Swine production is a for-profit activity; however, most farms have deficient internal controls and empirical management and do not even know the cost of the market hog produced. Knowing the production cost of what will be commercialized is crucial for any process that involves business management, and in pig production, it is no different. However, the lack of a standard method and simple and easily accessible tools make it difficult for producers to organize the economic management of their businesses. In this sense, the present work aimed to develop a free and easy-to-use tool that calculates swine production costs and serves as a management tool in commercial properties.® software (version 2207). Case studies were used to assist in the characterization and construction of the model. Through the panel method, the tool was validated by professionals in the sector. Costs were considered according to the Neoclassical Economic Theory of Costs and allocated in the order of variable costs, fixed operating costs, and opportunity costs of capital and land. These costs together create the total cost. The model provides the total cost per batch, per market pig, per arroba, and per kilogram, which facilitates the interpretation of the results and economic evaluations of the system. The model is adaptable to different types of swine farming, as well as the consideration of all costs involved in the production system, whether explicit or implicit. The model developed has the potential to be used as a management tool in commercial swine production systems, assisting the producer in the decision-making process through the management and control of production costs.This paper aims to present a tool that offers pig producers a standard method to calculate and control their production costs and, consequently, provides the necessary information to guide strategic decision-making. Following these premises, a mathematical model to estimate swine production costs were developed using Microsoft Excel Commercial pig production is marked by the continuous search for productivity and profitability ,2, whichThrough economic and productive analysis within the farm, the manager becomes aware of the results obtained in the activity, able to verify the production process step by step and thus locate the bottlenecks within the management of his business ,2,3. HowWith a market evidenced by dependence on commodity prices  and volaThe lack of a previously defined standard protocol for the calculation of production costs is one of the main factors that make it difficult to carry out cost analysis in livestock activities . In the The objective of this study was to develop a mathematical model to estimate swine production costs that would be flexible to meet the most varied types and organizational arrangements of swine production systems existing worldwide and offers pig producers a standard method to calculate and control their production costs, and consequently, provides the necessary information to guide strategic decision-making.Research on animals was conducted according to the institutional ethics committee on animal use (CEUA nº4257240619) and the institutional research ethics committee from Brazil Platform (CEP 3.780.942).This research was carried out in Pirassununga, State of São Paulo, Brazil, and its development consisted of three steps. Firstly, case studies were carried out to provide a detailed description of the production process and the characteristics of the independent swine production systems. In the second stage, there was the development of the model for calculating the costs of pig production, based on the Neoclassical Economic Theory of Costs and the characteristics of the production systems defined in the first stage. In the third stage, the presentation and validation of the calculation model for the agents in the swine production chain were carried out.The first stage of the study consisted of carrying out case studies to understand in detail the production process and the characteristics of the complete cycle swine production systems. The case study investigates methodology and addressed questions that refer to “how” and “why” the research is being conducted. The questions of the study were formulated to define the swine production unit to be analyzed, following the procedures proposed by Yin . The conAfter identifying pig producer partners, two case studies were conducted. Technical visits were carried out on two farms, and a questionnaire was given to the property manager as a way of validating the data collected with production employees, sector leaders, and technical managers.Information regarding the management of the farms was collected, and main fees and taxes were paid by pig farming, machinery, equipment, vehicles, buildings, and facilities. Nutritional, reproductive, and sanitary management, health, and biosecurity programs adopted on the farms were identified and described. The zootechnical variables of importance to control the productive and reproductive performance of each animal in the systems were listed. A survey was also carried out of the labor present on the site of each of the collaborating farms.The researchers also developed a SWOT analysis of Brazilian pig production to assess the activity. The SWOT analysis is a classical strategic planning instrument  that pro® software  was the tool used to develop the calculation model, in which all costs of the full-cycle swine production activity were included. All data collected in the field were considered and allocated as proposed by the Neoclassical Economic Theory of Costs, which guided the logic of costs, as Raineri et al. [Microsoft Exceli et al.  for feedIn variable costs, all the components that only change according to the quantity produced were grouped. Fixed costs, on the other hand, do not change when the volume of production varies in the short term. In the item “Compensation costs for capital and land”, the remuneration of the land and capital represented the opportunity cost of these production factors. Opportunity cost is a theoretical concept that represents the benefits that could have been obtained from an unchosen opportunity ,8,16. Th® model to generate the results proposed in the objectives, which consisted of the development of the mathematical model for calculating the production costs of pigs in a complete cycle and availability of the tool to the public. Later, using the Panel method, adapted from Raineri et al. [After structuring the calculation model, the information collected in the case studies was gathered and organized in the Microsoft Exceli et al. , the calThe Panel method included a meeting between researchers and a group of producers and technicians from the sector studied, during which participants discussed the model in detail and made the relevant changes . Thus, aA Term of Commitment, Secrecy, and Confidentiality was signed between researchers and those responsible for the enterprises in order to conduct the research. This term clarifies that all technical information obtained would be used solely and exclusively for the development of the research and would be considered confidential, as well as the identity of the property and owner.A SWOT analysis was developed to depict the state of Brazilian pig production . This isThe proposed cost allocation scheme aligns with the Neoclassical Economic Theory of Costs .According to the presented cost allocation, the item organization was divided into five groups: (A) variable costs; (B) fixed operating costs; (C) operating cost; (D) cost of remuneration for capital and land; and (C) total cost. The sum of items A and B results in item C, and the sum of items C and D results in the total cost of the activity, as described in Equations (1) and (2):lCOP represents the operating costs of swine production, referring to the weekly batch l, in Brazilian currency . lCV represents the variable costs of swine production, referring to the weekly batch of animals l, in Brazilian real. lCFOP represents the fixed operating costs of swine production, referring to the production of the batch of animals l, in Brazilian real. In Equation (2), lCT represents the total cost per batch of swine produced, referring to the weekly batch l, in Brazilian real; and lCO represents the weekly cost of remuneration for capital and land, in Brazilian real. It is important to note that the cost report is given based on the weekly batch l to be marketed. However, the costs related to the entire production cycle that led to the production of this batch are computed.In Equation (1), In full-cycle swine farms, what dictates the flow of production, operation, and the inner workings of the activity are the female groups, which are usually weekly groups. A weekly group of females is nothing more than a set of females that will be inseminated during the week to meet the demand, farrowing and weaning schedule, and the productive cycle of the farm. Thus, it was decided to carry out the calculations of consumption of inputs used in the production of swine weekly. The following formula was used to calculate the weekly groups:On what:GS: females’ weekly group.N: total number of dams in production on the farm.ppa: number of births per sow per year on the farm.txparto: farm’s birth average rate.φ: number of weeks contained in a 365-day year.The presentation of mathematical equations and nomenclatures used in the construction of the cost calculation model will be presented according to the allocation to facilitate understanding. Thus, the costs of all inputs are allocated as variable costs , and thelCV) of the activity were calculated from the input costs  of each item consumed by the animal categories c involved in the production system of the different production phases f present in a commercial swine farm in full cycle. These inputs, in turn, are consumed to produce the batch of animals l to be marketed weekly. In the animal categories, gilts, dams, ruffians, boars, piglets, and market hogs are examples. Regarding the phases, one can mention the sow in the gestation phase, the sow in the lactation phase, a piglet in the farrowing room, and/or a piglet in the nursery phase, a growing and/or finishing pig, for example.Variable costs . These data are then crossed with data from the productive herd, previously informed, and thus, the weekly feed intake of the phase is obtained (Equation (5)), including all animals receiving that diet in the specified phase. The weekly feed consumption in phase is multiplied by the price of the specified diet, and the cost of feeding animal category c in phase f is found, as described in Equation (4). Subsequently, the sum of the weekly feed costs of all categories and phases present in the production system is carried out, and the subtotal of the costs of feeding the group of animals is obtained, as can be seen in Equation (7).The costs computed as health costs refer to the use of vaccines and medicines with a controllable frequency in the herd. In the case studies, different items were found in each of the units studied, thus enabling the adequacy within the model to include the input to be used and the number of doses used to treat the animals per phase for a given animal category. The product of the number of doses per phase and the number of animals in the phase results in the calculated quantity of doses of vaccines and medicines used weekly for a certain animal category in that phase (Equation (9)). By crossing these data with the price of the dose used, the cost with the health of the animal category c in phase f is obtained, as shown in Equation (8). Subsequently, the sum of the weekly costs with the veterinarian’s expenses is performed in all categories and phases present in the production system, and the subtotal of weekly costs with the health of the productive herd is obtained, described in Equation (10).The costs computed with reproductive management were divided into three possible scenarios, namely: (i) the production of semen on the property, where the costs of semen collection, processing supplies, and laboratory equipment for semen evaluation are considered; (ii) the use of semen from a central distributer, where the quantity and prices of the commercial semen dose to be used in the property by gilts and sows are considered; and (iii) where the two scenarios are used, both internal semen production and the use of semen from a central distributer, and all these inputs are taken into account. In the three scenarios described, the materials used in the artificial insemination procedure, such as pipettes and tubes, are also considered. Through the weekly group of females and data previously entered in the model, it is possible to identify the number of inputs related to product management to be consumed weekly by the system (Equation (12)). The product of the weekly amount of inputs used and the unit price of such inputs result in the cost of reproductive management for the farm, as shown in Equation (11). The sum of costs per week for each scenario allows the weekly subtotal cost to be obtained with reproductive management on the farm (Equation (13)).l, the value found was divided by 4.345 (ω), which represents the number of weeks present in a month (Equation (14)). Performing the sum of expenses related to consumer goods such as gloves, needles, syringes, marker sticks, and control of rodents and flies, among others, the subtotal of expenses with consumer goods for the farm is then obtained (Equation (15)).The model was adapted to allow the insertion of the item I to calculate expenses with consumer goods, as well as the average monthly quantity consumed of this item and the unit price of each item entered. Subsequently, to represent the goods consumed by the weekly batch These subtotals made up what was called the “Pig Raising Subtotal Defrayal”, which is nothing more than the sum of the variable costs of food, health, reproduction, and consumer goods (Equation (16)). This data was characterized as important by the producers and managers of the farms where the case studies were carried out, as it allows the visualization of costs related directly to the animals.Subsequently, transportation, loading, and insurance expenses for lot l to be sold were calculated. The data referring to the distance, in kilometers, from the farm to the slaughterhouse and the price paid to the carrier per kilometer traveled were imputed (Equation (17)) to calculate the cost of transport. The rate charged by the insurer and the average capital invested in the lot is considered to calculate the lot insurance, as described in Equations (18) and (19). The sum of both results in the subtotal of weekly costs with transport, loading, and insurance of the weekly lot to be sold (Equation (20)).The last item that makes up the variable costs refers to the weekly variable financial expenses. This item, consisting of variable taxes and rates such as ICMS, Funrural, and GTA, among others, considered the main expenses raised in the case studies and followed the current accounting regulations for the calculation. The details are found in Equation (21).The equations for fixed operating costs and the nomenclatures and definitions of the formulas used are shown in CFOPl) of the activity, there are costs related to labor, electricity, telephone, internet, fuel, costs with depreciation, maintenance, and other fixed expenses, which include taxes and fixed fees collected from the activity. For the calculation of operational fixed items, it may eventually be necessary to apportion some items, as they are used in activities other than the swine production. In these cases, the user must allocate the data that represent the proportional costs referring to the use of the items by the swine production activity.In the composition of the fixed operating costs . The sum of the weekly labor costs of all employees on the farm results in the subtotal of weekly labor costs (Equation (24)).Only the consumption related to the swine production activity should be considered for the item electricity costs. For this, the number of KWh consumed monthly by swine farming and the rural tariff for electricity paid by the property, in R$/KWh, will be imputed. The multiplication of these two items provides the monthly cost of electricity by the activity; subsequently, this value is divided by ω, and the weekly cost of electricity is obtained (Equation (25)). For the calculation of weekly costs with telephone and internet services (Equation (26)), the prices of the packages used by the property were considered. In the case of more than one activity using this service, the cost must be apportioned, and only the portion referring to the swine production must be imputed in the model.The amounts computed as fuel costs refer to those related to the consumption of gasoline, alcohol, and diesel by the swine production process. To carry out the calculation, the user must input the price data per liter of fuel used and the number of liters consumed monthly (Equation (27)). Subsequently, the model divides the sum of these items by the fixed value of the number of weeks present in a month, thus obtaining the weekly fuel cost (Equation (28)).The item depreciation of assets corresponds to the financial reserve necessary to acquire an asset with the same characteristics at the end of its useful life. For the calculation of depreciation of swine production assets (Equation (29)), which includes improvements and facilities, machinery and equipment, and biological assets, the straight-line method was used, in which it is necessary to estimate the useful life in years, and the residual value of the production good. In practice, the residual value of the asset is known as a percentage of the new asset, as shown in Equation (31). The unit price of fixed capital and the unit quantity of assets are considered to calculate the initial values of the new asset (Equation (30)). In the specific case of installations, the Pcj can be given by the Basic Unit Cost of Civil Construction or by the real value in each specific case. For other capital goods, it corresponds to their market value. With such information imputed in the model, it is possible to calculate the weekly costs with capital depreciation (Equation (32)).The model also calculates the periodic maintenance of all items used in the swine production system. A rate established by the activity manager is multiplied by the value of the capital good in question to calculate the maintenance of the different capital goods used in the different productive sectors of the farm (Equation (33)). Subsequently, it is then possible to calculate the weekly costs with maintenance and conservation of all goods used by the activity (Equation (34)).The last item that makes up the fixed operating costs refers to the weekly fixed financial expenses. This item, consisting of taxes and fixed rates such as ITR, associations, and union memberships, among others, considered the main expenses raised in the case studies and followed the current accounting regulations for the calculation. Details can be found in Equation (35). With all this information imputed, it is then possible to calculate what is called the operational cost of the activity, as shown previously in Equation (1).Finally, the remuneration cost of capital and land, or the opportunity cost of capital and land, was divided into three items and sub-items ) by the producer refers to the portion calculated on the value of the property purchased and used in production and included in the fixed operational cost of production , such asRCG and for the RCI, is the Reference Rate of the Special Settlement and Custody System (Selic). The period used as the turning period was weekly to monitor the production costs of a weekly batch l.The remuneration of working capital, shown in Equation (39), refers to the capital used to fund the raising of the animals—as shown above (Equation (16))—present in variable costs. The rate used to remunerate working capital is also the manager’s option and must be previously entered into the system’s characterization data. An example of a rate to be used, both for the For remuneration of the land used by the swine production activity, the method that relates land use with the land lease value in the region where the property is located was chosen and can be observed in Equation (40). For this, it is necessary to know and impute the lease value in the characterization tab of the production system.After calculating the variable costs, fixed operating, and opportunity costs, it is then possible to obtain the total cost of production of the swine. As shown in Equation (2), the total cost is nothing more than the sum of these costs. In the calculation model, this total cost can be observed in a total monetary amount, or in total cost per market pig, per arroba, and per kilogram of the swine produced. The equations  that deml (lNt). The number of animals housed and the mortality rate of each phase was considered in each of the phases, as shown in Equation (44).To carry out such calculations as specified in Equations (41)–(43), it is necessary to know the number of animals finished at the end of the accommodation of lot f.f.The base number of animals in each of the phases was established based on the number of animals born alive, which is obtained as shown in Equation (45).To obtain the production in kilograms of market pigs, the Equation (46) was used.l.l.The number of weekly kilos to be sold was also calculated from the culling animals of the reproductive herd, both males and females. For such calculations, the number of animals discarded weekly and the average weight of these animals were considered (Equation (47)).l.s present on the farm.c.The model also calculates the profitability of the swine production system, which is shown in the economic report. The indicators analyzed are (i) total weekly revenue, (ii) profit or loss per weekly batch, (iii) total income to the producer, (iv) leveling point, (v) total factor productivity, and (vi) return on investment. The calculation formulas for these economic indicators , as welll is used, as already demonstrated in Equation (48). After calculating the total weekly revenue, it was then possible to calculate the average revenue per market pig produced and per kilogram of market pig produced, shown in Equations (49) and (50), respectively. With the results of the total weekly revenue, it is then possible to obtain the economic profit of the activity or loss. The calculation of profit is nothing more than the subtraction of the total cost of production of the batch of animals l from the total weekly income (Equation (51)), swine producers consider this one of the main economic indicators of the system.Both the revenue from the sale of market pigs and the revenue from the sale of culling animals were considered to calculate the total weekly revenue from the swine production activity. The prices used to calculate the revenue are previously informed by the user in the system characterization tab, where the market value of the swine sold in the farm region in the period of marketing of the batch of animals RBC then demonstrates how much the swine farmer is receiving for the production activity for each Brazilian real spent on the production of the batch under analysis. Another economic indicator analyzed is the Return on Investment (Equation (54)). Through this indicator, it is possible to know how much the swine production activity is gaining (or losing) concerning the investment made. This indicator is shown in percentage.The Leveling Point (Equation (52)) was also calculated, which is an economic indicator that demonstrates the level of production at which the value of marketing the product equals the costs to produce an item, in this case, the head or market pig produced. In other words, this indicator estimates the minimum quantity to be produced in this system with current productivity data, with these costs, so that there is no economic loss. The Benefit Cost Ratio, calculated as shown in Equation (53), is an indicator that shows revenue per cost unit. The Finally, there is the calculation of the producer’s total income, which considers the profit of the activity, the remuneration for the work of the producer and his family, which is nothing more than the wage compensation for corporate officers, and the remuneration on capital and the earth (Equation (55)). In this case, the factors of production are considered specific to the swine producer. Thus, the opportunity cost of capital and land, which is a cost of the activity, becomes the revenue for the producer since it is composed of the remuneration of the equity invested in pig farming. The producer’s total income is given in monetary amounts and in reais per kilogram of market pig produced.In a panel held with the São Paulo Association of Swine Producers, its representatives, and associates, the developed calculation model was evaluated, validated, and considered as complete, adequate, and representative of the swine production systems, fulfilling the proposed objectives.Through SWOT analysis, it was possible to identify both internal factors (which can be improved on-farm) and external factors that may affect pig production. When it comes to for-profit activities, one of the greatest challenges is related to producing efficiently, i.e., at lower costs, and how to run off the production . In thisThe cost allocation scheme adopted was guided by some assumptions, aiming at objectivity to allow understanding, comparison, and decision making, without neglecting other effectively necessary items. The first of them was to develop a production cost calculation model that fits the Economic Theory . The cosVariable costs include all components that participate in the process as the activity develops. That is, variable costs comprise all items that only affect production and are directly related to the number of swine produced ,21. As tThe labor was designated as a fixed cost because it is not directly associated with the number of animals housed or produced. It is known that there is a relationship between the number of animals housed per employee on a farm . HoweverAsset depreciation is a fixed cost item, corresponding to a financial reserve necessary to avoid the loss of capital of the swine producer. With such a reserve, it is possible, at the end of the asset’s useful life, to acquire another asset with the same characteristics ,16. DeprIn practice, there is a certain difficulty for the producers in calculating the depreciation of their assets, and, according to Gameiro and Caixeta Filho , one of This is one of the major bottlenecks found when analyzing studies that deal with the calculation of production costs. The difficulty in determining depreciation leads to studies that consider only variable costs, or only part of fixed costs, in the calculation, as in the case of the studies by Herrington and Tonsor  and RetaFor maintenance, some studies estimate the calculation of production costs of integrated livestock systems that allocate maintenance as variable costs ,35,36,37Another important item to be discussed is the opportunity cost of capital and land. According to Knight , all facIn the present study, in addition to considering the opportunity costs of immobilized capital and land, as commonly performed ,33,39, aFor the opportunity cost of land, a widely used criterion, which was adopted in this study, is the lease value in the region’s land market ,16,33,40The production cost is then calculated considering all costs, whether explicit or implicit, that occur in a swine production unit. It is important to include all the costs on the model for a realistic estimate of total cost and to be able to compare among the producers. According to Oliveira and Santos Filho , when seTools such as the model developed in the present study allow the producers more accurate management of their business, making it possible to monitor, simulate and predict risk scenarios for productive activity . In thisThe developed model calculates swine production costs for different production systems, addressing all implicit and explicit costs involved in the production system. It has the potential to be used as a management tool, as well as to generate important information for decision-making in commercial swine production systems. The application of Neoclassical Economic Theory to calculate production costs, such as the opportunity cost, is essential for the development of more accurate models. These are the distinctive points of the cost calculation model elaborated in this work, which presents clarity and versatility for use by swine producers, technicians, and scientists.


Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.Pulmonary cryptococcosis describes an invasive lung mycosis caused by  Cryptococcus neoformans or Cryptococcus gattii species complexes, is a cause of significant morbidity and mortality. Although Cryptococcus spp. are widely distributed in the environment, with over 30 species identified, only two—C. neoformans and C. gattii—cause the majority of human infection. Cryptococcosis is typically acquired via the respiratory tract through the inhalation of desiccated yeast cells or basidiospores with resultant primary lung infection ,,19,C. necognised ,21. An aC. neoformans are also well recognised [C. neoformans to generate such diploid hybrid variants may confer increased fitness in terms of persistence in the environment as well as in the host.Hybrid AD strains of cognised ; these acognised . Howevercognised , althougcognised . It has C. neoformans is the predominant pathogen although there is substantial overlap in the disease spectrum between the two pathogenic species complexes [Immunocompromise, especially T-cell mediated deficiencies including those due to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), predispose to cryptococcal infection. In HIV/AIDS, infection typically manifests with CD4 T-lymphocyte counts under 100 cells/μL . Other romplexes .The manifestations of pulmonary cryptococcosis are protean, spanning from an isolated lung mass (ranging from a simple nodule to a large cavitatory mass) A,B, to mIsolated cryptococcomas are a common respiratory manifestation in immunocompetent patients. In those without other comorbidities, cough (22.3%), chest pain (10.4%), sputum production (6.0%) and/or fever (23%) are the most frequent symptoms . PulmonaPneumocystis jirovecii pneumonia (PJP) is another differential necessitating appropriate diagnostic tests. Of note, the clinical presentation may be indistinguishable from other causes of opportunistic pneumomia. In high tuberculosis (TB)-burden settings, the clinical picture may be indistinguishable from TB and indeed concurrent infections are well described ; hence, Of key importance, disseminated infection  must be specifically considered in all patients with pulmonary cryptococcosis to ensure treatment modality and duration is appropriate ,39. A reC. gattii infection overlaps with that of C. neoformans and the same diagnostic modalities are employed. In many geographic regions, it is recommended that clinical isolates be routinely differentiated into C. neoformans complex and C. gattii complex for clinical and epidemiological purposes [Broadly, the clinical spectrum of purposes . C. neoformans, pulmonary involvement is seen in about two thirds of C. gattii infections, mostly with concurrent CNS disease [C. gattii may be very large (over 5–10 cm), with Pancoast syndrome a well-described complication [C. gattii [Similar to  disease . The pullication   testing which confers high specificity and at least moderate sensitivity in pulmonary disease ,52,53. Dulations , antibodCollection of appropriate specimens is critical to optimising diagnostic yield. Serum should be collected for detection of CrAg. Lung tissue samples taken from the site of disease via percutaneous or trans-bronchial biopsy are the optimal specimen types, particularly since many cryptococcal lung lesions are located peripherally . These sSampling of cerebrospinal fluid (CSF) via a lumbar puncture and appropriate brain imaging must be performed to exclude CNS infection in all patients with pulmonary cryptococcosis ,39, giveClassification of pulmonary cryptococcosis into mild-to-moderate or severe disease enables appropriate selection of a treatment regimen. Mild-to-moderate pulmonary cryptococcosis is defined by the absence of diffuse pulmonary infiltrates and lack of dissemination to other anatomical sites, while severe disease is defined as the presence of multiple pulmonary cryptococcomas, diffuse pulmonary infiltrates and/or dissemination to other sites including the CNS ,56.Chest imaging, using a plain radiograph A or highIn asymptomatic patients, an abnormality on chest radiograph is often the first indication of the infection, attesting to the key role of radiology in diagnosis of pulmonary cryptococcosis . It is nC. neoformans and C. gattii [Cryptococcal antigen (CrAg) testing may be conducted using lateral flow immunochromatography or latex agglutination approaches. The lateral flow CrAg assay, now the most widely used, detects the presence of capsular glucuronoxylomannan present in both . gattii . Its low. gattii . The ass. gattii ,52,53. I. gattii . The pos. gattii , and a pIn patients with pulmonary cryptococcosis, median serum CrAg levels of 1:16 are seen in immunocompetent hosts, or 1:32 in immunocompromised persons . SignifiCryptococcus spp. are readily recognised on a wet preparation by the presence of a thick gelatinous capsule (though some strains do fail to produce a capsule on subculture) [Cryptococcus spp. appear as narrow-based budding cells with Gram positive inclusions, sometimes visible against a non-staining or poorly staining capsule [As encapsulated yeasts, culture) . Distincculture) . On Gram capsule .Cryptococcus spp. as well as the absence of pseudohyphae provide additional morphological hallmarks to differentiate them from other yeasts such as Candida. More Cryptococcus-specific stains such as mucicarmine (which stains the polysaccharide capsule)  E or FontCryptococcus spp. in lung infection. Blood cultures may also yield Cryptococcus spp. although very uncommonly in isolated lung disease. Induced or expectorated sputa are not generally recommended as specimen types when Cryptococcus is suspected, due to contamination with upper respiratory commensal flora. Irrespective, the finding of C. neoformans or C. gattii in any sputum specimen should be reported to the clinician for further assessment of the presence of cryptococcal disease with a chest radiograph and lower respiratory sampling. Lung tissue or BALF specimens provide optimal sensitivity and specificity for culture of Cryptococcus spp. grow as glistening mucoid colonies on routine fungal culture media (such as Sabouraud’s dextrose agar) under aerobic conditions with an optimal temperature of 30 °C. Unlike other Cryptococcus spp., most C. neoformans and C. gattii isolates will tolerate temperatures up to 37 °C which is a key diagnostic feature [Cryptococcus spp. growing as characteristic brown colonies due to formation of melanin from the biphenol components of the media [Cryptococcus spp. to hydrolyse urea is another distinguishing biochemical feature.  feature . Growth he media . The abiCryptococcus spp. was performed using capsular agglutination reactions to the four historical serotypes–A, B, C and D  or the VITEK 2 system  [C. neoformans, there are breakpoints only for amphotericin B using EUCAST methodologies (susceptible isolates corresponding to a MIC ≤ 1 mg/L) [C. gattii. CLSI methods do not have clinical breakpoints for C. neoformans or C. gattii, although epidemiological cutoff values (ECVs) have been determined [If indicated, susceptibility testing is performed using a reference broth microdilution method  /EuropeanMO, USA) . For C.  1 mg/L) ; no clintermined .Cryptococcus spp. have largely retained low minimum inhibitory concentrations (MICs) to amphotericin B and flucytosine, but are uniformly resistant to echinocandins (though the mechanism is not well established). Concerningly, a trend of increasing fluconazole MICs has been described [escribed . Moreoveescribed . Amphoteescribed . C. neoformans, several studies have documented comparatively low MICs of standard antifungals against C. gattii, including amphotericin B and 5-flucytosine. Although some MICs appeared to be relatively higher for C. gattii than for C. neoformans, the clinical significance of this is unclear [Similar to  unclear ,86,87,88Cryptococcus spp. but do not differentiate between C. neoformans and C. gattii [Cryptococcus spp. is reported at 84% compared to CrAg [Nucleic acid amplification testing (NAAT) has previously been a minor contributor to the diagnostic toolkit for cryptococcosis but now may be coming into its own. Most commercial platforms, including multiplexed assays such as the AusDiagnostics atypical pneumonia or CSF panels  and BioFire meningitis/encephalitis (ME) panel  target the ITS region of . gattii ,90,91; tcytb gene have enabled identification of C. neoformans and C. gattii with 96% sensitivity and 100% specificity [Panfungal PCR assays accompanied by sequencing of the ITS amplicon provide detailed genotypic information which enables accurate speciation, but lengthy turnaround times can be problematic for achieving a prompt diagnosis in the acute phase, and the assay performs most optimally on tissue specimens where yeasts have been visualised on microscopy . New molcificity . Such asC. gattii infections are based largely on extrapolation from clinical trials of C. neoformans and on case series, individual case reports and expert opinion. Choice and duration of treatment for pulmonary cryptococcosis is dependent on host factors, primarily immune status and the severity and extent of disease ,9,56,94.Surgical resection is recommended in patients with large, surgically accessible pulmonary cryptococcomas ,48 or thIn immunocompetent individuals there have been multiple reports of spontaneous resolution of pulmonary cryptococcal lesions, particularly in the asymptomatic population . HoweverSevere pulmonary disease—defined as the presence of multiple pulmonary cryptococcomas, diffuse pulmonary infiltrates and/or dissemination to other sites including the CNS—should be treated similarly to cryptococcal meningitis. An induction phase with combination intravenous amphotericin B and 5-flucytosine for two to four weeks is followed by consolidation and maintenance phases with oral fluconazole for at least one year  5,9,39,,39,56. SC. gattii [The role of corticosteroids in optimising outcomes for cryptococcal disease is unclear, but generally these agents are not recommended. In patients with acute respiratory distress syndrome and no CNS disease, corticosteroids may be considered . In cryp. gattii . ConsultC. gattii infections may require modification of the aforementioned recommendations. In particular, a longer duration of induction as well as total duration of therapy may be indicated [C. gattii infections, surgical excision is often an important aspect of achieving an effective cure, in conjunction with antifungal therapy [Management of ndicated , largely therapy ,48. Cryptococcus spp., and detailed Phase II and Phase III clinical data are awaited [New agents under investigation for management of pulmonary cryptococcosis include the novel antifungal agents APX001A (Manogepix), VT-1129 and T-2307, which have demonstrated in vivo and in vitro activity against  awaited ,115,116. awaited , human t awaited ,119.Severe cryptococcal disease in patients with HIV infection should be managed as per recommendations for immunocompetent hosts. It is recommended that HIV-infected individuals with asymptomatic or mild-to-moderate pulmonary disease receive fluconazole therapy ,39,120, Immunocompromised individuals without HIV with severe cryptococcosis should be managed with induction, consolidation and maintenance therapy phases, as recommended for other patient groups. Patients with asymptomatic or mild-to-moderate pulmonary disease should receive standard fluconazole therapy as outlined above ,39,95. ADrug–drug interactions can be a significant challenge in this context. Careful QTc and therapeutic drug monitoring should be performed particularly when calcineurin inhibitors are co-administered with fluconazole due to known drug–drug interactions . AlternaData on the optimal management of pregnant women with pulmonary cryptococcosis are limited to case reports. Vertical transmission is rare, with isolated cases reported in the context of severe disseminated maternal disease with or without HIV coinfection ,128. ForTreatment of cryptococcosis in children is extrapolated from adult data as there are no randomised controlled trial data. While pulmonary cryptococcosis is rare in children, a high proportion of these present with disseminated disease ,133. ForMortality rates in pulmonary cryptococcosis are improving over time, but still vary widely based on immune status and comorbidities of the host as well as the presence or absence of concurrent meningitis or disseminated cryptococcosis . AccuratPulmonary cryptococcosis remains a concerning invasive mycosis, associated with substantial morbidity and mortality. Clinicians must be attuned to this condition as a differential diagnosis in patients with non-remitting respiratory symptoms, chest pain, fever and/or systemic features, or in those with the radiological finding of a single or multiple chest lesions. An accurate diagnosis requires close coordination between the treating physician, microbiologist, histopathologist and radiologist to collate the information gleaned from culture, microscopy, histology and imaging findings. Missed or late diagnoses remain commonplace, particularly in asymptomatic cases or those with an indolent course. Cryptococcus isolates to the species level [Ongoing research into improved diagnostic tools and algorithms as well as trials of novel targeted antifungals, adjunctive agents and alternative treatment regimens are eagerly anticipated. More sophisticated diagnostic approaches are in development to enable timely and accurate diagnosis of es level . The useThe ‘holy grail’ in management of pulmonary cryptococcosis would be a low-cost all-oral regimen to enable greater accessibility across resource limited settings as well as high-income countries. Such developments will be critical to ensure the optimisation of tolerability, quality of life and short- and long-term outcomes for the multitude of patients affected by pulmonary cryptococcosis worldwide.


Since the late 19th century, genital modifications  have been an important research subject in anthropology. According to a comparative and constructivist perspective, they were first interpreted as rites of passage, then as rites of institutions. In a complex dialogue with feminist movements, 20th-century scholars recognised that the cultural meanings of these modifications are multiple and changing in time and space. Conversely, according to WHO, since the 1950s, Female Genital Mutilation or Cutting (FGM/C) has been considered a form of Violence Against Women and Girls (VAWG). Interpreted as VAWG, FGM/C has progressively been isolated from its complementary male rite, selected for special condemnation, and banned. An order of discourse has been built by WHO and other international organisations. This article provides a genealogic deconstruction of the order of discourse lexicon, highlighting dislocations between anthropology and the human rights agenda. Today, genital modifications encompass FGM/C, male circumcision, clitoral reconstruction after FGM/C, gender reassignment surgery, and intersex and ‘cosmetic’ genital surgery. I propose to call these procedures Gendered Genital Modifications (GGMo). GGMo implicates public health, well-being, potential harm, sexuality, moral and social norms, gender empowerment, gender violence, and prohibitive and permissive policies and laws. The selective production of knowledge on FGM/C has reinforced the social and political polarisation between practices labelled as barbaric and others considered modern, accessible, and empowering. I suggest an anthropological interpretation for the socio-cultural meanings of health, sexuality, purity and beauty. I propose future interdisciplinary studies of how consent, bodily integrity and personal autonomy bear on concepts of agency and subjectivity in the sex/gender system. Since the late 19th century, the genital modification of females  were carried out, highlighting ages, procedures, tools and ritual operators. According to this vision, genital modifications were also interpreted as bodily techniques  through Since the mid-20th-century scholars recognised that the cultural meanings of genital modifications are multiple and changing in time and space. In a complex dialogue with feminist movements , scholarThe World Health Organization (WHO) and the main UN agencies have defined female genital mutilation or cutting (FGM/C) as ‘all procedures that involve partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons’ . Becausesex/gender system , selected  and legally banned. This now so-called “female genital mutilation” or “FGM” became associated with irrationality, misogyny, primitiveness and serious harm.Nevertheless, international actors opposed to female  genital modification have tended to ignore the male rites within practising societies while interpreting the female rites within the same societies in a highly reductive manner: as sex-discriminatory institutions of violence against women and girls (VAWG). Based on this interpretation, FGM/C began to be isolated: geographically, with a focus on African female genital modifications ; scientifically, with almost all subsequent research oriented around documenting harms as well as methods for elimination; politically, with opposition to FGM/C becoming a requirement for Western funding and favour; and anthropologically, becoming conceptually divorced from the parallel male rites occurring within the same At the same time, contemporary anthropological perspectives continue to stress and investigate the controversies  , projectHowever, a social change is now blurring this boundary. Questions are now increasingly raised about practices that have been biomedicalised in the West. In recent decades, various gendering surgeries have contributed to the biomedical construction of gender, often interpreted as new, technologically sophisticated, ‘liberal’ forms of genital modification. Gender reassignment surgery (GRS) and genital cosmetic surgery (GCS) emerged as ways to refashion one’s anatomy so that it is in line with one’s gendered and sexual preferences, desires  and idenAlthough these operations have all been constructed as being categorically distinct from FGM/C, they do share certain features with it that require consideration: they remove tissue from or otherwise modify a health vulva or penis and, when performed on infants or children, they raise ethical challenges concerning consent , autonomThis article aims to provide a genealogic deconstruction of the genital modification lexicon, focusing on fractures and dislocations between anthropological perspectives and global human rights policies. Regarding female genital modifications, I argue that the ‘FGM/C’ order of discourse has produced a real ‘heterogony of ends’ . I also highlight the uses and abuses of anthropological vocabulary. Finally, I suggest a new interdisciplinary method based on gendered ethnography  to analyse all genital modification practices. This method allows for providing due attention to the intersubjectivity of social actors and researchers as well as management of gender-power-related tensions that could arise in the field; it aims to produce knowledge that may contribute to scientific and non-scientific fields . ParaphrSince colonial times, genital modification has been the subject of politics and policies. As an illustration of this, we will remember the colonial dispute between British Christian missionaries and the Kikuyu, a Kenyan ethnic group, regarding the colonial ban on female ‘circumcision’ . On the Since the end of the Second World War, the issue of female genital modification has become a problem in the global North; this is because it fits into the discourse of human rights and the birth of major international organisations as outlined in the vision of the Universal Declaration of 1948 and in the Geneva Conference of the Society for the Protection of Children (1948) .One year earlier, in 1947, the Executive Board of the American Anthropological Association (AAA) prepared a statement on human rights and submitted it to the UN Commission on Human Rights. Briefly, the AAA critiqued what they saw as an ethnocentric position  endorsed by the UN, instead proposing to centre cultural diversity through the concept of cultural relativism: roughly, the belief that certain values, instantiated in practices, may be relative to specific cultures and should therefore not be denigrated simply on the grounds that they do not conform to one’s own cultural standards.The AAA’s statement, which was based on this notion of cultural relativism and the belief that no substantive declaration of rights could be meaningfully applied to all human beings irrespective of their cultural context , marked In 1958, the UN Economic and Social Council asked the WHO ‘to undertake an inquiry into the persistence of these practices  and into measures adopted or planned to stop the ritual operations’ . In 1959universal essentialist generalisations about “all women” are replaced by culture-specific essentialist generalisations that depend on totalising categories such as “Western culture,” “Non-western cultures,” “Western women,” “Third World women”’ [But it is in this same period, from a descriptive and interpretative view of cultural complexity (as evidenced by ethnography), we saw a dislocation of meaning within the notions of culture, ritual operations, and tradition, which are the basis of anthropological knowledge. They acquired political value and became descriptive notions in the sense of classification: Us and the Others. These anthropological concepts were considered using an ahistorical and essentialist perspective: ‘seemingly  women”’  and so o women”’  both witTo international organisations, anthropology seemed to be the most appropriate discipline to draw on, because it studies cultural diversity (the Others). The nascent theories of social change  and cultural pluralism were not functional for the purpose of political discourse. The only targeted concept was the culture , which was considered the basis of violence against women. In the anthropological sense, the culture is a symbolic system integrated, shared and dynamic, something we acquire during all our lives.It is no coincidence that, in addition to genital practices, other cultural practices  were considered by UN agencies as a type of social pressure through which men oppress women via patriarchy. This is a concept that feminist anthropology has intensely criticised when it is assumed in an ahistorical sense; it is believed that all men (men as a class or category) prevent women from freely expressing themselves or (otherwise) exercising agency, and, consequently, men become the silencers of women. In this rhetoric, women in the Global South emerge as victims to be saved because they are represented as uneducated, unlettered, custom-bound, oppressed, domesticated and forever victimised . The bodBased upon this framework, the operations that had been defined in 1967 as ‘male genital mutilation’ by anthropologist George Peter Murdock  were expThe years leading on from the 1970s and into the 1980s became a turning point for the consolidation process of the formula ‘Female Genital Mutilation’ in a political sense. On the academic front, Rose Hayes, for the first time, used the expression ‘female genital mutilation’ to describe the cultural/functional/structural complexity of infibulation in the Sudan . That arThe Hosken Report: Genital and Sexual Mutilation of Females. Hosken presented on this survey at the WHO’s Seminar on traditional practices affecting the health of women and children in Khartoum. This report was used as a textbook for years. Hosken herself condemned both female genitals cutting and the very discipline of anthropology because, at the time, most anthropologists were men and, according to her, ‘naturally’ embodied power, and domination. It was certainly not a coincidence that the topic of ‘FGM’ became a ‘separate subject’ of sorts studied primarily by (and for) women researchers and feminists.The adoption of the acronym ‘FGM’ took place in the political arena through the contributions of one of the most influential but ambiguous figures  of the pgender mainstreaming was introduced. In principle, gender mainstreaming  and empowerment (the process by which women gain power and control over their own lives and acquire the ability to make strategic choices) should have been positive concepts; however, both concepts became the passe-partout of global hegemonic differentialist politics. Some scholars illuminated how, because they represent a Western idea projected onto the Other’s social relations and sex/gender systems, these definitions are ambiguous and polymorphic. For example, the concept of gender mainstreaming refers to many different things . Further, the idea of empowerment implies that an external authority gives power to women, and those women are often wealthy, with their own agendas and preconceptions, which diminishes poor women’s agency [During the 3rd UN World Conference on Women in Nairobi (1985), the concept of s agency .Through these and other developments, the FGM vocabulary became solidified despite local mistrust, conflicts of interest, and other controversies, seen in large part as a medical  issue until the 1990s. The order of discourse then became a hegemonic act of humanitarian reason, which indicates that the introduction and promotion of moral sentiments into human affairs become the essential element of contemporary local and global policies . This pogukuna, a Rwandan genital manipulation [As a result, these ‘imperfect glossaries’ based on ahistorical notions  have been locally incorporated and become part of the vernacular. The process of vernacularisation ‘is one of appropriation and translation. Human rights ideas and feminist ideas are appropriated by national elites and middle-level social activists and translated into local terms’ . As somepulation )  . Morgan Returning to FGM/C, according to UNICEF, ‘more than 200 million girls and women alive today have been subjected to the practice, according to data from 30 countries where population data exist’ ; this prBecause the FGM discourse has been incorporated locally, moral economies and quantitative measurements produce social effects that must be critically investigated; it is especially important that we investigate their impact on the process of subjection  in the dBox 1 The challenge of bodies and sexualities gendered conceptualisationsIn recent decades, some scholars have stressed how the Western conceptualisations of bodies and sexuality are mainly connected to the dichotomy of male and female. Gender binarism opposes men to women, where the first one is presented as a superior and the second as an oppressed category. As ethnography has demonstrated since the 1930s, this framework is particularly problematic to many cultures. More recently, Oyeronke Oyěwùmi  and SylvOn the one hand, this reconsideration permits us to recognise the complex structures within which sexuality is elaborated in its pluralist articulations . On the other hand, it allows an understanding of how the experiences of gender and sexualities are shaped and re-defined by issues, such as neo-colonialism, neoliberal globalisation, (bio)powers, social stratification, and religion. Bodies and sexualities offer ‘unending lessons about pleasure, creativity, subversion, violence, oppression and living’  and the Box 2 Type IV: the dislocation of labia elongation/stretchingEliminating female genital mutilation is an interagency statement of the United Nations  [O, 2008) . This doType IV in 1995: pricking, piercing or incising of the clitoris and/or labia; stretching of the clitoris and/or labia; cauterisation by burning of the clitoris and surrounding tissue; scraping of tissue surrounding the vaginal orifice (angurya cuts) or cutting of the vagina (gishiri cuts); introduction of corrosive substances or herbs into the vagina to cause bleeding or for the purpose of tightening or narrowing it; and any other procedure that falls under the broad definition of female genital mutilation.Type IV in 2008: All other harmful procedures to the female genitalia for non-medical purposes; for example, pricking, piercing, incising, scraping and cauterisation.Note on the classification of female genital mutilation. In the paragraph titled Stretching, we can read: “Stretching or elongation of the clitoris and/or labia minora often referred to as elongation, has been documented in some areas, especially in southern Africa. (…) Labial stretching might be defined as a form of female genital mutilation because it is a social convention, and hence there is social pressure on young girls to modify their genitalia, and because it creates permanent genital changes” (p. 27).We can see that the WHO removed labia elongation/stretching from the classification of Type IV. However, in Appendix This statement is a tool, and this dislocation could generate some confusion especially in the humanitarian field. For example, in the last two decades, I analysed the Rwandan ritual of gukuna . In the local sexual cosmology, this modification with the kunyaza  is expected to increase fertility and sexual pleasure. When I started my fieldwork, in the late 1990s, the gukuna was conceptualised as a secret of “liquid female sexuality”  . In the gukuna showed some agency  and challenged victimising assumptions and hegemonic representations of both ‘FGM’ and ‘the African Woman’. On the other hand, Appendix gukuna as ‘FGM’ and so something to be eradicated, even if it is no longer explicitly mentioned under Type IV of the WHO typology.On the one hand, the anthropological interpretation of Box 3 An unusual concept of culture in an official Italian documentAfrican women in Italy: The Culture, we can read:In 2009, the Italian Ministry for Equal Opportunities financed the Quantitative and Qualitative Evaluation of the phenomenon of FGM in Italy; this was done at Istituto Piepoli - Marketing and Opinion, with funds allocated by criminal law 7/2006 on FGM. This research, known as the Piepoli report, has several limitations, which are also demonstrated by the European Institute for Gender Equalities (EIGE). The overall quantitative methodology is not clearly explained, particularly regarding data and quantification, and some conceptualisations represent a model of archaic and racist vocabulary. For example, in the section titled ‘The morality of African women requests an attitude of introversion. (…) African women have been socialised in cultures characterised by solid social networks with ritual components (…); they differ profoundly from other immigrant realities (…). The facial features, the tattoos, the scarifications, the language and the FGM permanently marks the belonging to a group: to the women’s group, to the African Women’s Group, to the group of this specific area and this female-specific tradition’ (p. 31).The European Institute for Gender Equality (EIGE) has criticised the entire methodology of this study . It’s imI was invited to many conferences in many Italian municipalities to discuss these limitations and to deconstruct this lexicon . My critFrom an anthropological point of view and out of FGM/C’s order of discourse, I suggest that hymenoplasty , 101, laConversely, despite multiple laws and prevention projects  aimed atIn the realm of development projects and immigration policies , some stin fieri construction in the interlacement between dynamics of production, reproduction and cultural reinvention) is increasingly necessary.These changes have been studied from biomedical, juridical and bioethical viewpoints;  however,individual body (lived experience), the social body (as symbol), and the body politic . The selective legislation regarding genital modification  places a higher value on the political body  than the other two dimensions. For these reasons, it is crucial to rebalance the approach, redistributing the importance of the three dimensions. It is fundamental to ethnographically examine the individual and social dimensions of genitalia and to historically situate the prejudicial production of the political dimension.Medical anthropology suggests three perspectives for understanding the mindful body: the It is also required that we investigate how—through the biomedicalisation of genital modification—the social dimension articulates with the individual one. The first dimension focuses on issues regarding gender binarism, purity and health, while the second focuses on the lived experience of harm/violence and/or empowerment as outcomes of the procedures. It is crucial to evaluate harmfulness and agency without neglecting the subjectivity of the people who undergo gendered genital modifications (GGMo).Furthermore, there is a lack of ethnography that addresses the biomedical setting of male cosmetic surgery, genital piercing and IS. It is important to study how cultural assumptions regarding genitals, beauty, sexuality, ageing, the inviolability of the body and gender norms are embedded in scientific knowledge and clinical work surrounding genital surgery in different settings. Understanding the point of view of professionals and the ‘delegated biopolitics’  is a newIn this context, the negotiation of consent and mobilisation of cultural meanings pertaining to health, beauty and sexual enhancement are presented as new challenges. The progressive medicalisation of FGM/C in certain contexts and the rise of other genital surgeries are issues that require attention. Furthermore, the literature that addresses intimate cosmetic surgery under neoliberalism does not adequately account for new gender surgery technologies.By theoretically discussing consent, violence and harm, philosophical and bioethical literature , along wThe anthropologist Veena Das argued that the concept of violence is extremely unstable. She proposed that, instead of policing the definition of violence, we accept its instability as crucial to the understanding of how the reality of violence includes its virtuality and has the potential to make and undo social worlds . Also, tFurthermore, the literature has not addressed gender binarism as the intersecting and distinguishing feature of these practices. The emerging movements GGMo is an increasingly popular biomedical set of practices that entails compelling issues, such as public health, well-being and potential harm; sexuality, virtue, and moral and social norms; gender empowerment and, conversely, gender violence; and prohibitive and permissive policies and laws. GGMo can be delivered through various methods, following different biomedical settings and different cosmologies. However, all forms of genital surgery entail issues surrounding gender enhancements and agency. Today, GGMo encompasses male circumcision, FGM/C, clitoral reconstruction after FGM/C, GRS, IS on newborns and CGS. Until now, the production of knowledge and public discourse has kept FGM/C separate from other forms of genital surgery. Furthermore, discussions of FGM/C have been built on a performative order of discourse, which is now incorporated by social actors and public opinion. Because it is considered a form of violence against women and girls, FGM/C’s social and cultural dimensions should receive increased scientific attention.In contrast, CGS, which can also involve children, has thus far remained unexplored, particularly concerning its potential harmfulness. We need to ask how these practices are selectively condemned and commended by the different actors in the field and which social and moral stakes are encompassed. Moreover, the theoretical stance that considers female GCS as the unracialized mirror of FGM/C has developed without any ethnographic description of how aesthetic genital surgery is morally legitimated, culturally sought, socially organised and delivered.The selective production of knowledge has reinforced the social and political polarisation between practices labelled as customary and barbaric and others considered to be modern, free and empowering. Important matters of racism, neo-colonialism, ethnocentrism and victimisation have arisen from this divide. Moreover, the laws and public policies criminalising FGM/C have resulted in the clandestine delivery of these practices.Until now, mutilation was the name given to a specific form of genital surgery cast as non-therapeutic and targeting only women and girls. Recently, the characteristic of harmfulness has been increasingly attributed to those practices that pertain to biomedicine, which include IS, GRS and male circumcision. New social movements have emerged , and they raise relevant questions about consent, the role of the state and biomedicine in preventing harm, and the moral threshold regarding the modifiability or inviolability of the gendered body. Understanding this change entails considering questions too often left to specialists in medicine and psychiatry . An anthropological and ethnographic approach that can account for the socio-cultural meanings of health, sexuality, purity and beauty is fundamental. Nevertheless, we need an integrated and collaborative anthropological analysis of how, in this realm, consent, integrity and autonomy articulate with the concepts of agency and subjectivity in the sex/gender system.Appendix 1


A persistent issue in the agricultural sector worldwide is the intensive damage caused to crops by the geminivirus family of viruses. The diverse types of viruses, rapid virus evolution rate, and broad host range make this group of viruses one of the most devastating in nature, leading to millions of dollars’ worth of crop damage. Geminiviruses have a small genome and can be either monopartite or bipartite, with or without satellites. Their ability to independently replicate within the plant without integration into the host genome and the relatively easy handling make them excellent candidates for plant bioengineering. This aspect is of great importance as geminiviruses can act as natural nanoparticles in plants which can be utilized for a plethora of functions ranging from vaccine development systems to geminivirus-induced gene silencing (GIGS), through deconstructed viral vectors. Thus, the investigation of these plant viruses is pertinent to understanding their crucial roles in nature and subsequently utilizing them as beneficial tools in functional genomics. This review, therefore, highlights some of the characteristics of these viruses that can be deemed significant and the subsequent successful case studies for exploitation of these potentially significant pathogens for role mining in functional biology. Geminiviridae family into fourteen genera, viz., Becurtovirus, Begomovirus, Capulavirus, Curtovirus, Eragrovirus, Grablovirus, Mastrevirus, Topocuvirus, Turncurtovirus, Citlodavirus, Maldovirus, Mulcrilevirus, Opunvirus, and Topilevirus, based on the vector (insect pest), host dissemination, genome organization, and pair sequence identities  . The nonInsect vectors perform an imperative role in the introduction of these viruses within plant cells while keeping its primary target as differentiated cells . Due to Co-replication of the plant genome and the virion is initiated by geminiviruses through cell cycle reprogramming in the infected cells in order to compensate for its inability to produce enzymes for host cell replication and autonomous movement . ConsequTypical geminiviral infection symptoms often include leaf curling, mosaic patterns of variegated colors, occasional vein swelling, and enations, often leading to the confirmation that cellular homeostasis and plant growth have been affected, thereby reflecting transcriptional changes. Geminiviral infectivity primes cellular signaling which leads to the misregulation of plant miRNAs concomitant to developmental shifts and hormone signaling. Although geminiviruses and their interactions with insect hosts have not been well understood, the latest studies have indicated that virus-mediated changes in defense and signaling pathways tend to occur. Past reviews have majorly focused on the pathogenicity of these viruses, their recombination, and synergism biology; hence, in this review, it is deemed appropriate to delve into the detailed understanding of utilization of these viruses as natural plant bioengineers. We have considered the already available information on the geminiviral genetic makeup and protein functions as well as the geminivirus–plant–insect tri-partnership in genetic manipulation. In this review, we have also focused on various essential characteristics of geminiviruses and have also extensively discussed the putative use of these significant pathogens for aspects ranging from functional biology to biopharmaceuticals.Agrobacterium strains inhabit plant cells by transferring their T-DNA (transfer DNA) and cause proliferation and production of opine-like substances which the bacteria use as its carbon source (Agrobacterium tumefaciens identified that the bacterium might be used for transferring infectious clones of Cauliflower mosaic virus (CaMV), and hence, the “agro-inoculation” or “agro-infection” technique was used as a sensitive assay to ascertain if transfer of DNA occurs during Agrobacterium inoculations of the geminivirus Maize streak virus (MSV) to a graminaceous plant, Zea mays  and MSV and the dicot-infecting Bean yellow dwarf virus (BeYDV). Therefore, the first account of facile transmission of MSV was reported without involving leafhoppers to the maize crop. Despite the constant availability of newer isolates, Mastreviruses and Begomoviruses have remained the most popular taxa of the geminiviral replicon study (GVR)  . The stuto hosts . Biolistto hosts .Agrobacterium pathogen–host interaction studies  and the plant virus-based vector usage were well thought out to be contending technologies. Lately, the merging of the two schools of thought brought the implication forward that agroinfection was the most effectual technique of application of “deconstructed” vectors to the host plant. This led to the rise of many groups of viruses like geminivirus, potexvirus, comovirus, and tobamoviruses for deconstructed viral vector development for rapid, enhanced levels of production of proteins in plants which could be a huge boon for the pharmaceutical industry  was introduced within the Ti plasmid of Agrobacterium and agro-infection of Nicotiana benthamiana, tomato, and potato was successfully conducted  deployment . With the Rep being under impact of the Aspergillus nidulans ethanol-inducible promoter, the gene of interest is constitutively expressed at reduced levels in the absence of ethanol. However, in the presence of ethanol, NV coat protein increased up to 10-fold in the cell cultures of tobacco and green fluorescent protein (GFP) got augmented up to 8 times  recircularization by the viral ployment . The casn proven . An LSL  8 times . These pTobacco etch virus (TEV) 5′ UTR and soybean vspB 3′ region flanking it, aiming at the enhanced translational efficacy of the LSL . When a suppressor of silencing, TBSV p19, was added, the yield was further increased as the silencing machinery was severely affected -based CPMV-HT 5′ leader  and HIV CPp24 at 0.55 mg/g FWT and 3.23 μg/g FWT, respectively. The system has reported a replication efficiency up to a 1,000-fold and a protein expression fold change up to 7 times, indicating that this is a robust system of overproduction of antibodies and vaccines (Beet curly top virus (BCTV) which comprises a Cassava vein mosaic virus promoter (CsVMV) has also been employed to synthesize vaccines like Hepatitis A-virus VP1 protein in modest levels in fusion with IgG (Tomato leaf curl virus (ToLCV), and it was deduced that a segment between CR and AC3 could replicate efficiently. Therefore, a viral vector was constructed which efficiently produced siRNAs, giving rise to a system that could be an efficient GIGS vector in a broad range of plants  to recover the production of recombinant protein using geminiviral vectors as the expression source of desired genes.Plant geminivirus-based replicating expression vectors have been widely employed in recent decades to improve the effectiveness of plant transient expression. The BeYDV-derived vectors have been successfully employed to explore the properties of phytohormones like α-naphthalene acetic acid, 6-benzyladenine, and gibberellins. leaves . The traNicotiana benthamiana showed that VEGF could be expressed in high levels and did not exhibit any cytotoxic effect on HaCaT (human keratinocyte) cells, while also inducing cell migration in vitro. VEGF is a very important factor which is pro-angiogenic and important for wound healing. The recombinant clone of the VEGF gene was made using the geminiviral vector pBYR2e, which indicated that the functional VEGF protein could be made in plants that can possibly be exploited for their use in tissue engineering and dermo-cosmetics  and basic fibroblast growth factor (bFGF), were cloned in a geminiviral vector and employed for rapid transformation to express the proteins in a transient manner in C. reinhardtii and C. vulgaris, respectively. The outcome demonstrated that the geminiviral vector could allow the expression of both the proteins in both the algal species, with yields of up to 1.14 g/g RBD and 1.61 ng/g FGF in C. vulgaris and 1.61 g/g RBD and 1.025 ng/g FGF in C. reinhardtii at 48 h post transformation. As a result, this study showed that DNA viral vectors could be used to produce recombinant proteins in a simple, quick, and effective manner, overcoming the challenges of genetic transformation in these unicellular green microalgae. This notion brings up the possibility of researching and optimizing green microalgae as a cost-effective platform for producing medicinal and industrially important recombinant proteins in shorter time frames with higher yields  was transiently expressed in osmetics . Using Ar yields . Transier yields . Such car yields .African cassava mosaic virus (ACMV), Cabbage leaf curl virus (CaLCuV), Pepper huasteco yellow vein virus (PHYVV), Tomato golden mosaic virus (TGMV), and Tomato yellow leaf curl china virus (TYLCCV) (NtSu gene (Nicotiana tabacum sulfur gene) which includes one unit of the magnesium chelate chloroplast enzyme , this vector offers a distinct advantage of direct plant inoculation, bypassing the agro-transformation method, and could be used to augment phenotypes, for identification of redundant functions, and for understanding epistasis biology  . ACMV hat enzyme . This syapproach ; Table 1 biology .Comt (coding for a caffeic acid O-methyl transferase), pAmt (a possible aminotransferase), and Kas (a β-keto-acyl-[acyl-carrier-protein] synthase) genes, resulting in a non-pungent chili pepper and was confirmed by assessing the reduced mRNA levels of individual genes and because of the heightened siRNA presence , and GFP.Like CaLCuV, TGMV-derived vectors were also tested for DNA A/B efficacy, with DNA B showing better silencing efficiency. The TGMV B vector was specialized to use endogenous fragments <100 bp, thereby showing improved specificity which could also be tissue specific. Magnesium chelatase and proliferating cell nuclear antigen (PCNA) were downregulated all over meristematic tissues which showed that two different genes could be silenced simultaneously using the same viral vector components, using the immune-localization technique ; Table 1echnique . The TYLechnique . DNAβ waTobacco rattle virus (TRV)-based pTYs and CaLCuV-based gene-silencing vectors (PCVA/PCVB). In response to pTYs and CaLCuV, the latter came out to be a more efficient system in terms of operation costs and expense because the pTY mode of VIGS requires the particle bombardment mode of plants using expensive instrumentation. CaLCuV-based GIGS involved the use of Agrobacterium and was relatively inexpensive and had a higher batch efficiency target. This geminiviral vector system has also been said to be equally efficient in other Brassica species, B. rapa, and B. nigra, and therefore a potent functional genomic tool for crop plants (The phytoene desaturase (PDS) gene was chosen as an efficient visual indication of VIGS and was used to improve the VIGS system in cabbage utilizing the p plants .in vitro RNA synthesis  and TRV are commonly used for gene targeting and functional validation studies by transient silencing/overexpression of plant genes. Although effective, the insert size needs to be very small for RNA interference to occur  symptoms. BeYDV-based replicons were used for transient assays which detected Cas9 reagent-induced mutations within the virome, effectively reducing the virus copy number (N. benthamiana which comprised the Cas9-sgRNA construct which inhibited Beet severe curly top virus (BSCTV) accumulation and mutagenesis at targeted sequences, while overexpression of the same construct in transgenic Arabidopsis and N. benthamiana made the plants highly resistant to virus infection. Targeted coding sequence mutations in various geminiviruses caused the generation of viral variants adept in replication and systemic spread while noncoding IR mutations within geminiviruses provided viral intervention activity which limits significantly the replication and infectious variant generation, leading to long-lasting crop protection strategies against plant viruses  are transiently expressed targeting the gene of interest. This model has been touted to be used for generation of knockout libraries and has the potential to revolutionize crop genetic engineering (GE) in future. Recently, geminiviral reporter vectors WDV-GFP and WDV-GUS were constructed to deliver profuse amount of DNA to rice cells to make a practical KI (knock-in) method by combining CRISPR/Cas9 to produce double-strand breaks, with a noticeable 19.4% increase in KI frequency  protocol which is basically a geminiviral-centered guide RNA delivery system for plant genetic engineering using CRISPR/Cas9 . Cas9 isrequency . Similarrequency , along wrequency , TAL-effrequency , and CRIrequency . MutagenArabidopsis producing virus-inducible Cas9 and gRNAs directly targeting the Rep gene were infected with BSCTV after validation in transient N. benthamiana. Plants had a very low virus load and displayed no symptoms. Crucially, there were no off-target genomic alterations in these plants (S. lycopersicum when infected with the Tomato yellow leaf curl virus (TYLCV), as well as the decrease of Cas9 expression in tomato when infected with TYLCV  restricts their usage in gene editing because Reps are recognized to interact with a number of host cell proteins involved in the cell cycle, DNA replication and restoration, and DNA methylation . Off-tare plants . Anotherth TYLCV . With viin planta by carrying in its construct the epitopes for vaccines and full therapeutic proteins within its tissues. This offers a good prospect for the biomanufacture of important vaccines through proper biocontainment for critical diseases and offers a candidate for urgent protein therapeutics development in case of pandemics.Geminiviruses are used as a system which is under expansion for the manufacture of plant-derived biopharmaceuticals. Transgenic plants are cheap and effective platforms for bulk vaccine and enzyme production . Plant vStaphylococcus enterotoxin B (SEB) vaccine production, which is considered as a tentative bio-warfare agent. The viral genes for coat and movement proteins have been deleted, and an expression cassette for a protein of interest has been inserted into BeYDV-derived expression vectors. When the geminiviral vector is delivered to leaf cells through Agrobacterium, it creates a large amount of recombinant DNA that may be used as a transcription template, resulting in a large amount of mRNA for the protein of interest  GP1 protein and the West Nile Virus (WNV) E protein were produced and accumulated at levels of 0.23 to 0.27 mg/g leaf fresh weight in lettuce plants. A curtovirus, namely, the BCTV, was deconstructed to develop an exogenous protein production system which worked efficiently on addition of a virus-based suppressor of RNA silencing plasmid (Cassava vein mosaic virus (CsVMV) promoter was used instead of the CAMV 35S promoter to create this vector. When the P19 gene-silencing suppressor was added, reporter gene expression rose by 320% at the RNA level and by 240% at the protein level. In N. benthamiana, the capsid protein of the Hepatitis A virus (HAV VP1) was linked to an Fc antibody fragment and expressed. After intraperitoneal vaccination, recombinant HAV VP1-Fc isolated by affinity chromatography was able to induce a serum IgG response. IFN- and IL-4 levels were also shown to rise after vaccination. The TYDV system, which offered a fresh twist to the mastrevirus-based geminiviral vector system, is made up of two expression cassettes: one encodes Rep/RepA under the control of the AlcA:AlcR promoter, and the other includes the gene of interest activated under the control of an ethanol inducible promoter, which may be triggered by simply spraying an ethanol solution on it. The gene of interest is broken into two sections, separated by a synthetic intron, and put into the INPACT (In Plant Activation) cassette. In this method, the gene of interest could only be translated from replicons created during geminivirus sequence activation and applied to remove the intron (The deconstructed vector of BeYDV has been used for interest . Antigenlly made . The deaproteins . From a  plasmid . The Case intron . This meThe easy scalability along with flexibility makes geminiviruses an attractive candidate for biomedical interventions in terms of vaccine production. This will provide innovative approaches ranging from developing modern, customized drugs to combating potential pandemics, and of course protecting the world’s poor from preventable infectious diseases.Plant viruses are usually seen mainly as disease-causing agents, which is only one part of the story. Through the decades of research, there has been an unraveling of a host of possibilities in the role elucidation of these pathogens. As we have extensively discussed in this review, geminiviruses and many other classes of viruses offer tremendous functional potential in genome editing, changing the way virus-induced agricultural havoc is generally tackled. Crops with a complex genome like wheat and recalcitrant crops like cassava and chili pepper have been successfully transformed using the aid of modified viruses, thereby opening immense prospects of engineering viral vectors for host genome improvements. Discovering new genes and their characteristics is also possible due to the rapid assays the transient GIGS procedures can present, making it a novel and pertinent molecular tool, bypassing the time taken for stable transformation protocols.The past 30 years have been watershed for gemini-vector design, for applications in plant improvement. Geminiviral vectors have been used in multiple processes like ncDNA expression, vaccine and antibody production, gene silencing systems and expression systems, and CRISPR/Cas9 system construction for rapid assays, in the area of functional genomics. The biopharmaceutical industry has also realized the potential for gemini-vector utilization for vaccine development, where several vaccines are in clinical trials, and few have been approved in the past. The fluidity of geminiviral vectors into morphing successfully on any given “omics” aspect makes it a much-undervalued system of study in the current times, although apprehensions seem to arise due to possible geminiviral vector-linked environmental concerns, even though plant viruses have never posed any threat to human health as consumption of infected food has been done from centuries, albeit unknowingly.Agrobacterium-mediated delivery of the gene of interest cloned in non-viral vectors, which then involves a lengthy plant transformation procedure and subsequent generation of stable lines. As rapid development in sciences also deal with identification of shorter yet effective experimental strategies, geminiviruses can be exploited as a model virus for shorter infiltration strategy development which could be a prospective replacement to the Agrobacterium transformation stages with direct mechanical inoculation plant transformation. Therefore, gemini-vector construction–deconstruction with host genome integrative sequences should be exploited aggressively for mimicking Agrobacterium-mediated stable line generation.An important perspective in genome manipulation is the identification of elements which could help in the development of geminiviral vectors for stable transgenics development. The current method extensively uses Another significant concept that should be delved into is the overexpression and silencing of small RNAs through geminiviral vectors within the plant host genome. A notable disadvantage with geminiviral vectors is that it can only accommodate smaller sequences coding for size-restricted proteins as recombinant vectors with larger sequences are not stable. However, this can be advantageous in that it could serve as the backbone for delivering small RNAs in plants, thereby helping in modulation of regulatory processes in the DNA/RNA level, modulation of unwanted characters, and targeted overproduction of desirable traits in plants. Further, under the control of a suitable promoter, these vectors can be used as vehicles for overexpression of small peptides for many applications, such as peptide antibiotic nicin. Such viral vectors can be very useful for expressing venom peptides, having applications for developing anti-venoms, like mite allergens . An in-dBB and VH planned and designed the review. BB drafted the manuscript and prepared the table and figure. VH edited the manuscript. Both authors read and approved the final version of the manuscript.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.