Key influence factors in magneto-controlled motion of micro-nano graphite flakes.

Magneto-controlling micro-nano materials' motion is a promising way that enable the noncontact, remote, and nondestructive controlling of their macrostructure as well as functionalities. Here, an optical microscope with an electromagnet was constructed toin-situmonitor the magneto-controlled motion process microscopically. Taking micro-nano graphite flake (MGF) as a model system, we experimentally demonstrate the key factors that influence the magneto-controlling of materials' motion. First, the product of intensity and gradient of the magnetic field (B∇B) has been confirmed as the dominant driving force and the flipping direction of the MGFs is accordingly determined by the vector direction ofB×∇B. Second, quantitatively comparative experiments further revealed that the threshold driving force has an exponential relationship with the structural aspect ratio (b/a) of MGFs. Third, the critical magneto-driving force is found as proportional to the viscosity of the solvent. Accordingly, a dynamic model is developed that describes the flip of the diamagnetic flake under external magnetic field excitation considering the shape factor. It is shown experimentally that the model accurately predicts the flip dynamics of the flake under different magnetic field conditions. In addition, we also discovered the delay effect, multiple cycle acceleration effect, and the fatigue effects due to gas adsorption in magneto-controlled MGFs flipping. These findings can be used to achieve magneto-controlling materials' macrostructure as well as their functionalities.

Role of finite element analysis for selection of single point fixation in zygomaticomaxillary complex fracture.

BACKGROUND: One-point fixation was superior to the two and three-points fixation in minimally displaced zygomaticomaxillary complex (ZMC) fracture regarding the cost, invasiveness, scaring, number of wounds, and operation time. Accordingly, this study aimed to predict which one-point fixation is the most stable in managing minimally displaced ZMC fracture. MATERIAL & METHODS: This study simulated the different one-point fixation approaches on three ZMC models after fracture reduction and application of all forces exerted on the fractured area. The findings were represented as stress impact on the ZMC fracture and plating system as well as the inter-fragments micro-motion. RESULTS: The von misses stresses of plates for the zygomaticofrontal, infra-orbital rim, and zygomaticomaxillary buttress model were (66.508, 1.285, and1.16 MPa) respectively. While the screws' von misses for the infraorbital rim, zygomaticofrontal, and zygomaticomaxillary buttress models were (13.8, 4.05, and 1.60 MPa) respectively. Whereas, the maximum principles stress at zygomaticofrontal, zygomaticomaxillary buttress, and infraorbital rim models were (37.03, 37.01, and 34.46 MPa) respectively. In addition, the inter-fragment micro-motion for zygomaticomaxillary buttress, infraorbital rim, and zygomaticofrontal models were (0.26, 0.25, and 0.15 mm) respectively. CONCLUSION: One-point fixation at zygomaticomaxillary buttress is the preferred point because it is exposed to low stresses, and the inter-fragment micro-motion is within the approved limit with the elements in the same direction of fixation which indicates the rigid fixation. In addition, it is less palpable and scarless. TRIAL REGISTRATION: clinical trial.gov (NCT05819372) at 19/04/2023.

Negative pressure induces dedifferentiation of hepatocytes via RhoA/ROCK pathway.

Biomechanical forces are known to regulate the biological behaviors of cells. Although negative pressure has been used for wound healing, it is still unknown about its role in regulating cell plasticity. We investigated whether negative pressure could induce the dedifferentiation of hepatocytes. Using a commercial device, we found that the exposure of primary human hepatocytes to -50 mmHg quickly induced the formation of stress fibers and obviously changed cell morphology in 72 h. Moreover, the exposure of hepatocytes to -50 mmHg significantly upregulated RhoA, ROCK1, and ROCK2 in 1-6 h, and dramatically enhanced the expression of marker molecules on "stemness", such as OCT4, SOX2, KLF4, MYC, NANOG, and CD133 in 6-72 h. However, all these changes in hepatocytes induced by -50 mmHg stimulation were almost abrogated by ROCK inhibitor Y27623. Our data suggest that an appropriate force of negative pressure stimulation can effectively induce the dedifferentiation of hepatocytes via RhoA/ROCK pathway activation.

Effective Nanocomposite Based on Bi2MoO6/MoS2/AuNRs for NIR-II Light-Boosted Photodynamic/Chemodynamic Therapy.

Bi2MoO6 (BMO) nanoparticles (NPs) have been widely used as a photocatalyst to decompose organic pollutants, but their potential for photodynamic therapy (PDT) is yet to be explored. Normally, the UV absorption property of BMO NPs is not suitable for clinical application because the penetration depth of the UV light is too small. To overcome this limitation, we rationally designed a novel nanocomposite based on Bi2MoO6/MoS2/AuNRs (BMO-MSA), which simultaneously possesses both the high photodynamic ability and POD-like activity under NIR-II light irradiation. Additionally, it has excellent photothermal stability with good photothermal conversion efficiency. The as-prepared BMO-MSA nanocomposite could induce the germline apoptosis of Caenorhabditis elegans (C. elegans) via the cep-1/p53 pathway after being illuminated by light with a wavelength of 1064 nm. The in vivo investigations confirmed the ability of the BMO-MSA nanocomposite for the induction of DNA damage in the worms, and the mechanism was approved by determining the egl-1 fold induction in the mutants that have a loss of function in the genes involved in DNA damage response mutants. Thus, this work has not only provided a novel PDT agent, which may be used for PDT in the NIR-II region, but also introduced a new approach to therapy, taking advantage of both PDT and CDT effects.

Immunohistochemistry and immunofluorescence utilization audit by subspecialty in an academic setting: A step toward stewardship.

There are immunohistochemistry (IHC) and immunofluorescence (IF) panels described in the literature and established by personal and institutional experiences that are in common use by pathologists in their daily practice. Stewardship is a difficult discussion because IHC utilization is influenced by many factors including the pathologist's experience, background, practice setting, personal bias, and medicolegal culture. We developed the methodology to audit the IHC/IF utilization in our academic subspecialty practice. We aim to share this methodology and to provide our data that can be used for consideration by other subspecialized academic practices. This analysis included a total of 63,157 specimens that were accessioned during 2022, representing 38,612 cases. The likelihood of ordering IHC/IF ranged from 1 % (in genitourinary pathology) to 59 % (in renal pathology). The average percentage of specimens with IHC/IF was 21 % for the entire practice. In cases where IHC/IF was ordered, the number of stained slides averaged 4.9 per specimen for the entire practice. The number of IHC/IF slides per specimen ranged from 1.9 (in gastrointestinal pathology) to 12.2 (in renal pathology). The highest number of antibodies ordered for a single specimen by subspecialty ranged from 11 (in cardiac pathology) to 63 (in dermatopathology). Renal pathology was the only subspecialty that had an average number of IHC/IF slides that was statistically significantly different from all other subspecialties. We described the various patterns of utilization by subspecialty and rationalized their subtle differences. We also analyzed the types of cases that exceeded the reimbursement limits set by the Centers for Medicare and Medicaid Services (CMS).

Angiotensin receptor blocker alleviates liver fibrosis by altering the mechanotransduction properties of hepatic stellate cells.

Angiotensin receptor blockers have been reported to be beneficial to liver fibrosis, but the relevant molecular and cellular mechanisms remain unclear. We herein investigated whether low-dose angiotensin receptor blocker alleviated liver fibrosis through mechanotransduction regulation. Hydrostatic pressure-induced liver fibrosis model was established in mice by ligating partially the inferior vena cava, and then randomly received a very low dose of losartan (0.5 mg/kg) or placebo treatment for 8 weeks. We found that losartan administration interfered the expression of several mechanotransductive molecules, and effectively alleviated liver fibrosis. Using a commercial device, we further confirmed that ex vivo loading of hepatic stellate cells to 50 mmHg hydrostatic pressure for 24 h significantly upregulated RhoA, ROCK, AT1R, and p-MLC2, which was effectively attenuated by adding 10 nM losartan in medium. Our in vivo and ex vivo experimental data suggest that low-dose angiotensin receptor blockers may alleviate hydrostatic pressure-induced liver fibrosis by altering the mechanotransduction properties of hepatic stellate cells.NEW & NOTEWORTHY Our ex vivo and in vivo experiments clearly indicated that low-dose losartan alleviated liver fibrosis, likely by modulating the mechanotransduction properties of HSCs. Uncovering the biomechanical signaling pathway of ARB treatment on liver fibrosis will be helpful to develop novel molecular targeting therapy for liver diseases.

Impact of Screening Modality on the Detection of Cervical Adenocarcinoma In Situ and Adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the impact of screening modality on the detection of cervical adenocarcinoma in situ (AIS) and adenocarcinoma. MATERIALS AND METHODS: This was a cross-sectional study of patients with AIS or adenocarcinoma who had undergone routine screening with cytology and high-risk human papillomavirus (HPV) cotesting between January 2007 and December 2017. Patients were stratified into 3 groups by screening test results: (1) HPV positive with abnormal cytology (HPV+/Pap+), (2) HPV negative with abnormal cytology (HPV-/Pap+), and (3) HPV positive with normal cytology (HPV+/Pap-). Demographic and clinical characteristics were collected. Data were analyzed with χ2, Fisher exact tests, and t tests as appropriate. RESULTS: Of the 118 patients diagnosed with AIS (n = 97) or adenocarcinoma (n = 21) after abnormal screening tests, 92 (78%) were detected by HPV+/Pap+, 15 (12.7%) were HPV+/Pap-, and 11 (9.3%) were HPV-/Pap+. Demographics were similar between groups, although the HPV+/Pap- patients had higher body mass indices. Rates of definitive hysterectomy were similar between groups (53.3%-80.0%, p = .11). CONCLUSIONS: In our cohort, a significant proportion of AIS and adenocarcinoma was detected by both HPV alone (with normal cytology) and cytology alone (with negative HPV), suggesting that cotesting with both HPV and cytology may be a more sensitive method of detection of AIS and adenocarcinoma.

Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. METHODS: This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. RESULTS: One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84-6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04-3.88; p = .039) compared to HER2-negative tumors. CONCLUSIONS: Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

ICTV Virus Taxonomy Profile: Endornaviridae.

The family Endornaviridae includes viruses with linear, single-stranded, positive-sense RNA genomes that range from 9.7 to 17.6 kb and have been reported infecting plants, fungi and oomycetes. The family consists of two genera, Alphaendornavirus and Betaendornavirus, into which viruses are classified based on their genome size, host and presence of unique domains. Alphaendornavirus includes species whose members infect plants, fungi and oomycetes, while the genus Betaendornavirus includes species whose members infect ascomycete fungi. This is a summary of the ICTV Report on the family Endornaviridae, which is available at www.ictv.global/report/endornaviridae.

Histologic Features of Hysterectomy Specimens From Female-Male Transgender Individuals.

Histologic changes in the female genital tract after prolonged androgen stimulation have been described in the past. However, these changes have not been systematically addressed in hysterectomy specimens from subjects undergoing surgical gender-reassignment, typically after treatment with exogenous androgens. The current study aims to provide practicing pathologists with a list of expected histologic features in hysterectomy specimens from female-male transgender individuals. Twenty-seven hysterectomy with bilateral salpingo-oophorectomy specimens were identified from our Laboratory Information System. Slides were retrieved and reviewed for features associated with androgen exposure. Clinical information for the 27 subjects (20-46 yr old, mean=29 yr) was obtained from the electronic medical records. Twenty-four subjects had received androgen 19 mo to 24 yr preoperatively. Focal decidua-like endometrial stromal change with glandular paucity was present in 16/27 (59%) uteri associated with predominantly inactive endometrial glands. Ectocervical or transformation zone transitional cell metaplasia was present in 17/27 (63%) subjects. Bilateral cystic follicles were present in all 23 subjects who underwent bilateral salpingo-oophorectomy and had preoperative androgen exposure. In these ovaries, follicular density appeared higher than that expected for age with counts ranging from 1.5 to 32.5 follicles/mm (average=10.7 follicles/mm). Predominantly inactive, sparse endometrial glands with focal decidua-like stromal change, cervical transitional cell metaplasia, bilateral cystic follicles and higher follicular density are observed in the majority of specimens from female-male transgender individuals. These histologic changes correlate with prolonged preoperative androgen administration. The significance of these findings relies on recognizing the spectrum of androgen-related histologic alterations and not confusing transitional cell metaplasia with cervical dysplasia.

Endometriosis-associated Ovarian Cancer is a Subset With a More Favorable Outcome and Distinct Clinical-pathologic Characteristics.

There is a controversy about whether endometriosis-associated ovarian cancer (EAOC) might represent a different entity from the corresponding ovarian cancer occurring de novo, in the absence of endometriosis. This study investigated the clinical-pathologic characteristics and outcome of EAOC compared with other ovarian carcinomas that are not associated with endometriosis (non-EAOC) in a large cohort. Seven hundred two patients meeting the inclusion criteria were further subclassified as group I when patients had ovarian carcinoma associated with or arising within endometriosis (EAOC) and group II when patients had non-EAOC. Age, gross features, histologic type, International Federation of Gynecology and Obstetrics stage, and disease-free survival (DFS) were compared between the groups. One hundred sixty-eight (23.9%) patients had EAOC, whereas 534 (76.1%) patients had non-EAOC. EAOCs were mostly endometrioid and clear cell type. Patients with EAOC were younger, present early, and had a lower rate of recurrence when compared with patients with non-EAOC, P<0.001. Patients with EAOC had longer DFS time, 51.9 mo (95% confidence interval, 44.9-58.8) versus 30.5 mo (95% confidence interval, 27.7-33.3) in non-EAOC patients. The 5 yr Kaplan-Meier estimate of DFS rate was 70% in 166 patients of group I and was 39.3% in 532 patients of group II, P<0.001. On multivariate analysis, International Federation of Gynecology and Obstetrics staging, histologic type, and treatment were the only significant factors affecting the hazards of recurrence. Patients with tumors associated with endometriosis are usually, younger, present early, have lower rate of recurrence, longer DFS, and their tumors are of lower grade and are more likely endometrioid or clear cell carcinoma.

Biological Insights into Chemotherapy Resistance in Ovarian Cancer.

The majority of patients with high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy; however, most will develop chemotherapy resistance. Gene signatures may change with the development of chemotherapy resistance in this population, which is important as it may lead to tailored therapies. The objective of this study was to compare tumor gene expression profiles in patients before and after treatment with neoadjuvant chemotherapy (NACT). Tumor samples were collected from six patients diagnosed with HGSOC before and after administration of NACT. RNA extraction and whole transcriptome sequencing was performed. Differential gene expression, hierarchical clustering, gene set enrichment analysis, and pathway analysis were examined in all of the samples. Tumor samples clustered based on exposure to chemotherapy as opposed to patient source. Pre-NACT samples were enriched for multiple pathways involving cell cycle growth. Post-NACT samples were enriched for drug transport and peroxisome pathways. Molecular subtypes based on the pre-NACT sample (differentiated, mesenchymal, proliferative and immunoreactive) changed in four patients after administration of NACT. Multiple changes in tumor gene expression profiles after exposure to NACT were identified from this pilot study and warrant further attention as they may indicate early changes in the development of chemotherapy resistance.

Diagnosis, Treatment and Clinical Features of Cutaneous Leishmaniasis in Saudi Arabia.

Cutaneous leishmaniasis (CL) has been one of the most common parasitic diseases in Saudi Arabia. This study exhibits the clinical features, diagnosis, cytokine profile and treatment of CL patients in Al-Taif province. Ninety CL suspects at a tertiary care general hospital were enrolled in one-year study. Patients were interviewed, clinically-examined, and subjected to laboratory tests: skin scraping smear microscopy, OligoC-TesT commercial PCR (Coris BioConcept) and kinetoplast DNA (kDNA) PCR for Leishmania diagnosis. Interferon-gamma (RayBio; Human IFN-γ) and nitric oxide (NO) levels in patients' sera were evaluated before treatment with sodium stibogluconate (pentostam) with 20-day intramuscular drug regimen. Positive rates of microscopy, commercial PCR and kDNA PCR were 74.4%, 95.5% and 100%, respectively. Patients came to hospital mostly in winter (45.0%). CL was frequently exhibited in Saudi patients (78.8%), male gender (70.7%), age <20 years (50.0%), rural-dwellers (75.5%) and patients with travel history (86.6%). Lesion was mostly single ulcer (93.3%), occurred in the face (67.7%). Upon pentostam treatment, 85.1% of ulcers showed rapid healing signs. Levels of IFN-γ and NO were significantly higher in the healing than the non-healing cases (P<0.001). The kDNA PCR proved more sensitive than microscopy and OligoC-TesT commercial PCR. Our results open perspectives for IFN-γ use as a biomarker predicting treatment response.

Does a groin node dissection in vulvar cancer affect groin recurrence and overall survival?: Results from a population-based cohort study.

BACKGROUND: To determine, in a population-based cohort of vulvar cancer patients, if groin node dissection (GND) decreases the risk of groin recurrence and increases overall survival. METHODS: This population-based retrospective cohort study includes all cases of invasive squamous cell carcinoma identified in a provincial cancer registry from 1998 to 2007. Data collection was completed for all clinical and pathologic factors by chart abstraction. Cumulative incidence functions for recurrence were estimated, accounting for death before recurrence as a competing risk. Multivariable Cox regression models examined the associations between GND and groin recurrence, and overall survival. RESULTS: Clinical and pathologic data were collected for 1109 patients, of which 1038 patients were eligible for GND. 647 patients (62%) had a GND, while 391 patients (38%) did not. Median follow-up was 2.8years. Cumulative incidence plots demonstrate that the risk of death without recurrence was consistently higher than groin recurrence in each year after diagnosis. On multivariate analysis, GND was not significantly associated with decreased groin recurrence (HR 0.91, 95% CI 0.58-1.44, p=0.70). The hazard of death was 15% lower for women who received GND (HR 0.85, 95% CI 0.63-1.16, p=0.32), but this difference was not statistically significant. CONCLUSIONS: There was no significant difference in groin recurrence or overall survival in those with or without GND in this population-based cohort, raising questions whether a subgroup of patients may not benefit from GND. Patients had a higher probability of dying before groin recurrence could occur. Future trial design should consider death as a competing risk.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Significant differentiation in the apolipoprotein(a)/lipoprotein(a) trait between chimpanzees from Western and Central Africa.

Elevated Lipoprotein(a) (Lp(a)) plasma concentrations are a risk factor for cardiovascular disease in humans, largely controlled by the LPA gene encoding apolipoprotein(a) (apo(a)). Lp(a) is composed of low-density lipoprotein (LDL) and apo(a) and restricted to Catarrhini. A variable number of kringle IV (KIV) domains in LPA lead to a size polymorphism of apo(a) that is inversely correlated with Lp(a) concentrations. Smaller apo(a) isoforms and higher Lp(a) levels in central chimpanzees (Pan troglodytes troglodytes [PTT]) compared to humans from Europe had been reported. We studied apo(a) isoforms and Lp(a) concentrations in 75 western (Pan troglodytes verus [PTV]) and 112 central chimpanzees, and 12 bonobos (Pan paniscus [PPA]), all wild born and living in sanctuaries in Sierra Leone, Republic of the Congo, and DR Congo, respectively, and 116 humans from Gabon. Lp(a) levels were severalfold higher in western than in central chimpanzees (181.0 ± 6.7 mg/dl vs. 56.5 ± 4.3 mg/dl), whereas bonobos showed intermediate levels (134.8 ± 33.4 mg/dl). Apo(a) isoform sizes differed significantly between subspecies (means 20.9 ± 2.2, 22.9 ± 4.4, and 23.8 ± 3.8 KIV repeats in PTV, PTT, and PPA, respectively). However, far higher isoform-associated Lp(a) concentrations for all isoform sizes in western chimpanzees offered the main explanation for the higher overall Lp(a) levels in this subspecies. Human Lp(a) concentrations (mean 47.9 ± 2.8 mg/dl) were similar to those in central chimpanzees despite larger isoforms (mean 27.1 ± 4.9 KIV). Lp(a) and LDL, apoB-100, and total cholesterol levels only correlated in PTV. This remarkable differentiation between chimpanzees from different African habitats and the trait's similarity in humans and chimpanzees from Central Africa poses the question of a possible impact of an environmental factor that has shaped the genetic architecture of LPA. Overall, studies on the cholesterol-containing particles of Lp(a) and LDL in chimpanzees should consider differentiation between subspecies.

Patient, tumor, and health system factors affecting groin node dissection rates in vulvar carcinoma: A population-based cohort study.

OBJECTIVE: To determine the rate of groin node dissection (GND) for invasive vulvar carcinoma in a population-based cohort, and the patient, tumor, or health system factors associated with having this procedure. METHODS: This retrospective population-based cohort includes all cases of invasive squamous cell carcinoma identified in the provincial cancer registry from 1998 to 2007. Chart abstraction was completed for all clinical and pathologic factors. Descriptive analyses with chi-squared tests were used for comparing proportions between patient groups. Multivariable logistic regression analysis was implemented to determine factors associated with having a GND. RESULTS: Data was collected for 1109 patients; 1038 patients were included in this analysis. 647 (62%) had a GND as part of primary management of their vulvar cancer, while 391 (38%) did not. When those with depth of invasion ≤1mm and no GND were removed, the GND rate increased to 68%. Reasons for no GND included age, obesity, advanced disease, or comorbidities. Factors significantly associated with omission of GND were increasing age (OR 0.98, CI 0.97-0.99), severe comorbidities (OR 0.57, CI 0.42-0.78), lower income quintile (OR 0.71, CI 0.54-0.95), and surgeon type (non-gynecologic oncologist vs gynecologic oncologist) (OR 0.43, CI 0.22-0.85), whereas depth of invasion >1mm was significantly associated with having a GND (OR 2.75, CI 2.08-3.62). CONCLUSION: This population-based cohort demonstrates 32% of invasive vulvar cancer patients did not have a GND at initial management. Vulvar cancer patients should be evaluated by clinicians with expertise in this rare disease to ensure that a GND is completed when feasible.

Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.

Molecular characterisation of novel mitoviruses associated with Sclerotinia sclerotiorum.

Seven putative mitoviral genomes, representing four species from three Sclerotinia sclerotiorum isolates, were fully sequenced. The genome lengths ranged from 2438 to 2815 nucleotides. The RNA-dependent RNA polymerase (RdRp) of one genome shared high amino acid (aa) sequence identity (98.5 %) with the previously described Sclerotinia sclerotiorum mitovirus 2 (SsMV2/NZ1) and was provisionally assigned the name SsMV2/14563. The RdRps of three of the genomes with closest aa sequence identity of 78.8-79.3 % to Sclerotinia sclerotiorum mitovirus 1 (SsMV1/KL1) were provisionally considered to represent a new species, and the corresponding virus was named Sclerotinia sclerotiorum mitovirus 5 (SsMV5/11691, SsMV5/14563 and SsMV5/Lu471). The remaining two novel genomes, for which the viruses were provisionally named Sclerotinia sclerotiorum mitovirus 6 (SsMV6/14563 and SsMV6/Lu471) and Sclerotinia sclerotiorum mitovirus 7 (SsMV7/Lu471), showed closest aa sequence identities to Sclerotinia sclerotiorum mitovirus 3 (SsMV3/NZ1; 57.5-57.8 %) and Cryphonectria cubensis mitovirus 1a (CcMV1a; 32 %), respectively. The RdRp proteins of all seven genomes contained the conserved aa sequence motifs (I-IV) previously reported for mitoviruses, and their 5' and 3' untranslated regions (UTRs) have the potential to fold into stem-loop secondary structures.

Molecular characterization of a novel victorivirus from the entomopathogenic fungus Beauveria bassiana.

New Zealand isolates of the entomopathogenic fungus Beauveria were examined for the presence of dsRNAs and virus-like particles. Seven out of nine isolates contained one or more high-molecular-weight dsRNAs and all seven contained isometric virus particles ranging in size from 30 to 50 nm. B. bassiana isolate ICMP#6887 contained a single dsRNA band of ~6 kb and isometric virus-like particles of ~50 nm in diameter. Sequencing revealed that the virus from ICMP#6887 had a genome of 5,327 nt with two overlapping ORFs coding for a putative coat protein (CP) and an RNA-dependent RNA-polymerase (RdRp). The sequence showed a highest CP identity of 58.3 % to Tolypocladium cylindrosporum virus 1 (TcV1) and a highest RdRp identity of 48.8 % to Sphaeropsis sapinea RNA virus 1 (SsRV1). Since both TcV1 and SsRV1 belong to the genus Victorivirus, the new virus from B. bassiana ICMP#6887 was tentatively assigned the name Beauveria bassiana victorivirus 1 (BbVV1-6887).