Development of data driven, sensor-based irrigation has become possible with recent advancements in technology, yet due to a cost-barrier to entry, equitable adoption remains out of reach. Therefore, a simple microcontroller based LoRa platform, Open_Irr, was developed in the Arduino IDE to record resistive measures of soil matric potential and automate irrigation events. A single Open_Irr Node may connect with ≤ 16 Watermark® soil sensors and manage 4 irrigation groups, with Node sampling frequency, irrigation settings, and radio transmission settings being end-user adjustable without programming knowledge. Multiple Nodes may connect with a single Gateway to provide a scale-neutral solution for irrigation automation. A preliminary trial was conducted in spring 2022 to validate the performance of the Open_Irr platform in water deficit scenarios. Open_Irr recorded soil matric potentials in line with a commercial Watermark® sensor reader (n = 655); regression analysis yielded a coefficient of determination of 0.91 with Bland-Altman estimated fixed bias of ∼ 2 kPa. The Open_Irr platform was demonstrated to automate dripline irrigation events at several matric potential thresholds through connection to external solenoid valves. This demonstration directly conveys suitability for commercial and academic horticultural applications where automation of irrigation events or imposition of edaphic water stress is desired. Open_Irr leverages an array of commercially available microcontroller modules and Watermark200ss soil matric potential sensors The Open_Irr platform, phonetically The LoRa functionality can be described as a proprietary radio communication technology developed by Cycelo (patent 9647718-B2) that encodes information using the Chirp Spread Spectrum technique to transmit data on radio waves with lower power requirements than Bluetooth® or cellular options. The LoRa functionality utilizes < 1 GHz radio frequencies that do not require a license to enable “free” data transfer at moderate ranges; transmission of several kilometers is possible under ideal conditions. For additional information regarding the LoRa communication protocol, we direct readers to a summary provided by “The Things Network” The most similar open-source hardware to Open_Irr is the ArduinoSoilH2O platform The Open_Irr platform is composed of “Node” and “Gateway” units to provide scalability but may be operated with or without a connected Gateway. Both the Node and Gateway are constructed utilizing the Moteino-Mega USB microcontroller board utilizing the ATMEL ATMEGA1284P processor; the 915 MHz LoRa transceiver was specified per the available “industrial/scientific/medical” frequency band in the originating region (USA). To facilitate an external radio antenna, U.FL connectors were soldered to the Moteino-Mega; 15 cm external U.FL to RP-SMA pigtails leading to 200 mm ½ wave 915 MHz duckbill antennas permitted external mounting on the environmental enclosure. Each unit contains a DS3231 real-time clock (RTC) module The Node device is configured with 2, 16-channel CD74HC4067 multiplexors The Gateway device is configured with a 4-pin terminal block screw connector connected to digital output pins of the Moteino-Mega USB like in the Node; these digital output pins  can be toggled to a HIGH (3.3 V) state in response to Watermark sensor values from radio transmissions received by connected Open_Irr Nodes. The Open_Irr Gateway device has 3 additional 3-pin switches to toggle RX, TX, and VCC states of a HC-05 Bluetooth module with the intention of Bluetooth user interface in a future iteration. At the time of writing, interfacing with the gateway must be made through a Serial terminal monitoring application. The Gateway should be continuously powered using the Micro-USB port of the Moteino-Mega through an AC/DC power supply . Temporary power outages are circumvented by integration of a 6-NiMH-AA battery cradle as in the Node device.The voltage divider circuit in either device was specified using 10 kΩ and 4.7 kΩ resistors and toggled using a FQP30N06 MOSFET to limit current drain. Digital pin 30 of the Moteino-Mega USB was defined as an output and connected to the gate of the MOSFET and a 10 kΩ pull-down resistor to ground; the MOSFET source pin was connected to the common ground. The MOSFET drain pin was connected sequentially to the 4.7 kΩ resistor, the analog pin 7 of the Moteino-Mega USB, the 10 kΩ resistor, and the battery VIN. Analog pin 7 on the Moteino-Mega was set as an input and used to read VIN from the battery cradle after digital pin 30 was set high to close the source-drain MOSFET circuit.L-by-6 W-by-4D inch locking latch IP68 rated environmental enclosure •Datalogging for multiple Watermark sensors.•Automation of data-driven irrigation events.•Research applications in drought stress and imposition of water deficit.•Controlled environment research applications.A 6Open_Irr_Node.ino: Open_Irr Node program written in the Arduino IDE, uploaded to Moteino-Mega USB microcontroller in the Node unit. Should only be altered by advanced users.Open_Irr_Gateway.ino: Open_Irr Gateway program written in the Arduino IDE, uploaded to Moteino-Mega USB microcontroller in the Gateway unit. Should only be altered by advanced users.Gerber_HardwareX_Open_Irr_Node_PCB.zip: Open_Irr Node gerber zip file. Provide to PCB manufacturers to obtain PCB.Gerber_HardwareX_Open_Irr_Gateway_PCB.zip: Open_Irr Gateway gerber zip file. Provide to PCB manufacturers to obtain PCB.Schematic_HardwareX_Open_Irr_Node.pdf: Open_Irr Node electrical schematic of included components.Schematic_HardwareX_Open_Irr_Gateway.pdf: Open_Irr Gateway electrical schematic of included components.•oThe Moteino-Mega USB must be soldered to the PCB so the Micro-USB connector faces up and is nearest the top edge of the PCB. However, before soldering the Moteino-Mega USB to the PCB, it is best to first solder the U.FL connector to the Moteino-Mega USB module. The U.FL connector must be soldered to the Moteino-Mega USB module so the wide surface mount wings of the U.FL connector attach to the wide surface mount platforms on the Moteino-Mega USB. Consequently, the narrow surface mount wing of the U.FL connector is soldered to the circular through hole for attaching a simple wire antenna on the Moteino-Mega USB module. The U.FL connector can be soldered to either side of the Moteino-Mega USB. Note: this is the most difficult component to solder – it is suggested to first place a small portion of solder on one of the wide surface mount platforms of the Moteino-Mega USB. Then, using forceps in one hand and the soldering iron in the other, reheat the solder and place the U.FL connector using forceps. The other surface mounts of the U.FL connector can now be carefully soldered .Fig. 3PlNode•oIdentical to Node.GatewaySoldering was performed by hand using a Hakko-FX888D-23BY soldering station with a T19-I sharp tip and temperature set at 343 °C. Printed circuit boards were ordered to ease construction; the required Gerber design files to provide to PCB manufacturers have been provided at the links above. After receipt of the PCB, components were soldered into place per the linked schematic and layouts in 2C protocol and connected Serial Clock (SCL) and Serial Data (SDA) lines to digital pins 16 and 17 respectively on the Moteino-Mega USB; the Square Wave (SQW) line was connected to digital pin 24 of the Moteino-Mega USB to handle timer interrupts.•oSolder the DS3231 module to the PCB so the integrated circuit faces up and the CR1220 battery cradle faces the PCB; the VIN pin will be on the top edge of the PCB and the RST pin will be closer to the bottom edge of the PCB.Node•oSolder the DS3231 module to the PCB so the integrated circuit faces up and the CR1220 battery cradle faces the PCB; the VIN pin will be on the left-hand side and the RST pin will be on the right-hand side.GatewayThe DS3231 RTC uses I•oSolder the MicroSD card module so all module components face up; the 5 V pin will be on the left-hand side and the CD pin will be on the right-hand side.Node•oIdentical to Node.GatewayThe MicroSD card module used SPI protocol and connected the Serial Clock (CLK) pin to digital pin 7 of the Moteino-Mega USB, Data Out (DO) pin to digital pin 6, Data In (DI) to digital pin 5, Chip Select (CS) pin to digital pin 28, and Chip Detect (CD) pin to digital pin 29.•oSolder each CD74HC4067 module so the integrated circuit faces up, in doing so there is only one way the modules fit on the PCB. Solder these 2-pin terminal block connectors so all openings face the left-hand side of the PCB. The two rectifying diodes are polar components and must be soldered so the stripe is nearest the bottom edge of the PCB.Node•oNot applicable.GatewayEach CD74HC4067 multiplexor was connected to ground through a rectifying diode. The Enable (EN) pins of each multiplexor connected to digital pin 22 of the Moteino-Mega USB, the Select 0,1,2, and 3  pins of each multiplexor connected to digital pins 18,19,20, and 21, respectively. The Signal (SIG) pin of one multiplexor connected to digital pin 26 of the Moteino-Mega USB; the SIG pin of the other multiplexor connected to analog pin 1 and to digital pin 27 through a 10 kΩ resistor. Channels 0 to 15 of one multiplexor connected to one side of the 16, 2-pin terminal blocks while channels 0 to 15 of the other multiplexor connected to the opposing side of the 2-pin terminal blocks, respectively. Wiring of the multiplexors was designed in this way to conform to manufacturer reading instructions of Watermark sensors •oSolder the 2-pin terminal block connector so the openings face the right-hand side of the PCB. The direction of the 3-pin switch is inconsequential.Node•oIdentical to Node.GatewayPower and ground from the battery cradle were routed to one side of a 2-pin terminal block. The powered side was connected to Voltage IN (VIN) 2 of the Moteino-Mega USB; the ground side was connected to one end of a 3-pin slide switch, the middle pin of the slide switch connected to the Ground (GND) 2 of the Moteino-Mega USB. The other end of the 3-pin slide was left unconnected to permit user toggle of Open_Irr battery power via the slide switch.•oSolder the MOSFET so the heat dissipation fin is nearest the bottom edge of the PCB.Node•oSolder the MOSFET so the heat dissipation fin is nearest the left-hand side of the PCB.GatewayPower from the battery cradle was also routed to a voltage divider circuit consisting of 10 and 4.7 kΩ resistors with analog pin 7 of the Moteino-Mega USB connected to the junction point of the voltage divider circuit. The voltage divider circuit was made toggleable by connecting the ground end of the divider circuit to the drain pin of a FQP30N06 metal–oxide–semiconductor field-effect transistor (MOSFET). The source pin of the MOSFET was connected to the common ground while the gate pin was connected to digital pin 30 of the Moteino-Mega USB and a 10 kΩ pull-down resistor to ground. Solder the MOSFET commensurate with the Gate-Drain-Source pins, G-D-S, indicated on the Silkscreen layer.•oSolder the 3-pin terminal block connectors so the screw heads of the male portion of the connector are nearest the bottom of the PCB. From left to right, as plugged into the female header, the DS18B20 temperature sensor connections are GND-Data-VCC .Fig. 4CoNode•oNot applicable.GatewaySixteen 3-pin terminal block connectors allow connection of 16 DS18B20 temperature sensors utilizing the Dallas 1-Wire protocol. These sensors have 3 leads in total  and the 1-Wire protocol allowed routing a common data line to digital pin 1 of the Moteino-Mega USB; the data line was also connected to 3.3Vin through a 4.7 kΩ pull-up resistor.•oSolder the 4-pin terminal block connector so the screw heads of the male portion of the connector are nearest the bottom of the PCB.Node•oIdentical to Node.GatewayOne 4-pin terminal block connector allowed external wire connection, left to right, to digital pins 12, 13, 14, and 3 of the Moteino-Mega USB (19 to 22 on the Gateway), respectively. Firmware options are provided to set the pins HIGH based on soil matric potential readings. It is intended for this output to act as a signal enabling ancillary equipment, such as irrigation infrastructure, to function based on sensor readings made by Open_Irr Nodes.•oNot applicableNode•oAlthough currently nonfunctional, the HC-05 Bluetooth module is soldered to the PCB so the EN pin is nearest the top edge of the PCB and the STATE pin is nearest the bottom edge of the PCB. Three additional 3-pin slide switches are soldered to the PCB which are intended to permit user toggle of the Bluetooth connection with the Open_Irr gateway, the direction of the switches is inconsequential.GatewayOne HC-05 Bluetooth module and three 3-pin slide switches are included in the Gateway unit to permit future Bluetooth communication with the Open_Irr Gateway.The environmental enclosure must be prepared to allow mounting the Open_Irr PCBs and installation of the radio antenna and cable grommets. A ¼-inch hole was drilled 2 in. to the right of the locking latch at a 1-inch depth relative to the enclosure body to facilitate antenna installation. Post construction and antenna attachment, the antenna hole was sealed with silicone to prevent water leaks .Fig. 5A A 1-inch-diameter hole was cut on the left hand side at a 3-inch depth relative to the enclosure body and 4 in. from either length of the enclosure to install a ¾-inch cable grommet .Fig. 6PlSimilarly, two additional 1-inch-diameter holes were cut at 2 ¼ inches from each end of the width of the enclosure and a 3-inch depth relative to the enclosure body to accommodate two additional ¾-inch cable grommets .Fig. 7PlInside the enclosure four 1 ½-inch by 3/8-inch (outer diameter) nylon spacers offset a support platform constructed from two 5/8-inch by 5/8-inch pieces of plastic stock cut to 6 ¾-inches in length. To prepare plastic stock for mounting inside the enclosure, drill two 1/8-inch-diameter holes ¼-inch from the long ends of the stock .Fig. 8PrOn the latch side of the enclosure, the plastic stock connects to a 2-inch brass ball-bearing hinge; to prepare the stock for hinge mounting, drill two 7/64-inch holes 68 mm proximal to either end of the stock .Fig. 9PlThe hinge connects to the plastic stock via two ½-inch (#6) hex head screws. The other side of the hinge connects to a 5-inch by 7-inch polycarbonate sheet 1/8-inch thick with two ½-inch (#8–32) bolts and nuts. To prepare the polycarbonate sheet for mounting the hinge, drill two 1/8-inch-diameter holes 45 mm from the long edge and 10 mm proximal to the narrow ends of the sheet. The Open_Irr PCBs were designed with 1/8-inch diameter through-holes to permit mounting onto the polycarbonate sheet using ½-inch (#6–32) bolts and nuts. To prepare the polycarbonate sheet for Node mounting, drill four 1/8-inch-diameter holes 20 mm and 6 mm proximal to the sides of the polycarbonate sheet. To prepare the polycarbonate sheet for Gateway mounting, drill two 1/8-inch-diameter holes 20 mm and 45 mm proximal to the narrow ends of the polycarbonate sheet and 6 mm proximal to the top edge of the sheet. The bottom two holes for mounting the gateway are also positioned 20 mm and 45 mm proximal to the narrow ends of the polycarbonate sheet and 54 mm proximal from the bottom edge of the sheet .Fig. 10PAfter all drilling is completed, the mounting solution can be installed in the environmental enclosure. Place the 2 ½-inch socket head screws (#10–32) through each piece of plastic stock, placing the 1 ½-inch nylon spacers on the other side. Then, screw into place inside the four corners of the environmental enclosure, ensure the vacant side of the brass hinge faces upward and can lay flat .Fig. 11PInstall the ¾-inch cable grommets so the rubber gasket is on the exterior of the enclosure. If soldering of the PCB has been completed, mount the respective Node or Gateway PCB to the polycarbonate sheet using ½-inch screws and nuts (#6–32) .Fig. 12MInstall the polycarbonate sheet inside the enclosure by attaching it to the brass hinge using ½-inch screws and nuts (#8–32), then attach the radio antenna to the enclosure using the U.FL to SMA pigtail/connector. The U.FL connector on the pigtail can now be attached to the U.FL connector on the Moteino-Mega USB .Fig. 13ABefore operation of Open_Irr Node or Gateway units, users must download the required Serial terminal monitoring software to interface and communicate with the system. Due to the interactive menu interface of the Open_Irr system in the Serial terminal, additional action in a programming development environment after initial firmware upload is not necessary for typical operation. If modification of Open_Irr firmware is required, see the troubleshooting notes for additional software resources and considerations. The latest firmware will be available on the projects GitHub page The Open_Irr system must be operated and configured through a device capable of Serial communication port monitoring e.g., computers, cell phones, and tablets. Computer users that have the Arduino IDE may utilize the Arduino program. Termite is a free alternative serial monitoring application available at several online repositories. For iPhone and Android, pick any reputable Serial monitoring application from the respective app store. In any Serial monitoring application, the baud rate must be set to 9600 and the user must select the communication port where the Open_Irr device is identified. Open_Irr devices become discoverable on a communication port automatically, the port number will be different between units but remain the same for an individual device. The Open_Irr device provides access to a configuration menu when a Serial port connection is established. The menu will appear as text in the Serial monitoring application utilized and the user will interface with the device by sending text commands in the Serial terminal monitoring application. There is no other user interface for configuration of the current Open_Irr system. The configuration menu reports the current values for most user-definable settings of the device. In addition to showing the current configuration, the menu provides the user with several prompts to configure the device. While the Open_Irr device is connected to a Serial terminal monitoring application and in troubleshooting mode, the user can type and enter “menu” into the Serial terminal monitoring application to return to the configuration menu. Menu options must be selected by typing and entering the desired case-sensitive command into the Serial port monitor terminal .Fig. 14ANote: user selection of any individual menu action must be made within 60 s, or the program will “timeout”, exiting the menu to operate under its current configuration. Menu actions are case-sensitive, use lower and uppercase letters where indicated. Menu functions describe how to configure the Open_Irr Node and Gateway devices in detail in When user configuration of an Open_Irr unit is completed, the user must select the “x” action in the menu to save the configuration changes to the devices EEPROM memory. Upon power cycle, Open_Irr devices populate a globally declared structure with the configuration from the EEPROM memory to call from during normal operation. It is our intention that users of Open_Irr devices will find the functionality limited but adequate through the current menu configuration options. Users with programming experience possessing other functionality requirements are encouraged to contribute to improving the Open_Irr platform through the device’s GitHub page •Node ID•Node battery pack voltage•oMonth/day/year HH:MM:SSDateTime of the DS3231 RTC module•oEach connector number followed by the measured sensor value from that connector (kPa)oEach sensor value followed by the raw resistance value (Ω) if reporting of resistance values is specified in the configuration settingsWatermark terminal block connector number (0 to 15)•oEach group number followed by the mean Watermark sensor value for the water management groupo▪Month/day/year HH:MM:SSEach group mean followed by the DateTime of the last irrigation event for that groupThe water management group number (G1 to G4)•oEach temperature sensor number followed by the value of the measurement in CelsiusThe DS18B20 temperature sensor number (0 to 15)Data from the Open_Irr system is stored on the MicroSD card in character separated value format using a comma “,” as the delimiter. A header describing the format of the saved data is provided in lines 1 to 8 of Open_Irr Nodes and 1 to 12 of Open_Irr Gateways with the delimited data beginning on line 9 and 13, respectively. On an Open_Irr Node the data is stored in the following order:•Gateway ID•Gateway battery pack voltage•Node data string as described aboveOn an Open_Irr Gateway the data from Node transmissions are stored in a similar fashion:An example Open_Irr Node data string without raw resistance values: 104,7.92,4/2/2022 18:15:55,0,-58,1,-55,2,-58,3,-76,4,-44,5,-54,6,-45,7,-60,8,-74,9,-44,10,-54,11,-62,G1,-52,3/31/2022 9:32:13,G2,1,1/1/1970 0:00:00,G3,1,1/1/1970 0:00:00,G4,1,1/1/1970 0:00:00,T0,22.50,T1,23.19.The Watermark sensors read by Open_Irr Nodes have two wires which are routed through a ¾-inch cable grommet to the 2-pin terminal block screw connectors, component 5 on the Node in The DS18b20 temperature sensors are also wired through a ¾-inch cable grommet and into the 3-pin terminal block screw connectors, Node component 6 in Both the Node and gateway may be powered by a battery providing 3.3 to 16 V; a battery pack containing 6-AA NiMH batteries is specified for this manuscript. When convenient, power from a 3 to 16 VDC wall power supply can be provided to the Micro-USB port on the Moteino-Mega USB, however, note that the 3-pin power switch will not function to shut the unit off when this connection is made .Fig. 17MFor battery operation, connect the positive and negative wires from the battery cradle to the respective location on the 2-pin terminal block screw connector, Node component 9 in The Open_Irr platform allows for triggering of irrigation events based on sensor readings through a low-logic (3.3 V) HIGH output signal on up to 4 pinouts .Fig. 18PIrrigation events on Nodes are based on connected sensor readings and defined using menu option “w”. On the Gateway, events are configured to occur based on sensor readings as received in radio transmissions from connected Nodes using menu option “w” and subsequently “G” as described in The Open_Irr system may operate on battery voltages from 3.3 V to 16 V, exceeding this will damage the unit. We do not recommend attempts to interface higher-voltage systems while attempting to put together an automated irrigation system with Open_Irr if the user is unfamiliar with electrical wiring. Avoid electrostatic discharge to Open_Irr units as damage to system components can occur. Adding dehumidifying packets into the Open_Irr enclosure when operated in humid environments will reduce oxidation of system components. Do not power or operate Open_Irr units without an antenna connected as irreversible damage to the radio transceiver can occur. Note that we have described a 915 MHz radio transceiver as the Open_Irr platform was developed in the United States, please consult national radio laws in the country and region of operation before build and deployment •The Arduino IDE •Drivers for Moteino-Mega module used in Open_Irr •Patched version of the Radiohead library •Supporting documentation and latest firmware can be found at the Open_Irr Github page tidyverse package Soil matric potential measures obtained from the Open_Irr platform were assessed with those obtained from a commercial handheld Watermark sensor reader blandr package in R The estimated slope of the linear model was 1.09 with a standard error of 0.01; the intercept was estimated as 0.03 with a standard error of 0.33. In this case, a slope > 1 indicated slight overestimation of matric potential (more negative) by Open_Irr relative to the handheld commercial device. The coefficient of determination was 0.91 indicating high agreement between the two measurement devices. In methodological comparisons a slope converging on 1 is ideal, however systematic scatter around the regression may indicate potential biases. In response, a Bland-Altman plot was constructed utilizing the The Bland-Altman estimate of fixed bias was −1.99 and considered significant at the 0.05 probability level suggesting soil matric potential values obtained through Open_Irr may be adjusted by 2 (less negative) to align with the commercial device. Practically, this difference may be nominal and originate from slight differences in the resistance conversion algorithm, such as temperature data source, inclusion of a calibration resistor, and miscellaneous resistance differences in the measurement circuits. Although not completely discernable in the range of matric potentials observed in this trial, continued formation of a funnel shape in the Bland-Altman figure at more negative matric potentials would suggest systematically increasing non-directional bias. Further study of the Open_Irr system at lower matric potentials in soils with higher clay content or experiments without live plants are needed to provide data for further speculation. Matric potentials at this extent were not explored in the preliminary trial as extreme water deficits would have manifested in tree mortality in the soil utilized.A characterization of radio transmission reliability from Open_Irr Nodes to Gateways was completed. For this characterization, a single Node was configured for a measurement interval of 1 min with 15 Watermark sensors and 3 temperature sensors, then placed on a mast ∼ 1.5 m above the ground outdoors. The addressed Gateway was mounted on an identical mast and placed at 100, 250, 500, and 1000 m from the Node within line of sight. The elevation delta remained within ± 10 m at each distance. Weather at the time of testing was cloudy with temperatures remaining between 4 and 16 °C. Both Open_Irr units were powered on for 1 h at each distance. Note: although a measurement interval of 1 min was specified, the program run time and radio transmission function reduced the expected number of transmissions from 60 to approximately 40. Comparison between the transmissions expected from the Node and those received by the Gateway resulted in a ratio of 158/160 when distances were pooled, indicating a reliability of 99% , top.FigTwo Node transmissions were not received by the Gateway, one at 250 m and one at 1000 m. Variability of the received signal strength indicator (RSSI) was low at each transmission distance, despite an occasional outlier, and was inversely related to transmission distance , middle.Malus domestica B.) B.9 rootstocks grafted with three scions  were planted in a climate-controlled greenhouse in pots containing Watermark and temperature sensors connected to Open_Irr Nodes. Five Nodes and 1 Gateway were deployed to monitor soil matric potential of the potted trees and automate irrigation events. From March to May, water management groups of the Nodes were configured to maintain unstressed conditions at −25 kPa to facilitate typical growth. On 16 May, the water management groups were configured to trigger irrigation events at −25, −40, −60, or −80 kPa corresponding to water management settings 1, 2, 3, and 4 of each Node. Other pertinent water management settings were: 15 min measurement frequency; (ii) a minimum of 15 min between irrigation events; and (iii) a 6 s irrigation event. To perform irrigation events, Open_Irr Node pinouts were wired to 4-channel 3.3 V logic relay modules The preliminary trial of the Open_Irr platform conducted in April of 2022 also intended to assess viability of automating irrigation events for purposes of horticultural water deficit study. Sixty apple (It was observed that Open_Irr correctly triggered irrigation events at the defined matric potential thresholds; in the case of −60 or −80 kPa approximately 1 week had elapsed until irrigation events were triggered .Fig. 24SThe irrigation threshold of −40 kPa resulted in observable wilting of leaves, while −60 and −80 kPa resulted in partial and total desiccation, respectively, of foliage from 16 May to 23 May. At this point in time the Open_Irr water management group settings prompted irrigation events for −60 and −80 kPa thresholds, which recurred until the sensors ceased to read matric potential above respective thresholds. In this case, a lag-interval for sufficient re-watering and reduced water uptake manifested in matric potential spike and fall i.e., wet-dry cycles. Subsequent irrigation events for −60 and −80 kPa settings were delayed, likely due to the physiological stress encountered. The Open_Irr platform reliably triggered irrigation events at set points; however, proper selection of matric potential thresholds will maximize Open_Irr efficacy in tandem with modification of irrigation protocols for intended plant physiologic condition. Fine tuning of the water management algorithm is ongoing. As deployed in this preliminary study, Open_Irr Nodes opened solenoid valves for 6 s during a single irrigation event. To gauge the replicability of the experimental set up, the flow rate of individual emitters, and solenoid valves were measured at the outset and end of the study .Fig. 25FP = 0.011 and P = 0.045 respectively. Numerically, confidence intervals constructed at the 0.05 probability level remained ± 8 and ± 26 ml min−1, respectively, and were considered suitable. Nevertheless, we recommend periodic calibration of any watering system connected to Open_Irr to assure accurate irrigation events, particularly for academic applications.Two sample t-tests indicated significant differences between the emitter and solenoid flow rates at the start and end of the trial, To aid end-user deployment and operation of Open_Irr, several important observations were made while implementing the preliminary study. Initially, irrigation events were envisioned to be performed by peristaltic dosing micro pumps for the greatest accuracy and precision of irrigation events. The micro dosing pumps utilized were found to be unsuitable due to backpressure on the irrigation lines which prevented uniform irrigation events and prompted redesign of the irrigation system as described above. Second, as the study progressed the 3.3 V logic capable relay modules periodically failed; failure was traced back to individual channel relay switches and in a few cases to circuit isolation optocouplers on the relay switch boards. The failure of relay modules prompted daily oversight incompatible with commercial implementation. In response, an integrated power switching module has been developed and tested; incorporation of this module to the Open_Irr platform is planned for the next revision of the Open_Irr PCB. Last, radio transmission of long data strings as “String” type data from Open_Irr Nodes to the Gateway for reparsing was unreliable. Therefore, a custom library “RadioString” was created to better handle these situations and has been incorporated into the Open_Irr program. The “RadioString” library is also publicly available To summarize, in fall of 2021 we initiated an endeavor to design a low-cost and open source datalogging platform to improve collection of soil water status and automate irrigation events for research and commercial applications in horticulture. The resulting Open_Irr system provides these functions at a competitive cost to end-users without requiring programming knowledge. Moreover, Open_Irr is a scale-neutral platform that provides end-users with the option to implement customized automated irrigation events. This function has the potential for widespread commercial applicability as demonstrated in a preliminary greenhouse trial using dripline irrigation and during the subsequent radio transmission range test. Moreover, the ability to specify the extremity of water deficit imposition is of further value to academic drought tolerance and cultivar screening endeavors for various crops. The authors hope that the Open_Irr platform will improve access to drought tolerance research tools, improve resiliency of current production systems and further the development of climate-smart and data-driven agricultural techniques.Andrew M. Bierer: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Spleen lesions and pseudolesions, detected incidentally in imaging, are not uncommon and may require further work-up. The imaging appearance of focal splenic lesions (FSLs) may not be pathognomonic, because of considerably overlapping features. Consequently, all imaging techniques lack specificity to fully characterize FSLs. Clinical correlation is mandatory, so as, first of all, to categorize the patient as having or not having a history of solid or hematologic malignancy. Nowadays, many patients have old imaging studies available for comparison and, consequently, it is important to understand if the lesion was previously present or not, and if the size is the same or has changed. In the absence of comparison studies, and with a lack of imaging features of benignity, further investigation may be necessary, using PET, biopsy, or short-term follow-up. Some algorithms have been proposed to manage incidental FSLs; however, none of these strategies has been validated by prospective studies to date. In this review we illustrate the topic of incidental FSLs and we analyze a number of published algorithms. Spleen incidentalomas are unexpected abnormalities, detected within the spleen by imaging modalities and not related to the presenting illness of the patient. Although less common than other incidentalomas, such as those in the liver or kidney, occasionally-detected spleen abnormalities in asymptomatic subjects are nowadays encountered with an increased frequency ,2,3. ThiFocal splenic lesions (FSLs) are detected in 0.1–0.6% of US examinations . In a stIn this review article we discuss the topic of splenic incidental lesions, illustrate the key features of splenic lesions and pseudolesions, and highlight findings suggestive of malignancy. Finally, we critically analyze a number of published management algorithms for spleen incidentalomas.The normal spleen shows extensive variations in terms of size, shape, and contour. These changes can be congenital or acquired, due to previous trauma, infarcts, infection, surgery, etc. Natural incisions of the splenic surface (clefs) are reported with an autopsy prevalence of 40–98% and are especially frequent at the superior border of the organ . Deep clIn children, particularly if imaged with high-resolution transducers, the spleen may show a slightly heterogeneous echotexture, the so-called reticulo–nodular patterns, with diffuse millimetric hypo-echoic images representing white-pulp lymphoid follicles. This pattern should not be interpreted as an abnormality  Figure .The spleen can appear as inhomogeneous during the arterial phase of a contrast-enhanced US (CEUS), CT, or MRI, study ,16. ThisSpleen calcifications can be solitary or multiple. Causes include healed granulomatous disease , Gamna–Gandy bodies, sickle cell disease, healed infarcts, hydatid disease, healed abscess, cysts, inflammatory pseudotumor, hamartomas, hemangiomas, lymphangioma, treated lymphoma, and metastases ,17 Figu. SplenicSpleen cysts include parasitic (Echinococcus granulosus), congenital (2.5% of the cases), pseudocysts, and neoplastic cysts  ,17. A soThe spleen is the third most common site for hydatid cysts, and, therefore, in some geographical regions, Echinococcus granulosus is one of the most common causes of spleen cystic lesion . CharactCystic content may be heterogeneous, particularly in the case of pseudocysts. Hemorrhage may complicate splenic cysts. On CT, these lesions will be hyperattenuating, sometimes exhibiting fluid–fluid levels. On MRI, hemorrhagic cysts usually demonstrate high signals on T1W scans and may show internal levels. There is no contrast enhancement at CT or MRI .The probability of incidentally encountering a spleen parenchyma hematoma or abscess in an asymptomatic patient is quite low. Hematomas are almost always due to recent blunt traumas, while abscesses are usually symptomatic ,25,26,27Spleen infarctions are usually caused by thromboembolic conditions, mostly originating from atrial fibrillation, vasculitis, or splenic vein thrombosis. alternatively, a splenic artery infiltration, such as in the case of pancreatic tail carcinoma, may determine an infarction. During transcatheter embolization procedures or abdominal surgery, an iatrogenic origin is also possible. Although larger spleen infarctions are usually painful, it is possible to encounter these changes incidentally, for example during cancer patient staging or follow-up. This happens particularly in the case of smaller and/or polar infarctions. Splenic infarcts usually appear as hypo-echoic/hypo-attenuating, wedge-shaped defects, extending to the capsule . These lSplenic hemangioma, single or multiple, is reported with an autopsy prevalence of up to 14% . The sizLymphangiomas are found more frequently in children and may be cystic  or, less commonly, capillary or cavernous ,17. TheyHamartomas have an incidence on autopsy series ranging between 0.024% and 0.13%, without any gender or age predilection, although size is usually larger in females ,19. ThesLymphoma represents the most common malignant tumor of the spleen. However, isolated primary lymphoma of the spleen is quite uncommon, representing less than 2% of all lymphomas . LymphomThe spleen represents an uncommon site of solid tumor metastasis. In a series, spleen metastases were found in 0.6% of autopsies, with 20% of the cases consisting of microscopic lesions . In anotPrimary splenic malignancies are quite rare, and affected patients are usually symptomatic at time of presentation . AngiosaIn subjects with no history of cancer, the probability that an incidentally detected spleen lesion is due to a primary tumor or to a metastasis is very low. The current literature for adults estimates the incidence of non-lymphomatous metastasis to the spleen at 1% . In a seIn most of the cancer patients undergoing staging or follow-up, a splenic lesion is usually benign, especially if single . Since sThe work-up of FSLs is difficult, due to the large number of different entities, the low rate of relevant primary lesions, the high rate of splenic lesions resulting from extra-splenic diseases with focal splenic involvement, the high percentage of benign lesions in asymptomatic patients, and the low accuracy for characterization of all imaging methods, compared with that for other organs . Some quLesions size matters. Heller and coworkers stated that in patients with a history of a primary neoplasm with a tendency to metastasize to the spleen, an incidentally discovered splenic lesion larger than 1 cm should be suspected as being metastasis while, even in the face of a known neoplasm, a very small lesion is likely to be benign .Various abnormalities may result in complex splenic cysts, including hemorrhagic cyst, hematoma, lymphangioma, infarction, metastases, and primary malignancy. MRI is especially useful for cystic SFL diagnosis.FSLs with benign imaging characteristics  do not require further imaging investigation or follow-up . If the In a retrospective study, Abrishami et al. evaluated the features that could aid in the differentiation of benign and malignant FSLs . Benign Hypo-echoic lesions represent the greatest diagnostic challenge at US . Echo-poIn a retrospective CT study on splenectomy patients, common findings of malignant lesions included their being enhanced, mainly solid, having ill-defined margins, absence of splenomegaly, absence of the walls, absence of calcification, enlargement of lymph nodes, and the presence of underlying malignancy . Heller Ill-defined margins and hypo-vascularity on CEUS, contrast-enhanced CT, or contrast-enhanced MRI are predictors of malignancy . In a reHypo-attenuating FSLs are frequently encountered in the portal–venous phase CT images of the abdomen. The majority of these findings represent benign lesions that require no further work-up. However, certain appearances, such as ill-defined lesion borders, presence of solid, contrast-enhancing components, and increased attenuation of the lesion, may be related to a potentially more relevant disease . In patiHyper-vascular lesions in the spleen include pseudoaneurysms, hemangiomas, hamartomas, sclerosing angiomatoid nodular transformation of the spleen, littoral cell angioma, angiosarcoma, pleomorphic sarcoma. Lymphoma and metastases are rarely hyper-enhancing, while sarcomas are quite uncommon ,42,43.CEUS has been found comparable to CT and MRI in differentiating FSLs ,45. Curr18F-fluorodeoxyglucose (FDG) uptake at PET imaging are usually malignant. However, it should always be considered that benign lesions  may also sometimes exhibit some kind of metabolic activity at PET imaging [FSLs showing an avid  imaging . In pati imaging . On the  imaging .The fear of bleeding from such a vascularized organ with a very thin capsule has always mitigated against the performance of percutaneous biopsies of the spleen. When concomitant abnormalities exist in other organs, histological sampling is usually performed from non-splenic sites . However18F-FDG PET/CT study; 20 patients with solid splenic masses on conventional imaging without known malignancy. The sensitivity and specificity, of PET/CT in differentiating benign from malignant solid splenic lesions in patients with and without malignant disease were 100% and 100% vs. 100% and 83%, respectively. Based on the debatable assumption that “conventional imaging often cannot differentiate benign from malignant solid splenic masses”, the authors created an algorithm. For patients with splenic mass on conventional imaging and a known malignancy, PET imaging was indicated, with further imaging follow-up suggested for non-avid lesions. For patients without a known malignancy, PET was indicated as an alternative to imaging follow-up, with PET suggested in the case of growth at follow-up. The main limitation of this algorithm is the high cost of a PET exam, considering the low probability of malignancy in subjects with no history of malignancy. Appling the suggested approach means, for example, submitting a patient with a non-specific, small, hypo-attenuating lesion of the spleen at contrast-enhanced CT, which is quite a frequent occurrence, usually due to hemangiomas/lymphangiomas, to PET/CT. Additionally, nothing is said on how to manage US incidentalomas, on the choice between follow-up or immediate investigation, and whether to use CT or MR imaging for further imaging.In 2005, Metser and co-workers built a PET-based algorithm for spleen masses detected at imaging . Two groIn 2013, the American College of Radiology (ACR) published a white paper on the management of incidental spleen findings in CT and MRI . UnfortuThe retrospective study conducted by Dhyani and coworkers focused on solitary, non-simple, cyst lesions of the spleen detected in young patients (<30 years old) . These lIn a review from Thut and colleagues  patient In the year 2021, based on a previous study by Ignee et al. , the WorIn 2022, Kim et al. published an imaging-based algorithm . Not takTo our knowledge, there is no published article on texture analysis applied to the differential diagnosis of FSLs.Spleen lesions are relatively uncommon and most are detected incidentally. Correlation with the context is essential. Clinical factors must be taken into account; most importantly, left upper quadrant pain, symptoms of infection, immune status, history of known malignancy, white blood cell count, associated imaging findings. Most incidentally detected spleen masses are benign. However, application of specific imaging criteria can help determine if a lesion should undergo further imaging or follow-up. The management of incidental FLLs may vary between single institutions and also among different countries, since an intensive use of expensive imaging modalities is not s possible everywhere. In underdeveloped countries, patients may not have imaging documentation from earlier conditions, and, due to financial conditions, further imaging techniques may not be possible. In this setting, follow-up may represent a more realistic choice than further investigation.


Renal cancer is the seventh most common cancer in men and the tenth in women. The aim of this article is to review the diagnosis, treatment, and follow-up of renal carcinoma accompanied by recommendations with new evidence and treatment algorithms. A new pathologic classification of RCC by the World Health Organization (WHO) was published in 2022 and this classification would be considered a “bridge” to a future molecular classification. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. Adjuvant treatment with pembrolizumab is an option for intermediate-or high-risk cases, as well as patients after complete resection of metastatic disease. More data are needed in the future, including positive overall survival data. Clinical prognostic classification, preferably IMDC, should be used for treatment decision making in mRCC. Cytoreductive nephrectomy should not be deemed mandatory in individuals with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Metastasectomy can be contemplated in selected subjects with a limited number of metastases or long metachronous disease-free interval. For the population of patients with metastatic ccRCC as a whole, the combination of pembrolizumab–axitinib, nivolumab–cabozantinib, or pembrolizumab–lenvatinib can be considered as the first option based on the benefit obtained in OS versus sunitinib. In cases that have an intermediate IMDC and poor prognosis, the combination of ipilimumab and nivolumab has demonstrated superior OS compared to sunitinib. As for individuals with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab and cabozantinib are the options of choice. When there is progression following initial immunotherapy-based treatment, we recommend treatment with an antiangiogenic tyrosine-kinase inhibitor. While no clear sequence can be advocated, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in the setting of metastatic RC. Renal cell carcinoma (RCC) constitutes 80% of all primary renal neoplasms. The incidence remains stable in recent years with 431,288 new cases and 179,368 deaths in 2020 according to data published by GLOBOCAN. In Spain, the estimated incidence in 2022 was 8078 new cases (5572 in men and 2506 in women). It is twice as common in males and the median age at diagnosis is 64 years. Known risk factors include smoking, obesity, and hypertension. It is more prevalent among people with chronic renal failure, dialysis, renal transplant recipients, or those with tuberous sclerosis. Two percent are hereditary, normally Von Hippel-Lindau disease. Patients with bilateral tumors or characteristic alterations should be tested for germline mutations [Most tumors of the kidney 60%) were diagnosed incidentally by radiologic procedures performed for other medical indications . The cla0% were dA physical examination should be performed together with a complete medical history. Laboratory tests include complete blood cell count, lactate dehydrogenase (LDH), serum creatinine, liver function study, serum-corrected calcium, and urinalysis .Diagnosis is typically suggested by abdominal ultrasound, albeit an abdominal computed tomography scan (CT) is the gold standard to assess local invasiveness, venous involvement, locoregional lymph node involvement, or distant metastases. Nevertheless, it reveals poor differentiation between solid masses, fat-poor angiomyolipoma, and oncocytoma . CT sensMagnetic resonance imaging (MRI) is useful when evaluating local invasion and inferior vena cava involvement is suspected, or in case of allergy to the CT contrast agent or renal insufficiency. Routine bone or brain imaging is not indicated . Bone scFluorodeoxyglucose (FDG) Positron Emission Tomography (PET) is not currently regarded to be the standard imaging modality for the diagnosis of renal cancer , given iThe 2017 TNM classification is the recommended clinical staging standard , 22  are recommended for routine clinical practice. Level of evidence: III. Grade of recommendation: D.In patients without previous tumor diagnosis, a renal tumor core biopsy is recommended before treatment with ablative therapies, as well as in cases of metastatic disease, prior to starting systemic treatment. Level of evidence: III. Grade of recommendation: A.Renal cell carcinoma (RCC) is a heterogeneous disease. Histological classification is based on the tumor origin from different cells located in nephron cells but is completed with molecular and clinical information. The most common type of RCC is clear-cell renal cell carcinoma (ccRCC), accounting for up to 75% of all RCCs. Other major types include papillary (10–15%), chromophobe (5%), oncocytic (< 5%), Xp11 translocation (< 1%), or collecting-duct carcinomas (< 1%) . There iPapillary RCC is considered the classical papillary RCC morphology type I, albeit certain single entities with papillary features can be regarded as variants of papillary RCC or provisional entities like papillary renal neoplasm with reversed polarity (PRNRP), biphasic hyalinizing psammomatous RCC (BHP RCC), biphasic squamoid/alveolar RCC, or thyroid-like follicular RCC (TLF RCC) Some have a specific molecular driver alteration, for example, KRAS mutations in PRNRP, NF2 mutations in BHP RCC, and EWSR1-PATZ1 fusions in TLF RCC.While certain entities with eosinophilic or oncocytic cytoplasm are well defined, such as SDH-deficient RCC, ESC RCC, and FH-deficient RCC, others are emerging entities, for instance, eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). TSC mutations are important and are common in ESC RCC; similarly, TSC1/2 mutations or activating mTOR mutations have also been identified in EVT and LOT .The differential diagnosis between cromophobe RCC and oncocytoma is essential. Chromophobe RCCs exhibit diffuse positivity for cytokeratin 7 (CK7), whereas oncocytomas are negative or present focal positivity for CK7. Molecular studies provide a more definitive diagnosis of subtypes.ChRCC is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations . CollectSarcomatoid features are present in < 10% of RCC tumor and are mainly observed in patients with predominant clear cell areas . MutatioSurgery is the treatment of choice in stages I to III.tumors smaller than 7 cm (T1) the recommended treatment is partial nephrectomy , a technique that enables similar results to be achieved with better preservation of renal function [In function . Radicalfunction . Active function .T2 tumors measuring > 7 cm, laparoscopic radical nephrectomy is the treatment of choice, while open surgery is called for in T3 and T4 tumors, albeit laparoscopic surgery can be contemplated in certain situations. Lymphadenectomy and suprarenalectomy are not indicated if there is no evidence of invasion on imaging tests(1), although the latter should be considered in upper pole tumors > 4 cm or > T3 [In  or > T3 .The evidence regarding the treatment of venous thrombus is based on retrospective studies and poses a challenge not exempt of complications. Surgical intervention should be evaluated when feasible, as it may be associated with prolonged survival .Until recently, several studies with angiogenesis and mTOR inhibitors had failed to demonstrate an overall survival benefit –42; howeP = 0.002). A non-statistically significant trend toward a benefit was seen in overall survival in the pembrolizumab arm .More recently, the results of a phase III trial have been published (Keynote-564), in which 994 intermediate- or high-risk patients  were randomized to receive pembrolizumab vs. placebo for 1 year . A benefNeoadjuvant treatment should be deemed experimental, in as much as it has only been studied in small trials.Partial nephrectomy is recommended in T1 tumors, as well as in bilateral tumors or in patients with only one functioning kidney. Level of evidence: I. Grade of recommendation A.Radical nephrectomy is recommended in T2-4 tumors. Level of evidence: II. Grade of recommendation: A.Treatment with adjuvant pembrolizumab is an option for intermediate- or high-risk patients, as well as after complete resection of oligometastatic disease. More data are required in the future, including positive overall survival data. Level of evidence: I. Grade of recommendation: C.Surgical intervention should be contemplated when feasible, as it may be associated with prolonged survival. Level of evidence: III.The Memorial Sloan Kettering Cancer Center classification was formerly used for cytokine therapy . CurrentPD-L1 status has been studied to determine both its prognostic and predictive role. A meta-analysis appeared to establish the negative prognostic value of higher levels of expression of PD-L1 . As for In recent years, several molecular models have been studied with the aim of identifying a predictive value. Beuselinck et al. identified four molecular subgroups with different sensitivity to sunitinib. The ones that associated better outcomes were ccrcc2 and ccrcc3 . These sTo date, other biomarkers in tumor tissue, such as tumor-infiltrating immune cells or tumor mutation burden, as well as circulating biomarkers, such as circulating DNA, soluble PD-L1, or cytokines and inflammatory markers, have failed to demonstrate a definitive prognostic or predictive role. In a recent communication, the presence of CD8 + T-cell tumor infiltration correlates with a lack of favorable PBRM1 mutations, suggesting that there is a correlation between immune phenotypes and somatic alterations .Clinical prognostic classification, preferably IMDC, should be used for treatment decision-making in mRCC. Level of evidence: I. Grade of recommendation: B.Genomic classification, including PD-L1 study, should not be used as a prognostic or predictive tool for treatment decision-making in mRCC. Level of evidence: II. Grade of recommendation: C.Recommendations:The role of surgery in advanced disease is limited to cytoreductive nephrectomy, metastasectomy in oligometastatic disease, and palliative nephrectomy due to symptoms.The role of cytoreductive nephrectomy has been modified based on improvements in systemic treatments.versus interferon alpha established the role of upfront cytoreductive nephrectomy after demonstrating an overall survival benefit [At the time of interferon immunotherapy, two randomized studies comparing nephrectomy followed by interferon alpha  benefit , 59.At the time of antiangiogenic monotherapy, two randomized studies evaluated the role and timing of nephrectomy in advanced disease –62. Usinversus non-nephrectomized patients and that said benefit does not differ whether they receive antiangiogenic therapy or immunotherapy [Some retrospective studies have assessed the role of cytoreductive nephrectomy. Two of them, in particular, are particularly salient. The National Cancer Database and the IMDC. The first analyzed 15,390 patients identified in the National Cancer Database who were treated between 2006 and 2013 and revealed that overall survival was significantly better in nephrectomized patients  . The secotherapy .There are no prospective studies with current immunotherapy evaluating the role of nephrectomy; thus, physicians are recommended to follow the recommendations put forth during the era of antiangiogenic therapy while we await the results of the ongoing studies NORDIC-SUN, CYTOSHRINK, and PROBE.As for metastasectomy in oligometastatic disease, there are different scenarios in which surgery can play a role, i.e., in subjects who present with synchronous oligometastatic (recommended when there are < 3 metastases), metachronous , or residual disease following a good response to systemic treatment. The strongest predictors of prolonged survival were a disease-free interval from nephrectomy to metastases > 1 year, ≤ 2 vs > 2 sites , ECOG 0–1, and absence of sarcomatoid features . DiffereDebulking or cytoreductive nephrectomy should not be deemed mandatory in patients with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Level of evidence: I. Grade of recommendation: A.Cytoreductive nephrectomy may play a role in the management of advanced renal cell carcinoma in individuals with limited metastatic burden amenable to surveillance or metastasectomy, in patients requiring palliation, and potentially delayed cytoreductive nephrectomy in patients with a favorable response or stable disease after initial systemic therapy. Level of Evidence: II. Grade of recommendation: B.Metastasectomy can be contemplated in selected patients having a limited number of metastases or long metachronous disease-free interval. Level of evidence: II. Grade or recommendation: C.Metastatic ccRCC includes a variety of poorly understood clinical situations with different prognoses, including patients with indolent oligometastatic relapses, and others with very aggressive disease associated with short survival. On the other hand, most therapies available exert their effect by acting on the microenvironment instead of the tumor cells themselves.For many decades, the only active treatments were non-specific immunotherapies (interferon and IL-2) that were associated with high toxicity and 10% long-term survival in a selected subgroup of patients .versus interferon in a population of patients having a poor prognosis [Following the discovery that RCC is closely associated with the loss of VHL gene activity, with increased VGEF and growth factors, angiogenesis, and anaerobic metabolism, a number of antiangiogenic tyrosine-kinase inhibitors (TKI) against the endothelium VGEF receptor (VEGFR) were developed and examined in phase III trials. These drugs exhibited a statistically significant increase in PFS against interferon (sunitinib ), placebrognosis .Recently, immune check point inhibitors (ICIs) promoting antigen presentation (Ipilimumab) or blocking antiPDL1/PD1 signaling to reverse tumor immune evasion mechanisms  have been developed against RCC. Due to the poor results achieved with TKIs in the intermediate and poor IMDC subgroups, the Checmate-214 phase III trial compared the combination of Ipilimumab-Nivolumab versus sunitinib in these subgroups and detected higher ORR and OS with the combination therapy . After aSeveral combinations of ICIs and TKI anti-VEGFR have been compared with sunitinib in phase III trials. The IMmotion 151 trial , demonstHowever, three trials have clearly demonstrated the statistically significant superiority of ICI-TKI combinations over sunitinib in ORR, PFS, and OS in the whole population of metastatic ccRCC. In the Keynote 426 study (pembrolizumab + axitinib vs sunitinib) , ORR wasUntil predictive factors became reliable, the choice of first-line treatment for patients with metastatic ccRCC should be based on the local availability of approved drugs, patient comorbidities and prognosis, including the need for a quick response, as well as the design of a global therapeutic strategy with salvage options for subjects who do not respond or who relapse Fig. .The combination of pembrolizumab + axitinib, nivolumab + cabozantinib, or pembrolizumab + lenvatinib can be considered the first options based on the benefit obtained in OS over sunitinib. Level of evidence: I. Grade of recommendation: A.Given its superiority on PFS over sunitinib, the combination of avelumab + axitinib is an alternative when other combinations are not available. Level of evidence: I. Grade of recommendation: B.Sunitinib, pazopanib, and tivozanib are reasonable options when the above-mentioned combinations are not available. Level of evidence: I. Grade of recommendation: B.Considering the whole population of patients with metastatic ccRCC:In patients with IMDC intermediate or poor prognosis, Ipilimumab + nivolumab should also be considered standard, given the benefit observed in OS over sunitinib. Level of evidence: I. Grade of recommendation: A. In this subpopulation, cabozantinib could be preferable to sunitinib based on the longer PFS obtained in a randomized phase II study. Level of evidence: I. Grade of recommendation: C Although not widely used, temsirolimus remains an option for poor-risk IMDC patients. Level of evidence: I. Grade of recommendation: C.No definitive evidence is available as to the benefit of the anti PD1/PDL1 plus either ipilimumab or TKI over sunitinib alone in the IMDC favourable subgroup. For asymptomatic patients with indolent and good-prognosis disease, active surveillance can be considered. Level of evidence: II. Grade of recommendation: C.In the context of an individualized decision-making based on IMDC subgroups, in addition to the above recommendations:In the past, the standard of care in first line was a TKI in monotherapy and many patients are still being treated with VEGF in monotherapy today. The anti-PD1 inhibitor nivolumab , 85 or tWith the advent of first-line IO-based combinations, the therapeutic sequence in mRCC has changed and prospective randomized studies exploring what to do after failure of IO-based combinations are lacking. Furthermore, the phase III TIVO-3 trial  revealedSeveral retrospective series have investigated the usefulness of multiple tyrosine kinase inhibitors  after IO treatment –100. On Prospective data exploring single-agent activity cabozantinib comes from a post hoc analysis of the METEOR trial. Of 32 patients who had received prior IO therapy , activity favored cabozantinib over everolimus consistent with the overall population, median PFS , and a trend in overall survival with an ORR of 22% versus 0% . A post Prospective data have also been published from small phase II trials with axitinib , cabozanIn patients with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab, and cabozantinib are the recommended options. Level of evidence: I. Grade of recommendation: A. Decisions to use either agent may be based on the expected toxicity and on contraindications for each drug, as randomized data is lacking.Axitinib, everolimus, lenvatinib + everolimus, and tivozanib are alternatives for second-line, providing that they are available and patients cannot receive nivolumab or cabozantinib. Level of evidence: I. Grade of recommendation: B. In addition, they may also be acceptable options following nivolumab and cabozantinib. Level of evidence: III. Grade of recommendation: C.For patients who progress after initial immunotherapy-based treatment, we suggest treatment with an anti-VEGFR TKI. Options include cabozantinib, axitinib, tivozanib, sunitinib, and pazopanib. Further research is required in this context. Level of evidence: III. Grade of recommendation: C.Patients should be encouraged to participate in clinical trials whenever possible.vs. 9.6 and 17.1 vs. 7.7 months, respectively) [p = 0.15), indicating a trend toward superiority of sunitinib over everolimus, although the results failed to reach statistical significance [Approximately, 15–20% of renal cell carcinomas (RCC) are classified as non-clear cell renal cell carcinoma (nccRCC), which are then further divided into multiple distinct subtypes based on histological and molecular characteristics. Subtypes of nccRCC include papillary, chromophobe, collecting duct, renal medullary, and translocation RCC, which account for 10–15%, 5–7%, 1–2%, < 1%, and < 1% of all RCCs, respectively . All subctively) , 108. Rectively) . Three sctively) –112. Theificance . Other aificance –116. Nevificance , 118. Asificance , cMET inificance –122. Addificance . Most ofificance , 125. Caificance , 127. CoClinical data are limited in nccRCC, which are usually excluded from controlled phase III trials. Therefore, enrolment into specific clinical trials is strongly recommended. Level of evidence: V. Grade of evidence: A.There are no available data regarding post-nephrectomy adjuvant treatment in localized nccRCC.Papillary: Sunitinib: Level of evidence: II. Grade of evidence: B. Pazopanib: Level of evidence: III. Grade of evidence: C. Everolimus: Level of evidence: II. Grade of evidence: C. Cabozantinib: Level of evidence: IV. Grade of evidence: c.Cromophobe: Sunitinib: Level of evidence: II. Grade of evidence: C. Pazopanib: Level of evidence: III. Grade of evidence: C. Everolimus: Level of evidence: II. Grade of evidence: C.Collecting duct/Medullary: Cisplatin or carboplatin- based regimen: Level of evidence: III. Grade of evidence: C.Sarcomatoid: Sunitinib. Level of evidence: II. Grade of evidence: B. Pazopanib: Level of evidence: III. Grade of evidence: C. Nivolumab+ipilimumab: Level of evidence: IV. Grade of evidence: C.In the first-line setting, the most robust data exist for sunitinib, although other targeted therapies, such as TKI and mTOR have limited data. While specific data are not available, the choice of treatment should be based on each specific subtype:After first-line, no recommendation is possible based on available data.This guideline has been developed based on the consensus of ten genitourinary medical oncologists, designed by the Spanish Society of Medical Oncology (SEOM) and the Spanish Oncology Genitourinary Group (SOGUG), and an external review panel comprising two experts designated by SEOM. The Infectious Diseases Society of America–US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines has been used to assign levels of evidence and grades of recommendation Table .Table 4L


Adults with tuberculosis-human immunodeficiency virus coinfection require professional nurses’ support to manage their illness, treatment and its effect on their daily lives. This scoping review maps recommendations in clinical or best practice guidelines that guide professional nurses to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings.We conducted a scoping review by searching for guidelines in six online databases, guideline clearing houses and search engines from 16th April 2022 to 25th May 2022. The title, abstract and full-text screening of guidelines were conducted independently and in duplicate by two reviewers based on predetermined eligibility criteria. The guidelines were critically appraised with the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Relevant data regarding the characteristics of the guideline, recommendations and underlying evidence were extracted, analysed and reported.The six guidelines on self-management support found were developed in four high-income countries. Five of the guidelines recorded <60% across all six domains of the AGREE II instrument. One high-quality guideline scored >60% in all AGREE II domains but was informed by outdated evidence produced between 1977 to 2010. Twenty-five practice, education and organisational/policy recommendations were extracted from the high-quality guideline. The guidelines did not report evidence-to-decision frameworks and the strength of the recommendations. The guidelines also lacked direct underlying evidence on the effectiveness and cost of self-management support. Lastly, the review found a paucity of contextual  evidence on self-management support among adults with tuberculosis-human immunodeficiency virus in the guidelines.There is a dearth of updated and relevant high-quality guidelines that guide healthcare professionals to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings. Systematic reviews of effectiveness, economic and contextual evidence related to self-management support interventions are required for guideline production. Tuberculosis-Human Immunodeficiency Virus (TB-HIV) coinfection is a significant health challenge facing many adults (aged 18 years and older) globally , 3.Self-management entails the tasks people living with chronic conditions (such as TB-HIV coinfection) undertake to manage their illness and its effect on their daily life . PreviouProfessional nurses provide care (including self-management support) to AWTB-HIV in primary healthcare settings such as TB or HIV clinics globally . Primarybest practice guidelines also refer to clinical practice guidelines because of their similarity in meaning. Best practice guidelines are “systematically developed, evidence-based documents that include recommendations for nurses and the interprofessional team, educators, leaders and policymakers, persons and their chosen families on specific clinical and healthy work environment topics” . Six best practice guidelines met the inclusion criteria. The data search, screening and selection process is presented in the PRISMA flow chart .The six included guidelines were published by five international organisations namely; the Health Care for the Homeless Clinicians’ Network (HCN) , NationaThe guidelines were published between 2010  and 2020Three guidelines indicated they were summary guidelines; however, complete versions of the guidelines were not found during guideline search or upon email requests to the authors. Five guidelines contained references . The authors of one guideline (NHS) provided additional references when contacted via email. None of the guidelines included a summary of findings table, which reports the characteristics of the underlying evidence for its recommendations. Three guidelines developed by RNAO and RACGP specified the level of evidence and strength of recommendations based on the study design of the underlying evidence , 38, 39.th and 75th percentile) overall assessment score in all guidelines was 2.5  out of a highest possible score of 7. None of the guidelines was recommended for use during the overall assessment. Only one guideline, (RNAO) [recommended with modifications. The remaining guidelines  were not recommended because of low methodological quality., (RNAO)  was recoThe recommendations within the high-quality clinical practice guideline (RNAO)  were extThe RNAO guideline contained 25 recommendations categorised under practice recommendations (n = 19), educational recommendations (n = 2) as well as organisation and policy recommendations (n = 4). The 19 practice recommendations were further organised under a general recommendation (n = 1), Assess (n = 5), Advise (n = 5), Agree (n = 1), Assist (n = 3), Arrange (n = 1) and Innovative Delivery Models (n = 3) . The guiIn the absence of an EtD framework or summary of findings table in the RNAO guideline, the references discussed under each recommendation were extracted as underlying evidence . The recThe underlying evidence regarding the effectiveness of self-management support was derived from systematic reviews of RCTs and non-RCTs, experimental and non-experimental studies and guidelines. The desirable effects of self-management support interventions found within the guideline were improved patient health outcomes . No undesirable effects of self-management support were identified. The guideline did not provide quantifiable evidence of the benefit or harms of self-management support. No summaries of findings tables were provided or referred to in the guideline.The level/certainty of evidence ratings adopted by the RNAO for each recommendation in their guideline was an adapted SIGN grading system based on the study design of the evidence . Thus, sThe RNAO guideline considered the resource  implications of implementing self-management support and recommended adequate funding for its provision by nurses. However, the underlying evidence informing the recommendations did not include economic analysis studies examining how large the resource requirements for self-management support are or should be. The guideline did not describe the certainty of evidence on the resource requirements (costs). Only one study  on the cThe guideline considered contextual evidence from six qualitative studies –48. No uThis review found one high-quality best practice guideline for professional nurses to provide self-management support to persons with chronic conditions within primary health settings. Although the best practice guideline was of high methodological quality, it was underpinned by outdated and indirect evidence which may not adequately address the specific self-management support needs of AWTB-HIV, who must simultaneously self-manage TB and HIV coinfection , 22. FurThe need to develop, adopt, adapt or contextualise guidelines on self-management support for resource-limited and high-burden TB-HIV coinfection settings may be more urgent in resource-limited settings since all of the existing guidelines were developed for high-income settings such as Australia, Canada, England and the United States of America. Previous reviews have reported similar dominance of high-income countries in developing guidelines –26. GuidThis scoping review, however, revealed that the methodological quality of most of the existing best practice guidelines for self-management support was low. The guidelines’ low methodological quality was due to the scant transparency around the methods, evidence and judgements used in developing their recommendations. Consequently, as found in this review, the guideline (RNAO) that adequately described its scope/purpose, stakeholder involvement processes, methods and evidence used in its development, funding sources and conflict of interest declaration obtained greater than 60% in all AGREE II domains.It was evident that all six guidelines required more rigorous and transparent processes in converting evidence to recommendations. The three guidelines  which rated the levels of evidence informing their recommendations primarily considered the study design of the evidence but not the related factors influencing the certainty of the evidence. Thus, important factors that could reduce the guideline developers’ level of confidence in the evidence informing the recommendations  were not reported . FurtherThe GRADE process and EtD framework provide guideline developers with a framework to transparently report their judgements regarding (1) the magnitude and certainty of evidence underlying their recommendations as well as (2) the contextual factors which informed their guideline recommendations . Based oThis scoping review appears to be the first to map out recommendations in best practice guidelines that guide professional nurses to provide self-management support to AWTB-HIV and persons with chronic conditions. It is not without limitations. For instance, only best practice guidelines in the English language were included in this review. Thus, equally relevant guidelines in other languages may have been omitted. Additionally, majority of the six guidelines found were developed in high-income countries, yet they informed most of the review’s findings and conclusions. These guidelines may need context adaptation to work in low-income countries because of social, economic and disease pattern differences between high and low-income countries. Furthermore, three guidelines were labelled as summary guidelines despite being full-text documents. Consequently, these guidelines may lack some relevant information required for their appraisal, although the reviewers considered additional information provided by the guideline authors. To limit reviewer bias, the judgements regarding guideline search, selections, data extraction, appraisal and report were conducted independently and thoroughly discussed among at least three reviewers till a consensus was achieved.Despite these limitations, this scoping review provides systematically generated evidence regarding the scope and methodological quality of guidelines informing self-management support. The findings can inform prospective development, adaptation and review of guidelines as well as primary studies on self-management support. This review highlights the need for internationally-recognised bodies such as the World Health Organisation to develop current high-quality self-management support guidelines to serve as blueprints for adaptation into resource-limited settings.Best practice guidelines that can guide healthcare providers’ self-management support exist in the literature. However, there is a paucity of current and high-quality evidence-based recommendations that guide professional nurses to provide self-management support to AWTB-HIV. The guidelines may need thorough updating in the context of developing countries to guide healthcare delivery. The existing self-management support guidelines are not informed by current and direct evidence involving AWTB-HIV thus cannot be reliably adapted for other settings. More experimental, economic and contextual studies which examine the benefits and harms, cost-effectiveness, equity, acceptability and feasibility of self-management support among AWTB-HIV are required to inform future self-management support recommendations. Additionally, a systematic review of current effectiveness, economic and contextual studies that promote self-management among adults with chronic conditions such as TB, HIV and TB-HIV coinfection can help to produce adaptable high-quality guidelines on self-management support.S1 Checklist(DOCX)Click here for additional data file.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S3 Appendix(DOCX)Click here for additional data file.