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Background The loss of global functional independence, along with bladder, bowel, and sexual dysfunctions, may contribute to psychological distress and life dissatisfaction after spinal cord injury (SCI). Aim To explore the relationship of erectile function and androgenic status with life satisfaction, independently from confounders recognizable in spinal cord–injured men. Methods 100 consecutive men (49 ± 17 years) admitted to a rehabilitation program because of chronic SCI (≥1 year) underwent clinical/biochemical evaluations, including the assessment of life and sexual satisfaction using the Life-Satisfaction Questionnaire-9 (LiSat-9), erectile function using the International Index of Erectile Function-5 (IIEF-5), global and bowel-bladder functional independence using the Spinal Cord Independence Measure (SCIM) and measurement of total testosterone (TT) levels. The free testosterone level was calculated using the Vermeulen formula. Outcomes The outcomes include the relationship between sexual health and life satisfaction in men with SCI. Results A LiSat-9 score Clinical Implications In men with chronic SCI, assessment of erectile function and testosterone levels can help to predict life satisfaction. Strengths & Limitations This is the first demonstration of the independent association of androgen deficiency and ED with life satisfaction in men with SCI. Prospective studies are warranted to clarify the cause-effect relationships. Conclusions In men with SCI, ED and low testosterone levels exhibit a significant independent association with life dissatisfaction; longitudinal intervention studies could explore possible effects of their treatment in improving sexual and life satisfaction in this population.

Single-crystalline semiconductor nanomembranes (NMs) bonded to compliant substrates are increasingly used for biomedical research and in health care. Nevertheless, there is a limited understanding of how individual cells sense the unique mechanical properties of these substrates and adjust their behavior in response to them. In this work, we performed proliferation assays, cytoskeleton analysis, and focal adhesion (FA) studies for NIH-3T3 fibroblasts on 220 and 20 nm single-crystalline Si on polydimethylsiloxane (PDMS) substrates with an elastic modulus of ∼31 kPa. We also characterized cell response on bulk Si as a reference. Our in vitro studies show that varying the thickness of the NM between 20 and 220 nm affects the proliferation rate of the cells, their cytoskeleton, fiber organization, spread area, and degree of FA. For example, cultured cells on 220 nm Si/PMDS exhibit the same response as on bulk Si, that is, they are well-spread with a pentagonal (or dendritic) shape and show a good organization of stress fibers and FAs. On the other hand, the cells on 20 nm Si/PDMS are spherical, with fiber organization and FAs in undetectable levels. We explained the results of our in vitro studies through a shear-lag mechanical model. The calculated FA-substrate contact stiffnesses for fibroblasts on bulk Si and 220 nm Si/PDMS closely match, and they are significantly higher than the stiffness of the integrin clutches and the plaque. Conversely, focal contacts with 20 nm Si/PDMS have comparable lateral compliance to adhesion-mediating intracellular organisms. In conclusion, our work relies on recent advances in NM technology to fill a critical knowledge gap about how individual cells sense and react to the mechanical properties of NM-based substrates. Our findings will have a major impact on the design of flexible electronic materials for applications in biomedical science and health care.

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio , as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

GOALS The Advanced Radiotherapy Centers of UPMC San Pietro FBF of Rome (CC#1) and UPMC Villa Maria of Mirabella Eclano (CC#2) conducted a study to review variations in department workloads and workflows experienced during the pandemic. The potential relation between these variations and the new procedures introduced to prevent and contain the COVID-19 infection was also studied. MATERIALS AND METHODS The data used were obtained from reports present in the ARIA�� system (v. 15.1 Varian Medical Systems, Palo Alto, CA, U.S.A.). To examine the workloads was used the Downtime, an indicator that directly quantifies the inactivity of the department, derived from the ratio between the daily stand-by time of the LINACs (TrueBeam STx��, Varian Medical Systems, Palo Alto, CA, U.S.A.) and the mean number of treatments performed every day. In order to examine the workflows and possible delays, we measured the time between the treatments ("Therapy intervals"). RESULTS The Downtime average at CC#1 slightly increased from 3.1% in 2019 to 3.8% in 2020. However, the monthly analysis shows significant reduction (March-April-May) and increase (November-December) peaks. At CC#2, the 2020 Downtime trend was fairly consistent (average value: 3.3%), with an increase during the first wave of the pandemic. The "5-10 min" Therapy intervals at CC#1, reviewed comparing the March-April-May 2020 quarter with 2019, were higher in the first months and lower in May; the "10-15 min" intervals were stable; the ">20 min" intervals slightly increased in March 2020. At CC#2, the trend in 2020 decreased during the months of higher health care emergency and increased during the summer months. CONCLUSIONS The fact that the trends of the indicators show peaks only during the periods of major health care emergency indicates an impact of the pandemic, both on the workload and on the workflow. However, they also highlight the staff's ability to rapidly adapt to the new procedures, without affecting the overall performance of the both centers., Journal of Biomedical Practitioners, V. 5 N. 2 (2021)

INTRODUZIONE I successi della moderna radioterapia sono spesso guidati da elevati standard di qualit��. Questo studio punta a valutare percorsi di cura automatizzati e personalizzabili per definire nuovi indicatori di qualit�� quantitativi in radioterapia oncologica, al fine di ottimizzare l���efficienza e la sicurezza dei servizi erogati. MATERIALI E METODI Per questo studio, sono stati coinvolti due centri oncologici internazionali appartenenti allo stesso network (UPMC San Pietro di Roma (CC#1) ed UPMC Villa Maria di Mirabella Eclano (CC#2)), entrambi dotati di un acceleratore lineare ed uno scanner TC. L���analisi dei dati ha preso in considerazione il periodo compreso tra gennaio 2019 e dicembre 2019. Seguendo il workflow delle attivit�� di entrambi i centri, nello sviluppo della cartella clinica elettronica, sono stati creati dei modelli automatizzati adattabili alle differenti tipologie di trattamento, e quindi personalizzabili per ciascun paziente: utilizzando il software ARIA v15 (Varian Medical System, CA, Palo Alto, USA), abbiamo convertito tutti gli step del percorso di cura del paziente in moduli che hanno la possibilit�� di essere collegati per andare a formare il processo di cura del paziente stesso. I ���Carepaths��� infatti, rappresentano dei moduli in un processo automatizzato all���interno dei quali sono presenti attivit�� (���task���) e appuntamenti (���appointment���), aventi dei tempi di esecuzione ben definiti entro i quali devono essere completati elettronicamente. Per avere un riferimento in merito alle prestazioni in termini quantitativi riguardo i centri, abbiamo focalizzato l���attenzione su tre fattori: percentuale di attivit�� completate in relazione al tempo di esecuzione, giorni trascorsi e compliance dello staff con l���utilizzo di questo sistema automatizzato. RISULTATI La misurazione delle attivit�� completate consente di definire la conformit�� del processo automatizzato ai percorsi assistenziali, mentre le tempistiche del completamento delle attivit�� consentono di determinare le aree di miglioramento. In questo studio, i "Timeout" vengono sempre eseguiti con puntualit��, ma i risultati su "Peer Review" e "Treatment Approval" non sono soddisfacenti. Un tempo di ritardo definito ci consente di tenere traccia delle attivit�� in modo preciso, e l���analisi di questi valori in entrambi i centri oncologici presi in analisi, ci consente di capire se il tempo di consegna per le attivit�� �� appropriato o se c'�� un margine di miglioramento. Tutti i dati osservati mostrano che la percentuale di attivit�� completate in entrambi i centri oncologici e i tempi trascorsi per il completamento delle stesse sono differenti. CONCLUSIONI I percorsi assistenziali automatizzati, con i relativi moduli, possono essere uno strumento valido ed efficiente per misurare le attivit�� in un reparto di radioterapia oncologica, soprattutto se utilizzati come strumento di miglioramento continuo della qualit�� delle prestazioni., Journal of Biomedical Practitioners, V. 5 N. 2 (2021)

Reconfiguration of amorphous complex oxides provides a readily controllable source of stress that can be leveraged in nanoscale assembly to access a broad range of 3D geometries and hybrid materials. An amorphous SrTiO3 layer on a Si:B/Si1-x Gex :B heterostructure is reconfigured at the atomic scale upon heating, exhibiting a change in volume of ≈2% and accompanying biaxial stress. The Si:B/Si1-x Gex :B bilayer is fabricated by molecular beam epitaxy, followed by sputter deposition of SrTiO3 at room temperature. The processes yield a hybrid oxide/semiconductor nanomembrane. Upon release from the substrate, the nanomembrane rolls up and has a curvature determined by the stress in the epitaxially grown Si:B/Si1-x Gex :B heterostructure. Heating to 600 °C leads to a decrease of the radius of curvature consistent with the development of a large compressive biaxial stress during the reconfiguration of SrTiO3 . The control of stresses via post-deposition processing provides a new route to the assembly of complex-oxide-based heterostructures in 3D geometry. The reconfiguration of metastable mechanical stressors enables i) synthesis of various types of strained superlattice structures that cannot be fabricated by direct growth and ii) technologies based on strain engineering of complex oxides via highly scalable lithographic processes and on large-area semiconductor substrates.

Self-assembly of metal nanomembranes is presented as a viable avenue to fabricate helical slow-wave structures for millimeter-through- THz traveling wave tube amplifiers. The work coordinates three-dimensional simulations of cold helices and one-dimensional models of beam-wave interaction to determine a useful range of design parameters for the slow-wave structures. These parameters include diameter and pitch. Based on the simulation results, we fabricate prototype helices with microscale diameter and pitch. The nanomembrane stiffness and the built-in stress control the geometry of the helices.

We present simulations of a travelling wave tube amplifier based o n a self-winding helix f or o peration a t THz frequencies. Helix fabrication relies on guided self-assembly of conductive nanomembranes. The structure is modeled and simulated using CST Studio time domain and Particle in Cell solvers. The impact of meshing on the simulation results as well as simulation time is evaluated. Electric field distribution as well as gain at 1 THz are calculated for a 0.25 µm-thick helix forming a 1 mm-long travelling wave tube amplifier.

We investigate the interaction between an electron beam and a THz guided electromagnetic wave in a helical slow-wave structure formed by self-assembly of a conductive ribbon. We have previously shown the controlled fabrication of this slow-wave structure and its potential to form the basis for widely deployable millimeter-through-THz traveling-wave tube amplifiers. The process allows the fabrication of helical slow-wave structures with single and double chirality. Here, we use three-dimensional simulations to perform a comparative analysis of beam–wave interaction in self-assembled gold helices with single and double chirality. First, the structures are modeled without the electron beam (cold helices) to calculate the distribution of the electric field generated by the high-frequency wave. We perform simulations of cold helices by using Computer Simulation Technology Microwave Studio. Second, we evaluate the interaction between an electron beam and the THz travelingwave by using a particle in cell simulator in Computer Simulation Technology Particle Studio. Simulation studies show that a switch in chirality in the middle of self-assembled helices generates a reflected wave that boosts beam–wave interaction. We demonstrate that this efficient energy exchange will potentially provide high gain in THz traveling-wave tube amplifiers based on self-assembled helices.

Graphene nanostructures are attracting a great deal of interest because of newly emerging properties originating from quantum confinement effects. We report on using interferometric lithography to fabricate uniform, chip-scale, semiconducting graphene nanomesh (GNM) with sub-10 nm neck widths (smallest edge-to-edge distance between two nanoholes). This approach is based on fast, low-cost, and high-yield lithographic technologies and demonstrates the feasibility of cost-effective development of large-scale semiconducting graphene sheets and devices. The GNM is estimated to have a room temperature energy bandgap of ~30 meV. Raman studies showed that the G band of the GNM experiences a blue shift and broadening compared to pristine graphene, a change which was attributed to quantum confinement and localization effects. A single-layer GNM field effect transistor exhibited promising drive current of ~3.9 μA/μm and ON/OFF current ratios of ~35 at room temperature. The ON/OFF current ratio of the GNM-device displayed distinct temperature dependence with about 24-fold enhancement at 77 K.

Simple Summary Germ cell tumors are a model of curable solid tumors due to their unique sensitivity to cisplatin-based chemotherapy. Patients are typically young adults, and despite high cure rate, about 20% of them do not achieve remission or relapse, and 50% of them succumb to the disease. The mechanisms behind their resistance to therapy are largely unknown. By using Testicular Germ Cell Tumor (TGCT) cell lines as a model, we investigated the mechanism of acquired resistance to cisplatin. We demonstrated that resistance occurred by a fine modulation of the DNA repair pathway choice. Namely, in resistant cells, repair of double-strand breaks by non-homologous end joining was dampened by the reduced expression of TP53-binding protein 1 (53BP1) and DNA-dependent protein kinase (DNA-PKcs). However, cisplatin-induced damage was repaired efficiently by homologous recombination. Additionally, we demonstrate that pharmacological inhibition of poly (ADP-ribose) polymerase (PARP) combined with cisplatin had an additive/synergistic effect on cisplatin-resistant cells, which represents the proof of concept for introducing PARP inhibitors in salvage therapy. Abstract Despite germ cell tumors (GCTs) responding to cisplatin-based chemotherapy at a high rate, a subset of patients does not respond to treatment and have significantly worse prognosis. The biological mechanisms underlying the resistance remain unknown. In this study, by using two TGCT cell lines that have acquired cisplatin resistance after chronic exposure to the drug, we identified some key proteins and mechanisms of acquired resistance. We show that cisplatin-resistant cell lines had a non-homologous end-joining (NHEJ)-less phenotype. This correlated with a reduced basal expression of TP53-binding protein 1 (53BP1) and DNA-dependent protein kinase (DNA-PKcs) proteins and reduced formation of 53BP1 foci after cisplatin treatment. Consistent with these observations, modulation of 53BP1 protein expression altered the cell line’s resistance to cisplatin, and inhibition of DNA-PKcs activity antagonized cisplatin cytotoxicity. Dampening of NHEJ was accompanied by a functional increase in the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. As a result, cisplatin-resistant cells were more resistant to PARP inhibitor (PARPi) monotherapy. Moreover, when PARPi was given in combination with cisplatin, it exerted an additive/synergistic effect, and reduced the cisplatin dose for cytotoxicity. These results suggest that treatment of cisplatin-refractory patients may benefit from low-dose cisplatin therapy combined with PARPi.

We present a transformative route to obtain mass-producible helical slow-wave structures for operation in beam-wave interaction devices at THz frequencies. The approach relies on guided self-assembly of conductive nanomembranes. Our work coordinates simulations of cold helices (i.e., helices with no electron beam) and hot helices (i.e., helices that interact with an electron beam). The theoretical study determines electromagnetic fields, current distributions, and beam-wave interaction in a parameter space that has not been explored before. These parameters include microscale diameter, pitch, tape width, and nanoscale surface finish. Parametric simulations show that beam-wave interaction devices based on self-assembled and electroplated helices will potentially provide gain-bandwidth products higher than 2 dBTHz at 1 THz. Informed by the simulation results, we fabricate prototype helices for operation as slow-wave structures at THz frequencies, using metal nanomembranes. Single and intertwined double helices, as well as helices with one or two chiralities, are obtained by self-assembly of stressed metal bilayers. The nanomembrane stiffness and built-in stress control the diameter of the helices. The in-plane geometry of the nanomembrane determines the pitch, the chirality, and the formation of single vs intertwined double helices.

Background Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26–28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams–Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms. In the above-indicated interval at 7q11.23, defined as WBS critical region, several genes, such as GTF2I, BAZ1B, CLIP2 and EIF4H, emerged as critical for their role in the pathogenesis of WBS and 7Dup both from mouse models and human studies. Methods We performed a high-throughput screening of 1478 compounds, including central nervous system agents, epigenetic modulators and experimental substances, on patient-derived cortical glutamatergic neurons differentiated from our cohort of induced pluripotent stem cell lines (iPSCs), monitoring the transcriptional modulation of WBS interval genes, with a special focus on GTF2I, in light of its overriding pathogenic role. The hits identified were validated by measuring gene expression by qRT-PCR and the results were confirmed by western blotting. Results We identified and selected three histone deacetylase inhibitors (HDACi) that decreased the abnormal expression level of GTF2I in 7Dup cortical glutamatergic neurons differentiated from four genetically different iPSC lines. We confirmed this effect also at the protein level. Limitations In this study, we did not address the molecular mechanisms whereby HDAC inhibitors act on GTF2I. The lead compounds identified will now need to be advanced to further testing in additional models, including patient-derived brain organoids and mouse models recapitulating the gene imbalances of the 7q11.23 microduplication, in order to validate their efficacy in rescuing phenotypes across multiple functional layers within a translational pipeline towards clinical use. Conclusions These results represent a unique opportunity for the development of a specific class of compounds for treating 7Dup and other forms of intellectual disability and autism.

Testicular germ cell tumors (TGCTs) are typically exquisitely sensitive to DNA interstrand cross-link (ICLs) agents. ICLs covalently link both strands of the DNA duplex, impeding fundamental cellular processes like DNA replication to cause cell death. A leading drug used for the treatment of TGCTs is cisplatin, which introduces ICLs and leads to formation of double strand breaks (DSBs), a DNA lesion that can be repaired in the S/G2 phases of the cell cycle by homologous recombination (HR, also termed homology-direct repair). Although most TGCTs respond to cisplatin-induced ICLs, a fraction is resistant to treatment. One proposed mechanism of TGCT resistance to cisplatin is an enhanced ability to repair DSBs by HR. Other than HR, repair of the ICL-lesions requires additional DNA repair mechanisms, whose action might also be implemented in therapy-resistant cells. This chapter describes GFP assays to measure (a) HR proficiency following formation of a DSB by the endonuclease I-SceI, and (b) HR repair induced by site-specific ICL formation involving psoralen. These experimental approaches can be used to determine the proficiency of TGCT cell lines in DSB repair by HR in comparison to HR repair of ICLs, providing tools to better characterize their recombination profile. Protocols of these assays have been adapted for use in Embryonal Carcinoma (EC) TGCT cell lines. Assays only require transient introduction of plasmids within cells, affording the advantage of testing multiple cell lines in a relatively short time.

The adult mammalian brain is mainly composed of mature neurons. A limited amount of stem cell-driven neurogenesis persists in postnatal life and is reduced in large-brained species. Another source of immature neurons in adult brains is cortical layer II. These cortical immature neurons (cINs) retain developmentally undifferentiated states in adulthood, though they are generated before birth. Here, the occurrence, distribution and cellular features of cINs were systematically studied in 12 diverse mammalian species spanning from small-lissencephalic to large-gyrencephalic brains. In spite of well-preserved morphological and molecular features, the distribution of cINs was highly heterogeneous, particularly in neocortex. While virtually absent in rodents, they are present in the entire neocortex of many other species and their linear density in cortical layer II generally increased with brain size. These findings suggest an evolutionary developmental mechanism for plasticity that varies among mammalian species, granting a reservoir of young cells for the cerebral cortex., eLife, 9, ISSN:2050-084X

The present study was designed to test an emotion regulation framework to understand individual differences in personality disorder (PD) traits in a non-clinical sample. Specifically, we tested whether: selected dimensions of emotion dysregulation were differentially related to PD traits; and whether emotion dysregulation and impulsivity had independent associations with PD traits. A community sample of 399 individuals (mean age = 37.91; 56.6% males) completed self-report measures of PDs, emotion dysregulation and impulsivity. Emotion dysregulation facets and impulsivity had uniform bivariate associations with PD traits, but also evidenced unique associations in multiple regression analyses. Nonacceptance of emotional responses was the emotion dysregulation dimension underlying a wide array of PD. A limited repertoire of effective emotion regulation strategies was characteristic of cluster C PD, whereas emotional unawareness distinctly predicted schizoid PD. Antisocial PD traits were uniquely related to difficulties controlling impulsive behavior when upset. Finally, histrionic, narcissistic, and obsessive-compulsive PD were related to better self-reported emotion regulation. Impulsivity further explained a significant amount of variance in schizotypal, antisocial, borderline (positively), and obsessive-compulsive PD traits (negatively). If replicated in clinical samples, our findings will support the usefulness of targeting both emotional dysregulation and impulsivity in PDs psychotherapy.

While deficits in metacognition, or the ability to notice and reflect upon mental states has been observed in schizophrenia and linked with poorer concurrent and future function, it is unknown whether these deficits are unique to schizophrenia. Accordingly, this study assessed metacognition using the Metacognitive Assessment Scale-Abbreviated (MAS-A) and the Metacognitions Questionnaire- 30 (MCQ-30) among 26 adults with schizophrenia, 23 with bipolar disorder and 23 healthy controls. Symptom levels of the psychiatric groups were assessed with the Brief Psychiatric Rating Scale. ANCOVA controlling for age and education revealed that the schizophrenia group had lower scores on the MAS-A total and its subscales compared to the bipolar group and healthy controls. The bipolar disorder group also had lower MAS-A scores than the healthy control group. No group differences were found for the MCQ-30. Examination of symptom correlates revealed MAS-A scores were most commonly related to negative symptoms in both clinical groups. The total score and need for control subscale of MCQ-30 was related to total symptomatology and positive symptoms in patients with bipolar disorder. Correlations between the two measures of metacognition revealed that higher MAS-A scores were significantly related to lower scores on the Need to Control Thoughts MCQ-30 subscale.

The oxidation of Ge covered with graphene that is either grown on or transferred to the surface is investigated by X-ray photoelectron spectroscopy, Raman spectroscopy, and transmission electron microscopy. Graphene properly grown by chemical vapor deposition on Ge(100), (111), or (110) effectively inhibits room-temperature oxidation of the surface. When graphene is transferred to the Ge surface, oxidation is reduced relative to that on uncovered Ge but has the same power law dependence. We conclude that access to the graphene/Ge interface must occur via defects in the graphene. The excellent passivation provided by graphene grown on Ge should enhance applications of Ge in the electronic-device industry.

Objectives To determine (1) whether the serum concentration of 25-hydroxy vitamin D (25(OH)D 3 ) was associated with depression levels in people with chronic spinal cord injury (SCI) and (2) whether any observed association was independent of potential confounders. Design Cross-sectional study. Setting Rehabilitation institute. Participants Patients with chronic SCI (N=100) recruited consecutively. Interventions Not applicable. Main Outcome Measures Patients underwent clinical and biochemical evaluations, including assessment of 25(OH)D 3 levels and the presence and severity of depressive symptoms, by using the interviewer-assisted self-report Beck Depression Inventory-II (BDI-II). Results Depression (BDI-II score ≥14) was observed in 15 of 28 women (53.6%) and 18 of 72 men (25.0%) of the study population. They exhibited significantly lower 25(OH)D 3 levels, lower functional independence degree in performing activities of daily living, poorer engagement in leisure time physical activity, and higher body mass index. Lower 25(OH)D 3 levels were associated with higher BDI-II scores as well as with the occurrence of depression. These associations persisted after adjustment for all significant predictors of the BDI-II score that were selected, as possible confounders, by univariate analysis. In receiver operating characteristic analysis, a 25(OH)D 3 level of Conclusions In people with chronic SCI, an inverse association exists between serum 25(OH)D 3 levels and depressive symptoms, widely independent of potential confounders, especially those, peculiar to this population, that can mediate the effects of depression on vitamin D levels.

We established locally varying strain fields in unmodified MoS2 nanosheets. The approach relies on dry release in place of multilayer MoS2 on textured Si substrates. By this process we demonstrated intense photoluminescence, a ∼70 meV decrease of the transition energy, and exciton funneling in ∼4 nm-thick MoS2 films.

Introduction Comparative studies on differences in sexual function outcomes between homosexual and heterosexual men are sparse and inconclusive. Aim To systematically evaluate whether, and to what extent, a statistically significant difference exists in the odds of erectile dysfunction (ED) and premature ejaculation (PE) between homosexual and heterosexual men. Methods A thorough search of Medline, SCOPUS, CINAHL, and Web of Science databases was carried out to identify case-control studies comparing the prevalence of ED and PE in homosexual and heterosexual men. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Odds ratios (ORs) of reporting ED and PE were combined using random effect models. The Cochrane Q and I2 tests were carried out to analyze the between-studies heterogeneity. Funnel plots and trim-and-fill analysis were used to assess publication bias. Main Outcome Measures The relationship between sexual orientation and odds of ED and PE was assessed by calculating pooled ORs with a 95% CI. Results 4 studies included in the quantitative analysis collectively provided information on 1,807 homosexual and 4,055 heterosexual men. The pooled ORs indicated that homosexual orientation was associated with 1.5-fold higher odds of reporting ED (OR = 1.49, 95% CI = 1.03–2.16; P = .04) and 28.0% lower odds of reporting PE in comparison to the heterosexual orientation (OR = 0.72, 95% CI = 0.52–1.00; P = .05). However, a significant heterogeneity among the studies was observed. Funnel plots revealed a possible publication bias only for the ED analysis, where the trim-and-fill test detected a putative missing study. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a significantly higher risk of ED in the homosexual group (adjusted OR = 1.60, 95% CI = 1.10–2.30; P = .01). Clinical Implications These findings can drive future studies on sexual needs and concerns of homosexual men, which might not exactly match those of heterosexual individuals. Strength & Limitations This is the first meta-analysis exploring the differences in the prevalence of ED and PE between homosexual and heterosexual men. However, the results should be interpreted with caution, because their generalization could be hindered by the non-probabilistic nature of the samples, and a measurement bias could result from the use of different non-standardized indicators of sexual dysfunctions. Conclusion Homosexual orientation is associated with higher odds of ED and lower odds of PE compared with heterosexual orientation. Further studies are warranted to elucidate the clinical significance of these findings and whether they reflect differences in patterns of sexual lifestyle. Barbonetti A, D’Andrea S, Cavallo F, et al. Erectile Dysfunction and Premature Ejaculation in Homosexual and Heterosexual Men: A Systematic Review and Meta-Analysis of Comparative Studies. J Sex Med 2019;16:624–632.

Heterostructures consisting of two-dimensional (2D) materials and conventional semiconductors have attracted a lot of attention due to their application in novel device concepts. In this work, we investigated the lateral transport characteristics of graphene/germanium heterostructures and compared them with the transport properties of graphene on SiO2. The heterostructures were fabricated by transferring a single layer of graphene (Gr) onto a lightly doped germanium (Ge) (100) substrate. The field-effect measurements revealed a shift in the Dirac voltage of Gr on the Ge substrates compared to that of the Gr on SiO2. Transfer length model measurements show a significant difference in the sheet resistance of Gr on Ge compared to that of the Gr on SiO2. The results from the electrical and structural characterization suggest that a charge transfer in the order of 1012 cm–2 occurs between Gr and Ge resulting in a doping effect in the graphene sheet. A compact electrostatic model extracted the key electronic pr...

DNA double-strand breaks (DSBs) are known to be powerful inducers of homologous recombination (HR), but single-strand breaks (nicks) have also been shown to trigger HR. Both DSB- and nick-induced HR (nickHR) are exploited in advanced genome-engineering approaches based on the bacterial RNA-guided nuclease Cas9. However, the mechanisms of nickHR are largely unexplored. Here, we applied Cas9 nickases to study nickHR in mammalian cells. We find that nickHR is unaffected by inhibition of major damage signaling kinases and that it is not suppressed by nonhomologous end-joining (NHEJ) components, arguing that nick processing does not require a DSB intermediate to trigger HR. Relative to a single nick, nicking both strands enhances HR, consistent with a DSB intermediate, even when nicks are induced up to ∼1kb apart. Accordingly, HR and NHEJ compete for repair of these paired nicks, but, surprisingly, only when 5' overhangs or blunt ends can be generated. Our study advances the understanding of molecular mechanisms driving nick and paired-nick repair in mammalian cells and clarify phenomena associated with Cas9-mediated genome editing.

A search is presented for long-lived charged particles that decay within the volume of the silicon tracker of the CMS experiment. Such particles can produce events with an isolated track that is missing hits in the outermost layers of the silicon tracker, and is also associated with little energy deposited in the calorimeters and no hits in the muon detectors. The search for events with this “disappearing track” signature is performed in a sample of proton-proton collisions recorded by the CMS experiment at the LHC with a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 101 fb − 1 recorded in 2017 and 2018. The observation of 48 events is consistent with the estimated background of 47.8 − 2.3 + 2.7 (stat) ± 8.1 (syst) events. Upper limits are set on chargino production in the context of an anomaly-mediated supersymmetry breaking model for purely wino and higgsino neutralino scenarios. At 95% confidence level, the first constraint is placed on chargino masses in the higgsino case, excluding below 750 (175) GeV for a lifetime of 3 (0.05) ns. In the wino case, the results of this search are combined with a previous CMS search to produce a result representing the complete LHC data set recorded in 2015–2018, the most stringent constraints to date. At 95% confidence level, chargino masses in the wino case are excluded below 884 (474) GeV for a lifetime of 3 (0.2) ns.

We fabricated and characterized disorder-free GaSb photovoltaic devices on Si. The fabrication process relies on epitaxial lift-off of pixelated GaSb membranes from GaSb substrates and their transfer onto Si. We demonstrated that our approach maintains the structural integrity and optoelectronic functionality of the GaSb absorbers after the epitaxial transfer. The performance parameters of the pixelated solar cells are V oc ~ 0.1V, J sc ~ 17 mA/cm2, FF ~ 29% and h~ 1.2%, which compare favorably to the characteristics of a 5x5 mm2, GaSb solar cells on a GaSb substrate.

In diverse applications employing very thin, single-crystalline semiconductor sheets, including flexible electronics and photonics, energy-storage devices, and solar cells, the impacts of surfaces and interfaces on charge transport need to be understood. The authors study the electrical conductance of very thin Si(001) sheets using a special, sensitive back-gating method, to quantify the influence of H termination on conductance for sheets of different thickness, and confirm that surface states play a dominant role in these conductance properties. Their approach is extensible to other important systems, $e.g.$ $I\phantom{\rule{0}{0ex}}I\phantom{\rule{0}{0ex}}I-V$ semiconductors and transition-metal dichalcogenides.

Summary Nanostructured origami is rapidly transitioning from an elegant technique to fabricate exquisite structures to a platform for integrating novel functionality into crystalline nanomembranes. Nanomembranes, with mechanical properties of typical sheets, can be bent, rolled, and twisted, to return to their original shape, while maintaining their single-crystal nature. The field has advanced from semiconductor bilayer microtubes 15 years ago to quite complex 3D kirigami and origami shapes that demonstrate the potential of 3D devices with unique electronic, optoelectronic, or electromagnetic function.

Friedreich ataxia is an inherited neurodegenerative disease that leads to progressive disability. There is currently no effective treatment and patients die prematurely. The underlying genetic defect leads to reduced expression of the mitochondrial protein frataxin. Frataxin insufficiency causes mitochondrial dysfunction and ultimately cell death, particularly in peripheral sensory ganglia. There is an inverse correlation between the amount of residual frataxin and the severity of disease progression; therefore, therapeutic approaches aiming at increasing frataxin levels are expected to improve patients' conditions. We previously discovered that a significant amount of frataxin precursor is degraded by the ubiquitin/proteasome system before its functional mitochondrial maturation. We also provided evidence for the therapeutic potential of small molecules that increase frataxin levels by docking on the frataxin ubiquitination site, thus preventing frataxin ubiquitination and degradation. We called these compounds ubiquitin-competing molecules (UCM). By extending our search for effective UCM, we identified a set of new and more potent compounds that more efficiently promote frataxin accumulation. Here we show that these compounds directly interact with frataxin and prevent its ubiquitination. Interestingly, these UCM are not effective on the ubiquitin-resistant frataxin mutant, indicating their specific action on preventing frataxin ubiquitination. Most importantly, these compounds are able to promote frataxin accumulation and aconitase rescue in cells derived from patients, strongly supporting their therapeutic potential., Highlights • New therapeutic strategy to treat Friedreich ataxia • New ubiquitin-competing molecules (UCM) directly target frataxin protein • UCM prevent frataxin ubiquitination and degradation • UCM increase frataxin and rescue aconitase in cells derived from patients

We established locally varying strain fields in unmodified MoS

International audience; Heterostructures consisting of two-dimensional (2D) materials and conventional semiconductors have attracted a lot of attention due to their application in novel device concepts. In this work, we investigated the lateral transport characteristics of graphene/germanium heterostructures and compared them with the transport properties of graphene on SiO2. The heterostructures were fabricated by transferring a single layer of graphene (Gr) onto a lightly doped germanium (Ge) (100) substrate. The field-effect measurements revealed a shift in the Dirac voltage of Gr on the Ge substrates compared to that of the Gr on SiO2. Transfer length model measurements show a significant difference in the sheet resistance of Gr on Ge compared to that of the Gr on SiO2. The results from the electrical and structural characterization suggest that a charge transfer in the order of 1012 cm–2 occurs between Gr and Ge resulting in a doping effect in the graphene sheet. A compact electrostatic model extracted the key electronic properties of the Gr/Ge interface. This study provides valuable insights into the electronic properties of Gr on Ge, which are vital to the development of novel devices based on mixed 2D and 3D structures.

Neurons are often cultured in vitro on a flat, open, and rigid substrate, a platform that does not reflect well the native microenvironment of the brain. To address this concern, we have developed a culturing platform containing arrays of microchannels, formed in a crystalline-silicon nanomembrane (NM) resting on polydimethylsiloxane; this platform will additionally enable active sensing and stimulation at the local scale, via devices fabricated in the silicon. The mechanical properties of the composite Si/compliant substrate nanomaterial approximate those of neural tissue. The microchannels, created in the NM by strain engineering, demonstrate strong guidance of neurite outgrowth. Using plasma techniques, we developed a means to coat just the inside surface of these channels with an adhesion promoter (poly-d-lysine). For NM channels with openings larger than the cross-sectional area of a single axon, strong physical confinement and guidance of axons through the channels are observed. Imaging of axons that grow in channels with openings that approximate the size of an axon suggests that a tight seal exists between the cell membrane and the inner surface of the channel, mimicking a myelin sheath. Such a tight seal of the cell membrane with the channel surface would make this platform an attractive candidate for future neuronal repair. Results of measurements of impedance and photoluminescence of bare NM channels are comparable to those on a flat NM, demonstrating electrical and optical modalities of our platform and suggesting that this scaffold can be expanded for active sensing and monitoring of neuron cellular processes in conditions in which they exist naturally.

The controlled application of strain in crystalline semiconductors can be used to modify their basic physical properties to enhance performance in electronic and photonic device applications. In germanium, tensile strain can even be used to change the nature of the fundamental energy band gap from indirect to direct, thereby dramatically increasing the interband radiative efficiency and allowing population inversion and optical gain. For biaxial tension, the required strain levels (around 2%) are physically accessible but necessitate the use of very thin crystals. A particularly promising materials platform in this respect is provided by Ge nanomembranes, that is, single-crystal sheets with nanoscale thicknesses that are either completely released from or partially suspended over their native substrates. Using this approach, Ge tensilely strained beyond the expected threshold for direct-band gap behavior has recently been demonstrated, together with strong strain-enhanced photoluminescence and evidence of population inversion. We review the basic properties, state of the art, and prospects of tensilely strained Ge for infrared photonic applications.

We investigated the effects of femtosecond, multi-pulse laser exposure on the structural changes in an Er3+-doped and heavy-metal co-doped, SiO2-based oxide glass. We analyzed microstructural alterations in the glass network and we monitored the formation of defects resulting from variable laser exposure conditions. To elucidate the subtle differences in glass network reorganization, generated by two laser irradiation wavelengths, we used Raman spectroscopy. We demonstrate how to decouple the very weak luminescence signals of laser-generated optically-active defects from the dominating emission of Er3+. We discuss the relationship between the initial and the irradiation-modified glass microstructure, including bond breaking, the formation of optically active defects and defect-assisted densification build-up in the glass network.

We successfully demonstrate new heavy metal-gallium-doped oxide glass media, which are capable of accommodating a significant level of Er3+ doping, while avoiding the deleterious effects of concentration quenching. We examine the effects of composition and microstructure of the glass networks on optical properties. Near-infrared and visible emission demonstrate the absence of concentration quenching and Er3+ clustering. Both Raman spectroscopy and X-ray absorption fine structure spectroscopy confirm that gallium enters the glass as a tetrahedral network former. The incorporation of gallium into the glass modifies the energy landscape and creates two distinct crystal field environments, which promote Er3+ radiative transitions.

Buckling and wrinkling of thin films on a compliant material has proved to be a resource in several applications, such as flexible electronics, thin-film metrology and fabrication of tunable optical components. A versatile approach for the fabrication of two-dimensional and linear arrays of buckled structures is demonstrated here using a stiff material, in the form of a nanomembrane, on a compliant substrate. The novelty of the fabrication process is that the substrates are strained by isotropic volume expansion in solvents. This work illustrates in detail the potential of our technology to fabricate ordered arrays of 3D structures on large-area compliant substrates, with important implications for a large number of fields. Furthermore, this paper discusses the interesting interface chemistry and mechanics leading to controllable and reproducible fabrication of our 3D structures.

Inhibition of the RAD51 homologous recombination factor prevents the repair of AID-initiated DNA breaks and induces apoptosis preferentially in AID-expressing human CLL., Activation-induced cytidine deaminase (AID) is critical in normal B cells to initiate somatic hypermutation and immunoglobulin class switch recombination. Accumulating evidence suggests that AID is also prooncogenic, inducing cancer-promoting mutations or chromosome rearrangements. In this context, we find that AID is expressed in >40% of primary human chronic lymphocytic leukemia (CLL) cases, consistent with other reports. Using a combination of human B lymphoid leukemia cells and mouse models, we now show that AID expression can be harnessed for antileukemic effect, after inhibition of the RAD51 homologous recombination (HR) factor with 4,4′-diisothiocyanatostilbene-2-2′-disulfonic acid (DIDS). As a proof of principle, we show that DIDS treatment inhibits repair of AID-initiated DNA breaks, induces apoptosis, and promotes cytotoxicity preferentially in AID-expressing human CLL. This reveals a novel antineoplastic role of AID that can be triggered by inhibition of HR, suggesting a potential new paradigm to treat AID-expressing tumors. Given the growing list of tumor types with aberrant AID expression, this novel therapeutic approach has potential to impact a significant patient population.

Antimonide compounds are fabricated in membrane form to enable materials combinations that cannot be obtained by direct growth and to support strain fields that are not possible in the bulk. InAs/(InAs,Ga)Sb type II superlattices (T2SLs) with different in-plane geometries are transferred from a GaSb substrate to a variety of hosts, including Si, polydimethylsiloxane, and metal-coated substrates. Electron microscopy shows structural integrity of transferred membranes with thickness of 100 nm to 2.5 μ m and lateral sizes from 24 × 24 μ m2 to 1 × 1 cm2. Electron microscopy reveals the excellent quality of the membrane interface with the new host. The crystalline structure of the T2SL is not altered by the fabrication process, and a minimal elastic relaxation occurs during the release step, as demonstrated by X-ray diffraction and mechanical modeling. A method to locally strain-engineer antimonide-based membranes is theoretically illustrated. Continuum elasticity theory shows that up to ∼ 3.5% compressive strain can be induced in an InSb quantum well through external bending. Photoluminescence spectroscopy and characterization of an IR photodetector based on InAs/GaSb bonded to Si demonstrate the functionality of transferred membranes in the IR range.

p21 is a well-established regulator of cell cycle progression. The role of p21 in DNA repair, however, remains poorly characterized. Here, we describe a critical role of p21 in a replication-coupled DNA double-strand break (DSB) repair that is mechanistically distinct from its cell cycle checkpoint function. We demonstrate that p21-deficient cells exhibit elevated chromatid-type aberrations, including gaps and breaks, dicentrics and radial formations, following exposure to several DSBinducing agents. p21 � /� cells also exhibit an increased DNA damage-inducible DNA-PKCS S2056 phosphorylation, indicative of elevated nonhomologous DNA end joining. Concomitantly, p21 � /� cells are defective in replication-coupled homologous recombination (HR), exhibiting decreased sister chromatid exchanges and HRdependent repair as determined using a crosslinked GFP reporter assay. Importantly, we establish that the DSB hypersensitivity of p21 � /� cells is associated with increased cyclin-dependent kinase (CDK)-dependent BRCA2 S3291 phosphorylation and MRE11 nuclear foci formation and can be rescued by inhibition of CDK or MRE11 nuclease activity. Collectively, our results uncover a novel mechanism by which p21 regulates the fidelity of replication-coupled DSB repair and the maintenance of chromosome stability distinct from its role in the G1-S phase checkpoint.

Wafer level integration of photonic detectors on a silicon substrate is expected to dramatically bring down the cost of detectors. State-of-the-art manufacturing of focal plane arrays (FPA) is based on wafer level processing including mesa delineation, surface passivation, metal evaporation, and indium deposition, followed by a die-level fabrication with dicing, flip-chip bonding to a silicon read-out integrated circuit, substrate thinning/removal, and packaging.i The latter steps are low-yield processesii that dramatically increase the cost and fabrication time. In the recent past, significant advancements have been made in the field of III-V materials integration onto alternate substrates, which are cheaper and easy to manufacture.

We present an approach to realize antimonide based superlattices on silicon substrates without using conventional Indium-bump hybridization. In this approach, PIN based superlattice detectors are grown on top of a 60 nm Al0.6Ga0.4Sb sacrificial layer on a GaSb host substrate. Following the growth, the individual pixels are transferred using our epitaxiallift off technique, which consists of a wet-etch to undercut the pixels followed by a dry-stamp process to transfer the pixels to a silicon substrate prepared with a gold layer. Structural and optical characterization of the transferred pixels was done using an optical microscope, scanning electron microscopy and photoluminescence. The interface between the transferred pixels and the new substrate was abrupt and no significant degradation in the optical quality was observed. An Indium-bump-free membrane detector was then fabricated using this approach. Spectral response measurements provided a 100% cut-off wavelength of 4.3 μm at 77 K. The performance of the membrane detector was compared to a control detector on the as-grown substrate. The membrane detector was limited by surface leakage current. The proposed approach could pave the way for wafer-level integration of photonic detectors on silicon substrates, which could dramatically reduce the cost of these detectors.

There is a need to better understand the antecedent of aggressive behaviors in order to tailor treatments and reduce the associated damage to the others and the self. Possible mechanisms underlying aggression are poor emotional awareness and emotion dysregulation, as well as impulsivity. Here, we examined the relationships among alexithymia, emotion dysregulation, impulsivity and aggression, comparing a mixed psychiatric sample (N=257) and a community sample (N=617). The clinical sample reported greater levels of alexithymia, emotion dysregulation, trait impulsivity and aggression, than the community sample. Furthermore, in the community sample, emotion dysregulation and impulsivity mediated the relationship (i.e., accounted for the shared variance) between alexithymia and aggression. In the clinical sample, only emotion dysregulation explained the alexithymia-aggression link. In particular, specific dimensions of the emotion dysregulation (i.e., Negative Urgency) and impulsivity constructs (i.e., cognitive and motor impulsivity) played a unique role in explaining these associations. Finally, controlling for depressive symptoms reduced some of the findings involving impulsivity to nonsignificant results. Overall, our findings add to the extant literature attesting to the relevance of alexithymia and emotion dysregulation for understanding aggression, and providing concrete recommendation for the treatment and prevention of aggressive tendencies.

The aim of this research is to identify the characteristics of interpersonal and social relations that are established within the Spinal Unit of the “San Raffaele, Sulmona”. The methods that have been used are “Sociogram” by Moreno as well as individual interviews, direct and indirect observation. The sample is composed of 15 para- and quadriplegic patients of the Spinal Unit (6 females and 9 males). From the sociogram and the analysis of the leader’s and the refused member’s personality characteristics we were able in the first place to identify the difficulties of the spinal group, and also to structure future interventions to decrease the difficulties and aid compliance to treatment, rehabilitation and quality of the Department life.