bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents
Authors: Perrone Benedetta , Ruffo Paola , Augimeri Giuseppina , Sisci Diego , Sinicropi Maria Stefania , Tripepi Giovanni , Mammì Corrado , Bonofiglio Daniela , Conforti Francesca Luisa
Published: October 2023

Background

The complex interplay between health, lifestyle and genetics represents a critical area of research for understanding and promoting human well-being. Importantly, genetics plays a key role in determining individual susceptibility to disease and response to lifestyle. The aim of the present study was to identify genetic factors related to the metabolic/inflammatory profile of adolescents providing new insights into the individual predisposition to the different effects of the substances from the environment.

Methods

Association analysis of genetic variants and biochemical parameters was performed in a total of 77 healthy adolescents recruited in the context of the DIMENU study.

Results

Polymorphisms of 3-hydroxy-3-methylglutaril coenzyme A reductase (HMGCR; rs142563098), C-reactive protein gene (CRP; rs1417938, rs1130864), cholesteryl ester transfer protein (CETP; rs5030708), interleukin (IL)—10 (IL-10; rs3024509) genes were significantly associated (p < 0.05) with various serum metabolic parameters. Of particular interest were also the correlations between the HMGCRpolymorphism (rs3846663) and tumor necrosis factor (TNF)-α levels, as well Fatty-acid desaturase (FADS) polymorphism (rs7481842) and IL-10 level opening a new link between lipidic metabolism genes and inflammation.

Conclusion

In this study, we highlighted associations between single nucleotide polymorphisms (SNPs) and serum levels of metabolic and inflammatory parameters in healthy young individuals, suggesting the importance of genetic profiling in the prevention and management of chronic disease.
Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum
Authors: Gamage Rashmi , Rossetti Ilaria , Niedermayer Garry , Münch Gerald , Buskila Yossi , Gyengesi Erika
Published: October 2023

Background

Low-grade, chronic inflammation in the central nervous system characterized by glial reactivity is one of the major hallmarks for aging-related neurodegenerative diseases like Alzheimer’s disease (AD). The basal forebrain cholinergic neurons (BFCN) provide the primary source of cholinergic innervation of the human cerebral cortex and may be differentially vulnerable in various neurodegenerative diseases. However, the impact of chronic neuroinflammation on the cholinergic function is still unclear.

Methods

To gain further insight into age-related cholinergic decline, we investigated the cumulative effects of aging and chronic neuroinflammation on the structure and function of the septal cholinergic neurons in transgenic mice expressing interleukin-6 under the GFAP promoter (GFAP-IL6), which maintains a constant level of gliosis. Immunohistochemistry combined with unbiased stereology, single cell 3D morphology analysis and in vitro whole cell patch-clamp measurements were used to validate the structural and functional changes of BFCN and their microglial environment in the medial septum.

Results

Stereological estimation of MS microglia number displayed significant increase across all three age groups, while a significant decrease in cholinergic cell number in the adult and aged groups in GFAP-IL6 mice compared to control. Moreover, we observed age-dependent alterations in the electrophysiological properties of cholinergic neurons and an increased excitability profile in the adult GFAP-IL6 group due to chronic neuroinflammation. These results complimented the significant decrease in hippocampal pyramidal spine density seen with aging and neuroinflammation.

Conclusions

We provide evidence of the significant impact of both aging and chronic glial activation on the cholinergic and microglial numbers and morphology in the MS, and alterations in the passive and active electrophysiological membrane properties of septal cholinergic neurons, resulting in cholinergic dysfunction, as seen in AD. Our results indicate that aging combined with gliosis is sufficient to cause cholinergic disruptions in the brain, as seen in dementias.
Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis
Authors: Zheng Rong , Zhang Weijie , Song Jufang , Zhong Yifei , Zhu Rong
Published: October 2023

Background

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were used to evaluate the diagnostic value of CRD.

Methods

Quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence analysis, and immunohistochemical staining were used to assess changes in mRNA and protein expression. Oxidative stress was evaluated by detecting the production of reactive oxygen species (ROS) and the activity of antioxidant enzymes. Cell apoptosis was detected by the TUNEL and flow cytometric methods. The interaction of miR-193b-5p and myeloid leukemia 1 (MCL-1) was examined by bioinformatics analysis and luciferase reporter assay. The protective effects of CRD on DN mice were evaluated by examining DN related biochemical indicators and renal histopathology.

Results

In response to HG, the level of miR-193b-5p was elevated, whilst the level of MCL-1 was downregulated, and CRD therapy reversed this behavior. MCL-1 was further identified to be miR-193b-5p target. CRD attenuated HG-induced cell damage, inflammation and abnormal energy metabolism. Mechanistic investigations on in vitro models confirmed that protective effect of CRD against HG challenge to HK-2 cells is mediated through the regulation of expression of miR-193b-5p/MCL-1 axis. By examining DN related biochemical markers and renal histopathology, the protective effects of CRD on DN mice was assessed.

Conclusions

In summary, CRD decreased oxidative stress and inflammation by increasing miR-193b-5p and inactivating downstream MCL-1 in DN, hinting the pivotal values of CRD and miR-193b-5p in the management of DN.
The Tuscany Regional Network for rare diseases: from European Reference Networks’ experience to registry based organisation and management model for rare diseases
Authors: Pieroni Federica , Marrucci Sonia , Di Pietro Linda , Berni Cecilia , Scaletti Cristina
Published: October 2023

Background

In the European Union, a disease is defined as rare when it affects fewer than 1 in 2000 people. Currently, there are up to 8000 described rare diseases (RDs), collectively affecting 30 million people in the European Union. In 2004 Tuscany region (Italy) established a Regional Network of hospital units to ensure highly specialised medical care in the field of RDs. Shortly after the Rare Diseases Registry of Tuscany (Registro Toscano Malattie Rare—RTMR) was implemented. Here we describe the analysis performed on RTMR data which has recently allowed to remap the Network based on European Reference Networks’ model.

Results

Data analysis was performed on 60,367 cases registered in RTMR, regarding 628 RDs. Two-hundred and fifteen active presidia have been evaluated. The assignment of each RD to the suitable European Reference Network has been made considering not only the number of registered cases, certifications and treatment plans for each Regional Presidium but also the competence in multidisciplinary management of the patient, from diagnosis to treatment. This evaluation has led to the establishment of twenty-one Regional Coordination Centres. They aggregate and coordinate Hospital Units which diagnose and treat one or a group of related RDs. In case of wide groups of RDs, Clinical Subnets are instituted. Updated statistics regarding RDs in Tuscany, list of RDs and Coordination Centres, as well as information about single Presidia are published and freely available on a designated webpage. Regional Decrees are regularly updated according to the network evolution.

Conclusions

The Rare Diseases Regional Network in Tuscany, based on the ERN model, has played a pivotal role in enhancing RD management and research. The remapping has led to a dynamic system, following not only scientific research but also the development of Presidia’s expertise. By pooling resources and expertise, the network has improved the availability and accessibility of specialized care for patients with RDs. Collaborative efforts, data sharing, and standardized registries are crucial for advancing RD research, improving diagnosis and treatment, and ultimately enhancing the quality of life for individuals living with RDs.
Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services
Authors: Sanza Michele , Monzio Compagnoni Matteo , Caggiu Giulia , Allevi Liliana , Barbato Angelo , Campa Jeannette , Carle Flavia , D’avanzo Barbara , Di Fiandra Teresa , Ferrara Lucia , Gaddini Andrea , Saponaro Alessio , Scondotto Salvatore , Tozzi Valeria D , Lorusso Stefano , Giordani Cristina , Corrao Giovanni , Lora Antonio
Published: October 2023

Background

Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily).

Methods

A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions.

RESULTS

31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments.

Conclusions

Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths.
Factors affecting cumulative live birth rate after the 1st oocyte retrieved in polycystic ovary syndrome patients in women during IVF/ICSI-ET
Authors: Li You , Xia Leizhen , Li Zengming , Zhang Ziyu , Jiang Ru
Published: October 2023

Background

The factors affecting the cumulative live birth rate (CLBR) of PCOS (Polycystic ovary syndrom) patients who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) needs more research for a better outcome.

Methods

Here we carried out a retrospective analysis of 1380 PCOS patients who received IVF/ICSI-ET for the first time from January 2014 to December 2016. We divided them into cumulative live birth group (group A) and non-cumulative live birth group (group B) according to whether there were live births.

Results

The conservative cumulative live birth rate was 63.48%. There were 876 cumulative live births (group A) and 504 non-cumulative live births (group B) according to whether the patients had live births or not. Competition analysis showed that duration of infertility, primary/secondary type of infertility, stimulation protocols, starting dose of gonadotrophins and oocyte retrieved numbers were significantly correlated with CLBR. The Cox proportional risk regression model of PCOS patients showed that stimulation protocols had a significant impact on CLBR. Patients in the GnRH (Gonadotropin-releasing hormone)-antagonist protocol group and the mild stimulation protocol had lower CLBR than those in the prolonged GnRH-agonist protocol, which was statistically significant. PCOS patients with the starting dose of gonadotrophins greater than 112.5u had lower CLBR than those with less than 100u, which was statistically significant. Women with 11–15 oocytes and 16–20 oocytes had higher CLBR than women with 1–9 oocytes, which was statistically significant.

Conclusions

When we used Prolonged GnRH-agonist protocol, or the first starting dose of gonadotrophins was 100u-112.5u, or the number of oocytes obtained was 11–15 and 16–20, the CLBR of PCOS patients increased significantly after the 1st oocyte collection.
Procalcitonin-guided antibiotic therapy may shorten length of treatment and may improve survival—a systematic review and meta-analysis
Authors: Papp Márton , Kiss Nikolett , Baka Máté , Trásy Domonkos , Zubek László , Fehérvári Péter , Harnos Andrea , Turan Caner , Hegyi Péter , Molnár Zsolt
Published: October 2023

Background

Appropriate antibiotic (AB) therapy remains a challenge in the intensive care unit (ICU). Procalcitonin (PCT)-guided AB stewardship could help optimize AB treatment and decrease AB-related adverse effects, but firm evidence is still lacking. Our aim was to compare the effects of PCT-guided AB therapy with standard of care (SOC) in critically ill patients.

Methods

We searched databases CENTRAL, Embase and Medline. We included randomized controlled trials (RCTs) comparing PCT-guided AB therapy (PCT group) with SOC reporting on length of AB therapy, mortality, recurrent and secondary infection, ICU length of stay (LOS), hospital LOS or healthcare costs. Due to recent changes in sepsis definitions, subgroup analyses were performed in studies applying the Sepsis-3 definition. In the statistical analysis, a random-effects model was used to pool effect sizes.

Results

We included 26 RCTs (n = 9048 patients) in the quantitative analysis. In comparison with SOC, length of AB therapy was significantly shorter in the PCT group (MD − 1.79 days, 95% CI: -2.65, − 0.92) and was associated with a significantly lower 28-day mortality (OR 0.84, 95% CI: 0.74, 0.95). In Sepsis-3 patients, mortality benefit was more pronounced (OR 0.46 95% CI: 0.27, 0.79). Odds of recurrent infection were significantly higher in the PCT group (OR 1.36, 95% CI: 1.10, 1.68), but there was no significant difference in the odds of secondary infection (OR 0.81, 95% CI: 0.54, 1.21), ICU and hospital length of stay (MD − 0.67 days 95% CI: − 1.76, 0.41 and MD − 1.23 days, 95% CI: − 3.13, 0.67, respectively).

Conclusions

PCT-guided AB therapy may be associated with reduced AB use, lower 28-day mortality but higher infection recurrence, with similar ICU and hospital length of stay. Our results render the need for better designed studies investigating the role of PCT-guided AB stewardship in critically ill patients.

Graphical abstract
Interaction of Mesonivirus and Negevirus with arboviruses and the RNAi response in Culex tarsalis-derived cells
Authors: Agboli Eric , Schulze Jonny , Jansen Stephanie , Cadar Daniel , Sreenu Vattipally B. , Leggewie Mayke , Altinli Mine , Badusche Marlis , Jöst Hanna , Börstler Jessica , Schmidt-Chanasit Jonas , Schnettler Esther
Published: October 2023

Background

Mosquito-specific viruses (MSVs) comprise a variety of different virus families, some of which are known to interfere with infections of medically important arboviruses. Viruses belonging to the family Mesoniviridae or taxon Negevirus harbor several insect-specific viruses, including MSVs, which are known for their wide geographical distribution and extensive host ranges. Although these viruses are regularly identified in mosquitoes all over the world, their presence in mosquitoes in Germany had not yet been reported.

Methods

A mix of three MSVs (Yichang virus [Mesoniviridae] and two negeviruses [Daeseongdong virus and Dezidougou virus]) in a sample that contained a pool of Coquillettidia richiardii mosquitoes collected in Germany was used to investigate the interaction of these viruses with different arboviruses in Culex-derived cells. In addition, small RNA sequencing and analysis of different mosquito-derived cells infected with this MSV mix were performed.

Results

A strain of Yichang virus (Mesoniviridae) and two negeviruses (Daeseongdong virus and Dezidougou virus) were identified in the Cq. richiardii mosquitoes sampled in Germany, expanding current knowledge of their circulation in central Europe. Infection of mosquito-derived cells with these three viruses revealed that they are targeted by the small interfering RNA (siRNA) pathway. In Culex-derived cells, co-infection by these three viruses had varying effects on the representative arboviruses from different virus families (Togaviridae: Semliki forest virus [SFV]; Bunyavirales: Bunyamwera orthobunyavirus [BUNV]; or Flaviviridae: Usutu virus [USUV]). Specifically, persistent MSV co-infection inhibited BUNV infection, as well as USUV infection (but the latter only at specific time points). However, the impact on SFV infection was only noticeable at low multiplicity of infection (MOI 0.1) and at specific time points in combination with the infection status.

Conclusions

Taken together, these results are important findings that will lead to a better understanding of the complex interactions of MSVs, mosquitoes and arboviruses.

Graphical Abstract
Biomarkers in Alzheimer’s disease: role in early and differential diagnosis and recognition of atypical variants
Authors: Dubois Bruno , von Arnim Christine A. F. , Burnie Nerida , Bozeat Sasha , Cummings Jeffrey
Published: October 2023

Background

Development of in vivo biomarkers has shifted the diagnosis of Alzheimer’s disease (AD) from the later dementia stages of disease towards the earlier stages and has introduced the potential for pre-symptomatic diagnosis. The International Working Group recommends that AD diagnosis is restricted in the clinical setting to people with specific AD phenotypes and supportive biomarker findings.

Main body

In this review, we discuss the phenotypic presentation and use of biomarkers for the early diagnosis of typical and atypical AD and describe how this can support clinical decision making, benefit patient communication, and improve the patient journey. Early diagnosis is essential to optimize the benefits of available and emerging treatments. As atypical presentations of AD often mimic other dementias, differential diagnosis can be challenging and can be facilitated using AD biomarkers. However, AD biomarkers alone are not sufficient to confidently diagnose AD or predict disease progression and should be supplementary to clinical assessment to help inform the diagnosis of AD.

Conclusions

Use of AD biomarkers with incorporation of atypical AD phenotypes into diagnostic criteria will allow earlier diagnosis of patients with atypical clinical presentations that otherwise would have been misdiagnosed and treated inappropriately. Early diagnosis is essential to guide informed discussion, appropriate care and support, and individualized treatment. It is hoped that disease-modifying treatments will impact the underlying AD pathology; thus, determining the patient’s AD phenotype will be a critical factor in guiding the therapeutic approach and the assessment of the effects of interventions.
Sustainable municipal wastewater treatment using an innovative integrated compact unit: microbial communities, parasite removal, and techno-economic analysis
Authors: El-Khateeb Mohamed , Hassan Gamal K. , El-Liethy Mohamed Azab , El-Khatib Kamel M. , Abdel-Shafy Hussein I. , Hu Anyi , Gad Mahmoud
Published: October 2023

Background

The upflow anaerobic sludge blanket (UASB) reactors rely on bacterial communities to break down pollutants in wastewater (municipal or industrial).

Methods and results

In this study, a novel combination of UASB followed by aerobic treatment has been proposed for the treatment of municipal wastewater focusing on bacterial communities using high-throughput sequencing and parasite removal in this novel combination of reactors. Moreover, economic estimation of the compact unit composed of two overlapping UASB reactors, followed by a downflow hanging non-woven fabric (DHNW) reactor, the anaerobic baffled reactor (ABR), and chlorine unit was investigated in this study based on community populations of 1000 and 10,000 inhabitants, with a municipal plant capacity of 54,000 and 540,000 m3/year. Cost estimation was conducted based on two scenarios, one considering the contingency cost and auxiliary facility, and the other excluding them. Non-metric multidimensional scaling (nMDS) revealed that the treatment stages structured the microbial communities. Proteobacteria was the most prevalent phylum in all treatment stages, followed by Bacteroidota in most stages. Firmicutes and Actinobacteria were also present in significant amounts. The treatment system achieved from 40 to 66.67% removal of parasites (parasitic nematode, Cryptosporidium, and microsporidia). Redundancy analysis (RDA) indicated a strong positive correlation between chemical and biological oxygen demand (COD/BOD) with Campylobacterales and could be used as a bioindicator of treatment performance.

Conclusion

These findings can inform the development of more efficient and sustainable wastewater treatment systems that take into account microbial ecology and economic considerations.
Patient education in atopic dermatitis: a scoping review
Authors: Wilken Bethany , Zaman M. , Asai Y.
Published: October 2023

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects children and adults. Poor treatment adherence in AD requires interventions to promote self-management; patient education in chronic diseases is key to self-management. Many international AD management guidelines published to date include a recommendation for educating patients as part of their treatment but there are no formal recommendations on how to deliver this knowledge.

Main

We performed a scoping review to map the existing literature on patient education practices in AD and to highlight the clinical need for improved patient education in AD. The literature search was performed with the online databases MEDLINE, Embase, Grey Matters, ClinicalTrails.gov and the International Clinical Trials Registry Platform (ICTRP). The search strategy yielded 388 articles. Of the 388 articles screened, 16 studies met the eligibility criteria, and the quantitative data was summarized by narrative synthesis. The majority of studies were randomized controlled trials conducted in Europe, Asia and North America. Since 2002, there have been limited studies evaluating patient education in the treatment of AD. Frequent education methods used included group-based educational programs, educational pamphlets, individual consultations and online resources. Education was most commonly directed at caregivers and their children. Only one study compared the efficacy of different education methods. In all included studies, the heterogenous nature of outcome measures and study design limited the consistency of results. Despite the heterogeneity of studies, patient education was shown to improve quality of life (QoL), disease severity and psychological outcomes in AD patients.

Conclusion

This scoping review highlights that patient education is effective in a variety of domains relevant to AD treatment. Further comparative studies and randomized trials with longer-term follow-up are needed to provide validated and consistent patient education recommendations for AD; these may depend on age and population.
Pax7 haploinsufficiency impairs muscle stem cell function in Cre-recombinase mice and underscores the importance of appropriate controls
Authors: Mademtzoglou Despoina , Geara Perla , Mourikis Philippos , Relaix Frederic
Published: October 2023

Ever since its introduction as a genetic tool, the Cre-lox system has been widely used for molecular genetic studies in vivo in the context of health and disease, as it allows time- and cell-specific gene modifications. However, insertion of the Cre-recombinase cassette in the gene of interest can alter transcription, protein expression, or function, either directly, by modifying the landscape of the locus, or indirectly, due to the lack of genetic compensation or by indirect impairment of the non-targeted allele. This is sometimes the case when Cre-lox is used for muscle stem cell studies. Muscle stem cells are required for skeletal muscle growth, regeneration and to delay muscle disease progression, hence providing an attractive model for stem cell research. Since the transcription factor Pax7 is specifically expressed in all muscle stem cells, tamoxifen-inducible Cre cassettes (CreERT2) have been inserted into this locus by different groups to allow targeted gene recombination. Here we compare the two Pax7-CreERT2 mouse lines that are mainly used to evaluate muscle regeneration and development of pathological features upon deletion of specific factors or pathways. We applied diverse commonly used tamoxifen schemes of CreERT2 activation, and we analyzed muscle repair after cardiotoxin-induced injury. We show that consistently the Pax7-CreERT2 allele targeted into the Pax7 coding sequence (knock-in/knock-out allele) produces an inherent defect in regeneration, manifested as delayed post-injury repair and reduction in muscle stem cell numbers. In genetic ablation studies lacking proper controls, this inherent defect could be misinterpreted as being provoked by the deletion of the factor of interest. Instead, using an alternative Pax7-CreERT2 allele that maintains bi-allelic Pax7 expression or including appropriate controls can prevent misinterpretation of experimental data. The findings presented here can guide researchers establish appropriate experimental design for muscle stem cell genetic studies.
Synthesis of Ni2+-functionalized polydopamine magnetic beads for facilitated purification of histidine-tagged proteins
Authors: Shariati Alireza , Hosseinzadeh Sara Ali , Barghi Zahra , Mortazavi Sogand Sadat , Atarod Kosar , Shariati Fatemeh Sadat , Farahmand Behrokh
Published: October 2023

Facilitated purification of proteins, at a low cost and a short time, is one of the key steps in the industrial production of recombinant proteins. In the current study, polydopamine nanoparticles (PDA-NPs) are considered in the synthesis of magnetic beads for purifying recombinant proteins due to advantages such as biocompatibility/ biodegradability, easy synthesis, as well as the ability to directly chelate metal ions. They were synthesized in Tris buffer (pH: 8:5), then chelated with Fe3+(20 mg) and Ni2+ ions at concentrations of 2, 3, 5, and 7 mg/ml. Prepared nanoparticles were characterized through scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), Inductively Coupled Plasma (ICP), and vibrating sample magnetometer (VSM). The size distribution of the particles was reported in the narrow range of 120–140 nm and 200 to 220 nm by the SEM image and DLS analysis, respectively. The chelation of ions on the surface of the nanoparticle was confirmed by the ICP technique with a magnetization of 35.42 emu/g. The highest adsorption rate of Ni2+ ions to polydopamine was obtained at a ratio of 1.4. The SDS-PAGE and western blot analysis confirmed the purification of eGFP and Hsp40 by PDA/Fe3+/Ni2+ at 26 and 40 kDa compared to the commercial nickel column. Moreover, the concentration of purified eGFP by PDA/Fe3+/Ni2+ was reported 138.83 µg/ml by the fluorescent signals, which is almost equal to or more than the protein purified by commercial Ni-NTA column (108.28 µg/ ml). The stability of PDA/Fe3+/Ni2+ has also been evaluated by ICP-OES for 10 days, and the result suggested that PDA magnetic beads were stable. Therefore, it can be concluded that PDA/Fe3+/Ni2+ have the ability to purify recombinant proteins in one less step and shorter time.
Transformer-based autoencoder with ID constraint for unsupervised anomalous sound detection
Authors: Guan Jian , Liu Youde , Kong Qiuqiang , Xiao Feiyang , Zhu Qiaoxi , Tian Jiantong , Wang Wenwu
Published: October 2023

Unsupervised anomalous sound detection (ASD) aims to detect unknown anomalous sounds of devices when only normal sound data is available. The autoencoder (AE) and self-supervised learning based methods are two mainstream methods. However, the AE-based methods could be limited as the feature learned from normal sounds can also fit with anomalous sounds, reducing the ability of the model in detecting anomalies from sound. The self-supervised methods are not always stable and perform differently, even for machines of the same type. In addition, the anomalous sound may be short-lived, making it even harder to distinguish from normal sound. This paper proposes an ID-constrained Transformer-based autoencoder (IDC-TransAE) architecture with weighted anomaly score computation for unsupervised ASD. Machine ID is employed to constrain the latent space of the Transformer-based autoencoder (TransAE) by introducing a simple ID classifier to learn the difference in the distribution for the same machine type and enhance the ability of the model in distinguishing anomalous sound. Moreover, weighted anomaly score computation is introduced to highlight the anomaly scores of anomalous events that only appear for a short time. Experiments performed on DCASE 2020 Challenge Task2 development dataset demonstrate the effectiveness and superiority of our proposed method.
Effects of exergaming on executive functions of children: a systematic review and meta-analysis from 2010 to 2023
Authors: Chen Jiaqi , Zhou Xiaojiao , Wu Xiangting , Gao Zan , Ye Sunyue
Published: October 2023

Background

Executive function plays a crucial role in children’s cognitive development, academic performance, as well as their physical and mental health. This study aims to assess the impact of exergaming on executive functions in pediatric populations.

Methods

The criteria of inclusion were randomized controlled trials of exergaming intervention and evaluation of executive function in children aged 4–12 years. A meta-analysis was performed in databases of China National Knowledge Infrastructure (in Chinese), Wan Fang (in Chinese), Web of Science, Embase, and PubMed, from January 2010 to February 2023, following the PRISMA guidelines. Risk of bias was assessed by the Jadad scale, the Cochrane risk of bias assessment tool, funnel plot, and regression-based Egger test. The Review Manager 5.3 was used to analyze the included articles using a random-effects model, and the effects were calculated as standardized mean difference (SMD).

Results

Eleven experimental studies with children (n = 508) were included. Exergaming was found to have a positive impact on children’s cognitive flexibility (SMD = 0.34, 95%CI [0.17,0.52], P < 0.01), inhibitory control (SMD = 0.57, 95%CI [0.31,0.83], P < 0.01), and working memory (SMD = 0.26, 95%CI [0.02,0.51], P < 0.05). The publication bias were observed.

Conclusions

Exergaming has the potential to improve executive functions in children. More studies with rigorous designs are warranted to explore the specific effects of exergaming intervention. This study was registered on the PROSPERO (CRD42023401526).
Comprehensive analysis of research related to rehabilitation and COVID-19, hotspots, mapping, thematic evolution, trending topics, and future directions
Authors: Abdelwahab Siddig Ibrahim , Taha Manal Mohamed Elhassan , Aldhahi Monira I.
Published: October 2023

Background

This study conducted a comprehensive analysis of research pertaining to the intersection of rehabilitation and COVID-19 (COV-REH). The main aim of this study is to analyze the thematic progression and hotspots, detect emerging topics, and suggest possible future research directions in the COV-REH.

Methods

Appropriate keywords were selected based on the Medical Subject Headings (MeSH) PubMed database and the Scopus database were used to retrieve a total of 3746 original studies conducted in the English language. The data extraction was performed on June 30, 2023. VOSviewer and Bibliometrix utilize CVS and BibTex files to facilitate the performance analysis and generate visual maps. The performance indicators reported for the research components of the COV-REH were compiled using the Scopus Analytics tool.

Results

From 2003 to 2023, 3470 authors from 160 organizations in 119 countries generated 3764 original research documents, with an annual growth of 53.73%. 1467 sources identified these scholarly works. Vitacca, M. (Italy), Harvard University (USA), and the USA published the most articles. This study included 54.1% of medical scholars. Telerehabilitation, exercise, quality of life, case reports, anxiety, and pulmonary rehabilitation were the primary themes of the COV-REH. One component of “telerehabilitation” is now the cardiac rehabilitation cluster. The trending topics in COV-REH are “symptoms,” “protocol,” and “community-based rehabilitation”.

Conclusions

This study proposed several significant research directions based on the current thematic map and its evolution. Given that COV-REH investigations have been determined to be multidisciplinary, this study contributes conceptually to several fields and has wide-ranging implications for practitioners and policymakers.
FGFR1 variants contributed to families with tooth agenesis
Authors: Yao Siyue , Zhou Xi , Gu Min , Zhang Chengcheng , Bartsch Oliver , Vona Barbara , Fan Liwen , Ma Lan , Pan Yongchu
Published: October 2023

Background

Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify possible genetic factors that underlie various forms of tooth agenesis and to investigate the possible molecular mechanisms through which human dental pulp stem cells may play a role in this condition.

Results

Using whole-exome sequencing of a Han Chinese family with non-syndromic tooth agenesis, a rare mutation in FGFR1 (NM_001174063.2: c.103G > A, p.Gly35Arg) was identified as causative and confirmed by Sanger sequencing. Via GeneMatcher, another family with a known variant (NM_001174063.2: c.1859G > A, p.Arg620Gln) was identified and diagnosed with tooth agenesis and a rare genetic disorder with considerable intrafamilial variability. Fgfr1 is enriched in the ectoderm during early embryonic development of mice and showed sustained low expression during normal embryonic development of Xenopus laevis frogs. Functional studies of the highly conserved missense variant c.103G > A showed deleterious effects. FGFR1 (c.103G > A) was overexpressed compared to wildtype and promoted proliferation while inhibiting apoptosis in HEK293 and human dental pulp stem cells. Moreover, the c.103G > A variant was found to suppress the epithelial-mesenchymal transition. The variant could downregulate ID4 expression and deactivate the TGF-beta signaling pathway by promoting the expression of SMAD6 and SMAD7.

Conclusion

Our research broadens the mutation spectrum associated with tooth agenesis and enhances understanding of the underlying disease mechanisms of this condition.
Comparison of whole blood cytokine immunoassays for rapid, functional immune phenotyping in critically ill patients with sepsis
Authors: Bonavia Anthony S. , Samuelsen Abigail , Liang Menglu , Hanson Jodi , McKeone Daniel , Chroneos Zissis C. , Halstead E. Scott
Published: October 2023

Background

Sepsis is characterized by highly heterogeneous immune responses associated with a spectrum of disease severity. Methods that rapidly and sensitively profile these immune responses can potentially personalize immune-adjuvant therapies for sepsis. We hypothesized that the ELLA microfluidic approach to measure cytokine production from the whole blood of septic and critically ill patients would deliver faster, more precise results than the existing optic-driven ELISpot quantification. We tested our hypothesis by measuring ex vivo-stimulated production of TNF and IFNγ in critically ill and septic patients (n = 22), critically ill and non-septic patients (n = 10), and healthy volunteers (n = 10) through both ELLA and ELISpot immunoassays. Blood samples were subjected to one of three stimulants for 4 h or 18 h durations during days 1, 7–10, and 14 of critical illness. Stimulants for lymphocytes included anti-CD3/anti-CD28 and phorbol 12-myristate 13-acetate (PMA), whereas LPS was used for monocytes. Stimulated TNF and IFNγ concentrations were then associated with 30-day mortality.

Results

Both ELISpot and ELLA immunoassays showed substantial agreement in TNF concentrations post 4 h and 18 h LPS stimulation, with concordance correlation coefficients at 0.62 and 0.60, respectively. ELLA had a broad dynamic measurement range and provided accurate TNF and IFNγ readings at both minimal and elevated cytokine concentrations (with mean coefficients of variation between triplicate readings at 2.1 ± 1.4% and 4.9 ± 7.2%, respectively). However, there was no association between the ELLA-determined cytokine concentrations on the first day of critical illness and 30-day mortality rate. In contrast, using the ELISpot for cytokine quantification revealed that non-survivors had reduced baseline TNF levels at 18 h, decreased LPS-induced TNF levels at 18 h, and diminished TNF levels post 4 h/18 h anti-CD3/28 stimulation.

Conclusions

Our study affirms the feasibility of obtaining dependable immune phenotyping data within 6 h of blood collection from critically ill patients, both septic and non-septic, using the ELLA immunoassay. Both ELLA and ELISpot can offer valuable insights into prognosis, therapeutic strategies, and the underlying mechanisms of sepsis development.
Isolation of xylose-utilizing yeasts from oil palm waste for xylitol and ethanol production
Authors: Kusumawati N. , Sumarlan S. H. , Zubaidah E. , Wardani A. K.
Published: October 2023

The energy crisis triggers the use of energy sources that are renewable, such as biomass made from lignocellulosic materials, to produce various chemical compounds for food ingredients and biofuel. The efficient conversion of lignocellulosic biomass into products with added value involves the activity of microorganisms, such as yeasts. For the conversion, microorganisms must be able to use various sugars in lignocellulosic biomass, including pentose sugars, especially xylose. This study aims to isolate xylose-utilizing yeasts and analyze their fermentation activity to produce xylitol and ethanol, as well as their ability to grow in liquid hydrolysate produced from pretreated lignocellulosic biomass. Nineteen yeast isolates could grow on solid and liquid media using solely xylose as a carbon source. All isolates can grow in a xylose medium with incubation at 30 °C, 37 °C, 42 °C, and 45 °C. Six isolates, namely SLI (1), SL3, SL6, SL7, R5, and OPT4B, were chosen based on their considerable growth and high xylose consumption rate in a medium with 50 g/L xylose with incubation at 30 °C for 48 h. Four isolates tested, namely SLI (1), SL6, SL7, and R5, can produce xylitol in media containing xylose carbon sources. The concentration of xylitol produced was determined using high-pressure liquid chromatography (HPLC), and the results ranged from 5.0 to 6.0 g/L. Five isolates tested, namely SLI (1), SL6, SL3, R5, and OPT4B, can produce ethanol. The ethanol content produced was determined using gas chromatography (GC), with concentrations ranging from 0.85 to 1.34 g/L. Three isolates, namely SL1(1), R5, and SL6, were able to produce xylitol and ethanol from xylose as carbon sources and were also able to grow on liquid hydrolyzate from pretreated oil palm trunk waste with the subcritical water method. The three isolates were further analyzed using the 18S rDNA sequence to identify the species and confirm their phylogenetic position. Identification based on DNA sequence analysis revealed that isolates SL1(1) and R5 were Pichia kudriavzevii, while isolate SL6 was Candida xylopsoci. The yeast strains isolated from this study could potentially be used for the bioconversion process of lignocellulosic biomass waste to produce value-added derivative products.

Graphical Abstract
Prevalence and associations of sarcopenia, obesity and sarcopenic obesity in end-stage knee osteoarthritis patients
Authors: Liao Junyi , Chen Jie , Xu Wei , Chen Jia , Liang Xi , Cheng Qiang , Tang Yongli , Huang Wei
Published: October 2023

Objective

To identify the prevalence of obesity, sarcopenia, sarcopenic obesity in end-stage knee osteoarthritis (KOA) patients and analyze influences of obesity and sarcopenia in the progression of KOA.

Methods

A cross-sectional study was carried out among end-stage KOA patients who consecutively admitted to Orthopedic Department for TKA. We suppose that the level of decreased physical activities would be influenced by unilateral or bilateral KOA. Patient information, albumin, hemoglobin, pace, step frequency, number of comorbid conditions were collected. Bioelectrical impedance analyzer was used to analyze body composition. Obesity, sarcopenia, sarcopenic obesity rate were analyzed with accepted diagnosis criteria. Correlations between body mass index (BMI) or age and fat mass (FM), appendicular skeletal muscle mass (ASM) were analyzed.

Results

138 patients (male 30, female 108) in southwest of China including 67 patients with unilateral KOA and 71 patients with bilateral KOA were analyzed. No statistic difference was found in mean albumin, prealbumin and hematocrystallin, body composition values and number of comorbid conditions. We found that BMI was positively correlated with FM (Male: R2 = 0.7177, p < 0.0001, Female: R2 = 0.8898, p < 0.0001), ASM (Male: R2 = 0.2640, p = 0.0037, Female: R2 = 0.2102, p < 0.0001), FM index (FMI) (Male: R2 = 0.6778, p < 0.0001, Female: R2 = 0.8801, p < 0.0001), and ASM index (ASMI) (Male: R2 = 0.3600, p = 0.0005, Female: R2 = 0.4208, p < 0.0001) in end-stage KOA patients. However, age was not obviously correlated with FM or FMI (Male: FM, R2 = 0.006911, p = 0.3924; FMI, R2 = 0.7554, p = 0.0009196; Female: FM, R2 = 0.001548, p = 0.8412; FMI, R2 = 0.002776, p = 0.7822). And slightly negatively correlated with ASM (Male: R2 = 0.05613, p = 0.0136, Female: R2 = 0.01327, p = 0.5433) and ASMI (Male: R2 = 0.02982, p = 0.3615; Female: R2 = 0.03696, p = 0.0462). The prevalence of obesity, sarcopenia and obesity sarcopenia differs according to different diagnosis criteria. No difference in the occurrence rate of obesity was found between bilateral KOA and unilateral KOA patients, and occurrence rates of sarcopenia and sarcopenic obesity were statistically higher in bilateral KOA than that in unilateral KOA patients.

Conclusions

Obesity, sarcopenia and sarcopenic obesity are highly prevalent in end-stage KOA patients, sarcopenic obesity are more prevalent in bilateral KOA patients than that in unilateral KOA patients.
Testosterone upregulates glial cell line-derived neurotrophic factor (GDNF) and promotes neuroinflammation to enhance glioma cell survival and proliferation
Authors: Kanwore Kouminin , Kanwore Konimpo , Guo Xiaoxiao , Xia Ying , Zhou Han , Zhang Lin , Adzika Gabriel Komla , Joseph Adu-Amankwaah , Abiola Ayanlaja Abdulrahman , Mu Peipei , Kambey Piniel Alphayo , Noah Marie Louis N’dzie , Gao DianShuai
Published: October 2023

Background

Testosterone contributes to male organism development, such as bone density, muscle development, and fat repartition. Estrogen (derived from testosterone) also contributes to female reproductive system development. Here, we investigated the effect of testosterone on glioma cells and brain neuron inflammation essential for cancer development and progression.

Methods

The human astrocyte and glioma cell lines were treated with 6 ng/ml exogenous testosterone in vitro. We performed cell counting kit-8, transwell, and wound healing assays to determine the effect of testosterone on glioma cell proliferation, migration, and invasion. The glioma cells were injected into the xenograft and treated with 5 µl concentrated testosterone. Transcriptional suppression of glial cell line-derived neurotrophic factor (GDNF) was performed to evaluate brain neuron inflammation and survival. The tumor tissues were assessed by hematoxylin–eosin staining and immunohistochemistry.

Results

Testosterone upregulates GDNF to stimulate proliferation, migration, and invasion of glioma cells. Pathologically, the augmentation of GDNF and cyclophilin A contributed to neuroprotection when treated with testosterone. Our investigation showed that testosterone contributes to brain neuron and astrocyte inflammation through the upregulation of nuclear factor erythroid 2-related factor 2 (NRF2), glial fibrillary acid protein (GFAP), and sirtuin 5 (SIRT5), resulting in pro-inflammatory macrophages recruitments into the neural microenvironment. Mechanically, testosterone treatment regulates GDNF translocation from the glioma cells and astrocyte nuclei to the cytoplasm.

Conclusion

Testosterone upregulates GDNF in glioma cells and astrocytes essential for microglial proliferation, migration, and invasion. Testosterone contributes to brain tumor growth via GDNF and inflammation.

Graphical Abstract

The contribution of testosterone, macrophages, and astrocytes, in old neuron rescue, survival, and proliferation. During brain neuron inflammation, the organism activates and stimulates the neuron rescue through the enrichment of the old neuron microenvironment with growth factors such as GDNF, BDNF, SOX1/2, and MAPK secreted by the surrounding neurons and glial cells to maintain the damaged neuron by inflammation alive even if the axon is dead. The immune response also contributes to brain cell survival through the secretion of proinflammatory cytokines, resulting in inflammation maintenance. The rescued old neuron interaction with infiltrated macrophages contributes to angiogenesis to supplement the old neuron with more nutrients leading to metabolism activation and surrounding cell uncontrollable cell growth.