bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-enhanced ultrasound combined targeted microbubbles for diagnosis of highly aggressive papillary thyroid carcinoma
Authors: Ma Jiaojiao , Wang Yuan , Xi Xuehua , Tang Jiajia , Wang Linping , Wang Liangkai , Wang Di , Liang Xiaolong , Zhang Bo
Published: March 2023

Background

Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC.

Purpose

To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC.

Methods

Using β-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system.

Results

Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 μm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs.

Conclusion

We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.
Potential involvement of circulating extracellular vesicles and particles on exercise effects in malignancies
Authors: Siqueira Ionara Rodrigues , Batabyal Rachael A. , Freishtat Robert , Cechinel Laura Reck
Published: March 2023

Physical activity and exercise have been widely related to prevention, treatment, and control for several non-communicable diseases. In this context, there are innumerous pre-clinical and clinical evidence indicating the potential role of exercise, beyond cancer prevention and survival, improved quality of life, including on psychological components, bone health and cachexia, from cancer survivors is described as well. This mini-review raises the potential role of circulating extracellular and particles vesicles (EVPs) cargo, as exerkines, conducting several positive effects on adjacent and/or distant tissues such as tumor, immune, bone and muscle cells. We highlighted new perspectives about microRNAs into EVPs changes induced by exercise and its benefits on malignancies, since microRNAs can be implicated with intricated physiopathological processes. Potential microRNAs into EVPs were pointed out here as players spreading beneficial effects of exercise, such as miR-150-5p, miR-124, miR-486, and miRNA-320a, which have previous findings on involvement with clinical outcomes and as well as tumor microenvironment, regulating intercellular communication and tumor growth. For example, high-intensity interval aerobic exercise program seems to increase miR‐150 contents in circulating EVPs obtained from women with normal weight or overweight. In accordance circulating EVPs miR-150-5p content is correlated with prognosis colorectal cancer, and ectopic expression of miR-150 may reduce cell proliferation, invasion and metastasis. Beyond the involvement of bioactive miRNAs into circulating EVPs and their pathways related to clinical and preclinical findings, this mini review intends to support further studies on EVPs cargo and exercise effects in oncology.
Trends and outcomes of fertility preservation for girls, adolescents and young adults with Turner syndrome: A prospective cohort study
Authors: Rodriguez-Wallberg Kenny A. , Sergouniotis Fotios , Nilsson Hanna P. , Lundberg Frida E.
Published: March 2023

Background

In Scandinavian countries, programs for fertility preservation (FP) are offered free of charge at tertiary-care university hospitals to all patients facing infertility risks due to malignant diagnoses or benign conditions. In this prospective study we aimed to investigate trends and outcomes of FP indicated by a diagnosis of Turner syndrome.

Methods

Prospective cohort study of patients with Turner karyotype receiving fertility preservation counselling at the Karolinska University Hospital between 1 January 1999 and 31 December 2021.

Results

The cohort included 100 women and girls that received counselling, whereof 27% were prepubertal girls, 59% were adolescents and 14% of adult age. Before 2006 all patients were referred for fertility counselling at the time of Turner diagnosis. Based on updated guidelines, mainly patients who showed signs of puberty were referred after 2006. As a result, spontaneous menarche was more common in the later period. In total, 39% of the cohort had monosomal karyotype (45X), 20% had 45X/46XX or 45X/47XXX mosaicisms and 36% had an X-chromosomal structural anomaly. Ovarian tissue cryopreservation was planned for 73% of all patients, and oocyte cryopreservation following gonadotropin stimulation was planned for 10% of the patients. Follicles were present in 25% of all biopsies analyzed. Adolescents were more likely to have follicles present (30%) than prepubertal girls (16%) or adult women (17%). The ten patients that underwent gonadotropin stimulation for oocyte cryopreservation underwent a total of 15 cycles and eight patients successfully preserved oocytes. In total, 26% of the cohort has undergone fertility treatment or expressed further interest in fertility preservation. Six women have given birth using donated oocytes and three following spontaneous conception. Two women have undergone re-transplantation of cryopreserved ovarian tissue, without regaining ovarian function, and none of the women that have cryopreserved oocytes has returned to use them.

Conclusion

Fertility counselling for girls with Turner syndrome should ideally be offered at onset of spontaneous puberty to improve the chances of fertility preservation. Since the girls and women in this cohort are still young, the return rate and utilization of the preserved tissue and oocytes is expected to increase with time.

Clinical Trial Registration

ClinicalTrials.gov, identifier NTC04602962.
Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease
Authors: Liu Peng , Zhu Wenhui , Wang Yang , Ma Guijie , Zhao Hailing , Li Ping
Published: March 2023

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease worldwide, and there is a lack of effective treatment strategies. Autophagy is a highly conserved lysosomal degradation process that maintains homeostasis and energy balance by removing protein aggregates and damaged organelles. Increasing evidence suggests that dysregulated autophagy may contribute to glomerular and tubulointerstitial lesions in the kidney under diabetic conditions. Emerging studies have shown that Chinese herbal medicine and its active compounds may ameliorate diabetic kidney injury by regulating autophagy. In this review, we summarize that dysregulation or insufficiency of autophagy in renal cells, including podocytes, glomerular mesangial cells, and proximal tubular epithelial cells, is a key mechanism for the development of DKD, and focus on the protective effects of Chinese herbal medicine and its active compounds. Moreover, we systematically reviewed the mechanism of autophagy in DKD regulated by Chinese herb compound preparations, single herb and active compounds, so as to provide new drug candidates for clinical treatment of DKD. Finally, we also reviewed the candidate targets of Chinese herbal medicine regulating autophagy for DKD. Therefore, further research on Chinese herbal medicine with autophagy regulation and their targets is of great significance for the realization of new targeted therapies for DKD.
Does digitalization make urban development greener? A case from 276 cities in China
Authors: Ma Lindong , Xu Weixiang , He Shouchao , Hong Yuanxiao , Yang Weixia , Zhao Yanping
Published: March 2023

Nowadays countries in the world are striving to transform their economic and social development modes to achieve the general goal of green development. With the rapid development of communication technology, digitalization has affected production and life, touching all aspects of society. Can digitalization make the world “greener”? To this end, this study conducts an empirical research based on the panel data of 276 cities in China from 2011 to 2020. Firstly, this paper separately measured the comprehensive level of urban digitalization and urban greening through the Entropy-TOPSIS method, then analyzed their spatial distribution characteristics and evolution process respectively, finally used the spatial Durbin model to explore the impact of digitalization on urban greening development. The following conclusions were drawn accordingly: (1). The development pattern of urban digitalization has changed from “multi-point” sporadic distribution to “group-type” aggregation with obvious spatial heterogeneity. The gap between cities is not narrowing. The Yangtze River Delta urban agglomeration has become an important high-level digital agglomeration area; (2). The urban greening develops with obvious spatial heterogeneity. The difference between eastern regions and western regions is prominent, and the urban spatial agglomeration characteristic is distinct. However, the spillover effect is weakened with distance, while the convergence characteristic becomes obvious; (3). Digitalization is significantly beneficial to the development of urban greening with obvious spatial heterogeneity. Digitalization in cities within urban agglomeration and in eastern regions has a stronger effect on promoting the urban greening, which is not obvious in cities located in western regions and non-urban agglomeration. Finally, according to the research results, suggestions for urban digitalization and greening development are put forward.
Genome-wide analyses of lung cancer after single high-dose radiation at five time points (2, 6, 12, 24, and 48 h)
Authors: Du Yajing , Zheng Yunna , Yu Kaiwen , Zhan Cheng , Qiao Tiankui
Published: March 2023

Background: An increasing number of clinicians are experimenting with high-dose radiation. This study focuses on the genomic effects of high-dose single-shot radiotherapy and aims to provide a dynamic map for non-small cell lung cancer (NSCLC).

Methods: We used whole-transcriptome sequencing to understand the evolution at molecular levels in A549 and H1299 exposed to 10 Gy X-rays at different times (2, 6, 12, 24, and 48 h) in comparison with the no radiation group. Ingenuity pathway analysis, ceRNA analysis, enrichment analysis, and cell cycle experiments are performed for molecular analyses and function analyses.

Results: Whole-transcriptome sequencing of NSCLC showed a significant dynamic change after radiotherapy within 48 h. MiR-219-1-3p and miR-221-3p, miR-503-5p, hsa-miR-455-5p, hsa-miR-29-3p, and hsa-miR-339-5p were in the core of the ceRNA related to time change. GO and KEGG analyses of the top 30 mRNA included DNA repair, autophagy, apoptosis, and ferroptosis pathways. Regulation of the cell cycle-related transcription factor E2F1 might have a key role in the early stage of radiotherapy (2.6 h) and in the later stage of autophagy (24 and 48 h). Functions involving different genes/proteins over multiple periods implied a dose of 10 Gy was related to the kidney and liver pathway. Radiation-induced cell cycle arrest at the G2/M phase was evident at 24 h. We also observed the increased expression of CCNB1 at 24 h in PCR and WB experiments.

Conclusion: Our transcriptomic and experimental analyses showed a dynamic change after radiation therapy in 48 h and highlighted the key molecules and pathways in NSCLC after high-dose single-shot radiotherapy.
A systematic review and meta-analysis of the effectiveness and safety of COVID-19 vaccination in older adults
Authors: Xu Kun , Wang Zihan , Qin Maorong , Gao Yangyu , Luo Na , Xie Wanting , Zou Yihan , Wang Jie , Ma Xingming
Published: March 2023

In the coronavirus disease 2019 (COVID-19) pandemic, vaccinations were essential in preventing COVID-19 infections and related mortality in older adults. The objectives of this study were to evaluate the effectiveness and safety of the COVID-19 vaccines in older adults. We systematically searched the electronic bibliographic databases of PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, Research Square, and OpenGrey, as well as other sources of gray literature, for studies published between January 1, 2020, and October 1, 2022. We retrieved 22 randomized controlled trials (RCTs), with a total of 3,404,696 older adults (aged over 60 years) participating, that were included in the meta-analysis. No significant publication bias was found. In the cumulative meta-analysis, we found that the COVID-19 vaccines were effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (OR = 0.38, 95% CI = 0.23–0.65, p = 0.0004) and in reducing the number of COVID-19-related deaths (OR = 0.16, 95% CI = 0.10–0.25, p < 0.00001) in elderly people. Antibody seroconversion (AS) and geometric mean titer (GMT) levels significantly increased in vaccinated older adults [OR = 24.42, 95% CI = 19.29–30.92; standardized mean difference (SMD) = 0.92, 95% CI = 0.64–1.20, respectively]. However, local and systemic adverse events after COVID-19 vaccine administration were found in older adults (OR = 2.57, 95% CI = 1.83–3.62, p < 0.00001). Although vaccination might induce certain adverse reactions in the elderly population, the available evidence showed that the COVID-19 vaccines are effective and tolerated, as shown by the decrease in COVID-19-related deaths in older adults. It needs to be made abundantly clear to elderly people that the advantages of vaccination far outweigh any potential risks. Therefore, COVID-19 vaccination should be considered as the recommended strategy for the control of this disease by preventing SARS-CoV-2 infection and related deaths in older adults. More RCTs are needed to increase the certainty of the evidence and to verify our conclusions.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319698, identifier CRD42022319698.
Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection
Authors: Bermingham William Hywel , Canning Benjamin , Wilton Thomas , Kidd Michael , Klapsa Dimitra , Majumdar Manasi , Sooriyakumar Kavitha , Martin Javier , Huissoon Aarnoud P.
Published: March 2023

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.
The role of myeloid derived suppressor cells in musculoskeletal disorders
Authors: Ren Yi , Bäcker Henrik , Müller Michael , Kienzle Arne
Published: March 2023

The immune system is closely linked to bone homeostasis and plays a pivotal role in several pathological and inflammatory conditions. Through various pathways it modulates various bone cells and subsequently sustains the physiological bone metabolism. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid-derived cells that can exert an immunosuppressive function through a direct cell-to-cell contact, secretion of anti-inflammatory cytokines or specific exosomes. These cells mediate the innate immune response to chronic stress on the skeletal system. In chronic inflammation, MDSCs act as an inner offset to rebalance overactivation of the immune system. Moreover, they have been found to be involved in processes responsible for bone remodeling in different musculoskeletal disorders, autoimmune diseases, infection, and cancer. These cells can not only cause bone erosion by differentiating into osteoclasts, but also alleviate the immune reaction, subsequently leading to long-lastingly impacted bone remodeling. In this review, we discuss the impact of MDSCs on the bone metabolism under several pathological conditions, the involved modulatory pathways as well as potential therapeutic targets in MDSCs to improve bone health.
Reasoning like a doctor or like a nurse? A systematic integrative review
Authors: Vreugdenhil Jettie , Somra Sunia , Ket Hans , Custers Eugène J. F. M. , Reinders Marcel E. , Dobber Jos , Kusurkar Rashmi A.
Published: March 2023

When physicians and nurses are looking at the same patient, they may not see the same picture. If assuming that the clinical reasoning of both professions is alike and ignoring possible differences, aspects essential for care can be overlooked. Understanding the multifaceted concept of clinical reasoning of both professions may provide insight into the nature and purpose of their practices and benefit patient care, education and research. We aimed to identify, compare and contrast the documented features of clinical reasoning of physicians and nurses through the lens of layered analysis and to conduct a simultaneous concept analysis. The protocol of this systematic integrative review was publisheddoi: 10.1136/bmjopen-2021-049862. A comprehensive search was performed in four databases (PubMed, CINAHL, Psychinfo, and Web of Science) from 30th March 2020 to 27th May 2020. A total of 69 Empirical and theoretical journal articles about clinical reasoning of practitioners were included: 27 nursing, 37 medical, and five combining both perspectives. Two reviewers screened the identified papers for eligibility and assessed the quality of the methodologically diverse articles. We used an onion model, based on three layers: Philosophy, Principles, and Techniques to extract and organize the data. Commonalities and differences were identified on professional paradigms, theories, intentions, content, antecedents, attributes, outcomes, and contextual factors. The detected philosophical differences were located on a care-cure and subjective-objective continuum. We observed four principle contrasts: a broad or narrow focus, consideration of the patient as such or of the patient and his relatives, hypotheses to explain or to understand, and argumentation based on causality or association. In the technical layer a difference in the professional concepts of diagnosis and the degree of patient involvement in the reasoning process were perceived. Clinical reasoning can be analysed by breaking it down into layers, and the onion model resulted in detailed features. Subsequently insight was obtained in the differences between nursing and medical reasoning. The origin of these differences is in the philosophical layer (professional paradigms, intentions). This review can be used as a first step toward gaining a better understanding and collaboration in patient care, education and research across the nursing and medical professions.
Case report: Endoscopic Hemoclip treatment for massive hematemesis caused by a Dieulafoy’s lesion on duodenal papilla caused acute pancreatitis
Authors: He Zhi-wei , Xu Hui , Shi Hua , Wang Yang-mei , Zhong Han , Liu Xiao-cong
Published: March 2023

Background

Dieulafoy’s lesion is an uncommon cause of hemorrhage of the digestive tract. It often presents with urgent and massive bleeding usually leading to shock, even death. Dieulafoy’s lesions have been reported throughout the digestive tract but which occurred on duodenal papilla were particularly rare and presented challenges in the choice of hemostasis.

Case presentation

A 66-year-old man with melena for 2 days was admitted. Gastrointestinal endoscopy revealed blood clots covering the duodenal papilla with oozing blood. During the procedure of trying to place a plastic stent into the duodenal papilla first, the hemorrhage began to present pulsating bleeding. The patient went into shock. With consent, two titanium clips were inserted to clamp the bleeding site to stop the bleeding. The patient complained of epigastric pain 14 h after the endoscopy. An abdominal CT scan showed signs of acute pancreatitis. Endoscopy was performed to remove the titanium clips and showed a vessel stump on the duodenal papilla. The patient was discharged from the hospital on the 14th day and followed for 6 months with no recurrence.

Conclusion

This case was diagnosed with a Dieulafoy’s lesion on the duodenal papilla, which has rarely been reported. Hematemesis was stopped by clamping the vessel stump with titanium clips but caused acute pancreatitis. Reviewing the treatment, electrocoagulation might be a better choice, and life support treatment, including central vena catheterization and an adequate supply of blood products, should be prepared in advance to provide extra time for the stent placement or vascular intervention treatment.
Elevated inorganic carbon and salinity enhances photosynthesis and ATP synthesis in picoalga Picocystis salinarum as revealed by label free quantitative proteomics
Authors: Singh Jyoti , Kaushik Shubham , Maharana Chinmaya , Jhingan Gagan Deep , Dhar Dolly Wattal
Published: March 2023

Saline soda lakes are of immense ecological value as they niche some of the most exclusive haloalkaliphilic communities dominated by bacterial and archaeal domains, with few eukaryotic algal representatives. A handful reports describe Picocystis as a key primary producer with great production rates in extremely saline alkaline habitats. An extremely haloalkaliphilic picoalgal strain, Picocystis salinarum SLJS6 isolated from hypersaline soda lake Sambhar, Rajasthan, India, grew robustly in an enriched soda lake medium containing mainly Na2CO3, 50 g/l; NaHCO3, 50 g/l, NaCl, 50 g/l (salinity ≈150‰) at pH 10. To elucidate the molecular basis of such adaptation to high inorganic carbon and NaCl concentrations, a high-throughput label-free quantitation based quantitative proteomics approach was applied. Out of the total 383 proteins identified in treated samples, 225 were differentially abundant proteins (DAPs), of which 150 were statistically significant (p < 0.05) including 70 upregulated and 64 downregulated proteins after 3 days of growth in highly saline-alkaline medium. Most DAPs were involved in photosynthesis, oxidative phosphorylation, glucose metabolism and ribosomal structural components envisaging that photosynthesis and ATP synthesis were central to the salinity-alkalinity response. Key components of photosynthetic machinery like photosystem reaction centres, adenosine triphosphate (ATP) synthase ATP, Rubisco, Fructose-1,6-bisphosphatase, Fructose-bisphosphate aldolase were highly upregulated. Enzymes peptidylprolyl isomerases (PPIase), important for correct protein folding showed remarkable marked-up regulation along with other chaperon proteins indicating their role in osmotic adaptation. Enhanced photosynthetic activity exhibited by P. salinarum in highly saline-alkaline condition is noteworthy as photosynthesis is suppressed under hyperosmotic conditions in most photosynthetic organisms. The study provided the first insights into the proteome of extremophilic alga P. salinarum exhibiting extraordinary osmotic adaptation and proliferation in polyextreme conditions prevailing in saline sodic ecosystems, potentially unraveling the basis of resilience in this not so known organism and paves the way for a promising future candidate for biotechnological applications and model organism for deciphering the molecular mechanisms of osmotic adaptation. The mass spectrometry proteomics data is available at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD037170.
Concise review: Current understanding of extracellular vesicles to treat neuropathic pain
Authors: Zhang Kexin , Li Pei , Jia Yuanyuan , Liu Ming , Jiang Jingjing
Published: March 2023

Extracellular vesicles (EVs) including exosomes are vesicular vesicles with phospholipid bilayer implicated in many cellular interactions and have the ability to transfer multiple types of cargo to cells. It has been found that EVs can package various molecules including proteins and nucleic acids (DNA, mRNA, and noncoding RNA). The discovery of EVs as carriers of proteins and various forms of RNA, such as microRNAs (miRNA) and long noncoding RNAs (lncRNA), has raised great interest in the field of drug delivery. Despite the underlying mechanisms of neuropathic pain being unclear, it has been shown that uncontrolled glial cell activation and the neuroinflammation response to noxious stimulation are important in the emergence and maintenance of neuropathic pain. Many studies have demonstrated a role for noncoding RNAs in the pathogenesis of neuropathic pain and EVs may offer possibilities as carriers of noncoding RNAs for potential in neuropathic pain treatment. In this article, the origins and clinical application of EVs and the mechanism of neuropathic pain development are briefly introduced. Furthermore, we demonstrate the therapeutic roles of EVs in neuropathic pain and that this involve vesicular regulation of glial cell activation and neuroinflammation.
Effectiveness of non-pharmacological therapies on cognitive function in patients with dementia—A network meta-analysis of randomized controlled trials
Authors: Luo Guangxin , Zhang Junqiu , Song Zeyi , Wang Ying , Wang Xiaojing , Qu Haifeng , Wang Fang , Liu Chengjiang , Gao Fujia
Published: March 2023

Objective

Non-pharmacological therapies (NPTs) have received increasing attention from researchers as a category of treatment to improve cognitive impairment in patients with dementia because of their fewer side effects. In this study, photobiomodulation (PBM), enriched environment (EE), exercise therapy (ET), computerized cognitive training (CCT), and cognitive stimulation therapy (CST) were selected to compare the effects of NPTs that improve dementia by quantifying information from randomized controlled trials (RCTs).

Methods

We did a systematic review and network meta-analysis. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database, Wan Fang Database, Chinese Biomedical Literature Database, Web of Science, and VIP Database from the time of database creation to 1 August 2022. Two investigators independently screened the literature, extracted information, and assessed the RCTs’ quality with the Cochrane Collaboration Network Risk of Bias 2.0. Network meta-analysis was performed using R language (X64 version 4.1.3) and STATA 17.0.

Results

We identified 1,268 citations and of these included 38 trials comprising 3,412 participants. For improving dementia, the results of the network meta-analysis showed that compared with the control group (CON), PBM (SMD = 0.90, 95% CI: 0.43–1.37), EE (SMD = 0.71, 95% CI: 0.02–1.41), ET (SMD = 0.42, 95% CI: 0.16–0.68), and CST (SMD = 0.36, 95% CI: 0.11–0.62) were significantly different (P < 0.05); There was no significant difference in CCT (SMD = 0.41, 95% CI: −0.07–0.88) (P > 0.05). The ranked results showed that PBM has more potential to be the best intervention (P = 0.90). In addition, there was a significant difference between PBM and CST in improving cognitive function (SMD = 0.54, 95% CI: 0.00; 1.08, P < 0.05).

Conclusion

In this study, NPTs have excellent potential to improve cognition in people with dementia, and PBM may have more significant benefits in improving cognition than the other four NPTs.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022363746.
BAMBI: A new method for automated assessment of bidirectional early-life interaction between maternal behavior and pup vocalization in mouse dam-pup dyads
Authors: Winters Carmen , Gorssen Wim , Wöhr Markus , D’Hooge Rudi
Published: March 2023

Vital early-life dyadic interaction in mice requires a pup to signal its needs adequately, and a dam to recognize and respond to the pup’s cues accurately and timely. Previous research might have missed important biological and/or environmental elements of this complex bidirectional interaction, because it often focused on one dyadic member only. In laboratory rodents, the Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care. The present study describes BAMBI (Bidirectional Automated Mother-pup Behavioral Interaction test), a novel automated PRT methodology based on synchronous video recording of maternal behavior and audio recording of pup vocalizations, which allows to assess bidirectional dam-pup dyadic interaction. We were able to estimate pup retrieval and pup vocalization parameters accurately in 156 pups from 29 dams on postnatal days (PND) 5, 7, 9, 11, and 13. Moreover, we showed an association between number of emitted USVs and retrieval success, indicating dyadic interdependency and bidirectionality. BAMBI is a promising new automated home-cage behavioral method that can be applied to both basic and preclinical studies investigating complex phenotypes related to early-life social development.
Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study
Authors: Krymchantowski Abouch V. , Jevoux Carla , Krymchantowski Ana Gabriela , Silva-Néto Raimundo Pereira
Published: March 2023

Background

Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks.

Objective

We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH).

Methods

A cross-sectional, prospective, randomized, open study with real-world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs.

Results

A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001).

Conclusions

The addition of an anti-CGRP monoclonal antibody to the treatment for medication overuse headaches in chronic migraineurs may result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs.
Case report: Left gaze and facial nerve palsies after ventral intermediate thalamic nucleus deep brain stimulation implantation
Authors: Cegielski Victoria , Gratton Sean
Published: March 2023

Deep brain stimulation (DBS) to the ventral intermediate nucleus (VIM) of the thalamus has become a common procedure for some refractory, medication-resistant movement disorders like essential tremors. The most common adverse effects from this surgery include dysarthria and gait disturbances. This case report details a left gaze and ipsilateral facial nerve palsy following overshot cannula insertion into the pons during a VIM DBS procedure. Initial patient presentation after surgery revealed significant impairment of horizontal gaze to the left. This improved during follow-up visits and after the recession of the bilateral medial recti. When considering complications of the VIM DBS procedure, surgeons should be aware of the risks of cannula overshot given the anatomic proximity between the thalamus and brainstem. Furthermore, patients should be aware of this risk when making their surgical decision. All patients who undergo VIM DBS should be assessed for cranial nerve deficits after placement.
The impact of different corneal refractive surgeries on binocular dynamic visual acuity
Authors: Wang Yuexin , Guo Yining , Li Yuanting , Zhang Yu , Yuan Yifei , Wu Tingyi , Chen Yueguo , Li Xuemin
Published: March 2023

Purpose

To investigate the influence of different corneal refractive surgeries on dynamic visual acuity (DVA), and explore its potential influence factors.

Methods

This was a prospective non-randomized study. Adult myopic patients undergoing bilateral laser-assisted sub-epithelial keratomileusis (LASEK), femtosecond laser-assistedin situkeratomileusis (FS-LASIK), or small incision lenticule extraction (SMILE) with Plano refraction target were enrolled. Uncorrected and corrected distance visual acuity (UDVA/CDVA), manifest refraction and binocular optotype-moving DVA of 40 and 80 degrees per second (dps) were evaluated pre-operatively and post-operatively up to 3 months.

Results

The study included 264 eyes of 132 subjects, with an average age of 27.0 ± 6.7 years, and females accounted for 59% of the participants. Significant improvement was observed at the 3-month visit for 40 dps (SMILE,P= 0.001; LASEK,P= 0.006; FS-LASIK,P= 0.010) and 80 dps (SMILE,P= 0.011; LASEK,P= 0.025; FS-LASIK,P= 0.012) DVA. Adjusting for pre-operative DVA, there was no significant difference in DVA among groups at 3 months post-operatively (P> 0.05 for multiple comparisons). Overall, multiple linear models demonstrated that post-operative DVA at 3 months was correlated with pre-operative DVA (40 dps, β = 0.349,P= 0.001; 80 dps, β = 0.447,P< 0.001), pre-operative spherical equivalent (40 dps, β = 0.311,P= 0.003; 80 dps, β = 0.261,P= 0.009) and post-operative UDVA (40 dps, β = −0.224,P= 0.024; 80 dps, β = −0.188,P= 0.05).

Conclusion

Dynamic visual acuity at 3 months post-operatively of the three corneal refractive surgeries was better than that before the surgery in adult myopic patients, and there was no significant difference among different surgical techniques. Post-operative DVA at 3 months was found correlated with pre-operative DVA, pre-operative SE, and post-operative UDVA. With further improvement, DVA could be a promising functional visual indicator for myopic patients undergoing refractive surgeries.
Effects of neurofeedback training combined with transcranial direct current stimulation on motor imagery: A randomized controlled trial
Authors: Sawai Shun , Murata Shin , Fujikawa Shoya , Yamamoto Ryosuke , Shima Keisuke , Nakano Hideki
Published: March 2023

Introduction

Neurofeedback (NFB) training and transcranial direct current stimulation (tDCS) have been shown to individually improve motor imagery (MI) abilities. However, the effect of combining both of them with MI has not been verified. Therefore, the aim of this study was to examine the effect of applying tDCS directly before MI with NFB.

Methods

Participants were divided into an NFB group (n = 10) that performed MI with NFB and an NFB + tDCS group (n = 10) that received tDCS for 10 min before MI with NFB. Both groups performed 60 MI trials with NFB. The MI task was performed 20 times without NFB before and after training, and μ-event-related desynchronization (ERD) and vividness MI were evaluated.

Results

μ-ERD increased significantly in the NFB + tDCS group compared to the NFB group. MI vividness significantly increased before and after training.

Discussion

Transcranial direct current stimulation and NFB modulate different processes with respect to MI ability improvement; hence, their combination might further improve MI performance. The results of this study indicate that the combination of NFB and tDCS for MI is more effective in improving MI abilities than applying them individually.
Analysis of the active ingredients and health applications of cistanche
Authors: Zhou Shiqi , Feng Duo , Zhou Yaxi , Duan Hao , Jiang Yongjun , Yan Wenjie
Published: March 2023

Cistanche is a tonic Chinese medicine commonly used in traditional Chinese medicine, with 2016, CFSA through the alxa desert cistanche safety evaluation, cistanche began to officially enter the food field. At present, the research on cistanche mainly focuses on the extraction, isolation and purification and pharmacological effects, and its pharmacological effects such as neuroprotective effects, immunomodulation, antioxidant anticancer and hepatoprotective liver protection have attracted the attention of researchers. This review mainly reviews the research status, chemical composition and health benefits, analyzes its application prospects in food, and aims to provide certain theoretical support for the safe application of cistanche in functional food.
Case report: A novel mutation in RTEL1 gene in dyskeratosis congenita
Authors: Nisar Haider , Khan Memoona , Chaudhry Qamar Un Nisa , Iftikhar Raheel , Ghafoor Tariq
Published: March 2023

Dyskeratosis congenita (DKC), also known as Zinsser–Cole–Engman syndrome, is a telomeropathy typically presenting as a triad of leukoplakia, nail dystrophy, and reticular hyperpigmentation. Reported genetic mutations linked to DKC include DKC1, TINF2, TERC, TERT, C16orf57, NOLA2, NOLA3, WRAP53/TCAB1, and RTEL1. Homozygous, compound heterozygous, and heterozygous mutations in RTEL1 (RTEL1, regulator of telomere elongation helicase 1) gene on chromosome 20q13 are known to cause autosomal dominant as well as recessive DKC. Pathogenic variants of RTEL1 gene in DKC patients include c.2288G>T (p. Gly763Val), c.3791G>A (p. Arg1264His), and RTEL p. Arg981Trp. We report a novel homozygous variant of RTEL1, transcript ID: ENST00000360203.11, exon 24, c.2060C>T (p.Ala687Val), in a patient of DKC presenting with leukoplakia, dystrophic nails, reticulate pigmentation, and positive family history of a similar phenotype. The novel variant, reported as a variant of uncertain significance, may therefore be considered diagnostic for DKC in a Pakistani population.
Severe pediatric asthma therapy: Omalizumab—A systematic review and meta-analysis of efficacy and safety profile
Authors: Fenu Grazia , La Tessa Andrea , Calogero Claudia , Lombardi Enrico
Published: March 2023

Background

Omalizumab is the first biological therapy used to treat moderate-to-severe asthma and certainly the one with the highest number of publications.

Methods

A systematic review and meta-analysis were performed to examine two critical outcomes of omalizumab therapy, asthma exacerbation rate, the reduction of the use of inhaled corticosteroids (ICS), and the improvement of the lung function as a secondary outcome using the following keywords in the MEDLINE database: “anti-IgE, severe asthma, children, and randomized controlled trial.” We specifically selected papers that included moderate-to-severe asthma patients and collected data on children and adolescents.

Results

Four RCT studies (total number of patients = 1,239) were included in the analysis. The reported data on exacerbations showed an overall improvement in the exacerbation rate with a decreased use of inhaled steroids and some other minimal clinically important difference (MCID).

Conclusions

Our systematic review confirms the known findings that omalizumab therapy decreases asthma exacerbation rate and reduces background therapy inhaled steroid dose. Therefore, add-on therapy with omalizumab shows a good efficacy and safety profile, thus proving to be a useful additional therapeutic option.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42023396785.
Case report: Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay: Three cases and a literature review
Authors: Chen Xiangyuan , Fu Fang , Mo Xiaolan , Cheng Suyun , Zeng Huasong
Published: March 2023

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is a serious autosomal recessive syndrome caused by biallelic mutations in cytosine–cytosine–adenosine tRNA nucleotidyltransferase 1 (TRNT1). The main clinical features of SIFD are periodic fevers, developmental delay, sideroblastic or microcytic anemia, and immunodeficiency. Herein, we report three cases of SIFD with compound heterozygous variants of TRNT1. Patients 1 and 2 were siblings; they presented with periodic fevers, arthritis, low immunoglobulin A, bilateral cataracts, anemia, and neurodevelopmental and developmental delay. Patient 3 had severed clinical features with recurrent fever and infections. She was treated with infliximab and symptomatic treatments but without therapeutic effect. She received a stem cell transplantation of umbilical cord blood but died of posttransplant infection and posttransplant graft-vs.-host disease 17 days after transplantation. Finally, a literature review revealed that TRNT1 variants differed among SIFD patients. Our cases and literature review further expand existing knowledge on the phenotype and TRNT1 variations of SIFD and suggest that the early genomic diagnosis of TRNT1 is valuable to promptly assess bone marrow transplantation and tumor necrosis factor inhibitor treatments, which might be effective for the immunodeficiency and inflammation caused by SIFD.
Urea cycle disorders and indications for liver transplantation
Authors: García Vega Marta , Andrade José D. , Morais Ana , Frauca Esteban , Muñoz Bartolo Gema , Lledín María D. , Bergua Ana , Hierro Loreto
Published: March 2023

Urea cycle disorders (UCD) are inborn errors of metabolism caused by deficiency of enzymes required to convert nitrogen from ammonia into urea. Current paradigms of treatment focus on dietary manipulations, ammonia scavenger drugs, and liver transplantation. The aim of this study was to describe the characteristics and indication of liver transplantation in UCD in a tertiary hospital. We performed a retrospective study of children with UCD seen in the period 2000–2021. Data was collected on clinical onset, hyperammonemia severity, evolution and liver transplantation. There were 33 patients in the study period, whose diagnosis were: ornithine transcarbamylase (OTC, n = 20, 10 females), argininosuccinate synthetase (ASS, n = 6), carbamylphosphate synthetase 1 (CPS1, n = 4), argininosuccinate lyase (ASL, n = 2) and N-acetylglutamate synthetase (NAGS, n = 1) deficiency. Thirty one were detected because of clinical symptoms (45% with neonatal onset). The other 2 were diagnosed being presymptomatic, by neonatal/family screening. Neonatal forms (n = 14) were more severe, all of them presented during the first week of life as severe hyperammonemia (mean peak 1,152 µmol/L). Seven patients died (6 at debut) and all survivors received transplantation. There was no mortality among the late forms. Of the 27 patients who did not die in the neonatal period, 16 (59%) received liver transplantationwith 100% survival, normal protein tolerance and usual need of citrulline supplementation. The transplant's metabolic success was accompanied by neurologic sequelae in 69%, but there was no progression of brain damage. Decision of continuous medical treatment in 11 patients appeared to be related with preserved neurodevelopment and fewer metabolic crises.
Detoxification of comfrey (Symphytum officinale L.) extract using natural deep eutectic solvent (NADES) and evaluation of its anti-inflammatory, antioxidant, and hepatoprotective properties
Authors: Syarifah Andiri Niza , Suryadi Herman , Hayun Hayun , Simamora Adelina , Mun’im Abdul
Published: March 2023

Comfrey (Symphytum officinale L.) contains rosmarinic acid which has different pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the medicinal use of comfrey is limited by the hepatotoxic effect of lycopsamine in comfrey, which overshadows the health benefits of rosmarinic acid. Natural deep eutectic solvents (NADES) have a wide range of extraction properties, that provides a new approach to the detoxification of comfrey. In the present study, betaine-based and choline chloride-based NADES were screened for selective extraction of rosmarinic acid over lycopsamine. Ultrasonication was used in conjunction with NADES extraction. The chemical profile of the NADES extracts on antioxidant, anti-inflammatory and hepatotoxic activities were investigated using some chemical reagents. Betaine-urea (1:2 molar ratio, 50% water) obtained the highest content of rosmarinic acid and a low level of lycopsamine (1.934 and 0.018 mg/g, respectively). Betaine-urea was also shown to be more effective to extract rosmarinic acid compared to methanol-UAE under the same conditions, which gave lower rosmarinic acid and higher lycopsamine levels (0.007 and 0.031 mg/g, respectively). Betaine-urea extracts showed higher antioxidant and anti-inflammatory properties as compared with other NADES extracts, however, had lower hepatotoxic profile. This study recommends the use of betaine-urea to detroxify comfrey to open wider opportunities for the development of comfrey for medicinal use.