Field and genetic evidence support the photosynthetic performance index (PIABS) as an indicator of rice grain yield.

The rice breeding process for grain yield could be effectively enhanced by developing efficient tools that accelerate plant selection through the rapid determination of reliable predictors. In this study, we have described various associations between grain yield and photosynthetic parameters, which can be easily and quickly obtained using a non-invasive technique on the flag leaf during the anthesis stage. Among the analyzed photosynthetic parameters, the photosynthetic performance index (PIABS) stood out due to its strong association with grain yield. A genome-wide association analysis conducted on plants from a rice diversity panel at the tillering stage revealed the presence of a quantitative trait locus on chromosome 9. This locus was characterized by a group of candidate chloroplastic genes that exhibited contrasting haplotypes for PIABS. An analysis of these haplotypes revealed a clear division into two groups. One group consisted of haplotypes linked to high values of PIABS, which were predominantly associated with Japonica spp. subpopulations. The other group consisted of haplotypes linked to low values of PIABS, which were exclusively associated with Indica spp. subpopulations. Japonica spp. genotypes exhibited higher values in the yield component panicle weight compared with the Indica spp. genotypes. The findings of this study indicate that PIABS could serve as an early predictor of yield parameters during the tillering stage in rice breeding processes.

Potentially under-recognized late-stage physical and psychosexual complications of non-therapeutic neonatal penile circumcision: a qualitative and quantitative analysis of self-reports from an online community forum.

The removal of non-pathogenic foreskin from the penis of healthy neonates and infants for non-religious reasons is routinely practiced in many parts of the world. High level data from well-designed randomized controlled trials of circumcision in neonates and infants does not guide clinical practice. Reliable counts of immediate and short term circumcision complications are difficult to estimate. Emerging evidence suggests routine neonatal circumcision could lead to long term psychological, physical, and sexual complications in some men. The stigma associated with discussing circumcision complications creates a prevalence paradox where the presence of significant circumcision complications is higher than reported. Prior to the Internet, there were very few forums for men from diverse communities, who were troubled about their circumcision status, to discuss and compare stories. To investigate the long term consequences of circumcision, we reviewed 135 posts from 109 individual users participating in a circumcision grief subsection of Reddit, an internet discussion board. We identified three major categories of complications: physical such as pain during erections and lost sensitivity, psychological such as anxiety and violation of autonomy, and sexual such as feeling that the sexual experience was negatively altered or being unable to complete a sexual experience. We also identified a "discovery process" where some men described coming into awareness of their circumcision status. These findings suggest that neonatal circumcision can have significant adverse consequences for adult men. The removal of normal foreskin tissue should be limited to adult men who choose the procedure for cosmetic reasons or when medically indicated.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.

Patterns of physiological parameters and nitrogen partitioning in flag leaf explain differential grain protein content in rice.

The grain protein content (GPC) in rice is low, and more efforts with agronomic and molecular approaches were performed to increase them. However, the rice research focusing on the plant physiological behaviour that modulates the phenomenon of grain protein filling is very scarce. This work contains physiological parameters related to photosynthetic activity in the flag leaf in the grain filling period and N partitioning assays of high (Nutriar) and traditional (Camba) GPC cultivars. Results indicated a higher photosynthetic capacity, a better capacity to provide CO2 to the chloroplast and a healthier PSII structure in Camba relative to Nutriar. Chlorophyll fluorescence parameters decreased more steeply over time in the high protein variety, and a strong negative correlation was observed between GPC and PSII structure parameters. N content in the flag leaf at anthesis showed lower values and higher remobilisation during the grain filling period in Nutriar compared to Camba. The results of this work suggested that the inactivation of some PSII structures in higher GPC cultivars is associated with N remobilisation and would contribute to an increase in the free N available to be translocated to the grain.

Stem canker caused by Phomopsis spp. Induces changes in polyamine levels and chlorophyll fluorescence parameters in pecan leaves.

Pecan plants are attacked by the fungus Phomopsis spp. that causes stem canker, a serious and emerging disease in commercial orchards. Stem canker, which has been reported in several countries, negatively affects tree canopy health, eventually leading to production losses. The purpose of this study was to inquire into the physiology of pecan plants under stem canker attack by Phomopsis spp. To this end, pecan plants were inoculated with an isolate of Phomopsis spp. and several parameters, such as polyamines, proline, sugars, starch, chlorophyll fluorescence and canopy temperature were analysed. Under artificial inoculation, a high disease incidence was observed with symptoms similar to those in plants showing stem canker under field conditions. Furthermore, the infected stem showed dead tissue with brown necrotic discolouration in the xylem tissue. The free polyamines putrescine, spermidine, and spermine were detected and their levels decreased as leaves aged in the infected plants with respect to the controls. Chlorophyll fluorescence parameters, such as Sm, ψEO, and QbRC decreased under plant infection and therefore the K-band increased. Canopy temperature and proline content increased in the infected plants with respect to the controls while sugar content decreased. These data suggest that stem canker caused by Phomopsis spp. induces physiological changes that are similar to those observed in plants under drought stress. To our knowledge, this is the first study that documents the physiological and biochemical effects derived from pecan-Phomopsis interaction.

M-TRAP: Safety and performance of metastatic tumor cell trap device in advanced ovarian cancer patients.

OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.

Including Medical Management in the Urologic Approach to Idiopathic Retroperitoneal Fibrosis.

OBJECTIVE: To characterize the timing and effectiveness of medical management in resolving stent-dependent ureteral compression secondary to idiopathic retroperitoneal fibrosis (RPF), the long-term relevant outcomes, and the side effects of treatment. METHODS: A retrospective review of RPF patients diagnosed from 2002-2018 was performed. Patients with hydronephrosis due to ureteral involvement that were managed with medication and with temporary stenting as needed, but without initial ureterolysis, were included. Patient demographics and RPF management details were obtained, including the following subsequent events: ureterolysis, nephrectomy, recurrent upper tract obstruction, and medication side effects. RESULTS: Fifty-two patients met inclusion criteria. Resolution of ureteral obstruction with medical management and temporary renal drainage as needed occurred in 36 (69%) patients with a median stent duration of 16 months, and median clinical and radiographic follow up of 4.2 and 3.3 years, respectively. Recurrent obstruction after a stent-free period occurred in 9 (18%) patients. Ureterolysis was performed in 8 (15%) patients at a median of 2.2 years for medication intolerance, lack of radiographic response to medication, or persisting pain. Potential medication side effects occurred in 6 (12%) patients. CONCLUSIONS: Medical management supported successful resolution of ureteral obstruction in 69% of patients without the need for ureterolysis after temporary renal drainage using stents, with rare incidence of worsening renal dysfunction or medication side effect. To date, this is the largest reported series of systematically managed RPF patients with obstructive uropathy receiving initial medical therapy and serves to counsel patients and advise urologists and nephrologists of the expected course and advantages and disadvantages of medical versus surgical management.

Voiding recovery after radical parametrectomy in cervical cancer patients: An international prospective multicentre trial - SENTIX.

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in <7 days and 293 (97.7%) in <30 days. Only seven (2.3%) patients recovered after >30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

Laparoscopic Power Morcellation: Techniques to Avoid Tumoral Spread.

STUDY OBJECTIVE: To show 3 different techniques for achieving an endobag morcellation without adding extra time and cost to the surgery. DESIGN: Stepwise demonstration of the 3 techniques with narrated video footage. SETTING: Morcellation is a useful procedure for fragmenting and extracting specimens during laparoscopic surgery without the need to perform a laparotomy. Patients who otherwise would not be eligible for minimally invasive surgery (i.e., those with a large uterus or myomas) could benefit from laparoscopic advantages. However, morcellation has a major limitation: the risk of dissemination of unsuspected malignancies. In 2017, the Food and Drug Administration released an updated assessment of the use of laparoscopic power morcellators for treatment of leiomyomas. A total of 23 studies were included in the analysis, and 20 studies (90 910 women) contributed to the estimated prevalence of leiomyosarcoma at the time of surgery for presumed leiomyomas. Depending on the modeling methodology used, the estimated prevalence of uterine sarcoma was 1 in 305 to 1 in 360 women, and for leiomyosarcoma, the estimated prevalence was 1 in 570 to 1 in 750 women [1]. Currently available evidence has suggested that if an undiagnosed uterine malignancy is intra-abdominally morcellated, there is a risk of intraperitoneal dissemination of the disease [2]. Therefore, the European Society of Gynecological Oncology emitted a statement in 2016 recommending avoiding morcellation if there is any suspicion of sarcoma and using endobag containers for morcellation of the surgically removed uterine myomas [3]. In addition, in the United States, the Food and Drug Administration recommends performing laparoscopic power morcellation for myomectomy or hysterectomy only with a tissue containment system, legally marketed in the United States [4]. INTERVENTIONS: There are several techniques described in the literature for contained uterine myomas morcellation [5]. In this video, we present 3 of them: First, an indirect-view morcellation is described. In this technique, we placed the myoma in the bag and exteriorize it through one of the trocars. Once outside the abdomen, we placed the morcellator through the bag opening and did the morcellation inside the bag while checking through the umbilicus camera. Special attention must be paid to avoid any damage to the bag because the visualization is limited in this technique. Second, a direct-view technique is described, in which we exteriorized the opening of a 15-mm bag through the suprapubic trocar and a closed end of the bag through the umbilicus. We made a hole in the umbilicus end of the bag and introduced the camera trocar through it. Once done, we introduced the morcellator through the opening and the camera in the umbilicus port. Third, a single-port-contained morcellation is explained. The bag was exteriorized through the umbilicus, and a skin retractor was placed. A glove was placed outside the retractor to isolate the bag. Once placed, 2 of the fingers were opened and used as trocars (one for the morcellator and the other for a 30° camera). After using this technique, the scope should be replaced to minimize the risk of contamination. The following are possible limitations of each technique: in the indirect-view technique, owing to the limited visualization, the surgeon must pay special attention to avoid tearing the bag while morcellating the specimen. In the direct-view technique method, the surgeon needs to ensure the proper closure of the bag before removing it from the abdomen to avoid possible dissemination risk. Finally, in the single-port technique, the surgeon must have previous experience in this type of approach, minimizing the risk of contamination by changing the scope after the morcellation process. CONCLUSION: Laparoscopic power morcellation may provide several benefits for our patients, when performing a hysterectomy or a multiple myomectomy. We presented 3 different and feasible techniques for laparoscopic power morcellation using an endobag container.

Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker.

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

Dragonflies and damselflies (Odonata) from Puerto Rico: a checklist with notes on distribution and habitat.

BACKGROUND: Conservation of tropical freshwater fauna requires a solid understanding of species biodiversity patterns. We provide an up to date annotated list of Odonata of Puerto Rico, which is based on current reports. The list is complemented with notes on the geographic and altitudinal distribution of this order on the island. We also compare current composition relative to early reports conducted when Puerto Rico was mostly an agricultural region. METHODS: We surveyed adult Odonata all over Puerto Rico with the aid of undergraduate students. Students were trained on capturing, preserving, and data basing specimens. All material was centralized, identified by the lead author, and deposited in the Zoology Museum at the University of Puerto Rico (MZUPR), Río Piedras campus. Surveys were complemented with focal collections by the authors and a literature review of published records for Puerto Rico and the Caribbean. We requested records from specialists to obtain the most complete list of species for the island. RESULTS: An annotated list of Odonata from Puerto Rico is presented, reporting 49 species distributed in two suborders and four families. We provide information on species distribution among municipalities and elevations around Puerto Rico. A historic list of species was developed for the 1930s-1940s, when agriculture covered most of Puerto Rico, based on literature and museum specimens. Both current and historic records are similar and suggest that the Odonata fauna is dominated by generalist species and has changed little since the agricultural period. Our list provides a point of reference to understand biodiversity patterns in Puerto Rico and the Caribbean and for assessing the effects of land use change on aquatic insect diversity.

COVID-19: gynecologic cancer surgery at a single center in Madrid.

OBJECTIVES: While numerous medical facilities have been forced to suspend oncological surgery due to system overload, debate has emerged on using non-surgical options on cancer cases during the pandemic. The goal of our study was to analyze, in a retrospective cohort study, the results of gynecological cancer surgery and evaluate postoperative complications in a single center in one of the most affected areas in Europe. METHODS: We retrospectively analyzed the records of patients who were referred between March 2020 and May 2020 for primary surgical treatment of breast, endometrial, ovarian, cervical, or vulvar cancer. RESULTS: The study included a total of 126 patients. Median age was 60 years (range 29-89). Patients were referred with breast (76/126, 60.3%), endometrial (29/126, 23%), ovarian (14/126, 11.1%), cervical (5/126, 4%), or vulvar cancer (2/126, 1.6%). Polymerase chain reaction (PCR) test for detection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was only conducted in 50% of cases due to the low availability of tests during the first phase of our study, and was indicated only in suspected cases according to the healthcare authorities' protocol. Median hospital stay was 1 day (range 0-18). Excluding breast surgery, laparoscopy was the most used procedure (43/126, 34.1%). 15 patients had a postoperative complication (15/126, 11.9%); only in 2 patients (2/15 13.3%) were there reports of Clavien-Dindo grade 3 or 4 complications. 6 patients tested positive for COVID-19 following a PCR diagnostic test, and these surgeries were cancelled. CONCLUSIONS: Adequate protective measures in the setting of COVID-19 free institutions enabled the continuity of cancer surgery without significant compromise of the safety of patients or healthcare workers.

Diagnostic Accuracy of Interferon Gamma-Induced Protein 10 mRNA Release Assay for Tuberculosis.

Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.

Close relationship between the state of the oxygen evolving complex and rice cold stress tolerance.

The results of the present work suggested a relationship between the growth stability and functional/structural parameters associated to the primary photochemistry and oxygen evolving complex (OEC) in tolerant rice plants under suboptimal low temperatures (SLT) stress. This was concluded from the absence of changes in net photosynthetic rate and in fraction of reaction centers to reduce quinone A, and very small changes in P680 efficiency to trap and donate electrons to quinone A and in fraction of active OEC in tolerant plants under cold stress but not in sensitive plants. The SLT stress also induced OEC activity limitations in both genotypes, but in a greater extent in sensitive plants. However, an assay using an artificial electron donor to replace OEC indicated that the P680+ capacity to accept electrons was not altered in both genotypes under SLT stress from the beginning of the stress treatment, suggesting that the OEC structure stability is related to rice SLT tolerance to sustain the photosynthesis. This hypothesis was also supported by the fact that tolerant plants but not sensitive plants did not alter the gene expression and protein content of PsbP under SLT stress, an OEC subunit with a role in stabilizing of OEC structure.

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Genomic Profiling of Uterine Aspirates and cfDNA as an Integrative Liquid Biopsy Strategy in Endometrial Cancer.

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the efficacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapies.

Increased Risk of Hypogonadal Symptoms in Shift Workers With Shift Work Sleep Disorder.

OBJECTIVE: To examine the association between shift work sleep disorder (SWSD), a primary circadian rhythm disorder characterized by excessive day-time sleepiness associated with shift work, and hypogonadal symptoms in shift workers. METHODS: Men presenting to an andrology clinic between July 2014 and June 2017 completed questionnaires assessing shift work schedule, SWSD risk, and hypogonadal symptoms ([quantitative] Androgen Deficiency in the Aging Male [qADAM, ADAM]). The impact of nonstandard shift work and SWSD on responses to qADAM and ADAM was assessed using ANOVA and linear regression. RESULTS: About 24.1% (619/2571) of men worked nonstandard shifts. Of those, 196 (31.7%) were considered to have SWSD. Controlling for age, comorbidities, and testosterone (T) levels, nonstandard shift workers had qADAM scores 1.12 points lower than day-time workers (P <.01). Subgroup analysis of nonstandard shift workers showed that those with SWSD had qADAM scores 5.47 points lower than men without SWSD (P <.01). In this same subgroup analysis, SWSD was independently associated with lower T levels (mean decrease 100.4 ng/dL, P <.01) when controlling for age, comorbidities, and prior T supplementation. CONCLUSION: Nonstandard shift workers with SWSD have even worse hypogonadal symptoms and lower T levels than day-time workers and nonstandard shift workers without SWSD. This suggests that poor sleep habits, as identified by SWSD, may contribute to the more severe hypogonadal symptoms seen in nonstandard shift workers.