**3. Cause of myocarditis and classification**

Myocarditis is classified by cause, clinical type, and pathological picture. In clinical medicine, myocarditis presenting as a sudden development should be attended to because any delay of treatment presents a risk of fatal circulatory failure. It should be recognized that there is different prognosis depending on the clinical type of myocarditis. The classification of myocarditis is shown in Table 1.

#### **3.1 Causes**

Several causes or mechanisms of the development of myocarditis have been detected, among which infection is the most the frequent and important. In earlier years, myocarditis was often caused by rheumatic fever and diphtheria. More recently, in advanced nations it is mostly caused by viral infections. Bowles et al. (1986) reported that Coxsackie B virus was detected in patients with myocarditis using a dot blot hybridization method. Coxsackie virus, an enterovirus belonging to the picornavirus family, was extracted from patients with polio in 1982 and is particularly compatible with myocardium (Clements, 1993). Half of group A types and all of group B types of the Coxsackie virus cause myocarditis accompanied by symptoms of the common cold.

Presently, it is possible to detect many viruses with polymerase chain reaction or in situ hybridization. Therefore, we can detect myocarditis due to viral infection in most cases. In

In this chapter, we explain the causes, mechanisms as presently known, classification, and clinical course of myocarditis. Additionally, we outline the recommended treatment for the

The clinical course of myocarditis varies. The symptoms range widely, from slight to severe, and it is difficult to investigate myocarditis epidemiologically. In 2002 in Japan, a large-scale investigation for cardiomyopathy was performed and reported that cardiomyopathy was found in 21.3 per 100,000 population (Miura et al., 2002). However, the subjects of this investigation were consulted patients with data provided by hospitals. It is thought that actual morbidity is higher, because there are many non-consulted persons with occult cardiomyopathy, such as early stage dilated cardiomyopathy or hypertrophic cardiomyopathy with no symptoms. Therefore, we still cannot grasp the exact morbidity of myocarditis in Japan. Okada et al. (1989) reported that among 10,000 autopsied cases during 1958–1978 there were 115 cases of myocarditis. In another report, occult myocarditis was found in 0.6% of autopsied cases in which cardiac disease had not detected while the patients were alive (Feely et al., 2000). Therefore, it should be recognized that myocarditis is not clinically infrequent and includes a mild type that displays no symptoms. The mortality rate for myocarditis has not been established. An investigative committee of the Ministry of Public Welfare and Labor in Japan reported in 1986 that 13 (4.7%) of 274 patients died within 1 month in a small-scale investigation targeting acute-phase myocarditis (Kawamura et al., 1986). Among those cases, the causes of death were cardiogenic shock in six cases (46%), congestive heart failure in five cases (38%), and complete atrioventricular block in two cases (15%). Intensive treatment for severe cardiac dysfunction and fatal arrhythmias

are important to reduce mortality during the acute phase of severe myocarditis.

Myocarditis is classified by cause, clinical type, and pathological picture. In clinical medicine, myocarditis presenting as a sudden development should be attended to because any delay of treatment presents a risk of fatal circulatory failure. It should be recognized that there is different prognosis depending on the clinical type of myocarditis. The

Several causes or mechanisms of the development of myocarditis have been detected, among which infection is the most the frequent and important. In earlier years, myocarditis was often caused by rheumatic fever and diphtheria. More recently, in advanced nations it is mostly caused by viral infections. Bowles et al. (1986) reported that Coxsackie B virus was detected in patients with myocarditis using a dot blot hybridization method. Coxsackie virus, an enterovirus belonging to the picornavirus family, was extracted from patients with polio in 1982 and is particularly compatible with myocardium (Clements, 1993). Half of group A types and all of group B types of the Coxsackie virus cause myocarditis

Presently, it is possible to detect many viruses with polymerase chain reaction or in situ hybridization. Therefore, we can detect myocarditis due to viral infection in most cases. In

**3. Cause of myocarditis and classification**

classification of myocarditis is shown in Table 1.

accompanied by symptoms of the common cold.

**3.1 Causes**

acute phase of myocarditis.

**2. Epidemiology and prognosis**

Table 1. classification of myocarditis. modified from the guideline for the diagnosis and treatment of myocarditis (JCS, 2005).

1. Nonsteroidal anti-inflammatory drugs Indomethacin, oxyphenbutazone, phenylbutazone 2. Psychotropic drugs (Tricyclic) antidepressant: imipramine, clomipramine, amitriptyline Antimanic: lithium carbonate, lithium oxalic acid Antiepileptic: phenytoin, carbamazepine 3. Diuretic: acetazolamide, hydrochlorothiazide, spironolactone, chlorthalidone 4. Depressor: methyldopa 5. Anticancer drug: adriamycin, daunorubicin, mitoxantrone 6. Antibiotics Amphotericin B, penicillin, ampicillin, tetracycline Chloramphenicol, streptomycin 7. Sulfaminum: sulfadiazine, sulfisoxazole 8. Antiphthisic: isoniazid (INH), para-aminosalicylic acid (PAS) 9. Biological agents: tetanus toxoid, α-interferon, interleukin 2 (IL-2) 10. Antidiabetic: sulfonylurea 11. Others: catecholamines, cocaine, amphetamine, arsenic

Table 2. Drugs that cause myocarditis.

Acute Myocarditis in Emergency Medicine 73

differential diagnosis between viral myocarditis and eosinophilic myocarditis is often impossible because the eosinophil count is normal during the early phase of eosinophilic myocarditis (Morimoto et al., 2003). White blood cells (WBCs) gradually increase with the development of an inflammatory reaction; and materials toxic to the myocardium released from eosinophilic leukocytes cause severe contraction of the myocardium as the eosinophil

In most cases, the increase in eosinophils is detected in a peripheral blood examination. However, some patients who suffer from circulatory insufficiency exhibit a delayed increase in eosinophils (Gets et al., 1991). Therefore, we should perform more frequent eosinophil counts during the acute phase. Infiltration of eosinophilic leukocytes, degranulation, and

The main causes are an allergic reaction, drugs, and parasitic infection. Most cases, however, are treated as idiopathic myocarditis (Forrester et al., 1976). It has been reported that the mortality rate among patients with acute-phase eosinophilic myocarditis is approximately

Myocarditis is clinically classified as acute or chronic. Since it is possible to detect the exact onset of acute myocarditis, it is easier to estimate the circulatory parameters for diagnosis and establish the strategy for treatment of acute myocarditis than for chronic myocarditis. In some cases of acute myocarditis, we treat it as fulminant myocarditis that has developed suddenly and may progress to severe circulatory failure during the acute phase (Aoyama et al., 2002). The worldwide morbidity and mortality rates associated with fulminant myocarditis are not yet clear. Cupta et al. (2008) reported that the frequency of fulminant

The global concept of chronic myocarditis has not been established, although several studies have suggested that viral infection (Fujioka et al., 2000) or autoimmunity (Lauer et al., 2000) play a role in its development. There are clinically two types of chronic myocarditis, and they have different clinical courses. One type has persistent, continuous symptoms, and the

In an investigation of clinical types of myocarditis in 48 patients reported by Kodama et al. (2001), nine were the acute type, 21 were the fulminant type, three were the chronic persistent symptom type, and 15 were the chronic unremarkable symptom type. The mortality rates during the first admission were 22% for the acute type, 43% for the fulminant type, 33% for the chronic persistent symptom type, and 40% for the chronic unremarkable symptom type. The long-term prognosis for patients who recovered from their cardiac dysfunction during the early phase was good. However, the long-term prognosis for patients who were diagnosed with the chronic, unremarkable symptom type was not good because they developed irreversible circulatory dysfunction, such as dilated

Clinically, symptoms range from slight problemsfever, pharyngeal pain, cough, vomiting, diarrhea, and arthropathies, as observed with the common coldto severe circulatory failure. Therefore, we cannot list any symptoms characteristic of acute-phase myocarditis. In

myocarditis is 10% among all cases of acute myocarditis in the United States.

destruction of myocardium are observed in the biopsy specimen.

7% (Morimot et al., 2003), (Mori et al., 2004).

other has unremarkable symptoms (JCS, 1996).

**4. Clinical symptoms and diagnosis**

**4.1 Clinical symptoms and physical symptoms**

count exceeds 500/nm3.

**3.3 Clinical classification**

cardiomyopathy.

recent reports, adenovirus, sharing the same receptors as the Coxsackie virus, parvovirus B19, human herpes virus 6, and hepatitis C virus, are known to cause myocarditis (Okabe et al., 1997).

Myocarditis does not always develop in patients infected by a virus compatible with the myocardium (e.g., the Coxsackie virus). In such cases, symptoms of myocarditis are unremarkable or slight, and the mechanism of development of myocarditis remains unknown. Based on the results in experimental animal models, Cupta et al. (2008) suggested a developmental pattern of myocardial damage by an infective virus and the host's reactions as follows: (1) initial infection of virus in myocardial cells; (2) innate immune reaction; (3) defense by adaptive immunity; and (4) recovery of inflammatory reaction.

Several kinds of drugs, external physical stimulations such as exposure to irradiation or excessive heat, metabolic disorders, pregnancy, collagen diseases, sarcoidosis, and Kawasaki disease are important causes of myocarditis. It should be well noted that drug-induced myocarditis, particular in Japan, Europe, and the United States, is caused by many of the drugs that are administered or prescribed to patients in advanced countries. Drugs that cause myocarditis are shown in Table 2.

#### **3.2 Histological classification**

Histologically, myocarditis is classified as lymphocytic myocarditis, giant cell myocarditis, eosinophilic leukocyte myocarditis, and granuloma myocarditis. Most cases of lymphocytic myocarditis are caused by infection. Other types are due to materials toxic to the myocardium, a drug allergy, or an autoimmune reaction.

#### **3.2.1 Lymphocytic myocarditis**

Lymphocytic myocarditis is the most frequent histological type, and most cases are caused by a viral infection. Kodama et al. found that 85% of patients with myocarditis were diagnosed with the lymphocytic variety (Kodama et al., 2001). The primary symptomsfever and pharyngeal painare not specific for myocarditis during the early phase, but symptoms of circulatory failure, such as edema, are specific and are observed during the developed phase. The severity of circulatory failure ranges widely from slight to fulminant.

#### **3.2.2 Giant cell myocarditis**

Giant cell myocarditis is encountered infrequently. Clinically, it has a poor prognosis because it can easily progress to fulminant myocarditis. After the onset, circulatory failure develops suddenly and in many cases rapidly progresses to a fatal state. It is suggested that an allergic reaction or an autoimmune reaction participates in this development. Infiltration by inflammatory cells and multinucleated cells are observed in the myocardium (Davidoff et al., 1991). Cardiac function markedly deteriorates with massive necrosis of the myocardium. Identification of multinucleated cells is necessary for a definitive diagnosis. It is difficult to decide on the timing of a biopsy because multinucleated cells are seen only during the acute phase. In patients presenting with a chronic course, cardiac sarcoidosis must be excluded (Shield et al., 2002).

#### **3.2.3 Eosinophilic myocarditis**

The clinical symptoms of eosinophilic myocarditisfever, pharyngeal pain, coughduring the early phase are similar to those seen with myocarditis due to a viral infection. The

recent reports, adenovirus, sharing the same receptors as the Coxsackie virus, parvovirus B19, human herpes virus 6, and hepatitis C virus, are known to cause myocarditis (Okabe et

Myocarditis does not always develop in patients infected by a virus compatible with the myocardium (e.g., the Coxsackie virus). In such cases, symptoms of myocarditis are unremarkable or slight, and the mechanism of development of myocarditis remains unknown. Based on the results in experimental animal models, Cupta et al. (2008) suggested a developmental pattern of myocardial damage by an infective virus and the host's reactions as follows: (1) initial infection of virus in myocardial cells; (2) innate immune reaction; (3)

Several kinds of drugs, external physical stimulations such as exposure to irradiation or excessive heat, metabolic disorders, pregnancy, collagen diseases, sarcoidosis, and Kawasaki disease are important causes of myocarditis. It should be well noted that drug-induced myocarditis, particular in Japan, Europe, and the United States, is caused by many of the drugs that are administered or prescribed to patients in advanced countries. Drugs that

Histologically, myocarditis is classified as lymphocytic myocarditis, giant cell myocarditis, eosinophilic leukocyte myocarditis, and granuloma myocarditis. Most cases of lymphocytic myocarditis are caused by infection. Other types are due to materials toxic to the

Lymphocytic myocarditis is the most frequent histological type, and most cases are caused by a viral infection. Kodama et al. found that 85% of patients with myocarditis were diagnosed with the lymphocytic variety (Kodama et al., 2001). The primary symptomsfever and pharyngeal painare not specific for myocarditis during the early phase, but symptoms of circulatory failure, such as edema, are specific and are observed during the developed phase. The severity of circulatory failure ranges widely from slight to

Giant cell myocarditis is encountered infrequently. Clinically, it has a poor prognosis because it can easily progress to fulminant myocarditis. After the onset, circulatory failure develops suddenly and in many cases rapidly progresses to a fatal state. It is suggested that an allergic reaction or an autoimmune reaction participates in this development. Infiltration by inflammatory cells and multinucleated cells are observed in the myocardium (Davidoff et al., 1991). Cardiac function markedly deteriorates with massive necrosis of the myocardium. Identification of multinucleated cells is necessary for a definitive diagnosis. It is difficult to decide on the timing of a biopsy because multinucleated cells are seen only during the acute phase. In patients presenting with a chronic course, cardiac sarcoidosis must be excluded

The clinical symptoms of eosinophilic myocarditisfever, pharyngeal pain, coughduring the early phase are similar to those seen with myocarditis due to a viral infection. The

defense by adaptive immunity; and (4) recovery of inflammatory reaction.

cause myocarditis are shown in Table 2.

myocardium, a drug allergy, or an autoimmune reaction.

**3.2 Histological classification**

**3.2.1 Lymphocytic myocarditis**

**3.2.2 Giant cell myocarditis**

(Shield et al., 2002).

**3.2.3 Eosinophilic myocarditis**

fulminant.

al., 1997).

differential diagnosis between viral myocarditis and eosinophilic myocarditis is often impossible because the eosinophil count is normal during the early phase of eosinophilic myocarditis (Morimoto et al., 2003). White blood cells (WBCs) gradually increase with the development of an inflammatory reaction; and materials toxic to the myocardium released from eosinophilic leukocytes cause severe contraction of the myocardium as the eosinophil count exceeds 500/nm3.

In most cases, the increase in eosinophils is detected in a peripheral blood examination. However, some patients who suffer from circulatory insufficiency exhibit a delayed increase in eosinophils (Gets et al., 1991). Therefore, we should perform more frequent eosinophil counts during the acute phase. Infiltration of eosinophilic leukocytes, degranulation, and destruction of myocardium are observed in the biopsy specimen.

The main causes are an allergic reaction, drugs, and parasitic infection. Most cases, however, are treated as idiopathic myocarditis (Forrester et al., 1976). It has been reported that the mortality rate among patients with acute-phase eosinophilic myocarditis is approximately 7% (Morimot et al., 2003), (Mori et al., 2004).


**4.2 Novel formulation approaches for improving skin delivery of NSAIDs 4.2.1 Micromemulsions**

Microemulsions are transparent liquid dispersions with a droplet size of 20-200 nm. Their formulations include four fundamental components, which are water, oil, surfactant and co-surfactant. The advantages of microemulsions include enhancing solubility of drugs, thermodynamic stability, ease of preparation and low costs (Neubert, 2011). Microemulsions have recently attracted attention in enhancing dermal permeation of lypophilic drugs as well as hydrophilic drugs. The oils and surfactants included in the composition of microemulsions also act as penetration enhancers. Besides, the composition of formulation and the internal structure of phases enhance diffusion of the drug inside the carrier and improve the partition of drug to SC (Kogan & Garti, 2006). The most important disadvantage of microemulsions is potential risk of skin irritation due to their high content of surfactants. Kantarc et al. (2007) prepared microemulsion formulations containing diclofenac sodium, and optimized it in with vitro tests. The irritant effect of formulations was investigated on healthy volunteers, and their safety was demonstrated. In another study, lecithin microemulsions of ketoprofen were developed (Paolino et al., 2002). Permeation of drug from microemulsion formulation was compared to the conventional dermal ketoprofen formulation. In this study performed with healthy volunteers, it was demonstrated that ketoprofen microemulsions enhanced the permeation of drug and has good skin tolerability (Amrish & Kumar, 2009). Dalmora et al. (2001) administered microemulsions loaded with piroxicam to rats in vivo, and demonstrated that dermal anti-inflammatory effect was extended, and inflammation inhibition lasted for nine days following single-dose administration. In vivo antiinflammatory activity study has also demonstrated that microemulsions containing flurbiprofen performed better than conventional gel formulation (Ambade et al., 2008). In another study, nano/submicron emulsions of flurbiprofen were suggested as dermal carriers (Fang et al., 2004).

#### **4.2.2 Vesicular carriers**

Vesicular systems such as liposomes, niosomes and transfersomes have been developed for optimization of dermal penetration of drugs and particularly for dermal targeting. Vesicular systems have the advantages of controlling release rate of the active ingredient and to ensure localization of dermally administered drugs in dermal layers. Besides, transdermal administration of vesicular systems helps to carry drug molecules into systemic circulation (El Sayed et al., 2007; Ceve, 2004).

#### <IP_ADDRESS> Liposomes

Liposomes are described as lipidic vesicles containing water. Cholesterol and phospholipids or amphiphilic ingredients of these compounds are typically used as lipids. Liposomes can capture hydrophilic molecules or contain lipophilic molecules in their membranes. Some liposomes can be adsorbed in the skin surface or may go into fusion. Fusion of liposomes may increase the drag force required for permeation of the molecule and facilitate dermal penetration of the drug. However, fusion of liposomes on the skin surface does not apply for macromolecular drugs. Another mechanism is penetration of liposomes to SC before fusion with SC lipids and releasing the drug there. With this mechanism, particularly the drug in liposomes that are dermally administered can be localized in different layers of the skin (El Magraby et al., 2008; Williams, 2003).

Mezei & Gulasekharam (1980) used liposomes as "dermal drug carrier system" for the first time. However, liposomes are localized in the outermost layer of the skin (SC). Therefore, it is advantageous in cases where retaining drug in SC is desirable. It does not seem possible with these systems to penetrate the drug to deeper tissues of the skin or into systemic circulation. Therefore, it is rather preferred to increase dermal moisture for cosmetic purposes (El Magraby et al., 2008; Williams, 2003).


**5. Conclusion and future work**

It is natural that the spread of ubiquitous computing to increase the number of devices with low computing power scattered all over the planet. The security of data transmissions from these devices should be improved in a preventative manner to avoid possible attacks. Regarding WSNs, RSA public key algorithm is the most commonly used is standardized, and achieves efficiency relatively good. The algorithm based on elliptic curves have been extensively studied in academia as an alternative to RSA, and the results show that it is possible to achieve good results with smaller keys. The algorithm MQQ was discovered recently and showed significant results when compared to RSA and ECC, taking as parameters authenticity and digital signature. This algorithm is post-quantum, and may even be a good solution when the quantum computation is standardized. Despite the satisfactory results of MQQ front of RSA and ECC algorithms, there is not a work about performance evaluation specific to encryption and decryption of data.


*2.6.1 Parkinson's disease (PD)*

The strategy of gene therapy has been applied to this disease in order to improve the advanced symptoms of PD. Gene therapy was applied to transfer 'Glutamic Acid Decarboxylase (GAD), a chemical produced by a gene into the basal ganglia. GAD showed an increased amount of a neurotransmitter called as Gamma-Aminobutyric Acid (GABA), responsible for inhibiting brain signals and decreasing activity in the nervous system Decreased GABA activity leads to certain brain-related disorders [34].

#### *2.6.2 Alzheimer's disease (AD)*

AD and other frontotemporal dementias (FTDs) are caused by the accumulation of amyloid-β peptide (Aβ) and protein tau in the brain. It is characterized by having memory loss, difficulty in learning and communicating along with the inability to organize things. The use of recombinant Adeno-Associated Viruses (rAAVs) has provided new ways for studying AD and other related neurological disorders [35]. Such strategies or approaches have added novel dimensions to medical treatments.

#### *2.6.3 Cystic fibrosis*

Cystic fibrosis is a disease known to affect the lungs primarily. Its symptoms include inflammation, airway obstruction leading to respiratory tract infection and deformity. Insertion of the Cystic Fibrosis Transmembrane Regulator (CFTR) gene directly into the epithelium cells of the respiratory tract bear the capability to lessen the symptoms but not totally cure the disease in patients suffering from cystic fibrosis [36].

#### **2.7 Cell therapy**

Cell-based therapy is one of the most important and well-known forms of all treatments in the fields of modern science & medicine. It is not only a curative option for treating deadly or threatening diseases but is also making 'Regenerative Medicine' the most vital technique in health care with the specific goal of replacing diseased cells, tissues or organs and thereby restoring their normal function(s) [4]. Over the years, there has been a gush of interests and work done in understanding the potential of stem cells. They are the cells found naturally in the living bodies, characterized by two defining properties of eternal self-renewal and the propensity to differentiate into an adult cell type. There are three main types of stem cells: Totipotent (a cell developing into a healthy organism independent of the permissive environment), Pluripotent (a cell developing into any type of adult cell) and Multipotent (a cell developing into a limited type of cell) [37].

Following is the account of different stem cells used for the treatment of various diseases:-

#### *2.7.1 Pluripotent stem cells*

Reportedly, pluripotent cells have been used successfully to treat animals per se. Animals diagnosed with diabetes are incorporated with cells containing insulin responsive to glucose levels. Additionally, the treatment of the animals suffering from acute spinal cord injury and visual impairment is performed with myelinated neurons and retinal epithelial cells, respectively. Researchers are still conducting studies with the use of pluripotent stem cells to cure several disorders such as Parkinson's disease, muscular dystrophy and heart failure.

*Two-Dimensional and Three-Dimensional Cell Culture and Their Applications DOI: http://dx.doi.org/10.5772/intechopen.100382*


**1. Introduction**

More than one billion tons of biomass will be available for bioenergy production in the USA by 2030 [1–3]. Among other resources, corn stover (CS) has a huge potential to contribute to the renewable energy portfolio, as more than 250 million dry tons of CS are produced annually in the USA [1,4]. With proper feedstock handling and preprocessing, CS could become an abundant source of bioenergy [5,6]. However, a significant amount of agricultural waste, including CS, is burnt or left unprocessed in the field due to high logistical costs. This results in serious environmental problems and economic forfeiture [7,8]. Therefore, the utilization of potential bioenergy from waste biomass sources such as CS needs to be considered with urgency.

Air classification (AC) is a low-cost preprocessing technology that has been developed particularly in agricultural processing and mining applications. In AC, the separations are performed based on a combination of material size, density, and drag properties, utilizing screens and air streams to effectively separate high-density fractions from lowdensity fractions. In general, large amounts of soil, rocks, and other foreign matters are incorporated into the feedstock during harvest and collection. The inorganics, dirt, rocks,

**Citation:** Islam, M.T.; Saha, N.; Hernandez, S.; Klinger, J.; Reza, M.T. Integration of Air Classification and Hydrothermal Carbonization to Enhance Energy Recovery of Corn Stover. *Energies* **2021**, *14*, 1397. https://doi.org/10.3390/en14051397

Academic Editor: Byong-Hun Jeon

Received: 28 January 2021 Accepted: 1 March 2021 Published: 4 March 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

and foreign materials are mostly dense materials compared to the lignocellulosic structure of biomass. Therefore, AC separates a significant amount of these exogenous inorganics and creates an enriched stream of biomass (often called the light ash fraction, LAF) and a soil-laden reject stream (also known as the high ash fraction, HAF) [9–11]. Lacey et al. [11] showed such separations for chipped forest residues after AC and reported remarkable ash (wt. %) reductions (>32 wt. %) in the final throughputs. Emerson et al. [9] also found quite reasonable reductions in ash (wt. %) for hybrid poplar (from 2.34 wt. % to 1.67 wt. %) and shrub willow (from 2.60 wt. % to 2.14 wt. %). Recently, Thompson et al. [2] showed that AC can effectively upgrade CS by removing 30 wt. % ash at a mild 7.5 Hz fan speed, or approximately 2.1 m/s counter-stream air flow of AC. It has also been reported that a large fraction of HAF byproduct is produced during AC, accounting for more than 12 wt. % of the initial CS. This HAF of CS contains more than 80 wt. % organic content that can be further utilized [2]. Instead, an estimated HAF disposal cost of USD 28.86 per ton has been suggested by Reza et al. [12] and Humbird et al. [13], accounting for 2.5 cents of the USD 2.15 per gallon minimum ethanol selling price. In order to make AC more economically viable, the further utilization of HAF needs to be implemented in conjunction with AC technologies and system-wide economics and sustainability for full material utilization. However, to the best of the authors' knowledge, no work has been done to date to utilize the waste energy in value-added fuel. Therefore, to make use of the vital unrecovered energy from this solid waste and integrate it with the AC technology, the HAF could be converted into essential products.

Hydrothermal carbonization (HTC) is a promising thermochemical process that transforms biomass, such as CS, into a carbon-rich solid product called hydrochar [5,14,15]. The reaction temperature varies between 180 and 260 ◦C, and the pressures are maintained above the saturation pressure. The ionic products of water increase three orders of magnitude (KH2O (573K)/KH2O (298K) = 103) [5,15,16] and the dielectric constant of water reduces from 78.5 (298 K, 0.1 MPa) to 27.1 (523 K, 5 MPa) [15,17]. As a result, biomass undergoes a series of reactions, i.e., hydrolysis, decarboxylation, dehydration, condensation polymerization, and aromatization, in subcritical water due to the increased reactivity and solvent-like properties [18,19]. For agricultural residues, the HTC reaction products can be divided into three streams: 41–90 wt. % solids with 80–95 wt. % of the original calorific value; 2–10 wt. % gas consisting mainly of CO2; the rest is process liquid [20–24]. The energy-dense solid hydrochar can be pelletized to improve the mass and energy density of the feedstock and reduce the cost of transportation, handling and storage [25–27].

During HTC, the low density and low viscosity of subcritical water, in combination with the acidic process liquid and the modification of the biomass structure, aid in the leaching of inorganics from biomass structures [18,28–31]. The reduction of ash is particularly important for hydrochars' application as fuel, as this can significantly reduce the ash-fusion temperatures, leading to slagging in fuel boilers [1]. Therefore, HTC could be used to recover the energy in the HAF stream while reducing ash from the hydrochar. However, HTC is an energy-intensive process as it requires high temperatures and high pressure. Therefore, an energy balance in the integrated AC–HTC is warranted to evaluate the net energy recovery from the integrated process compared to the individual AC and HTC processes. Therefore, the main goal of this work was to study the feasibility of three different scenarios, to determine the energy recovery from CS: 1. AC-only process; 2. HTC-only process; 3. Integrated AC–HTC process. First, the AC of CS was performed to separate LAF and HAF. Then HTC on HAF was performed at various temperatures and the hydrochars were pelletized with LAF. The energy recovery from the integrated AC–HTC process was compared with AC-only and HTC-only, wherein the original (ORG) CS was used for both technologies.