Simultaneous Reduction of Number of Spots and Energy Layers in Intensity Modulated Proton Therapy for Rapid Spot Scanning Delivery.

Reducing proton treatment time improves patient comfort and decreases the risk of error from intra-fractional motion, but must be balanced against clinical goals and treatment plan quality. We formulated the proton treatment planning problem as a convex optimization problem with a cost function consisting of a dosimetric plan quality term plus a weighted $l_1$ regularization term. We iteratively solved this problem and adaptively updated the regularization weights to promote the sparsity of both the spots and energy layers. The proposed algorithm was tested on four head-and-neck cancer patients, and its performance was compared with existing standard $l_1$ and group $l_2$ regularization methods. We also compared the effectiveness of the three methods ($l_1$, group $l_2$, and reweighted $l_1$) at improving plan delivery efficiency without compromising dosimetric plan quality by constructing each of their Pareto surfaces charting the trade-off between plan delivery and plan quality. The reweighted $l_1$ regularization method reduced the number of spots and energy layers by an average over all patients of 40% and 35%, respectively, with an insignificant cost to dosimetric plan quality. From the Pareto surfaces, it is clear that reweighted $l_1$ provided a better trade-off between plan delivery efficiency and dosimetric plan quality than standard $l_1$ or group $l_2$ regularization, requiring the lowest cost to quality to achieve any given level of delivery efficiency. In summary, reweighted $l_1$ regularization is a powerful method for simultaneously promoting the sparsity of spots and energy layers at a small cost to dosimetric plan quality. This sparsity reduces the time required for spot scanning and energy layer switching, thereby improving the delivery efficiency of proton plans.

Simultaneous reduction of number of spots and energy layers in intensity modulated proton therapy for rapid spot scanning delivery.

BACKGROUND: Reducing proton treatment time improves patient comfort and decreases the risk of error from intrafractional motion, but must be balanced against clinical goals and treatment plan quality. PURPOSE: To improve the delivery efficiency of spot scanning proton therapy by simultaneously reducing the number of spots and energy layers using the reweighted l 1 $l_1$ regularization method. METHODS: We formulated the proton treatment planning problem as a convex optimization problem with a cost function consisting of a dosimetric plan quality term plus a weighted l 1 $l_1$ regularization term. We iteratively solved this problem and adaptively updated the regularization weights to promote the sparsity of both the spots and energy layers. The proposed algorithm was tested on four head-and-neck cancer patients, and its performance, in terms of reducing the number of spots and energy layers, was compared with existing standard l 1 $l_1$ and group l 2 $l_2$ regularization methods. We also compared the effectiveness of the three methods ( l 1 $l_1$ , group l 2 $l_2$ , and reweighted l 1 $l_1$ ) at improving plan delivery efficiency without compromising dosimetric plan quality by constructing each of their Pareto surfaces charting the trade-off between plan delivery and plan quality. RESULTS: The reweighted l 1 $l_1$ regularization method reduced the number of spots and energy layers by an average over all patients of 40 % $40\%$ and 35 % $35\%$ , respectively, with an insignificant cost to dosimetric plan quality. From the Pareto surfaces, it is clear that reweighted l 1 $l_1$ provided a better trade-off between plan delivery efficiency and dosimetric plan quality than standard l 1 $l_1$ or group l 2 $l_2$ regularization, requiring the lowest cost to quality to achieve any given level of delivery efficiency. CONCLUSIONS: Reweighted l 1 $l_1$ regularization is a powerful method for simultaneously promoting the sparsity of spots and energy layers at a small cost to dosimetric plan quality. This sparsity reduces the time required for spot scanning and energy layer switching, thereby improving the delivery efficiency of proton plans.

Reconstruction of Concha-Type Microtia Using a Delayed Postauricular Skin Flap.

SUMMARY: Understanding how to remove and retain the relatively large residual auricle is important in concha-type microtia reconstruction. The authors present a method for concha-type microtia reconstruction using a delayed postauricular skin flap. A total of 40 patients with concha-type microtia who underwent ear reconstruction using a delayed postauricular skin flap were retrospectively examined. Reconstruction was performed in three stages. The first stage consisted of preparing a delayed postauricular skin flap and dealing with the residual auricle including removal of the upper residual auricular cartilage. In the second stage, an autogenous rib cartilage framework was placed and covered with a delayed postauricular skin flap, postauricular fascia flap, and autologous medium-thickness skin graft. The ear framework was carefully articulated and secured with the retained residual auricular cartilage to achieve a smooth junction between the two. The third stage involved modification of the reconstructed ear. Patients were followed up for 12 months after ear reconstruction. All reconstructed auricles had a good appearance, and there was a smooth connection between the reconstructed auricle and the residual ear, with similar color as well as a flat and thin scar. All patients were satisfied with the results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Efficient Quantum Private Comparison without Sharing a Key.

Quantum private comparison (QPC) allows at least two users to compare the equality of their secret information, for which the security is based on the properties of quantum mechanics. To improve the use of quantum resources and the efficiency of private comparison, a new QPC protocol based on GHZ-like states is proposed. The protocol adopts unitary operations to encode the secret information instead of performing quantum key distribution (QKD), which can reduce the amount of computation required to perform QKD and improve the utilization of quantum resources. The decoy photon technique used to detect channel eavesdropping ensures that the protocol is resistant to external attacks. The quantum efficiency of the protocol reaches 66%. Compared with many previous QPC schemes, the proposed protocol does not need to share a key and has advantages in quantum efficiency and quantum resources.

Comparison of the Clinical Effect of Double Eyelid Blepharoplasty with the Orbital Septum Method and the Classical Method.

OBJECTIVE: To observe the clinical effect between orbital septum incision and classical incision of double eyelid plasty. METHODS: We retrospectively analyzed 381 patients who underwent double eyelid blepharoplasty in the Department of Plastic and Laser Cosmetology of Hunan Provincial People's Hospital from January 2019 to December 2019. The patients were divided into two groups according to different surgical methods: group A (n = 146) received the classical method and group B (n = 235) received the orbital septum method. The incidence of early postoperative complications, scar depression from 6 months to 1 year after the operation, the condition of 'meat strip' (the accumulation of soft tissue in front of the tarsal plate after double eyelid surgery, including skin, muscle, and fascia fat, results in a hypertrophic appearance of the upper eyelid) below the double eyelid line, and the symmetry of double eyelids were analyzed and evaluated. RESULTS: The total number of early postoperative complications in group A was seven cases (incidence rate: approximately 4.80%), and the total number of early postoperative complications in group B was two cases (incidence rate: approximately 0.85%), with a statistically significant difference (P < 0.05). The degree of scar depression in group B was significantly lighter than that in group A from 6 months to 1 year after the operation (P < 0.05). The score of 'meat strip' below the double eyelid line in group B was significantly lighter than that in group A (P < 0.05). The symmetry of double eyelids in group B was better than that in group A (P < 0.05) CONCLUSION: Compared to the classical double eyelid method, the orbital septum method has the advantages of reducing early postoperative complications, reducing the severity of the scar, slighting the 'meat strip,' and improving symmetry, which results in higher postoperative satisfaction LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Distributed and scalable optimization for robust proton treatment planning.

BACKGROUND: The importance of robust proton treatment planning to mitigate the impact of uncertainty is well understood. However, its computational cost grows with the number of uncertainty scenarios, prolonging the treatment planning process. PURPOSE: We developed a fast and scalable distributed optimization platform that parallelizes the robust proton treatment plan computation over the uncertainty scenarios. METHODS: We modeled the robust proton treatment planning problem as a weighted least-squares problem. To solve it, we employed an optimization technique called the alternating direction method of multipliers with Barzilai-Borwein step size (ADMM-BB). We reformulated the problem in such a way as to split the main problem into smaller subproblems, one for each proton therapy uncertainty scenario. The subproblems can be solved in parallel, allowing the computational load to be distributed across multiple processors (e.g., CPU threads/cores). We evaluated ADMM-BB on four head-and-neck proton therapy patients, each with 13 scenarios accounting for 3 mm setup and 3.5% range uncertainties. We then compared the performance of ADMM-BB with projected gradient descent (PGD) applied to the same problem. RESULTS: For each patient, ADMM-BB generated a robust proton treatment plan that satisfied all clinical criteria with comparable or better dosimetric quality than the plan generated by PGD. However, ADMM-BB's total runtime averaged about 6 to 7 times faster. This speedup increased with the number of scenarios. CONCLUSIONS: ADMM-BB is a powerful distributed optimization method that leverages parallel processing platforms, such as multicore CPUs, GPUs, and cloud servers, to accelerate the computationally intensive work of robust proton treatment planning. This results in (1) a shorter treatment planning process and (2) the ability to consider more uncertainty scenarios, which improves plan quality.

Epicanthus correction with a modified asymmetric Z-plasty.

The study aimed to explore the clinical efficacy of the modified asymmetric Z-plasty with a central axis from the point near the edge of the skin fold of the medial canthus to the point of the innermost palpebral edge of medial canthus for epicanthus correction. A total of 130 followed-up patients who received modified asymmetric Z-plasty for epicanthus correction in Hunan Provincial People's Hospital from January 2019 to December 2019 were included. All patients were followed up with at 1, 3, and 6 months after surgery, and the scarring and surgical outcomes were assessed. The results showed the surgical wounds were healing well, and the sutures were removed at 7 days postoperatively in all patients. At 6 months postoperatively, epicanthus correction was successful in all patients, the lacrimal caruncle was moderately exposed, the incision was not red, and there were no obvious prominent scars. Slightly prominent and uneven scars below the edge of the lower eyelid were observed in 3 patients. Among these 3 patients, 1 patient received no further treatment, and the outcomes were considered acceptable; the outcomes were improved in the remaining 2 patients after a single session of fractional laser treatment, and none of these patients received further surgery. In conclusion, the modified asymmetric Z-plasty with a central axis from the point near the edge of the skin fold of the medial canthus to the point of the innermost palpebral edge of medial canthus is relatively simple and provides good surgical results for epicanthus correction.

Irx3 promotes gap junction communication between uterine stromal cells to regulate vascularization during embryo implantation†.

Appropriate embryo-uterine interactions are essential for implantation. Besides oocyte abnormalities, implantation failure is a major contributor to early pregnancy loss. Previously, we demonstrated that two members of the Iroquois homeobox transcription factor family, IRX3 and IRX5, exhibited distinct and dynamic expression profiles in the developing ovary to promote oocyte and follicle survival. Elimination of each gene independently caused subfertility, but with different breeding pattern outcomes. Irx3 KO (Irx3LacZ/LacZ) females produced fewer pups throughout their reproductive lifespan which could only be partially explained by poor oocyte quality. Thus, we hypothesized that IRX3 is also expressed in the uterus where it acts to support pregnancy. To test this hypothesis, we harvested pregnant uteri from control and Irx3 KO females to evaluate IRX3 expression profiles and the integrity of embryo implantation sites. Our results indicate that IRX3 is expressed in the endometrial stromal cells at day 4 of pregnancy (D4) with peak expression at D5-D6, and then greatly diminishes by D7. Further, studies showed that while embryos were able to attach to the uterus, implantation sites in Irx3 KO pregnant mice exhibited impaired vascularization and abnormal expression of decidualization markers. Finally, we also observed an impaired response of the Irx3 KO uteri to an artificial deciduogenic stimulus, indicating a critical role of this factor in regulating the decidualization program. Together, these data established that IRX3 promotes female fertility via at least two different mechanisms: (1) promoting competent oocytes and (2) facilitating functional embryo-uterine interactions during implantation.

A Case of Parotid Gland Fistula After Microtia Reconstruction Successfully Treated With Botulinum Toxin Type A.

Parotid gland fistula after microtia reconstruction is relatively rare, with only 3 cases having been reported in the literature. It may be caused by the presence of an accessory parotid gland or surgical damage to parotid gland tissues. The principal treatment is dressing the wound. Here, we report the first case of parotid fistula after microtia reconstruction using a delayed retroauricular flap, which healed following wound dressing and an injection of botulinum toxin type A (CBTXA) into the parotid gland.

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the Gentianella acuta, is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out. AIM: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC. MATERIALS AND METHODS: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings. RESULTS: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM). CONCLUSION: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.

IRX3 and IRX5 collaborate during ovary development and follicle formation to establish responsive granulosa cells in the adult mouse†.

Healthy development of ovarian follicles depends on appropriate interactions and function between oocytes and their surrounding granulosa cells. Previously, we showed that double knockout of Irx3 and Irx5 (Irx3/5 DKO) in mice resulted in abnormal follicle morphology and follicle death. Further, female mouse models of individual Irx3 or Irx5 knockouts were both subfertile but with distinct defects. Notably, the expression profile of each gene suggests independent roles for each; first, they are colocalized in pre-granulosa cells during development that then progresses to include oocyte expression during germline nest breakdown and primordial follicle formation. Thereafter, their expression patterns diverge between oocytes and granulosa cells coinciding with the formulation and maturation of intimate oocyte-granulosa cell interactions. The objective of this study was to investigate the contributions of Irx5 and somatic cell-specific expression of Irx3 during ovarian development. Our results show that Irx3 and Irx5 contribute to female fertility through different mechanisms and that Irx3 expression in somatic cells is important for oocyte quality and survival. Based on evaluation of a series of genetically modified mouse models, we conclude that IRX3 and IRX5 collaborate in the same cells and then in neighboring cells to foster a healthy and responsive follicle. Long after these two factors have extinguished, their legacy enables these intercellular connections to mature and respond to extracellular signals to promote follicle maturation and ovulation.

A convex optimization approach to radiation treatment planning with dose constraints.

We present a method for handling dose constraints as part of a convex programming framework for inverse treatment planning. Our method uniformly handles mean dose, maximum dose, minimum dose, and dose-volume (i.e., percentile) constraints as part of a convex formulation. Since dose-volume constraints are non-convex, we replace them with a convex restriction. This restriction is, by definition, conservative; to mitigate its impact on the clinical objectives, we develop a two-pass planning algorithm that allows each dose-volume constraint to be met exactly on a second pass by the solver if its corresponding restriction is feasible on the first pass. In another variant, we add slack variables to each dose constraint to prevent the problem from becoming infeasible when the user specifies an incompatible set of constraints or when the constraints are made infeasible by our restriction. Finally, we introduce ConRad, a Python-embedded open-source software package for convex radiation treatment planning. ConRad implements the methods described above and allows users to construct and plan cases through a simple interface.

Dynamic expression patterns of Irx3 and Irx5 during germline nest breakdown and primordial follicle formation promote follicle survival in mouse ovaries.

Women and other mammalian females are born with a finite supply of oocytes that determine their reproductive lifespan. During fetal development, individual oocytes are enclosed by a protective layer of granulosa cells to form primordial follicles that will grow, mature, and eventually release the oocyte for potential fertilization. Despite the knowledge that follicles are dysfunctional and will die without granulosa cell-oocyte interactions, the mechanisms by which these cells establish communication is unknown. We previously identified that two members of the Iroquois homeobox transcription factor gene family, Irx3 and Irx5, are expressed within developing ovaries but not testes. Deletion of both factors (Irx3-Irx5EGFP/Irx3-Irx5EGFP) disrupted granulosa cell-oocyte contact during early follicle development leading to oocyte death. Thus, we hypothesized that Irx3 and Irx5 are required to develop cell-cell communication networks to maintain follicle integrity and female fertility. A series of Irx3 and Irx5 mutant mouse models were generated to assess roles for each factor. While both Irx3 and Irx5 single mutant females were subfertile, their breeding outcomes and ovary histology indicated distinct causes. Careful analysis of Irx3- and Irx5-reporter mice linked the cause of this disparity to dynamic spatio-temporal changes in their expression patterns. Both factors marked the progenitor pre-granulosa cell population in fetal ovaries. At the critical phase of germline nest breakdown and primordial follicle formation however, Irx3 and Irx5 transitioned to oocyte- and granulosa cell-specific expression respectively. Further investigation into the cause of follicle death in Irx3-Irx5EGFP/Irx3-Irx5EGFP ovaries uncovered specific defects in both granulosa cells and oocytes. Granulosa cell defects included poor contributions to basement membrane deposition and mis-localization of gap junction proteins. Granulosa cells and oocytes both presented fewer cell projections resulting in compromised cell-cell communication. Altogether, we conclude that Irx3 and Irx5 first work together to define the pregranulosa cell population of germline nests. During primordial follicle formation, they transition to oocyte- and granulosa cell-specific expression patterns where they cooperate in neighboring cells to build the foundation for follicle integrity. This foundation is left as their legacy of the essential oocyte-granulosa cell communication network that ensures and ultimately optimizes the integrity of the ovarian reserve and therefore, the female reproductive lifespan.

Morphology and connectivity of parabrachial and cortical inputs to gustatory thalamus in rats.

The ventroposterior medialis parvocellularis (VPMpc) nucleus of the thalamus, the thalamic relay nucleus for gustatory sensation, receives primary input from the parabrachial nucleus, and projects to the insular cortex. To reveal the unique properties of the gustatory thalamus in comparison with archetypical sensory relay nuclei, this study examines the morphology of synaptic circuitry in the VPMpc, focusing on parabrachiothalamic driver input and corticothalamic feedback. Anterogradely visualized parabrachiothalamic fibers in the VPMpc bear large swellings. At electron microscope resolution, parabrachiothalamic axons are myelinated and make large boutons, forming multiple asymmetric, adherent, and perforated synapses onto large-caliber dendrites and dendrite initial segments. Labeled boutons contain dense-core vesicles, and they resemble a population of terminals within the VPMpc containing calcitonin gene-related peptide. As is typical of primary inputs to other thalamic nuclei, parabrachiothalamic terminals are over five times larger than other inputs, while constituting only 2% of all synapses. Glomeruli and triadic arrangements, characteristic features of other sensory thalamic nuclei, are not encountered. As revealed by anterograde tracer injections into the insular cortex, corticothalamic projections in the VPMpc form a dense network of fine fibers bearing small boutons. Corticothalamic terminals within the VPMpc were also observed to synapse on cells that were retrogradely filled from the same injections. The results constitute an initial survey describing unique anatomical properties of the rodent gustatory thalamus.