Biorefinery feasibility is highly influenced by the early design of the best feedstock transformation pathway to obtain value-added products. Pretreatment has been identified as the critical stage in biorefinery design since proper pretreatment influences subsequent reaction, separation, and purification processes. However, many pretreatment analyses have focused on preserving and valorizing six-carbon sugars for future use in bioconversion processes, leaving aside fractions such as hemicellulose and lignin. To date, there has been no pretreatment systematization for the removal of lignocellulosic fractions. This work defines pretreatment efficacy through operational, economic, environmental, and social indicators. Thus, using the data reported in the literature, as well as the results of the simulation schemes, a multi-criteria weighting of the best-performing schemes for the isolation or removal of cellulose, hemicellulose, and lignin was carried out. As a main result, it was concluded that dilute acid is the most effective for cellulose isolation and hemicellulose removal for producing platform products based on six- and five-carbon sugars, respectively. Additionally, the kraft process is the best methodology for lignin removal and its future use in biorefineries. The results of this work help to elucidate a methodological systematization of the pretreatment efficacy in the design of biorefineries as an early feasibility stage considering sustainability aspects. The latter after a comprehensive study of the raw materials to be used and a sustainability analysis based on the latest state of the art technologies and approaches which include aspects of the three pillars of sustainability” [The integral use of biomass for its subsequent conversion into high-value-added products is an approach associated with the biorefinery concept, where the product portfolio may comprise bulk and/or specialized chemical products . The bioability” . Therefoability” . The maxability” . Additioability” . Different steps are involved during the biorefinery design by the early-stage approach: hierarchy, sequencing, and integration . The hieBiorefinery design involves different stages, starting with evaluating and selecting potential feedstocks. Then, the biomass is pretreated to recover or isolate its fractions to be further subjected to a combination of biological and/or chemical processes . Based oThe main purpose of biomass pretreatment should be the access of biocatalysts to plant polysaccharides to be converted into platform products . AdditioInitially, biorefineries were proposed to produce biofuels through the efficient use of biomass, focusing on cellulose valorization through enzymatic hydrolysis and further fermentation . Therefo2-catalyzed steam explosion pretreatment [Scheffersomyces shehatae and Zymomonas mobilis [The early selection of pretreatments was performed through the removal index  and structural factors of the feedstock , the pretreatments are not selective to a single fraction; instead, more than two fractions can be obtained in the hydrolyzed liquor. For example, acidification of biomass with SOf lignin . Therefoellulose . Aliphatellulose . From Taellulose . Therefotructure . Based oAfter pretreatment, by-products are obtained from the hydrolysis of macromolecules, especially hemicellulose and lignin, including five- and six-carbon sugars in the form of oligomers and monomers, aliphatic acids, furans, and phenolic compounds, among others. Each by-product can be used in other thermochemical and biochemical processes as raw material (platform product) to obtain value-added products or have an inhibitory effect in bioconversions. In hemicellulose hydrolysis pretreatments, mainly xylose and xylo-oligomers are produced from the cleavage of the glycosidic bond in the xylan chain, as well as small amounts of glucose, galactose, and arabinose . Based oThe rich phenolic content of lignin makes it promising to use this heteropolymer in different industrial processes of food, pharmacy, and perfumery. Solubilized or precipitated lignin has been studied to produce vanillin as an additive in the chemical industry . Other sFurfural and HMF are also produced by the dehydration of monosaccharides at high temperatures. Furfural has gained importance as a solvent or as a precursor for the production of pesticides. In contrast, HMF has been widely used as an additive in petroleum-based polymer blends, such as polyester and polyurethane. Furfural and HMF inhibit yeast growth and decrease the yield and productivity of ethanol fermentations. However, anaerobic fermentations have been performed in recombinant transformants with xylose as substrate followed by the addition of furfural, leading to increased ethanol production due to the reduction of furfural to furfuryl alcohol to decrease the production of undesirable by-products such as xylitol . AlkalinThe results of the technical analysis of the selected pretreatment schemes are summarized in The pretreatment selection should involve operational aspects and the overall performance of the process. It is also necessary to identify scaling factors or technology development level since, in many cases, its implementation on an industrial scale depends on technical, economic, and environmental design factors. Therefore, the most appropriate selection of the isolation scheme should involve the technology readiness level  categories since they involve effects on humans either by ingestion, inhalation or dermal exposure to ammoniaThe potential environmental impact of the pretreatment schemes during the isolation of the cellulose fraction is shown in The environmental impact of the pretreatment schemes for the isolation of the hemicellulose fraction is presented in v/v. Therefore, downstream ammonia removal becomes a complex process, considering subsequent separation stages. In addition, the lignin obtained from pretreatments such as RAAE cannot be used in food-type production schemes because the contaminant traces cannot be eliminated.. The impact associated with using hazardous substances during the process triggers complications in the development of pretreatment since it requires the installation of extensive and rigorous safety protocols.The potential environmental impact generated by the pretreatment schemes for the isolation of the lignin fraction is shown in 9 m3 in 2019, and (ii) total water available in the country, with reported values of 2145 × 109 m3 in 2019 (AQUASTAT). Likewise, indicators referring to the demand for electricity from the processing units were analyzed with the national electricity capacity of 72,824 GWh in 2021 and the consumption of diesel (in energy terms) for the generation of thermal energy from the different steam qualities of the pretreatment schemes with the amount of energy provided by Colombia in 2021 (2.40 × 1011 MJ) (UPME). For the latter analysis, a boiler thermal efficiency of 80% was assumed. For the social analysis, a comparison of indicators contextualized by the capacity in Colombia was performed. These ratios considered statistics at the national scale for certain economic sectors. Based on water consumption in pretreatment schemes for cooling and processing, two indicators were calculated: (i) water for the industrial sector, where Colombia demanded 3.73 × 10Based on the results of each evaluative indicator, an overall assessment of pretreatment efficacy was carried out by weighing the heuristic analysis. Heuristic analyses have been described as subjective analyses based on theoretical, experimental, or simulated results. Some investigations have shown satisfactory results of raw material selection  or transThe single-step pretreatment efficacy results give a tentative route to the future reaction and downstream processes that should be involved in the early design of biorefineries. Although the heuristic analysis provides design support, there are certain challenges to be considered in the biorefinery approach. (i) Insufficient separation of hemicellulose and lignin in the hydrolyzed liquor requires additional steps for lignin precipitation through acids, whose concentration can alter the soluble carbohydrates to form degradation compounds. (ii) In pretreatments that are acid-catalyzed, such as dilute acid, organosolv, or steam explosion, extra design factors must be considered due to the high temperatures used together with the corrosive action of the acids. Therefore, hot acid corrosion-resistant alloys must be used for reactor design, which makes the cost of the reactor, exchangers, filters, and piping an important element of the CapEx as well as possible maintenance costs. (iii) The main demand for process water in biotechnological processes comes from the pretreatment stage due to the high feed ratios needed to hydrolyze the lignocellulosic matrix, which sometimes makes it necessary to add costly chemical reagents that are difficult to recover and that alter the environmental impact of the waste streams. However, processes such as organosolv and kraft have been implemented at high scales considering the recovery of reagents. For example, green liquor causticization of the kraft process after the black liquor incineration. (iv) High energy use in the first stage of the process (pretreatment), such as organosolv. Therefore, it is proposed to contemplate energy integration stages to reduce the demand and costs associated with thermal energy.During biorefinery design, the integral use of raw materials to produce high-value-added compounds is essential. Moreover, the objective is to minimize the environmental impact and costs associated with waste generation and maximize profits through the production of more compounds. Therefore, the design of pretreatment schemes through efficacy should involve using the other lignocellulosic fractions that were not considered a target product. For example, alkali pretreatment for lignin removal was studied without contemplating the future utilization of cellulose-rich WIS, followed by unhydrolyzed hemicellulose. Therefore, the pretreatment efficacy study may involve additional schemes sequentially to utilize each fraction best. Since pretreatment is the critical stage in the design of biorefineries, as explained by the onion diagram, it is required to optimize the processes to maximize the production of platform products. Different authors have studied sequential pretreatments to improve operationally future processing steps, such as enzymatic hydrolysis , bufferiThe pretreatment assessment in biorefinery schemes was performed based on indicators involving literature data and simulation results. This assessment began with selecting a processing objective: to identify pretreatments that best isolate each lignocellulosic fraction separately for further valorization. A screening of pretreatment schemes was performed considering composition and fraction removal constraints. Afterward, ten indicators were described and assessed, involving technical, economic, environmental, and social aspects. Finally, each indicator was scored based on data from the literature and simulation depending on what is most suitable in the final biorefinery design to improve the sustainability of the process. The best pretreatment schemes were selected based on the efficacy results performed by the heuristic analysis.A literature review was performed to determine the best pretreatments to isolate each lignocellulosic fraction individually, either as a water-insoluble solid (WIS) or in the pretreatment liquor, considering thermal, chemical, and thermochemical processes. The screening involved more than 100 updated review and research-type papers (articles from 2018 to 2022) concerning pretreatments with experimental and simulation sections. Biomass containing a lignocellulosic compositional range of 25% < cellulose < 50%, 20% < hemicellulose < 40%, and 10% < lignin < 35% was chosen to restrict the analysis scope to comparable raw materials by composition. After the screening, six pretreatments were selected that best removed or isolated the fractions of interest based on the removal index (I). This indicator involves comparing energy and water consumption to national or regional availability, providing a perspective of the level of risk to the communities surrounding the biorefineries that involve the pretreatment schemes. The energy and water demand of the process must be minimized so as not to affect the energy grid and water sources in the country.The pretreatment efficacy in biorefineries was assessed based on ten evaluative indicators to obtain the isolated lignocellulosic fraction or a platform product from the fraction of interest. The indicators were classified as technical (indicators (i)–(vi)), economical (indicators (vii) and (viii)), environmental (indicators (ix)), and social (indicator (x)). (i) Lignocellulosic fraction removal EffiI indicators, the pretreatment schemes were simulated in Aspen Plus v9.0 software , considering production yields, removals, operating conditions, and feed ratios described in the literature. A processing flow rate of 50 tons d−1 of rice husk and a simulation scope up to filtration or separation of liquor and WIS fractions were assumed. The raw material characterization is presented in For the assessment of the −1, 8.07 USD ton−1, 8.15 USD ton−1, and 0.1 USD kWh−1 were used for low-pressure steam, medium-pressure steam, high-pressure steam, and electricity, respectively. The cooling and process water cost was calculated using a Chemical Engineering Plant Cost Index (CEPCI) of 701.4 for 2021. The maintenance was calculated as 6% of the CapEx and the depreciation using an interest rate of 17% based on the straight-line method. Finally, the labor cost was estimated considering a wage of 5.21 USD h−1 for an eight-hour shift per day.The overall pretreatment yields were calculated for each lignocellulosic fraction based on the initial raw material flow rate. For the cellulose yield, the six-carbon total content in the WIS was considered, as shown in Equation (5). The oligomers and monosaccharides of five carbons were used for hemicellulose yield (see Equation (6)). Meanwhile, Equation (7) involves the solubilized lignin in the liquor fraction. On the other hand, utility requirements were calculated for steam, cooling water, and electricity. For the CapEx analysis, the direct cost of the processing equipment was estimated using the Aspen Process Economic Analyzer v9.0 software  and based on the mass and energy balances of the simulations. The CapEx was calculated considering the sum of the direct cost with mechanical, civil, and instrumentation work as well as piping and electrical wiring. The OpEx involves raw materials, utilities, maintenance, depreciation, and labor costs. The raw material cost includes the feedstock and chemical reagents costs see . For utiThe environmental analysis was carried out based on the indicators established by the Environmental Protection Agency (EPA). The Waste Reduction Algorithm (WAR) software  calculated the potential environmental impact (PEI), considering only the pretreatment stage as the control volume. Thus, the PEI was calculated as the difference between the environmental impact generated by the process input and output streams through five impact categories: terrestrial toxicity potential (TTP), human toxicity potential by inhalation or dermal exposure (HTPE), human toxicity potential by ingestion (HTPI), smog formation or photochemical oxidation potential (PCOP), and acidification potential or acid rain (AP). Social analysis is considered one of the three fundamental pillars in determining the sustainability of a process. Therefore, this work proposed an analysis to determine the social impact of implementing pretreatment schemes for rice husks related to the local community. It is important to point out that other categories associated with workers, value chain agents, and consumers were excluded from the analysis since they could not be identified and evaluated. For example, a life cycle analysis that includes the agronomic and transport stages of rice husks is not carried out, hindering the analysis of employees in the value chain. Therefore, the scope of the social analysis also involved pretreatment schemes from raw material intake to filtration for obtaining the WIS and the hydrolysate. In this work, it was assumed that two operators would be working in the pretreatment stage; therefore, an analysis of employment generated was not performed since it would be constant for all the schemes. It has previously been reported that two employees can be assumed for each processing section, involving raw material and reagent reception, pretreatment, reaction, and separation . Table 1The social impact caused by the pretreatment schemes was evaluated by considering a subcategory related to the use of natural resources, energy demand, and fossil fuel extraction. Thus, the first two indicators associated with using natural resources aim to assess the level of water use in the industrial sector and the renewable available in the country. For the water use in the industrial sector, the flow used in each scheme (cooling water and process water) and the total water used at the national scale in the industrial sector are correlated. Furthermore, for the renewable water available in the country, the flow used in each scheme is related to the total water available at the national scale. The AQUASTAT database from the Food and Agriculture Organization of the United Nations (FAO) was used to calculate these indicators . On the This work demonstrated the definition of pretreatment efficacy in biorefinery schemes assessed through ten sustainable indicators involving operational considerations, cost-effectiveness, environmental impact, and social issues, described as follows: (i) lignocellulosic fraction removal; (ii) accessibility index; (iii) formation of by-products or hydrolyzed products; (iv) formation of inhibitory compounds; (v) technology readiness level; (vi) energy demand; (vii) capital costs; (viii) operating costs; (ix) environmental impact; and (x) social impact. Through an in-depth literature review and process simulation, it was possible to identify the best pretreatment schemes for individual cellulose isolation and the removal of hemicellulose and lignin. It was concluded that at a preliminary analysis, the best pretreatments for cellulose isolation in the WIS are dilute acid, wet air oxidation, or organosolv. On the other hand, if biorefineries are planned to valorize the hemicellulose fraction, it is recommended to implement LHW, steam explosion, or dilute acid pretreatments. In lignin-based biorefineries, it is proposed to use kraft, alkali, or LHW pretreatments. As a main result, an approximation of sustainable pretreatments in the Colombian context is described due to the assessment of techno-energetic, economic, environmental, and social indicators.. These results would help future work on designing complex biorefineries to choose the best pretreatment scheme as it drastically influences the reaction and downstream processes for product separation.


Neurotology is a rapidly expanding field of knowledge. The study of the vestibular system has advanced so much that even basic definitions, such as the meaning of vestibular symptoms, have only recently been standardized.To present a review of the main subjects of neurotology, including concepts, diagnosis and treatment of Neurotology, defining current scientific evidence to facilitate decision-making and to point out the most evidence-lacking areas to stimulate further new research.This text is the result of the I Brazilian Forum of Neurotology, which brought together the foremost Brazilian researchers in this area for a literature review. In all, there will be three review papers to be published. This first review will address definitions and therapies, the second one will address diagnostic tools, and the third will define the main diseases diagnoses. Each author performed a bibliographic search in the LILACS, SciELO, PubMed and MEDLINE databases on a given subject. The text was then submitted to the other Forum participants for a period of 30 days for analysis. A special chapter, on the definition of vestibular symptoms, was translated by an official translation service, and equally submitted to the other stages of the process. There was then a in-person meeting in which all the texts were orally presented, and there was a discussion among the participants to define a consensual text for each chapter. The consensual texts were then submitted to a final review by four professors of neurotology disciplines from three Brazilian universities and finally concluded. Based on the full text, available on the website of the Brazilian Association of Otorhinolaryngology and Cervical-Facial Surgery, this summary version was written as a review article.The text presents the official translation into Portuguese of the definition of vestibular symptoms proposed by the Bárány Society and brings together the main scientific evidence for each of the main existing therapies for neurotological diseases.This text rationally grouped the main topics of knowledge regarding the definitions and therapies of Neurotology, allowing the reader a broad view of the approach of neurotological patients based on scientific evidence and national experience, which should assist them in clinical decision-making, and show the most evidence-lacking topics to stimulate further study. Neurotology is a medical discipline that explores the interface between otorhinolaryngology and neurology, comprising the clinical evaluation and treatment of sensorineural hearing and balance disorders. In recent years, new knowledge and new test modalities have been incorporated into neurotology. In order to gather the scientific evidence of neurotology into an easily accessible and succinct document, the ABORL-CCF, through its Department of Neurotology, developed the Neurotology Forums project to present to doctors who treat neurotological diseases an organized meeting of scientific evidence, facilitating the management of the neurotological patient.This text was the result of the I Neurotology Forum, held with the leading specialists in the field in Brazil on September 2, 2017. Prior to the meeting, the texts had been written based on a literature review to gather scientific evidence divided by topics. For this first Forum, the topic definitions and therapies was chosen. In addition to a literature review, contact was made with the Barany Society, which authorized the official translation of the concepts defined in the world consensus of the international classification of vestibular diseases,The texts written by the experts were then screened by the other Forum participants a few weeks in advance. Each author presented their text on the day of the meeting and, after debating them among those present, the texts were finalized by consensus. The texts were then grouped and standardized. On October 27, 2018, at a final meeting with representatives of the Neurotology training services in the country, the text was read again, and minor final adjustments were made. The recommendations of this first Forum, based on the literature, are objectively described and summarized in this article. For further reading, the reader may refer to the Forum text published in full on the ABORL-CCF website.Resolution of the Federal Council of Medicine 1718/2004, ratified by ABORL-CCF at the ABORL-CCF Ordinary General Meeting).The physician must respect the legal determinations and guidelines dictated by the Federal Council of Medicine (CFM) and ABORL-CCF. The teaching of private medical acts in any form of knowledge transmission to non-medical professionals, including those pertaining to advanced life support, except remote emergency care, is prohibited until optimal resources are reached .The medical report with diagnosis is the exclusive competency and prerogative of the physician, who is responsible for diagnosing the diseases and prescribing treatments, whereas the other professionals will act only within the scope of their respective legislations, according to the jurisprudence of the Superior Courts. People who perform acts of diagnosis of diseases and prescription of treatments should be reported to the authorities for illegal practice of Medicine, a crime provided for in the Penal Code with penalties ranging from six months to two years in prison .Considering the increasing complexity of medical problems, it is essential the team of physicians and other health professionals, such as nurses, pharmacists, physiotherapists and speech therapists, respect the limits of their competencies, prerogatives and their strict professional scope  vertigo is the sensation of self-motion when no self-motion is occurring or the sensation of distorted self-motion during an otherwise normal head movement. The term encompasses false spinning sensations (spinning verti- go) and also other false sensations like swaying, tilting, bobbing, bouncing, or sliding (non-spinning vertigo).(Non-vertiginous) dizziness is the sensation of disturbed or impaired spatial orientation without a false or distorted sense of motion.external vertigo, oscillopsia, visual lag, visual tilt, and movement-induced blur.Vestibulo-visual symptoms are visual symptoms that usually result from vestibular pathology or the interplay between visual and vestibular systems. These include false sensations of motion or tilting of the visual surround and visual distortion (blur) linked to vestibular  failure. There are five vestibulo-visual symptoms: Unsteadiness, directional pulsion, balance-related near-fall, and balance-related fall.Postural symptoms are balance symptoms related to maintenance ofpostural stability, occur- ring only while upright . There are four postural symptoms: Clinical history is the main tool in the search for patient diagnosis. According to the Bárány Society, vestibular syndromes have been classified into 3 distinct groups: acute, episodic, and chronic.These are characterized by the abrupt onset of vestibular symptoms that persist for days or weeks, commonly associated with nausea, vomiting, gait unsteadiness, movement intolerance and presence of nystagmus. After the initial peak of symptoms, there occurs improvement during the first week and gradual recovery over weeks to months. AVS may occur spontaneously, following trauma or exposure to toxic agents, among others.These present as recurrent episodes of vestibular symptoms lasting from seconds to hours. The inter-crisis period may be asymptomatic or maintain some degree of milder dizziness in relation to the crises.They are characterized by the persistence of vestibular symptoms over a long period of time. The main diagnoses are persistent postural-perceptual dizziness (PPPD), chronic idiopathic unilateral vestibulopathy, persistent unilateral vestibulopathy after vestibular neuritis, unilateral vestibulopathy secondary to vestibular schwannoma, unilateral vestibulopathy after medical procedure, chronic bilateral vestibulopathy. Other diagnoses: CANVAS, posterior fossa tumors.•Calcium channel antagonists: sedative action, as they antagonize slow calcium channels and also because they have antihistamine action on H1 receptors. In addition to these effects, peripheral vasodilation action is described.They may be prescribed in the acute phase of vestibular diseases for symptomatic relief. Their use should be as short as possible so as not to impair the vestibular compensation and avoid unwanted side effects. The main classes of medications and their mechanisms of action are:B.Level of Evidence: recommended.•Antihistamines: vestibular sedatives with anti-cholinergic and antihistamine effect on H1 receptor. They can be used in acute vertigo, for the relief of nausea and vomiting,Degree of recommendation: Level of Evidence: B.recommended.•Benzodiazepines: vestibular sedatives because they potentiate the inhibitory action of GABA. They may also be used in acute vertigoDegree of recommendation: B.Level of Evidence: recommended.Degree of recommendation: •Betahistine: it is a histaminergic modulator acting as a weak H1 agonist and a strong H3 heteroreceptor antagonist. Its action in the labyrinth involves mechanisms that facilitate fluid circulation in the stria vascularis via the precapillary sphincter, thereby reducing endolymphatic pressure.14They are indicated for symptom control and prophylaxis of new crises of vertigo. The main medications in this class and their mechanisms of action are:A.Level of Evidence: recommended.•Ginkgo biloba EGb761 Extract: it is an herbal medicine, consisting of two active fractions: flavonoids and terpenoids. It has antiplatelet, antioxidant, antihypoxemic, anti-free radical, and antiedema actions in both the central nervous system and the inner ear.16Degree of recommendation: B.Level of Evidence: recommended.Degree of recommendation: They are used for the prophylaxis of vestibular migraine crises and Meniere’s disease and treatment of PPPD. The start of the therapy should be gradual to assess possible adverse reactions and treatment should be continued for at least 6 months after symptom control. Withdrawal, when indicated, should also be gradual to avoid withdrawal reactions by the patient.There are at least seven types of neurotransmitters involved in the transmission of vestibular system impulses. The top seven are glutamate, acetylcholine, GABA, dopamine, norepinephrine, histamine and serotonin. Most antidepressant medications work by modulating the action of serotonin. Serotonin receptors are found in the peripheral vestibular system and the vestibular nucleus in the central nervous system.•Prophylaxis of vestibular migraine crises: Nortriptyline , Amitriptyline , Venlafaxine .•Prophylaxis of Meniere's syndrome crises: Sertraline , Escitalopram .•Treatment of persistent postural-perceptual dizziness: Sertraline , Paroxetine , Imipramine , Fluvoxamine , Milnacipran , Fluoxetine , Citalopram .Listed below are the recommendations of each antidepressant according to the diagnosis:They are used in the treatment of vestibular paroxysms and prophylaxis of vestibular migraine crises and in the control of tinnitus. The start of the therapy should be gradual to assess possible adverse reactions. Withdrawal, when indicated, should also be gradual to avoid withdrawal reactions by the patient.Anticonvulsants are classified according to their site of action and potency: enhancers of GABA-mediated synaptic inhibition , sodium channel blockers , calcium channel blockers , inhibitors of glutamate synaptic receptors (lower the excitability threshold). The most commonly used are carbamazepine, oxcarbazepine, topiramate, valproate, gabapentin and lamotrigine.•Treatment of vestibular paroxysm: Carbamazepine , Oxcarbazepine , Gabapentin , Phenytoin , Valproic Acid .•Prophylaxis of vestibular migraine crises: Topiramate , Valproate , carbamazepine , Gabapentin , Lamotrigine .Anticonvulsants with their degree of recommendation, according to diagnosis, are listed below:20•Diuretics: they can be used to treat Meniere’s disease, with cases being assessed individually. Although several experimental and radiological studies demonstrate the reversal of hydrops with the use of diuretics, the mechanism of action of these medications is still much discussed.They help control vestibular symptoms, fluctuating hearing, aural fullness and tinnitus in patients with Meniere’s disease.C.Level of Evidence: optional.Degree of recommendation: These are distinct therapeutic procedures for vestibular rehabilitation exercises. While rehabilitation exercises, such as Cawthorne-Cooksey or Brandt-Daroff protocols, aim at mechanisms of neuronal plasticity such as adaptation, habituation and sensory substitution, otoliths repositioning maneuvers aim to effectively release and reposition otoliths out of the endolymphatic duct and ampoule and back to their physiological utricular position. They should be carried out by the doctor to resolve the positional vestibular symptoms in BPPV.A.Level of Evidence: strong.•Maneuvers for the posterior canal:•Maneuvers for the lateral canal - canalithiasis (geotropic variant):•Maneuvers for the lateral canal - cupulolithiasis (apogeotropic variant):•Maneuvers for the anterior canal: these were not discussed in the forum since anterior canal BPPV is a very rare and uncertain diagnosis and its pathophysiology is not well understood.•Complications of repositioning maneuvers: severe complications are rare but should not be underestimated. Observation of the patient’s risk factors, and the use of appropriate techniques help to prevent them, and their performance under medical supervision is necessary for the treatment. The main complications are severe vertigo crisis, with nausea, vomiting and sweating, with frequent need for medication, conversion to another semicircular canal , requiring an adequate diagnosis of the new affected canal with indication of another therapeutic maneuver, intracanalicular otolith obstruction  requiring reversal of position, osteoarticular and vascular cervical lesions, and endolymphatic hydrops.32Degree of recommendation: Used to control vestibular symptoms in Meniere’s disease and to recover rapidly progressive sensorineural hearing loss. Gentamicin application is reserved for the treatment of Meniere’s disease unresponsive to clinical treatment. Because of the possibility of hearing loss, cochlear function should be monitored. Intratympanic corticosteroid therapy can be used for sudden sensorineural hearing loss, immune-mediated inner ear diseases, and rapidly progressive sensorineural hearing loss, as primary, combined, or rescue therapy to oral corticosteroid therapy.34Level of evidence: B (vertigo control) and C (hearing loss).recommended.Degree of recommendation: •Traditional: vestibular adaptation exercises intensify vestibular-ocular reflex gain and tolerance to head movements, improve gaze stability, vestibulo-visual interaction during head movements, and postural stability in conflicting sensory environments. Sensory substitution exercises seek to intensify residual vestibular function and replace the reduced or absent vestibular function with alternative strategies of gaze stabilization and static and dynamic postural control. On the other hand, habituation exercises aim to desensitize the movements and/or positions that trigger vestibular symptoms through repetitive stimuli.It is a physiological form of treatment of peripheral and/or central vestibular symptoms, allowing patients to perform their usual activities to the best of their capacities. It is based on eye, head and body exercise protocols. The exercises use vestibular adaptation mechanisms, substitution of sensory or motor strategies and habituation to accelerate vestibular compensation and regain body balance.36A.Level of Evidence: strong.•With platforms: the use of platforms may be a therapeutic option included in the vestibular rehabilitation protocol. Platforms are equipment where the individual remains in an upright position, being submitted to body stability challenges caused by movements in the mid-lateral or anteroposterior direction or with flexion and extension of the ankle. There are studies showing more significant improvement in the Dizziness Handicap Inventory (DHI) and body sway scores in patients treated with the platform, compared to conventional vestibular rehabilitation.Degree of recommendation: C.Level of Evidence: recommended.•Vibrotactile substitution: the use of vibrotactile substitution equipment may be a therapeutic option included in the vestibular rehabilitation protocol. It is a technique that accelerates central compensation through vestibular rehabilitation by substitution. It consists of placing a vibrating device on the patient, most commonly an adjustable waist belt, which consists of a main unit, responsible for detecting movement sways, and four vibratory units, located in the anterior, posterior, right lateral and left lateral positions,41Degree of recommendation: B.Level of Evidence: recommended.•Virtual Reality: aims to recreate environmental changes by stimulating sensory systems to adjust the reflexes involved in postural control and balance strategies.Degree of recommendation: B.Level of Evidence: recommended.•Neuromodulation: vestibular rehabilitation through neuromodulation may be performed in patients with peripheral or central chronic vestibular dysfunction for at least 1 year who have performed and completed previous vestibular rehabilitation therapy protocol with limited results, and whose symptoms and limitations to perform activities of daily living still persist.Degree of recommendation: B.Level of Evidence: recommended.Degree of recommendation: Procedures that may be used in selected cases of disabling vertigo refractory to clinical treatment. Labyrinthectomy is limited to patients with socially useless hearing, while vestibular neurectomy is one of the options for patients with useful hearing.C.Level of Evidence: optional.Degree of recommendation: The purpose of the procedure is the symptomatic control of patients who are refractory to the clinical treatment of Meniere’s disease. However, no class or scientific society was found that adopted a recommendation for this subject. The procedure becomes an individual option of each professional, considering the characteristics of the case.C.Level of Evidence: optional.Degree of recommendation: It is a treatment option for the control of vertigo symptoms and is only indicated for patients with disabling symptoms of superior semicircular canal dehiscence (SSCD) syndrome. There is still no evidence to determine the most effective surgical technique. A systematic review published in 2017C.Level of Evidence: optional.Degree of recommendation: It is a safe surgical treatment indicated for the management of patients with perilymphatic fistula, as long as its diagnosis is established.Level of Evidence: C.recommended.Degree of recommendation: The large amount of information presented in this article is a demonstration of the advancement of neurotology in recent years. The authors hope that this review may help the physician to understand, approach and treat patients with vestibular symptoms.The authors declare no conflicts of interest


Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted infections worldwide. Since the symptoms of Ct infection are often subtle or absent, most people are unaware of their infection until they are tested or develop severe complications such as infertility. It is believed that the primary culprit of Ct-associated tissue damage is unresolved chronic inflammation, resulting in aberrant production of cytokines, chemokines, and growth factors, as well as dysregulated tissue influx of innate and adaptive immune cells. A member of the IL-6 cytokine family, leukemia inhibitory factor (LIF), is one of the cytokines induced by Ct infection but its role in Ct pathogenesis is unclear. In this article, we review the biology of LIF and LIF receptor (LIFR)-mediated signaling pathways, summarize the physiological role of LIF in the reproductive system, and discuss the impact of LIF in chronic inflammatory conditions and its implication in Ct pathogenesis. Under normal circumstances, LIF is produced to maintain epithelial homeostasis and tissue repair, including the aftermath of Ct infection. However, LIF/LIFR-mediated signaling – particularly prolonged strong signaling – can gradually transform the microenvironment of the fallopian tube by altering the fate of epithelial cells and the cellular composition of epithelium. This harmful transformation of epithelium may be a key process that leads to an enhanced risk of infertility, ectopic pregnancy and cancer following Ct infection. Chlamydiae family is a diverse group of obligatory intracellular bacteria, comprised of both pathogens and commensals, and found in varying habitats that can extend as far as the bottom of the Arctic Ocean (Chlamydia trachomatis (Ct) is a human pathogen and the most common bacterial cause of sexually transmitted infections worldwide  and serious complications such as tubal factor infertility (TFI), ectopic pregnancy and chronic pelvic pain , and an intracellular form of replicative reticulate body (RB) -mediated signaling pathways, summarize the physiological role of LIF in the reproductive system, and discuss the impact of LIF in chronic inflammatory conditions and its implication in Ct pathogenesis.ody (RB) . Infecting cells . Immediafections . These infection . Notablynfection , which anfection . Of notesurvival . Some RBsurvival . While Asurvival . As suchxposures . The mosrocesses . While nnfection , leukeminfection , and than humans  as well n humans . TherefoLIF is encoded by a single copy gene on chromosome 22 in humans and chromosome 11 in mice . The codMenstruation is a key feature of the mammalian female reproductive system that is characterized by monthly remolding, shedding and regeneration of the endometrium under the influence of ovarian hormones and divided into an estrogen (E2)-dominated proliferative phase and a progesterone (P4)-dominated secretory phase . Cell tyin vitro  signaling and upregulation of inducible nitric oxide synthase (NOS2) to control Ct replication in organoids. In addition, LIF/LIFR signaling is involved in tissue injury and repair responses that are needed for maintaining epithelial homeostasis and organoid renewal  (Grant number: 201803PJT-159700) to JW. KW is supported by a Dalhousie Medical Research Foundation (DMRF) – Infection, Immunity, Inflammation & Vaccinology (I3V) Graduate Studentship.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Fusobacterium. We also identified functional pathways which merit further investigation, including RNA degradation (ko03018) and primary immunodeficiency (ko05340). In addition, our analysis of gene abundance data identified the gene K06147  as being over abundant in OSCC samples. Our results are generalizations which identified some currents that we believe could guide further research. Our work faced several limitations related to the heterogeneity of the available data. Wide variation in methods for sample collection, methods for controlling for known behavioral risk factors, computing platform choice, and methods for case-control design all posed confounding factors in this work. We examined the current methods of data collection, data processing, and data reporting in order to offer suggestions toward the establishment of best practices within this field. We propose that these limitations should be addressed through the implementation of standardized data analytic practices that will conform to the rigor and reproducibility standards required of publicly funded research.The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has motivated a search for associations between the oral microbiome and oral cancer, in hopes of identifying possible biomarkers that facilitate earlier diagnosis and improved prognosis for patients with that disease. The present study examined the relationship between the microbiome in the human oral cavity and oral squamous cell carcinoma (OSCC). We searched the literature for case-control studies which focused on the relationship between the human oral microbiome and OSCC. We aggregated three types of data from these studies: bacteriome data at the genus level, predicted functional pathway data, and gene abundance data. From these data, we noted several microbial genera which may be associated with oral cancer status, including  Oral squamous cell carcinoma (OSCC) is among the most common types of head and neck cancer, and it is the cancer with the highest incidence rate among South-Central Asian populations  has increased, so has the number of approaches for studying these interactions and influences at the taxonomic, functional, and genetic levels  AND (bacteria OR bacterium OR microbiome)” returned nearly 140 abstracts published before July 31, 2020. To distill these into a well-defined set of studies for further review, we established a set of criteria. Each paper that we included in our systematic review and meta-analysis met these criteria:Available in English and report on experiment-based results .Pertained to cancer of the oral cavity. Studies that included samples from the throat area  were considered in the review only Reported on human patient research  were permitted.Reported on a study which had a case-control design and an objective of differentiating between the oral microbiome of the OSCC case samples and that of cancer-free samples. We chose to exclude studies of cancer progression .After reviewing abstracts returned by PubMed, we searched Web of Science and SCOPUS databases using the same keywords. Following aggregation and filtering all results through our criteria, eleven remaining studies were included in our literature review . We subgThe data from our eleven reviewed studies as show in Regarding the data type, 16S data representing the microbiome were pervasive. Given the available data, we also focused our meta-analysis on 16S data of bacterial specimens. Although other components of the microbiome, including the mycome and the virome, have also been studied in the etiology of oral cancer . Of the eleven studies reviewed, only those by Zhao et al. , Perera Among the five studies that provided full data, Perera et al.  and TakaAnalysis of case vs. control samples within each of the five studies;Analysis of merged case vs. merged control samples within data from all intra-subject controlled studies;Analysis of case vs. case samples between all intra-subject controlled studies;Analysis of control vs. control samples between all intra-subject controlled studies.In We used QIIME2  method to identify the distinguishing taxa within the OSCC and control groups. The authors of this method have shown LEfSe has relatively low false positive rate and considers both the statistical significance and the effect size in determining microbiome-associated biomarkers  and the corresponding biom table of ASVs across samples were input into PICRUSt2  . AdditioTo determine the effects of confounding factors on the observed microbial differences between OSCC and cancer-free sites, we compared the microbial composition and functions between OSCC samples from each of the intra-subject controlled studies. Data from Zhou et al. had a much lower alpha diversity than that of the other two studies .Prevotella and Actinomyces were enriched among samples from Zhao, which illustrated the heterogeneity of the case samples.The Wilcoxon test identified over 80 genera as being significantly differentially abundant between the case samples from the Zhang, Zhao, and Zhou studies . Being aA total of four pathways at KEGG level 3 were identified as being upregulated in the Zhou analysis  with an Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Prevotella, and Streptococcus   and RNA degradation (ko03018), both of which have been researched in the cancer literature. Primary immunodeficiency has been found significantly enriched among gingivo-buccal oral cancer samples  was found to be upregulated among OSCC samples in the case vs. control analysis , these rWhile the data from our quantitative meta-analyses do suggest microbial relationships and functions which merit further study, the strongest evidence in these data indicates the need to standardize experimental designs and reporting of results in this growing field. The limitations to the meta-analytic work are numerous in the presence of such heterogeneity of data. In particular, aggregating data across multiple studies combines and compounds the biases that are known to be prevalent among contemporary analyses of oral microbiome data  used in their respective analysis pipelines. Some authors have argued that the bias introduced by differences in analysis pipeline structure is the most significant challenge in metagenomic analyses , and upregulation/downregulation of many pathways such as ko03018 (RNA degradation).In summary, our meta-analysis provided evidence of specific microbial genera, genes, and functional pathways having an association with OSCC status in oral cavity tissues. These potential biomarkers included an increased abundance of The standardization of data collection, processing, and analysis techniques is an area of great need in the field of human oral microbiome study given the substantial decreases in sequencing costs and rapid increases in published studies. While it is both exciting and informative to study the human oral bacteriome and oral disease in meta- and mega- analyses, potentially powerful insights from future studies will be clouded by the confounding issues we have discussed due to the absence of standards in methodology, reporting, and data availability.https://www.ncbi.nlm.nih.gov/bioproject/PRJNA525734. 2. Zhang et al. , synthesized the results, and wrote the first draft of the manuscript. MW performed all of the computations in LEfSe for the taxonomic, functional, and genetic data sets, created Venn diagrams, and collaborated with TP in drafting the manuscript. CC and CP completed the literature search. SD, SG, DD, and JB designed the meta-analysis comparisons and edited the manuscript. XX and EZ planned and designed the experiments, reviewed the manuscript, and mentored TP through the analysis process. All authors read and approved the final manuscript.JB, DD, SG, XX, and EZ were supported by University of Iowa Strategic Initiatives Fund: P3 Program in Support of Strategic Priorities. EZ was supported by University of Iowa College of Dentistry Seed Grant.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The central giant cell granuloma (CGCG) consists of a benign non-neoplastic proliferative lesion comprising about 7% of jaw lesions. It affects mostly children and young adults; the female to male ratio is 2:3The CGCG is generally asymptomatic; its clinical behavior may be non-aggressive or aggressive. This lesion may invade the floor of the maxillary sinus, the orbit, and the nasal fossae. There may also be facial asymmetry, nasal deviation, and mobility of associated teeth.The etiopathogeny is unclear; there are different clinical presentations and several forms of treatment.The diagnostic hypotheses depend on the aggressiveness, development rate, inflammation, pain, mobility of teeth and other manifestations of the lesion. The differential diagnosis includes peripheral giant cell granulomas, aneurismatic bone cysts, and the brown tumor of hyperparathyroidism.The histology of CGCG of the jaws shows multinucleated giant cells and round, oval or spindle-shaped mononucleated cells within fibrous connective tissue, associated with focal hemorrhage and significant vascularization.Treatments are: excision biopsies, curettage with safety margins, and partial or full resection of the affected bone; injecting corticosteroids into the affected region has been successful.Supportive care includes antibiotics, analgesics, and corticosteroids for about 10 days after surgery; postoperative monitoring with radiographic exams is needed to assess disease progression.Based on these ideas, the purpose of this study was to report a case of CGCG, with an emphasis on the clinical procedures, radiography and laboratory tests for the diagnosis and surgical treatment.A female white patient aged 33 years presented at the buccomaxillofacial surgery and trauma unit of the Pedro I Hospital in the city of Campina Grande, PB, complaining of loss of stability of her dental prosthesis and increased volume on the left side of the jaw. The patient thought that this was due to the recent removal of a tooth, which the patient described as rather traumatic.No changes were seen in the extra-oral physical examination. Within the mouth, the left maxillary region was enlarged, with expanded bone cortical plates. Upon palpation, the lesion was hard and showed intra-osseous extension.The panoramic radiograph and computed tomography revealed a radiopaque mass containing radiolucent images. The lesion was removed surgically with a safety margin, and meticulous curettage was carried out to improve the prognosis. The patient was admitted into hospital for the procedure ; before Histological sections revealed connective tissue fragments with two cell populations (mononucleated and multinucleated). Mononucleated cells were spindle-shaped, with elongated nuclei and clear cytoplasm. The multinucleated giant cells contained several nuclei and a large eosinophilic cytoplasm.The patient was monitored during one month, after which routine visits during 6 months were scheduled; the postoperative period was uneventful.Ahmed et al.The etiology of CGCG remains unclear; some factors, such as trauma and multiple exodontia, may be associated with this disease;The patient was asymptomatic, there was no bleeding, the cortical plates were bulging, there was mild facial asymmetry, and the lesion was palpable in the examination of the mouth; these findings were also reported by other authors such as Neville et al.The histopathology of CGCG generally is described as populations of mononucleated and multinucleated cells; inflammation may also be found.Surgery is the traditional and generally accepted approach for the treatment of CGCG.The CGCG is an infrequent disease of unclear etiology. Although benign, it may be high destructive. The conclusive diagnosis is made by histopathological studies. The treatment of choice should be selected according to the peculiarities of each case.


Light detection and ranging (LiDAR) is often combined with an inertial measurement unit (IMU) to get the LiDAR inertial odometry (LIO) for robot localization and mapping. In order to apply LIO efficiently and non-specialistically, self-calibration LIO is a hot research topic in the related community. Spinning LiDAR (SLiDAR), which uses an additional rotating mechanism to spin a common LiDAR and scan the surrounding environment, achieves a large field of view (FoV) with low cost. Unlike common LiDAR, in addition to the calibration between the IMU and the LiDAR, the self-calibration odometer for SLiDAR must also consider the mechanism calibration between the rotating mechanism and the LiDAR. However, existing self-calibration LIO methods require the LiDAR to be rigidly attached to the IMU and do not take the mechanism calibration into account, which cannot be applied to the SLiDAR. In this paper, we propose firstly a novel self-calibration odometry scheme for SLiDAR, named the online multiple calibration inertial odometer (OMC-SLIO) method, which allows online estimation of multiple extrinsic parameters among the LiDAR, rotating mechanism and IMU, as well as the odometer state. Specially, considering that the rotating and static parts of the motor encoder inside the SLiDAR are rigidly connected to the LiDAR and IMU respectively, we formulate the calibration within the SLiDAR as two separate sets of calibrations: the mechanism calibration between the LiDAR and the rotating part of the motor encoder and the sensor calibration between the static part of the motor encoder and the IMU. Based on such a SLiDAR calibration formulation, we can construct a well-defined kinematic model from the LiDAR to the IMU with the angular information from the motor encoder. Based on the kinematic model, a two-stage motion compensation method is presented to eliminate the point cloud distortion resulting from LiDAR spinning and platform motion. Furthermore, the mechanism and sensor calibration as well as the odometer state are wrapped in a measurement model and estimated via an error-state iterative extended Kalman filter (ESIEKF). Experimental results show that our OMC-SLIO is effective and attains excellent performance. Given the high reliability and accuracy of light detection and ranging (LiDAR) sensors, LiDAR odometry (LO) and LiDAR simultaneous localization and mapping (SLAM) methods have played an important role in areas such as robotics, autonomous driving, and surveying ,2,3. HowBy incorporating an inertial measurement unit (IMU), LiDAR inertial odometry (LIO) can present a better performance for localization and mapping in motion . To makeTo address the above issues, we propose firstly a novel self-calibration odometry scheme for SLiDAR, named the online multiple calibration spinning LiDAR inertial odometer (OMC-SLIO) method, which allows online estimation of multiple extrinsic parameters among the LiDAR, rotating mechanism and IMU, as well as the odometer state. Considering the rotating and static parts of the motor encoder inside the SLiDAR are rigidly connected to the LiDAR and IMU, respectively, we formulate the self-calibration within the SLiDAR as two independent sets of calibrations: the mechanism calibration between the LiDAR and the rotating part of the motor encoder and the sensor calibration between the static part of the motor encoder and the IMU. Thus, we construct a well-defined kinematic model from the LiDAR to the IMU with the angular information of the motor encoder. Based on the constructed kinematic model, a two-stage motion compensation method is presented to remove point cloud rotation and motion distortion simultaneously. Finally, we wrap the mechanism calibration, sensor calibration and the odometer state in a measurement model and perform online estimation based on the ESIEKF framework. Experimental results show that our OMC-SLIO is effective and attains excellent performance.The remainder of this paper is organized as follows. There are plenty of works regarding diverse calibrations among IMUs, cameras and LiDAR, and here we focus on the extrinsic calibration between LiDAR and the IMU and the mechanism calibration of SLiDAR.There are some tailored offline calibration methods for the LiDAR-IMU system. Ref.  uses preRegarding online extrinsic calibration in LIO, related works are around the tightly-coupled scheme based on a filter or a nonlinear optimization. Both LINS  and FASTAs for the mechanism calibration of SLiDAR, some traditional calibration methods require ad-hoc tools ,30,31 orFor calibration in a more general scene, a point-point constraint scheme is utilized ,34,35. BDifferent from the work in Considering that the rotation and static parts of the encoder are rigidly attached to the LiDAR and IMU, respectively, we can formulate the multiple calibrations inside the SLiDAR platform as two independent sets of calibrations; one is between the LiDAR and the rotating part of the encoder , and the other is between the static part of encoder and the IMU . To illustrate the formulation of multiple calibrations, the internal coordinate relation for SLiDAR is shown in L, S, B and I respectively denote the LiDAR, the rotation part of the encoder, the static part of the encoder and the IMU. The corresponding coordination systems are denoted as The subscripts of Obviously, In addition, as our SLiDAR system is unidirectional, mechanism calibration parameters along the spinning direction cannot be estimated due to unobservability . FurtherFor SLiDAR, the overlap between the consecutive LiDAR scanning frame is minor due to the rapid LiDAR rotation; we therefore adopt a scan-to-submap match approach to ensure enough associations. Meanwhile, built upon an efficient ESIEKF framework , we aggrIn preprocessing, the planar points are extracted from LiDAR scanning points, the spinning angles are obtained from the encoder, and the IMU states are propagated upon every IMU measurement. In global transformation, extracted planar points are projected to global space via successive transformations consisting of mechanism calibration, motion compensation, sensor calibration and IMU global poses. Specifically, motion compensation covers two kinds of distortions from LiDAR spinning and platform moving. The global planar points are used to associate the global planes in the submap of global mapping. Then, the residuals derived from point-to-plane constraints are passed into ESIEKF to update states. If converged, global mapping and odometry output will be updated, otherwise, global transformation and feature association will be executed again with updated states.In the following, we will introduce more details on preprocessing, global transformation and ESIEKF; readers can refer to related works for details of global mapping .The frequencies of the data received from the LiDAR, encoder and IMU are different; for instance, the LiDAR is 10Hz and both the encoder and IMU are 200 Hz in our SLiDAR platform. Thus, before preprocessing, the raw encoder spinning angle, IMU angular rate and IMU acceleration will be temporarily stored in the respective buffers, until receiving one frame of the LiDAR scanning points is completed.For the raw LiDAR scanning points, the planar points will first be extracted as in LOAM , and theN − 1 measured spinning angles, and Note that as the timestamp of the latest rotation angle may be earlier than the timestamp at the end of the current LiDAR scan, this will result in some backward points not being able to be interpolated to correspond to the rotation angle. Therefore, we utilize the accumulated spinning angle measurements to estimate the current spinning rate in the preprocessing. Denote For associating planar features in the submap, we need to project the raw point Denote Furthermore, denote Then, denote Furthermore, assume that Finally, denote In the following, we will derive the details of the two-stage motion compensation, LiDAR spinning compensation and platform moving compensation, respectively.Different from the common LiDAR odometry, which only resolves the moving distortion, SLiDAR will incur the extra LiDAR spinning distortion. Based on the coordinate relation of SLiDAR in First, we interpolate the measured spinning angles to get the corresponding spinning angle of the LiDAR point, then rotate the point to the frame Assume the sample period of the spinning angle is If Since LiDAR spinning is only along the X-axis, soSimilarly, we can get the spinning angle Notably, From formulations (3), (4), (9) and (10), we can getRegarding platform moving compensation, the back-propagation of IMU measurements is employed to get the related pose for each point, and the point is then transformed to the scanning end-time with its corresponding related pose . DifferePerforming the forward propagation on IMU inputs in , we can refer to .We denote the back-propagated IMU poses at the time For general IMUs, the propagated values With the ESIEKF optimization framework , we aggrWe take the IMU frame i-th IMU measurement can be expressed as [With the zero-order hold discretization, the discrete state transition model at the essed as :(20)xi+1fined in , ∆t is tAssume the optimal estimated state of the last LiDAR scanning Upon each IMU input fined in ) is updafound in . Note thDenote the current iteration of IEKF as Ignoring the measurement noise ed to in , and theAfter every iteration, the prior distribution of found in , and xˆkFurthermore, combine the prior in formulation (38) and the posteriori distribution in formulation (35), which leads to the maximum a-posteriori estimate (MAP) for In order to verify the proposed OMC-SLIO, we designed a SLiDAR experimental platform, as shown in We chose the state-of-the-art (SOTA) self-calibration methods, FAST-LIO  and LIO-Furthermore, to validate the correctness of our formulated SLiDAR calibration, we adopted two specific offline calibration methods to estimate the mechanism external parameters  and sensWe conducted two sets of comparison experiments. One set of comparison experiments was conducted in a lab room with a Nokov Motion Capture System (NMCS) shown in , where tIn the lab room test, the positioning result from the NMCS is regarded as the ground truth. The absolute translation errors (ATE) presented by MAE and RMSE and the average processing time (APT) for each LiDAR scanning (10 Hz) are listed in In Specifically, our OMC-SLIO shows a significant improvement in Z-directional localization, with a 40% improvement in accuracy compared to FAST-SLIO. Furthermore, the Z-direction localization of all methods exhibited the largest MAE and RMSE values, owing to the weaker laser beam reflection intensity from the smooth ground  presented via MAE and RMSE and the average processing time (APT) for each LiDAR scanning (10 Hz) are presented in There is no doubt that SLOAM and SLIO-SAM still fail when applied to SLiDAR. Specifically, compared with FAST-SLIO, our OMC-SLIO has an average improvement of 50% in positioning accuracy in the X and Y directions and 35% in the Z direction, as shown in In this section, we discuss why our OMC-SLIO can show better performance for SLiDAR compared to the comparative self-calibration odometer method, as shown in the previous experimental section.The best positioning accuracy using Calib-SLIO verified the practicability of the calibration formulation within the SLiDAR. To some extent, our OMC-SLIO can be considered as an online version of Calib-SLIO. Our OMC-SLIO online calculates both mechanism and sensor parameters within SLiDAR, thus achieving excellent positioning and mapping accuracy. In the set of underground parking experiments, we used the offline estimated extrinsic parameters of Calib-SLIO as the ground truth. Then, all the extrinsic parameters estimated online using FAST-SLIO and OMC-SLIO were averaged and taken as the final extrinsic parameter results. Note that FAST-SLIO estimates only the extrinsic parameters of the sensor, while our OMC-SLIO estimates both the extrinsic parameters of the mechanism and the sensor. As shown in In this paper, we propose a novel self-calibration odometry scheme for SLiDAR, named as online multiple calibration spinning LiDAR inertial odometer (OMC-SLIO), which allows online estimation of multiple extrinsic parameters among the LiDAR, rotating mechanism and IMU, as well as the odometer state. To the best of our knowledge, this is the first multi-extrinsic self-calibration LIO method for SLiDAR. By analyzing the relationships of the internal sensors, we formulate the calibration inside the SLiDAR as mechanism calibration and sensor calibration and build the kinematic model with the encoder information. Further, based on the kinematic model, we present a two-stage motion compensation to eliminate the point cloud distortion caused by LiDAR rotation and platform motion. Finally, the two sets of extrinsic parameters and odometer state are wrapped in a measurement model and estimated with the error-state iterative extended Kalman filter (ESIEKF). We design a 3D SLiDAR platform and conduct experiments in a lab room and underground parking. Experimental results show that our OMC-SLIO is effective and attains excellent performance. Further, the extrinsic parameters comparison test verifies that our OMC-SLIO can better estimate the multiple external parameters of SLiDAR and shows why our OMC-SLIO can achieve higher accuracy in localization and mapping. To maintain the consistence of the localization and mapping of our proposed OMC-SLIO, we will introduce the pose graph optimization resulted from the multiple frames match or the loop closure in future work.


This study examines the impact of employment values on college students’ choice intention of slow employment, as well as the role of employment anxiety and social support in this process. A questionnaire survey is conducted among students from several universities in Haidian and Changping Districts of Beijing to test a theoretical model. It is found that the employment long-term income orientation and employment cost avoidance orientation significantly positively predicted the choice intention of slow employment, and employment anxiety plays a mediating role in this relationship. The short-term income orientation of employment significantly negatively affects the choice intention of slow employment. Social support moderates the impact of the long-term and short-term employment income orientation on employment anxiety and the mediation effect of employment anxiety. This study contributes to the literature on college students’ employment psychology and behavior, and it provides an approach for colleges and universities, society at large, families, and college students to reduce the choice intention of slow employment and achieve fuller employment. The number of students opting for slow employment is increasing in historical terms. The slow employment of college students gradually evolves from an individual phenomenon to an increasingly common group phenomenon. Continuous structural contradictions and uncertainties, such as those owing to the COVID-19 pandemic, have exacerbated this phenomenon, making it more difficult for college students to achieve fuller and higher-quality employment , 137 people in key universities (excluding Projects 985 and 211 universities), 169 people in ordinary universities and 92 people in other institutions. By major, 138 students focused on science and engineering, 277 on economics and management, 144 on the humanities, and 79 on other areas.Employment values are divided into three employment value orientations: long-term employment income orientation, short-term employment income orientation, and employment cost avoidance orientation. Adopting the measurements of employment values developed by Using the definition of slow employment, eight items are designed: the overall choice intention of slow employment; the willingness to have free time; study tours; participation in training; support for education; preparation for entrepreneurship; preparation for exams; and spending time, energy, and money for slow employment. Responses are obtained on a 7-point scale, and its mean value reflects the intensity of the choice intention of slow employment. The greater the value is, the greater the willingness to choose slow employment is. In this study, the coefficient of Cronbach’s α is 0.899.The employment anxiety scale of The measurement of social support refers to the scale modified by First, the reliability and validity of the data were tested. Mplus7 was mainly used here. Second, IBM SPSS Statistics 26.0 was used to analysis the correlations among study variables, the relationship between employment values and the choice intention of slow employment, the mediating effect of employment anxiety about employment values between the choice intention of slow employment, and the moderating role of social support in the relationship between employment values and employment anxiety and in the mediating effect of employment anxiety.To test the degree of deviation of the common method, the Harman single factor test was used. The results of unrotated factor analysis indicate that the variation interpretation amount of the first factor is 29.899%, which is less than 40%. Thus, there is no factor that can explain most variation, and the danger posed by common method bias is not serious. Furthermore, using confirmatory factor analysis of these data, the discriminant validity of the variables can be identified through model comparison. The descriptive statistical results are presented in P < 0.01) and employment anxiety , and employment anxiety significantly positively predictes the choice intention of slow employment . The bootstrap method indicates that employment anxiety playes a partial mediating role between employment long-term income orientation and choice intention of slow employment, ab = 0.03, SE = 0.01 , and the mediation effect accounts for 10% of the total effect. The short-term employment income orientation significantly negatively predicts the choice intention of slow employment ; however, it does not significantly predict employment anxiety . Employment anxiety demonstrates no significant mediation effect between the short-term employment income orientation and choice intention of slow employment . The employment cost avoidance orientation significantly predictes the choice intention of slow employment  and employment anxiety ; employment anxiety significantly positively predicts the choice intention of slow employment . The bootstrap method, indicated that employment anxiety plays a partial mediating role between the employment cost avoidance orientation and slow employment choice intention, ab = 0.04, SE = 0.01 , and the mediation effect accounts for 8.70% of the total effect. H1a, H1b, H1c, H2a, and H2c are thus verified.First, Model 4, provided in the process macro program, was used to control gender, grade, school type, and major category to test the direct and mediation effects. The results are reported in P < 0.1). The interaction between the short-term employment income orientation and social support significantly positively predicts employment anxiety . The interaction between the employment cost avoidance orientation and social support negatively predicts employment anxiety  but not to a significant degree. H3a and H3b are thus verified.Second, Model 7, computed using the process macro program, was used to control gender, grade, school type, and major category to test the moderation effect of social support. The results are reported in To better explain the moderated mediation model, social support was divided into the high (M + 1 sd) and low groups (M – 1 sd), and simple slope analyses were performed for the two groups, with significant moderation effects see , 3. The Finally, further analysis of the moderation effects of social support reveals that social support also plays a moderated role in mediation effects see . With hiThe long-term employment income orientation has a significant positive impact on the choice intention for slow employment, and employment anxiety plays a mediating role, whereas, social support positively moderates the positive impact of long-term employment income orientation on employment anxiety. While pursuing individuality and ideals, some college students focusing on the long-term benefits of employment may plan their careers or improve their employment competitiveness for a period of time after graduation . BecauseBecause the degree of employment anxiety among college students who pay attention to short-term income as they hunt for job is not only affected by the internal and external environment , short-tCollege students who are not oriented to avoiding employment costs are willing to expend more money and spend more time on employment seeking to find a satisfying job, implying that their willingness to find employment is stronger than that of slow employment, and job search time and costs help improve employment opportunities ; therefoThe choice intention of slow employment is related not only to the individual employment of college students but also to the phenomenon of slow employment. This study verified the influence mechanism of employment values on the choice intention of slow employment using a questionnaire survey. First, employment values present college students’ views on employment and have an important impact on the choice intention of slow employment. Second, different employment value orientations have different effects on college students’ choice intention of slow employment. The long-term employment income and employment cost avoidance orientations have significant positive impacts on the choice intention of slow employment, and both can affect the choice intention of slow employment by means of employment anxiety. The short-term employment income orientation has a significant negative impact on the choice intention of slow employment, and the mediation effect for employment anxiety is insignificant. Third, social support plays a crucial moderating role in the impact of employment values on employment anxiety. At high and low levels of social support, the impact of different employment value orientations on the choice intention of slow employment presents different characteristics: at high levels of social support, the long-term employment income orientation has a stronger positive predictive effect on employment anxiety; however, social support changes from low to high, and the predictive effect of the short-term employment income orientation on employment anxiety changes from negative to positive.This study takes the employment values as the starting point for a study of college students’ choice intention of slow employment, contributing to the relevant research literature on college students’ employment values and slow employment. College students are the key focus group in employment research. The spread of the phenomenon of slow employment among college students is not conducive to achieving fuller and higher-quality employment. However, currently, the researches on slow employment begin from this phenomenon and addressed various reasons and countermeasures of the slow employment phenomenon, and the specific study from the perspective of behavior subject is not perfect. This study supplements that research and these conclusions of can also provide theoretical support for the study of the employment psychology of college students after COVID-19. Based on Hofstede’s long-term and short-term cultural values and Pan’s employment income and cost views , this stThe impact of employment values on the choice intention of slow employment indicates that if we want to reduce college students’ choice intention of slow employment and promote the realization of fuller and higher-quality employment among them, we should first promote the establishment of good employment values and explain the long-term and short-term benefits of employment. While discussing the establishment of employment values, we should not blindly emphasize the long-term benefits of the spiritual aspects of development space and work–life balance. In an uncertain employment environment, we should help college students think clearly about and understand the long-term benefits of employment, guiding them to realize the long-term benefits of employment, and formulate a series of practical implementation plans. Furthermore, we should help college students correctly understand the short-term employment benefits of material aspects, such as salary, welfare, and working environment and help them establish clearer short-term employment goals to encourage them to actively obtain and achieve full employment.The mediating role of employment anxiety can enable us to better understand college students’ employment psychology and guide them to seek to actively obtain employment through classification. For college students seeking to understand the long-term benefits of employment, communication should be deployed to help students make career plans more rapidly, improve their career adaptability, reduce their employment anxiety, and shorten the time spent in slow employment . To bettThe fact that social support plays a moderating role shows us that colleges and universities should integrate employment resources with family, enterprises, government, and society to help college students understand the employment situation, emphasize employment dynamics and increase employability. Colleges and universities should develop more exchange activities to promote employment, encourage college students to exchange employment experience and skills, and increase college students’ employment confidence. Colleges and universities can strengthen cooperation with business, enhance the interaction between college students and businesses to lead to employment, broaden the employment channels of college students, and promote the full employment of college students. Families and colleges and universities can build communication platforms among themselves to provide appropriate and timely help for the different needs of college students and solve the spiritual and material problems in employment. Furthermore, colleges and universities, families, news media, and other agents should jointly create a positive employment atmosphere, providing appropriate encouragement and support while reducing pressure on college student, their employment anxiety, and the ability of slow employment owing to anxiety to breed. Moreover, we should mobilize the employment enthusiasm of college students and enable them to eliminate slow employment or shorten its time.This study has several limitations as well. First, family conditions have a crucial impact on college students’ choice of slow employment. Although material support is reflected in social support, it has never been examined separately or controlled. More factors must be considered in subsequent research. Second, there is still room for improvement in the measurement of employment values with reference to the research of The results and limitations of this study indicate some promising directions for future research. In particular, it would be interesting to study the moderating role of different social subjects  to deeply investigate the influence degree of different social subjects. Another direction would be to find the different influence mechanisms to analyze the impact of employment values on the choice intention of slow employment. If we investigate college graduates who exhibit the behavior of slow employment, we can also explore the influence of employment values on the behavior of slow employment and its influence mechanism. Briefly, influenced by the external environment, college students’ slow employment is a group phenomenon in which many issues deserve our attention and examination.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.TW contributed to conceptualization, data analysis, writing, and revision. SL contributed to data collection, theoretical model construction, and original draft preparation. Both authors contributed to the article and approved the submitted version.


The human spine has been optimised through the evolutionary process resulting in a unique structural combination of hard  and soft tissues . The spine and surrounding musculature provide flexibility and structural stability while subjected to loads of varying magnitudes and directions during daily activities and protect the spinal cord and nerve roots from excessive strain. These biological tissues have complex heterogeneous, anisotropic, nonlinear, and hierarchical properties, making their biomechanical characterization challenging. Moreover, aging, diseases, and injuries may affect biomechanical stability, leading to vertebral fractures and/or intervertebral disc (IVD) degeneration, which may induce pain and disability. Different interventions are available to fix or slow the damage progression of the affected tissues, from pharmacological and conservative treatments to surgeries. However, due to the complexity of the microstructure and material properties of the tissues that compose the spine, assessing disease progression or treatment effects on the spine’s biomechanical properties are not trivial.Experimental assessments such as motion capture, complex mechanical loading using dedicated multi-axial rigs, strain analyses with strain gauges, and digital image or volume correlation have been used to characterize biomechanical properties of the spine at different dimensional levels, but they lack the flexibility of testing the same structure in different loading conditions until failure. Moreover, the intrinsic variability of the geometrical, structural, and material properties due to sex, age, size, disease progression, treatments, etc. makes it difficult to test all possible scenarios experimentally. In particular, it is very challenging to measure the influence of the properties of the microstructural components  on bulk tissue material properties. Moreover, damage accumulation of these viscoelastic and poroelastic tissues with age or disease also contributes to experimental challenges in the characterisation of their material behaviour. Therefore, computational models of spine segments and entire lumbar, thoracolumbar, and cervical spines have been developed to evaluate the biomechanical properties of healthy and diseased spines , and to optimize spinal treatment. While generic or subject-specific computational models can be parameterized, efficiently test several loading conditions and comprehensively study the spine biomechanics, the experimental studies remain invaluable to inform, calibrate and validate the models. In fact, increasing the model credibility, based on model verification, validation, sensitivity analyses, and uncertainty quantification is fundamental for developing tools that can be used to support clinical decisions .The current Research Topic presents a unique collection of studies that increase our knowledge about spine biomechanics and stimulate discussions for the improvement of techniques used for computational model development and validation.Müller et al. have used MBD models with subject-specific geometry to predict the load distribution in a healthy lumbar spine as function of the lordosis angle. They confirm earlier assumptions by Roussouly and Pinheiro-Franco . A comprehensive sensitivity analysis showed that increased segment mass led to increased disc loads and muscle activity, that disc stiffness affected only disc translation, and that by increasing muscle strength, the muscle activity largely decreased. These results show that these models can be used to study the effect of diseases and treatments, after appropriate model validation. Firouzabadi et al. have compared spine loads during static manual material handling activities for males and female subjects, using a whole body MBD model. Female subjects had larger compressive and shear loads when normalized to the body weight and larger forces in the oblique abdominal muscles, while male subjects had larger back extensor muscle forces. The study highlights the importance of considering sex-specific parameters.Four studies have used multi-body dynamics (MDB) models for evaluation of ROM, load distribution, muscle forces, and activation on both thoracolumbar and cervical spine. o-Franco  that larPickering et al. have developed a pipeline to create models of paediatric IVDs and performed a sensitivity analysis on the material model inputs. They found that IVD collagen fiber bundles are the main contributors of IVD mechanical behaviour and should therefore be integrated in patient specific FE models of the paediatric spine. In another study, Du et al. have created FE models of the IVD based on magnetic resonance imaging (MRI) data from bovine spine and evaluated the model sensitivity to different geometrical and material input parameters, highlighting that it is fundamental to model well the geometry of the vertebral endplates. It should be noted that while FE models have great potential in assessing the biomechanical behaviour of spine segments, process automation is needed to improve the efficiency and reduce operator dependency for clinical application. Caprara et al. have developed an automatic pipeline to create subject-specific FE models of the lumbar spine from CT images by using deep learning techniques to segment the geometries, statistical shape models to create the meshes, and FE models to simulate different loading conditions and predict ROM of the segments. This automatic tool, the results of which agreed with literature data, has the potential of improving the clinical applicability of biomechanical simulations. FE models have been widely used to test the effect of spine fixation for treating vertebral fractures, IVD degeneration, spine deformities and other diseases as well. Sensale et al. have performed a verification and sensitivity analysis for subject-specific FE models of a single vertebra implanted with two pedicle screws. They have reported that the diameter of the screw is more important than its length for minimising screw and bone deformations. Moreover, they highlighted the importance of modelling realistic screw geometry. Bereczki et al. have developed an L2-L4 spine segment FE model to study the stability of different implants for oblique lumbar interbody fusion when implanted in healthy or osteoporotic bone. They showed that spine segment stability was affected by the used implant and that osteoporosis increases the ROM for all tested constructs. Gierig et al. have used a large FE model of the lumbar spine that also included the pelvis and spinopelvic devices to study the best configuration in fixing spinopelvic fractures and to show its superiority compared to non-surgical treatment. Ke et al. have used an FE model of C2-T1 spine segments to evaluate different surgical treatments of adjacent diseased segment (ADS) after a primary anterior cervical discectomy and fusion (ACDF). The model suggests that a second ACDF leads to better outcomes compared to laminoplasty in the tested case. In another study, Wo et al. have used a combination of an FE model of C2-C7 cervical segment, wear tests and animal study on non-human primate, to study the biomechanics of cervical subtotal discectomy prosthesis (CSDP) as an alternative for ACDF. The FE models showed the influence of the implant position on the CSDP performance including ROM, bone-implant stress, and forces at the facet joints. Nikkhoo et al. have used poro-elastic FE models to study the biomechanical stability of rigid (Ti rods) or semi-rigid (PEEK) posterolateral fixation for ADS. They showed that, compared with Ti constructs, the PEEK prosthesis may be preferable as it is associated with a slightly higher ROM at the instrumented level and lower IVD height loss, fluid loss, axial stress, and collagen fiber strain in the adjacent disc. Tachi et al. have used an FE model of the spine of patients with adolescent idiopathic scoliosis to pre-plan the surgical correction procedure with pre-bent spinal rods. This preplanning system can be used to optimize which spine levels to instrument and the rod shape.Ten manuscripts have used detailed structural FE models to evaluate the mechanical properties of the IVD, single vertebra, or spine segments. While many FE models have been utilized to characterize biomechanical properties of vertebral bodies and spine segments, there are still challenges to accurately model of the IVD material, create efficient spinal segment models, and to using FE models predictions to optimise treatment strategies. Favier et al. coupled L1-L5 spine FE model with lower strain-driven algorithm to predict local bone changes induced by physiological loading conditions calculated from a previously developed full-body MBD model. They showed that in order to maintain trabecular and cortical bone health, a combination of moderate and more demanding activities (large spine movement and lifting tasks) are needed. In fact, moderate intensity activities alone were not found to be sufficient to maintain bone health in the vertebrae. Panico et al. have tested the effect of simulating realistic muscle forces in FE models of lumbar fixation implants. They coupled a previously developed MBD model of the thoraco-lumbar spine with articulated ribcage with a detailed FE model of T10-T12 segments to compare the results of models with realistic and simplified (pure moments) loading. Intact spine segments and instrumented spine segments with rods and screws were simulated. The realistic FE models showed similar ROM but higher stresses in the pedicle screws and in the posterior rods compared to the simplified models, showing the importance of using realistic loading when evaluating implant stresses. Pachocki et al. have used a global FE model that includes a concrete road safety barrier, an impacting vehicle, and an occupant. The occupant model includes a lumbar spine FE model to study the biomechanics of injuries during road barrier collision. The two-scales model estimated the loading condition on the spine model from a larger FE dynamic model of the subject in the impacting vehicle. They have shown that during the crash the loading on the lumbar spine is eccentric and leads to high axial loads and flexion bending moments on L1-L5, explaining why fractures are associated with this loading scenario.The above-mentioned studies showed how FE models can assist surgeons in identifying the best prosthesis in cases of different spine diseases. However, there are still challenges in creating more realistic computational models accounting for the hierarchical properties of the spine with multi-scale approaches, that for example, better estimate the loading scenarios or the effect of bone remodelling over time, and in validating the outputs of the models to improve their credibility and their future clinical applicability. ex vivo or in vivo experimental data to inform and validate FE models of the IVD. Deneuville et al. have performed a proof-of-concept study using ex vivo MRI imaging of an L1-L3 ovine spine segment under different loading conditions before and after inducing damage of the IVD to evaluate its effect on the deformation of the nucleus pulposus. They combined this experiment with an FE model of the spine segments to evaluate the effect of the IVD damage on the stress field, showing the potential of this approach to study IVD biomechanics from MR images. Mengoni et al. have validated the outputs of MRI based FE models of the IVD, against ex vivo experiments performed on bovine specimens to measure the IVD bulge. The results showed that including subject-specific geometrical and material properties of the IVD in the FE models does not improve substantially the predictions of IVD stiffness and bulge. Finally, Zhou et al. Have developed a multiscale and multiphasic FE model of the IVD and validated it against experiments for the bovine caudal vertebra. In most cases the multiscale model, developed from experimental data of fiber and matrix mechanical behaviour, accurately predicted the structural response of the IVD, highlighting the importance of modelling the fibers, matrix-fiber interactions, and the fluid-based load bearing mechanism of this complex structure.Three manuscripts in the Research Topic have collected etc.), more credible through comprehensive and systematic validation process using ex vivo and in vivo data, certifiable by regulatory bodies, adaptable to study a single subject or generic to study a patient population. To conclude, while there is no doubt that research in this exciting area will keep progressing and improving our knowledge of the Biomechanical Properties of the Healthy, Diseased and Treated Spine as demonstrated in this Research Topic, the research community should encourage and strengthen interdisciplinary collaborative research involving bioengineering, biology, and medicine.This Research Topic includes 20 peer-reviewed papers tackling different challenges in the topic of development and validation of computational modelling of spine biomechanics. Every paper reports the potential and current limitations of the developed approaches, highlighting progress that the research community has done in this area, and where we should focus to improve clinical applicability. We would like to emphasise that, while the presented research is fundamental for understanding the biomechanics of the spine and further develop computational models to support clinical decision making, a lot of work needs to be done to see these approaches used routinely. We anticipate that future studies that use biomechanical models of the human spine will be even more realistic and biofidelic (e.g., considering complex individualized loading and boundary conditions taking into account the everyday behaviour, functional behaviours and adaptations after surgical procedures or pain experiences, activation patterns, individualized material properties,