Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease.

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.

Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

Oral paracoccidioidomycosis: a retrospective study of 95 cases from a single center and literature review.

BACKGROUND: The ecoepidemiological panorama of paracoccidioidomycosis (PCM) is dynamic and still ongoing in Brazil. In particular, data about the oral lesions of PCM are barely explored. The aim of this study was to report the clinicopathological features of individuals diagnosed with oral PCM lesions at an oral and maxillofacial pathology service in Rio de Janeiro, Brazil, in the light of a literature review. MATERIAL AND METHODS: A retrospective study was conducted on oral biopsies obtained from 1958 to 2021. Additionally, electronic searches were conducted in PubMed, Embase, Scopus, Web of Science, Latin American and Caribbean Center on Health Sciences Information, and Brazilian Library of Dentistry to gather information from large case series of oral PCM. RESULTS: Ninety-five cases of oral PCM were surveyed. The manifestations were more frequent among males (n=86/90.5%), middle-aged/older adults (n=54/58.7%), and white individuals (n=40/51.9%). The most commonly affected sites were the gingiva/alveolar ridge (n=40/23.4%) and lip/labial commissure (n=33/19.3%); however, one (n=40/42.1%) or multiple sites (n=55/57.9%) could also be affected. In 90 (94.7%) patients, "mulberry-like" ulcerations/moriform appearance were observed. Data from 21 studies (1,333 cases), mostly Brazilian (90.5%), revealed that men (92.4%; male/female: 11.8:1) and individuals in the fifth and sixth decades of life were the most affected (range: 7-89 years), with the gingiva/alveolar ridge, palate, and lips/labial commissure being the sites most frequently affected. CONCLUSIONS: The features of oral PCM lesions are similar to those reported in previous studies from Latin America. Clinicians should be aware of the oral manifestations of PCM, with emphasis on the clinicodemographic aspects and differential diagnoses, especially considering the phenomenon of the emergence of reported cases in rural and/or urban areas of Brazil.

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

This corrects the article DOI: 10.1103/PhysRevLett.125.011801.

First Directional Measurement of Sub-MeV Solar Neutrinos with Borexino.

We report the measurement of sub-MeV solar neutrinos through the use of their associated Cherenkov radiation, performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The measurement is achieved using a novel technique that correlates individual photon hits of events to the known position of the Sun. In an energy window between 0.54 to 0.74 MeV, selected using the dominant scintillation light, we have measured 10 887_{-2103}^{+2386}(stat)±947(syst) (68% confidence interval) solar neutrinos out of 19 904 total events. This corresponds to a ^{7}Be neutrino interaction rate of 51.6_{-12.5}^{+13.9} counts/(day·100 ton), which is in agreement with the standard solar model predictions and the previous spectroscopic results of Borexino. The no-neutrino hypothesis can be excluded with >5σ confidence level. For the first time, we have demonstrated the possibility of utilizing the directional Cherenkov information for sub-MeV solar neutrinos, in a large-scale, high light yield liquid scintillator detector. This measurement provides an experimental proof of principle for future hybrid event reconstruction using both Cherenkov and scintillation signatures simultaneously.

Angina bullosa haemorrhagica: A 14-year multi-institutional retrospective study from Brazil and literature review.

BACKGROUND: Angina bullosa haemorrhagica (ABH) is characterized by the recurrent appearance of blood blisters on the oral mucosa, mainly in adults' soft palate. In general, the blisters rupture spontaneously, lacking the necessity for biopsy. We report the clinical features of 23 ABH cases, emphasizing the clinical behavior and the management of these conditions. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 12,727 clinical records of oral and maxillofacial lesions from four dental services in Brazil were analyzed. Clinical data were collected from the clinical records and evaluated. RESULTS: The series comprised 12 males (52.2%) and 11 females (47.8%), with a mean age of 56.8 ± 14.6 years (ranging: 24-82 years) and a 1.1:1 male-to-female ratio. Most of the lesions affected the soft palate (n = 15, 65.2%). Clinically, the lesions presented mainly as an asymptomatic (n = 17, 73.9%) blood-filled blister that ruptured after a few minutes or hours, leaving an erosion. The masticatory trauma was the most frequent triggering event. No patient had coagulation disorders. A biopsy was performed in only four cases (17.4%). Treatment was symptomatic with a favorable outcome. CONCLUSIONS: ABH is still poorly documented in the literature, and its etiology remains uncertain. ABH mainly affects the soft palate of elderly adults and has a favorable evolution in a few days. The therapeutic approach is often focused only on the relief of symptoms. However, it can share some clinical features with more serious diseases. Therefore, clinicians must recognize these lesions to avoid misdiagnosis.

Primary melanoma of the oral cavity: A multi-institutional retrospective analysis in Brazil.

BACKGROUND: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas. MATERIAL AND METHODS: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed. RESULTS: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months. CONCLUSIONS: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.

Oral pigmented lesions: a retrospective analysis from Brazil.

BACKGROUND: Pigmented lesions are uncommon in the oral mucosa, and studies investigating the incidence and types of these lesions are desired to improve the diagnostic knowledge of clinicians. The aim of this study was to analyze the distribution of oral pigmented lesions in a Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. Oral pigmented lesions were retrieved from the files of two oral and maxillofacial pathology services from Brazil over a 45-year period (1974-2019). The clinical data and the diagnoses of each case were retrieved and included in a Microsoft Excel® database. RESULTS: From 77.074 lesions diagnosed in this period, 761 (0.99%) represented pigmented lesions of the oral mucosa, including 351 (46.1%) melanocytic and 410 (53.9%) non-melanocytic lesions, with a higher incidence in females (73.2%) between the fourth and seventh decades of life. Amalgam tattoo (53.6%) represented the most common lesion, followed by melanotic macule (18.3%) and racial pigmentation (10.8%). Other pigmented lesions included nevus (9.9%), post-inflammatory pigmentation (3%), melanoma (2.1%), melanoacanthoma (1.4%), smoker's melanosis (0.4%), drug-induced pigmentation (0.3%), and melanotic neuroectodermal tumor of infancy (0.1%). The buccal mucosa was the most commonly affected site (25.2%), followed by the alveolar ridge (14.5%), and gingiva (11.8%). CONCLUSIONS: The current findings were similar to previous studies with minor differences due methodology and characteristics of the services from where lesions were retrieved. The knowledge of these data may contribute to a better understanding of oral pigmented lesions and assist clinicians to better recognize and manage them.

First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-ß decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}<3×10^{-12} and α^{'}/α<6.5×10^{-24} at 90% credible interval, respectively, were obtained.

Final Results of GERDA on the Search for Neutrinoless Double-ß Decay.

The GERmanium Detector Array (GERDA) experiment searched for the lepton-number-violating neutrinoless double-ß (0νßß) decay of ^{76}Ge, whose discovery would have far-reaching implications in cosmology and particle physics. By operating bare germanium diodes, enriched in ^{76}Ge, in an active liquid argon shield, GERDA achieved an unprecedently low background index of 5.2×10^{-4} counts/(keV kg yr) in the signal region and met the design goal to collect an exposure of 100 kg yr in a background-free regime. When combined with the result of Phase I, no signal is observed after 127.2 kg yr of total exposure. A limit on the half-life of 0νßß decay in ^{76}Ge is set at T_{1/2}>1.8×10^{26} yr at 90% C.L., which coincides with the sensitivity assuming no signal.

Radiographic estimation of the growth rate of initially underdiagnosed ameloblastomas.

BACKGROUND: To evaluate the specific growth rate (SGR) of ameloblastoma. MATERIAL AND METHODS: cases of ameloblastoma initially underdiagnosed (e.g. cases overlooked or diagnosed as reactive lesions) which had adequate radiographic documentation to evaluate their progression were retrospectively selected. Two panoramic radiographs were analyzed to determine the specific growth rate (SGR) of each tumor, defined as the logarithm of the ratio of final tumor area (when the diagnosis of ameloblastoma was made) to the initial tumor area (when the lesion was underdiagnosed), divided by the time interval between the radiographic images. The tumor area was measured using the software ImageJ. RESULTS: Twelve patients with mandibular ameloblastomas were selected, including 5 males and 7 females, with a mean age of 24.9 years (range: 14-61 years). In four cases, the lesion was associated with the crown of an impacted third molar. In three cases, it was initially diagnosed as a periapical lesion. Three cases were extrafollicular and were not noticed in the initial radiographs. Two cases were initially diagnosed as ameloblastoma, but the surgery was delayed for personal reasons. The mean interval of time between the two radiographic images was 4.3 years (range: 0.4-9 years). Based on our analysis, ameloblastoma grows in average 40.4% per year (range: 14.9-88.7%). CONCLUSIONS: Ameloblastoma is a progressively growing tumor, but its growth rate seems to be smaller than initially reported in the literature. Better understanding the radiographic progression of ameloblastoma might improve its early diagnosis, management, and prognosis.

Improved Limit on Neutrinoless Double-ß Decay of

The GERDA experiment searches for the lepton-number-violating neutrinoless double-ß decay of ^{76}Ge (^{76}Ge→^{76}Se+2e^{-}) operating bare Ge diodes with an enriched ^{76}Ge fraction in liquid argon. The exposure for broad-energy germanium type (BEGe) detectors is increased threefold with respect to our previous data release. The BEGe detectors feature an excellent background suppression from the analysis of the time profile of the detector signals. In the analysis window a background level of 1.0_{-0.4}^{+0.6}×10^{-3} counts/(keV kg yr) has been achieved; if normalized to the energy resolution this is the lowest ever achieved in any 0νßß experiment. No signal is observed and a new 90% C.L. lower limit for the half-life of 8.0×10^{25} yr is placed when combining with our previous data. The expected median sensitivity assuming no signal is 5.8×10^{25} yr.

A retrospective analysis of oral and maxillofacial pathology in a pediatric population from Rio de Janeiro-Brazil over a 75-year period.

BACKGROUND: The aim of this study was to analyze the distribution of oral and maxillofacial lesions affecting children and adolescents patients from a single oral pathology laboratory from Rio de Janeiro, Brazil. MATERIAL AND METHODS: Oral and maxillofacial lesions biopsied in patients younger than 19-years were retrieved from the oral pathology files of the Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro over a 75-year period (1942-2017). The clinical data and the diagnoses of each case were included in a Microsoft Excel® database, being classified into 13 categories according to the etiology. A descriptive analysis of the variables age, gender and final diagnosis was made. RESULTS: From 19.095 lesions diagnosed in this period, 2408 (12.61%) were from patients aged 0 to19 years, with a higher incidence in females in the second decade. Salivary gland pathology was the most common group of lesions (24.30%), followed by reactive lesions (16.82%) and odontogenic cysts (14.66%). Mucocele was the most common lesion (21.72%), followed by dentigerous cyst (6.48%) and fibrous hyperplasia (6.44%). Malignant lesions were observed in 1.12% of all cases with Burkitt lymphoma as the most frequent. CONCLUSIONS: Our results were similar to previous studies and knowledge of these data may contribute to the understanding of oral lesions that most commonly affects children.

Test of Electric Charge Conservation with Borexino.

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is an important cause of cancer-related death. Prediction of recurrence is an important issue in the treatment of disease, particularly for stage II patients. The level of telomere-specific reverse transcriptase (hTERT), the catalytic component of the telomerase complex, increases along with CRC progression, but its prognostic value is still unclear. METHODS: One hundred and thirty-seven CRC patients were studied for hTERT expression in tumour cells by real-time PCR. hTERT level was evaluated as a prognostic factor of overall survival (OS) in all patients and of disease recurrence in a subgroup of 50 stage II patients. RESULTS: The median hTERT level was 93.8 copies (interquartile range 48-254). Patients with high hTERT levels (above the median) showed a significantly worse survival than those with low hTERT levels (below the median; log-rank test P<0.0001; hazard ratio (HR)=3.30 (95% confidence interval (CI) 1.98-5.52); P<0.0001). The negative prognostic value of high hTERT level is independent of the pathological stage and microsatellite instability (HR=2.09 (95% CI 1.20-3.64), P=0.009). Moreover, in stage II CRC, high hTERT levels identified patients with a higher risk of disease recurrence (HR=3.06 (95% CI 1.03-9.04), P=0.043) and death (HR=3.24 (95% CI 1.37-7.71), P=0.008). CONCLUSION: hTERT level is an independent prognostic marker of OS in CRC patients. In addition, assessment of hTERT level could improve stratification of stage II CRC patients for the risk of disease recurrence.

Results on neutrinoless double-ß decay of 76Ge from phase I of the GERDA experiment.

Neutrinoless double beta decay is a process that violates lepton number conservation. It is predicted to occur in extensions of the standard model of particle physics. This Letter reports the results from phase I of the Germanium Detector Array (GERDA) experiment at the Gran Sasso Laboratory (Italy) searching for neutrinoless double beta decay of the isotope (76)Ge. Data considered in the present analysis have been collected between November 2011 and May 2013 with a total exposure of 21.6 kg yr. A blind analysis is performed. The background index is about 1 × 10(-2) counts/(keV kg yr) after pulse shape discrimination. No signal is observed and a lower limit is derived for the half-life of neutrinoless double beta decay of (76)Ge, T(1/2)(0ν) >2.1 × 10(25) yr (90% C.L.). The combination with the results from the previous experiments with (76)Ge yields T(1/2)(0ν)>3.0 × 10(25) yr (90% C.L.).

Abnormalities in amphibian populations inhabiting agroecosystems in Northeastern Buenos Aires Province, Argentina.

The occurrence of abnormalities in amphibians has been reported in many populations, and its increase could be related to environmental pollution and habitat degradation. We evaluated the type and prevalence of abnormalities in 5 amphibian populations from agroecosystems with different degrees of agricultural disturbance (cultivated and reference areas). We detected 9 types of abnormalities, of which the most frequent were those occurring in limbs. The observed prevalence of abnormality in assessed populations from cultivated and reference areas was as follows: Rhinella fernandezae (37.1 and 10.2%, respectively), Leptodactylus latrans adults (28.1 and 9.2%) and juveniles (32.9 and 15.3%), and Hypsiboas pulchellus (11.6 and 2.8%). Scinax granulatus populations did not show abnormalities. Pseudis minuta, which was only detected in the reference area, exhibited a prevalence of 13.3%. For R. fernandezae, L. latrans, and H. pulchellus, generalized linear mixed models showed that prevalence of abnormalities was significantly higher (p < 0.05) in cultivated than in reference areas. L. latrans juveniles were more vulnerable to abnormalities than adults (p < 0.05). The presence of abnormalities in some species inhabiting different agroecosystems suggests that environmental stress factors might be responsible for their occurrence. While we detected pesticides (endosulfan, cypermethrin, and chlorpyrifos) and lower dissolved oxygen levels in ponds of the cultivated area, no data are currently available on how other factors, such as injuries from predators and parasite infections, vary by land use. Further research will be necessary to evaluate possible causes of abnormalities detected in the present study mainly in the context of factor interactions.

Clinical and molecular features of attenuated adenomatous polyposis in northern Italy.

BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is characterized by the presence of 10-99 colorectal adenomas. The disease may be associated with mutations in either APC or MUTYH genes. We purposed to evaluate the contribution of adenomatous polyposis coli (APC) and MutY homologue (MUTYH) germline alterations to the AFAP phenotype and to identify genotype/phenotype correlations. METHODS: During counselling for familial adenomatous polyposis (FAP), 91 probands (and 107 affected individuals) who met the criteria of AFAP were identified. Eighty-two families were screened for constitutional mutations of the APC and MUTYH genes. RESULTS: MUTYH mutations were detected in 21 families (25.6 % of the 82 tested), and APC mutations in 7 (8.5 %). Overall, constitutional alterations were found in 34.1 % of the probands. Patients with APC mutations were younger at cancer onset and had a higher mean number of polyps (48.5 ± 33.0 in APC+ individuals vs. 35.7 ± 24.9 in MUTYH+ individuals, and 33.2 ± 18.4 in the "no mutation" group). Clinical features rendered the "no mutation" group closer to MUTYH+ than to the APC+ group. Colorectal cancer at diagnosis was detected in 40 % of AFAP individuals. CONCLUSIONS: AFAP is a new clinical entity with its frequency in the general population still undefined. The number of adenomas varies greatly, with an average of 30-40 lesions. The molecular basis of AFAP can be established in approximately 1/3 of the patients. Both MUTYH and APC genes are implicated in AFAP, though the role of MUTYH is of considerably greater relevance.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.