bluuebunny/crossref_metadata_2025 huggingface dataset:
Does it matter that standard preparedness indices did not predict COVID-19 outcomes?
Authors: Stoto Michael A. , Nelson Christopher D. , Kraemer John D.
Published: September 2023

A number of scientific publications and commentaries have suggested that standard preparedness indices such as the Global Health Security Index (GHSI) and Joint External Evaluation (JEE) scores did not predict COVID-19 outcomes. To some, the failure of these metrics to be predictive demonstrates the need for a fundamental reassessment which better aligns preparedness measurement with operational capacities in real-world stress situations, including the points at which coordination structures and decision-making may fail. There are, however, several reasons why these instruments should not be so easily rejected as preparedness measures.

From a methodological point of view, these studies use relatively simple outcome measures, mostly based on cumulative numbers of cases and deaths at a fixed point of time. A country’s “success” in dealing with the pandemic is highly multidimensional – both in the health outcomes and type and timing of interventions and policies – is too complex to represent with a single number. In addition, the comparability of mortality data over time and among jurisdictions is questionable due to highly variable completeness and representativeness. Furthermore, the analyses use a cross-sectional design, which is poorly suited for evaluating the impact of interventions, especially for COVID-19.

Conceptually, a major reason that current preparedness measures fail to predict pandemic outcomes is that they do not adequately capture variations in the presence of effective political leadership needed to activate and implement existing system, instill confidence in the government’s response; or background levels of interpersonal trust and trust in government institutions and country ability needed to mount fast and adaptable responses. These factors are crucial; capacity alone is insufficient if that capacity is not effectively leveraged. However, preparedness metrics are intended to identify gaps that countries must fill. As important as effective political leadership and trust in institutions, countries cannot be held accountable to one another for having good political leadership or trust in institutions. Therefore, JEE scores, the GHSI, and similar metrics can be useful tools for identifying critical gaps in capacities and capabilities that are necessary but not sufficient for an effective pandemic response.
Highly efficient Agrobacterium rhizogenes-mediated transformation for functional analysis in woodland strawberry
Authors: Yan Huiqing , Ma Dandan , Yi Peipei , Sun Guilian , Chen Xingyan , Yi Yin , Huang Xiaolong
Published: September 2023

Background

The diploid woodland strawberry (Fragaria vesca) is an excellent model plant for investigating economically significant traits and several genetic resources within the Rosaceae family. Agrobacterium rhizogenes-mediated hairy root transformation is an alternative for exploring gene functions, especially the genes specifically expressed in roots. However, the hairy root transformation has not been established in strawberry.

Results

Here, we described an efficient and rapid hairy root transgenic system for strawberry using A. rhizogenes. Strain of A. rhizogenes MSU440 or C58C1 was the most suitable for hairy root transformation. The transformation efficiency was highest when tissues contained hypocotyls as explants. The optimal procedure involves A. rhizogenes at an optical density (OD600) of 0.7 for 10 min and co-cultivation duration for four days, achieving a transgenic efficiency of up to 71.43%. An auxin responsive promoter DR5ver2 carrying an enhanced green fluorescent protein (eGFP) marker was transformed by A. rhizogenes MSU440, thereby generating transgenic hairy roots capable of high eGFP expression in root tip and meristem of strawberry where auxin accumulated. Finally, this system was applied for functional analysis using jGCaMP7c, which could sense calcium signals. A significant upsurge in eGFP expression in the transgenic hairy roots was displayed after adding calcium chloride. The results suggested that this approach was feasible for studying specific promoters and could be a tool to analyze gene functions in the roots of strawberries.

Conclusion

We established a rapid and efficient hairy root transformation in strawberry by optimizing parameters, which was adequate for promoter analysis and functional characterization of candidate genes in strawberry and other rosaceous plants.
Comparison of different surgical treatments for stage II progressive collapsing foot deformity: a finite element analysis
Authors: Chen Fanglin , Yuan Chengjie , Liang Mian , Le Guoping , Xu Jian
Published: September 2023

Background

This study analyzed the advantages and disadvantages of different procedures for stage IIA progressive collapsing foot deformity (PCFD) through three-dimensional finite element models.

Methods

A previous validated stage IIA PCFD FEA model was established consisting of 16 bones, 56 ligaments, 5 muscles and soft tissues. The ligament properties of the spring, deltoid, short plantar and long plantar ligaments, and plantar fascia were attenuated according to a previous publication. Medial column fusion (MCF), medializing calcaneal osteotomy (MCO), lateral column lengthening (LCL), and subtalar joint arthroereisis (SJA) operations were simulated in this model. The indexes of plantar stress distribution, maximum von Mises of the medial and lateral columns, strain of the medial ligaments and plantar fascia that supported the medial longitudinal arch, arch height, talo-first metatarsal angle, calcaneus pitch angle, and talonavicular coverage angle were all compared before and after simulated single-foot weight loading.

Results

The maximum plantar stress of PCFD decreased with MCO and SJA but increased with MCF and LCL. MCF and LCL failed to significantly reduce the stress on the medial column fragments, thereby increasing their stress. Both MCO and SJA relieved medial plantar stress. MCF had no significant effect on stress relief of the medial ligament. MCO, LCL, and SJA were all shown to reduce the pressure on the medial plantar ligament, with LCL having the most obvious effect. All four procedures corrected the arch deformity; however, MCF was not as effective as the other methods. SJA is the best method for restoring arch height and correcting arch deformities. For stage IIA PCFD, isolated MCF failed to reduce pressure on the medial column; however, isolated MCO significantly reduced the pressure on the medial plantar and ligamentous soft tissues while restoring the foot’s arch and correcting the hindfoot valgus.

Conclusion

SJA with type II sinus tarsi implant effectively transferred pressure from the medial plantar tract to the lateral side and restored the arch. Isolated LCL was not found suitable for stage IIA PCFD.
Validation of the Chinese version of the Brief Pain Inventory in patients with knee osteoarthritis
Authors: Wang Shunxing , Yao Shuxin , Shang Lei , Xu Chao , Ma Jianbing
Published: September 2023

Background

Knee osteoarthritis (KOA) primarily presents with symptoms of pain and compromised functionality. Pain is a subjective manifestation that necessitates the employment of reliable evaluation tools for practical assessment, thereby enabling the formulation of appropriate interventional strategies. The Brief Pain Inventory (BPI) is a widely utilized questionnaire for evaluating the status of chronic pain. The purpose of the present study is to translate the short form of BPI into Chinese version (BPI-CV) and conduct cross-cultural adaptation to evaluate the psychometric characteristics of BPI-CV in KOA patients.

Methods

BPI-CV was translated and cross-culturally adapted according to internationally recognized guidelines. A cohort comprising 150 patients diagnosed with KOA successfully completed the demographic questionnaire, BPI-CV, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the EuroQoL Group's five-dimension questionnaire (EQ-5D). Internal consistency and test–retest analysis were used to evaluate the reliability. The internal consistency of the scale items was evaluated by calculating the Cronbach's α value (> 0.7). We chose to employ two scales commonly used in the evaluation of KOA patients: the disease-specific WOMAC scale and the universal EQ-5D scale. Construct validity was determined through Pearson correlation analysis, comparing BPI scores with those obtained from the WOMAC and EQ-5D scales. Exploratory factor analysis was used to structural validity.

Results

The BPI-CV was well accepted with no ceiling or floor effect. Cronbach's α for assessing internal consistency was 0.894. Test–retest reliability was excellent with an ICC of 0.852 (95%CI 0.785–0.905). The BPI-CV showed moderate to strong correlations with the pain dimension (r = 0.496–0.860) and the functional interference dimension (r = 0.517–0.712) of the WOMAC and the EQ-5D (r = 0.527–0.743). Three factors resulted using exploratory factor analysis: pain severity, activity interference, and emotional interference, accounting for 79.0% of the total variance. Standard error of measurement was 0.539.

Conclusion

BPI-CV has good feasibility, reliability, and validity. It can be recommended for KOA patients in mainland China.
Long-term clinical outcomes of the Biomet M2a-38: a retrospective review of 335 total hip arthroplasty cases
Authors: Jones Caché S. , Gaillard-Campbell Dani , Gross Thomas P.
Published: September 2023

Background

At the turn of the century, over one-third of total hip arthroplasties comprised metal-on-metal bearings. As this patient population and their implants age, it is crucial to understand associated late failure modes and expected long-term functional outcomes. We report the long-term results of a large metal-on-metal uncemented total hip arthroplasty system with unique design characteristics compared to others that have been reported with high failure rates.

Methods

We retrospectively analyze our prospective clinical database to determine overall implant survivorship and functional outcomes. Further, we compare these results to the clinical outcomes reported in orthopedic registries and in other published studies with similar metal-on-metal total hip arthroplasty cohorts.

Results

Implant survivorship at 10 years was 99.1% and continued to 97.6% survivorship at 20 years. Implant survivorship at 20 years did not vary significantly between sexes (Male: 98.3%, Female: 97.2%; log-rank p-value = 0.46). Mean whole blood cobalt levels were 2.6 µg/L in unilateral cases, 5.3 µg/L in bilateral patients, and 3.4 µg/L for the combined cohort. Average blood chromium levels were 1.4 µg/L in unilateral patients, 2.9 µg/L in bilateral patients, and 1.8 µg/L for group combined. We observed a 0.9% rate of failure due trunnion corrosion at a mean of 13.1 years postoperatively (10.6–15.6 years) but had no bearing wear failures.

Conclusions

Our 20-year implant survivorship of 97.6% with the M2a-38 bearing surpassed registry benchmarks for THA. This large-bearing (38 mm), full hemisphere coverage metal-on-metal system had no bearing wear failures, one failure of instability, one failure of fixation, and three trunnion failures, perhaps suggesting an optimum balance between stability of the joint and the trunnion.
Surgical removal of an unusual huge solitary fibrous tumor in the mediastinum: a case report
Authors: Mardani Parviz , Nekooeian Mohammad , Zangeneh Saba , Kamran Hooman , Shahriarirad Reza , Anbardar Mohammad Hossein , Amirian Armin , Vafabin Masoud
Published: September 2023

Background

Intrathoracic Solitary Fibrous Tumors (SFT) mainly arise from the pleura; however, these tumors may also originate from the mediastinum. We present a rare case of posterior SFT extending to several mediastinal sites and with an unusual large size, successfully treated with surgical resection.

Case presentation

A 66-year-old female presented with an initial manifestation of ambiguous pain in the chest and dysphagia and later developed pitting edema in both lower extremities and cachexia five months before admission. Chest imaging confirmed a mediastinal mass (17 × 15 × 8 cm) which was surgically removed. Immunohistochemistry confirmed the diagnosis of a solitary fibrous tumor with positive B-cell lymphoma 2, STAT6, and CD99, negative S100 and smooth muscle actin, and low levels of Ki67 (5–7%). The patient’s follow-up course was unremarkable.

Conclusion

Mediastinal SFTs may grow extremely huge, with the potential to invade multiple adjacent sites. Surgical removal of the tumor remains the mainstay of treatment in these cases.
Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of ‘state-target identification and treatment’: a scooping review
Authors: Lian Jing , Lin Dongxin , Huang Yuchan , Chen Xiaohui , Chen Lian , Zhang Fan , Tang Peiling , Xie Jinling , Hou Xiaotao , Du Zhengcai , Deng Jiagang , Hao Erwei , Liu Junhui
Published: September 2023

Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour’s microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation—an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour’s inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1β), transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin’s novel model of “state-target differentiation” and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy—a harmonious integration of state identification, target recognition, and simultaneous regulation—aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.
Sociodemographic characteristics, attitudes, and knowledge associated with previous screening for cervical cancer among women in western Jamaica
Authors: Jolly Pauline E. , Junkins Anna , Aung Maung
Published: September 2023

Background

About 90% of new cervical cancer cases and deaths worldwide in 2020 occurred in low- and middle-income countries. This can be attributed to the low rates of cervical cancer screening in these countries. This study was conducted to identify factors associated with lack of cervical cancer screening among women in western Jamaica with the aim to increase screening and decrease cervical cancer risk.

Methods

This cross-sectional study assessed associations between previous Pap testing or lack of testing in five years or more, sociodemographic characteristics, attitudes, and knowledge of cervical cancer among women recruited from clinics and community events in the four parishes of western Jamaica. Analyses included chi-square tests, Fisher’s exact tests, and logistic regression.

Results

Of the 223 women included in the study, 109 (48.9%) reported Pap testing five years or more previous to the study. In the multivariate analysis, women from St. James (Odds Ratio [OR]: 3.35, 95% Confidence Interval [CI]: 1.12–9.99), Trelawny (OR: 5.34, 95% CI: 1.23–23.25), and Westmoreland (OR: 3.70, 95% CI: 1.10–12.50) had increased odds of having had Pap test screening compared to women from Hanover. Women ≥ 50 years of age compared to women 18–29 years of age (OR: 6.17, 95% CI: 1.76–21.54), and employed compared to unemployed women (OR: 2.44, 95% CI: 1.15–5.20) had increased odds of Pap test screening. Similarly, women with one (OR: 4.15, 95% CI: 1.06–16.22) or two or more children (OR: 8.43, 95% CI: 2.24–31.63) compared to women with no children had higher odds of screening. Women who were aware, compared to women who were unaware, of the purpose of Pap tests had increased odds of screening (OR: 3.90, 95% CI: 1.55–9.82). Lastly, women who believed Pap tests were painful compared to women who did not, had decreased odds of having had a Pap test (OR: 0.33, 95% CI: 0.16–0.71).

Conclusions

Uptake of Pap tests among the women was suboptimal and varied among parishes. Young women and women without children were less likely to have ever been screened. Increased education of the purpose of Pap tests to treat pre-cancer to prevent cancer and minimization of the notion that Pap tests are painful could promote screening among women in this population.
Functional polarization of tumor-associated macrophages dictated by metabolic reprogramming
Authors: Zeng Wentao , Li Fei , Jin Shikai , Ho Ping-Chih , Liu Pu-Ste , Xie Xin
Published: September 2023

Macrophages are highly plastic in different tissues and can differentiate into functional subpopulations under different stimuli. Tumor-associated macrophages (TAMs) are one of the most important innate immune cells implicated in the establishment of an immunosuppressive tumor microenvironment (TME). Recent evidence pinpoints the critical role of metabolic reprogramming in dictating pro-tumorigenic functions of TAMs. Both tumor cells and macrophages undergo metabolic reprogramming to meet energy demands in the TME. Understanding the metabolic rewiring in TAMs can shed light on immune escape mechanisms and provide insights into repolarizing TAMs towards anti-tumorigenic function. Here, we discuss how metabolism impinges on the functional divergence of macrophages and its relevance to macrophage polarization in the TME.
Development of a sustainable multianalyte MEKC method for quantitation of the antihyperlipidemic drugs ezetimibe together with three statins. Greenness and whiteness appraisal studies
Authors: Elbordiny Haydi S. , Elonsy Sohila M. , Daabees Hoda G. , Belal Tarek S.
Published: September 2023

Implementing powerful and sustainable research that complies with green analytical chemistry (GAC) and white analytical chemistry (WAC) fundamentals can downsize the environmental compliance costs and fruitfully affects practical and economic issues. Within this framework, rapid and white analytical micellar electrokinetic capillary chromatography (MEKC) methodology was developed for the synchronized estimation of the antihyperlipidemic drugs Ezetimibe (EZE), Atorvastatin (ATO), Rosuvastatin (ROS) and Simvastatin (SIM). The technique was established using fused silica capillary (50 cm, 50 µm id) and the background electrolyte was 0.025 M borate buffer pH 9.2 containing 0.025 M sodium dodecyl sulfate (SDS) and 10% v/v acetonitrile as the organic modifier. Diode array detector was adjusted at 243 nm for ATO and ROS and 237 nm for EZE and SIM. Separation was accomplished within 10 min with migration times of 4.12, 5.42, 8.23 and 8.74 min for ROS, ATO, EZE and SIM respectively. The 4 drugs were quantitated in the concentration range of 10–100 μg/mL and the correlation coefficients were not less than 0.9993. The high sensitivity was illustrated by values of the detection and quantitation limits. The limits of detection for ROS, ATO, EZE and SIM were 0.52, 0.75, 0.42 and 0.64 μg/mL, respectively, whereas, the limits of quantitation values were 1.73, 2.50, 1.40 and 2.13 μg/mL for the studied drugs, respectively. In addition to validation, as reported by the ICH guidelines, greenness and whiteness assessment using the novel AGREE calculator and the holistic functionality model RGB12 were performed. The results proved the efficiency and whiteness of the suggested technique to be routinely implemented in quality control laboratories for the assay of the four drugs and the binary mixtures of EZE with either ATO, ROS or SIM in fixed-dose combined tablets.
Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer
Authors: Wang Jun , Niu Yanqin , Yang Ming , Shu Lirong , Wang Hongxian , Wu Xiaoqian , He Yaqin , Chen Peng , Zhong Guocheng , Tang Zhixiong , Zhang Shasha , Guo Qianwen , Wang Yun , Yu Li , Gou Deming
Published: September 2023

Background

Breast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear.

Methods

Improved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 49 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hypermethylated regions as diagnostic markers for breast cancer was evaluated.

Results

Mean size of cfDNA fragments (100–220 bp) mapped to hypomethylated regions decreased more in patients with breast cancer (4.60 bp, 172.33 to 167.73 bp) than in healthy individuals (2.87 bp, 174.54 to 171.67 bp). Furthermore, proportion of short cfDNA fragments (100–150 bp) in hypomethylated regions when compared with it in hypermethylated regions was found to increase more in patients with breast cancer in two independent discovery cohort. The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for breast cancer diagnosis in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity).

Conclusion

We identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.
Motor control differs for increasing and decreasing force production during ankle Isometric exercises in children
Authors: Xiong Qiliang , Mo Jieyi , Yi Chen , Jiang Shaofeng , liu Yuan
Published: September 2023

Background

Performance of the central nervous system (CNS) in increased and decreasing muscle force around the ankle joint is essential for upright tasks of daily living. Previous studies have shown altered CNS control when they decrease force compared with when they increase force in young and older adults. But whether such alteration exists during childhood with incomplete maturation of CNS systems remain unclear. Therefore, this study aimed to evaluate the disparities in intramuscular EMG-EMG coherence, which serve as indicators of corticospinal drive to muscles during ankle isometric increasing and decreasing force generation in children.

Methods

We measured intramuscular EMG-EMG coherence activity of the tibialis anterior (TA) and the associated ability to perform isometric efforts at the ankle in 12 typically developing children (mean ± SD age = 5.91±1.37 years) and 12 healthy young adults (mean ± SD age = 23.16±1.52 years). The participants maintained isometric contractions at 20% of their maximal voluntary contractions (MVC) during ankle dorsiflexion to match a triangle trajectory for 7 s, including ramping up in 3.5 s (increasing force phase) and then linearly ramping down to rest in 3.5 s (decreasing force phase). The variability of force control was characterized by the coefficient of variance (CoV) of force output. Intramuscular EMG-EMG coherence from TA in two frequency bands, the beta band (15–30 Hz) and gamma band (30–45) that could reflect the corticospinal drive, were calculated for the comparison. A repeated measures ANOVA with the within-subjects factor of force generation phase (increasing force vs. decreasing force)x between-subjects factor of the group (children and young adults) was used for statistical analysis.

Results

Regarding the within-subjects difference, our results exhibited significantly higher CoV of force (p < 0.01) and lower EMG-EMG coherence of TA when they decrease force compared with when they increase force in both children and young adult groups. Regarding the between-subjects difference, the CoV of force was significantly higher (p < 0.01) in children compared to young adults, while the EMG-EMG coherence in children showed a significantly lower (p < 0.01) coherence compared with young adults. Furthermore, the EMG-EMG coherence measures were negatively correlated with the CoV of force.

Conclusions

The findings suggest that the age-related development would increase the corticospinal drive to TA muscle to deal with ankle isometric dorsiflexion during childhood, which could be also modulated with the force production phases, including increasing and decreasing force.
Early onset Parkinson’s disease in the cycle of 3,4-methylenedioxymethamphetamine and substance use: a case report
Authors: Hui Tianyi , Guo Song
Published: September 2023

Background

Current evidence linking the development of Parkinson’s disease after the use of 3,4-methylenedioxymethamphetamine is mixed and limited, with only a few positive case reports demonstrating this.

Case presentation

We examine this interesting case of a 49-year-old Chinese gentleman who used 3,4-methylenedioxymethamphetamine and subsequently developed early onset Parkinson’s disease at age 38 years. He had a family history of Parkinson’s disease, though the onset of his symptoms was significantly earlier than those of his family members. MDMA was a likely precipitating factor for the early onset of his symptoms. He then conversely used methamphetamines to augment his treatment of Parkinson’s symptoms. In the treatment of his Parkinson’s disease, dopamine replacement therapy and deep brain stimulation could perpetuate addictive behaviors such as dopamine dysregulation syndrome, and similarly perpetuate substance use in vulnerable individuals. He had also been diagnosed with a human immunodeficiency virus infection at age 43, and his antiretroviral therapy contributed to depressive symptoms, which then complicated the management of his substance use.

We examined the importance of managing his subsequent psychiatric and medical comorbidities to prevent their debilitating psychosocial impacts.

Conclusions

This case implies that 3,4-methylenedioxymethamphetamine use may precipitate the early development of Parkinson’s disease in patients with genetic vulnerability. This highlights the risk in patients potentially paradoxically using substances to alleviate symptoms of Parkinson’s, which can in turn perpetuate the disease process.
Rheumatoid arthritis: the old issue, the new therapeutic approach
Authors: Babaahmadi Mahnaz , Tayebi Behnoosh , Gholipour Nima Makvand , Kamardi Mehrnaz Tayebi , Heidari Sahel , Baharvand Hossein , Eslaminejad Mohamadreza Baghaban , Hajizadeh-Saffar Ensiyeh , Hassani Seyedeh-Nafiseh
Published: September 2023

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease of unknown etiology. The most common form of this disease is chronic inflammatory arthritis, which begins with inflammation of the synovial membrane of the affected joints and eventually leads to disability of the affected limb. Despite significant advances in RA pharmaceutical therapies and the availability of a variety of medicines on the market, none of the available medicinal therapies has been able to completely cure the disease. In addition, a significant percentage (30–40%) of patients do not respond appropriately to any of the available medicines. Recently, mesenchymal stromal cells (MSCs) have shown promising results in controlling inflammatory and autoimmune diseases, including RA. Experimental studies and clinical trials have demonstrated the high power of MSCs in modulating the immune system. In this article, we first examine the mechanism of RA disease, the role of cytokines and existing medicinal therapies. We then discuss the immunomodulatory function of MSCs from different perspectives. Our understanding of how MSCs work in suppressing the immune system will lead to better utilization of these cells as a promising tool in the treatment of autoimmune diseases.
Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes
Authors: Sleiman Yvonne , Reiken Steven , Charrabi Azzouz , Jaffré Fabrice , Sittenfeld Leah R. , Pasquié Jean-Luc , Colombani Sarah , Lerman Bruce B. , Chen Shuibing , Marks Andrew R. , Cheung Jim W. , Evans Todd , Lacampagne Alain , Meli Albano C.
Published: September 2023

Background

Polymorphic ventricular tachycardia (PMVT) is a rare genetic disease associated with structurally normal hearts which in 8% of cases can lead to sudden cardiac death, typically exercise-induced. We previously showed a link between the RyR2-H29D mutation and a clinical phenotype of short-coupled PMVT at rest using patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs). In the present study, we evaluated the effects of clinical and experimental anti-arrhythmic drugs on the intracellular Ca2+handling, contractile and molecular properties in PMVT hiPSC-CMs in order to model a personalized medicine approach in vitro.

Methods

Previously, a blood sample from a patient carrying the RyR2-H29D mutation was collected and reprogrammed into several clones of RyR2-H29D hiPSCs, and in addition we generated an isogenic control by reverting the RyR2-H29D mutation using CRIPSR/Cas9 technology. Here, we tested 4 drugs with anti-arrhythmic properties: propranolol, verapamil, flecainide, and the Rycal S107. We performed fluorescence confocal microscopy, video-image-based analyses and biochemical analyses to investigate the impact of these drugs on the functional and molecular features of the PMVT RyR2-H29D hiPSC-CMs.

Results

The voltage-dependent Ca2+channel inhibitor verapamil did not prevent the aberrant release of sarcoplasmic reticulum (SR) Ca2+in the RyR2-H29D hiPSC-CMs, whereas it was prevented by S107, flecainide or propranolol. Cardiac tissue comprised of RyR2-H29D hiPSC-CMs exhibited aberrant contractile properties that were largely prevented by S107, flecainide and propranolol. These 3 drugs also recovered synchronous contraction in RyR2-H29D cardiac tissue, while verapamil did not. At the biochemical level, S107 was the only drug able to restore calstabin2 binding to RyR2 as observed in the isogenic control.

Conclusions

By testing 4 drugs on patient-specific PMVT hiPSC-CMs, we concluded that S107 and flecainide are the most potent molecules in terms of preventing the abnormal SR Ca2+release and contractile properties in RyR2-H29D hiPSC-CMs, whereas the effect of propranolol is partial, and verapamil appears ineffective. In contrast with the 3 other drugs, S107 was able to prevent a major post-translational modification of RyR2-H29D mutant channels, the loss of calstabin2 binding to RyR2. Using patient-specific hiPSC and CRISPR/Cas9 technologies, we showed that S107 is the most efficient in vitro candidate for treating the short-coupled PMVT at rest.
Estimation of LFM signal parameters using RD compressed sampling and the DFRFT dictionary
Authors: Meng Shuo , Meng Chen , Wang Cheng
Published: September 2023

In this paper, a method combining random demodulator (RD) and discrete fractional Fourier transform (DFRFT) dictionary is suggested to directly estimate the parameters of linear frequency modulation (LFM) signals from compressed sampling data. First, the RD system parameters are modified in accordance with the characteristics of the LFM signal to produce effective compressed sampling data. Next, a DFRFT dictionary is built using the fractional Fourier transform theory, and sparse representation coefficients are obtained by reconstructing the compressed sampling data using the recovery algorithm and DFRFT dictionary. The signal exhibits characteristics that make it pulse under the best fractional transform order, so the problem of signal parameter estimation can be reduced to searching for the location of the maximum value of sparse representation coefficients. The location is determined by a parameter optimization algorithm, and from there, the initial frequency and Chirp rate of the LFM signal can be estimated. Lastly, simulation and real data tests are performed to confirm that the suggested method can directly be utilized to estimate the parameter of LFM signals using compressed sampling data in addition to having high sparse representation ability for LFM signals.
Professional identity formation among undergraduate pre-medical students: a scoping review protocol
Authors: Endalcachew Meklit , Deberg Jennifer , Swee Melissa , Suneja Manish , Kumar Bharat
Published: September 2023

Background

Professional Identity formation is the process by which learners internalize a profession’s values, behaviors, and perceptions. With respect to physicians, this occurs at multiple levels of medical education, including the undergraduate, graduate, and continuing medical education stages. Professional identity formation likely starts even earlier, during the undergraduate pre-medical years but, to date, no known scoping or systematic review has been conducted on this topic. The objective of this scoping review is to systematically map the literature on professional identity formation among undergraduate pre-medical students.

Methods

This review protocol has been designed following the Arksey and O’Malley framework. We will search MEDLINE, CINAHL, Embase, and Scopus, as well as relevant grey literature, conference proceedings, and citations of selected articles. Inclusion criteria are articles (1) written in the English language, (2) involving undergraduate pre-medical students in the USA and Canada, and (3) containing original data about professional identity formation. Two independent reviewers will evaluate the titles, abstracts, and full articles for eligibility. A third reviewer will help resolve any disputes. Once the full text of articles are obtained, data will be abstracted using a standardized form. A narrative summary of findings will then be conducted, as well as a consultation exercise with university pre-medical students, pre-med advisors, and first-year medical students.

Discussion

By conducting this scoping review, we expect to gain a better understanding of how the experiences of undergraduate pre-medical students impact their professional identity formation. These findings will help to identify gaps in the literature, to better characterize professional identity formation in the specific context of the undergraduate pre-medical track, and to outline potential approaches to facilitate professional identity formation among undergraduate pre-medical students.

Systematic review registration

The protocol is registered with the Open Science Framework (htps://osf.io/nfzxc).
EBUS-GS with the GeneXpert MTB/RIF assay for diagnosis of Mycobacterium tuberculosis infection of isolated pulmonary nodules
Authors: Cao Jie , Gu Ye , Wu Xiao-cui , Cheng Li-ping , Wang Lei , Qu Qing-rong , Sha Wei , Sun Qin
Published: September 2023

Objective

Investigate the use of endobronchial ultrasonography with a guide sheath (EBUS-GS) combined with Gene Xpert MTB/RIF (Xpert) for diagnosis of Mycobacterium tuberculosis (MTB) infection in isolated pulmonary nodules.

Methods

Patients who had isolated pulmonary nodules and unknown diagnoses at our institution from October 2020 to December 2021 were prospectively examined using EBUS-GS and Xpert. The diagnostic values of using EBUS-GS or bronchoalveolar lavage fluid (BALF) with acid-fast staining, MGIT 960 culture, pathological examination, and Xpert for isolated pulmonary nodules caused by MTB infection were compared using receiver operating characteristic (ROC) analysis.

Results

There were 135 patients, 64 with isolated pulmonary tuberculomas and 71 with non-tuberculous lesions. The sensitivity of EBUS-GS with Xpert was significantly higher than BALF with Xpert (57.81% vs. 34.78%, P = 0.017). Use of EBUS-GS with Xpert and MGIT 960 culture further increased the sensitivity to 62.50% (95%CI 50.64–74.36) and increased the specificity to 100%. The AUC values of BALF with MGIT 960 culture was 0.663(95%CI 0.543–0.783) and BALF with Xpert was 0.674 (95%CI 0.556–0.792). The AUC values of EBUS-GS with MGIT 960 culture was 0.680 (95%CI 0.554–0.743), with pathological examination was 0.713 (95%CI 0.573–0.760), and with Xpert was 0.789 (95%CI 0.655–0.829).

Conclusion

Use of EBUS-GS with Xpert had high sensitivity and specificity in the diagnosis of isolated pulmonary tuberculoma. This method has significant potential for use in clinical practice.
Reconsidering routine admission for children under age 3 undergoing partial tonsillectomy: A prospective study
Authors: Biadsee Ameen , Nathanson Craig , Dagan Or , Kassem Firas , Stahl Avishai , Mishali Tova , Ebner Yaniv , Rotenberg Brian
Published: September 2023

Background

Partial Tonsillectomy (PT) is an alternative method to treat sleep disordered breathing (SDB) and/or obstructive sleep apnea (OSA). The current guidelines do not differentiate it from traditional tonsillectomy. Thus, children younger than 3 years old undergoing PT are admitted for surveillance similar to traditional tonsillectomy due to possible postoperative complications. The aim of this study is to assess the risks of PT in children 3 years old and younger, compared to older children.

Methods

Children underwent inpatient partial tonsillectomy and/or adenoidectomy, due to SDB/OSA, from 2018 to 2020. A special protocol was designed, including follow-up at 2-, 4-, 6-, 8- and 24-h after surgery. Variables analyzed included visual analogue pain score, oral intake, oxygen saturation, pulse rate, postoperative hemorrhage, urine output, temperature, analgesics and fluid administration. Furthermore, major interventions were recorded. Comparison of all variables between children younger than 3 years old with older children was performed.

Results

Ninety-two children were included; mean age of the whole cohort was 44.5 ± 21.9 months. Thirty-five (38%) children were 3-years old or younger and n = 57 (62%) were older than 3 years old, with no significant statistical difference in sex ( p = 0.22). Mean age in the younger group was 25.7 ± 6.9 months, and 56.1 ± 20.1 months in the older group. In total we had 7 children with post-operative complications; 4 with fever, 3 with low intake. There were no major interventions recorded in either group. The complications were more common in the older group (n = 5) than the younger group (n = 2) without a statistical significance ( p = 0.59). There were no differences in VAS, use of painkillers, oral intake, urine output, oxygen saturation and tachycardia among the two groups.

Conclusion

This study supports that children undergoing ambulatory PT may be at low risk of complications, regardless of age.

Graphical Abstract
Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment
Authors: Jiang Hao , Tian Hailong , Wang Zhihan , Li Bowen , Chen Rui , Luo Kangjia , Lu Shuaijun , Nice Edouard C. , Zhang Wei , Huang Canhua , Zhou Yuping , Zheng Shaojiang , Gao Feng
Published: September 2023

Background

Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC.

Methods

Inspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis.

Results

This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models.

Conclusions

Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.

Graphical Abstract
Insights into sublethal effects of Metarhizium anisopliae on the biotic potentials of Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) on maize
Authors: Ullah Muhammad Irfan , Qadeer Muqadas , Arshad Muhammad , Khalid Samina , Saleem Usman , Riaz Muhammad Asam , Mumtaz Amina , Rizwan Muhammad , Sayed Samy M. , Alhelaify Seham Sater , Alharthy Ohoud Muslat , Mushtaq Muntazir
Published: September 2023

Background

Entomopathogenic fungi are an important biological agent in integrated pest management, playing a critical role in controlling insect populations. In the present study, the sublethal effects of the entomopathogenic fungus, Metarhizium anisopliae (Ascomycota: Hypocreales), were investigated on the biotic potential of Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), which is a major pest of economically important crops.

Results

Obtained results revealed that exposure to LC50 concentration of M. anisopliae resulted in a significantly longer larval developmental time (3.25–6.45 days) than the control group (2.42–5.49 days). Similarly, pupal duration was longer in the LC50 treatment (8.24 days) than in the control (6.91 days). Adult longevity was also significantly reduced in the LC50 (9.64 days) and LC30 (10.49 days) treatments compared to the control group (11.7 days). The number of eggs laid by female S. frugiperda exposed to LC50 value of M. anisopliae during the immature stages was significantly lower (464.79 eggs) than that in the control groups (696.93 eggs). Furthermore, all population and age-stage-specific parameters were significantly affected by the sublethal exposure to M. anisopliae at LC30 and LC50 values.

Conclusion

These results suggest that sublethal exposure to M. anisopliae negatively impacts the life table parameters of S. frugiperda. However, the use of M. anisopliae at sublethal levels may have potential benefits for integrated pest management strategies seeking to reduce the use of chemicals.
Investigating the importance of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as potential diagnostic biomarker in Iranian population
Authors: Pezeshki Milad , Hosseini Sayed Mostafa , Ansari Jamshid , Ahmadi Azam
Published: September 2023

Background

In Iran, lung cancer is the third most common type of cancer and its prevalence is increasing rapidly. Identification informative genetic polymorphisms in cancer causing genes including epidermal growth factor receptor (EGFR) as key gene in control of cellular proliferation via intrinsic tyrosine/kinase activity, exonuclease 1 (EXO1) as one of the upregulated gene in different human malignancies and leptin (LEP) participate in carcinogenesis in lung cancer appears to be used as potential genetic markers for predicting lung cancer risk. There is no study about investigate association of the EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer in Iranian population. The aim of this study was investigating the association of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as a potentially diagnostic biomarker in Iranian population.

Methods

In this case–control study, A total of 100 patients with lung cancer and 100 age and gender-matched healthy controls were recruited into this study and the association between EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with the risk of lung cancer was investigated by using PCR–RFLP technique and bioinformatics approach.

Results

The rs712829 of EGFR gene show that a significant statistical difference between G allele and risk of lung cancer (P = 0.001, OR = 2.976, CI = 95%, 1.557–5.691), in contrast, the T allele and TT genotype show a protective role against the risk of lung cancer. Result of in silico analysis indicated that the rs712829 alter splicing and promoter regulation of EGFR gene and associated with the risk of lung cancer. PCR–RFLP result for rs1047840 of Exo1 gene showed that the AA genotype and A allele of this polymorphism associated with risk of lung cancer, whereas the GG genotype show a protective effect against the risk of lung cancer (P = 0.004, OR = 5.391, CI = 95%, 1.690–17.200). On the other hand, in silico analysis showed that the existence of rs1047840 in Exo1 gene influence lung cancer susceptibility. For rs7799039 of LEP gene, PCR–RFLP analysis showed that, there is no significant association between this polymorphism and the risk of lung cancer.

Conclusion

The rs712829 of EGFR gene and rs1047840 of Exo1 are associated with risk of lung cancer among Iranian population and can be used as a potentially candidate biomarker for early detection and primary prevention.