Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann\u2013Whitney U test for continuous variables. Results: A slight reduction ( 126.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop 1212% versus 123.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts

Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism

Multiple network properties overcome random connectivity to enable stereotypic sensory responses

Connections between neuronal populations may be genetically hardwired or random. In the insect olfactory system, projection neurons of the antennal lobe connect randomly to Kenyon cells of the mushroom body. Consequently, while the odor responses of the projection neurons are stereotyped across individuals, the responses of the Kenyon cells are variable. Surprisingly, downstream of Kenyon cells, mushroom body output neurons show stereotypy in their responses. We found that the stereotypy is enabled by the convergence of inputs from many Kenyon cells onto an output neuron, and does not require learning. The stereotypy emerges in the total response of the Kenyon cell population using multiple odor-specific features of the projection neuron responses, benefits from the nonlinearity in the transfer function, depends on the convergence:randomness ratio, and is constrained by sparseness. Together, our results reveal the fundamental mechanisms and constraints with which convergence enables stereotypy in sensory responses despite random connectivity

Evolutionary Rate Covariation Identifies New Members of a Protein Network Required for Drosophila melanogaster Female Post-Mating Responses

Seminal fluid proteins transferred from males to females during copulation are required for full fertility and can exert dramatic effects on female physiology and behavior. In Drosophila melanogaster, the seminal protein sex peptide (SP) affects mated females by increasing egg production and decreasing receptivity to courtship. These behavioral changes persist for several days because SP binds to sperm that are stored in the female. SP is then gradually released, allowing it to interact with its female-expressed receptor. The binding of SP to sperm requires five additional seminal proteins, which act together in a network. Hundreds of uncharacterized male and female proteins have been identified in this species, but individually screening each protein for network function would present a logistical challenge. To prioritize the screening of these proteins for involvement in the SP network, we used a comparative genomic method to identify candidate proteins whose evolutionary rates across the Drosophila phylogeny co-vary with those of the SP network proteins. Subsequent functional testing of 18 co-varying candidates by RNA interference identified three male seminal proteins and three female reproductive tract proteins that are each required for the long-term persistence of SP responses in females. Molecular genetic analysis showed the three new male proteins are required for the transfer of other network proteins to females and for SP to become bound to sperm that are stored in mated females. The three female proteins, in contrast, act downstream of SP binding and sperm storage. These findings expand the number of seminal proteins required for SP's actions in the female and show that multiple female proteins are necessary for the SP response. Furthermore, our functional analyses demonstrate that evolutionary rate covariation is a valuable predictive tool for identifying candidate members of interacting protein networks. © 2014 Findlay et al

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

Light-Induced Organic Transformations by Covalent Organic Frameworks as Reticular Platforms for Selective Photosynthesis

Photoassisted synthesis of value-added organic products has developed greatly in the last decades in response to the pressing need for a transition toward sustainable processes and renewable energy. One of the formidable challenges of the light-induced chemical steps is provided by the control of the catalytic efficiency and selectivity under photocatalytic conditions. An attractive perspective is foreseen by triggering the photoreaction events in confined spaces, wherein light harvesting and photocatalytic units are framed into functional architectures. Division of tasks among specialized compartments responds to a bioinspired strategy with the final aim to orchestrate the rate of concurrent and sequential events, to maximize performance while directing the reaction selectivity. Covalent organic frameworks (COFs) are a class of emerging materials that can meet these requirements, with the potential to bridge the existing gap between molecular and heterogeneous photocatalysis. Here, a rich pool of molecular building blocks and chemical linkages is available to afford crystalline porous solids with tailored photophysical properties emerging from the interconnected COF structure walls, while catalytic cofactors can be provided by engineering of the pore surface. In this Perspective, we highlight recent developments where COFs have been successfully employed as photocatalysts for selective organic transformations. The relationship between the COF reticular structure and its photocatalytic behavior is discussed, in terms of the light-conversion pathways and photoredox events, including electron and/or energy transfer mechanisms. The possible role of confinement effects, intrinsic in long-range order porous COF materials, remains largely unexplored in photocatalytic applications. New progress is expected to arise from close interdisciplinary cooperation involving synthetic chemistry and materials science communities

Impact of medically assisted fertility on preterm birth.

Preterm birth is a frequent problem in women who undergo treatment for infertility. Many factors appear to contribute to the occurrence of this complication. Infertile women seem to have a predisposition to giving birth preterm and to having low birthweight babies. These complications also occur in women with a history of infertility who achieve pregnancy without treatment and who have singleton pregnancies. Assisted reproduction patients treated with in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) have a disproportionately high occurrence of preterm births even with singleton pregnancies. Spontaneous preterm labour may be related to underlying medical conditions of the female partner, as its occurrence is not increased in subjects treated with ICSI (i.e. when the infertility problem is associated with male reproductive dysfunction in normal female partners). Multiple pregnancy is the factor most likely to be related to preterm birth in infertile women. The administration of drugs to induce ovulation either alone or combined with intrauterine insemination causes a significant increase in multiple pregnancies. The occurrence of higher order multiple pregnancy is also increased. Multiple pregnancy in women undergoing IVF or ICSI is related to the number of embryos transferred at the end of treatment. The transfer of more than two embryos in women under 35 is not associated with an increased chance of conception, while the occurrence of multiple pregnancy is significantly increased. Women over 40 may benefit from the transfer of more than two embryos, with fewer risks of multiple pregnancy. Single embryo transfer is increasingly considered a workable clinical option, particularly in young women. Hopefully, a more cautious approach to infertility management will reduce the occurrence of multiple pregnancy, spontaneous preterm labour and the high number of low birthweight infants born after treating these women

Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation.

OBJECTIVE: To prove that low-dose hCG alone can be clinically used to replace FSH-containing gonadotropins to complete controlled ovarian hyperstimulation (COH). DESIGN: Controlled, prospective, randomized study. SETTING: Academic center. PATIENT(S): Infertile patients who are candidates for assisted reproduction. INTERVENTION(S): Patients received [1] recombinant FSH or hMG throughout COH (group A); [2] ovarian priming with recombinant FSH/hMG followed by low-dose hCG (200 IU/day) alone (group B). MAIN OUTCOME MEASURE(S): Medication consumption; daily serum and follicular fluid (FF) measurements of LH, FSH, hCG, E2, P, T, and androstenedione (A); number and size of follicles; intracytoplasmic sperm injection (ICSI) outcome. RESULT(S): In group B: [1] duration and dose of recombinant FSH/hMG administration were reduced; [2] preovulatory serum hCG, E2, and T were higher, whereas FSH was lower; [3] FF hCG, E2, T levels, and E2/T, E2/A, and E2/P ratios were higher, whereas A was lower; [4] small but not large preovulatory follicles were reduced; [5] fertilization rates were higher; and [6] serum and FF P levels, and ICSI outcome did not differ. CONCLUSION(S): Low-dose hCG alone in the late COH stages: [1] reduced recombinant FSH/hMG consumption whereas ICSI outcome was comparable to traditional COH regimens; [2] stimulated follicle growth and maturation independent of FSH administration; [3] was associated with a reduced number of small preovulatory follicles; [4] did not cause premature luteinization; [5] resulted in a more estrogenic intrafollicular environment

Hair analysis in order to evaluate drug abuse in driver's license regranting procedures

In Italy, driving under the influence of drugs determines the suspension of the offender\u2019s driver\u2019s license. To regain the license the person must be drug free during an observation period. People whose license has been revoked or suspended can obtain, or re-obtain their driver\u2019s license subject to the judgment of a medical commission. The exclusion of illicit drug use is determined by means of toxicological analysis, mainly on urine or hair matrices. We reported the results of several years of experience of the forensic toxicology laboratory of the University of Macerata in the use of hair analysis for the assessment of past exposure to drugs in people suspected of driving under the influence of drugs. From 2004 to 2013, 8,612 hair samples, were analyzed for opiates, cocaine and delta-9-tetrahydrocannabinol (\u3949-THC) using gas chromatography /mass spectrometry (GC/MS) method. We used a cutoff (SoHT or national guidelines) to determine the positive data, regardless of the hair sample concentrations. 1,213 samples resulted positive, 71.7% were positive for cocaine and metabolites, 19.8 % for morphine and metabolites, 8.5% for delta-\u3949-THC. We also studied the timeframe of the abuse, as well as gender and age distribution of positive subjects. Moreover, we analyzed the possible deterrent effect of the hair analysis on driving under the influence of psychoactive substances