Anterior dislocation of the sacroiliac joint (ADSIJ) is caused by strong violence, and because of its low morbidity, there are no standardized diagnostic and therapeutical guidelines at this moment. This study aims to explore the surgical techniques and preliminary outcomes of the lateral‐rectus approach (LRA) for treating ADSIJ.A retrospective study was conducted of 15 patients with ADSIJ from January 2016 to January 2021. The patients' age ranged from 1.8 years old to 57 years old (37 ± 18 years old). All patients underwent open reduction and internal fixation (ORIF) through the LRA. Eight patients were combined with lumbosacral plexus injury and underwent neurolysis during operation. Patients' fracture type, mechanism of injury, associated injuries, operation time and intraoperative bleeding volume were accessed by reviewing medical history. Quality of fracture reduction was evaluated with the Matta score. At 1‐year follow‐up, the functional rehabilitation was evaluated by the Majeed rehabilitation criteria. For those with lumbosacral plexus injury, the neuromotor function was evaluated using muscle strength grading proposed by the British Medical Research Council (BMRC) and recovery was recorded.All 15 patients underwent the operation successfully. The surgical time ranged from 70 to 220 min (126 ± 42 min), and the intraoperative blood loss ranged from 180 to 2000 mL (816 ± 560 mL). Eighty percent of the cohort (12/15) were rated as excellent and good in the Matta score for fracture reduction quality after operation without surgical incision‐related complications. At 1‐year follow‐up, the overall excellent and good rate was 73.3% (11/15) according to the Majeed criteria, the neuromotor function recovered completely in six cases and partially in two cases according to the BMRC muscle strength grading, and the recovery of sensory function was evaluated as excellent in six cases, good in one case and poor in one case, with an overall excellent and good rate of 87.5%.The LRA can well expose the surrounding structures of the sacroiliac joint from the front, which helps surgeons reduce and fix the anterior dislocation of the sacroiliac joint under direct vision and effectively decompress the entrapment of the lumbosacral plexus to achieve better clinical efficacy. Fifteen patients suffered anterior dislocation of sacroiliac joint and eight of them had lumbosacral plexus injury. They were treated with the lateral rectus approach (LRA) and had good clinical efficacy. Anterior dislocation of the sacroiliac joint (ADSIJ) refers to the displacement of the iliac partially or entirely shifting to the front of the sacrum after pelvic injury, forming an interlock Fig. . ADSIJ iThe sacroiliac joint belongs to the amphiarthrosis joint, which is composed of the articular surface of the sacrum and the iliac bone and the ligament complex. The sacral surface is slightly depressed while the iliac surface is relatively convex, which has an interlocking effect to stabilize the joint like an enarthrosis. The bone and strong ligament complex jointly resist the deforming force. The occurrence of sacroiliac joint dislocation indicates that patients suffer from lateral extrusion or rotation force of injury. Since the sacrum is wide in the front and narrow in the back, sacroiliac injury is more often manifested as posterior or vertical dislocation.The dislocation of the sacroiliac joint can be classified into two subtypes: A, the posterior dislocation of the sacroiliac joint; and B, the anterior dislocation of the sacroiliac joint. The type B can be further subdivided into two subgroups, including: (i) anterior dislocation of the sacroiliac joint combined with no fracture or stable fractures of hip bones; and (ii) anterior dislocation of the sacroiliac joint combined with the unstable fractures of hip bones and/or contralateral SI joint injury.After the occurrence of ADSIJ, the posterior pelvic ring is severely damaged, combining with anterior pelvic ring injury, which makes the whole ring vertically and rotationally unstable.The most widely used anterior approaches for exposing sacroiliac joint include the iliac fossa approach, the para‐rectus approach, and the lateral‐rectus approach (LRA). However, the iliac fossa approach may cause the injury of vascular bundle and lateral femoral cutaneous nerve (LFCN).via the LRA from January 2016 to January 2021 and evaluated their surgical methods and treatment effects.Our team has been using the LRA to treat patients with ADSIJ since 2016, which has achieved good clinical efficacy. This study retrospectively analyzed the clinical data of patients who suffered ADSIJ injury and underwent surgery The purposes of this study were to: (i) analyze the characteristics of ADSIJ injury; and (ii) evaluate the surgical techniques and preliminary outcomes of the LRA for treating ADSIJ injury.This study has been approved by the ethics committee  and informed consent was obtained from all included participants.A total of 15 ADSIJ patients with surgical treatment were included in this study. There were seven males and eight females. The average age ranged from 1.8 years old to 57 years old (mean 37.0 ± 18.1 years old). All 15 patients were associated with anterior pelvic ring fractures. Among them, there were six patients combined with contralateral posterior pelvic ring injury, eight patients with ipsilateral lumbosacral plexus injury, seven patients with pelvic organ injuries, and two patients with ipsilateral acetabular fracture. The time from injury to surgery ranged from 7 to 145 days (mean 19.8 ± 35.0 days). The causes for the injury can be classified as falling from height (four cases), traffic accidents (six cases) and crush injuries (five cases). The classification of the ADSIJ were as followed: seven cases of type B.a and eight cases of type B.b. All these data, including the amount of intraoperative bleeding and operation time, are shown in Table Inclusion criteria included: (i) pelvic ring injury caused by trauma; (ii) anterior sacroiliac joint dislocation; (iii) patients were treated with surgery; and (iv) surgical field was exposed through the LRA.Exclusion criteria included: (i) sacroiliac joint separation or posterior dislocation; (ii) no obvious fracture displacement; and (iii) incomplete follow‐up or loss to follow‐up.Related routine preoperative examinations were performed for all patients after admission. The pelvic CT scan  was performed on all patients. And the data was inputted into Mimics software  for three‐dimension (3D) reconstruction. An equal‐large 3D model was manufactured by a 3D printer  to help surgeons clearly understand the type of fracture and the anterior dislocation of the sacroiliac joint. Patients with LSP injuries underwent LSP MRI scan reconstruction to determine the location of nerve injury, which can assist surgeons to formulate a detailed preoperative plan of neurolysis. The color Doppler ultrasonography of the lower extremity was performed 1 day before surgery to rule out deep vein thrombosis of the lower extremity. A broad‐spectrum antibiotic was given intravenously 30 min before surgery. And the antibiotic was given again with over 3 h of operation time or over 1000 mL of intraoperative blood loss. The blood was prepared, and intraoperative autologous blood transfusion was performed.Patients were placed in the supine position after general anesthesia with endotracheal intubation. And sterile bandage of the affected lower extremity was performed for intraoperative traction.The standard incision of the LRAAfter separating the peritoneum and the muscle bluntly, the medial window was opened, and the anterior pelvic ring was exposed. For the patients companied with S1 nerve injuries, the presacral window was made to expose the front of the sacrum and sacral foramen. The middle window could reveal from the greater sciatic foramen to the auricular surface of the ilium that could be seen because of ADSIJ injury. After exposing the middle window through the space between the iliopsoas muscle and external iliac vessels, it was exposed upward along the sciatic foramen to the iliac auricular surface of the sacroiliac joint with anterior dislocation. The soft tissue around the articular surface had been carefully separated before the Schanz nail was inserted into anterior superior iliac crest, for the lumbosacral plexus and iliac vessels might be attached to the surface. After the Schanz nails were set, surgeons could loosen the sacroiliac joint by spinning the ilium outward and forward carefully in case of hurting the lumbosacral plexus and reduce the ilium while pulling the affected lower limbs. If the reduction were difficult to achieve, surgeons could try spinning and pulling the Schanz nails outward to enlarge the gap between the ilium and sacrum, insert the periosteal detacher into it simultaneously to release the blockage, and then reduce the ilium by traction. Fixation was completed with two plates placed supra‐pectineally and infra‐pectineally across the sacroiliac joint, or with a reconstruction plate placed in front of the sacroiliac joint and an S1 sacroiliac screw. Reduction of old ADSIJ injury (more than 3 weeks) was relatively more difficult than that of the fresh one (less than 3 weeks), which required ilium osteotomy and sacroiliac joint bone grafting after eliminating the tissue stuck in the joint to avoid aggravating the nerve damage by repeatedly pulling the iliac bone back and forth during the operation. In our cohort of 15 patients, three of them went through iliac articular surface osteotomy.The reduction and fixation of the ADISJ can be performed with a 3.5 or 4.5 mm reconstructed plate or an anterior sacroiliac anatomic plate. One screw is drilled through the sacrum, parallel to the sacroiliac articular surface. The screw direction is consistent with the direction of the longitudinal axis of the iliac bone, which can make screws reach enough depth within the ilium to achieve structural stability. Full‐threaded cancellous bone screws, with a length between 30 and 40 mm, are common choices for fixing the plate on the iliac wing. After the fixation of the first plate, add the other plate to the ilium. The two plates can be placed parallel or crossed at an angle of 60° ~ 90°. Locking plates are an ideal alternative for osteoporotic patients to increase the strength of fixation.After the operation, the drainage tube was routinely placed, and it was pulled out when the drainage volume was less than 50 mL. Routine anticoagulation was started 6 h after operation to prevent deep vein thrombosis of lower extremities. Within 24 h after operation, patients were instructed to perform isotonic and isometric contractions of lower extremity muscles, and actively or passively move hip and knee joints. Those with LSP injury were given corresponding nerve stimulation treatment. The rehabilitation and exercising time of the patients hinged on the severity of the fracture, reduction and fixation, combined injuries, etc. Generally, the patients could walk with partial weight‐bearing 4–6 weeks after the operation. At 1, 3, 6 and 12 months after the operation, the pelvic X‐rays and CT scans were performed to evaluate the fracture reduction quality, the position of the internal fixator, the healing of fractures and the data of limbs functional recovery were recorded. Patients with LSP injuries were treated with acupuncture and moxibustion 1 week after operation to promote the recovery of nerve function.The operation time, intraoperative blood loss for the exposure, reduction, and fixation of ADSIJ were recorded. Pelvis X‐rays and CT scans were performed postoperatively for all patients. Fracture healing was assessed based on the follow‐up imaging results and physical examination.Fracture healing status was evaluated according to imaging results and physical examination. As long as the X‐ray showed blurred fracture lines and continuous callus formation, and the patients showed no pain at the sacroiliac joint during walking, it was evaluated as clinical fracture healing.The postoperative pelvic fracture reduction quality was measured using the Matta criteriaThe Majeed functional scoreAccording to the British Medical Research Council (BMRC) nerve injury classification,All data in the study were analyzed using SPSS 26.0 . The measurement data was accessed by the Shapiro–Wilk test to determine whether the data is normally distributed. Normally distributed data are presented in the form of mean ± standard deviation.The average operation time of the LRA in treating ADSIJ ranged from 70 to 220 min (mean 126 ± 42 min), and the average intraoperative blood loss ranged from 180 to 2000 mL (mean 816 ± 560 mL), which are less than those of the LRA in treating pelvic fracture with lumbosacral plexus injury reported in the literature.In this group, 15 ADSIJ patients achieved clinical healing, and such complications as displacement of fracture, delayed union or nonunion of fractures, incision infection and other clinical complications did not occur. Postoperative reduction quality of ADSIJ using the Matta criteria was as follows: excellent in eight cases, good in four cases, and fair in three cases, with a total excellent and good rate of 80%.The follow‐up time was 12 ~ 36 months. According to the Majeed functional score, there were six cases of excellent, five of good, three of fair, and one of poor at 1‐year follow‐up after operation. The overall excellent and good rate was 73.3%. According to BMRC, the recovery of lumbosacral plexus function in eight patients with lumbosacral plexus injury after operation was evaluated as follows: six cases of M5, one case of M4, and one case of M2 in motor function recovery. The recovery of sensory function was evaluated as excellent in six cases, good in one case, and poor in one case, with an overall excellent and good rate of 87.5%.via the bilateral LRA 15 days after the injury , Innovation fund cultivation project of National Clinical Research Center for Orthopedics Sports Medicine and Rehabilitation (2021‐NCRC‐CXJJ‐PY‐06). National Key Research and Development Program of China (2022YFC2504303).The authors have declared that there are no competing interests.


Allosteric regulation, in many cases, involves switching the activities of natural enzymes, which further affects the enzymatic network and cell signaling in the living systems. The research on the construction of allosteric switchable catalysts has attracted broad interests, aiming to control the progress and asymmetry of catalytic reactions, expand the chemical biology toolbox, substitute unstable natural enzymes in the biological detection and biosensors, and fabricate the biomimetic cascade reactions. Thus, in this review, we summarize the recent outstanding works in switchable catalysts based on the allosterism of single molecules, supramolecular complexes, and self‐assemblies. The concept of allosterism was extended from natural proteins to polymers, organic molecules, and supramolecular systems. In terms of the difference between these building scaffolds, a variety of design methods that tailor biological and synthetic molecules into controllable catalysts were introduced with emphasis. Allosteric regulation controls the activities of natural enzymes and expands the chemical biology toolbox for the research on switchable catalysts. These rationally designed substitutes for unstable natural enzymes have been applied in areas such as biosensors and biomimetic cascade reactions. This review extended the concept of allosterism to artificial scaffolds and introduced a variety of design methods for controllable catalysts. From the global energy issue to human health, these human‐made catalysts have offered new solutions to benefit humankind with nature's wisdom. For instance, the alarming fact that currently most of the global energy supply is generated from non‐renewable carbon‐based fuels has concerned the sustainable development of humanity, while mimicking hydrogenase and splitting of water into molecular hydrogen with solar energy might be a promising way to solve the world's energy issue. Also, the respiration process in organisms not only provides energy but also could cause cardiovascular disease, which is one of the biggest killers to humans. Artificial peroxidases would relieve the oxidative pressure from respiration and postpone the aging process. Compared with traditional synthetic catalysts, the study of biocatalysts tends to focus on the design of enzyme‐like catalytic mechanisms and the development of biological production technologies. Recently, versatile molecular scaffolds were utilized to afford exceptional examples aiming at natural enzymes’ expertise: facilitating the formation of enzyme‐substrate complex and reducing the activation energy barrier of catalytic reactions. Essential knowledge and critical factors  that govern the enzyme activity have been explored by studying different models such as small organic molecules, polymers, supramolecular complexes, natural proteins, and protein assemblies. These multidisciplinary works have spawned many successful bioinspired enzymes, some of which even showed high efficiencies comparable to their natural counterparts.Billions of years of evolution allow organisms to possess a variety of natural enzymes that can control the progress of biochemical reactions with incredible substrate specificity and activity under physiological conditions. Therefore, it is of broad interest to learn from nature's masterpieces and develop bioinspired enzymes for promising applications in biosensors,2, 3 In this case, the ideal artificial enzymes must not only show high activity but also be well regulated to perform their functions intelligently. On the other hand, the study of cascade reactions and industrial productions needs the development of controllable catalysts to manipulate the reaction progress for both academic research and practical application. Hence, it is of great value to mimic living systems through the design of switchable bioinspired enzymes by changing their structure and properties in response to external stimuli.Besides high catalytic efficiencies, regulation mechanisms of natural enzymes are also critical. The biosynthesis and consumption of saccharides, lipids, and amino acids are all regulated by turning on/off the key enzymes in the specific metabolic pathways. Also, the homeostasis in organisms must be maintained by the control of enzyme activities to ensure the stable concentrations of substances under normal physiological conditions. For instance, taking overdosed high‐efficiency antioxidant agents to inhibit ROS damage would inevitably lead to disorders of the body's cellular signal transduction systems, which is not conducive to normal metabolism.53 In  With the vigorous development and wide application of stimulus‐responsive materials, molecular machines, protein/peptide assemblies, and many other scaffolds have been discovered. Generally, these reversible processes control the on/off regulation of enzymes by changing the conformations of the enzyme scaffolds to reveal/embed the catalytic sites upon specific conditions.To facilitate the control of catalytic activities, natural enzymes have acquired the ability of allosteric regulation through evolution Scheme . The cat54 Wit Compared to previous reports on this topic, this review broadened the notion of “allosteric effect” and run through a variety of catalyst‐design ideas which apply to both synthetic molecules and biomolecules. Typically, the inherent allosteric behavior of natural proteins could be utilized as universal building scaffolds for switchable protein catalysts. Recent advances in the field of bioinspired switchable catalysts designed by allosteric molecules, supramolecular complexes, and self‐assemblies are introduced 3] was obtained based on the helix heptapeptide template (P1a) reported previously by connecting three copies of P1a to a functionalized Tris(2‐aminoethyl)amine (Tren) platform. [T(P1)3] could bind up to four metal ions (CuII or ZnII): one in the Tren subsite and three in the azacyclononane subunits. The binding of the metals to the Tren platform would induce a change in which the three short, helical peptides are aligned in a parallel manner with the azacyclonane units pointing inward within the pseudocavity they define. Thus, the activity of the catalyst could be controlled in opposite ways by ZnII according to the type of substrate used. In the cases of the 2‐hydroxypropyl‐p‐nitrophenyl phosphate (HPNP) cleavage, ZnII could switch on the activity as a positive allosteric regulator. For an oligomeric RNA substrate, however, ZnII switches off the activity as a negative allosteric regulator. This tripodal peptide‐based supramolecular catalyst provides a striking example of the selective mode of action toward two different phosphate esters and shows how, by increasing the complexity of a supramolecular catalyst.Scrimin and co‐workers built a metal ion regulated peptide template as an allosteric supramolecular catalyst for the cleavage of phosphate esters.65 The2+ binding. By computational design and the incorporation of a carboxylate residue into the hydrophobic pocket of CaM (F92E)  has been chosen as a scaffold because CaM would form a hydrophobic environment upon Ca) Figure , it show2+‐responsive bioinspired antioxidant selenoenzyme was constructed by computational design and engineering of an allosteric protein scaffold, as the oxidative injury is usually coupled with high Ca2+ concentration in mitochondria. The active center selenocysteine was inserted into the allosterically variable site on the scaffold by site‐directed mutation and a cysteine‐auxotrophic system. This selenoenzyme can reduce excessive hydroperoxides into harmless hydroxyl compounds at the expense of glutathione and be switched on/off by Ca2+‐induced allosterism of the recoverin protein, as the active center is exposed in the Ca2+‐bound conformation and embedded in the Ca2+‐free conformation  is in the same order of magnitude as that of natural glutathione peroxidase (GPx) in human plasma, and completely reversible after multiple Ca2+‐bound and Ca2+‐free cycles. Such a selenium‐containing system has also been utilized to construct an ATP‐switched antioxidant enzyme.The incorporation of non‐natural amino acid residues also expands the application of this allosteric design strategy. Recently, a Cascaffold,69 as 2.2 It is critical to incorporate the synthetic switch at proper positions on the enzymes to achieve the switchable activity.Synthetic allosteric catalysts not only allow for the development of economic catalysts for industrial applications but also provide access to regulating non‐natural reactions in which the activity/selectivity can be switched by the effector. Compared with large molecules such as proteins, synthesized molecules have a simple, stable, and controllable structure, and can be easily modified. Various functional groups afforded many stimulus‐responsive molecules that are sensitive to light, pH, metal coordination, redox, and mechanical forces. These allosteric molecules could conduct large geometrical changes upon external conditions, thus the catalytic group would undergo a dramatic transformation of the chemical environment by coordination, steric, electronic, and aggregation effects. Moreover, the combination of allosteric synthetic molecules with protein catalysts by chemical modification or genetic engineering also offers a critical strategy to develop smart biocatalysts which have both dynamic features and high efficiency. The hybridization of artificial molecular switches and natural enzymes have been applied in switchable glutathione S‐transferase and split‐luciferase complementation.71 It  Depending on the size of the modified functional groups to the benzene rings, the light that triggers the conformational change could vary on the wavelength. The robust light‐responsive feature of azobenzene derivatives makes these synthetic allosteric molecules universal in many large‐scale systems, such as the core of dendrimers, molecular switch modified on proteins, and supramolecular assemblies. Besides, Branda's group reported the first case of a light‐driven chiral metal catalyst based on the framework of 1,2‐dithienylhexafluorocyclopentene. By introducing a chiral oxonate at the ortho positions of two thienyl groups, they synthesized a bisoxazoline chiral ligand, which can be reversibly switched between State I and State II by light. The author chose the cyclopropanation of styrene as the target reaction. In State I, the formation of intramolecular bidentate coordination metal catalysts afforded moderate enantioselectivity. While in State II the photo‐induced ring‐closure catalytic species formed monodentate coordination, resulting in almost racemic products.Azobenzene derivatives have been widely studied due to the large geometrical change between trans/cis isomers upon radiation.72 Dep In different states, the yield of the catalytic reaction ranged from 7% to 83% with dramatically different stereoselectivity, showing the potential of synthetic allosteric molecules in asymmetric catalysis. Subsequently, they explored the universality of this light‐driven chiral molecular motor catalyst and extended its application to other asymmetric catalytic reactions. Based on the successful application of molecular motors in the asymmetric catalysis of small organic molecules, Feringa's team further expanded it to the field of metal catalysis. Recently, they developed the second‐generation molecular motor to construct a new artificial stimulus‐response chiral catalytic system. Unlike the first‐generation molecular motor, the second‐generation molecular motor has different metastable states during the rotation process. They introduced the biphenyldiol unit into the molecular switch and found that the chiral center could induce the helical chirality of the molecular switch. Meanwhile, under the irradiation of different wavelengths of light, the stable State I and its semi‐stable State II showed reversible transformation. With this chiral molecular switch as the ligand, in the asymmetric addition reaction of diethylzinc to benzaldehyde derivatives, the two‐state ligands (State I and State II) afforded opposite configuration, and the maximum difference in ee value reached 113%.Moreover, Feringa and coworkers develop a 360° rotation and four‐states photoswitchable molecular motor that could promote Michael additions  (PNIPAM) is extensively studied as a typical temperature‐responsive polymer scaffold with an LCST of 32°C, which is close to the temperature under physiological conditions. However, using PAMAM as a scaffold for the construction of switchable catalysts remains rare. Temperature‐responsive polymers were usually applied as phase separation agents in multicomponent systems to achieve temperature‐responsive catalysis. For instance, Lu and coworkers developed a yolk‐shell system in which a single Au nanoparticle was encapsulated in a thermosensitive polystyrene‐poly(N‐isopropylacrylamide) shell. The porosity and the hydrophobicity of the polymer shell could be dramatically changed by temperature, which acted as a trigger to enhance the catalytic selectivity for given substrates. Recently, another thermoresponsive polymer tannin‐aminopropyltriethoxysilane was coated on the surface of halloysite nanotubes together with PNIPAM to immobilize Au nanoparticles. These multicomponent systems with rigid nanostructures showed significant thermoresponsive catalytic performance in the reduction of 4‐nitrophenol, and the highest activity was acquired at the LCST of 45°C.In addition to small molecular switches, many polymers exhibit allosteric behavior near the lower critical solution temperature (LCST). Poly(e) shell.80 The3Reversibility is one of the most significant features of supramolecular interactions, which have been widely utilized to design switchable catalysts. The reversible binding and dissociation of weak interactions have bred the allosteric behaviors of proteins. In this section, we expanded the meaning of “allosteric” to describe the conformational change of a supramolecular system rather than one single molecule. Undoubtedly, this “change” caused by the allosteric behavior of supramolecular systems offers the opportunity to control the catalytic activity. Specifically, the different binding states between the host molecule and the guest molecule could exhibit opposite chemical environments, which would lead to a notable change in stability, solubility, and catalytic activity. In this case, the external stimulus that triggers the shift between two binding states of the supramolecular system would act as the allosteric effector. With the development of supramolecular chemistry, many host‐guest systems have been extensively studied. It is a research hotspot to incorporate catalytic groups into these systems and investigate the effects of confined space and dynamic molecular recognition on catalytic reactions.3.1 Then the amphiphilic complex could assemble into supramolecular nanotubes by stacking in water. Inspired by the fact that natural GPx contains positively charged residues to enhance the enzyme‐substrate recognition, the nanotube was further modified with the guanidine group to improve the antioxidant activity. Due to the synergistic multiple catalytic sites and large superficial area, the nanotubes were four orders of magnitude more active than diphenyl diselenide. Based on the above‐mentioned assembled nanotubes, PNIPAM was linked to the Tellurium‐containing cyclodextrin by ATRP polymerization and click chemistry methods to get the temperature response characteristics . Also, the catalytic rotaxane could control the rate of nucleophilic addition or substitution reactions via examining catalysis with a better switching effect. Additionally, the “on‐state” of the rotaxane was able to promote tandem iminium‐enamine reaction sequences and the Diels–Alder reaction of dienals through a trienamine activation mode. Furthermore, Leigh's team added a benzene ring group near the catalytic center, which is equivalent to introducing an asymmetric factor, enabling the smart enzyme system to perform asymmetric catalysis with high stereoselectivity. Through experienced synthesis technology, Leigh and coworkers also developed a molecular pentafoil knot that allosterically initiates or regulates catalyzed chemical reactions by controlling the in situ generations of a carbocation formed through the knot‐promoted cleavage of a carbon‐halogen bond  metal at the structure control sites, distal from the Cr (III) metal centers at functional sites within the same macrocyclic assembly. When the catalyst activity is in a closed state, the initial rate kinetics for the ring‐opening of cyclohexene oxide could be reduced to 30%. Moreover, the selectivity and activity of this supramolecular catalyst in the asymmetric ring‐opening of cyclohexene oxide were enhanced compared to a Cr(III)‐salen monomeric analog. As the first demonstration of an allosteric catalyst made possible through supramolecular coordination chemistry, it shows how one can use the weak‐link approach to design and build supramolecular complexes with a unique function. One year later, Mirkin and coworkers further develop another “molecular tweezer” by utilizing the Rh coordination as the structural control site at the center of the designed catalyst. When the Rh center coordinated with CO and Cl ligands, the synthetic catalyst exhibited a linear form. However, the intramolecular coordination between Rh could replace the CO and Cl ligand and bend the catalyst into a tweezer form. This allosteric transformation also led to a significant impact on the catalytic performance for the ring‐opening of cyclohexene oxide.Mirkin et al. have reported a tetrametallic complex prepared via the weak‐link approach to supramolecular chemistry, that behaves as an allosteric catalyst for the ring‐opening of cyclohexene oxide.87 The The triple‐layer complex (TLC) is composed of two transition metal nodes, two chemically inert blocking exterior layers, and a single catalytically active interior Al(III)‐salen complex, which can act as a ring‐opening polymerization catalyst with є‐caprolactone (є‐CL) as the substrate. This complex could be reversibly activated and deactivated with an assemble/disassemble trilayer structure through acetonitrile and Cl– abstracting agent 4∙Et2O). In the activated state with a semi‐open structure, the conversion rate of 100% can be achieved within 40 h of catalysis, while the conversion rate in the deactivated state (with a fully closed triple‐layer structure) is almost zero within 100 h.Later, Mirkin and coworkers further developed an allosteric supramolecular structure in which a monometallic catalytic site has been buried in the middle layer of a triple‐layer complex Figure .89]8990[94Natural enzymes usually prefer to work together in the form of oligomers in sophisticated biological processes. The critical and complicated regulatory conjunctions in metabolic pathways are often controlled by a multi‐component complex, which includes a variety of coordinated enzymes, regulatory factors, and structural motifs. These protein complexes as the supervisors of biological activities have well‐organized nanostructures and specific functions. Generally, the self‐assembly of natural enzymes brings higher stability, better coordination between enzymes, and dynamic feature in favor of metabolic regulation. The assembly and dissociation of components not only are related to significant physiological indexes but also control enzymatic activity smoothly and efficiently. If the dynamic binding‐dissociation process of one host‐guest system could be utilized to control the catalytic activity, reversible supramolecular self‐assemblies at the nanoscale could also exhibit “allosteric” morphologies to convey the function of switchable catalysis.4.1Studies on the combination of the catalyst design and protein self‐assembly have emerged, and one key issue in this field is that natural enzymes would suffer a significant loss of catalytic activities once they were assembled into an artificially designed protein assembly. Because the catalytic sites of these enzymes are formed after millions of years of evolution, and the tiny structural fluctuations caused by the assembly process could severely affect the catalytic activity. Besides, it is quite difficult to design new connections between protein building blocks from scratch. In this case, the redesign of new catalytic sites on the existing protein assembly scaffolds would be more promising to develop switchable biocatalysts. The intrinsic properties of protein building blocks  would be reflected in the entire assemblies, which extend the application of these catalysts. Due to the intrinsic stable feature of SP1, the artificial selenoenzyme based on the SP1 scaffold exhibited high thermal stability that it remains active under 85°C for days or 37°C for months. Also, SP1 as a negatively charged protein building block could further assemble with positively charged particles by electrostatic interactions. Based on the dynamically controllable protein assembly, the selenium‐modified protein SP1 (Seleno‐SP1) was assembled with the dendrimer PD5 into a robust and controllable nanowire. The trick in this protein‐dendrimer hybrid assembly is that the selenium catalytic sites locate on the plane of SP1 disks, which allows the control of embedding/revealing catalytic sites upon the repeated reversible assembly and dissociation process, respectively  and arginine (NH2‐RSGQQKFQFQFEQQ‐Am) was developed to form amyloid‐like nanofibers with sol‐gel transformation. Enzymology experiments showed that the Michaelis constant of the binary peptide assembly was significantly lower than that of the monolithic assembly formed by the histidine‐containing peptide alone, which proved that the substrate‐binding ability provided by arginine and the catalytic center formed a synergistic effect. As a single peptide molecule could not provide such complex conformation similar to the catalytic center of a natural enzyme, but the self‐assembly strategy can benefit the binding between peptide‐based catalysts and the substrate, stabilizing the transition state and maintaining higher catalytic efficiency.Given the example above, one would expect that there must be a critical relationship between the ordered arrangement of supramolecular structures and the catalytic activity. If the catalytic cavity of the enzyme‐like peptide assembly is similar to that of natural enzymes, which contains not only the catalytic site but also essential groups to enhance the enzyme‐substrate binding, it is anticipated that the catalytic activity of peptide‐based catalysts could be improved. To investigate whether this strategy works, a binary peptide assembly system containing histidine  Expanding the catalytic scope of bioinspired enzyme models. The successful designs are mainly concentrated on simple reactions such as oxidoreduction and deprotonation, while switchable catalysts for sophisticated and multistep organic reactions remain rare. (ii) Building novel allosteric scaffolds for switchable biocatalysts. The technology for connecting different protein domains by gene insertion and swapping has been developed, and new synthetic allosteric molecules will emerge, providing more scaffolds for the design of switchable catalysts. (iii) Developing in vivo applications for switchable catalysts. A successful bioinspired enzyme should be capable of its natural counterpart's biological function, which is rarely demonstrated in vivo. To meet practical demand, it is essential to construct switchable bioinspired catalysts that can make a difference at the cellular and macroscopical level. In the end, we hope that this review of switchable bioinspired catalysts may inspire fresh ideas and accelerate the pace of further explorations.Exploration editorial board. The authors declare no conflict of interest.Xue Xue is a member of the


In this study, the precise positioning and alignment of arrays of two different guest molecules in a crystalline host matrix has been engineered and resulted in new optically active materials. Sub‐nm differences in the diameters of two types of 1D channels are sufficient for size‐selective inclusion of dyes. Energy transport occurs between the arrays of different dyes that are included in parallel‐positioned nanochannels by Förster resonance energy transfer (FRET). The color of individual micro‐sized crystals are dependent on their relative position under polarized light. This angular‐dependent behavior is a result of the geometrically constrained orientation of the dyes by the crystallographic packing of the host matrix and is concentration dependent. Förster resonance energy transfer (FRET) between arrays of donor‐acceptor chromophores in a metal–organic framework has been observed. These arrays of aligned chromophores have been formed by size‐selective inclusion in differently nanosized channels, resulting in micro‐sized crystals with anisotropic optical properties. The concept and the development of molecular host–guest chemistry have resulted in many fascinating and emerging technologies.Other factors hampering the development of such materials are the unpredictability and limited correlation between crystallographic structures and crystal morphologies. Moreover, low uniformity and lack of monodispersity limit the further use of individual single‐crystals. The work by Al‐Ghoul and Hmadeh is an example of making differently sized and uniform MOFs.AdDB,c‐axis. This structural feature is atypical,[We have demonstrated recently that the organic ligand, atypical,40, 41AdDB, were prepared as host matrix for the assembly of new materials for optical applications. Coordination of this ligand to bivalent cadmium cations resulted in the same coordination structure as recently found for other first row metals,[We demonstrate here the size‐selective inclusion of two types of dyes in different nanosized‐channels. The resulting crystals are dichroic: they exhibit color‐to‐color transitions and different color intensities when exposed to polarized light. The arrays of donor and acceptor dyes assembled in parallel channels display energy transfer by nonradiative dipole‐dipole coupling. The FRET is confirmed by fluorescence lifetime measurements in combination with photobleaching of the acceptor dye.48, 49AdDB), and cadmium nitrate in dimethylformamide (DMF) under solvothermal conditions (105 °C) for 24 hours   imaging showed the formation of well‐defined hexagonal prisms having a high monodispersity , methyl orange (MO) and lithium 7,7,8,8‐tetracyanoquinodimethane (TCNQ) (=group I). Significantly lower amounts of dyes are embedded into the crystals when larger dyes are used with a “width” between 0.7–1.2 nm: sodium fluorescein (SF), sodium 5‐aminofluorescein (AF) and fluorescein isothiocyanate isomer I (FITC) (=group II). The largest molecules we used do not enter the host matrix: sodium acid red‐52 (AR) and brilliant blue R250 (BBR); width >1.2 nm (=group III)  is a strong indication that selective functionalization of the different channels of the crystals is possible based on the dimensions of the guest molecules . These sieving experiments show that the smallest channel is only accessible to the dyes of group I, whereas the larger channel is accessible to both small and large dyes (groups I and II).To explore and demonstrate the selective sieving effects of our crystals, we suspended them in a series of eight methanol solutions with differently‐sized dyes , and this effect is dependent on the concentration of the dyes. Optical images of crystals saturated with dyes recorded at different angular directions show moderate or minor color changes for the small and medium‐sized molecules (Group I and II) . Interestingly, crystals loaded with lower amounts of one of the smaller dyes i.e., sodium resorufin, do show clear changes in the intensity of the purple color Figure C. We posExperiments performed with a medium‐sized dye, sodium fluorescein , and is in good agreement with what one would expect by functionalization of only the smaller channels (≈0.05 mmol g−1). To provide support for this conclusion, we first saturated the crystals with the smaller dye, sodium resorufin, and subsequently added the larger dye, sodium fluorescein, to the reaction mixture , sodium resorufin (acceptor) would emit the transferred energy.e Figure C,D. As cc‐axis. Combining these two different optical properties within a single host crystal resulted in polarization‐dependent dichroism.The crystals functionalized with the two dyes are dichroic under polarized light Figure . The sodMO), or 7,7,8,8‐tetracyanoquinodimethane lithium salt (TCNQ) in crystals saturated with sodium fluorescein (SF) . The scope of this self‐assembly process was further demonstrated by size‐selective functionalization of the different nanosized channels of the host crystals with the sodium salts of fluorescein isothiocyanate isomer I (FITC) and resorufin (SR) . The crystals functionalized with TCNQ and SF, and FITC and SR are also dichroic .Although optical dichroism is known for molecular crystals,40, 41SF) and the excitation spectrum of sodium resorufin (SR) both in solution and included in the MOFs indicates the possibility of efficient energy transfer . The energy‐transfer properties and underlying mechanism of this donor‐acceptor system were studied by analyzing their fluorescence properties. The large channels of the crystals were first saturated with sodium fluorescein (=donor). Then, the smaller channels of the yellow crystals were loaded with four different amounts (SR1‐SR4) of sodium resorufin (=acceptor) by applying different soaking times. This process was monitored by UV/Vis measurements of the dye solutions resulting in purple crystals  when exciting the donor at λ=480 nm ,SR1: 23 %, SR2: 61 %, SR3: 84 %, SR4: 88 %) (Table S4). The lifetime of the acceptor is changing for the crystals with the highest concentration of this dye, which is in agreement with different stacking interactions.Fluorescence measurements on the same set of individual crystals show a decrease in the lifetime for the donor as a function of the amount of the acceptor . In accordance with the steady‐state emission spectrum, FLIM images of crystals saturated with sodium fluorescein and with different amounts of sodium resorufin showed also the varied degree of energy transfer between this donor—acceptor pair.Confocal fluorescence lifetime imaging microscopy (FLIM) showed the homogeneous distribution of the dyes and the energy transfer across the entire crystals  by irradiation of small areas on individual crystals at λ=600 nm as shown schematically in Figure SF) and its original lifetime—whereas the unexposed areas of the crystals continue to display energy transfer. Figures SF) and acceptor (SR), respectively. It can be seen that photobleaching of the acceptor (SR) results in longer fluorescence lifetime of the donor (SF); see the unbleached (a) and photobleached (b) areas. These changes in fluorescence lifetimes are accompanied by changes in the fluorescence intensities  should be addressed to the authors.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.


Pterocarpus erinaceus Poir (African rosewood) in Ghana. Here, we assessed variation in seed set, seed morphological and chemical traits, germinability, and seedling growth of African rosewood from four distant provenances  in Ghana. We sought to answer how local environmental conditions influence the expression of seed traits by examining the relationship between seed traits and maternal environmental factors  using regression models and correlation analysis. Seed size, mass, and nutrient composition differed considerably among provenances. Seed size and mass increased as the seed source moved further away from the forest‐savanna transition toward the Guineo‐Sudanian savanna regions. Temperature mainly accounted for the variability observed in seed traits. Phenology curves of the seed source vegetation expressed a strong correlation with monthly rainfall. Overall, the occurrence of samara containing whole seeds was low (<50%) except for Tumu provenance. Seeds were rich in carbohydrate and crude protein content consistent with most leguminous plants while mean percentage germination ranged between 30 and 62% among provenances. Our results highlight the adaptive strategies of African rosewood to different environments through the expression of their seed traits and suggest the need for priority action to maintain its conservation.Among plant populations, variation in seed traits has important consequences on species recruitment and performance under different environmental conditions. Knowing such variations and understanding its environmental drivers could help with conservation efforts that protect against the loss of diversity. This information is however lacking in the extinction‐threatened  Seed germination performance of Pterocarpus erinaceus provenances demonstrates adaptive responses that are reflective of their maternal environment. The highest mean percentage of seed germination was realized at 62%. Seed traits associated with recruitment may influence species resilience and ultimately reduce the risk of extinction against disruptions from the rapidly changing climate  and undeveloped seeds. The phenomenon is explained to have ecological importance for the trees, being an adaptive mechanism to discourage seed predators and increase the proportion of full and viable seeds that escape predation both before and after dispersal  maternal environments (provenances) with limited resources and/or with pronounced environmental stress will influence the adjustment of seed morphological traits to have a better competitive advantage  and that (1b), producing seeds of larger sizes and bigger mass will maximize germination success. Larger seed sizes and masses are known to exhibit greater tolerance to heat and other environmental stresses, with higher seed germination and growth rates. Therefore, in limited resources and stressed environments also associated with higher metabolic costs, we expected mother plants to invest more in size and mass of seeds  is a medium‐sized leguminous tree species  endemic to the dry forests and savanna woodlands of West Africa  in each provenance in February. Plus trees are phenotypically superior trees and form the basis of efficient and reliable seed collection  spatially separated within the savanna zones in Ghana were selected for this study Figure . They ar2.3SI¯) proposed by Walsh and Lawler , which covered the season of leaf flushing and subsequent growth, flowering, fruiting, and seed development up to the time of fruit harvest. Rainfall data were obtained from the Ghana Meteorological Agency (GMA) except for Tumu, where data were obtained from the office of Ministry of Food and Agriculture at the Sissala East Municipality. The rainfall pattern in each provenance location was characterized by determining the seasonality index of rainfall over the seed production year. Seasonality index  because it allows for the quantification of the seasonal variations in rainfall and hence spatial comparisons of rainfall seasonality. Again, the values are easily interpretable by comparing them with a standardized range of values and their explanations.The index varies between zero  and 1.83 . We chose this parameter  Terra Land Surface Temperature and Emissivity Daily Global datasets at 1 km spatial resolution on Google Earth Engine (GEE) data catalog. GEE is a cloud‐computing platform that houses satellite images with different temporal and spatial resolutions on a global scale  was calculated as the sum of exchangeable cations  and exchangeable acidity (Al + H). Particle size analysis was done using the pipette method.Soil was sampled to 10 cm soil depth at four randomly located points at the base of each plus tree where the fruits were collected  is a vegetation index that correlates strongly with aboveground net primary productivity  and red lights are reflected bands of wavelengths of the sunlight. It uses the underlying principle that for vegetated surfaces, red wavelengths are characterized by high absorption by leaf chlorophyll and hence low reflectance, while near‐infrared (NIR) wavelengths are characterized by low absorption and hence high reflectance. Where vegetation is under stress, the reflectance values change in the opposite direction . In the germination experiment, 5 replicates of 20 whole seeds each were sown in germination bowls filled with river sand for each provenance except Carpenter where we used three replicates as a result of inadequate seeds. The set‐up was watered every morning and germination was observed and scored up to 24 days after sowing by which time germination had ceased , CSIR‐Forestry Research Institute of Ghana (CSIR‐FORIG). A mean photosynthetic photon flux density (PPFD) of 73.5 μmol mPoorter, . SuccessPoorter, . The preBarstow, . Again, Barstow, . The seeBarstow, :RGR=lnXX2 and X1 are the variables measured in the two assessments . ∆t is the time interval between the two assessment occasions in weeks.Where 2.6All data sets were tested for assumptions of normality and homogeneity of variances using Shapiro–Wilk's test and Levene's test, respectively. Seed morphological traits  were compared among provenances using Kruskal‐Wallis rank‐sum test because of unequal variances and non‐normality of the data. Subsequent pairwise comparisons were conducted using Dunn's test with a 95% confidence interval. Chi‐squared test was used to compare the number of counts in each seed set characteristic  among provenances. The seedlings growth measurements were log‐transformed to meet assumptions of normality before subjecting the data to a one‐way analysis of variance.We investigated germination response to the maternal environment and its proximate composition using generalized linear models (GLMs). The GLMs were adopted because of their suitability in analyzing non‐normal heteroskedastic data characteristic of binomial germination proportions . The second axis correlated with potassium and exchangeable acidity  using a linear mixed‐effects model. The fixed effects were mean monthly temperature, absolute rainfall , the two soil PCA axes, and NDVI, while provenance locations were included as random effects. All values of the explanatory variables were scaled or standardized  to facilitate comparisons among variables before being included in the model. After the initial model fit with all potential variables, a model simplification procedure was carried out by dropping non‐significant explanatory variables, one per time to select the model only retaining variables that collectively resulted in the lowest value of the Akaike Information Criterion (AIC) . In Tumu provenance, a greater percentage of fruits contained whole seeds, followed by underdeveloped seeded fruits and empty fruits. The pattern was different in all three remaining provenances where most fruits collected had underdeveloped seeds, followed by whole‐seeded fruits and empty fruits .The linear mixed‐effects model including only the variables that collectively improved the model with lower AIC revealed that there were significant relationships between the environmental factors and seed morphological traits. The environmental factors explained between 21% and 66% of variations in the seed morphological traits studied Table . Among t3.4p > .05). However, temperature expressed a positive relationship with the final germination score at a lower likelihood , while the soil nutrients showed a negative association with final germination score . The odds of germination increased with seed mass . Crude protein, carbohydrate, and final germination score were not related .Mean emergence among provenances was generally low and ranged between 30% (Carpenter and Wa) and 62% (Tumu) (See supplementary Table 3.5p > .05) in mean stem length, root length, and root collar diameter (Table p > .5).Seedlings from the different provenances expressed similar growth performance at the end of the 6 months observation showing non‐significant differences  with limited resources and/or with pronounced environmental stress would influence the adjustment of seed morphological traits to have a better competitive advantage . Our findings are partially in support of this hypothesis as maternal environmental factors strongly influenced seed traits in different ways. Temperature and soil nutrients showed strong significant positive relationships with seed size traits , whereas absolute rainfall expressed a significant negative relationship with seed length.Maternal environmental factors including temperature, rainfall, and solar radiation are known to have important effects on seed traits, being attributed to account for the underlying mechanisms in geographical gradients of seed size . Again, seed nitrogen content strongly correlated with soil nitrogen content in agreement with hypothesis 2a. Our results are consistent with the findings of other studies that have reported a relationship between soil nutrients and seed traits including nutrient composition (Carón et al., 4.3Seeds from Tumu and Ejura provenances attained 50% germination and more, while seeds from Wa and Carpenter provenances recorded very low emergence of just about 30% final germination. The relatively low germination observed in our study, coupled with concurring high occurrence of underdeveloped seeds suggests the possible destruction of seed embryo by insect larvae, which renders most seeds unviable. Again, this is likely considering that African rosewood seeds are not associated with deep dormancy, and some studies suggest that the species do not require dormancy‐breaking treatments prior to sowing (Zida et al., Consistent with our initial hypothesis, a bigger seed mass improved germination outcome. The relationship between seed mass and germination success has been reported in several studies as well (e.g., Baskin & Baskin, 4.4At the end of the growth experiment, regardless of their seed source or sizes, the seedlings reached similar growth rates and sizes. This was in disagreement with our third hypothesis, where we expected seedlings from large seeds to be of bigger sizes. The 6‐month‐long duration of the experiment coupled with a common growth environment for all the seedlings recruited in this study may account for the similarity in their growth rates and sizes (Zida et al., 5We found significant variations in the seed size and mass traits of African rosewood, proportion of fruits that contained whole seeds, and germination capacity among provenances, which were related to maternal environmental factors. The results indicate that temperature is the key environmental factor that defines seed traits among populations of the species in Ghana. These findings point to the importance of provenances in maximizing the cultivation success of the species. In particular, we suggest prioritizing provenances in the Tumu and Upper West regions of the country for propagation and plant regeneration. Furthermore, considering the high levels of seed predation prior to dispersal among the provenances which reduced the viability of seeds, we recommend future studies to ascertain the prevalence of this phenomenon and its impact on populations of the species. There is also a need for developing technologies that improve the growth rate of the species to meet local demands and its utilization in plantation programs. Finally, our results highlight the adaptive strategies by mother plants to enhance offspring fitness in African rosewood. The study therefore makes an important contribution to restoring the populations of this endangered species.Special thanks to the National Tree Seed Centre, CSIR‐Forestry Research Institute of Ghana and Asare‐Gyebi Kwadwo for the assistance with seed collection. Thanks to the three anonymous reviewers for their helpful comments on the earlier version of this manuscript.This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.The authors declare no conflict of interest.Data S1.Click here for additional data file.


My son's interpretation of ‘MAC Attack’ differs drastically from mine. His comes from a ravenous urge for two all‐beef patties on a sesame seed bun, whereas I am referring to one of the endless limitations placed on my practice by Medicare administrative contractors (MACs). The most recent ‘MAC Attack’ by Novitas, First Coast Service Options and CGS, representing 14 US states, restricted the use of Cellular and/or Tissue‐Based Products (CTPs), also known as ‘skin substitutes’, to four applications per diabetic foot or venous leg ulcer.The key to success in healing wounds with CTPs is wound bed preparation: debridement, control of bacterial burden, maintaining an appropriate moisture balance, off‐loading for diabetic foot ulcers and compression for venous leg ulcers. Reduction of bacterial load is crucial prior to the application of CTPs; however, wound care specialists often rely solely on clinical signs and symptoms to detect bacterial load. The ability to detect clinically significant levels of bacteria using examination is poor (sensitivity less than 15%).4 CFU/g.The most studied diagnostic in the detection of bacteria in acute and chronic wounds is fluorescence imaging—a point‐of‐care, non‐invasive, modality that safe uses violet light to detect bacterial loads greater than 10Despite being an accurate, bedside method of bacterial detection, the adoption of fluorescence imaging has been slow. Real‐time fluorescence imaging has been reported to improve both CTP and autologous skin grafting outcomes based on the presence or absence of bacterial fluorescence prior to application.Wound specialists must expand their toolkit to optimise wound bed preparation prior to the application of CTPs or face stricter and broader restrictions. Fluorescence imaging in combination with physical examination enhances the identification of bacteria, which in turn improves wound healing outcomes with CTPs. Finally, as the wound care community builds a robust body of evidence on the optimisation of CTPs, the evidence garnered can be used to assuage the next ‘MAC attack.’


Pollen grains attached to insects are a valuable source of ecological information which can be used to reconstruct visitation networks. Morphological pollen identification relies on light microscopy with pollen usually stained and mounted in fuchsin jelly, which is also used to remove pollen from the bodies of insects. Pollen embedded in fuchsin jelly could potentially be used for DNA barcoding and metabarcoding  and thus provide additional information for pollination networks. In this study, we determine whether fuchsin‐embedded pollen can be used for downstream molecular applications. We evaluate the quality of plant barcode (ITS) sequences amplified from DNA extracted from both fresh (untreated) pollen, and pollen which had been embedded in fuchsin jelly. We show that the addition of fuchsin to DNA extraction does not impact DNA barcode sequence quality during short‐term storage. DNA extractions from both untreated and fuchsin‐treated pollen produced reliable barcode sequences of high quality. Our findings suggest that pollen which has been collected, stained, and embedded in fuchsin jelly for preliminary microscopy work can be used within several days for downstream genetic analysis, though the quality of DNA from pollen stored in fuchsin jelly for extended periods is yet to be established. In this study we determine whether fuchsin‐embedded pollen can be used for downstream molecular applications. We evaluate the quality of plant barcode (ITS) sequences amplified from DNA extracted from both fresh (untreated) pollen, and pollen which had been embedded in fuchsin jelly. Our study demonstrates that good quality sequence data can be obtained from fuchsin embedded pollen. This will allow visitation studies to include data from both morphological and molecular techniques. Understanding plant‐pollinator interactions has implications for the study of ecosystem evolution and given that pollination is key ecosystem service the conclusions of this manuscript also have important socio‐economic impacts. Philips (Asteraceae); Senecio speciosus Wiild (Asteraceae); Hypoxis angustifolia Lam. (Hypoxidaceae); Moraea modesta Killick (Iridaceae). Five flowering individuals were separately bagged and collected from each of the species. Two pollen samples were collected per individual. One sample (referred to as ‘untreated’) was used directly for DNA extractions. The second sample (‘treated’) was embedded in fuchsin jelly. Each pollen sample comprised a single anther. In the case of the Asteraceae species, an entire disc floret was removed first and then an anther removed under a dissecting microscope. The single anthers were removed using forceps and placed into individual 1.5‐ml plastic Eppendorf microcentrifuge tubes. The anther for the fuchsin‐embedded treatment was transferred to a glass slide and embedded in fuchsin jelly  by heating on a heat‐block set to 55°C for ~1 min or until just melted. With the exception of the omission of crystalline phenol, fuchsin jelly was made following  with minor modifications suitable to the sample tissue/material: The BashingBead™ Buffer was pipetted directly into the microcentrifuge tubes containing the pollen sample, and not a ZR BashingBeadTM Lysis Tube (2.0 mm). Each pollen sample was crushed with a micropipette tip and allowed to settle for ~10 min before rinsing the pipette tip off with the buffer and removing it. The microcentrifuge tube was vortexed briefly, and the subsequent steps in the protocol were followed without amendments. Eluted DNA was stored at −20°C.Concentrations of the eluted DNA samples were calculated by measuring the absorbance of the sample at 260/280 nm using a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific). Samples were then couriered to a commercial company (Genomyx Laboratories) for amplification and Sanger sequencing. The plant ITS region was amplified using the primer pair ITSAB101F (5′‐ACGAATTCATGGTCCGGTGAAGTGTTCG‐3′) and 26SE  by the quality scores assigned to each base  GenBank to authenticate and quality check the data. Forward and reverse fragments were combined to create high‐quality consensus sequences. Sequence quality was assessed from trace files using Phred quality scores . Extracted DNA from both treatments produced sequence trace files with high Phred quality scores . Likewise, RFU value was not significantly different between the treatments . There was no effect of fuchsin on base‐call quality ; formal analysis ; investigation ; methodology ; writing – original draft . Steven D. Johnson: Conceptualization ; formal analysis ; funding acquisition ; supervision ; writing – review and editing . Sandi Willows‐Munro: Conceptualization ; formal analysis ; project administration ; supervision ; writing – review and editing .This work was funded by grants 46372 and 5258 to SDJ from the National Research Foundation, South Africa.All authors declare that they have no conflicts of interest.Appendix S1Click here for additional data file.


Visual impairment is a widespread public health issue that can have a negative impact on quality of life, education and socioeconomic development.1Ocular abnormalities often manifest with typical phenotypic features, such as leukocoria2We have created a mHealth system called the Apollo Infant Sight (AIS), which includes an app collecting data and a deep learning (DL) system analyzing the collected data.We evaluated the performance of our automated intelligent detection system (AIS) in both clinical and at‐home settings Figure . Initial3We have comprehensively assessed AIS by internal validation, external validation and at‐home implementation, preliminarily verifying the feasibility of using the system for early detection of visual impairment in young children. In the future, a large‐scale screening trial to verify the utility of AIS in population‐based screening remains to be conducted. Additionally, further work should improve the performance of AIS for reducing the missed diagnosis of patients with slight visual impairment and reduce the risk of privacy exposure by using ‘digital mask’, a technology based on 3D reconstruction and DL algorithms to erase identifiable features irreversibly and retain disease‐relevant features of facial images.The authors declare no conflicts of interest.


Centrocercus urophasianus) before and after landscape‐level changes induced by a >40,000 ha, high‐intensity megafire that burned sagebrush steppe in eastern Idaho, USA. We also incorporated functional responses into predictive resource selection functions (RSFs) to map breeding habitat before and after the fire. Megafire had strong effects on the distribution of available resources and resulted in context‐dependent habitat use that was heterogeneous across different components of habitat. We observed functional responses in the use and selection of a variety of resources (shrubs and herbaceous vegetation) for both nesting and brood rearing. Functional responses in the use of nesting habitat were influenced by the overarching effect of megafire on vegetation, whereas responses during brood rearing appeared to be driven by individual variation in available resources that were conditional on nest locations. Importantly, RSFs built using data collected prior to the burn also had poor transferability for predicting space use in a post‐megafire landscape. These results have strong implications for understanding and predicting how animals respond to a rapidly changing environment, given that increased severity, frequency, and extent of wildfire are consequences of global change with the capacity to reshape ecosystems. We therefore demonstrate a conceptual framework to better understand space use and aid habitat conservation for wildlife in a rapidly changing world.Global change has altered the nature of disturbance regimes, and megafire events are increasingly common. Megafires result in immediate changes to habitat available to terrestrial wildlife over broad landscapes, yet we know surprisingly little about how such changes shape space use of sensitive species in habitat that remains. Functional responses provide a framework for understanding and predicting changes in space use following habitat alteration, but no previous studies have assessed functional responses as a consequence of megafire. We studied space use and tested for functional responses in habitat use by breeding greater sage‐grouse ( We studied space use of breeding greater sage‐grouse before and after landscape‐level changes to nesting and brood‐rearing habitats that were induced by a megafire event that burned sagebrush steppe in eastern Idaho, USA. Megafire had strong effects on the distribution of resources and resulted in context‐dependent habitat use and selection that were heterogeneous across different components of sage‐grouse habitat. Functional responses in the use and selection of nesting habitat were shaped by the overarching effect of megafire on vegetation, and models built using data collected prior to the megafire had poor transferability for predicting space use in a post‐megafire landscape. Changes to plant communities are also facilitated by larger fires, whereby conversion to grassland can result because sagebrush seedbanks in the soil are often minimal and seed dispersal distances are short  are a sagebrush obligate and an umbrella species for the conservation of sagebrush ecosystems  plant communities. The Grassy Ridge Fire burned >40,000 ha of the Sand Creek study site in July–August 2018, thus qualifying as a megafire  and conducted analyses to understand and predict context‐dependent changes in habitat use as a function of changes to resource availability. We conducted population‐level analyses and assessed functional responses in both the use and selection of nest sites, as well functional responses in the use and selection of resources by females during brood rearing. For each of the three stages of the breeding season , we used distinct analyses to: (1) document and test for context‐dependent habitat use in relation to changes in the availability of individual resources, and (2) predict resource selection before and after megafire while accounting for changes in resource availability through functional responses. These analyses were complimentary, evaluating habitat use and selection independently and considering both inferences about and prediction of space use. Therefore, these analyses furthered our understanding of the usefulness of functional responses as a framework for understanding and predicting the effects of megafire on patterns of habitat use and selection by sage‐grouse . We trapped and monitored female grouse at locations throughout each study area, from 2015 to 2020 at Sand Creek and from 2017 to 2020 at the Medicine Lodge site. We monitored female sage‐grouse daily to document breeding season space use. We programmed PTTs to collect six locations per day, with an upload frequency that depended on the season: more frequent data acquisition during nesting and early brood rearing and less frequent during other periods. We assumed that a female had initiated incubation at a nest (n = 309) when we recorded locations at the same coordinates for ≥3 days. We then added 26 days to the initiation date to predict the hatch date. When a female had several consecutive locations away from the nest site, we visited and inspected the nest to determine fate  based on eggshell and nest‐site conditions in combination with estimated hatch timing. We documented nest fate so that we could identify females with broods.We used standard spotlighting techniques . We limited our analyses to females with successful broods because the monitoring did not involve field‐intensive brood counts prior to the 42‐day flush surveys; thus, we did not know when unsuccessful broods were lost, and consequently had no way to distinguish brood use data from habitat use of the female after losing a brood. We split brood location data into early brood‐rearing (hatch to 21 days posthatch) and late brood‐rearing (22–42 days posthatch) because we believed space use may differ as hens with broods became more mobile and moved farther away from their nest sites. During the first 21 days posthatch, >95% of locations across all birds were <1.7 km from their nest site. We observed larger movements away from nests (>1.7 km) for most females with broods (62.7%), and these movements usually began on or after 21 days . However, we visually evaluated location data and defined this cutoff between early and late periods differently for birds that began directional movements away from nests earlier than 21 days posthatch. Specifically, we adjusted the cutoff earlier for females that clearly began to move out of nesting areas  with broods prior to 21 days posthatch. We adjusted the early‐late brood‐rearing cutoff for 21.9% of females with broods (range = 5–20 days). This resulted in 7239 and 9442 used locations from 67 females with broods across the early and late periods, respectively.We monitored the movements of all females, conducted flush surveys at 42 days posthatch . We used the Bureau of Land Management (BLM) habitat assessment framework (HAF) with integrated terrestrial assessment, inventory, and monitoring (AIM) vegetation sampling protocol (hereafter HAF‐AIM) to measure microsite vegetation characteristics  fractional component time series data . For example, sagebrush cover at the 100 m extent was calculated for a given 30‐m pixel by averaging continuous cover values over all raster pixels within 100 m; moving window analyses replicated this process for each pixel within a raster. Similarly, this process was replicated for each spatial extent and for each vegetation metric. We also derived a raster to measure the spatial heterogeneity of sagebrush cover across the same range of spatial extents. First, we reclassified pixel‐scale continuous sagebrush cover values into biologically relevant . Specifically, we measured the distance from each nest site and random point to the nearest sage‐grouse lek (included in nesting models only), distance from the nearest mesic habitat patch  or mesic grass habitat patch (brood habitat models), topographic roughness . When β1 ≠ 1 resource use changes in a nonrandom fashion as resource availability changes, hence the additive difference between used and available habitat (approach 1) or the selection ratio (approach 2) is not constant, providing evidence for a functional response  to test for functional responses in the use and selection of nest sites , whereas the brood (n = 67 broods) was the sample unit for brood analyses . Analysis approaches 1 and 2 were also replicated over each spatial extent to assess the robustness of our inferences across scales.Under the null hypothesis of proportional use, deviations from the null hypothesis are indicated by statistical tests on the values of the regression coefficients. For analysis approaches 1 and 2, proportional use or selection occurs when e Tables . The comd Tables  because 2.6The utility of RSFs for conservation and management purposes is the creation of mapped predictions, thus we developed RSFs using model selection techniques that explicitly optimize model complexity for out‐of‐sample prediction . For nest selection analyses, we fit models that included linear and quadratic main effects and the 1st‐order functional response interaction , whereas larger sample sizes allowed us to also include functional response interactions for quadratic terms  for brood selection analyses. For each covariate, we selected the shape (linear vs. quadratic) and scale (100–1000 m) to optimize out‐of‐sample prediction, as described above. Preliminary analyses suggested unrealistic results with quadratic terms for some covariates due to the sparsity of data across portions of the observed data range. Thus, we did not consider quadratic terms for annual herbs, litter, or bare ground in our nest‐selection RSFs. Similarly, we did not consider functional response interactions with quadratic terms for annual herbs, perennial herbs, and litter in our brood selection RSFs.We used a multi‐step process to arrive at a final RSF model. For the first step, we conducted univariate analyses to optimize the scale (100–1000 m) for each remotely sensed vegetation covariate, and to evaluate support for quadratic terms and functional response interactions for quadratic terms (brood models only) in the final model  for all covariates, and included second‐order functional response interactions (βxi2×A¯x) for brood models when supported by univariate analyses. However, several variables were excluded from the global model because of strong correlation with variables that had better performance in univariate analyses . For transect‐scale variables in nesting RSFs, we included a fixed effect for each variable and its functional response interaction in the global model, as preliminary analyses found no support for quadratic relationships. We conducted model selection from the global model and used LASSO regression to identify the final model complexity .After identifying the optimal scale and shape through univariate analyses, we built multivariate and multiscale RSFs. For this final step, we included in our global model each remotely sensed variable at its optimal scale and shape, included first‐order functional response interactions  for average available habitat. However, our sampling of available habitat for brood selection was conditioned on nest locations. Thus, the average available habitat for each covariate in brood selection RSFs was mapped at a 30‐m resolution via moving window analyses, with window sizes of 1.7 km (early brood‐rearing period) and 8 km (late brood‐rearing period), respectively. We exponentiated the final RSFs to map the pixel‐scale relative probability of selection for nesting, early brood‐rearing, and late brood‐rearing periods. Because few females with broods ventured >500 m inside the boundary of the fire, we also manually set areas >500 m inside the fire perimeter to zero for the early and late brood maps, as these areas were effectively unavailable . We also generated a composite RSF that aggregated final model predictions across nesting and brood‐rearing periods by multiplying the three rasters, effectively weighting the brood locations by the probability of a site being used for nesting . We then created rasters of average available conditions (before fire [2017] and after fire [2018]) for each covariate whose functional response terms were included in the final RSFs. For nest‐selection RSFs, the average available habitat for each covariate was again defined using site‐year combinations; thus, for each site (Medicine Lodge and Sand Creek) and year (2017 and 2018) combination, each 30‐m pixel was given the same value  to high (10) use  uniquely accounted for changing environmental conditions and average available habitat measured at a variety of spatial scales, where we optimized the extent of each covariate, along with overall model complexity, for out‐of‐sample prediction. Importantly, habitat relationships and their mapped predictions from RSFs lacked transferability to a post‐megafire landscape when built using only data collected before the Grassy Ridge Fire. Consequently, a more complete understanding and better prediction of space use in the aftermath of megafire was facilitated through the lens of functional responses, as space use patterns were not static in the face of large‐scale environmental change.Rangifer tarandus caribou; Moreau et al., Lynx canadensis; Holbrook et al., Puma conclor; Knopff et al., Canis lupus), and caribou  that changed among the specific components of vegetation and between nesting and brood rearing. This heterogeneity of responses to individual resources, along with the commonality where functional responses were consistently observed across resources, complicates the transferability of habitat models to new locations in space and time, especially in the presence of changing conditions. Indeed, predictive RSFs built using only prefire data had very poor transferability to post‐megafire conditions, resulting in unstable selection relationships and unreliable mapped predictions. This lack of transferability was apparent irrespective of whether or not the models contained functional response interaction terms. Thus, statistically controlling for changes in availability through functional response interactions may not be enough, and observing space use over a broader range of environmental conditions than exist prior to disturbance may also be necessary for making reliable predictions in a rapidly changing environment  and remotely sensed resources measured across a variety of spatial extents . Relaxed selection is expected for specialist species that require specific amounts or types of habitat because they will seek that habitat out even if it is not widely available  of nesting habitat provided evidence for decreased use of areas with bare ground as it became more available on the landscape after the burn, but multiplicative scale analyses (approach 2) failed to provide statistical evidence for disproportionate selection. Similarly, additive scale analyses provided evidence for increased use of fine‐scale forb richness as average forb richness increased, whereas multiplicative scale analyses again failed to provide evidence for disproportionate selection. Differences in results for additive and multiplicative scale analyses under increased and decreased use scenarios are common . This issue is often not addressed by researchers characterizing types of functional responses observed within RSFs, and it is often unclear where exactly on the three‐dimensional response surface the two‐dimensional graphical representations are arising from ; data curation (supporting); formal analysis (lead); methodology (lead); writing – original draft (lead); writing – review and editing . Shane B. Roberts: Conceptualization ; data curation (supporting); funding acquisition (supporting); methodology (supporting); project administration (supporting); writing – review and editing . Courtney J. Conway: Conceptualization ; funding acquisition (supporting); methodology (supporting); project administration (lead); supervision ; writing – review and editing . Devin K. Englestead: Conceptualization ; data curation (lead); funding acquisition (lead); methodology (supporting); project administration (supporting); writing – review and editing .The authors declare that they have no competing interests.Appendix S1:Click here for additional data file.


Temperature is a fundamental driver of species' vital rates and thus coexistence, extinctions and community composition. While temperature is neither static in space nor in time, little work has incorporated spatiotemporal dynamics into community‐level investigations of thermal variation.We conducted a microcosm experiment using ciliate protozoa to test the effects of temperatures fluctuating synchronously or asynchronously on communities in two‐patch landscapes connected by short or long corridors.We monitored the abundance of each species for 4 weeks—equivalent to ~28 generations—measuring the effects of four temperature regimes and two corridor lengths on community diversity and composition.While corridor length significantly altered the trajectory of diversity change in the communities, this did not result in different community structures at the end of the experiment. The type of thermal variation significantly affected both the temporal dynamics of diversity change and final community composition, with synchronous fluctuation causing deterministic extinctions that were consistent across replicates and spatial variation causing the greatest diversity declines.Our results suggest that the presence and type of thermal variation can play an important role in structuring ecological communities, especially when it interacts with dispersal between habitat patches. Temperature variability is increasing due to global climate change, but limited work has investigated the effects at the metacommunity level. This study uses a multiple trophic level experimental system to demonstrate that the type of thermal variation—spatial, temporal, or both—influences diversity trends and community composition through time. We provide additional complexity by 3D printing custom‐designed landscapes of patches connected by corridors of varying lengths, enabling us to investigate the role of dispersal‐driven spatial dynamics. By monitoring the abundance of each species at regular intervals throughout the duration of the 4‐week experiment, we were able to investigate species dynamics over approximately 28 generations  and 3D‐printed (Lulzbot TAZ 6) in black PLA filament. The corridor was either 5 cm (‘short’) or 10 cm (‘long’). This difference in corridor length, previously used in experiments of spatial dynamics of the ciliate Colpidium striatum  connected by a linear corridor, were custom‐designed using FreeCAD 3D‐design software  can thrive. The media was inoculated with bacteria 3 days prior to the start of the experiment, so that the bacteria levels were sufficient for the protists to survive. On day 0, the start of the experiment, the protist community was added to the experimental landscapes at densities of 1 individual ml−1 for the predators and 10 individuals ml−1 for the bacterivores and omnivore . On Thursdays the subsample was pipetted back into the patch. The experiment lasted for 28 days which equates to approximately 28 protist generations , we took a further subsample of appropriate volume. If the abundance of any one species was too low to ensure it was a true representation of the patch‐level densities , we counted the number of individuals in the whole patch. Once a week, on Mondays, we replenished nutrients by discarding the 2 ml subsample and replacing this with 2 ml fresh sterile media ’ is a natural cubic spline function with three knots for the time variable ‘NumDays’ with days as units (continuous variable), ‘Temp_Regime’ is the temperature treatment used in the experiment  and ‘Corridor’ represents whether a long or short corridor separated the two patches . Interactions between variables are indicated by a colon and represent changes in temporal trend for each categorical level. Replicate was included as a random factor to account for potential non‐independence within replicates. Additionally, a first‐order auto‐regressive covariance structure (ar1(NumDays)) was included to control for serial autocorrelation in the model residuals  using the ‘We then used a top‐down approach to arrive at the best descriptive models using the corrected Akaike information criterion (AICc) which better performs with small sample sizes , to quantify compositional variance (hereafter ‘community dispersion’), using the ‘betadisper’ function in vegan. In combination, PERMANOVA and PERMDISP can provide a measure of across‐and within‐treatment differences, respectively  differed between landscapes, we performed principal component analyses (PCA) on the landscape‐level abundances at day 14 (the midpoint) and day 28 . Each species' abundance was scaled to mean zero and unit variance prior to analysis to ensure each species were equally weighted. To investigate the effects of temperature regime and corridor length on landscape community composition, we performed permutation ANOVA (PERMANOVA) on the Bray–Curtis dissimilarity matrix constructed upon the scaled species abundances using the ‘adonis2’ function in the ‘33.1χ23,25 = 202.466, p < 0.001), temperature regime , the interaction between time and temperature regime , and the interaction between time and corridor length  had significant effects on landscape diversity  or between the temperature treatments with different corridor lengths . However, we found an overall significant effect of temperature regime on landscape diversity . In particular, the static difference landscapes had lower landscape diversity compared with the constant (Bonferroni adjusted p < 0.001) and to the fluctuating asynchronous landscapes , landscape diversity did not differ between the landscapes with long and short corridors  or corridor length: temperature treatment interaction , whereas temperature treatment had a significant effect on beta diversity . This was driven by the fluctuating synchronous landscapes showing significantly higher values of inter‐patch dissimilarity than the fluctuating asynchronous landscapes  than the static difference and fluctuating asynchronous regimes at the midpoint of the experiment , landscape diversity was not shaped by a three‐way interaction between corridor length and temperature regime though time Table . The infHomalozoon vermiculare maintained higher abundance in the short‐corridor landscapes, likely due to higher between‐patch movement of the prey providing sustained food availability for these slow‐moving individuals. Consequently, prey species abundances were lower in short corridor landscapes , resulting in lower landscape diversity. The same pattern was exhibited for Didinium nasutum which, although not directly affected by the corridor length (due to its high movement capacity, Figure While we also observed a weak overall effect of corridor length on the trajectory of landscape diversity through time Table , the treAs with any experimental system, freshwater ciliate microcosms are somewhat limited in their ability to represent the full remit of dynamics seen in natural systems. However, our experiment did contain a range of important interaction types that structure any community—predation and competition—as well as a variety of feeding modes—omnivory, bacterivory, and predation. We were also able to incorporate metacommunity dynamics in our system via the addition of dispersal corridors, providing an additional layer of realism. Consequently, while our experimental system does not provide an exact replica of natural systems, it incorporates many of the dynamics that are important for structuring biodiversity responses to environmental change.While general effects of thermal variation are well studied, there remains limited investigation into the differences between different types of thermal variation in how they shape community dynamics. Our experiment showed that different types of thermal variation can affect whether communities are deterministic or stochastic and how community abundance and composition is supported through time. This key finding suggests that continuing to overlook these effects when investigating the impacts of climatic change may significantly increase the uncertainty in how communities will react to continued anthropogenic change.Ellie Wolfe, Francesco Cerini, Christopher F. Clements, and Marc Besson conceived the ideas and designed the experiments. Ellie Wolfe, Francesco Cerini, and Marc Besson performed the experiments. Ellie Wolfe, Francesco Cerini, and Duncan O'Brien performed the statistical analyses. Ellie Wolfe and Francesco Cerini wrote the first draft of the manuscript. All authors contributed substantially to the manuscript revisions. Ellie Wolfe and Francesco Cerini contributed equally to the manuscript.The authors declare they have no conflicts of interest.Data S1Click here for additional data file.


Current sessions of multidisciplinary team meetings (MDMs) have several limitations, including increased costs and duration, as well as limited discussion time for each case. To address these issues, we have developed a computer application called OCTOPUS, which helps manage the patients' list for MDMs. The application allows for the generation of automatic MDM decisions based on predetermined criteria filled in by the patient's doctor and algorithms that comply with the latest oncology guidelines from the National Comprehensive Cancer Network. These decisions must be validated by the MDM faculty members. In cases of nonagreement or complex cases, the application proposes a “face‐to‐face MDM.” The internal mailing system connects all members and allows for the request of a second opinion regarding pathology or imaging results. Initial results suggest that this ergonomic tool provides more flexibility in time management and improved uniformity in selecting cases that would most benefit from face‐to‐face MDMs. In cancer management, universal guidelines are followed within multidisciplinary team meetings (MDMs), also known as tumor boards or multidisciplinary oncology meetings. These meetings aim to provide patients with the optimal health care plan and access to diverse clinical expertise to reduce reported inequalities in care.Our objective is to develop a reliable tool for therapeutic decision‐making in cancer cases and a more standardized method of selecting patients for in‐person MDMs, in order to improve the cost‐effectiveness and time management of these meetings.Approval from the Fez University Ethics Committee was not required for this study as it does not involve human data. We developed a web application named OCTOPUS that performs automatic processing of oncology cases and provides therapeutic proposals, which must be validated by MDM members.OCTOPUS generates automatic therapeutic decisions based on predetermined criteria filled in by the patient's doctor and algorithms based on National Comprehensive Cancer Network's (NCCN) guidelines. A preliminary study was conducted on upper aerodigestive tract cancers, using available online data on cancer management according to NCCN's guidelines. The backend of the application is built on Laravel, a PHP Language Framework, and SQL Language. The front end relies on technologies such as jQuery, CSS, HTML, and Bootstrap, among others. The elaboration process went through 3 phasesWe noticed that therapeutic decisions in otolaryngology MDM files are based on a few factors such as tumor location, tumor, node, metastasis staging, tumor pathology, poor prognosis factors, whether surgery, chemotherapy, or radiation is feasible, and if there is a tumor relapse.We established diagrams that summarize therapeutic plans for each sublocation of upper aerodigestive tract tumors according to the latest guidelines of the NCCN.□Identification interfaces:At our university hospital, we suggested 2 types of login sessions, resident session and professor/consultant session.–Resident session: is a personal session where residents can add MDMs patients' files to the list for discussion. They fill in the required data that summarizes the patient's case.–Professor/consultant session: In our hospital, the ORL MDMs team includes.Otolaryngologist, an oncologist, a radiotherapist, a radiologist, and a pathologist. Each one has a personal session.□MDMs workspace:OCTOPUS offers different options depending on the user profile.–Professors log in to check the MDMs patients' list. Each file has to be reviewed in no longer than 15 days. We chose a deadline of fifteen days to match, at worst, the face‐to‐face MDMs that are carried out every 2 weeks in our institution.–Professors can check patients' recapitulative charts and the treatment options proposed by the application for each case.–When residents log in, they can add new files, delete or edit a file as long as it has not been submitted to the MDMs.–The resident can also consult the final report and attach it to the patient's electronic record.–Residents are allowed to see only their patients' final reports.□Decisions:Professors/consultants can:–Choose a therapeutic decision from what the application suggests.–Propose another “more suitable” therapeutic decision. The latter can be seen by other members and can be “checked” as the therapeutic decision evenly as all decisions suggested by the application.–Choose the option that the case should be discussed in a face‐to‐face MDMs.–If a unanimous decision cannot be reached, OCTOPUS displays the option of “face‐to‐face MDMs” in the final report.□The internal mailing system: The internal mailing system offers the possibility of requesting a special MDM member opinion, such as reviewing a patient's imaging or pathology results or soliciting a local expert opinion.The overall design plan of the application is reported in Figure Octopus displays the patient list and a summary review of each patient's data that includes the necessary details for making an adequate decision Figure .Figure Supporting Information: Data displays an example of a cancer management chart according to NCCN guidelines, as well as the settings and interfaces of the application.κ coefficient. The expert was blinded regarding the automatic decision.Table There is a general agreement on the problems encountered in traditional MDM settings. The outbreak of COVID‐19 highlighted the urgency of rethinking many medical practices for the sake of efficiency and safety in a global trend toward digitalization and telemedicine for better quality and cost management.Naouar Ouattassi, designed the study, established therapeutic algorithms, and drafted the manuscript; Anas Azdad, Hamza Dabaghi, and Arsalane Zarghili, developed the application; Mohamed Nouredine El Amine El Alami, designed the study and reviewed the manuscript for significant insights.The software used for the development of this application is the original version (with license) belonging to the computer engineering department of the Faculty of Science and Technology, University Sidi Mohammed BenAbdellah, Fez, Morocco.Not applicable.Supplemental data: displays an example of a cancer management chart according to NCCN guidelines, as well as the settings and interfaces of the application.Click here for additional data file.