SwarmDeepSurv: Swarm Intelligence Advances Deep Survival Network for Prognostic Radiomics Signatures in Four Solid Cancers

Survival models exist to study relationships between biomarkers and treatment effects. Deep learning-powered survival models supersede the classical Cox proportional hazards (CoxPH) model, but substantial performance drops were observed on high-dimensional features because of irrelevant/redundant information. To fill this gap, we proposed SwarmDeepSurv by integrating swarm intelligence algorithms with the deep survival model. Furthermore, four objective functions were designed to optimize prognostic prediction while regularizing selected feature numbers. When testing on multicenter sets (n = 1,058) of four different cancer types, SwarmDeepSurv was less prone to overfitting and achieved optimal patient risk stratification compared with popular survival modeling algorithms. Strikingly, SwarmDeepSurv selected different features compared with classical feature selection algorithms, including the least absolute shrinkage and selection operator (LASSO), with nearly no feature overlapping across these models. Taken together, SwarmDeepSurv offers an alternative approach to model relationships between radiomics features and survival endpoints, which can further extend to study other input data types including genomics

Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal

The control of onchocerciasis, or river blindness, is based on annual or six-monthly ivermectin treatment of populations at risk. This has been effective in controlling the disease as a public health problem, but it is not known whether it can also eliminate infection and transmission to the extent that treatment can be safely stopped. Many doubt that this is feasible in Africa. A study was undertaken in three hyperendemic onchocerciasis foci in Mali and Senegal where treatment has been given for 15 to 17 years. The results showed that only few infections remained in the human population and that transmission levels were everywhere below postulated thresholds for elimination. Treatment was subsequently stopped in test areas in each focus, and follow-up evaluations did not detect any recrudescence of infection or transmission. Hence, the study has provided the first evidence that onchocerciasis elimination is feasible with ivermectin treatment in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other areas in Africa, the principle of onchocerciasis elimination with ivermectin treatment has been established

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

A dynamic inequality generation scheme for polynomial programming

Hierarchies of semidefinite programs have been used to approximate or even solve polynomial programs. This approach rapidly becomes computationally expensive and is often tractable only for problems of small size. In this paper, we propose a dynamic inequality generation scheme to generate valid polynomial inequalities for general polynomial programs. When used iteratively, this scheme improves the bounds without incurring an exponential growth in the size of the relaxation. As a result, the proposed scheme is in principle scalable to large general polynomial programming problems. When all the variables of the problem are non-negative or when all the variables are binary, the general algorithm is specialized to a more efficient algorithm. In the case of binary polynomial programs, we show special cases for which the proposed scheme converges to the global optimal solution. We also present several examples illustrating the computational behavior of the scheme and provide comparisons with Lasserre’s approach and, for the binary linear case, with the lift-and-project method of Balas, Ceria, and Cornuejols

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs

Alder-mosquito interactions in alpine hydrosystems : possible applications in dipteran pest control

International audienc

Le programme de lutte contre l'onchocercose en Afrique de l'Ouest : développement socio-économique et risque de recrudescence de la transmission : 1. Etude expérimentale de la transmission des souches d'Onchocerca volvulus du Sud-Ouest de la Sierra Leone par Simulium sirbanum

Dans l'hypothèse du retour des émigrés des régions savanicoles installés depuis plusieurs années en forêt, au sud de la Sierra Leone, nous avons mené une étude expérimentale de transmission "croisée" entre les femelles de simulies savanicoles, #Simulium sirbanum à l'ouest du Mali (Missira) et la souche forestière d'#Onchocerca volvulus du sud-ouest de la Sierra Leone. Cette étude permettra de savoir s'il existe un risque de recrudescence de la transmission de l'onchocercose lié à la réinstallation de ces émigrés dans leur région natale. La forte limitation du passage de microfilaires de la souche forestiere d'#O. volvulus dans l'hémocèle des simulies savanicoles et le très faible rendement parasitaire des femelles de #S. sirbanum vis-à-vis de cette souche aboutissent à une intensité de transmission négligeable de cette souche forestière par les vecteurs savanicoles de l'onchocercose. Le retour dans leur pays d'origine de migrants savanicoles installés en forêt au sud de la Sierra Leone depuis plusieurs années ne saurait donc être, à court terme, source de recrudescence de la transmission de l'onchocercose dans les régions savanicoles de l'aire du Programme de lutte contre l'onchocercose. Ces zones ont été assainies grâce à une lutte antivectorielle efficace engagée depuis 1975, aujourd'hui soutenue par une chimiothérapie associée réduisant le réservoir du parasite chez l'homme. Cependant, la préservation de cet acquis nécessite une surveillance épidémiologique accrue, car les interactions à long terme entre vecteur et parasite pourraient entraîner une adaptation réciproque et éventuellement une recrudescence de la maladie. (Résumé d'auteur