. Waldenström’s macroglobulinaemia-associated paraproteinaemia is linked to an increase in serum viscosity, which results in a hypercoagulable state. Burning bilateral foot pain in a man with alcohol dependence and controlled atrial fibrillation presenting to the emergency department was attributed to peripheral neuropathy, given satisfactory angiographic evidence of bilateral foot arterial blood supply. Subsequently, his presentation as an emergency with acute bilateral critical lower limb ischemia that was managed by bilateral above-knee amputations, prompted a wider search for other etiologies. We present a hitherto unreported case of Waldenström’s macroglobulinaemia-related acute bilateral lower limb ischemia, which required bilateral above-knee amputations.

Case presentation

A 50-year-old Caucasian man, who was an alcohol dependent heavy smoker, presented with burning pain in his right foot that was deemed to be related to alcoholic neuropathy. A computerized tomographic angiogram demonstrated an occluded right distal anterior tibial artery but a patent posterior tibial artery supplying the foot arch, findings that were associated with noncritical ischemia. After multiple presentations within a week, he was admitted following sudden clinical deterioration with acute confusion, hyponatremia, and bilateral foot pain. Over the course of 24 hours, the patient deteriorated rapidly, with bilateral lower limb ischemia requiring bilateral above-knee amputations. Subsequent investigations revealed a diagnosis of Waldenström’s macroglobulinaemia.

Conclusions

To the best of our knowledge, this is the only reported case of Waldenström’s macroglobulinaemia-induced bilateral lower limb ischemia requiring major bilateral amputations.
Psoriatic arthritis successfully treated with second-line anti-interleukin-6 treatment: a case report and review of the literature
Authors: Kutsuna Tatsuhiko , Hino Kazunori , Hasegawa Hitoshi , Watamori Kunihiko , Kidani Teruki , Imai Hiroshi , Miura Hiromasa
Published: November 2022

Background

Psoriatic arthritis treatment with antitumor necrosis factor has been shown to reduce disease activity. Nonetheless, more than 30% of patients do not achieve a sufficient response to tumor necrosis factor blockers. Currently, treatment with interleukin-6 inhibitors is expected to be effective and suppress the joint destruction in patients with psoriatic arthritis; however, evidence regarding their efficacy is limited to a few reports.

Case presentation

A 78-year-old Japanese woman with psoriatic arthritis associated with rapid joint destruction was successfully treated with a second-line anti-interleukin-6 receptor agent. In this case, a tumor necrosis factor inhibitor induced an inadequate response, and the right knee and left hip joints required artificial joint replacement surgery. However, second line treatment with anti-interleukin-6 treatment was effective, and the right elbow joint function was preserved.

Conclusions

We experienced a case of psoriatic arthritis, in which anti-interleukin-6 treatment repaired a bone cyst in the lateral epicondyle of the humerus and enthesitis of the distal interphalangeal joints. The patient is currently in clinical remission with no restrictions in daily life activities. Anti-interleukin-6 treatment may address the unmet needs of patients with psoriatic arthritis who are resistant or intolerant to antitumor necrosis factor treatment, with rapidly destructive large joints but with well-managed skin manifestations.
Biocatalytic production of the antibiotic aurachin D in Escherichia coli
Authors: Kruth Sebastian , Schibajew Lina , Nett Markus
Published: November 2022

Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with recombinant Escherichia coli cells expressing the biosynthesis enzyme AuaA. In order to achieve a high-level production of this membrane-bound farnesyltransferase in E. coli, the expression of the auaA gene was translationally coupled to an upstream cistron in accordance with a bicistronic design (BCD) strategy. Screening of various BCD elements led to the identification of optimized auaA expression cassettes, which increased the aurachin D titer in E. coli up to 29-fold in comparison to T7-mediated expression. This titer could be further raised by codon optimization of auaA and by introducing the mevalonate pathway into the production strain. The latter measure was intended to improve the availability of farnesyl pyrophosphate, which is needed as a cosubstrate for the AuaA-catalyzed reaction. In sum, the described efforts resulted in a strain producing aurachin D with a titer that is 424 times higher than that obtained with the original, non-optimized expression host.

Graphical Abstract
Reconnoitering the significance of security using multiple cloud environments for conveyance applications with blowfish algorithm
Authors: Shitharth S , Alotaibi Fahad S. , Manoharan Hariprasath , Khadidos Adil O. , Alyoubi Khaled H. , Alshareef Abdulrhman M.
Published: November 2022

In recent years the process of transportation needs a highly effective traffic system in order to monitor all consumer goods as many goods are left out at different locations. To handle such moving cases cloud platform is highly helpful as with respect to geographical location the goods are mapped in correct form. However incorporation of single cloud platform does not provide sufficient amount of storage about all goods thus a multiple cloud platform is introduced in proposed system. As multiple cloud platform is provided the security features of each data base system is also checked and enhanced using encryption keys. Moreover for proper operating conditions of multiple cloud platforms an analytical model is designed that synchronizes necessary data at end system. The defined analytical model focuses on solving multiple objectives that are related to critical energy problems where demand problems are reduced. Further the encryption process is carried out using Improved BlowFish Algorithm (IBFA) by allocating proper resources with decryption keys. To validate the effectiveness of proposed method five scenarios are considered where all scenario outcomes proves to be much higher than existing models by an average of 43%.
Biochemical and histopathological studies of sulfonylurea derivative as a new chemotherapeutic agent against liver cancer in free- and nano-coated forms
Authors: Sroor Farid M. , Basyouni Wahid M. , Aly Hanan F. , Younis Eman A. , Mahrous Karima F. , Haroun Ahmed A.
Published: November 2022

The most frequent type of primary liver cancer is hepatocellular carcinoma (HCC), accounting for approximately 90% of primary liver cancers and a third leading cause of cancer deaths. In the current study, the synthesized compound 3 was re-formulated using tetraethyl orthosilicate (TEOS) with weight ratio (1:1) via sol-gel technique. The prepared material has been examined using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray elemental analysis (EDX), and scanning and transmission electron microscopes (SEM and TEM). Herein, we investigate the mode of action of 3 as potent anti-liver cancer in vivo as normal and nano-forms. Rats were given a single dosage of 50 mg/kg b.wt. of HCC through an intraperitoneal injection (ip). A single dosage of CCl4 (2 ml/kg IP) was also given to rats 2 weeks later. Several liver, tumor and oxidative stress biomarkers were detected including liver enzymes; alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatse (ALP), gamma glutamyl transferase (GGT), glutathione (GSH), lipid peroxide (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), α-fetoprotein and α-L-Fucosidase. Hepatic pathological pictures were also performed for the documentation of the presence of HCC and supported the biochemical results. Moreover, the DNA damage in liver tissues of male rats using comet assay was studied. The results showed that the HePG2 (− ve) group of rats exhibited a significant reduction (P < 0.05) in DNA damage values (9.30 ± 0.89) relative to other treatment groups. Nevertheless, the DNA damage values in the HePG2 (+ ve) and 5-flurouracil groups were significantly higher (P < 0.01) compared to the HePG2 (− ve) group. Additionally, HePG2 (coated 3) and HePG2 (3) groups exhibited significant decrease in the DNA damage compared to those in HePG2 (+ ve) group.
Early intubation and clinical outcomes in patients with severe COVID-19: a systematic review and meta-analysis
Authors: Lee Hyeon-Jeong , Kim Joohae , Choi Miyoung , Choi Won-Il , Joh Joonsung , Park Jungeun , Kim Junghyun
Published: November 2022

Background

Evidence regarding the timing of the application of mechanical ventilation among patients with severe coronavirus disease (COVID-19) is insufficient. This systematic review and meta-analysis aimed to evaluate the effectiveness of early intubation compared to late intubation in patients with severe and critical COVID-19.

Methods

For this study, we searched the MEDLINE, EMBASE, and Cochrane databases as well as one Korean domestic database on July 15, 2021. We updated the search monthly from September 10, 2021 to February 10, 2022. Studies that compared early intubation with late intubation in patients with severe COVID-19 were eligible for inclusion. Relative risk (RR) and mean difference (MD) were calculated as measures of effect using the random-effects model for the pooled estimates of in-hospital mortality, intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation (MV), hospital LOS, ICU-free days, and ventilator-free days. Subgroup analysis was performed based on the definition of early intubation and the index time. To assess the risk of bias in the included studies, we used the Risk of Bias Assessment tool for Non-randomized studies 2.0.

Results

Of the 1523 records identified, 12 cohort studies, involving 2843 patients with severe COVID-19 were eligible. There were no differences in in-hospital mortality (8 studies, n = 795; RR 0.91, 95% CI 0.75–1.10, P = 0.32, I2 = 33%), LOS in the ICU (9 studies, n = 978; MD −1.77 days, 95% CI −4.61 to 1.07 days, P = 0.22, I2 = 78%), MV duration (9 studies, n = 1,066; MD −0.03 day, 95% CI −1.79 to 1.72 days, P = 0.97, I2 = 49%), ICU-free days (1 study, n = 32; 0 day vs. 0 day; P = 0.39), and ventilator-free days (4 studies, n = 344; MD 0.94 day, 95% CI −4.56 to 6.43 days, P = 0.74, I2 = 54%) between the early and late intubation groups. However, the early intubation group had significant advantage in terms of hospital LOS (6 studies, n = 738; MD −4.32 days, 95% CI −7.20 to −1.44 days, P = 0.003, I2 = 45%).

Conclusion

This study showed no significant difference in both primary and secondary outcomes between the early intubation and late intubation groups.

Trial registration This study was registered in the Prospective Register of Systematic Reviews on 16 February, 2022 (registration number CRD42022311122).
Application of different foliar iron fertilizers for improving the photosynthesis and tuber quality of potato (Solanum tuberosum L.) and enhancing iron biofortification
Authors: Zhang Ruyan , Zhang Weina , Kang Yichen , Shi Mingfu , Yang Xinyu , Li Hong , Yu Huifang , Wang Yong , Qin Shuhao
Published: November 2022

Background

The potato (Solanum tuberosum L.) is an important food crop in the alkaline soil area of northwest China. It is abundant in ascorbic acid (vitamin C), which facilitates iron absorption in the body. The large consumption of potato makes it a good food source of iron absorption for human body. However, iron deficiency in alkaline soil regions reduced chlorophyll synthesis in the leaves, resulting in lower photosynthesis and less sugar supply to the plant's healthy organs, significantly restricted crop development and yield, and inflicted major economic losses.

Methods

In this study, a 2-year (2020–2021) field trial was designed. Under foliar application of five different iron fertilizers: ferric sulfate [(Fe2(SO4)3], T1; ferrous sulfate (FeSO4·7H2O), T2; citric acid/ferric sulfate (CA/Fe2(SO4)3), T3; citric acid/ferrous sulfate (CA/FeSO4·7H2O), T4; ethylenediamine tetra acetic acid (EDTA-Fe·Na), T5, changes in potato plant photosynthesis were compared to no iron fertilization, CK conditions. The effects of various iron fertilizers on the yield, quality, and iron content of potato tubers, their correlations to chlorophyll levels, and the characteristics of photosynthetic fluorescence were studied.

Results

The results indicated that spraying iron fertilizers increased the yield, quality and Fe content of the tubers, which might be due to the improvement of the plants’ photosynthetic pigment content, gas exchange parameters and chlorophyll fluorescence. In two consecutive years of cultivation, we found that potato tuber yield and Fe content increased in potatoes treated with five iron fertilizer sprays. Among them, tuber yield increased most significantly by T5 and T3 treatments compared to CK, while Fe content was significantly higher by the T5 treatment than by CK and other treatments. Tuber yield was increased by 33.28% and 18.85% in 2020 and 50.74% and 54.48% in 2021 by T5 and T3 treatments, respectively, compared to CK. Fe content was increased by 112.64% and 54.98% in 2020 and 2021 by T5 treatment, respectively, compared to CK.

Conclusions

EDTA-Fe·Na and CA/Fe2(SO4)3 excelled over the other iron fertilizers. The findings of this study are instructive for developing cost-effective iron fertilizer management systems to maximize the impact of iron biofortification on human health.

Graphical Abstract
Wheat and chaff: the degree to which strategic management principles are integrated within corporate social responsibility reporting among large Canadian firms
Authors: Fuller Mark
Published: November 2022

This empirical study examines the degree to which strategic principles are reflected in the corporate social responsibility (CSR) reporting practices among Canada’s largest corporations. In a two-phased approach, three time periods of corporate disclosure from 2016 to 2020 were studied. Using an organizational flowchart derived from the literature, CSR disclosures were organized according to six degrees of strategic integration. Analysis reveals a bimodal distribution of firms, with one mode representing firms with a fully integrated reporting framework, and another mode representing firms with the partial integration of strategic management principles. Inconsistent patterns of progress in reporting practices were discovered, with some firms demonstrating improved reporting practices while others stagnated or declined. Overall, a generalized improvement in strategic integration during our multi-year examination was observed. While this work has implications for corporate social responsibility theory, recommendations for CSR practitioners are also discussed.
Therapy-resistant nature of cancer stem cells in view of iron metabolism
Authors: Wang Wenqian , Tabu Kouichi , Aimaitijiang Alapati , Taga Tetsuya
Published: November 2022

Due to increased resistance to standard chemo/radiotherapies and relapse, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for the development of effective cancer treatments. In order to develop innovative cancer therapies that target CSCs, much attention has focused on the iron metabolism of CSCs, which has been considered to contribute to self-renewal of CSCs. Here, we review recent advances in iron metabolism and conventional iron metabolism-targeted cancer therapies, as well as therapy resistance of CSCs and potential treatment options to overcome them, which provide important insights into therapeutic strategies against intractable cancers. Potential treatment options targeting iron homeostasis, including small-molecule inhibitors, nanotechnology platforms, ferroptosis, and 5-ALA-PDT, might be a focus of future research for the development of innovative cancer therapies that tackle CSCs.
Psychotic relapse in people with schizophrenia within 12 months of discharge from acute inpatient care: protocol for development and validation of a prediction model based on a retrospective cohort study in three psychiatric hospitals in Japan
Authors: Sato Akira , Watanabe Norio , Maruo Kazushi , Moriyama Toshihiro , Furukawa Toshi A.
Published: November 2022

Background

Schizophrenia is a severe mental illness characterized by recurrent psychoses that typically waxes and wanes through its prodromal, acute, and chronic phases. A large amount of research on individual prognostic factors for relapse in people with schizophrenia has been published, and a few logistic models exist to predict psychotic prognosis for people in the prodromal phase or after the first episode of psychosis. However, research on prediction models for people with schizophrenia, including those in the chronic phase and after multiple recurrences, is scarce. We aim to develop and validate a prediction model for this population.

Methods

This is a retrospective cohort study to be undertaken in Japan. We will include participants aged 18 years or above, diagnosed with schizophrenia or related disorders, and discharged between January 2014 and December 2018 from one of the acute inpatient care wards of three geographically distinct psychiatric hospitals. We will collect pre-specified nine predictors at the time of recruitment, follow up the participants for 12 months after discharge, and observe whether our primary outcome of a relapse occurs. Relapse will be considered to have occurred in one of the following circumstances: (1) hospitalization; (2) psychiatrist’s judgment that the person needs hospitalization; (3) increasing doses of antipsychotics; or (4) suicidal or homicidal ideation or behavior resulting from such ideation. We will develop a Cox regression model and avoid overfitting by penalizing coefficients using the elastic net. The model will be validated both internally and externally by bootstrapping and “leave-one-hospital-out” cross-validation, respectively. We will evaluate the model’s performance in terms of discrimination and calibration. Decision curve analysis will be presented to aid decision-making. We will present a web application to visualize the model for ease of use in daily practice.

Discussion

This will be the first prediction modeling study of relapse after discharge among people with both first and multiple episodes of schizophrenia using routinely collected data.

Trial registration

This study was registered in the UMIN-CTR (UMIN000043345) on February 20, 2021.
Neural stem cell research in Africa: current realities and future prospects
Authors: Azeez Idris A. , Awogbindin Ifeoluwa O. , Olayinka Juliet N. , Folarin Royhaan O. , Adamu Abubakar S. , Ior Lydia D. , Shehu Asmau M. , Mukhtar Abubakar I. , Ajeigbe Olufunke F. , Emokpae Aghariagbonse O. , Usende Ifukibot L. , Babatunde Bamidele R. , Yusha'u Yusuf , Olateju Oladiran I. , Kamoga Ronald , Benson Ayoola I. O. , Oparaji Kenneth C. , Owemidu Idowu O. , Iliyasu Musa O. , Imam Maryam I. , Olopade James O.
Published: November 2022

Neural stem cells (NSCs) are immature progenitor cells that are found in developing and adult brains that have the potential of dividing actively and renewing themselves, with a complex form of gene expression. The generation of new brain cells in adult individuals was initially considered impossible, however, the landmark discovery of human neural stem cells in the hippocampus has been followed by further discoveries in other discreet regions of the brain. Investigation into the current state in Africa of the research and use of NSCs shows relatively limited activities on the continent. Information on the African application of NSCs for modelling disease mechanisms, drug discovery, and therapeutics is still limited. The International Brain Research Organization (IBRO)-African Regional Committee (ARC), with support from the Company of Biologists, and the Movement Disorder Society, sponsored the first African Basic School on NSC in Ibadan, Nigeria, with the vision of bringing together young neuroscientists and physicians across different fields in neuroscience to learn from leaders who have applied NSCs in stem cell research, the pathophysiology of neurodegenerative diseases, neuroanatomy, and neurotherapeutics. Twenty early-career researchers in academic institutions at junior and senior faculty cadres were selected from South Africa, Uganda and Nigeria. The students and organizer of the school, who wrote this review on the state of NSCs research in Africa, recommended the following: (1) other African countries can take a cue from South Africa and Nigeria in probing the phenomena of adult neurogenesis in unique animal species on the continent; (2) Africa should leverage the expertise and facilities of South African scientists and international collaborators in scaling up NSC research into these unique species and (3) Centers of Excellence should be established on the continent to serve as research hubs for training postgraduate students, and facilities for African scientists who trained overseas on NSCs.
Zebrafish parental progeny investment in response to cycling thermal stress and hypoxia: deposition of heat shock proteins but not cortisol
Authors: Lim Michael Y.-T. , Bernier Nicholas J.
Published: November 2022

The maternal match hypothesis predicts that maternal exposure to a stressor may help prepare offspring to cope with the same disturbance in later life. Although there is support for this hypothesis, the signals involved in non-genetic inheritance are unclear. In this study, we tested how adult zebrafish exposure to diel cycles of thermal stress (27–36°C), hypoxia (20–85% dissolved oxygen) or the combined treatment affects maternal and embryonic levels of cortisol and heat shock proteins (HSPs). While parental exposure to the thermal, hypoxic or combined treatment for 2 weeks did not affect whole-body cortisol levels, the combined exposure increased ovarian cortisol levels by 4-fold and reduced embryonic cortisol content by 60%. The combined treatment also elicited 3- and 19-fold increases in embryo transcripts involved in cortisol breakdown (11bhsd2) and export (abcb4), respectively. The thermal stress and combined exposure also elicited marked increases in ovary and embryo hsp70a (20- to 45-fold) and HSP70 (3- to 7-fold), and smaller increases in ovary and embryo hsp90aa and hsp47 (2- to 4-fold) and in embryo HSP90 and HSP47 (2- to 6-fold). In contrast, except for increases in ovary hsp90aa (2-fold) and embryo HSP90 (3-fold), the hypoxia treatment had little effect on HSP expression and transfer. Overall, while the embryonic deposition of HSPs largely paralleled the ovarian cellular stress response, the inverse relationship between ovary and embryo cortisol levels suggests the existence of barriers against cortisol deposition in response to environmental stressors. We conclude that the endocrine and cellular stress responses make stressor-specific and distinct contributions to non-genetic inheritance.
Global profiling of the RNA and protein complexes ofEscherichia coliby size exclusion chromatography followed by RNA sequencing and mass spectrometry (SEC-seq)
Authors: Chihara Kotaro , Gerovac Milan , Hörb Jens , Vogel Jörg
Published: November 2022

New methods for the global identification of RNA–protein interactions have led to greater recognition of the abundance and importance of RNA-binding proteins (RBPs) in bacteria. Here, we expand this tool kit by developing SEC-seq, a method based on a similar concept as the established Grad-seq approach. In Grad-seq, cellular RNA and protein complexes of a bacterium of interest are separated in a glycerol gradient, followed by high-throughput RNA-sequencing and mass spectrometry analyses of individual gradient fractions. New RNA–protein complexes are predicted based on the similarity of their elution profiles. In SEC-seq, we have replaced the glycerol gradient with separation by size exclusion chromatography, which shortens operation times and offers greater potential for automation. Applying SEC-seq toEscherichia coli, we find that the method provides a higher resolution than Grad-seq in the lower molecular weight range up to ∼500 kDa. This is illustrated by the ability of SEC-seq to resolve two distinct, but similarly sized complexes of the global translational repressor CsrA with either of its antagonistic small RNAs, CsrB and CsrC. We also characterized changes in the SEC-seq profiles of the small RNA MicA upon deletion of its RNA chaperones Hfq and ProQ and investigated the redistribution of these two proteins upon RNase treatment. Overall, we demonstrate that SEC-seq is a tractable and reproducible method for the global profiling of bacterial RNA–protein complexes that offers the potential to discover yet-unrecognized associations between bacterial RNAs and proteins.
Prevalence, causes and impacts of human trafficking in Asian countries: A scoping review
Authors: Khan Zeeshan , Kamaluddin Mohammad Rahim , Meyappan Saravanan , Manap Jamiah , Rajamanickam Ramalinggam
Published: November 2022

Background: In Asian countries, human trafficking is often encountered as forced labor, forced marriage, sex trafficking, men, women, and children exploitation. This review points out how human trafficking activities are prevalent in Asian countries and also reveals different causes that are the basis of increasingly human trafficking in Asian countries such as poverty, unemployment, political uncertainty, war, natural disaster, corruption and weak policies. Human trafficking also creates huge health, physical, psychological and social implications on individuals and the overall society.

Methods: The purpose of this study is to collect evidence on human trafficking in Asian countries. A scoping review methodology was used to systematically search online databases including Sage Journals Online, Wiley Online, Hein Online, Taylor & Francis Online, Web of Science, and Scopus literature to amalgamate information on this issue. For the purposes of this article, 64 studies met the inclusion criteria after searching and screening a total number of 1,278 studies.

Results: The findings of this study were classified under three categories: prevalence of human trafficking in Asia, causes of human trafficking in Asia (poverty and unemployment, environmental and manmade disaster, weak policies and corruption), and impacts of human trafficking including social, health, physical, psychological impacts.

Conclusion: Keeping in mind the prevalence and impacts of human trafficking, the author also recommends some meaningful and practical steps for policymakers and researchers to effectively tackle human trafficking in Asian countries.
Regular antenatal care visits were associated with low risk of low birth weight among newborns in Rwanda: Evidence from the 2014/2015 Rwanda Demographic Health Survey (RDHS) Data
Authors: Biracyaza Emmanuel , Habimana Samuel , Rusengamihigo Donat , Evans Heather
Published: November 2022

Background: Low birth weight (LBW) remains the global unfinished agenda in most countries of the world especially in low- and middle-income countries. LBW subsequently has harmful effects on the lifestyle, psychosocial and physiological development of the child. Although it is known that antenatal care (ANC) visits are important interventions contributing to prediction of newborn birth weight, little has been conducted on effect of ANC visits on birth weight in Rwanda. This study aimed at determining the association between regular ANC visits and risk of LBW among newborns in Rwanda.

Methods: A cross-sectional study design was conducted to analyse the effects of ANC on LBW using the 2014/2015 Rwanda Demographic Health Survey. Associations of socio-demographic, socio-economic, and individual factors of the mother with LBW newborns were performed using bivariate and multiple logistic regression analyses.

Results: Prevalences of LBW and macrosomia were 5.8% and 17.6%, respectively. Newborns delivered from mothers attending fewer than four ANC visits were at almost three-times greater risk of having LBW [aOR=2.8; 95%CI (1.5–5.4), p=0.002] compared to those whose mothers attending four or more ANC visits. Residing in a rural area for pregnant women was significantly associated with LBW [aOR=1.1; 95%CI (0.7–1.6), p=0.008]. Maternal characteristics, such as anemia, predicted an increase in LBW [aOR=3.5; 95%CI (1.5–5.4),p<0.001]. Those who received no nutritional counseling [aOR=2.5; 95%CI (2–8.5), p<0.001] and who were not told about maternal complications [aOR=3.3; 95%CI (1.5–6.6), p=0.003] were more prone to deliver newborns with LBW than those who received them. Pregnant women who received iron and folic acid were less likely to have LBW newborns [aOR=0.5; 95%CI (0.3–0.9), p=0.015].

Conclusion: ANC visits significantly contributed to reducing the incidence of LBW. This study underscores the need for early, comprehensive, and high-quality ANC services to prevent LBW in Rwanda.
Chronic kidney disease (CKD) and associated risk in rural South Africa: a population-based cohort study
Authors: Fabian June , Gondwe Mwawi , Mayindi Nokthula , Chipungu Shingirai , Khoza Bongekile , Gaylard Petra , Wade Alisha N , Gómez-Olivé F. Xavier , Tomlinson Laurie A , Ramsay Michele , Tollman Stephen , Winkler Cheryl , George Jaya A , Naicker Saraladevi
Published: November 2022

Background: In Africa, true prevalence of chronic kidney disease (CKD) is unknown, and associated clinical and genetic risk factors remain understudied. This population-based cohort study aimed to investigate CKD prevalence and associated risk factors in rural South Africa.

Methods: A total 2021 adults aged 20-79 years were recruited between 2017-2018 from the Agincourt Health and Socio-Demographic Surveillance System in Bushbuckridge, Mpumalanga, South Africa. The following were collected: sociodemographic, anthropometric, and clinical data; venous blood samples for creatinine, hepatitis B serology; DNA extraction; spot urine samples for dipstick testing and urine albumin: creatinine ratio (UACR) measurement. Point-of-care screening determined prevalent HIV infection, diabetes, and hypercholesterolemia. DNA was used to test for apolipoprotein L1 (APOL1) kidney risk variants. Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose CKD as low eGFR (<60mL/min/1.73m2) and /or albuminuria (UACR ≥ 3.0mg/mmol) confirmed with follow up screening after at least three months. eGFR was calculated using the CKD-EPI(creatinine) equation 2009 with no ethnicity adjustment. Multivariable logistic regression was used to model CKD risk.

Results: The WHO age-adjusted population prevalence of CKD was 6.7% (95% CI 5.4 - 7.9), mostly from persistent albuminuria. In the fully adjusted model, APOL1 high-risk genotypes (OR 2.1; 95% CI 1.3 - 3.4); HIV infection (OR 1.8; 1.1 - 2.8); hypertension (OR 2.8; 95% CI 1.8 - 4.3), and diabetes (OR 4.1; 95% CI 2.0 - 8.4) were risk factors. There was no association with age, sex, level of education, obesity, hypercholesterolemia, or hepatitis B infection. Sensitivity analyses showed that CKD risk factor associations were driven by persistent albuminuria, and not low eGFR. One third of those with CKD did not have any of these risk factors.

Conclusions:  In rural South Africa, CKD is prevalent, dominated by persistent albuminuria, and associated with APOL1 high-risk genotypes, hypertension, diabetes, and HIV infection.