Nest box bacterial loads were studied during the prebreeding period in relation to nest box occupancy by Great Tits and Blue Tits in the previous season at two different study sites: an urban park site and a deciduous forest site. This analysis revealed that the interior bacterial load was higher in the nest boxes used in the previous season for breeding; however, the results were significant only in the forest area. In general, the bacterial load was significantly higher in the nest boxes placed in the forest study area than at the urban park site.Among the environmental factors that affect bird nesting in nest boxes, the influence of microbial communities is relatively poorly understood. In this study, nest boxes used for breeding by secondary cavity nesters were sampled before the start of the breeding season to assess the bacterial loads of the nest box in relation to their previous year status. Different parts of the wooden nest box offer variable conditions for the development of bacteria. During the breeding season, the nest box entrance hole is wiped out by birds, delivering bacteria to their bodies, but during winter, it is exposed to unfavourable external conditions. The interior of the nest box, in turn, is also wiped by birds, but the conditions during winter are more stable there. Therefore, samples from the entrance hole and the interior of the nest box were taken at two different study sites: an urban parkland and a natural forest. We predicted that both the occupancy of the nest boxes during the previous breeding season by birds and the nesting sites would influence the bacterial load of the nest box. To verify this prediction, two categories of nest boxes were sampled at both study sites: nest boxes occupied by any of the two tit species (Great Tit or Blue Tit) in the previous season for breeding and nest boxes that had remained empty that year. The interior bacterial load of the nest box was higher in the nest boxes occupied in the previous breeding season, but only in the forest area. Furthermore, the bacterial load of both the entrance hole of the nest box and the interior was significantly higher in the forest study area in both occupied and unoccupied nest boxes. Our results show that the bacterial load of the nest box is positively related to the presence of nests in the previous breeding season and can vary between different sites. Microorganisms are ubiquitous in a variety of environments, and they inhabit all the available spaces there. One microhabitat, the avian nest, constitutes a unique environment for a variety of them ,2,3,4. BAmong the wide variety of locations where different species of birds breed, nests located in cavities are unique, as cavities constitute a particularly suitable environment for different types of microorganism ,3,15,16.In general, it is highly probable that the bacterial load of the nest box itself depends on a variety of environmental characteristics of a particular location. The physical properties of habitats include several characteristics such as humidity, thermal conditions, the chemical properties of the soil, and probably many other characteristics that influence the assemblages of bacteria on different spatial scales (see  for a reParus major) and the Blue Tit (Cyanistes caeruleus), at two different study sites: an urban parkland and a deciduous forest. For several years in our study area, both species have interchangeably used nest boxes for breeding in consecutive breeding seasons; however, in a particular year, some of the nest boxes may remain unoccupied throughout the breeding season. This may potentially lead to variation in the abundance of bacteria in nest boxes that probably remains on particular level all year round, including at the end of winter, directly before the onset of the breeding period. The second potential source of variation in the bacterial loads in the nest boxes may be due to habitat differences between the two study sites. It is well-known that urban parks are simplified and highly transformed versions of natural habitats for numerous bird species, including secondary hole nesters such as parids. The different physical conditions that prevail at either site  can probably shape the microbial communities in nest boxes. Moreover, it is likely that not only the specific conditions themselves in these two sites matter. In the case of the rich, seminatural forest site, the conditions are probably more stable over the years. On the other hand, the urban parkland area offers rather unstable conditions due to human-made interventions. This creates quite different conditions for the bacterial assemblages that inhabit both sites.For the reasons mentioned above and given that, in our previous study, we demonstrated a negative influence of the bacterial load on the physiological condition of wild birds , we condNest boxes themselves are structures that create many microenvironments for bacteria. The various surfaces of the nest box differ with respect to the intensity of contact with birds that carry microorganisms on their feathers, beaks, or legs. For that reason, particular parts of nest boxes such as the entrance hole are wiped out by birds regularly during the breeding season  and by individuals spending nights there in the winter. The interior of the nest box, in turn, is in contact with adult birds during the period of nest construction and subsequently with nestlings that have direct contact with the inner walls. Particular parts of nest boxes are also exposed to external conditions such as temperature, humidity, or insolation to different extents, which creates more or less stable microhabitats for microorganisms, including bacteria. It is very likely that during the winter months, the entrance hole area, which is directly exposed to weather conditions, may offer less favourable conditions for bacteria than the nest box interior. Therefore, we decided to sample both the interior and the entrance hole of the nest box. We estimated the interior bacterial loads of the nest box and the entrance hole to verify the following prediction: since the two parid species are similar in terms of nest type material and other breeding characteristics, the nest boxes used for breeding by any of the two parid species during the previous year  would have higher bacterial loads than the nest boxes that had remained empty that year . The second objective of this study was to test whether there was a significant difference in the bacterial load between the two study sites: the urban parkland site and the forest site.Betula pendula), beeches (Fagus sylvatica), and numerous alien species planted intentionally by garden administrators [Quercus robur and Q. petrea) are the dominant tree species in the forest. Both study sites were supplied with standard wooden nest boxes, each made of pinewood and with the same diameter of the entrance hole, 29 mm (200 in the parkland area and 300 in the forest area). After each breeding season in mid-October, each nest box at each the study site was cleaned with a wire brush, so that there were no visible nest remnants.This study was carried out in 2020 in two different habitats: an urban parkland and a deciduous forest. The study sites are located ~ 10 km apart and are separated by the city of Łódź. The urban parkland study site  consists of Łódź Botanical Garden, which covers a total area of approximately 67 ha. It is primarily of anthropogenic origin and has fragmented tree and bush cover with very few remnants of natural stands, including birches . In total, 80 samples were taken from the field. Some of them were inappropriate for further analysis due to technical problems, and finally, 71 were analysed. Only nest boxes with no or very little faeces at the bottom were sampled.In the first half of March 2020, 40 nest boxes (20 at each study site) were randomly chosen for bacterial sampling. Neighbouring nest boxes were excluded from the study. Also, given that the nest boxes at both sites are at least 50 m apart from each other and only a proportion of them are occupied for breeding each year , the nest box samples were independent of each other. Approximately half of the nest boxes at each study site had been occupied by one of the two tit species (Great Tit or Blue Tit) in the previous year for breeding, while the other half had remained empty that year (5 occupied by Blue Tits and 6 by Great Tits in the parkland and 4 occupied by Blue Tits and 6 by Great tits in the forest). Since the nest boxes are used interchangeably between years by both species, the data for Great Tits and Blue tits were pooled. Using disinfected latex gloves, an entrance hole was swabbed in each nest box with circular movements for 30 s with a sterile cotton swab previously moistened with sterile phosphate-buffered saline . Subsequently, a restricted area of ca. 2.5 cmOnce in the laboratory, bacteria from the swabs were transferred to a solution in the same manner as in our previous study on the bacterial load  . The intWe found that the interior bacterial load of the nest box was higher in the nest boxes used for breeding in the previous season, but this difference was significant only at the forest site. We also found that both the bacterial load of the entrance hole and the bacterial load of the nest box were significantly higher in the forest than in the parkland, in the nest boxes both occupied and unoccupied in the previous season.The occupancy of the nest box in the previous year affected the bacterial load of the nest box. Our results are ambiguous on this point, since this effect was significant in the case of the interior of the nest box but not in the case of the nest box entrance and only in the forest study site. It is not clear why this effect was only found at one study site. A possible explanation may be related to the intensity of use of the nest boxes as roosting sites during the autumn–winter period. It is well-known that wintering tits spend the night in nest boxes  in wet versus dry habitats. This is in line with our results, since rich, mature forests retain more moisture than urban parklands, with their many open areas, no or little tree cover, and, therefore, openness to direct sunlight. However, the richness of the plant species is not the only difference between the two sites. The Botanical Garden is a place where various agrotechnological works are conducted throughout the year (own observations). These procedures include intensive grass mowing, branch cutting, and the application of different chemicals, such as insecticides, which probably affect different organisms, including bacteria that are present not only in plants but also in soil. For example, in 2013 and 2014, a large-scale molluscicide treatment was applied in the garden to eradicate the invasive Spanish slug Arion vulgaris  and noctules  occasionally use empty nest boxes to breed and roost during the summer/autumn period, and they are more frequent in the forest (own observations). The pine marten (Martes martes), in turn, is a predatory species that tries to reach the nest in the nest box and grab an adult bird or nestlings with its paws as prey. In some breeding seasons, the predation rate was very high in the forest [In addition to basic habitat characteristics, including plant species composition and soil characteristics, there are probably other factors that can contribute to bacterial loads in nest boxes. It is known that different taxa of animals visit nest boxes for a variety of purposes. Many invertebrates  are opportunistic species that use nest boxes year-round as shelters or roosting places or to build nests and raise their offspring  (,36, own e forest  but not Our study demonstrates that the observed difference in the bacterial loads of the nest boxes may have been affected by their status as occupied by breeding birds in the previous season, which may have resulted from habitat-related differences between the two study sites. The most important factors are probably associated with the richness of plant species and the physical properties of the soil, with additional factors resulting from the specificity of the two study sites. However, taking into account the complex and yet relatively weakly understood relations between microorganisms, their hosts, and the environment, other factors probably play a role, and we are still far from understanding this issue. It is also clear that other site-specific characteristics, such as the presence of ectoparasites, various assemblages of invertebrates using nest boxes as opportunist species, and other external factors related to the structure of a particular site, may influence the environment for bacteria. We suggest that in future studies, these parameters should be taken into account and used in multi-factor modelling. Furthermore, we should interpret our results with care, since we do not have data on the richness of bacterial species at both study sites. We should stress here that our study, conducted in a single year and in two types of environment with only a relatively low number of nest boxes, does not allow for generalisations, and the results should be considered as tentative. However, we think that these results are valuable, since our study suggests that the bacterial load may be a potentially important factor for the life history traits of secondary cavity-nesting birds, because it may vary considerably between habitats. Furthermore, we showed that at the end of winter, directly before the breeding period, the bacterial loads in nest boxes are at relatively high levels and remain one of the significant factors that affect the nesting environment for secondary cavity-nesting species. Therefore, since studies on cavity-nesting birds with the use of artificial wooden nest boxes are widely conducted across a broad geographical range and a variety of habitats and given that the bacterial load can affect the host’s physiological health state, we consider our study prospective, as a promising foundation for future research.


Injection molding is a method commonly used to manufacture plastic products. This technology makes it possible to obtain products of specially designed shape and size. In addition, the developed mold allows for repeated and repeatable production of selected plastic parts. Over the years, this technology grew in importance, and nowadays, products produced by injection molding are used in almost every field of industry. This paper is a review and provides information on recent research reports in the field of modern injection molding techniques. Selected plastics most commonly processed by this technique are discussed. Next, the chosen types of this technique are presented, along with a discussion of the parameters that affect performance and process flow. Depending on the proposed method, the influence of various factors on the quality and yield of the obtained products was analyzed. Nowadays, the link between these two properties is extremely important. The work presented in the article refers to research aimed at modifying injection molding methods enabling high product quality with high productivity at the same time. An important role is also played by lowering production costs and reducing the negative impact on the environment. The review discusses modern injection molding technologies, the development of which is constantly progressing. Finally, the impact of the technology on the ecological environment is discussed and the perspectives of the process were presented. Injection molding technology is one of the most common methods used in the plastics processing industry. It is a method that can be used for mass production of products with complex shapes ,2. It isThe paper discusses the most commonly processed plastics by injection molding. It also focuses on literature reports describing the influence of process parameters on its performance and the final properties of products. In addition, interesting research work carried out in various types of injection molding is discussed; in particular: water-assisted injection molding; gas-assisted injection molding; microcellular injection molding; variable mold temperature technologies; microinjection molding; and rapid thermal cycling molding. The impact of the process on the ecological environment is further discussed and prospects for further development are presented.Polypropylene belongs to the polyolefin group and is one of the most widely used plastics in injection molding . The advResearch on the use of polypropylene in injection molding techniques was presented by Farotti et al. The paper presents the results of a study of the mechanical characteristics of commercial PP. The analysis was aimed at determining the correlation between the input injection molding parameters and the mechanical behavior of the material. Particular attention was paid to determining the influence of parameters such as plastic melting point, mold temperature, injection pressure, and cooling time. Based on the analysis, the influence of mold temperature and injection pressure on the mechanical properties of the polymer was confirmed. Increasing the values of these factors can lead, among other things, to distortion of the obtained product . An inteKosciuszko et al. then proposed an analysis of the change in the value of re-molding shrinkage and voids formed in PP moldings. The study was carried out by determining the dependence on the degree of porosity and time after removal of the molded part from the injection mold cavity. It was proven that the cell injection process, together with a longer holding phase, allows the reduction in gas pores, which translates into the reduction in cavities and unevenness of products .Polyethylene is one of the most popular and widely used polymers. It is obtained by polycondensation of ethylene . Due to Due to its plasticity and ease of processing, one of the most popular ways of producing PE products is injection molding. The molten polymer is injected into an injection mold and then cooled and hardened to obtain the desired shape. The injection molding method can be used to obtain many different types of products from this plastic. Among other things, it is used to produce various types of packaging, such as bottles and boxes. It is also widely used in the production of medical products, such as syringes, but also in the automotive industry and in household goods. In addition, many toys are obtained from PE through the use of injection molding ,40,41.2, injection time 0.6 s, and holding time 30 s [PE processing by injection molding is the subject of many scientific studies. Leyva-Porras et al. were concerned with determining the effects of processing variable parameters on the microstructure and crystallinity of LDPE samples that were injection molded. The polymer was injected at different cylinder and mold temperatures. It was proven that the interaction of the two temperatures has the greatest effect on the size of the spherulite. In turn, the mold temperature has a significant effect on crystallinity . Subsequime 30 s . In contime 30 s .Polystyrene is a plastic obtained by polymerizing styrene, and belongs to the polyolefin group ,48. ThisSubsequently, SadAbdai et al. proposed work on the numerical calculation of the fiber orientation tensor of an injection-molded short glass fiber polystyrene (SGF-PS) composite part, shaped as a rectangular plate. Again, the effect of selected injection parameters, such as mold wall temperature, injection flow rate, and also fiber content on the change in orientation of this sample was checked. Based on simulations, the injection flow rate was found to have a greater effect on the fiber orientation than the mold wall temperature . PolystyAcrylonitrile-butadiene-styrene copolymer (ABS) is an amorphous polymer obtained by emulsion polymerization or bulk polymerization of acrylonitrile with styrene in the presence of polybutadiene ,62. ThisABS is a material eagerly used in injection molding . Many stPolyvinyl chloride (PVC) is one of the most popular and widely used synthetic polymers. It is a thermoplastic polymer that consists of repeating units of vinyl chloride  PVC is wPolymethyl methacrylate, also known as acrylic glass, is a thermoplastic artificial polymer with a transparent and glass-like structure. It is one of the most widely used polymers due to its unique properties, such as high transparency, UV resistance, mechanical strength, and ease of processing . It is uPolyamide, also known as nylon, is one of the most important thermoplastic engineering materials used in injection molding. It is a versatile polymer with high mechanical strength, abrasion resistance, low hardness, and well-defined thermal properties. Polyamide was repeatedly analyzed as a material that can be processed by injection molding methods ,90. The Polymer processing technologies developed significantly in recent years. One of the new methods is water-assisted injection molding (WAIM). WAIM technology is proving to be a promising technology due to the lightness of the products produced, shorter cycle times, and greater potential for hollow product production. Water- or gas-assisted technologies can be categorized as F-PAIM or fluid projectile-assisted injection molding methods. The F-PAIM process can be divided into two types: the short-shot method and the overflow method. These methods differ depending on whether the mold cavity is filled with molten polymer completely or partially . Figure In the case of the short shot method, the cavity is filled with molten polymer only partially. In the system designed for the WAIM method, an additional water injection unit is distinguished in addition to the conventional system for injection molding. For the most part, this unit consists of a water pump, a water tank equipped with a temperature controller, a pressure accumulator, and automatic circuit control. The control system is responsible for parameters such as the time and pressure of water injection. Usually, such a unit has its own hydraulic system, is mobile, and can be adapted to different forms of machine. Different designs of water pins can be used: immobile pin type ,100 and The problem with the WAIM method is the phenomenon of “fingering” of water. This occurs when water bubbles get outside the water channels. It was proven that amorphous materials molded by the WAIM method produce less fingering than when using semi-crystalline polymers. The smallest side effects were also obtained for water channels with a rib gouged on top. Water pressure and injection size are also important parameters . The pheGas-assisted injection molding (GAIM) is an injection molding method in which gas is also injected along with the injected plastic ,113. InjA significant problem in injection molding is the possibility of scorch marks on parts of finished products. Reducing scorch marks by reducing the clamping pressure can be achieved with gas-assisted technology . The useMicrocellular injection molding (MIM) is a technique that enables the production of lightweight plastic products with a microcellular internal structure. The process in question allows for a material reduction of 30% to 40%. In addition, the resulting products have higher impact strength and an internal structure composed of a high density of small bubbles. In the injection molding process, liquid plastic is injected into the mold under high pressure, and then the pressure is quickly reduced, which causes the formation of microcells in the plastic structure . Microce3 [3/(g·cm−3) and 111% of neat LCBPP foams to 172.1 MJ/m3/(g·cm−3) and 440% of LCBPP/MD blend foams in terms of specific breaking energy and elongation at break, respectively [Microcell molding leads to a structure with lower density, increased stiffness, and better thermal insulation properties compared to standard injection molding. This technique may prove useful in the production of fiber-assisted thermoplastic door panels . The hig3 . Composi3 . The stu3 . Similar3 . Wang etectively . The MIMectively . Reinforectively  Lee et aectively , and Yu ectively . Liu et ectively . In turnectively . On the ectively .Injection molding is a widely used process for manufacturing plastic products. Many parameters of the process determine its efficiency, effectiveness, and also the final properties of the product. One of the most important aspects is temperature control and distribution. High temperature is necessary to melt the polymer, while mold cooling is crucial in curing the finished product. Variable mold temperature technologies include systems that allow temperature control during the injection molding process. These parameters are optimized over the years and adjusted to meet specific production and material molding requirements. One well-known method is heating the mold with water under high pressure. Newly developed systems can provide temperatures up to about 180–200 °C. However, it is important to properly develop pipe connections that provide the appropriate flow rate of pressurized hot water . Next, hThe demand in the production of precision microdetails influenced the emergence of microinjection molding (µIM) technolgoies. Miniaturization of plastic parts advanced significantly in recent years through continuous work on process optimization (µIM) ,156. TheResearch on the microforming process is developing at a very intensive pace, leading to the gradual elimination of the limitations of this process. In the process of injection microforming, thermoplastic materials are mostly used, and thermosetting materials are used to a lesser extent ,158. HowSpecialized microinjection molds were designed to produce biodegradable microneedles with a drug delivery channel . SubsequThe rapid thermal cycle molding method is a technique that involves rapid heating and cooling of the mold. This method provides improved quality and efficiency in the molding process. The benefit is to achieve a molded part with very good aspect quality with high gloss without defects, such as joint lines and collapses. With rapid thermal cycling in mind, the mold is heated quickly to the thermal deformation temperature of the polymer before the melt is filled, and then cooled after the packing step . The RTCThe analysis of RTCM injection molding technology is the subject of many research works. The interest is not only in the optimization of process parameters, but also in the investigation of the mechanisms occurring during plastic processing. The molecular mechanism of replication ability for conventional injection molding and RTCM was presented by Zhang et al. It was proved that the high mold temperature in the RTCM technique ensures that the high teperature is maintained for a long time and Brownian movements are very active in this case. The melt flow of the polymer is crucially related to the mold temperature and the pressure there . Another−1 [Multicomponent injection molding is an advanced plastic injection molding method that allows different materials to be combined in one simultaneous molding process. This technique allows you to create products with different colors, chemical properties, hardness, textures, and other characteristics. The main technical challenges are the selection of process parameters that allow simultaneous processing of two or more components. Equally important is equipping the injection machine with several injection units ,186. Mul−1 . The pos−1 . The use−1 ,192,193.Metal injection molding is an advanced manufacturing technique that allows the molding of metal parts with complex shapes and precise dimensions using a process similar to traditional plastic injection molding ,195. TakReaction injection molding (RIM) is a technology for producing plastic parts by reactive in situ polymerization. The process uses two or more liquid monomers. The technique is often used; however, its limitation and main challenge is the effective control of mixing between the injected liquid monomers ,206,207.A summary of references relating to selected injection processing methods is presented in A summary of the presented injection molding technologies is presented in There are many applications of WAIM technology, which is especially recommended for the injection of pipe and pipe-like elements. The developing technology allows the use of this method in the production of increasingly complex elements, also branched. Where there is a need for thin-wall moldings, this method is willingly used. GAIM is a method similar in principle to WAIM, but it allows for making a much wider range of moldings without great shape limitations. It is widely used to improve the quality of moldings . Its great advantage is the possibility of reducing the weight of injected details by gas injection, which results in saving granulate. It can also be used in other applications to reduce their density, e.g., for the production of oars.Microcellular injection molding is another modern plastic processing technology. The low specific weight of the moldings and significantly improved mechanical properties allow this injection method to be widely used in the aviation industry. MIM can be considered as a new process that combines conventional injection molding with microcellular foaming. The process is considered environmentally friendly, energy-saving, and allows the production of lightweight foamed parts with complex geometries. The multitude of additional technologies that can be combined with MIM increases the scale of possible applications in many applications and indicates a great development potential.A very intensively developing branch of plastics processing is the MCIM multicomponent injection molding with its various variants. It gives the possibility of producing details in various colors with different textures and, above all, from materials with different mechanical properties. The joining of materials takes place during one production cycle. It is very common to find a combination of a thermoplastic with one or more elastomer, such as in various types of protectors where the core is hard and the carcass, i.e., the protective element, is made of a softer material.The use of forms made in the RTCM technology is becoming more and more popular, especially in the automotive industry in the production of high gloss details. In particular, it concerns the production of seat elements, headrests, dashboards, and mirrors. The greatest benefit of using this technology is the ability to obtain moldings without the typical disadvantages of other injection technologies, such as dips, hoists, joining lines, and the ability to obtain a high-gloss aspect surface of the detail without the need for additional treatment in the form of varnishing.There are many methods of multicomponent injection, such as on-mold injection with a rotating half-mold, with a rotary core, and you can also inject a second and third elastomer after transferring the element from the first mold cavity to the second using a robot. The possibilities offered by this technology are very large and are used in the production of automotive components, sports equipment, as well as for the production of masks or diving glasses. The application possibilities are practically unlimited when we need to obtain an element consisting of two, three, or more different plastics. It is most often used for the production of details with a hard matrix of thermoplastics such as PP or PA with additional elastomers or to obtain multicolored parts directly from injection molding.Currently, MIM is not as widespread as the previously presented injection technologies, but its market share is constantly growing. It is used in the production of complex small elements whose serial production in the classic version is much more expensive or even impossible to achieve. The RIM method and its derivatives, such as PU-RIM, are used to produce thin-walled elements that, thanks to the technology used, can be produced on smaller machines, which contributes to reducing production costs.The environmental impact assessment is a process to identify, predict, and mitigate the environmental effects of biophysical process proposals. Injection molding technology, similar to any other processing method, affects the environment. An important parameter in the environmental assessment is the infrastructure of industrial factories, disposal of the resulting waste, and electricity consumption ,213,214.PLA injection molding was proven to use about 38.2% less energy than FDM technology. In addition, less carbon dioxide is generated per kilogram of PLA molded into the final product compared to additive technology .Research related to injection molding focuses on understanding and improving the process itself, aiming to achieve higher quality and precision of manufactured products while reducing cycle times and lowering production costs. In this context, researchers are studying the various materials used in the injection molding process, such as plastics, elastomers, and composites, in search of new, more efficient, and environmentally friendly raw materials that can be adapted to specific applications. An important aspect of the research is identifying key parameters of the injection molding process and analyzing their impact on the quality of the final products. This makes it possible to optimize the settings of injection molding machines, leading to better mechanical properties, durability, and aesthetics of products. Researchers also use numerical models and computer simulations to better understand the complex phenomena occurring in the injection molding process. This approach enables faster testing of different scenarios and prediction of results, leading to more efficient solutions. In addition, the research focuses on developing and evaluating new technologies related to injection molding. This includes the exploration of new types of injection molding machines, innovative molding techniques, the search for new materials, and the implementation of intelligent quality control systems that contribute to the progress and development of the field.Injection molding currently has promising growth prospects in the industry, as automation and robotization of injection molding processes are becoming more advanced. This is leading to increased productivity, precision, and production repeatability, while reducing operating costs. In addition, the introduction of new materials and technologies is opening up new opportunities for injection molding. Examples include higher-strength materials, which are finding applications in the automotive and aerospace industries, and biodegradable plastics, which are responding to the growing demand for greener solutions. Today’s consumers increasingly expect personalized products, and injection molding enables flexibility in design and production, allowing products to be easily customized to meet individual customer needs and preferences. In addition, injection molding plays an important role in sustainable development by reducing raw material consumption, minimizing waste, and promoting recycling. In the medical industry, injection molding is extremely important in the production of medical devices, medical packaging, laboratory instruments, and others. Due to the growing demand for advanced medical technologies, this field is expected to continue to grow, which will contribute to the further development of injection molding. In conclusion, the outlook for injection molding in the industry is promising. Technology development, process flexibility, sustainability, and the growing demand for personalized solutions are all contributing to the growing popularity of this manufacturing method.


A large number of proteins are successfully used to treat various diseases. These include natural polypeptide hormones, their synthetic analogues, antibodies, antibody mimetics, enzymes, and other drugs based on them. Many of them are demanded in clinical settings and commercially successful, mainly for cancer treatment. The targets for most of the aforementioned drugs are located at the cell surface. Meanwhile, the vast majority of therapeutic targets, which are usually regulatory macromolecules, are located inside the cell. Traditional low molecular weight drugs freely penetrate all cells, causing side effects in non-target cells. In addition, it is often difficult to elaborate a small molecule that can specifically affect protein interactions. Modern technologies make it possible to obtain proteins capable of interacting with almost any target. However, proteins, like other macromolecules, cannot, as a rule, freely penetrate into the desired cellular compartment. Recent studies allow us to design multifunctional proteins that solve these problems. This review considers the scope of application of such artificial constructs for the targeted delivery of both protein-based and traditional low molecular weight drugs, the obstacles met on the way of their transport to the specified intracellular compartment of the target cells after their systemic bloodstream administration, and the means to overcome those difficulties. The effect of the vast majority of drugs is ultimately realized inside the cell due to their interaction with biomacromolecules. All drugs that have an effect on intracellular processes can be roughly divided into four main groups . TraditiMany drug delivery vehicles that facilitate penetration into cells, regardless of the cell type, are in fact close to this group. Such delivery systems include, for example, cell-penetrating peptides (CPP) , bacteriLow molecular weight substances recognized by special transmembrane transporters can be considered the second group of drugs for intracellular targets B. More tThe third group of drugs exert their effect on the regulation of intracellular processes through cell surface receptors and pathways for further signal transduction C 12]. E. E12]. ERecently, more and more drug developments have begun to appear, allowing therapeutics to exert their effect inside the specific compartment of the specific cell type ,17,18,19The current field of multifunctional protein-engineered therapeutics intended for selective drug delivery into a specific compartment of target cells, their prospects, and their limitations are summarized in this review. These constructs can carry either low molecular weight drugs or therapeutic amino acid sequences.Cell and intracellular specificity, as the keys to selective targeting, will be discussed first. Then, we will shed light on the extracellular and intracellular barriers for therapeutics to overcome on their way to the intracellular target. This will be followed by a review of internalizable protein-based delivery systems and their intracellular fate after cell entry.To ensure the selectivity of the effect with respect to the cell type, the drug used must have the ability to recognize them. Optimally, the drug should identify the desired cell from its outside. This minimizes the side effects of drugs, preventing their action on non-target cells. Recognition can be achieved by binding to cell surface receptors. It is estimated that more than 1350 human genes encode surface cell receptors and provide regulation in the cell in response to external signals . They maThe greatest attention to the characteristics of the cells differentiating them from other cell types is paid in the development of anti-cancer drugs . HoweverThe actual differences in the content of proteins in cells are significantly greater, as each tissue usually consists of several basic cell types. There are many different cell types in the human body; however, their actual number remains a debatable issue . CurrentMoreover, approaches to the study of the spatio-temporal regulation of the proteome in the cell and its post-translational regulatory modifications are beginning to appear . The priIt is noteworthy that information related to aging-dependent changes in gene expression by different cell types in the body is also beginning to emerge. The data were obtained for mice ranging in age from one month to old age ,36. SimiDespite the vast amount of knowledge accumulated on the specificity of protein expression in the cell, in general, data on differences in the proteome in the body are currently far from complete. This is especially true for personal individual differences as well as differences at the level of a single cell. Moreover, as of 2021, the expression of 1421 predicted proteins coded in the human genome has not been detected yet, although this number is decreasing every year . NeverthIt should be noted that, as in the case of specificity with respect to cell type, a significant part of the proteins has a predetermined intracellular localization, which can be illustrated by data from the Human Protein Atlas database  41]. Th. Th41]. As a substantial proportion of drugs act or are at least more effective on specific intracellular targets, the recognition of the desired cell type should in many cases be followed by the subsequent intracellular transport of the delivered therapeutics to a target subcellular compartment . NumerouThe nucleus represents one of the most obvious and widely studied subcellular targets for a number of drug classes. Gene therapy setting, where either genetic material or a gene editing system should be delivered to the nucleus, can be regarded as a canonical example of nuclear-targeted therapeutics. The other examples include but are not limited to photosensitizers ,45, radiBeing the cell’s “power station” and programmed cell death master regulator as well as a key player in many other vital processes such as cell differentiation and division, mitochondria represent an attractive target for various, especially anticancer, therapeutics. Mitochondria-targeted chemotherapeutics , nucleicThe restoration of proper functioning is also among the most widely utilized approaches in lysosomal targeting. This strategy is widely used for the treatment of lysosomal storage diseases, with a number of therapeutics already used in clinical settings for the treatment of several enzyme deficiency disorders  . On the ER stress and the subsequent unfolded protein response supposed to underlie such pathologies as neurodegeneration, cancer, and diabetes represent an attractive target for therapeutic modulation . To achiOther cell organelles, e.g., Golgi apparatus, plasma membrane, and peroxisomes, are also used for precise targeting in the development of strategies for treating serious diseases, such as cancer .A variety of protein- or peptide-based systems aimed at targeted subcellular delivery are exemplified in The increase in the size of drugs or drug nanoformulations compared to small molecules makes it possible to use more of the embedded necessary functions and also dramatically expands the range of substances that could be used for treatment. Currently, a huge number of such drugs are under development, including proteins and polypeptides, polymers, structures based on nucleic acids, and pharmaceutical carriers carrying many small-sized drug molecules. Their common feature is their size in the nanometer range, and all of them face similar problems on the way to their locus in quo. Any drug administered systemically into the bloodstream must overcome several natural barriers to reach the cell interior . These bThe interaction with blood proteins is of great importance for the substance injected into the blood . The mosIn addition to the interaction with proteins, the walls of blood vessels, which serve to separate blood from other organs, are a natural barrier on the way of intravenously injected substances to other tissues. This barrier becomes especially significant if the drug should act on deeper lying tissue cells. The physiological upper limit of the pore size for transvascular flow through the capillary walls of blood capillaries varies for different types of tissues . This liVascular endothelial cells form a complexly regulated system designed to ensure the transcytosis of antibodies and other blood proteins, such as albumin . TranscyThe extracellular matrix, with a network of fibrillar proteins and negatively charged proteoglycans, may be another barrier on the way of some macromolecules to target cells that are not exposed to the bloodstream ,101. TheWhen the drug finally overcomes the aforementioned barriers on its way to the cell, further aspects regarding its direct impact on intracellular targets arise. For an accurate effect on the intracellular target, it is necessary to take into account at least two interrelated issues: the intracellular location of the target and what else can be changed as a result of the drug action. Moreover, upon the development of such drugs, one should take into account their fate after cell entry, including intracellular processing and degradation. A huge amount of experimental material has been accumulated on the intracellular distribution of proteins and other macromolecules as well as their effects on intracellular processes. The systematization of these data and the transfer of high-throughput proteome analysis methods to the subcellular level have begun to attract close attention .A living cell, like a living organism, is a structured system divided by phospholipid membranes into compartments. The penetration of macromolecules into the cell is a strictly regulated process . The simThe interaction and exchange of contents between the endosomes and other membrane organelles, as well as with the plasma membrane, are carried out by a vesicular transport system ,117. TheThere are also other organelles in the cell, the nucleus or mitochondria, surrounded by two layers of membranes into which proteins are transported only from the cytosol but not from other membrane organelles ,119. A lAn in-depth description of the pathways for the targeting of each individual intracellular organelle is provided in In addition to the membrane intracellular barriers, the movement of macromolecules to the therapeutic target can also be hindered by the intracellular environment itself due to the large concentration of macromolecules and the presence of organelles in the cell, which complicate diffusion. An extremely high concentration of proteins in the cell leads to the effect of macromolecular crowding, which is caused by a sharp reduction in the solvent volume available for moving macromolecules, with an increase in their concentration ,132. In There is no single list of barriers that a macromolecular agent must overcome in order to reach its target. This list depends on the intracellular location of the target, on what type of cells the target is located in and where those cells are located in the body. Accordingly, there is no single solution to the problem of drug delivery into the cell. It is also clear that the properties of the delivery system may also depend on the drug being delivered. Particles close in size to such typical pathogens as viruses and bacteria, due to their size, are convenient means for the delivery to macrophages and other MPS cells and probably to some tumors due to the EPR effect. Their advantages include the possibility of the delivery and subsequent local release of a large number of low molecular weight drugs with an already known effect. For delivery inside most other types of cells, especially those lying deep in the tissue, it is more preferable to use something smaller. The lower limit of the size of such delivery systems is the aforementioned renal filtration limit. Quite large proteins exceeding ca. 60 kDa fall into this range. The most well-known solution to the problem of the renal excretion of insufficiently large molecules is the addition of polyethylene glycol . A long Recognition of the cell type, transport of macromolecules into cells, and signal transduction via intracellular pathways are all largely carried out through the interaction or modification of proteins. The variety of amino acid sequences makes it possible to combine the necessary transport functions with therapeutic ones within a single molecule encoded by a single gene ,144,145.The use of artificial polypeptides as a delivery system imposes its own natural limitations associated with the attachment of the active principle. Larger nanoparticles can be loaded with a large number of low molecular weight drugs. The payload of protein molecules with low molecular weight drugs is usually inferior to relatively large nanoparticles, especially liposomes. The attachment of the active principle may also require the presence of a degradable linker for its therapeutic effect. An obvious solution to increase the effect of the delivered substance is the use of a component that provides the production of a large amount of active principle. Therefore, a delivered drug that is capable of generating a greater number of active products upon an external stimulus or on its own is attractive for creating effective macromolecular drug delivery systems. These include, for example, photosensitizers that produce a variety of reactive oxygen species (ROS) when irradiated with light of the appropriate wavelength. These ROS are extremely reactive, so they are not able to spread over a long range in biological media and can damage biological molecules in the immediate vicinity of the emission site . AnotherThe advantage of proteins is the possibility of including the necessary regulatory sequence or a fragment with the necessary enzymatic activity directly into the delivery system as part of a single amino acid sequence. Examples of such protein drugs are immunotoxins for the treatment of cancer. They are fused proteins that include catalytic subunits of natural toxins, for example, ADP-ribosylating pseudomonas exotoxin and diphtheria toxin, or a ligand to the receptors of malignant cells, which can be presented by both an artificial antibody and a natural ligand . Three iThe targeted intracellular delivery to cells of a specified type using macromolecules requires combining many transport functions in a single molecule. In general, this is a non-trivial task; however, the already created molecules have demonstrated that its solution is quite possible . The idea of using the combination of several amino acid sequences and transport modules for the delivery of a drug into the nuclei of target cells was originated by A.S. Sobolev and first published in 2000 . The devMoreover, tumor recognition specificity can be further enhanced by the inclusion of masking domains for the selective unmasking of cell targeting domains by tumor-specific proteases cleavage ,159,160.As noted above, there is a large class of cell surface receptor proteins whose main function is cell regulation. These receptors are able to bind natural ligands and undergo endocytosis. There are quite a few successful drugs that are natural ligands to internalizable receptors. Their artificial analogues are also often used. Many of these drugs, such as insulin, ACTH, and somatotropin derivatives, have become widespread . In addiDespite this apparent success, the antibodies that are already approved and being tested cover only a small fraction of possible targets for disease treatment. The technologies used in their creation include the production of chimerical polypeptides and can be used to solve a much wider range of tasks. There are a huge number of therapeutic targets inside cells that are undruggable for small molecules , so intrFrom the point of view of drug delivery into a specified cell type, the use of receptors has several obvious consequences that depend on the type of ligand chosen. When using natural ligands to receptors for drug delivery into the cell by endocytosis, in addition to the uptake of ligand–receptor complexes, receptor-mediated regulation of cellular processes takes place. This can lead to side effects in cells that narrow the therapeutic window. Artificial ligands created on the basis of antibodies and antibody mimetics, as a rule, are antagonists for receptors. This leads to the blocking of the process activated by the natural agonist. This blocking can also cause side effects. A typical example is the side effects that occur during the treatment of malignancies by blocking the tyrosine kinase receptors ,177. In As was mentioned above, a number of uptake ways of macromolecules and nanoparticles are known ,111,112.As already mentioned, the endocytosed ligand–receptor complex, when passing through the initial stages of the endocytic pathway, undergoes sorting . This paFor many years, a promising research direction that uses CPP to deliver drugs into the cytosol has been developing ,198,199.In addition, most CPPs work effectively only at micromolar concentrations, which are significantly higher than the dissociation constants of the ligand–receptor complexes of cell surface receptors. Therefore, when using concentrations optimal for specific receptor-mediated delivery, it is difficult to ensure an effective exit from endosomes using such sequences. It should also be taken into account that the delivery of macromolecules to cells has been shown only for an extremely small (about 4%) part of the sequences proposed as CPPs . ResearcCorynebacterium diphtheriae toxin [Clostridium botulinum C2 toxin [Clostridium difficile [Another option for delivery to the cytosol is to use fragments of a number of bacterial toxins that are specialized for this process . They inae toxin , anthraxae toxin , ClostriC2 toxin , binary ifficile ,205, andifficile ,207,208.ifficile ,212,213.ifficile . Neverthifficile ,214. Theifficile ,215,216.ifficile  may be sAs noted above, drug delivery to the cytosol also opens the way to molecular targets in the nucleus and mitochondria that are attractive for therapy. The nucleus is the main object for regulating gene expression, both for disease correction and for in vivo cell reprogramming. The endosomes’ escape is necessary, but it is not sufficient for the transport of drugs into the cell nucleus from the cytosol. The transport of macromolecules from the cytosol into the nucleus is provided by the NPC . The NPCThe mitochondria are also a cellular compartment that is accessible to the drug only from the cytosol . StudiesAnother cellular compartment that receives proteins from the cytosol is the peroxisome . PeroxisDelivery to other intracellular compartments can be provided by vesicular transport from endosomes . As alreOne of the possible ways of intracellular vesicular trafficking is the protein exchange between the endosomes and the TGN ,251,252.The Golgi complex constantly exchanges content with the ER via vesicular transport. The short KDEL sequence provides a dynamic exchange of many proteins between the ER and Golgi . The KDEThere is also a channel between the ER and the cytosol through which cellular proteins can be transported from one compartment to another. For transport from the cytosol to the ER, it works mainly for newly synthesized proteins that are designed to function in the ER or outside the cell. This transport is mediated by the Sec61 translocon, which interacts with the ribosomes of the rough ER. Thousands of secretory and membrane proteins follow this pathway ,271. TheThe vast majority of human proteins enter the lumen of the ER during translation. However, about 200 proteins are known, mostly small and mostly containing a hydrophobic site at the c-terminus, which are translocated post-translationally . Thus, iThe development of drug delivery systems that control the interaction between a drug and a biological microenvironment is one of the main current paradigms for the creation of new pharmaceutical products . ProteinProteins offer the unique opportunity to combine several biological functions within a relatively small structure. An example of this kind of artificial molecule is modular nanotransporters that combine several transport functions: binding to the receptor and endocytosis, endosome escape and transport into the cell nucleus ,193,224.Generation of datasets on protein expression in individual cell types;Many-fold differing expression of a significant part of the protein targets, both by cell types and by subcellular localization;A significant change of protein expression in various pathologies, primarily in cancer;Elucidation of the plethora of barriers on the way of a macromolecule to its target site after administration at the whole-body-, tissue- and cellular-level and the ways to overcome them.The performed analysis reveals that protein constructs for delivery to a certain cell compartment of a specified cell type can be considered a distinctly promising class of drugs and delivery systems for precise drug targeting. Such protein constructs can serve either as components of intensively developed drug nanoparticles or as a significant extension to the list of promising therapeutic agents. The main prerequisites for the development of this research direction are:Accumulation of data on the subcellular distribution of proteins in cells of various types and their individual differences;Significant development of interactome maps with its transition from ascertaining the presence of interaction between proteins to its concentration and kinetic dependences;Progress in predicting the spatial structure of the created artificial protein constructs and their interaction with the proteome.Moreover, significant efforts are already being made in research in the following areas, which are of crucial importance for further movement in the aforementioned direction:The creation and development of protein structures for precise impacts on intracellular targets requires huge efforts and investments, which do not seem, however, overwhelming compared to the funds that humanity spends on wealth accumulation and conflicts.


Salmonella enterica serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries. Limited information is available regarding its genomic diversity, especially from South Asian countries that are collectively responsible for >80% of all paratyphoid cases. At the 2021 International Conference on Typhoid and Other Salmonelloses, researchers from the around the globe presented their work on Salmonella Paratyphi A genomics. Presentations described recent genomic data from South Asia and the development of Paratype, an open-access single-nucleotide polymorphism–based genotyping scheme, to segregate Salmonella Paratyphi A genomes in a systematic and sustainable manner. In this review, we attempt to summarize the progress made thus far on Salmonella Paratyphi A genomics and discuss the questions that remain to better understand the pathogen and develop interventions to fight it. Salmonella Paratyphi A isolates have been sequenced from South Asia in the past 2 years. An open-access tool, Paratype, has been developed to track genotypes and antimicrobial resistance. However, genomic data are still limited from sub-Saharan Africa, the Middle East, and South America.More than 1000  Salmonella enterica serovar Paratyphi A, transmitted through contaminated food and water, is the primary causative agent of paratyphoid fever. With the expansion of antibiotic therapy and improvements in water, sanitation, and hygiene, there has been a 41% decline in the overall global burden of paratyphoid fever from 1990 to 2017 . We. WeSalmoutations  that couSalmonella Paratyphi A biology and epidemiology in recent years portends positive signs in the field of genomics and global health. Paratyphoid fever is endemic in many LMICs and 2 of the studies discussed here were largely conducted in their respective countries. The development of Paratype, a genotyping scheme from Bangladesh, also represents one of the first examples of bioinformatic tools developed by scientists in LMICs and would be useful for the public health community across the Global North and Global South. Such efforts must be nurtured if the decentralization of genomics and decolonization of the global health agenda are to be achieved. An area that requires immediate attention is the paucity of bioinformatics skills among researchers in LMICs that prevents them from analyzing their own data. Moreover, development of bioinformatics tools is often supported by unrestricted grants to research groups at universities as funding agencies in global health often focus on primary data generation. However, tools such as Paratype have the potential to empower researchers across countries and require dedicated funding streams to ensure that such tools are regularly maintained and updated. We must address these gaps if we want to make global health truly global and remove the neglect from neglected tropical diseases.The progress that has been made on Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.ofad077_Supplementary_DataClick here for additional data file.


Population-based cancer registries (PBCRs) are important sources of data on cancer burden in a defined population. They are a cornerstone for establishing, implementing and monitoring and evaluating a rational cancer control programme. Despite the long history of PBCRs in more developed countries of the world, PBCRs in sub-Saharan Africa are still poorly developed and cancer control is poor. Compared to PBCRs in Europe and the United States, cancer registries in sub-Saharan Africa are still functioning at a basic level. Only a few cancer registries in sub-Saharan Africa contribute data regularly to the International Agency for Cancer Registries’ (IACR) GLOBOCAN and Cancer in Five Continents’ publication series. In Nigeria, there have been efforts at strengthening existing PBCRs and creating new ones, and implementing national cancer control programmes. It is however unclear how successful these efforts have been. It is therefore necessary to reflect on documented activities so far in order to identify gaps and proffer solutions. A population-based cancer registry (PBCR) is a system that collects information from multiple sources on all reportable malignant neoplasms occurring in a geographically defined population . PopulatThe concept of PBCR has been in existence for more than five decades . The firData from PBCRs provide valuable information on the impact of interventions across the cancer control spectrum including prevention, early detection, treatment, rehabilitation and palliation. For example, in 1994, the cancer registry in Taiwan compared the incidence of liver cancer in children between the age of 6 and 9 years, who were born before the introduction of hepatitis B vaccination for newborns and those who were born after. They found a four-fold decrease in incidence following the introduction of vaccination . SimilarThe World Health Organisation recommends that as an initial step to setting up a National Cancer Control Programme (NCCP), an analysis of the cancer burden, risk factors in the target area and capacity assessment  are conducted . This caDespite these well-recognised utilities of PBCRs, they are either entirely not available in many developing countries or are poorly developed. It is therefore difficult to accurately determine the cancer burden – in terms of incidence, distribution and survival – in these countries. Without these data, implementing a rational cancer control plan and evaluating it is impossible.Although Nigeria started the process of developing cancer registries in the 1970s, those efforts have not been very successful . The absWe have conducted a narrative review to allow critical analysis of review articles and published government reports. This approach best suits the aim of our research because of the diverse issues and fields that are being analysed. According to some authors, narrative reviews are effective where the aggregation of data is difficult because different subject themes are being analysed .A literature search was conducted on PUBMED and Google Scholar using the Query: ‘PBCRs AND NCCP AND sub-Saharan Africa OR low-middle-income countries’. The search on PUBMED yielded 359 results and 1920 on Google Scholar. Duplicate studies were eliminated; studies that included non-African countries, and those that focused on a particular demographic population, e.g., children, and specific cancer sites, e.g., breast cancer, were also excluded. The search was further refined to include only review articles (this is because we wanted to focus on only information that is relevant to the objectives of the study) published from 2005, and in English language. Only articles that focused on the features and dynamics of PBCRs and cancer control were selected. Ten articles were finally included in the review. In addition, a country each was selected from west (Ghana), east (Kenya), and southern Africa (South Africa), and the official policy document of their NCCP was included in the review. We have shown the process of literature search and selection in the flow chart . The incCIV, failed because they did not meet the criteria set for data quality. However, data from other sub-Saharan African countries, such as Malawi, Zimbabwe, Kenya and Uganda, were included [The Nigerian National Systems of Cancer Registries (NSCR) was established in 2009 as a collaboration between the Federal Ministry of Health (FMOH), the Society of Oncology and Cancer Research of Nigeria and the Institute of Human Virology of Nigeria with the primary objectives of providing training, capacity development, monitoring and providing technical and scientific support to cancer registries in Nigeria. A publication in 2015 reported the activities of this organisation, its achievements, the challenges it encountered, a map for future directions and suggestions for future activities pertaining to strengthening PBCRs . Notableincluded .Cancer in Nigeria 2009–2016 – is also available for download. There are a total of six newsletters published, the most recent was in January 2017. The website also hosts data from five cancer registries – Abuja, Edo, Ekiti, Sokoto and Calabar – with application procedures to be able to access these data [In the 13 years of its existence, the NSCR has been able to train more than 70 registry directors, cancer registrars and data clerks on basic cancer epidemiology and the use of CanReg5 – a cancer registration software developed by the IARC . In its Cancers in Nigeria was last published in 2016, and there is no evidence to suggest that the data from contributing cancer registries have been updated recently [The efforts deployed by the NSCR to strengthen PBCR although many and laudable, do not appear to have the coordination and sustainability necessary to cause a bigger impact. For example, the last newsletter published was about 6 years ago, in 2017 . The pubrecently .The first cancer registry in Nigeria was an HBCR at the Pathology Department of the University College Hospital, Ibadan. It was established in the 1960s . Cancer The first NCCP was officially launched in 2008 and was expected to be operational for 5 years, elapsing in 2013 . On 4 NoAlthough the NCCP 2023–2027 has been launched, there is no report yet of the just concluded NCCP 2018–2022. Therefore, it is rather early to assess the success of the programme. It would be interesting to note the baseline surveys conducted to arrive at baseline data upon which the success or otherwise of the interventions can be assessed. It would also be interesting to note how successful the prevention and screening strategies have been, considering that up till now there is no national cancer screening programme for neither cervical cancer, breast cancer, prostate cancer or colorectal cancer. The human papillomavirus vaccination has not been incorporated into the extended programme for immunisation (EPI). The bill on tobacco smoking has been passed and adopted. Out of the eight public comprehensive cancer centres in the country, only three currently have functioning megavoltage radiotherapy machines and rendering services. The others are limited to rendering surgery, chemotherapy and palliative care to cancer patients. There has been a regular supply of syrup morphine for pain control in palliative care patients at all tertiary health facilities offering oncology services. The chemotherapy access programme initiative has been successful in providing chemotherapeutic agents to patients at a subsidised rate. Advocacy by stakeholders in the cancer care space has led to the incorporation of certain monoclonal antibodies used in cancer treatment into the national health insurance where the pharmaceutical company, the National Health Insurance Agency, and the patient share the cost of the medicine.Ghana launched its cancer control programme in 2011 and planned to span for 5 years from 2012 to 2016 . The GhaSimilar to Nigeria, the history of cancer registries in Ghana is fraught with many failed attempts. The most recent was initiated in 2016, as a part of the NCCP, and aimed at strengthening the process [Policy: a policy document on cancer control mandating cancer registration using the CanReg5 software.Data source: which involved training cancer registrars who actively visit relevant departments to abstract data from the patient medical records.Administrative structure: this includes a registry director, registry manager, an advisory board comprising heads of departments of pathology, oncology, surgery, child health, gynaecology, internal medicine, public health and representatives from birth and death registries, private laboratories and private hospitals.External support and training: which ensures funding, training of staff and technical support.Coverage area: this defines the geographical location covered by the PBCR .The efforts of the PBCR in Ghana have been slightly impactful even if there is still some room for improvement. In a review of cancer incidence published in GLOBOCAN 2012, incidence estimates submitted from Ghana were classified as F, which is the least acceptable quality for inclusion in the analysis . The IARThe first National Cancer Control Strategy (NCCS) in Kenya was launched in 2011–2016. The second edition which was launched in 2017 elapsed in 2022 [Kenya has a very active PBCR system, the Kenya Medical Research Institute (KEMRI) Cancer Registry . The NaiSouth Africa only launched its National Cancer Strategic Framework (NCSF) in 2017 and was scheduled to elapse in 2022 . The MinThe NCSF policy spells out the process of care from surveillance, publicity and education, screening and diagnosis, treatment, supportive care and rehabilitation, patient care pathways, and care packages for individual patients at each level of health care. The document however fails to clearly outline specific activities at each level aimed at clearly defined objectives. The roles of each stakeholder in the cancer care space are also not clear. There are no baseline data against which any improvements can be measured. Although the document identifies common modifiable risk factors, it fails to outline clear activities which will be implemented to mitigate these risk factors. Similarly, for screening, the document listed cancer types that will be prioritised for screening programmes; however, it did not comment on which screening modalities would be deployed.South Africa currently does not have a PBCR. The NCR-SA is a pathology-based registry established in 1986 . In the Although the basic function of PBCRs, i.e., providing data on incidence rates of cancers in a defined geographical location, was the primary focus of the first cancer registries in Europe and America, their roles have since evolved . Well-deA synthesis of the literature search shows that PBCRs in Nigeria are still a very long way from achieving most of the successes that PBCRs in more developed countries have achieved. For example, the cancer registries in Nigeria rely on the manual collection of relevant hospital records from pathology departments, surgical outpatient departments, oncology clinics and wards by trained registrars who visit several hospitals within their geographical location periodically. This process is burdensome, inefficient and may result in the collection of poor data. The quality of the data collected may be fraught with errors because of human factors, such as lack of attention to detail as a result of fatigue, large volumes of work, and discontent with remuneration. Furthermore, the data collected using this method are often limited and fail to capture other crucial information that can contribute significantly to providing a more accurate picture of the cancer burden in Nigeria. Compared to the United States, for example, where cancer registries have been linked to electronic medical records since 2004, advanced data collation and analyses using machine learning are being done .2) [2 and a population of about 48 million in 47 administrative counties. Kenya has three main PBCRs located in Nairobi, Eldoret and Kisumu counties, and cover less than 10% of the Kenyan population [Another dimension to look at PBCRs in Nigeria is the number of registries relative to its population. Nigeria is a large country   and the 2) . The geopulation . NigeriaApart from the number of PBCRs relative to the population size, a critical aspect is the functionality and effectiveness of the registries. The International Agency for Cancer Registries is an organisation recognised worldwide that collects quality cancer registration data from member organisations and publishes them periodically. It serves to ensure that the data published are of the highest quality based on a set of criteria. Only registries that produce quality data are included. Hence the successful publication of a registry’s data in the GLOBOCAN or CIV can be used as a measure of its functionality and effectiveness. The PBCRs in Nigeria have not successfully published their data in either of GLOBOCAN or CIV in decades. On the other hand, PBCRs in neighbouring Ghana and Kenya have published theirs in recent years.The poor functioning of the PBCRs in Nigeria will invariably constitute a major setback to the success of its national cancer control plans. The unavailability of accurate data on the burden of cancer on the population makes it difficult to identify key priority areas of intervention and allocate scarce resources to meet immediate needs and plan for the future. It is therefore pertinent that the existing PBCRs be strengthened to function more effectively in order to plan better for cancer control.PBCRs in Nigeria are not functioning optimally. This will constitute a major setback to the implementation, evaluation and overall success of the NCCP. The Kenyan PBCRs are performing at a higher level and can serve as a model for the Nigerian PBCR given that both countries are low-and-middle income countries (LMICs) and in sub-Saharan Africa. It is critical that PBCRs in Nigeria are revisited and strengthened to be able to provide accurate data on the cancer burden in the country, as well as provide insight into the capacity of the existing service delivery systems to provide quality and equitable care for its citizens.The NSCR is a veritable tool for coordinating the activities of the existing PBCRs. However, the organization seems to have lost its zeal in the past few years. This may be as a result of inadequate funding by the federal government, lack of political will, and paucity of resources from other sources besides the government. Besides the role of the NSCR, the individual PBCRs must be strengthened by local ownership and investment. This can be achieved by state governments, hospital management and collaborations between public health systems in each geo-political region and non-governmental organisations. Strengthening PBCRs to function optimally will ease the task of the NSCR.Globally, the activities of PBCRs are coordinated by the IACR. It is therefore important that PBCRs in Nigeria aim to publish their data in the IARC GLOBOCAN publications. This will serve as a critical indicator of the success of our PBCRs and herald the success of our NCCP.The author(s) declare that they have no conflict of interest.We have not received any financial support to conduct this study.


Background: Meta-analyses (MAs) and network meta-analyses (NMAs) are high-quality studies for assessing drug efficacy, but they are time-consuming and may be affected by biases. The capacity of artificial intelligence to aggregate huge amounts of information is emerging as particularly interesting for processing the volume of information needed to generate MAs. In this study, we analyzed whether the chatbot ChatGPT is able to summarize information in a useful fashion for providers and patients in a way that matches up with the results of MAs/NMAs. Methods: We included 16 studies (13 NMAs and 3 MAs) that evaluate biologics (n = 6) and both biologic and systemic treatment (n = 10) for moderate-to-severe psoriasis, published between January 2021 and May 2023. Results: The conclusions of the MAs/NMAs were compared to ChatGPT’s answers to queries about the molecules evaluated in the selected MAs/NMAs. The reproducibility between the results of ChatGPT and the MAs/NMAs was random regarding drug safety. Regarding efficacy, ChatGPT reached the same conclusion as 5 out of the 16 studies (four out of four studies when three molecules were compared), gave acceptable answers in 7 out of 16 studies, and was inconclusive in 4 out of 16 studies. Conclusions: ChatGPT can generate conclusions that are similar to MAs when the efficacy of fewer drugs is compared but is still unable to summarize information in a way that matches up to the results of MAs/NMAs when more than three molecules are compared. Meta-analyses (MAs) and network meta-analyses (NMAs) are crucial for synthesizing the enormous amount of information gathered to answer specific questions and are generally considered some of the best tools for evidence-based practice in medicine as they are based on the findings of multiple studies that were identified in comprehensive, systematic literature searches ,2,3. A MThe capacity of artificial intelligence (AI) to aggregate huge amounts of information by automatically extracting the written text of medical papers and converting the text into a more structured set of data is emerging as particularly interesting for processing the volume of information needed to generate MAs ,8,9. An We investigated the abilities of ChatGPT to compare the different systemic therapeutic interventions for moderate-to-severe psoriasis. As ChatGPT’s training data have a cut-off date of 2021, and as the AI may, therefore, not have access to the most recent information that has been published after that date , we compThe conclusions of these MAs/NMAs with the ranking of the investigated drugs with respect to their efficacy and/or tolerance were summarized. We asked ChatGPT, which is directly available on the internet free of charge (at the time of redacting), to assess the efficacy and tolerance of the evaluated drugs in selected MAs/NMAs in order to investigate whether the conclusion of the AI matched those of the MAs/NMAs. The queries were sent to ChatGPT between 15 January 2023 and 30 May 2023. The questions were formulated to ChatGPT in different ways (1) to have an overview of the drugs with the highest efficacy and the best tolerance, (2) to have a ranking of the efficacy of the investigated molecules using the same efficacy and safety outcomes as those of the MAs/NMAs, (3) to verify whether ChatGPT’s answers matched the main conclusions of the MAs/NMAs. To evaluate the coherence and the acceptability of ChatGPT’s answers, the results of the queries were submitted to two clinical experts in the field of psoriasis. The details of the queries and of ChatGPT’s outputs, and the ranking of the evaluated molecules are available in the We identified 28 MAs/NMAs published between January 2021 and May 2023, investigating and comparing the effect of systemic therapies for moderate-to-severe adult plaque psoriasis ,25,26,27The main results of the MAs/NMAs are summarized in In total, we collected 16 studies, among which 10 focused exclusively on biologics and six evaluated both biologic and systemic treatment . A total of 13 of those 16 selected studies were NMAs, and three were MAs .Despite significant heterogeneity across all the MAs/NMAs , there was some consistency in the efficacy and safety rankings of the investigated molecules, with anti-interleukin (IL) 17 and anti-IL23 biologics having the highest short-term and long-term efficacy ,17,18,21Depending on the day and time that the queries were sent, ChatGPT’s outputs could vary between vague, general answers and very detailed outputs. We had to reformulate some queries in order to obtain more precise answers, as sometimes general queries did not lead to specific outputs. Depending on the queries, the questions had to be inputted two to five times (mean: 2.5 times) to get an analyzable answer. We chose to select the more detailed answers for easier comparisons with the different MAs/NMAs.The conclusions of ChatGPT’s outputs were compared to those of the MAs/NMAs and rated in The safety of the molecules was compared in two MAs ,23 and tWe also noted, in one query, that ChatGPT’s answers contained obvious mistakes, such as presenting infliximab (an anti-TNFα drug) and secukinumab (an anti-IL17 drug) as biologics targeting IL-12 and IL-23, and guselkumab, risankizumab, and tildrakizumab  as anti-IL17A biologics . HoweverMore importantly, the whole assessment was completed in less than a few hours over 3 weeks, representing huge time savings compared to the months it usually takes to conduct traditional MAs/NMAs.The MAs/NMAs on anti-psoriatic drugs combine the results of multiple studies in order to provide a more robust estimate of the relative efficacy of different treatments and are usually generated by experts in the field of psoriasis. However, they require complex statistical techniques and a significant amount of time to produce  and may Although some consistency in efficacy rankings was observed for certain drugs across the MAs/NMAs, the rankings for other drugs varied by indirect comparisons. The factors potentially contributing to the heterogeneity of the results of the selected MAs/NMAs include the use of different methodologies for statistical analyses, the variation in drug dosing and treatment duration, the difference in the number and type of evaluated drugs, and the outcome definitions. Many biases may impair the reliability of the conclusions of MAs, and large randomized controlled trials do not always confirm the results of prior MAs .The acceptability and coherence of ChatGPT’s answers could be rated as adequate for most queries by two experts in the field of psoriasis. Although substantial heterogeneity could be evidenced across the MAs/NMAs, the ranking by ChatGPT of the investigated drugs, with respect to their efficacy, was generally comparable to those of the selected studies. When fewer (three) drugs were compared, ChatGPT’s conclusions were identical to those of the MAs/NMAs. It is worth noting that this was valid for MAs published in 2021 or after because ChatGPT’s knowledge cut-off is 2021 .There were, however, some discrepancies between the conclusions of the NMAs and the answers of ChatGPT when several molecules were compared. For instance, although for the majority of the recently published NMAs, ixekizumab and risankizumab ,17,18,21Despite these mistakes, it appears both exciting and frightening that with an AI-based system, coherent answers to complex questions can be easily obtained within seconds. In addition to its ease and speed of getting results, ChatGPT may be less affected by human bias and potential conflicts of interest than MAs/NMAs in the interpretation of data. The other strengths of ChatGPT are that it might provide more up-to-date information (there are often significant lag times before the publication of MAs) , and it ChatGPT relies on open-access data and has no access to the paid content of subscription-based scientific journals. The research community has also recognized a need to incorporate the “grey literature” into MAs to reduce the risks of publication bias (the selective publication of studies based on their results) and reporting bias  . There iHowever, in opposition to MAs/NMAs, ChatGPT and other AI are (still) unable to provide a statistical analysis with the corresponding confidence intervals. AI is also (still) unable to address the biases and limitations in individual studies. As ChatGPT’s cut-off knowledge is 2021, its AI may also not have access to the most recent information that has been published or has occurred after that date . AnotherThere may also be fears about any reliance on large language models for scientific thinking, as these models are trained on past information, whereas social or scientific progress can often come from thinking or being open to thinking differently from the past. In addition, the widespread use of chatbots such as ChatGPT raises a range of ethical concerns that need to be critically examined  .To our knowledge, there has so far been no similar attempt to compare the results of MAs/NMAs and the information gathered from ChatGPT. Recently, Anghelescu et al.  presenteThere are several limitations to our study. The sources of information used by language models like ChatGPT are vast and diverse, encompassing a wide range of data, including scientific studies, articles, books, and online sources. On the contrary, the sources used in MAs are usually more limited and specific, focusing on peer-reviewed studies and controlled trials that meet certain inclusion criteria, and it is so far impossible to confirm that the results of MAs are more reliable than those of an AI. Another major limitation in the interpretation of our data is that it is unknown to what extent, among the variety of sources analyzed by ChatGPT, the results and conclusions of the investigated MAs/NMAs have been used, especially when considering that GPT-3.5 is a series of models that was trained on a blend of text and code from before Q4 2021 ,11. Due While MAs and NMAs are usually regarded as one of the best tools to compare drug efficacy, they can be affected by a number of biases mainly because they are generated by humans. Besides, collecting data and evaluating the results of MAs/NMAs is often a long and arduous process. It is then quite disconcerting to receive an AI-based output in seconds that would take a human team years to develop and whose answers are more or less comparable to the conclusions of MAs/NMAs regarding the ranking of drug efficacy in the treatment of moderate-to-severe plaque psoriasis. However, at this point, it would be hazardous to rely solely on an AI to gather information since some mistakes from ChatGPT were found in this study, such as wrongly attributing certain drug characteristics or sometimes providing different rankings in terms of drug safety. Moreover, MAs/NMAs are scientific methods using statistical analyses, whereas an AI can be continuously trained to avoid this kind of mistake, and a language model such as ChatGPT could have the potential to be a fast and complementary method for processing the large volumes of data necessary to generate or verify the results of MAs/NMAs. However, since ChatGPT has so far had limitations in providing an accurate and complete overview of the available evidence, this technology should be applied under rigorous human supervision and control. The potential of other AI techniques or other pre-trained language models, such as BERT  to simplify the process of summarizing data from the medical domain requires further investigation.