bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of different irrigant activation techniques for cleaning root canal anastomosis
Authors: Montaser O. K. , Fayyad D. M. , Abdelsalam N.
Published: March 2023

Objective

This study compared in vitro the anastomosis cleaning efficacy of different irrigant activation techniques at different levels; control group non-activation (NA), passive ultrasonic irrigation (PUI) using Irrisafe, and EDDY sonic activation.

Methods

Sixty anastomosis-containing mesial roots of mandibular molars were mounted in resin, sectioned at 2, 4, and 6 mm from the apex. Then reassembled and instrumented in a copper cube. For the irrigation technique roots were randomly divided into 3 groups (n = 20): group 1: NA, group 2: Irrisafe, group 3: EDDY. Stereomicroscopic images of anastomoses were taken after instrumentation and after irrigant activation. ImageJ program was used to calculate the percentage of anastomosis cleanliness. The percentage of cleanliness was calculated before and after final irrigation within each group and were then compared using paired t-tests. Intergroup and intragroup analyses were performed to compare between different activation techniques at the same root canal level (2, 4 and 6 mm) (intergroup) and to evaluate if each technique had different cleanliness efficacy according to the root canal level (intragroup) using one-way analysis of variance and post hoc tests (p < 0.05).

Results

All three irrigation techniques significantly improved anastomosis cleanliness (p < 0.001). Both activation techniques were significantly better than the control group at all levels. Intergroup comparison revealed that EDDY significantly achieved the best overall anastomosis cleanliness. The difference between EDDY and Irrisafe was significant in favor to EDDY at 2 mm and insignificant at 4 and 6 mm. The intragroup comparison showed that improvement in anastomosis cleanliness (i2-i1) in the needle irrigation without activation group (NA) was significantly higher in the apical 2 mm level compared to the 4 & 6 levels. While the difference in anastomosis cleanliness improvement (i2-i1) between levels in both Irrisafe and EDDY groups was insignificant.

Conclusions

Irrigant activation improves anastomosis cleanliness. EDDY was the most efficient in cleaning anastomoses located in the critical apical part of the root canal.

Clinical relevance

Cleaning and disinfection of the root canal system followed by apical and coronal sealing is the key for healing or prevention of apical periodontitis. Remnants of debris and microorganisms retained within the anastomoses (isthmuses), or other root canal irregularities may lead to persistent apical periodontitis. Proper irrigation and activation are essential for cleaning root canal anastomoses.
Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer
Authors: Neo Soek-Ying , Siew Yin-Yin , Yew Hui-Chuing , He Yaqian , Poh Keng-Ling , Tsai Yi-Chen , Ng Shu-Ling , Tan Wei-Xun , Chong Teck-Ian , Lim Claire Sophie En-Shen , Ho Samuel Shan-Wei , Singh Deepika , Ali Azhar , Linn Yeh-Ching , Tan Chay-Hoon , Seow See-Voon , Koh Hwee-Ling
Published: March 2023

Background

The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable.

Objective

This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells.

Methods

Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1β production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages.

Results

Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1β production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels.

Conclusions

We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.
A phylogenomic analysis of Limosilactobacillus reuteri reveals ancient and stable evolutionary relationships with rodents and birds and zoonotic transmission to humans
Authors: Li Fuyong , Li Xudong , Cheng Christopher C. , Bujdoš Dalimil , Tollenaar Stephanie , Simpson David J. , Tasseva Guergana , Perez-Muñoz Maria Elisa , Frese Steven , Gänzle Michael G. , Walter Jens , Zheng Jinshui
Published: March 2023

Background

Gut microbes play crucial roles in the development and health of their animal hosts. However, the evolutionary relationships of gut microbes with vertebrate hosts, and the consequences that arise for the ecology and lifestyle of the microbes are still insufficiently understood. Specifically, the mechanisms by which strain-level diversity evolved, the degree by which lineages remain stably associated with hosts, and how their evolutionary history influences their ecological performance remain a critical gap in our understanding of vertebrate-microbe symbiosis.

Results

This study presents the characterization of an extended collection of strains of Limosilactobacillus reuteri and closely related species from a wide variety of hosts by phylogenomic and comparative genomic analyses combined with colonization experiments in mice to gain insight into the long-term evolutionary relationship of a bacterial symbiont with vertebrates. The phylogenetic analysis of L. reuteri revealed early-branching lineages that primarily consist of isolates from rodents (four lineages) and birds (one lineage), while lineages dominated by strains from herbivores, humans, pigs, and primates arose more recently and were less host specific. Strains from rodent lineages, despite their phylogenetic divergence, showed tight clustering in gene-content-based analyses. These L. reuteri strains but not those ones from non-rodent lineages efficiently colonize the forestomach epithelium of germ-free mice. The findings support a long-term evolutionary relationships of L. reuteri lineages with rodents and a stable host switch to birds. Associations of L. reuteri with other host species are likely more dynamic and transient. Interestingly, human isolates of L. reuteri cluster phylogenetically closely with strains from domesticated animals, such as chickens and herbivores, suggesting zoonotic transmissions.

Conclusions

Overall, this study demonstrates that the evolutionary relationship of a vertebrate gut symbiont can be stable in particular hosts over time scales that allow major adaptations and specialization, but also emphasizes the diversity of symbiont lifestyles even within a single bacterial species. For L. reuteri, symbiont lifestyles ranged from autochthonous, likely based on vertical transmission and stably aligned to rodents and birds over evolutionary time, to allochthonous possibly reliant on zoonotic transmission in humans. Such information contributes to our ability to use these microbes in microbial-based therapeutics.
Proteomics and metabolomics profiling reveal panels of circulating diagnostic biomarkers and molecular subtypes in stable COPD
Authors: Zhang Zili , Wang Jian , Li Yuanyuan , Liu Fei , Chen Lingdan , He Shunping , Lin Fanjie , Wei Xinguang , Fang Yaowei , Li Qiongqiong , Zhou Juntuo , Lu Wenju
Published: March 2023

Background

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease with high morbidity and mortality, especially in advanced patients. We aimed to develop multi-omics panels of biomarkers for the diagnosis and explore its molecular subtypes.

Methods

A total of 40 stable patients with advanced COPD and 40 controls were enrolled in the study. Proteomics and metabolomics techniques were applied to identify potential biomarkers. An additional 29 COPD and 31 controls were enrolled for validation of the obtained proteomic signatures. Information on demographic, clinical manifestation, and blood test were collected. The ROC analyses were carried out to evaluate the diagnostic performance, and experimentally validated the final biomarkers on mild-to-moderate COPD. Next, molecular subtyping was performed using proteomics data.

Results

Theophylline, palmitoylethanolamide, hypoxanthine, and cadherin 5 (CDH5) could effectively diagnose advanced COPD with high accuracy (auROC = 0.98, sensitivity of 0.94, and specificity of 0.95). The performance of the diagnostic panel was superior to that of other single/combined results and blood tests. Proteome based stratification of COPD revealed three subtypes (I–III) related to different clinical outcomes and molecular feature: simplex COPD, COPD co-existing with bronchiectasis, and COPD largely co-existing with metabolic syndrome, respectively. Two discriminant models were established using the auROC of 0.96 (Principal Component Analysis, PCA) and 0.95 (the combination of RRM1 + SUPV3L1 + KRT78) in differentiating COPD and COPD with co-morbidities. Theophylline and CDH5 were exclusively elevated in advanced COPD but not in its mild form.

Conclusions

This integrative multi-omics analysis provides a more comprehensive understanding of the molecular landscape of advanced COPD, which may suggest molecular targets for specialized therapy.
Laboratory evaluation of the efficacy of deltamethrin-laced attractive toxic sugar bait formulation on Anopheles stephensi
Authors: Kumar Sarita , Sharma Aarti , Samal Roopa Rani , Kumar Manoj , Verma Vaishali , Sagar Ravinder Kumar , Singh Shri Pati , Raghavendra Kamaraju
Published: March 2023

Background

Attractive toxic sugar bait (ATSB) is a promising “attract and kill”-based approach for mosquito control. It is a combination of flower nectar/fruit juice to attract the mosquitoes, sugar solution to stimulate feeding, and a toxin to kill them. Selecting an effective attractant and optimizing concentration of toxicant is significant in the formulation of ATSB.

Methods

Current study formulated an ATSB using fruit juice, sugar and deltamethrin, a synthetic pyrethroid. It was evaluated against two laboratory strains of Anopheles stephensi. Initial studies evaluated comparative attractiveness of nine different fruit juices to An. stephensi adults. Nine ASBs were prepared by adding fermented juices of plum, guava, sweet lemon, orange, mango, pineapple, muskmelon, papaya, and watermelon with 10% sucrose solution (w/v) in 1:1 ratio. Cage bioassays were conducted to assess relative attraction potential of ASBs based on the number of mosquito landings on each and the most effective ASB was identified. Ten ATSBs were prepared by adding the identified ASB with different deltamethrin concentrations (0.015625–8.0 mg/10 mL) in 1:9 ratio. Each ATSB was assessed for the toxic potential against both the strains of An. stephensi. The data was statistically analysed using PASW (SPSS) software 19.0 program.

Results

The cage bioassays with nine ASBs revealed higher efficacy (p < 0.05) of Guava juice-ASB > Plum juice-ASB > Mango juice-ASB in comparison to rest of the six ASB’s. The bioassay with these three ASB’s ascertained the highest attractancy potential of guava juice-ASB against both the strains of An. stephensi. The ATSB formulations resulted in 5.1–97.9% mortality in Sonepat (NIMR strain) with calculated LC30, LC50, and LC90 values of 0.17 mg deltamethrin/10 mL, 0.61 mg deltamethrin/10 mL, and 13.84 mg deltamethrin/10 mL ATSB, respectively. Whereas, 6.12–86.12% mortality was recorded in the GVD-Delhi (AND strain) with calculated LC30, LC50, and LC90 values of 0.25 mg deltamethrin/10 mL, 0.73 mg deltamethrin/10 mL and 10.22 mg deltamethrin/10 mL ATSB, respectively.

Conclusion

The ATSB formulated with guava juice-ASB and deltamethrin (0.0015625–0.8%) in 9:1 ratio showed promising results against two laboratory strains of An. stephensi. Field assessment of these formulations is being conducted to estimate their feasibility for use in mosquito control.
Free-living core body temperature monitoring using a wrist-worn sensor after COVID-19 booster vaccination: a pilot study
Authors: Etienne Samuel , Oliveras Ruben , Schiboni Giovanni , Durrer Lukas , Rochat Fabien , Eib Philipp , Zahner Michele , Osthoff Michael , Bassetti Stefano , Eckstein Jens
Published: March 2023

Core body temperature (CBT) is a key vital sign and fever is an important indicator of disease. In the past decade, there has been growing interest for vital sign monitoring technology that may be embedded in wearable devices, and the COVID-19 pandemic has highlighted the need for remote patient monitoring systems. While wrist-worn sensors allow continuous assessment of heart rate and oxygen saturation, reliable measurement of CBT at the wrist remains challenging. In this study, CBT was measured continuously in a free-living setting using a novel technology worn at the wrist and compared to reference core body temperature measurements, i.e., CBT values acquired with an ingestible temperature-sensing pill. Fifty individuals who received the COVID-19 booster vaccination were included. The datasets of 33 individuals were used to develop the CBT prediction algorithm, and the algorithm was then validated on the datasets of 17 participants. Mean observation time was 26.4 h and CBT > 38.0 °C occurred in 66% of the participants. CBT predicted by the wrist-worn sensor showed good correlation to the reference CBT (r = 0.72). Bland–Altman statistics showed an average bias of 0.11 °C of CBT predicted by the wrist-worn device compared to reference CBT, and limits of agreement were − 0.67 to + 0.93 °C, which is comparable to the bias and limits of agreement of commonly used tympanic membrane thermometers. The small size of the components needed for this technology would allow its integration into a variety of wearable monitoring systems assessing other vital signs and at the same time allowing maximal freedom of movement to the user.
Content and quality of physical activity ontologies: a systematic review
Authors: Braun Maya , Carlier Stéphanie , De Backere Femke , De Paepe Annick , Van De Velde Marie , Van Dyck Delfien , Marques Marta M. , De Turck Filip , Crombez Geert
Published: March 2023

Introduction

Ontologies are a formal way to represent knowledge in a particular field and have the potential to transform the field of health promotion and digital interventions. However, few researchers in physical activity (PA) are familiar with ontologies, and the field can be difficult to navigate.

This systematic review aims to (1) identify ontologies in the field of PA, (2) assess their content and (3) assess their quality.

Methods

Databases were searched for ontologies on PA. Ontologies were included if they described PA or sedentary behavior, and were available in English language. We coded whether ontologies covered the user profile, activity, or context domain. For the assessment of quality, we used 12 criteria informed by the Open Biological and Biomedical Ontology (OBO) Foundry principles of good ontology practice.

Results

Twenty-eight ontologies met the inclusion criteria. All ontologies covered PA, and 19 included information on the user profile. Context was covered by 17 ontologies (physical context, n = 12; temporal context, n = 14; social context: n = 5). Ontologies met an average of 4.3 out of 12 quality criteria. No ontology met all quality criteria.

Discussion

This review did not identify a single comprehensive ontology of PA that allowed reuse. Nonetheless, several ontologies may serve as a good starting point for the promotion of PA. We provide several recommendations about the identification, evaluation, and adaptation of ontologies for their further development and use.
Lipid metabolism, BMI and the risk of nonalcoholic fatty liver disease in the general population: evidence from a mediation analysis
Authors: Lu Song , Xie Qiyang , Kuang Maobin , Hu Chong , Li Xinghui , Yang Huijian , Sheng Guotai , Xie Guobo , Zou Yang
Published: March 2023

Background

Body mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD.

Method

Using data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation.

Result

After fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (AllP-value < 0.001). Mediation analysis showed that both traditional and non-traditional lipid parameters mediated the association between BMI and NAFLD (AllP-value of proportion mediate < 0.001), among which non-traditional lipid parameters such as RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio accounted for a relatively large proportion, 11.4%, 10.8%, 10.2%, and 10.2%, respectively. Further stratified analysis according to sex, age, and BMI showed that this mediation effect only existed in normal-weight (18.5 kg/m2 ≤ BMI < 25 kg/m2) people and young and middle-aged (30–59 years old) people; moreover, the mediation effects of all lipid parameters except TC accounted for a higher proportion in women than in men.

Conclusion

The new findings of this study showed that all lipid parameters were involved in and mediated the risk of BMI-related NAFLD, and the contribution of non-traditional lipid parameters to the mediation effect of this association was higher than that of traditional lipid parameters, especially RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio. Based on these results, we suggest that we should focus on monitoring non-traditional lipid parameters, especially RC and RC/HDL-C ratio, when BMI intervention is needed in the process of preventing or treating NAFLD.
Multisystem ALK-positive histiocytosis: a multi-case study and literature review
Authors: Liu Wei , Liu Hong-jie , Wang Wei-ya , Tang Yuan , Zhao Sha , Zhang Wen-yan , Yan Jia-qi , Liu Wei-ping
Published: March 2023

Background

Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated.

Results

Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients’, whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case.

Conclusions

We observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease.
Utilization of cervical cancer screening services and its associated factors in Iran: a case–control study
Authors: Dadipoor Sara , Alavi Azin , Kader Zainab , Eshaghi Sani Kakhaki Hadi , Mohseni Shokrollah , Shahabi Nahid
Published: March 2023

Background

Considering the high incidence rate of cervical cancer (CC) in Iran, screening is an effective way of reducing the impact of the disease due to early detection. Thus, the recognition of the factors affecting the use of cervical cancer screening (CCS) services is essential.The present study aimed to determine the associated factors of CCS in women living in the suburbs of Bandar Abbas in the south of Iran.

Methods

The present case–control study was conducted between January and March 2022 in the suburban areas of Bandar abbas. Two hundred participants were assigned to the case group and 400 participants were assigned to the control group. A self-constructed questionnaire was used to collect the data. This questionnaire contained demographic information, reproductive information, knowledge of CC, knowledge of CCS and access to the screening. Univariate and multivariate regression analyses were run to analyze the data. The data were analyzed in STATA 14.2 at a significance level of p < 0.05.

Results

The mean and standard deviation of participants’ age in the case group was 30.33 ± 4.892, and in the control group was 31.35 ± 6.149. The mean and standard deviation of knowledge in the case group was 10.21 ± 1.815 and in the control group was 7.24 ± 2.447. The mean and standard deviation of access was 43.72 ± 6.339 in the case and 37.17 ± 4.828 in the control group. The results of multivariate regression analysis showed the following factors increased the odds of CCS: knowledge (OR medium = 18.697, OR high = 13.413), access (OR medium = 4.028, OR high = 8.126), being married (OR = 3.193), being educated (OR diploma = 2.587, OR university degree = 1.432), middle and high SES (OR Middle = 6.078, OR Upper = 6.608), and not smoking (OR = 1.144). Also, women's reproductive status, including history of sexually transmitted diseases (OR = 2.612), use of oral contraceptives (OR = 1.579), sexual hygiene (OR = 8.718).

Conclusions

In the light of the present findings, it can be concluded that besides increasing suburban women’s knowledge, their access to screening facilities should be improved. The present findings showed the need to remove the barriers to CCS in women of low SES to increase the rate of CCS. The present findings contribute to a better understanding of factors involved in CCS.
Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension
Authors: Kim Kyuho , Moon Ji Hye , Ahn Chang Ho , Lim Soo
Published: March 2023

Background

Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension.

Methods

This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24.

Results

Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r =  − 0.252 and r =  − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria.

Conclusions

These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease.

Trial registration: ClinicalTrials.gov NCT05189015.
Is anterior knee pain following anterior cruciate ligament reconstruction a consideration for graft choice, and the influence of COVID: a qualitative analysis in recreational athletes
Authors: Sanjevic Anastasia , Tourvas Evangelos , Cairns Mark A. , Alnuaimi Fahad , Theodoropoulos John , Dwyer Tim , Chahal Jas , Ogilvie-Harris Darrell
Published: March 2023

Background

We set out to investigate whether anterior knee pain following anterior cruciate ligament reconstruction has a significant effect on patients, and whether it should influence graft choice.

Methods

This was a qualitative analysis of a set of recreational athletes treated at a university hospital at about 1 year following anterior cruciate ligament reconstruction surgery. Participants were interviewed by an orthopaedic fellow and resident using structured, open-ended questions. Inductive theme analysis was used to code the data.

Results

There were 4 major themes: (1) Our hypothesis was that patients would be given adequate information to make an appropriate graft choice. This hypothesis was rejected. Discussion took place, but with little details or rationale for the graft choice. The predominant theme was that the surgeon made the decision, and there was a lack of reliable information for the patient to make a choice. (2) The overall theme was that most patients had no anterior knee pain, and it did not interfere with activities of daily living. (3) One theme was that patients were able to resume all sports without restriction, but in some, the anterior knee pain interfered with the more demanding activities such as impact, cutting, and pivoting. A separate theme was that fear was a major impediment to return to sports and was not related to the anterior knee pain. (4) The overriding theme was that the generalized closures associated with the COVID-19 pandemic slowed the rehabilitation process. Although virtual care was available in general, it was not particularly satisfactory. Patients indicated that they had not been able to return to the gym or to their sporting activities as a result.

Conclusions

Amongst non-competitive athletes, anterior knee pain post-anterior cruciate ligament reconstruction surgery does not significantly affect activities of daily living. Although there is a minor effect on sporting activities, the inability to return to sports is related to factors such as the COVID-19 pandemic, fear, or insufficient rehabilitation, rather than anterior knee pain. Overall, anterior knee pain is not a significant factor that plays a role in determining graft choice.
A systematic evaluation of normalization methods and probe replicability using infinium EPIC methylation data
Authors: Welsh H. , Batalha C. M. P. F. , Li W. , Mpye K. L. , Souza-Pinto N. C. , Naslavsky M. S. , Parra E. J.
Published: March 2023

Background

The Infinium EPIC array measures the methylation status of > 850,000 CpG sites. The EPIC BeadChip uses a two-array design: Infinium Type I and Type II probes. These probe types exhibit different technical characteristics which may confound analyses. Numerous normalization and pre-processing methods have been developed to reduce probe type bias as well as other issues such as background and dye bias.

Methods

This study evaluates the performance of various normalization methods using 16 replicated samples and three metrics: absolute beta-value difference, overlap of non-replicated CpGs between replicate pairs, and effect on beta-value distributions. Additionally, we carried out Pearson’s correlation and intraclass correlation coefficient (ICC) analyses using both raw and SeSAMe 2 normalized data.

Results

The method we define as SeSAMe 2, which consists of the application of the regular SeSAMe pipeline with an additional round of QC, pOOBAH masking, was found to be the best performing normalization method, while quantile-based methods were found to be the worst performing methods. Whole-array Pearson’s correlations were found to be high. However, in agreement with previous studies, a substantial proportion of the probes on the EPIC array showed poor reproducibility (ICC < 0.50). The majority of poor performing probes have beta values close to either 0 or 1, and relatively low standard deviations. These results suggest that probe reliability is largely the result of limited biological variation rather than technical measurement variation. Importantly, normalizing the data with SeSAMe 2 dramatically improved ICC estimates, with the proportion of probes with ICC values > 0.50 increasing from 45.18% (raw data) to 61.35% (SeSAMe 2).
Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report
Authors: Kongmalai Tanawan , Chuanchaiyakul Nalinee , Srinoulprasert Yuttana , Thongtang Nuntakorn
Published: March 2023

Background

Elevated plasma cholesterol and/or plasma triglyceride levels in nephrotic syndrome patients are the result of impaired lipoprotein clearance and a compensatory increase in hepatic lipoprotein synthesis. Plasma proprotein convertase subtilisin/kexin type 9 levels directly correlate to the amount of proteinuria in nephrotic syndrome patients. Proprotein convertase subtilisin/kexin type 9 monoclonal antibody has been used to treat dyslipidemia in some refractory nephrotic syndrome cases. As a therapeutic protein, proprotein convertase subtilisin/kexin type 9 monoclonal antibody simply deteriorates if stored in inappropriate temperatures or conditions.

Case presentation

In this article, we present the case of a 16-year-old Thai female with severe combined dyslipidemia secondary to refractory nephrotic syndrome. She received proprotein convertase subtilisin/kexin type 9 monoclonal antibody (alirocumab) treatment. However, the drugs were mistakenly frozen in a freezer for up to 17 hours before being stored at 4 °C. After using two frozen devices, serum total cholesterol, free proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) significantly decreased. Nonetheless, the patient developed a skin rash 2 weeks after the second injection and the lesion spontaneously resolved without any treatment approximately 1 month later.

Conclusions

The effectiveness of proprotein convertase subtilisin/kexin type 9 monoclonal antibody seems to be stable after being stored under freeze–thaw conditions. However, improperly stored drugs should be discarded to avoid any potential undesirable side effects.
Single-cell analyses reveal distinct expression patterns and roles of long non-coding RNAs during hESC differentiation into pancreatic progenitors
Authors: Luo Hai-Tao , He Qian , Yang Wei , He Fei , Dong Jun , Hu Chao-Feng , Yang Xiao-Fei , Li Ning , Li Fu-Rong
Published: March 2023

Background

Deep understanding the differentiation process of human embryonic stem cells (hESCs) is essential for developing cell-based therapeutic strategy. Substantial efforts have been made to investigate protein-coding genes, yet it remains lacking comprehensive characterization of long non-coding RNAs (lncRNAs) during this process.

Methods

hESCs were passaged every 5–6 days and had maintained stable karyotype even until the 50th generation. Pancreatic progenitor specification of in vitro differentiation from hESCs was performed and modified. The nuclei were stained with 4,6-Diamidino-2-phenylindole (DAPI). Droplet-based platform (10X Genomics) was applied to generate the single-cell RNA sequencing (scRNA-seq) data. The quality of the filtered read pairs was evaluated by using FastQC. Batch effects were removed using the size factor method. Dimension reduction and unsupervised clustering analyses were performed using Seurat R package. The Monocle 2 and MetaCell algorithms were used to order single cells on a pseudotime course and partition the scRNA-seq data into metacells, respectively. Co-expression network was constructed using WGCNA. Module- and hub-based methods were adopted to predict the functions of lncRNAs.

Results

A total of 77,382 cells during the differentiation process of hESCs toward pancreatic progenitors were sequenced. According to the single-cell map, the cells from different time points were authenticated to constitute a relatively homogeneous population, in which a total of 7382 lncRNAs could be detected. Through further analyzing the time course data, conserved and specific expression features of lncRNAs during hESC differentiation were revealed. Based upon pseudotime analysis, 52 pseudotime-associated lncRNAs that grouped into three distinct expression patterns were identified. We also implemented MetaCell algorithm and network-based methods to explore the functional mechanisms of these lncRNAs. Totally, 464 lncRNAs, including 49 pseudotime-associated lncRNAs were functionally annotated by either module-based or hub-based methods. Most importantly, we demonstrated that the lncRNAHOTAIRM1, which co-localized and co-expressed with severalHOXgenes, may play crucial role in the generation of pancreatic progenitors through regulation of exocytosis and retinoic acid receptor signaling pathway.

Conclusions

Our single-cell analyses provide valuable data resources for biological researchers and novel insights into hESC differentiation processes, which will guide future endeavors to further elucidate the roles of lncRNAs.
Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational modelling
Authors: Somin Sarawoot , Kulasiri Don , Samarasinghe Sandhya
Published: March 2023

Treatment for Alzheimer’s disease (AD) can be more effective in the early stages. Although we do not completely understand the aetiology of the early stages of AD, potential pathological factors (amyloid beta [Aβ] and tau) and other co-factors have been identified as causes of AD, which may indicate some of the mechanism at work in the early stages of AD. Today, one of the primary techniques used to help delay or prevent AD in the early stages involves alleviating the unwanted effects of oxidative stress on Aβ clearance. 4-Hydroxynonenal (HNE), a product of lipid peroxidation caused by oxidative stress, plays a key role in the adduction of the degrading proteases. This HNE employs a mechanism which decreases catalytic activity. This process ultimately impairs Aβ clearance. The degradation of HNE-modified proteins helps to alleviate the unwanted effects of oxidative stress. Having a clear understanding of the mechanisms associated with the degradation of the HNE-modified proteins is essential for the development of strategies and for alleviating the unwanted effects of oxidative stress. The strategies which could be employed to decrease the effects of oxidative stress include enhancing antioxidant activity, as well as the use of nanozymes and/or specific inhibitors. One area which shows promise in reducing oxidative stress is protein design. However, more research is needed to improve the effectiveness and accuracy of this technique. This paper discusses the interplay of potential pathological factors and AD. In particular, it focuses on the effect of oxidative stress on the expression of the Aβ-degrading proteases through adduction of the degrading proteases caused by HNE. The paper also elucidates other strategies that can be used to alleviate the unwanted effects of oxidative stress on Aβ clearance. To improve the effectiveness and accuracy of protein design, we explain the application of quantum mechanical/molecular mechanical approach.
Eating disorders during lockdown: the transcultural influence on eating and mood disturbances in Ibero-Brazilian population
Authors: Baenas Isabel , Neufeld Carmem Beatriz , Ramos Rita , Munguía Lucero , Pessa Rosane P. , Rodrigues Tânia , Jiménez-Murcia Susana , Gonçalves Sónia , Teodoro Marília C. , Pinto-Bastos Ana , Almeida Nazaré O. , Granero Roser , Etxandi Mikel , Soares Shauana R. S. , Fernández-Aranda Fernando , Machado Paulo P. P.
Published: March 2023

Background

COVID-19 pandemic has implied exceptional restrictive measures to contain its widespread, with adverse consequences on mental health, especially for those people with a background of mental illness, such as eating disorders (EDs). In this population, the influence of socio-cultural aspects on mental health has been still underexplored. Then, the main aim of this study was to assess changes in eating and general psychopathology in people with EDs during lockdown regarding the ED subtype, age, and provenance, and considering socio-cultural aspects (e.g., socioeconomical factors such as work and financial losses, social support, restrictive measures, or health accessibility, among others).

Methods

The clinical sample was composed of 264 female participants with EDs (74 anorexia nervosa (AN), 44 bulimia nervosa (BN), 81 binge eating disorder (BED), and 65 other specified feeding and eating disorder (OSFED)), with a mean age of 33.49 years old (SD = 12.54), from specialized ED units in Brazil, Portugal, and Spain. The participants were evaluated using the COVID-19 Isolation Eating Scale (CIES).

Results

A global impairment in mood symptoms and emotion regulation was reported in all the ED subtypes, groups of age, and countries. Spanish and Portuguese individuals seemed more resilient than Brazilian ones (p < .05), who reported a more adverse socio-cultural context (i.e., physical health, socio-familial, occupational, and economic status) (p < .001). A global trend to eating symptoms worsening during lockdown was observed, regardless of the ED subtype, group of age, and country, but without reaching statistical significance. However, the AN and BED groups described the highest worsening of the eating habits during lockdown. Moreover, individuals with BED significantly increased their weight and body mass index, similarly to BN, and in contrast to the AN and OSFED groups. Finally, we failed to find significant differences between groups of age although the younger group described a significant worsening of the eating symptoms during lockdown.

Conclusions

This study reports a psychopathological impairment in patients with EDs during lockdown, being socio-cultural aspects potential modulatory factors. Individualized approaches to detect special vulnerable groups and long-term follow-ups are still needed.
Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles
Authors: Zhang Zi-Sen , Liu Yi-Yan , He Shuang-Shuang , Bao Dai-Qin , Wang Hong-Chen , Zhang Jie , Peng Xiao-Yong , Zang Jia-Tao , Zhu Yu , Wu Yue , Li Qing-Hui , Li Tao , Liu Liang-Ming
Published: March 2023

Background

Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are protective against sepsis via regulating vascular reactivity and permeability.

Methods

We conducted a series of in vivo experiments using wild-type (WT), platelet-derived growth factor receptor beta (PDGFR-β)-Cre + mT/mG transgenic mice and Tie2-Cre + Cx43flox/flox mice to examine the relative contribution of pericytes in sepsis, either induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. In a separate set of experiments with Sprague–Dawley (SD) rats, pericytes were depleted using CP-673451, a selective PDGFR-β inhibitor, at a dosage of 40 mg/(kg·d) for 7 consecutive days. Cultured pericytes, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were used for mechanistic investigations. The effects of pericytes and pericyte-derived microvesicles (PCMVs) and candidate miRNAs on vascular reactivity and barrier function were also examined.

Results

CLP and LPS induced severe injury/loss of pericytes, vascular hyporeactivity and leakage (P < 0.05). Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization (P < 0.05). Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels (P < 0.05). Additionally, PCMVs transferred miR-145 and miR-132 to VSMCs and VECs, respectively, exerting a protective effect on vascular reactivity and barrier function after sepsis (P < 0.05). miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2 (Sphk2)/sphingosine-1-phosphate receptor (S1PR)1/phosphorylation of myosin light chain 20 pathway, whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.

Conclusions

Pericytes are protective against sepsis through regulating vascular reactivity and barrier function. Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
Acute malnutrition recovery rates improve with COVID-19 adapted nutrition treatment protocols in South Sudan: a mixed methods study
Authors: Lyles Emily , Banks Sandra , Ramaswamy Maya , Ismail Sule , Leidman Eva , Doocy Shannon
Published: March 2023

Background

Globally, emergency nutrition program adaptations were implemented as part of COVID-19 mitigation strategies, but the implications of the adoption of all protocol changes at scale in the context of deteriorating food security are not yet well characterized. With ongoing conflict, widespread floods, and declining food security, the secondary impacts of COVID-19 on child survival in South Sudan is of great concern. In light of this, the present study aimed to characterize the impact of COVID-19 on nutrition programming in South Sudan.

Methods

A mixed methods approach including a desk review and secondary analysis of facility-level program data was used to analyze trends in program indicators over time and compare two 15-month periods prior to the onset of COVID-19 (January 2019 – March 2020; “pre-COVID period”) and after the start of the pandemic (April 2020 – June 2021; “COVID” period) in South Sudan.

Results

The median number of reporting Community Management of Acute Malnutrition sites increased from 1167 pre-COVID to 1189 during COVID. Admission trends followed historic seasonal patterns in South Sudan; however, compared to pre-COVID, declines were seen during COVID in total admissions (− 8.2%) and median monthly admissions (− 21.8%) for severe acute malnutrition. For moderate acute malnutrition, total admissions increased slightly during COVID (1.1%) while median monthly admissions declined (− 6.7%). Median monthly recovery rates improved for severe (92.0% pre-COVID to 95.7% during COVID) and moderate acute malnutrition (91.5 to 94.3%) with improvements also seen in all states. At the national level, rates also decreased for default (− 2.4% for severe, − 1.7% for moderate acute malnutrition) and non-recovery (− 0.9% for severe, − 1.1% for moderate acute malnutrition), with mortality rates remaining constant at 0.05–0.15%.

Conclusions

Within the context of the ongoing COVID-19 pandemic in South Sudan, improved recovery, default, and non-responder rates were observed following adoption of changes to nutrition protocols. Policymakers in South Sudan and other resource-constrained settings should consider if simplified nutrition treatment protocols adopted during COVID-19 improved performance and should be maintained in lieu of reverting to standard treatment protocols.
A new neutron-gamma porosity measurement method for pulsed neutron logging tools
Authors: Fu Xinyue , Wu Wensheng , Wang Hu , Ge Yunlong
Published: March 2023

As an alternative method for the compensated neutron porosity measurement method, the neutron-gamma porosity measurement method is widely used in cased holes. However, the neutron-gamma porosity measurement method has some problems, such as the lack of detailed theoretical analysis and low sensitivity in high-porosity formations. The purpose of this paper is to clarify the theory of neutron-gamma porosity measurement, improve the measurement sensitivity, and eliminate the effects of environmental factors. Based on the neutron diffusion theory and the gamma transport theory, the distribution of capture gamma rays is described. A new neutron-gamma porosity measurement method is developed based on inelastic and capture gamma-ray distribution. The applicability of the new method in different environments is analyzed using the Monte Carlo method, and the effectiveness of this method is verified using the synthetic model. The results indicate that the capture gamma-ray ratio is only related to the source-detector distance, gamma-ray attenuation length, and neutron migration length. By combining density, different neutron cross sections, inelastic gamma-ray count ratio, and capture gamma-ray count ratio, the parameter secondary gamma-ray hydrogen index (SGH) related to hydrogen index can be extracted. The dynamic range of SGH is much higher than thermal neutron count ratio and the capture gamma-ray count ratio. The errors in porosity calculation by this method under different borehole and lithologic conditions are generally less than 2 pu. The calculation error of this method is close to that of the compensated neutron porosity measurement method. In addition, the applicability of the new method is analyzed without density data, and the results indicate that the calculation results are basically consistent with the results of calculation with density data. The new method has great potential for extensive applications in cased holes or open holes as an alternative for the compensated neutron porosity logging measurement method.