Addendum to the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group: sonographic evaluation of the parametrium.

Preoperative sonographic staging in patients with suspected parametrial endometriosis is essential to plan the surgical intervention and to anticipate the need for a multidisciplinary approach, and hence optimize surgical outcome. The results of a recent metanalysis suggest that defining more accurately the ultrasonographic criteria of parametrial involvement in endometriosis is needed. The aim of this addendum to the IDEA-consensus is to highlight the sonographic characteristics of the parametrium and identify ultrasound techniques to diagnose deep endometriosis in this area. This article is protected by copyright. All rights reserved.

Search for New Physics in Electronic Recoil Data from XENONnT.

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.

Ultrasound features of highly vascularized uterine myomas (uterine smooth muscle tumors) and correlation with histopathology.

OBJECTIVE: To correlate the ultrasound appearance of highly vascularized uterine myomas with their histopathological diagnosis. METHODS: This was a prospective observational study of patients with a preoperative ultrasound diagnosis of a highly vascularized uterine myoma (color score of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA) criteria), characterized by circumferential and intralesional vascular pattern, who underwent myomectomy or hysterectomy. For each patient, ultrasound characteristics were recorded at baseline, including the number of lesions, the size, echogenicity and border regularity of the lesion, presence of cystic areas and shadowing within the myoma, and visualization of the endometrium. Ultrasound features were correlated with the definitive histological diagnosis. Ultrasound features were then compared between malignant and benign lesions. RESULTS: We included 70 patients with highly vascularized uterine myomas on power/color Doppler. Their mean age was 46.5 ± 11.4 years and 13 (18.6%) were postmenopausal. At histological examination, 65 (92.9%) uterine myomas were benign lesions, comprising 32 typical leiomyomas, 29 leiomyoma variants and four adenomyomas. The remaining five (7.1%) uterine myomas were malignant masses, comprising two uterine sarcomas, one leiomyosarcoma, one neuroendocrine tumor and one uterine smooth muscle tumor of uncertain malignant potential (STUMP). The mean age of patients with a malignant lesion was significantly higher than the age of those with a benign lesion (64.8 ± 16.0 vs 42.4 ± 5.1; P < 0.001). Four out of five patients with a malignant lesion were over 45 years old. Ultrasound demonstrated cystic areas within the lesion in 10/32 (31.3%) typical leiomyomas, 16/29 (55.2%) leiomyoma variants, all four adenomyomas and in the cases of STUMP and leiomyosarcoma. Lesion borders were regular in 64/65 (98.5%) benign lesions and 2/5 (40%) malignant lesions (P < 0.05). No significant differences were observed between benign and malignant lesions with respect to echogenicity, presence of shadowing and size. The endometrium was visible in 55/65 women with benign lesions and in 2/5 with malignant lesions (P = 0.03). CONCLUSIONS: Our results showed that ultrasound features of uterine myomas, such as circumferential and intralesional vascularity, cystic areas and lesion borders, are important parameters for differential diagnosis, especially when combined with the patient's age. Such features could be useful to differentiate typical myomas from benign variants and malignant lesions in a preoperative setting and to select patients that may benefit from conservative management rather than surgery. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of sonography for non-invasive detection of ovarian and deep endometriosis using #Enzian classification: prospective multicenter diagnostic accuracy study.

OBJECTIVE: To compare the preoperative detection of endometriosis using transvaginal sonography (TVS) supplemented by transabdominal sonography (TAS) with surgical assessment of disease, using the #Enzian classification for endometriosis. METHODS: This was a prospective multicenter diagnostic accuracy study of women undergoing TVS/TAS and radical surgery for deep endometriosis (DE) at different tertiary referral centers. The localization and grade of severity of the endometriotic lesions and adhesions were described according to the criteria of the #Enzian classification, both at preoperative ultrasound examination and during surgery. According to the #Enzian classification, the small pelvis is divided into three compartments for DE: A (rectovaginal septum and vagina); B (uterosacral and cardinal ligaments, parametrium and pelvic sidewalls); and C (rectum). In addition, further locations (F) are classified as adenomyosis (FA), urinary bladder involvement (FB) and ureteric involvement with signs of obstruction (FU). Other intestinal locations (FI) and other extragenital locations (FO) are also included. Ovarian endometriosis and adhesions at the level of the tubo-ovarian unit are listed as O and T, respectively. The #Enzian grade of severity (Grade 1-3) was determined for #Enzian compartments O, T, A, B and C based on the size of the lesion or the severity of the adhesions. Concordance between preoperative assessment using TVS/TAS and evaluation at surgery was assessed. The sensitivity, specificity, positive and negative predictive values and accuracy of TVS/TAS in the detection of endometriotic lesions/adhesions in the different #Enzian compartments were calculated. RESULTS: In total, 745 women were included in the analysis. Preoperative TVS/TAS and surgical findings showed a concordance rate ranging between 86% and 99% for the presence or absence of endometriotic lesions/adhesions, depending on the evaluated #Enzian compartment. The concordance rate between TVS and surgery ranged between 71% and 92% for different severity grades, in #Enzian compartments O, T, A, B and C. Determining the presence or absence of adhesions at the level of the tubo-ovarian unit and classifying them accurately as Grade 1, 2 or 3 on TVS was more difficult than determining the presence and severity of endometriotic lesions in #Enzian compartments O, A, B and C. The sensitivity of TVS/TAS for the detection of endometriotic lesions ranged from 50% (#Enzian compartment FI) to 95% (#Enzian compartment A), specificity from 86% (#Enzian compartment Tleft ) to 99% (#Enzian compartment FI) and 100% (#Enzian compartments FB, FU and FO), positive predictive value from 90% (#Enzian compartment Tright ) to 100% (#Enzian compartment FO), negative predictive value from 74% (#Enzian compartment Bleft ) to 99% (#Enzian compartments FB and FU) and accuracy from 88% (#Enzian compartment Bright ) to 99% (#Enzian compartment FB). CONCLUSIONS: The localization and severity of endometriotic lesions/adhesions, as described and classified according to the #Enzian classification, can be diagnosed accurately and non-invasively using TVS/TAS. The #Enzian classification provides a uniform classification system for describing endometriotic lesions, which can be used both at TVS/TAS and during surgical evaluation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

222 Rn emanation measurements for the XENON1T experiment.

The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a 222 Rn activity concentration of 10 µ Bq / kg in 3.2 t of xenon. The knowledge of the distribution of the 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the 222 Rn activity concentration in XENON1T. The final 222 Rn activity concentration of ( 4.5 ± 0.1 ) µ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment.

Search for Coherent Elastic Scattering of Solar

We report on a search for nuclear recoil signals from solar ^{8}B neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 to 1.6 keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant ^{8}B neutrinolike excess is found in an exposure of 0.6 t×y. For the first time, we use the nondetection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as nonstandard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 and 11 GeV c^{-2} by as much as an order of magnitude.

Preoperative imaging of deep endometriosis: pitfalls of a diagnostic test before surgery.

The usefulness of a test is determined by the clinical interpretation of its sensitivity and specificity. The pitfalls of a test with a surgical endpoint are described in this article, taking the diagnosis of deep endometriosis by imaging as an example, without discussing the management of deep endometriosis. Laparoscopy is not a 100% accurate "gold standard". Since it is not performed in women without symptoms, results are valid only for the group of women as specified in the indication for surgery. The confidence limits of accuracy estimations widen when accuracy is lower and when observations are less. Since positive and negative predictive values are inaccurate when prevalence of the disease is low, prevalence figures in the group of women investigated should be available. The accuracy of imaging should be stratified by clinically important aspects such as localisation and size of the lesion. The use of other variables as soft markers during ultrasonographic examination should be specified. It should be clear whether the accuracy of the test reflects symptoms and clinical examination and imaging combined, or whether the accuracy of the added value of imaging which requires Bayesian analysis. When imaging is used as an indication for surgery, circular reasoning should be avoided and the number of symptomatic women not undergoing surgery because of negative imaging should be reported. In conclusion, imaging reports should permit the clinician to judge the validity of the accuracy estimations of a diagnostic test, especially when used as an indication for surgery and when surgery is the gold standard to diagnose a disease.

Constraining the Spin-Dependent WIMP-Nucleon Cross Sections with XENON1T.

We report the first experimental results on spin-dependent elastic weakly interacting massive particle (WIMP) nucleon scattering from the XENON1T dark matter search experiment. The analysis uses the full ton year exposure of XENON1T to constrain the spin-dependent proton-only and neutron-only cases. No significant signal excess is observed, and a profile likelihood ratio analysis is used to set exclusion limits on the WIMP-nucleon interactions. This includes the most stringent constraint to date on the WIMP-neutron cross section, with a minimum of 6.3×10^{-42} cm^{2} at 30 GeV/c^{2} and 90% confidence level. The results are compared with those from collider searches and used to exclude new parameter space in an isoscalar theory with an axial-vector mediator.

First Results on the Scalar WIMP-Pion Coupling, Using the XENON1T Experiment.

We present first results on the scalar coupling of weakly interacting massive particles (WIMPs) to pions from 1 t yr of exposure with the XENON1T experiment. This interaction is generated when the WIMP couples to a virtual pion exchanged between the nucleons in a nucleus. In contrast to most nonrelativistic operators, these pion-exchange currents can be coherently enhanced by the total number of nucleons and therefore may dominate in scenarios where spin-independent WIMP-nucleon interactions are suppressed. Moreover, for natural values of the couplings, they dominate over the spin-dependent channel due to their coherence in the nucleus. Using the signal model of this new WIMP-pion channel, no significant excess is found, leading to an upper limit cross section of 6.4×10^{-46} cm^{2} (90% confidence level) at 30 GeV/c^{2} WIMP mass.

Light Dark Matter Search with Ionization Signals in XENON1T.

We report constraints on light dark matter (DM) models using ionization signals in the XENON1T experiment. We mitigate backgrounds with strong event selections, rather than requiring a scintillation signal, leaving an effective exposure of (22±3) tonne day. Above ∼0.4 keV_{ee}, we observe <1 event/(tonne day keV_{ee}), which is more than 1000 times lower than in similar searches with other detectors. Despite observing a higher rate at lower energies, no DM or CEvNS detection may be claimed because we cannot model all of our backgrounds. We thus exclude new regions in the parameter spaces for DM-nucleus scattering for DM masses m_{χ} within 3-6 GeV/c^{2}, DM-electron scattering for m_{χ}>30 MeV/c^{2}, and absorption of dark photons and axionlike particles for m_{χ} within 0.186-1 keV/c^{2}.

Search for Light Dark Matter Interactions Enhanced by the Migdal Effect or Bremsstrahlung in XENON1T.

Direct dark matter detection experiments based on a liquid xenon target are leading the search for dark matter particles with masses above ∼5 GeV/c^{2}, but have limited sensitivity to lighter masses because of the small momentum transfer in dark matter-nucleus elastic scattering. However, there is an irreducible contribution from inelastic processes accompanying the elastic scattering, which leads to the excitation and ionization of the recoiling atom (the Migdal effect) or the emission of a bremsstrahlung photon. In this Letter, we report on a probe of low-mass dark matter with masses down to about 85 MeV/c^{2} by looking for electronic recoils induced by the Migdal effect and bremsstrahlung using data from the XENON1T experiment. Besides the approach of detecting both scintillation and ionization signals, we exploit an approach that uses ionization signals only, which allows for a lower detection threshold. This analysis significantly enhances the sensitivity of XENON1T to light dark matter previously beyond its reach.

Dark Matter Search Results from a One Ton-Year Exposure of XENON1T.

We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber with a fiducial mass of (1.30±0.01) ton, resulting in a 1.0 ton yr exposure. The energy region of interest, [1.4,10.6] keV_{ee} ([4.9,40.9] keV_{nr}), exhibits an ultralow electron recoil background rate of [82_{-3}^{+5}(syst)±3(stat)] events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6 GeV/c^{2}, with a minimum of 4.1×10^{-47} cm^{2} at 30 GeV/c^{2} and a 90% confidence level.

First Dark Matter Search Results from the XENON1T Experiment.

We report the first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of this kind. The blinded search used 34.2 live days of data acquired between November 2016 and January 2017. Inside the (1042±12)-kg fiducial mass and in the [5,40] keV_{nr} energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (1.93±0.25)×10^{-4} events/(kg×day×keV_{ee}), the lowest ever achieved in such a dark matter detector. A profile likelihood analysis shows that the data are consistent with the background-only hypothesis. We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c^{2}, with a minimum of 7.7×10^{-47} cm^{2} for 35-GeV/c^{2} WIMPs at 90% C.L.

Search for Electronic Recoil Event Rate Modulation with 4 Years of XENON100 Data.

We report on a search for electronic recoil event rate modulation signatures in the XENON100 data accumulated over a period of 4 yr, from January 2010 to January 2014. A profile likelihood method, which incorporates the stability of the XENON100 detector and the known electronic recoil background model, is used to quantify the significance of periodicity in the time distribution of events. There is a weak modulation signature at a period of 431_{-14}^{+16} day in the low energy region of (2.0-5.8) keV in the single scatter event sample, with a global significance of 1.9σ; however, no other more significant modulation is observed. The significance of an annual modulation signature drops from 2.8σ, from a previous analysis of a subset of this data, to 1.8σ with all data combined. Single scatter events in the low energy region are thus used to exclude the DAMA/LIBRA annual modulation as being due to dark matter electron interactions via axial vector coupling at 5.7σ.

Search for Event Rate Modulation in XENON100 Electronic Recoil Data.

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an unbinned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1σ for all periods, suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8σ, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of weakly interacting massive particles to electrons is excluded at 4.8σ.

Decrease of atmospheric neutron counts observed during thunderstorms.

We report here, in brief, some results of the observation and analysis of sporadic variations of atmospheric thermal neutron flux during thunderstorms. The results obtained with unshielded scintillation neutron detectors show a prominent flux decrease correlated with meteorological precipitations after a long dry period. No observations of neutron production during thunderstorms were reported during the three-year period of data recording.

Loss of Drosophila pseudouridine synthase triggers apoptosis-induced proliferation and promotes cell-nonautonomous EMT.

Many developing tissues display regenerative capability that allows them to compensate cell loss and preserve tissue homeostasis. Because of their remarkable regenerative capability, Drosophila wing discs are extensively used for the study of regenerative phenomena. We thus used the developing wing to investigate the role played in tissue homeostasis by the evolutionarily conserved eukaryotic H/ACA small nucleolar ribonucleoprotein pseudouridine synthase. Here we show that localized depletion of this enzyme can act as an endogenous stimulus capable of triggering apoptosis-induced proliferation, and that context-dependent effects are elicited in different sub-populations of the silenced cells. In fact, some cells undergo apoptosis, whereas those surrounding the apoptotic foci, although identically depleted, overproliferate. This overproliferation correlates with ectopic induction of the Wg and JAK-STAT (Janus kinase-signal transducer and activator of transcription) mitogenic pathways. Expression of a p35 transgene, which blocks the complete execution of the death program and generates the so-called 'undead cells', amplifies the proliferative response. Pseudouridine synthase depletion also causes loss of apicobasal polarity, disruption of adherens cell junctions and ectopic induction of JNK (c-Jun N-terminal kinase) and Mmp1 (matrix metalloproteinase-1) activity, leading to a significant epithelial reorganization. Unexpectedly, cell-nonautonomous effects, such as epithelial mesenchymal transition in the contiguous unsilenced squamous epithelium, are also promoted. Collectively, these data point out that cell-cell communication and long-range signaling can take a relevant role in the response to pseudouridine synthase decline. Considering that all the affected pathways are highly conserved throughout evolution, it is plausible that the response to pseudouridine synthase depletion has been widely preserved. On this account, our results can add new light on the still unexplained tumor predisposition that characterizes X-linked dyskeratosis, the human disease caused by reduced pseudouridine synthase activity.

Automated three-dimensional coded contrast imaging hysterosalpingo-contrast sonography: feasibility in office tubal patency testing.

OBJECTIVE: To evaluate the feasibility of transvaginal hysterosalpingo-contrast sonography (HyCoSy) with new automated three-dimensional coded contrast imaging (3D-CCI) software in the evaluation of tubal patency and visualization of tubal course. METHODS: Patients undergoing HyCoSy with automated 3D-CCI software were evaluated prospectively. First, to evaluate the feasibility of 3D visualization of tubal course, we performed consecutive volume acquisitions while injecting SonoVue contrast agent. We then performed conventional two-dimensional (2D) real-time HyCoSy to confirm tubal patency status by detection of saline and air bubbles moving through the Fallopian tubes and around the ovaries. We also evaluated visualization with CCI of the contrast agent around the ovaries, side effects and pain during and after the procedure, by visual analog scale (VAS) (ranging from 0 to 10, with 0 corresponding to no pain and 10 corresponding to maximum pain). RESULTS: A total of 126 patients (252 tubes) underwent 3D-CCI HyCoSy followed by 2D real-time HyCoSy. According to the final 2D real-time evaluation, bilateral tubal patency was observed in 111 patients, bilateral tubal occlusion in four patients and unilateral tubal patency in 11 patients. The concordance rate for tubal patency status between the first 3D volume acquisition and the final 2D real-time evaluation was 84% and that between the second 3D volume acquisition and the final 2D real-time evaluation was 97%. A pain score >5 on VAS was recorded in 58% of patients during the procedure, but a pain score ≤ 5 was recorded in 85.7% of patients immediately after the procedure. CONCLUSIONS: HyCoSy with automated 3D-CCI technology retains the advantages of conventional 2D HyCoSy while overcoming the disadvantages. 2D HyCoSy is highly observer-dependent and is only accurate in the hands of experienced investigators; by obtaining a volume of the uterus and tubes, automated 3D volume acquisition permits visualization of the tubes in the coronal view and of the tubal course in 3D space, and should allow less experienced operators to evaluate tubal patency status relatively easily.

Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology.

OBJECTIVE: To correlate with histopathological features the adenomyosis-induced morphological alterations of the outer myometrium and the inner myometrium ('junctional zone', JZ) detectable on two- (2D) and three-dimensional (3D) transvaginal ultrasound imaging (TVS), and to evaluate their diagnostic accuracy for adenomyosis. METHODS: Premenopausal patients scheduled for hysterectomy for benign pathology were enrolled in this prospective study. Before hysterectomy all patients underwent detailed 2D-TVS and 3D volume acquisition of the entire uterus. The major sonographic signs of adenomyosis were noted. On the multiplanar coronal and longitudinal views obtained by 3D-TVS we measured the maximum and minimum JZ thickness from the basal endometrium to the internal layer of the outer myometrium (JZmax, JZmin), the difference between them (JZdif = JZmax - JZmin) and the ratio JZmax/total maximum myometrial thickness. Results of these examinations were correlated blindly to the presence of adenomyosis on histological specimens. RESULTS: A total of 72 premenopausal patients underwent 2D- and 3D-TVS before hysterectomy. The histological prevalence of adenomyosis was 44.4% (32/72 patients). In diagnosing adenomyosis, the presence of myometrial cysts was the most specific 2D-TVS feature (specificity, 98%; accuracy, 78%) and heterogeneous myometrium was the most sensitive (sensitivity, 88%; accuracy, 75%). The 3D-TVS markers JZdif ≥ 4 mm and JZ infiltration and distortion had high sensitivity (88%) and the best accuracy (85% and 82%, respectively). For 2D-TVS and 3D-TVS, respectively, the overall accuracy for diagnosis of adenomyosis was 83% and 89%, the sensitivity was 75% and 91%, the specificity was 90% and 88%, the positive predictive value was 86% and 85% and the negative predictive value was 82% and 92%. CONCLUSIONS: The coronal section of the uterus obtained by 3D-TVS permits accurate evaluation and measurement of the JZ, and its alteration has good diagnostic accuracy for adenomyosis.