bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of electrophysiology in the correction of spastic torticollis by triple surgery—report of 96 cases
Authors: Wu Jun , Xu Hao , Wang Lu , Li Jun
Published: June 2023

Objective

To investigate the effect and value of electrophysiology in the ‘triple operation’ (selective excision of spastic muscles in the neck, selective resection of the posterior branch of the cervical nerve and accessory neurotomy) of spastic torticollis.

Methods

Preoperative electromyography (EMG) examination was performed on 96 patients with spastic torticollis treated in our hospital from January 2015 to December 2019. The results were used to assess the responsible muscles’ primary or secondary position and the function of antagonistic muscles and to formulate a personalised surgical plan. A Cascade PRO 16-channel electrophysiological diagnostic system (produced by Cadwell, USA) was used to record the evoked EMG. Target muscles were denervated under intraoperative electrophysiological monitoring and re-examined by EMG six months later to evaluate the efficacy.

Results

The satisfactory rate of target muscle denervation was 95%, and the overall good rate was 79.1%.

Conclusion

Electrophysiological examination and intraoperative application may have a positive value in the selection of the operative method, improving the rate of denervation and evaluating the prognosis of the ‘triple operation’.
The efficacy of medial meniscal posterior Root tear Repair with or without high tibial osteotomy: a systematic review
Authors: Wang Hangle , Man Qian , Gao Yitian , Xu Lingyi , Zhang Jingwei , Ma Yong , Meng Qingyang
Published: June 2023

Background

Medial meniscal posterior root tear (MMPRTs) is a common lesion of the knee joint, and repair surgery is a well-established treatment option. However, patients with obvious varus alignment are at an increased risk for MMPRT and can suffer from a greater degree of medial meniscus extrusion, which leads to the development of osteoarthritis following repair. The efficacy of high tibial osteotomy (HTO) as a means of correcting this malformation, and its potential benefits for MMPRT repair, remains unclear.

Purpose

To explore whether HTO influenced the outcome of MMPRT repair in clinical scores and radiological findings.

Study design

Systematic review.

Methods

According to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library databases for studies reporting the outcomes of MMPRT repair and extracted data about characteristics of patients, clinical functional scores and radiologic outcomes. One reviewer extracted the data and 2 reviewers assessed the risk of bias and performed a synthesis of the evidence. Articles were eligible if they reported the results of MMPRT repair with exact mechanical axis (registered in the International Prospective Register of Systematic Reviews, CRD42021292057).

Results

Fifteen studies with 625 cases of high methodological quality were identified. Eleven studies were assigned to the MMPRT repair group (M) with 478 cases performing MMPRT repair only, and others belonged to the MMPRT repair and HTO group (M and T) performing HTO and MMPRT repair. Most of the studies had significantly improved clinical outcome scores, especially in M groups. And the radiologic outcomes showed that the osteoarthritis deteriorated in both groups with similar degree in about 2-year follow-up.

Conclusion

HTO is a useful supplement in treating MMPRT patients with severe osteoarthritis and the clinical and radiological outcomes were similar with MMPRT repair alone. Which would be better for patients’ prognosis generally, performing MMPRT repair alone or a combination of HTO and MMPRT repair, was still controversial. We suggested taking K-L grade into account. Large-scale randomized control studies were called for in the future to help make better clinical decisions.

Level of evidence

III
Enhanced bone regeneration by low-intensity pulsed ultrasound and lipid microbubbles on PLGA/TCP 3D-printed scaffolds
Authors: Jin Lin , Shan Jiali , Hao Yanhong , Wang Yingchun , Liu Liping
Published: June 2023

Background

To investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds.

Methods

BMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation.

Results

BMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration, 2.0 MHz frequency, 0.3 W/cm2 sound intensity and 20% duty cycle. After 14 days, the type I collagen expression and alkaline phosphatase activity in the scaffold increased significantly compared to those in the control group, and alizarin red staining showed more calcium salt production during osteogenic differentiation. After 21 days, scanning electron microscopy experiments showed that osteogenesis was obvious in the PLGA/TCP scaffolds.

Conclusion

LIPUS combined with lipid microbubbles on PLGA/TCP scaffolds can promote BMSCs growth and bone differentiation, which is expected to provide a new and effective method for the treatment of bone regeneration in tissue engineering.
Mediastinal parathyroid carcinoma: a case report and review of the literature
Authors: Bao Yan , Kang Ganjun , Wu Xiaoyan , Li Jing , Huang Yan , Wang Ye
Published: June 2023

Background

Parathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (PHPT) and particularly rare in the mediastinum. Herein, we present a case of mediastinal PC and conduct a related literature review.

Case presentation

We described a case of a 50-year-old female patient with PHPT due to mediastinal PC. She was initially admitted to a local hospital in her hometown with hypercalcemia and high blood concentrations of PTH (parathyroid hormone). The patient underwent neck parathyroidectomy and pathological examination suggested parathyroid adenoma. Although the overproduction of serum calcium and PTH declined after the surgery, calcium and PTH increased again one month later, so the patient was transferred to our hospital. A 99mTc-sestamibi scan revealed an ectopic finding in the mediastinum, which was also indicated on the CT image. After removing the mediastinal mass, the metabolism of calcium and PTH quickly reverted to normal and the pathologic features of the mass were consistent with PC. By reviewing the related literature, we noticed that only scattered reports were published before 1982, and those were not included in the present review due to their differences with current radiological examination and treatment methods. After excluding outdated studies, we summarized and analyzed 20 reports of isolated mediastinal PC and concluded that. Parathyroidectomy remains the only curative treatment for the disease. Furthermore, the success of treatment directly depends on accurate preoperative localization.

Conclusion

With this study, we emphasize the importance of accurate preoperative diagnosis of mediastinal PC and improve clinicians’ understanding of the disease.
Does participation in the European Trauma Course lead to new behaviours and organisational change? A Portuguese experience
Authors: Neutel Elizabete , Kuhn Sebastian , Driscoll Peter , Gwinnutt Carl , Moreira Zélia , Veloso Ana , Manso Maria Conceição , Carneiro António
Published: June 2023

Background

Medical educational courses can be successful from an immediate feedback perspective but not lead to new behaviour or organisational changes in the workplace. The aim of this study was to assess the self-perceived impact of the European Trauma Course (ETC) on Reanima trainees’ behaviour and organisational change.

Methods

A 40-item questionnaire based on Holton's evaluation model was used to evaluate the candidate's perceptions. The results were analysed with descriptive and inferential statistical analysis using nonparametric tests with α = 0.05.

Results

Out of 295 participants, 126 responded to the survey. Of these, 94% affirmed that the ETC modified their approach to trauma patients, and 71.4% described a change in their behaviour. Postcourse responders changed their behaviour in their initial approach to trauma care in the nontechnical skills of communication, prioritisation and teamwork. Being an ETC instructor strongly influenced the acquisition of new material, and this group was able to implement changes in attitudes. Individuals with no previous trauma course experience identified lack of self-efficacy as a significant obstacle to introducing new work-based learning. In contrast, responders with ATLS training noted a lack of ETC colleagues as the main impediment for moving from conceptualisation to experimentation in the workplace.

Conclusions

Participation in the ETC led to behavioural changes in the workplace. However, the ability to influence others and bring about wider organisational changes was more difficult to achieve. Major factors were the status of the person, their experience and self-efficacy. National organisational impact was obtained, which went far beyond our aspirations in acknowledging change in individual daily practice.

Future research studies will include the effect of implementing the ETC methodology on the outcome of trauma patients.
Positive attitudes toward adoption of a multi-component intervention strategy aimed at improving HIV outcomes among adolescents and young people in Nampula, Mozambique: perspectives of HIV care providers
Authors: Mogoba Phepo , Lesosky Maia , Mukonda Elton E. , Zerbe Allison , Falcao Joana , Zandamela Ricardino , Myer Landon , Abrams Elaine J.
Published: June 2023

Background

Service providers' attitudes toward interventions are essential for adopting and implementing novel interventions into healthcare settings, but evidence of evaluations in the HIV context is still limited. This study is part of the CombinADO cluster randomized trial (ClinicalTrials.gov NCT04930367), which is investigating the effectiveness of a multi-component intervention package (CombinADO strategy) aimed at improving HIV outcomes among adolescents and young adults living with HIV (AYAHIV) in Mozambique. In this paper we present findings on key stakeholder attitudes toward adopting study interventions into local health services.

Methods

Between September and December 2021, we conducted a cross-sectional survey with a purposive sample of 59 key stakeholders providing and overseeing HIV care among AYAHIV in 12 health facilities participating in the CombinADO trial, who completed a 9-item scale on attitudes towards adopting the trial intervention packages in health facilities. Data were collected in the pre-implementation phase of the study and included individual stakeholder and facility-level characteristics. We used generalized linear regression to examine the associations of stakeholder attitude scores with stakeholder and facility-level characteristics.

Results

Overall, service-providing stakeholders within this setting reported positive attitudes regarding adopting intervention packages across study clinic sites; the overall mean total attitude score was 35.0 ([SD] = 2.59, Range = [30–41]). The study package assessed (control or intervention condition) and the number of healthcare workers delivering ART care in participating clinics were the only significant explanatory variables to predict higher attitude scores among stakeholders (β = 1.57, 95% CI = 0.34–2.80, p = 0.01 and β = 1.57, 95% CI = 0.06–3.08, p = 0.04 respectively).

Conclusions

This study found positive attitudes toward adopting the multi-component CombinADO study interventions among HIV care providers for AYAHIV in Nampula, Mozambique. Our findings suggest that adequate training and human resource availability may be important in promoting the adoption of novel multi-component interventions in healthcare services by influencing healthcare provider attitudes.
miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis
Authors: Li Genpeng , He Linye , Huang Jing , Liu Jiaye , Chen Wenjie , Zhong Jinjing , Wei Tao , Li Zhihui , Zhu Jingqiang , Lei Jianyong
Published: June 2023

Background

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT.

Methods

Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT.

Results

We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1.

Conclusions

Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT.
Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation
Authors: Baringer Stephanie L. , Palsa Kondaiah , Spiegelman Vladimir S. , Simpson Ian A. , Connor James R.
Published: June 2023

Background

Apo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood–brain barrier. Apo-Tf indicates an iron-deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephaestin as an aid to the process. Until now, the molecular mechanisms of apo- and holo-Tf influence on iron release was largely unknown.

Methods

Here we use a variety of cell culture techniques, including co-immunoprecipitation and proximity ligation assay, in iPSC-derived endothelial cells and HEK 293 cells to investigate the mechanism by which apo- and holo-Tf influence cellular iron release. Given the established role of hepcidin in regulating cellular iron release, we further explored the relationship of hepcidin to transferrin in this model.

Results

We demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway. Furthermore, holo-Tf directly interacts with ferroportin, whereas apo-Tf directly interacts with hephaestin. Only pathophysiological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin, but similar hepcidin levels are unable to interfere with the interaction between apo-Tf and hephaestin. The disruption of the holo-Tf and ferroportin interaction by hepcidin is due to hepcidin’s ability to more rapidly internalize ferroportin compared to holo-Tf.

Conclusions

These novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein–protein interactions, and offer a model for how holo-Tf and hepcidin cooperate to suppress iron release. These results expand on our previous reports on mechanisms mediating regulation of brain iron uptake to provide a more thorough understanding of the regulatory mechanisms mediating cellular iron release in general.
Bioactive compounds and biomedical applications of endophytic fungi: a recent review
Authors: Hashem Amr H. , Attia Mohamed S. , Kandil Eslam K. , Fawzi Mahmoud M. , Abdelrahman Ahmed S. , Khader Mohamed S. , Khodaira Mohamed A. , Emam Abdallah E. , Goma Mohamed A. , Abdelaziz Amer M.
Published: June 2023

Human life has been significantly impacted by the creation and spread of novel species of antibiotic-resistant bacteria and virus strains that are difficult to manage. Scientists and researchers have recently been motivated to seek out alternatives and other sources of safe and ecologically friendly active chemicals that have a powerful and effective effect against a wide variety of pathogenic bacteria as a result of all these hazards and problems. In this review, endophytic fungi and their bioactive compounds and biomedical applications were discussed. Endophytes, a new category of microbial source that can produce a variety of biological components, have major values for study and broad prospects for development. Recently, endophytic fungi have received much attention as a source for new bioactive compounds. In addition, the variety of natural active compounds generated by endophytes is due to the close biological relationship between endophytes and their host plants. The bioactive compounds separated from endophytes are usually classified as steroids, xanthones, terpenoids, isocoumarins, phenols, tetralones, benzopyranones and enniatines. Moreover, this review discusses enhancement methods of secondary metabolites production by fungal endophytes which include optimization methods, co-culture method, chemical epigenetic modification and molecular-based approaches. Furthermore, this review deals with different medical applications of bioactive compounds such as antimicrobial, antiviral, antioxidant and anticancer activities in the last 3 years.
Composition of Anopheles species and bionomic characteristics over the peak malaria transmission season in Bandarban, Bangladesh
Authors: Al-Amin Hasan Mohammad , Rodriguez Isabella , Phru Ching Swe , Khan Wasif A. , Haque Rashidul , Nahlen Bernard L. , Burton Timothy A. , Alam Mohammad Shafiul , Lobo Neil F.
Published: June 2023

Background

Joint efforts by government and non-government organizations have helped to reduce malaria in Bangladesh and set the country on a clear path to eventual malaria elimination. However, achieving that goal would be challenging without a comprehensive understanding of vector bionomics.

Methods

Targeted capturing of Anopheles mosquitoes over a rainy season, utilizing specific sampling methods, including human landing catches (HLCs), CDC-light traps (CDC-LTs), and pyrethrum spray catches (PSCs) were aimed to characterize entomological drivers of transmission in four sites of Bandarban, Bangladesh.

Results

Molecular characterization of a subset of 4637 mosquitoes has demonstrated the presence of at least 17 species whose capture rates were representative of the rainy season. Species compositions and bionomic traits did not vary between sites with Anopheles maculatus having the highest landing rate by HLCs and Anopheles vagus having the highest capture rate with CDC-LTs. Interestingly, Anopheles species compositions and capture rates varied significantly (p < 0.05) for An. vagus, between HLCs and its often-used proxy—CDC-LTs- suggesting impacts on downstream analysis. CDC-LTs capture rates demonstrated differing compositions with indoor and outdoor biting rates. For example, Anopheles nigerrimus and Anopheles nivipes were more endophagic by HLCs and more exophagic by CDC-LTs. The use of a cow-baited CDC-LT also demonstrated significantly different results when compared to a human-baited CDC-LT considering the high degree of anthropophily in these species. The exception to both zoophily and indoor resting was An. vagus, which demonstrated both anthropophily and high resting rates indoors—pointing to this species being a possible primary vector at this site.

Conclusion

A diverse Anopheles fauna in Bandarban has been confirmed through molecular methods, highlighting the potential impact of sampling techniques. Given the complexity of the local ecosystem, a better understanding of mosquito behaviour and ecology is required to achieve the goal of malaria elimination in Bangladesh.
Development and psychometric evaluation of a new patient -reported outcome measure for psoriasis self-management efficacy: the self-management efficacy questionnaire among patients with psoriasis (SMEQ-PSO)
Authors: Sun Yuanhui , Zhang Xiujie , Yang Zhen , Wang Aiping
Published: June 2023

Background

It is significant for the healthy outcome of patients with psoriasis (PSO) to improve their self-management efficacy. A standardized assessment tool, however, was lacking. Therefore, we aimed to develop a self-management efficacy questionnaire for patients with PSO (SMEQ-PSO) and evaluate its psychometric properties.

Methods

A cross-sectional study developing clinical evaluation tool was conducted from October 2021 to August 2022. In the process of developing SMEQ-PSO, three phases were involved: item generation, item evaluation, and psychometric evaluation.

Results

The SMEQ-PSO with five dimensions and 28 items was developed. The questionnaire’s content validity index was 0.976. Exploratory factor analysis indicated a five-factor structure (self-efficacy of psychosocial adaptation, self-efficacy of daily life management, self-efficacy of skin management, self-efficacy of disease knowledge management and self-efficacy of disease treatment management) that explained 62.039% of the total variance. Confirmatory factor analysis indicated appropriate fit of the five-factor model. The overall Cronbach’α coefficient was 0.930, the test-retest reliability was 0.768 and the split half reliability coefficients was 0.952.

Conclusions

The 28-item SMEQ-PSO is a reliable and valid tool that can be used to assess the self-management efficacy among patients with PSO and provide personalized interventions based on their individual circumstances to improve their health outcomes.
Quantitative measurement of finger usage in stroke hemiplegia using ring-shaped wearable devices
Authors: Yamamoto Naoya , Matsumoto Takato , Sudo Tamami , Miyashita Megumi , Kondo Toshiyuki
Published: June 2023

Background

In post-stroke rehabilitation, positive use of affected limbs in daily life is important to improve affected upper-limb function. Several studies have quantitatively evaluated the amount of upper-limb activity, but few have measured finger usage. In this study, we used a ring-shaped wearable device to measure upper-limb and finger usage simultaneously in hospitalized patients with hemiplegic stroke and investigated the association between finger usage and general clinical evaluation.

Methods

Twenty patients with hemiplegic stroke in an inpatient hospital participated in this study. All patients wore a ring-shaped wearable device on both hands for 9 h on the day of the intervention, and their finger and upper-limb usage were recorded. For the rehabilitation outcome assessments, the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Simple Test for Evaluating Hand Function (STEF), Action Research Arm Test (ARAT), Motor Activity Log-14 (MAL), and Functional Independence Measure Motor (FIM-m) were performed and evaluated on the same day as the intervention.

Results

Finger usage of the affected hand was moderately correlated with STEF ($$r=0.48$$r=0.48,$$p<0.05$$p<0.05) and STEF ratio ($$r=0.47$$r=0.47,$$p<0.05$$p<0.05). The finger-usage ratio was moderately correlated with FMA-UE ($$r=0.56$$r=0.56,$$p<0.05$$p<0.05) and ARAT ($$r=0.53$$r=0.53,$$p<0.05$$p<0.05), and strongly correlated with STEF ($$r=0.80$$r=0.80,$$p<0.01$$p<0.01) and STEF ratio ($$r=0.80$$r=0.80,$$p<0.01$$p<0.01). The upper-limb usage of the affected side was moderately correlated with FMA-UE ($$r=0.46$$r=0.46,$$p<0.05$$p<0.05), STEF ($$r=0.55$$r=0.55,$$p<0.05$$p<0.05) and STEF ratio ($$r=0.54$$r=0.54,$$p<0.05$$p<0.05), and strongly correlated with ARAT ($$r=0.57$$r=0.57,$$p<0.01$$p<0.01). The upper-limb usage ratio was moderately correlated with ARAT ($$r=0.48$$r=0.48,$$p<0.05$$p<0.05) and STEF ($$r=0.55$$r=0.55,$$p<0.05$$p<0.05), and strongly correlated with the STEF ratio ($$r=0.61$$r=0.61,$$p<0.01$$p<0.01). By contrast, there was no correlation between MAL and any of the measurements.

Conclusions

This measurement technique provided useful information that was not biased by the subjectivity of the patients and therapists.
Understanding inequalities in mental health by family structure during COVID-19 lockdowns: evidence from the UK Household Longitudinal Study
Authors: Green Michael J. , Craig Peter , Demou Evangelia , Katikireddi S. Vittal , Leyland Alastair H. , Pearce Anna
Published: June 2023

Purpose

The COVID-19 pandemic increased psychiatric distress and impacts differed by family structure. We aimed to identify mechanisms contributing to these inequalities.

Methods

Survey data were from the UK Household Longitudinal Study. Psychiatric distress (GHQ-12) was measured in April 2020 (first UK lockdown; n = 10,516), and January 2021 (lockdown re-introduced following eased restrictions; n = 6,893). Pre-lockdown family structure comprised partner status and presence of children (< 16 years). Mediating mechanisms included: active employment, financial strain, childcare/home-schooling, caring, and loneliness. Monte Carlo g-computation simulations were used to adjust for confounding and estimate total effects and decompositions into: controlled direct effects (effects if the mediator was absent), and portions eliminated (PE; representing differential exposure and vulnerability to the mediator).

Results

In January 2021, after adjustment, we estimated increased risk of distress among couples with children compared to couples with no children (RR: 1.48; 95% CI 1.15–1.82), largely because of childcare/home-schooling (PE RR: 1.32; 95% CI 1.00–1.64). Single respondents without children also had increased risk of distress compared to couples with no children (RR: 1.55; 95% CI 1.27–1.83), and the largest PE was for loneliness (RR: 1.16; 95% CI 1.05–1.27), though financial strain contributed (RR: 1.05; 95% CI 0.99–1.12). Single parents demonstrated the highest levels of distress, but confounder adjustment suggested uncertain effects with wide confidence intervals. Findings were similar in April 2020 and when stratified by sex.

Conclusion

Access to childcare/schooling, financial security and social connection are important mechanisms that need addressing to avoid widening mental health inequalities during public health crises.
Formation of a traditional Chinese medicine self-assembly nanostrategy and its application in cancer: a promising treatment
Authors: Huang Ju , Zhu Yu , Xiao Hang , Liu Jingwen , Li Songtao , Zheng Qiao , Tang Jianyuan , Meng Xiangrui
Published: June 2023

Traditional Chinese medicine (TCM) has been used for centuries to prevent and treat a variety of illnesses, and its popularity is increasing worldwide. However, the clinical applications of natural active components in TCM are hindered by the poor solubility and low bioavailability of these compounds. To address these issues, Chinese medicine self-assembly nanostrategy (CSAN) is being developed. Many active components of TCM possess self-assembly properties, allowing them to form nanoparticles (NPs) through various noncovalent forces. Self-assembled NPs (SANs) are also present in TCM decoctions, and they are closely linked to the therapeutic effects of these remedies. SAN is gaining popularity in the nano research field due to its simplicity, eco-friendliness, and enhanced biodegradability and biocompatibility compared to traditional nano preparation methods. The self-assembly of active ingredients from TCM that exhibit antitumour effects or are combined with other antitumour drugs has generated considerable interest in the field of cancer therapeutics. This paper provides a review of the principles and forms of CSAN, as well as an overview of recent reports on TCM that can be used for self-assembly. Additionally, the application of CSAN in various cancer diseases is summarized, and finally, a concluding summary and thoughts are proposed. We strongly believe that CSAN has the potential to offer fresh strategies and perspectives for the modernization of TCM.
Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum
Authors: Najafi Ali , Tasharrofi Behnoosh , Zandsalimi Farshid , Rasulinezhad Maryam , Ghahvechi Akbari Masood , Zamani Gholamreza , Ashrafi Mahmoud Reza , Heidari Morteza
Published: June 2023

Background

Spinal muscular atrophy (SMA) could be classified as 5q and non-5q, based on the chromosomal location of causative genes. A rare form of non-5q SMA is an autosomal-recessive condition called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), phenotypically characterized by myoclonic and generalized seizures with progressive neurological deterioration. SMA-PME is a clinically heterogeneous disorder that arises from biallelic pathogenic variants in ASAH1 gene.

Methods

Following clinical and primary laboratory assessments, whole-exome sequencing was performed to detect the disease-causing variants in three cases of SMA-PME from different families. Also, Multiplex ligation-dependent probe amplification (MLPA) was employed for determining the copy numbers of SMN1 and SMN2 genes to rule out 5q SMA.

Results

Exome sequencing revealed two different homozygous missense mutations (c.109 C > A [p.Pro37Thr] or c.125 C > T [p.Thr42Met]) in exon 2 of the ASAH1 gene in the affected members of the families. Sanger sequencing of the other family members showed the expected heterozygous carriers. In addition, no clinically relevant variant was identified in patients by MLPA.

Conclusion

This study describes two different ASAH1 mutations and the clinical picture of 3 SMA-PME patients. In addition, previously reported mutations have been reviewed. This study could help to fortify the database of this rare disease with more clinical and genomic data.
Entomopathogenic fungus treatment changes the gut bacterial diversity of Rhipicephalus microplus ticks
Authors: Mesquita Emily , da Costa Diogo Paes , Meirelles Laura Nóbrega , Camargo Mariana Guedes , Corrêa Thaís Almeida , Bittencourt Vânia Rita Elias Pinheiro , da Silva Coelho Irene , Santos Huarrisson Azevedo , Humber Richard Alan , Golo Patrícia Silva
Published: June 2023

Background

Ticks are obligate bloodsucking parasites responsible for significant economic losses and concerns with human and animal health, mainly due to the transmission of pathogens. Entomopathogenic fungi have been intensively studied as an alternative strategy for tick control that can be used in combination with synthetic acaricides in the integrated management of ticks. Here, we investigated how the gut bacterial community of Rhipicephalus microplus is shaped after Metarhizium anisopliae treatment and how the tick susceptibility to the fungus is affected after disrupting gut bacterial microbiota.

Methods

Partially engorged tick females were artificially fed with pure bovine blood or blood plus tetracycline. Two other groups received the same diet and were topically treated with M. anisopliae. The guts were dissected, and the genomic DNA was extracted 3 days after the treatment; the V3–V4 variable region of the bacterial 16S rRNA gene was amplified.

Results

The gut of ticks that received no antibiotic but were treated with M. anisopliae exhibited lower bacterial diversity and a higher occurrence of Coxiella species. The Simpson diversity index and Pielou equability coefficient were higher in the gut bacterial community when R. microplus were fed with tetracycline and fungus-treated. Ticks from fungus-treated groups (with or without tetracycline) exhibited lower survival than untreated females. Previous feeding of ticks with the antibiotic did not change their susceptibility to the fungus. Ehrlichia spp. were not detected in the gueated groups.

Conclusions

These findings suggest that myco-acaricidal action would not be impacted if the calf hosting these ticks is under antibiotic therapy. Moreover, the hypothesis that entomopathogenic fungi can affect the bacterial community in the gut of R. microplus engorged females is endorsed by the fact that ticks exposed to M. anisopliae exhibited a dramatic reduction in bacterial diversity. This is the first report of an entomopathogenic fungus affecting the tick gut microbiota.

Graphical Abstract
Retrospective batch analysis to evaluate the diagnostic accuracy of a clinically deployed AI algorithm for the detection of acute pulmonary embolism on CTPA
Authors: Langius-Wiffen Eline , de Jong Pim A. , Hoesein Firdaus A. Mohamed , Dekker Lisette , van den Hoven Andor F. , Nijholt Ingrid M. , Boomsma Martijn F. , Veldhuis Wouter B.
Published: June 2023

Purpose

To generate and extend the evidence on the clinical validity of an artificial intelligence (AI) algorithm to detect acute pulmonary embolism (PE) on CT pulmonary angiography (CTPA) of patients suspected of PE and to evaluate the possibility of reducing the risk of missed findings in clinical practice with AI-assisted reporting.

Methods

Consecutive CTPA scan data of 3316 patients referred because of suspected PE between 24-2-2018 and 31-12-2020 were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The output of the AI was compared with the attending radiologists’ report. To define the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, an experienced cardiothoracic radiologist adjudicated.

Results

According to the reference standard, PE was present in 717 patients (21.6%). PE was missed by the AI in 23 patients, while the attending radiologist missed 60 PE. The AI detected 2 false positives and the attending radiologist 9. The sensitivity for the detection of PE by the AI algorithm was significantly higher compared to the radiology report (96.8% vs. 91.6%, p < 0.001). Specificity of the AI was also significantly higher (99.9% vs. 99.7%, p = 0.035). NPV and PPV of the AI were also significantly higher than the radiology report.

Conclusion

The AI algorithm showed a significantly higher diagnostic accuracy for the detection of PE on CTPA compared to the report of the attending radiologist. This finding indicates that missed positive findings could be prevented with the implementation of AI-assisted reporting in daily clinical practice.

Critical relevance statement

Missed positive findings on CTPA of patients suspected of pulmonary embolism can be prevented with the implementation of AI-assisted care.

Key points

The AI algorithm showed excellent diagnostic accuracy detecting PE on CTPA.

Accuracy of the AI was significantly higher compared to the attending radiologist.

Highest diagnostic accuracy can likely be achieved by radiologists supported by AI.

Our results indicate that implementation of AI-assisted reporting could reduce the number of missed positive findings.

Graphical abstract
Suspension culture improves iPSC expansion and pluripotency phenotype
Authors: Cuesta-Gomez Nerea , Verhoeff Kevin , Dadheech Nidheesh , Dang Tiffany , Jasra Ila Tewari , de Leon Mario Bermudez , Pawlick Rena , Marfil-Garza Braulio , Anwar Perveen , Razavy Haide , Zapata-Morin Patricio Adrián , Jickling Glen , Thiesen Aducio , O’Gorman Doug , Kallos Michael S. , Shapiro A. M. James
Published: June 2023

Background

Induced pluripotent stem cells (iPSCs) offer potential to revolutionize regenerative medicine as a renewable source for islets, dopaminergic neurons, retinal cells, and cardiomyocytes. However, translation of these regenerative cell therapies requires cost-efficient mass manufacturing of high-quality human iPSCs. This study presents an improved three-dimensional Vertical-Wheel® bioreactor (3D suspension) cell expansion protocol with comparison to a two-dimensional (2D planar) protocol.

Methods

Sendai virus transfection of human peripheral blood mononuclear cells was used to establish mycoplasma and virus free iPSC lines without common genetic duplications or deletions. iPSCs were then expanded under 2D planar and 3D suspension culture conditions. We comparatively evaluated cell expansion capacity, genetic integrity, pluripotency phenotype, and in vitro and in vivo pluripotency potential of iPSCs.

Results

Expansion of iPSCs using Vertical-Wheel® bioreactors achieved 93.8-fold (IQR 30.2) growth compared to 19.1 (IQR 4.0) in 2D (p < 0.0022), the largest expansion potential reported to date over 5 days. 0.5 L Vertical-Wheel® bioreactors achieved similar expansion and further reduced iPSC production cost. 3D suspension expanded cells had increased proliferation, measured as Ki67+expression using flow cytometry (3D: 69.4% [IQR 5.5%] vs. 2D: 57.4% [IQR 10.9%],p = 0.0022), and had a higher frequency of pluripotency marker (Oct4+Nanog+Sox2+) expression (3D: 94.3 [IQR 1.4] vs. 2D: 52.5% [IQR 5.6],p = 0.0079). q-PCR genetic analysis demonstrated a lack of duplications or deletions at the 8 most commonly mutated regions within iPSC lines after long-term passaging (> 25). 2D-cultured cells displayed a primed pluripotency phenotype, which transitioned to naïve after 3D-culture. Both 2D and 3D cells were capable of trilineage differentiation and following teratoma, 2D-expanded cells generated predominantly solid teratomas, while 3D-expanded cells produced more mature and predominantly cystic teratomas with lower Ki67+expression within teratomas (3D: 16.7% [IQR 3.2%] vs.. 2D: 45.3% [IQR 3.0%],p = 0.002) in keeping with a naïve phenotype.

Conclusion

This study demonstrates nearly 100-fold iPSC expansion over 5-days using our 3D suspension culture protocol in Vertical-Wheel® bioreactors, the largest cell growth reported to date. 3D expanded cells showed enhanced in vitro and in vivo pluripotency phenotype that may support more efficient scale-up strategies and safer clinical implementation.
Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model
Authors: Gonzalez Hector , McCarthy Sean , Masterson Claire , Byrnes Declan , Sallent Ignacio , Horan Emma , Elliman Stephen J. , Vella Gabriele , Prina-Mello Adriele , Silva Johnatas D. , Krasnodembskaya Anna D. , MacLoughlin Ronan , Laffey John G. , O’Toole Daniel
Published: June 2023

Background

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichiacoli-induced pneumonia.

Methods

EV size, surface markers and miRNA content were assessed pre- and post-nebulisation. BEAS2B and A459 lung cells were exposed to lipopolysaccharide (LPS) and treated with nebulised bone marrow (BM) or umbilical cord (UC) MSC-EVs. Viability assays (MTT) and inflammatory cytokine assays were performed. THP-1 monocytes were stimulated with LPS and nebulised BM- or UC-EVs and phagocytosis activity was measured. For in vivo experiments, mice received LPS intratracheally (IT) followed by BM- or UC-EVs intravenously (IV) and injury markers assessed at 24 h. Rats were instilled with E. coli bacteria IT and BM- or UC-EVs delivered IV or by direct nebulisation. At 48 h, lung damage was assessed by physiological parameters, histology and inflammatory marker presence.

Results

MSC-EVs retained their immunomodulatory and wound healing capacity after nebulisation in vitro. EV integrity and content were also preserved. Therapy with IV or nebulised MSC-EVs reduced the severity of LPS-induced lung injury and E. coli-induced pneumonia by reducing bacterial load and oedema, increasing blood oxygenation and improving lung histological scores. MSC-EV treated animals also showed lower levels of inflammatory cytokines and inflammatory-related markers.

Conclusions

MSC-EVs given IV attenuated LPS-induced lung injury, and nebulisation of MSC-EVs did not affect their capacity to attenuate lung injury caused by E. coli pneumonia, as evidenced by reduction in bacterial load and improved lung physiology.
Age estimation by spheno-occipital synchondrosis fusion in South Indian population using computed tomography
Authors: Nayak Rajesh , Panakkal Nitika C. , T Visakh
Published: June 2023

Background

Age estimation has paramount importance for the forensic practitioner. Depending on the timing of fusion, the spheno-occipital synchondrosis will be open during childhood and then later fuse during adulthood. Since there have been a lot of inconsistencies in terms of fusion degree, that can be attributed to variability in population or methodology. The aim of the present study was to determine the age of beginning of the spheno-occipital synchondrosis in the South Indian population using computed tomography.

Results

The study reported a mean age of 8.38 ± 1.21 for males and 8.2 ± 1.16 for females in the stage 0 (completely open) category. Spheno-occipital synchondrosis began to fuse (stage 1) at the mean age of 11.64 ± 1.19 for males and 10.21 ± 1.19 for females.

Conclusions

Spheno-occipital synchondrosis begins to close at the age of less than 15 years in males. Similarly, for females, the spheno-occipital synchondrosis begins to close at the age of less than 14 years. Also, a strong sexual dimorphism is seen as each stage of synchondrosis and starts earlier in females compared to males. In addition, the study also showed the degree of fusion increasing with age. This estimation will not only help in forensic and anthropological studies but also in assessing craniofacial growth in orthodontics.
The possible protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on tramadol-induced testicular damage in rats
Authors: Mahmoud Abeer Ramzy Hussieny , Moursi Suzan M. M. , Esmaeel Safya E. , Mohamed Nesma Ismail Sharawy , Ali Nagah ElSayed Mohammed
Published: June 2023

Background

Tramadol provokes oxidative stress that gives rise to apoptosis with alterations in the cellular structure and adversely influences male fertility. A specific inhibitor of nuclear factor kappa B (NF-κB), pyrrolidine dithiocarbamate (PDTC), has observable antioxidant and anti-inflammatory characteristics and enhances the improvement of organs damage caused by various agents. The impact of PDTC on testicular damage caused by tramadol has not been previously examined.

Objective

This study was designed to investigate the potential impact of pyrrolidine dithiocarbamate on testicular damage provoked by chronic tramadol usage.

Materials and methods

Forty healthy adult male albino rats were included in this study. Rats were randomly and equally divided into 4 groups: group (I), control group; group (II), pyrrolidine dithiocarbamate (PDTC) group; group (III), tramadol (Tr) group; and group (IV), Tr + PDTC group. This study measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and free testosterone levels. Testicular malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX), and caspase-8 and caspase-3 activities were also detected. Immuno-histochemical evaluation of inducible NOS (iNOS) expression in testicular tissue along with histopathological examination of testicular tissue has been studied.

Results

Tramadol caused a significant reduction in serum FSH, LH and testosterone levels, epididymal sperm count, and motility, as well as testicular GPX and SOD activities. On the other hand, a significant elevation of testicular MDA, IL-1β, IL-6, and TNF-α levels and caspase-8 and caspase-3 activities were found. However, PDTC administration with tramadol showed significantly increased sperm production and motility and alleviated tramadol-induced disturbance in other measured parameters in the Tr + PDTC group compared to the Tr group. Moreover, co-administration of PDTC with tramadol significantly alleviated the histopathological structure of testicular tissue and the increased iNOS expressions noticed in the tramadol-treated group.

Conclusion

Considering the protective effects of PDTC against the reproductive toxicity induced by tramadol, this compound can be used as a possible protective and treating target for tramadol-induced reproductive toxicity.
Taxonomy of Hyphodermella: a case study to show that simple phylogenies cannot always accurately place species in appropriate genera
Authors: Shen Shan , Liu Shi-Liang , Zhou Li-Wei
Published: June 2023

The genus is a special and crucial taxonomic rank compared with others above the species level, because a species has to be placed in a certain genus instead of any other higher ranks. With more and more new species being described, the placements of their generic position are sometimes incorrect due to the simple phylogenies resulting from inappropriate sampling. Here, we focus on the taxonomy of a small wood-inhabiting fungal genus Hyphodermella. With the most comprehensive sampling to date, the phylogenetic position of Hyphodermella within Phanerochaetaceae is rearranged by employing the same ITS and nLSU regions as in previous studies and also the ITS, nLSU, rpb1, rpb2 and tef1α regions. Three species are excluded from Hyphodermella: H. poroides is placed in a newly introduced monotypic genus Pseudohyphodermella, while H. aurantiaca and H. zixishanensis are transferred to Roseograndinia. Hyphodermella suiae is described as a new species from South China and Vietnam. Keys to eight species in Hyphodermella and five in Roseograndinia are provided. Beyond solving the taxonomic issue of Hyphodermella itself, the current study also aims to suggest that all fungal taxonomists especially beginners should keep in mind to sample as many comprehensive taxa as possible in phylogenetic analyses.
Acute presentation of locally advanced squamous cell carcinoma of frontal sinus—imaging findings of a rare entity: case report
Authors: Lahiri Ashim Kumar , Singh Kulvinder , Sherif Deia Mohamed Mohamed
Published: June 2023

Background

The squamous cell carcinoma is the most common subtype of malignant sinonasal tumours, predominantly involving the maxillary sinuses and nasal cavities in 70 to 80% of cases, and the frontal sinus is extremely rarely involved, in less than 1% of cases. Early clinical and radiological diagnosis is difficult due to overlap of findings with inflammatory sinonasal disease.

Case presentation

A 55-year-old Caucasian male patient had presented to the emergency department with three-month history of progressive right frontal swelling, acute frontal pain, recent exacerbation of right eye vision impairment and new lid swelling. There was no recent history of trauma and no neurological deficit on examination. Contrast-enhanced CT head was performed which demonstrated large bony destruction of frontal sinus with partly enhancing necrotic-looking tumour within the sinus. There was further intraorbital and intracranial extension of disease. Subsequent MRI confirmed these findings with better demonstration of intracranial and intraorbital component of the disease. The PET imaging did not reveal any avid disease elsewhere. Histopathology confirmed squamous cell carcinoma.

Conclusions

Frontal sinus squamous cell carcinoma is a rare and the least common site within the paranasal sinuses. Early clinical and imaging diagnosis could be challenging; however, the index of suspicion should be high with indeterminate imaging findings. CT and MRI are the complimentary imaging techniques.