Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

Novel approach of ultrasound-guided lateral recess block for a patient with lateral recess stenosis: A case report

BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.

Smart prediction of liquefaction-induced lateral spreading

The prediction of liquefaction-induced lateral spreading/displacement(Dh)is a challenging task for civil/geotechnical engineers.In this study,a new approach is proposed to predict Dh using gene expression programming(GEP).Based on statistical reasoning,individual models were developed for two topographies:free-face and gently sloping ground.Along with a comparison with conventional approaches for predicting the Dh,four additional regression-based soft computing models,i.e.Gaussian process regression(GPR),relevance vector machine(RVM),sequential minimal optimization regression(SMOR),and M5-tree,were developed and compared with the GEP model.The results indicate that the GEP models predict Dh with less bias,as evidenced by the root mean square error(RMSE)and mean absolute error(MAE)for training(i.e.1.092 and 0.815;and 0.643 and 0.526)and for testing(i.e.0.89 and 0.705;and 0.773 and 0.573)in free-face and gently sloping ground topographies,respectively.The overall performance for the free-face topology was ranked as follows:GEP>RVM>M5-tree>GPR>SMOR,with a total score of 40,32,24,15,and 10,respectively.For the gently sloping condition,the performance was ranked as follows:GEP>RVM>GPR>M5-tree>SMOR with a total score of 40,32,21,19,and 8,respectively.Finally,the results of the sensitivity analysis showed that for both free-face and gently sloping ground,the liquefiable layer thickness(T_(15))was the major parameter with percentage deterioration(%D)value of 99.15 and 90.72,respectively.

Lateral earth pressure of granular backfills on retaining walls with expanded polystyrene geofoam inclusions under limited surcharge loading

Existing studies have focused on the behavior of the retaining wall equipped with expanded polystyrene(EPS)geofoam inclusions under semi-infinite surcharge loading rather than limited surcharge loading.In this paper,the failure mode and the earth pressure acting on the rigid retaining wall with EPS geofoam inclusions and granular backfills(henceforth referred to as EPS-wall),under limited surcharge loading are investigated through two-and three-dimensional model tests.The testing results show that different from the sliding of almost all the backfill in the EPS-wall under semi-infinite surcharge loading,only an approximately triangular backfill slides in the wall under limited surcharge loading.The distribution of the lateral earth pressure on the EPS-wall under limited surcharge loading is non-linear,and the distribution changes from the increase of the wall depth to the decrease with the increase of the limited surcharge loading.An approach based on the force equilibrium of a differential element is developed to predict the lateral earth pressure behind the EPS-wall subjected to limited surcharge loading,and its performance was fully validated by the three-dimensional model tests.

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

A dual-RPA based lateral flow strip for sensitive,on-site detection of CP4-EPSPS and Cry1Ab/Ac genes in genetically modified crops

Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.

Management and classification of the fracture of lateral process of talus:An overview and literature update

Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or misdiagnosed.In recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years.In this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.

OSMR is a potential driver of inflammation in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly understood.However,inflammation is known to play an important role in the development of this condition.To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis.Therefore,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis.The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response.Furthermore,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis.These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.

Pathological mechanisms of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of research.Thus,the journey to understanding or treating amyotrophic lateral sclerosis is still a long one.According to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways.The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis.Here,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis.In addition,we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis.Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

NRF2 signaling cascade in amyotrophic lateral sclerosis:bridging the gap between promise and reality

Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.

How do lateral septum projections to the ventral CA1 influence sociability?

Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.

An approach for determination of lateral limit angle in kinematic planar sliding analysis for rock slopes

Planar sliding is one of the frequently observed types of failure in rock slopes.Kinematic analysis is a classic and widely used method to examine the potential failure modes in rock masses.The accuracy of planar sliding kinematic analysis is significantly influenced by the value assigned to the lateral limit angleγlim.However,the assignment ofγlim is currently used generally based on an empirical criterion.This study aims to propose an approach for determining the value ofγlim in deterministic and probabilistic kinematic planar sliding analysis.A new perspective is presented to reveal thatγlim essentially influences the probability of forming a potential planar sliding block.The procedure to calculate this probability is introduced using the block theory method.It is found that the probability is correlated with the number of discontinuity sets presented in rock masses.Thus,different values ofγlim for rock masses with different sets of discontinuities are recommended in both probabilistic and deterministic planar sliding kinematic analyses;whereas a fixed value ofγlim is commonly assigned to different types of rock masses in traditional method.Finally,an engineering case was used to compare the proposed and traditional kinematic analysis methods.The error rates of the traditional method vary from 45%to 119%,while that of the proposed method ranges between 1%and 17%.Therefore,it is likely that the proposed method is superior to the traditional one.

Hydrodynamic characteristics and particle tracking of 90° lateral intakes at an inclined river slope

Lateral intakes are common in rivers.The pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division width.The hydraulic characteristics of lateral withdrawal from inclined river slopes at different intake elevations should be investigated.Meanwhile,the division width exhibits significant vertical non-uniformity at an inclined river slope,which should be clarified.Hence,a three-dimensional(3-D)hydrodynamic and particle-tracking model was developed with the Open Source Field Operation and Manipulation(Open FOAM),and the model was validated with physical model tests for 90°lateral withdrawal from an inclined side bank.The flow fields,withdrawal sources,and division widths were investigated with different intake bottom elevations,withdrawal discharges,and main channel velocities.This study showed that under inclined side bank conditions,water entered the intake at an oblique angle,causing significant 3-D spiral flows in the intake rather than two-dimensional closed recirculation.A lower withdrawal discharge,a lower bottom elevation of the intake,or a higher main channel velocity could further strengthen this phenomenon.The average division width and turbulent kinetic energy were smaller under inclined side bank conditions than under vertical bank conditions.With a low intake bottom elevation,a low withdrawal discharge,or a high main channel velocity,the sources of lateral withdrawal were in similar ranges near the local inclined bank in the vertical direction.Under inclined slope conditions,sediment deposition near the intake entrance could be reduced,compared to that under vertical slope conditions.The results provide hydrodynamic and sediment references for engineering designs for natural rivers with inclined terrains.

At-rest lateral earth pressure of compacted expansive soils:Experimental investigations and prediction approach

This paper presents experimental studies on a compacted expansive soil,from Nanyang,China for investigating the at-rest lateral earth pressureσL of expansive soils.The key studies include(i)relationships between theσL and the vertical stressσV during soaking and consolidation,(ii)the influences of initial dry densityρd0 and moisture content w 0 on the vertical and lateral swelling pressures at no swelling strain(i.e.σV0 andσL0),and(iii)evolution of theσL during five long-term wetting-drying cycles.Experimental results demonstrated that the post-soakingσL-σV relationships are piecewise linear and their slopes in the passive state(σL>σV)and active state(σL<σV)are similar to that of the consolidationσL-σV relationships in the normal-and over-consolidated states,respectively.The soakingσL-σV relationships converge to the consolidationσL-σV relationships at a thresholdσV where the interparticle swelling is restrained.TheσL0 andσV0 increase monotonically withρd0;however,they show increasing-then-decreasing trends with the w 0.The extent of compaction-induced swelling anisotropy,which is evaluated byσL0/σV0,reduces with an increase in the compaction energy and molding water content.TheσL reduces over moisture cycles and the stress relaxation in theσL during soaking is observed.An approach was developed to predict the at-rest soakingσL-σV relationships,which requires conventional consolidation and shear strength properties and one measurement of theσL-σV relationships during soaking.The proposed approach was validated using the results of three different expansive soils available in the literature.

On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay

The application of pesticides (mostly insecticides and fungicides) during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea. Thus, it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits. However, the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues. In this study, nine types of lateral flow immunochromatographic strips (LFICSs) were developed to detect the pesticides of interest (fenpropathrin, chlorpyrifos, imidacloprid, thiamethoxam, acetamiprid, carbendazim, chlorothalonil, pyraclostrobin, and iprodione). To reduce the interference of tea substrates on the assay sensitivity, the pretreatment conditions for tea samples, including the extraction solvent, extraction time, and purification agent, were optimized for the simultaneous detection of these pesticides. The entire testing procedure (including pretreatment and detection) could be completed within 30 min. The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.

Analytical model for predicting time-dependent lateral deformation of geosynthetics-reinforced soil walls with modular block facing

To date,few models are available in the literature to consider the creep behavior of geosynthetics when predicting the lateral deformation(d)of geosynthetics-reinforced soil(GRS)retaining walls.In this study,a general hyperbolic creep model was first introduced to describe the long-term deformation of geosynthetics,which is a function of elapsed time and two empirical parameters a and b.The conventional creep tests with three different tensile loads(Pr)were conducted on two uniaxial geogrids to determine their creep behavior,as well as the a-Pr and b-Pr relationships.The test results show that increasing Pr accelerates the development of creep deformation for both geogrids.Meanwhile,a and b respectively show exponential and negatively linear relationships with Pr,which were confirmed by abundant experimental data available in other studies.Based on the above creep model and relationships,an accurate and reliable analytical model was then proposed for predicting the time-dependent d of GRS walls with modular block facing,which was further validated using a relevant numerical investigation from the previous literature.Performance evaluation and comparison of the proposed model with six available prediction models were performed.Then a parametric study was carried out to evaluate the effects of wall height,vertical spacing of geogrids,unit weight and internal friction angle of backfills,and factor of safety against pullout on d at the end of construction and 5 years afterwards.The findings show that the creep effect not only promotes d but also raises the elevation of the maximum d along the wall height.Finally,the limitations and application prospects of the proposed model were discussed and analyzed.