A systematic review of progenitor survival and maturation in Parkinsonian models

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients.The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain.Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024.After screening,76 articles were included in the analysis from which 178 separate transplant studies were identified.From these,graft survival could be assessed in 52 studies and differentiation in 129 studies.Overall,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

Long-term follow-up result of short metaphyseal femoral stem in primary total hip arthroplasty:A retrospective study

BACKGROUND Total hip arthroplasty(THA)has increased along with an increasing demand for improved quality of life.Combined with prolonged life expectancy,the number of revision surgeries is expected to increase.Stress shielding is a significant issue with traditional femoral stems used in THA,making revision surgeries particularly challenging in younger patients.This has sparked renewed interest in studying safety and functional outcomes of short metaphyseal femoral stems,which have the potential to alleviate these challenges and simplify revision surgeries.AIM To evaluate the long-term outcomes of short-stem THA.METHODS A total of 124 hips that underwent THA using the short femoral stem(TRILOCK®Depuy)between May 2006 and November 2008 were included in this study.Patients were followed for a period of 15 years.Outcomes were assessed in terms of pain relief,hip joint range of motion,improvement in mobility,and functional outcomes using the modified Harris Hip Score,Oxford hip score,and Western Ontario and McMaster Universities Osteoarthritis index score.RESULTS A total of 124 hips in 98 patients were evaluated.Significant improvements in functional outcomes were observed over the 15-year follow-up period,with no cases of subsidence,implant loosening,or complications necessitating revision surgery.The only complication reported was heterotopic ossification in 1 patient.CONCLUSION Short metaphyseal stems provide better functional outcomes with early mobilization,and its long-term follow-up without subsidence,implant loosening,or proximal femoral bone loss simplifies revision surgery in younger patients.

Current role of biomarkers in the initiation and weaning of kidney replacement therapy in acute kidney injury

The occurrence of acute kidney injury(AKI)in critically ill patients is often associated with increased morbidity and mortality rates.Despite extensive research,a consensus is yet to be arrived,especially regarding the optimal timing and indications for initiation of kidney replacement therapy(KRT)for critically ill patients.There is no clear guidance available on the timing of weaning from KRT.More recently,various biomarkers have produced promising prognostic pre-diction in such patients,regarding the need for KRT and its termination.Most of these biomarkers are indicative of kidney damage and stress,rather than re-covery.However,large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT.This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.

When Does Sora Show:The Beginning of TAO to Imaginative Intelligence and Scenarios Engineering

DURING our discussion at workshops for writing“What Does ChatGPT Say:The DAO from Algorithmic Intelligence to Linguistic Intelligence”[1],we had expected the next milestone for Artificial Intelligence(AI)would be in the direction of Imaginative Intelligence(II),i.e.,something similar to automatic wordsto-videos generation or intelligent digital movies/theater technology that could be used for conducting new“Artificiofactual Experiments”[2]to replace conventional“Counterfactual Experiments”in scientific research and technical development for both natural and social studies[2]-[6].Now we have OpenAI’s Sora,so soon,but this is not the final,actually far away,and it is just the beginning.

Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Multidisciplinary approach toward enhanced recovery after surgery for total knee arthroplasty improves outcomes

Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee osteoarthritis.When enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was reduced.ERAS is an evidence-based scientific protocol aimed at ameliorating the surgical stress response.ERAS aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation phase.Implementation of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient satisfaction.Multidisciplinary collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.

Effects of hormone replacement therapy on mood and sleep quality in menopausal women

BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.

Microglial autophagy in neurogenesis:a new player in Alzheimer's disease

While extensive studies have illuminated the impact of Alzheimer's disease(AD) on neuronal survival,there is growing evidence that abnormal postnatal neurogenesis in early AD brains contributes to disease progression.Postnatal neurogenesis serves as a mechanism to replace dead or damaged neurons.New neurons generated from neural stem cells(NSCs) in the subgranular zone(SGZ) of the dentate gyrus integrate into the existing hippocampal circuit.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Generation of mitochondrial replacement monkeys by female pronucleus transfer

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

Which approach of total hip arthroplasty is the best efficacy and least complication?

BACKGROUND Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function.Approaches of the hip have been exhaustively explored about pros and cons.The efficacy and the complications of hip approaches remains inconclusive.This study conducted an umbrella review to systematically appraise previous meta-analysis(MAs)including conventional posterior approach(PA),and minimally invasive surgeries as the lateral approach(LA),direct anterior approach(DAA),2-incisions method,mini-lateral approach and the newest technique direct superior approach(DSA)or supercapsular percutaneouslyassisted total hip(SuperPath).AIM To compare the efficacy and complications of hip approaches that have been published in all MAs and randomized controlled trials(RCTs).METHODS MAs were identified from MEDLINE and Scopus from inception until 2023.RCTs were then updated from the latest MA to September 2023.This study included studies which compared hip approaches and reported at least one outcome such as Harris Hip Score(HHS),dislocation,intra-operative fracture,wound compliData were independently selected,extracted and assessed by two reviewers.Network MA and cluster rank and surface under the cumulative ranking curve(SUCRA)were estimated for treatment efficacy and safety.RESULTS Finally,twenty-eight MAs(40 RCTs),and 13 RCTs were retrieved.In total 47 RCTs were included for reanalysis.The results of corrected covered area showed high degree(13.80%).Among 47 RCTs,most of the studies were low risk of bias in part of random process and outcome reporting,while other domains were medium to high risk of bias.DAA significantly provided higher HHS at three months than PA[pooled unstandardized mean difference(USMD):3.49,95%confidence interval(CI):0.98,6.00 with SUCRA:85.9],followed by DSA/SuperPath(USMD:1.57,95%CI:-1.55,4.69 with SUCRA:57.6).All approaches had indifferent dislocation and intraoperative fracture rates.SUCRA comparing early functional outcome and composite complications(dislocation,intra-operative fracture,wound complication,and nerve injury)found DAA was the best approach followed by DSA/SuperPath.CONCLUSION DSA/SuperPath had better earlier functional outcome than PA,but still could not overcome the result of DAA.This technique might be the other preferred option with acceptable complications.

Corrigendum to“Towards a business model for second-life batteries:Barriers,opportunities,uncertainties,and technologies”[J.Energy Chem.78(2023)507–525]

In the Acknowledgments Section,please replace“Shell oil”for“TotalEnergies”.The authors would like to apologise for any inconvenience caused.For the sake of clarity(“Shell oil”should be removed and in boldblack“TotalEnergies”inserted),this section should say:The authors would like to thank Moura Batteries for the financial support.

ChatGPT and exercise prescription:Human vs.machine or human plus machine?

The power of artificial intelligence(AI)to create stories,music,art,and other creative projects has been demonstrated and criticized over recent decades in media,mainly because of the idea that AI will replace human jobs.Most recently,in November 2022,reactions to Chat Generative Pre-training Transformer(ChatGPT)release for public use reverberated in news and social media headlines,while its users exceeded100 million in just a few weeks.ChatGPT is a natural language processing program created by AI non-profit OpenAI Inc.

Role of pituitary adenylate cyclase-activating polypeptide in peripheral nerve regeneration:a cellular and molecular perspective

Neuro regeneration is a very complex phenomenon characterized by the generation of new neurons and synapses,involving connections between adjacent cells and axonal projections.Neuroregeneration supplies additional longterm resources to replace those altered by the injury and ensure lasting functional recovery.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic:A Cross-sectional Study

Objective The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement.The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019(COVID-19)pandemic and analyzed the influence of psychological state on medication safety.Methods Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits.Depression was evaluated by the Self-Rating Depression Scale(SDS).Anxiety was evaluated by the Self-Rating Anxiety Scale(SAS).Medication adherence was evaluated by the Morisky scale.Results A total of 309 patients(aged 52.2±11.4 years)were included in the present study.The SDS score of all included patients was 36.9±9.4 points,of which 11(3.6%)patients were diagnosed as having depression.The SAS score of all included patients was 43.1±9.3 points,of which 71(23%)patients were diagnosed as having anxiety.Seven patients(2.3%)had both anxiety and depression.Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression.Regarding anxiety,patients who underwent repeated operations had a 2.264-fold greater risk,and patients who received combination medication had a 2.140-fold greater risk.More bleeding events and coagulation disorders could be observed in patients with anxiety,depression or both.When anxiety occurred,patients showed worse medication adherence.However,depression had no significant effect on medication adherence.Conclusion During the COVID-19 pandemic,the detection rate of mental illnesses such as anxiety and depression was high,which seriously affected the medication safety of warfarin.Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Recent progress and future prospects of high-entropy materials for battery applications

Due to the energy crisis caused by limited fossil fuel reserves,extensive use of the renewable energy sources such as wind or solar energy is deemed to replace the use of traditional fossil fuels in the future^([1−3]).However,most renewable energy sources face the same problem,which is the intermittency of energy.For example,solar energy cannot be utilized at night.That means the continuous energy demand required for large-scale power grids can’t be satisfied by a single solar panel model.

Self-adaptive gas flow and phase change behaviors during hydrate exploitation by alternate injection of N_(2) and CO_(2)

Since hydrate resources play a part of the stratigraphic framework structure in sediments,establishing a safe and economic method for hydrates exploitation remains the primary challenge to this day.Among the proposed methods,the spontaneous displacement of CH_(4) from hydrate cages by CO_(2) seems to be a perfect mechanism to address gas production and CO_(2) storage,especially in today's strong demand for carbon reduction and replacing clean energy.After extensive lab researches,in the past decade,injecting a mixture of CO_(2) and small molecule gas has become a key means to enhance displacement efficiency and has great potential for application.However,there is a lack of in-depth research on gas flow in the reservoir,while the injected gas always passes through low-saturated hydrate areas with high permeability and then occurs gas channel in a short term,finally resulting in the decreases in gas production efficiency and produced gas quality.Therefore,we explored a new injection-production mode of alternate injection of N2 and CO_(2) in order to fully coordinate the advantages of N_(2) in enhanced hydrate decomposition and CO_(2) in solid storage and heat compensation.These alternate"taking"and"storing"processes perfectly repair the problem of the gas channel,achieving self-regulation effect of CH_(4) recovery and CO_(2) storage.The 3-D experimental results show that compared to the mixed gas injection,CH_(4) recovery is increased by>50%and CO_(2) storage is increased by>70%.Additionally,this alternate injection mode presented a better performance in CH_(4) concentration of produced gas and showed outstanding N_(2) utilization efficiency.Further,we analyzed its self-adaptive gas flow mechanism and proposed an application model of"one injection and multiple production".We look forward to this study accelerating the application of CO_(2)-CH_(4) replacement technology.

Efficient cache replacement framework based on access hotness for spacecraft processors

A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity of contemporary high-performance spacecraft processors.To harness these non-uniform access behaviors,an efficient cache replacement framework featuring an auxiliary cache specifically designed to retain evicted hot data was proposed.This framework reconstructs the cache replacement policy,facilitating data migration between the main cache and the auxiliary cache.Unlike traditional cacheline-granularity policies,the approach excels at identifying and evicting infrequently used data,thereby optimizing cache utilization.The evaluation shows impressive performance improvement,especially on workloads with irregular access patterns.Benefiting from fine granularity,the proposal achieves superior storage efficiency compared with commonly used cache management schemes,providing a potential optimization opportunity for modern resource-constrained processors,such as spacecraft processors.Furthermore,the framework complements existing modern cache replacement policies and can be seamlessly integrated with minimal modifications,enhancing their overall efficacy.