Single- and multiple-trait quantitative trait locus analyses for seed oil and protein contents of soybean populations with advanced breeding line background.

Soybean seed oil and protein contents are negatively correlated, posing challenges to enhance both traits simultaneously. Previous studies have identified numerous oil and protein QTLs via single-trait QTL analysis. Multiple-trait QTL methods were shown to be superior but have not been applied to seed oil and protein contents. Our study aimed to evaluate the effectiveness of single- and multiple-trait multiple interval mapping (ST-MIM and MT-MIM, respectively) for these traits using three recombinant inbred line populations from advanced breeding line crosses tested in four environments. Using original and simulated data, we found that MT-MIM did not outperform ST-MIM for our traits with high heritability (H2 > 0.84). Empirically, MT-MIM confirmed only five out of the seven QTLs detected by ST-MIM, indicating single-trait analysis was sufficient for these traits. All QTLs exerted opposite effects on oil and protein contents with varying protein-to-oil additive effect ratios (-0.4 to -4.8). We calculated the economic impact of the allelic variations via estimated processed values (EPV) using the National Oilseed Processors Association (NOPA) and High Yield + Quality (HY + Q) methods. Oil-increasing alleles had positive effects on both EPVNOPA and EPVHY+Q when the protein-to-oil ratio was low (-0.4 to -0.7). However, when the ratio was high (-4.1 to -4.8), oil-increasing alleles increased EPVNOPA and decreased EPVHY+Q, which penalizes low protein meal. In conclusion, single-trait QTL analysis is adequately effective for high heritability traits like seed oil and protein contents. Additionally, the populations' elite pedigrees and varying protein-to-oil ratios provide potential lines for further yield assessment and direct integration into breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01489-2.

Patients with cancer who will be cured and projections of complete prevalence in Italy from 2018 to 2030.

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

Performance and mechanistic study of biochar and magnesium-enhanced phytoremediation in cadmium-contaminated soil by alfalfa.

Recently, phytoremediation has been regarded as a green and environment friendly technique to treat metals contaminated soils. Thus, in this study, pot experiments were designed to investigate the combine effects of biochar and magnesium (MPs) to purify cadmium (Cd)-contaminated soils by Medicago sativa L. (alfalfa). The results showed that the combined use of biochar and Mg significantly increased the accumulation of Cd and promoted the transport of Cd from root to shoot in alfalfa, simultaneously. Importantly, the combined use of biochar and Mg could increase the accumulation of Cd in shoot and whole plant (shoot + root) of alfalfa up-to 59.1% and 23.1%, respectively. Moreover, the enhancement mechanism can be analyzed from several aspects. Firstly, the photosynthesis was enhanced, which was beneficial to plant growth. The product of photosynthesis provided energy for uptake and transport of Cd. Meanwhile, its transport in phloem could promote the transport of Cd. Secondly, the enhancement of antioxidant capacity of alfalfa effectively protected the membrane structure of alfalfa, which indicated that Cd could enter alfalfa from the channel on the cell membrane. Lastly, the chemical form of Cd and microbial community structure in soil were changed. Overall, these changes reduced the Cd toxicity in soil, enhanced the resistance capability of alfalfa, increased the Cd uptake by alfalfa and promoted the growth of alfalfa. Thus, the obtained results suggested that the combined use of biochar and Mg is an effective approach to enhance phytoremediation performance for purifying Cd-contaminated soils.

Atypical vulvar lipoma - A case report and literature review.

Atypical spindle cell lipomatous tumors of the vulva are rare masses. We report a case of atypical spindle cell lipoma of the vulva and provide a succinct review of the current understanding of these benign masses. Specifically, this report describes a case of a 20-year-old nulligravid female who presented for evaluation of a labial mass that had been growing for one year. A pelvic MRI revealed a 7 cm fatty growth. The vulvar mass was surgically resected. This case report describes the pathologic staining pattern for these masses and reviews characteristics of these benign tumors such that they are not mistaken for malignancy.

Substance use and mental health factors associated with self-reported higher risk cannabis use among people with HIV screened in primary care.

Background: While cannabis use is prevalent among people with HIV (PWH), factors associated with higher-risk use require further study. We examined factors associated with indicators risk for cannabis use disorder (CUD) among PWH who used cannabis. Methods: Participants included adult (≥18 years old) PWH from 3 HIV primary care clinics in Kaiser Permanente Northern California who reported past three-month cannabis use through the computerized Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) screening. Primary outcome was TAPS cannabis score (range 1-3), categorized as any use (1) and higher risk for CUD (≥2). Measures included sociodemographics (age, sex, race, neighborhood deprivation index [NDI]), Charlson Comorbidity Index (CCI), HIV RNA, CD4 cell counts, higher risk tobacco use (TAPS tobacco score≥2), depression, and anxiety symptoms. Unadjusted and multivariable logistic regression examined factors associated with higher risk for CUD. Results: Of the complete sample (N=978; 94.1% Male; 58.3% White; Age Mode=51-60), 35.8% reported higher risk for CUD. Unadjusted models indicated younger age, Black race, higher CCI, depression, anxiety, and higher risk tobacco use were associated with higher risk, while only Black race (OR=1.84, 95% CI[1.29, 2.63]), anxiety (OR=1.91, 95% CI[1.22, 2.98]), and higher risk tobacco use (OR=2.27, 95% CI[1.47, 3.51]) remained significant in the multivariable model. Conclusions: Black race, anxiety and tobacco use, but not HIV clinical markers, were associated with higher risk for CUD among PWH. Clinical efforts to screen and provide interventions for preventing CUD alongside anxiety and tobacco use among PWH should be evaluated.

Prevalence of viral DNA in high-grade serous epithelial ovarian cancer and correlation with clinical outcomes.

INTRODUCTION: Currently 11 infectious agents are classified as carcinogenic but the role of infectious agents on outcomes of epithelial ovarian cancer is largely unknown. OBJECTIVE: To explore the association between infectious agents and ovarian cancer, we investigated the prevalence of viral DNA in primary ovarian cancer tumors and its association with clinical outcomes. METHODS: Archived tumors from 98 patients diagnosed with high-grade serous epithelial ovarian cancer were collected between 1/1/1994 and 12/31/2010. After DNA extraction, Luminex technology was utilized to identify polymerase chain reaction-amplified viral DNA for 113 specific viruses. Demographic data and disease characteristics were summarized using descriptive statistics. We used logistic regression and Cox proportional hazards model to assess associations between tumor viral status and disease outcome and between tumor viral presence and overall survival (OS), respectively. RESULTS: Forty-six cases (45.9%) contained at least one virus. Six highly prevalent viruses were associated with clinical outcomes and considered viruses of interest (VOI; Epstein-Barr virus 1, Merkel cell polyomavirus, human herpes virus 6b, and human papillomaviruses 4, 16, and 23). Factors independently associated with OS were presence of VOI (HR 4.11, P = 0.0001) and platinum sensitivity (HR 0.21, P<0.0001). Median OS was significantly decreased when tumors showed VOI versus not having these viruses (22 vs 44 months, P<0.0001). Women <70 year old with VOI in tumors had significantly lower median OS versus age-matched women without VOI (20 vs 57 months, P = 0.0006); however, among women ≥70 years old, there was no difference in OS by tumor virus status. CONCLUSIONS: The presence of a VOI was significantly associated with a lower OS. These findings may have implications for clinical management of ovarian cancer but require additional studies.

Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model.

Introduction: Clinically, a Lactobacillus rich vaginal microbiota (VMB) is considered optimal for reproductive outcomes, while a VMB populated by anaerobes is associated with dysbiosis and the clinical condition bacterial vaginosis (BV), which is linked to increased susceptibility to sexually transmitted infections and adverse reproductive outcomes. Mouse models that mimic eubiotic and dysbiotic VMB are currently lacking but could play a critical role in improving protective interventions. Methods: In this study, probiotic, eubiotic, and dysbiotic models were developed in C57BL/6 mice, using probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, eubiotic Lactobacillus crispatus, or dysbiotic Gardnerella vaginalis strains. Endogenous sex hormones were manipulated by either ovariectomizing (OVX) mice or administering 17ß-estradiol or progesterone pellets in OVX mice. Hormone-altered mice were inoculated with probiotic Lactobacillus species, L. crispatus, or G. vaginalis, and colonization was tracked using quantitative plating assays. Glycogen and MUC-1 levels in hormone-treated mice were determined with ELISA and MUC-1 staining. Results: Following a single administration, L. rhamnosus and L. reuteri persisted in the mouse vaginal tract for up to eight days, L. crispatus persisted for up to three days, and G. vaginalis persisted for up to two days, as measured by quantitative plating assays and qPCR. Colonization of G. vaginalis was facilitated by the presence of mucin. The lack of endogenous hormones in OVX mice dramatically decreased VMB bacterial load compared to normal mice. None of the exogenous bacteria including Lactobacilli could colonize OVX mice for more than 24 hours. Treatment with 17ß-estradiol but not progesterone restored the endogenous VMB and colonization with Lactobacilli and G. vaginalis. Interestingly, 17ß-estradiol treated mice had significantly increased levels of glycogen compared to OVX and progesterone-treated mice. Discussion: Based on the results, we have shown that estrogen played a significant role in the ability for human VMB species to colonize in our mouse models, potentially through a glycogen mediated mechanism. These results suggest there is a dynamic interaction between sex hormones and the VMB, which can affect bacterial diversity and the ability for a VMB to colonize.

Relationships among Inflammatory Biomarkers and Objectively Assessed Physical Activity and Sleep during and after Chemotherapy for Gynecologic Malignancies.

Little is known regarding associations between inflammatory biomarkers and objectively measured physical activity and sleep during and after chemotherapy for gynecologic cancer; thus, we conducted a longitudinal study to address this gap. Women with gynecologic cancer (patients) and non-cancer controls (controls) completed assessments before chemotherapy cycles 1, 3, and 6 (controls assessed contemporaneously), as well as at 6- and 12-month follow-ups. Physical activity and sleep were measured using wrist-worn actigraphs and sleep diaries, and blood was drawn to quantify circulating levels of inflammatory markers. Linear and quadratic random-effects mixed models and random-effects fluctuation mixed models were used to examine physical activity and sleep over time, as well as the associations with inflammatory biomarkers. On average, patients (n = 97) and controls (n = 104) were 62 and 58 years old, respectively. Compared to controls, patients were less active, more sedentary, had more time awake after sleep onset, and had lower sleep efficiency (p-values < 0.05). Across groups, higher levels of TNF-α were associated with more sedentary time and less efficient sleep (p-values ≤ 0.05). Higher levels of IL-1ß, TNF-α, and IL-6 were associated with lower levels of light physical activity (p-values < 0.05). Associations between inflammatory biomarkers, physical activity, and sleep did not differ between patients and controls. Given these results, we speculate that inflammation may contribute to less physical activity and more sleep problems that persist even 12 months after completing chemotherapy.

Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.

OBJECTIVE: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies. METHODS: B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carcinoma (EC, n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening arrays containing most of the human proteome. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. We focused on antibodies targeting tumor-promoting syndecan binding protein (SDCBP) to demonstrate anti-tumor activity. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer and endometriosis cell lines and tumor samples. Recombinant IgG4 was generated using the variable heavy and light chains of dominant B cell receptors (BCRs) reacting against the extracellular domain of SDCBP, and used in in vivo studies in human CCC- and high-grade serous ovarian carcinoma (HGSOC)-bearing immunodeficient mice. RESULTS: Nine accessible proteins detected by both IgA and IgG were identified in all samples - including SDCBP, which is expressed in ovarian carcinomas of multiple histologies. Administration of α-SDCBP IgG4 in OVCAR3 (HGSOC), TOV21G and RMG-I (CCC) tumor-bearing mice significantly decreased tumor volume compared to control irrelevant IgG4. CONCLUSIONS: Spontaneous antibody responses exert suboptimal but measurable immune pressure against malignant progression in ovarian carcinomas. Using tumor-derived antibodies for developing novel immunotherapeutics warrants further investigation.

Prognostic features of endometrial cancer metastasis to the central nervous system.

OBJECTIVES: Central nervous system metastases (CNSm) secondary to endometrial cancer (EC) are rare. As a result, prognostic factors for this patient population are not well described. METHODS: EC patients with CNSm were identified retrospectively from two academic centers. EC patients without CNSm (non-CNSm) were used as controls. Chi-square and Fisher's exact tests were used for analysis of categorial variables. Wilcoxon tests were used for quantitative measures. Overall survival (OS) was compared with Log-rank test. Cox proportional hazard models were used to estimate hazard ratios for OS. RESULTS: 22 EC patients with CNSm and 354 non-CNSm patients were included. Compared to non-CNSm EC, the CNSm cohort was younger (58.5 vs 62.0 years, p = 0.018) with lower BMI (27.7 vs. 33.7 kg/m2, p = 0.005), and had more advanced stages (p = ≤ 0.001), grade 3 tumors (81.8% CNSm vs 25.1% non CNSm, p≤0.001) and serous histology (22.7% vs 8.5%, p = 0.010). Median survival after CNSm diagnosis was 9 months (95% CI 4, NA). CNSm was a strong poor prognostic factor (HR death 4.96, p = 0.022). Improved OS was seen with CNS as the only disease site (83m CNSm only vs 30m additional sites, p = 0.007) and less than five CNSm (49m <5 vs. 23m ≥5, p = 0.004). Surgical resection of CNSm (OS 83m surgery vs 33m no surgery, p = 0.003) or multimodal therapy (83m multimodal vs 33m single therapy, p = 0.027) resulted in longer OS. CONCLUSIONS: CNSm is a poor prognostic factor in EC, however, low volume disease with aggressive treatment may result in more favorable survival outcomes.

Cumulative burden of symptomatology in patients with gynecologic malignancies undergoing chemotherapy.

OBJECTIVE: Patients with gynecologic malignancies commonly experience distressing symptoms during chemotherapy. This study sought to evaluate whether symptoms accumulated over the course of several chemotherapy cycles, which could provide essential information for planning supportive interventions. METHOD: Patients with gynecologic malignancies completed questionnaires about fatigue, depressive symptoms, sleep, and physical activity 1 week before and after chemotherapy cycles 1, 3, and 6. Multilevel models examined the effects of time (pre- and postchemotherapy), treatment cycle (1, 3, 6), and their interaction on symptoms. Logistic regression models examined the effects of time, treatment cycle, and their interaction on the proportion of participants exceeding thresholds for clinically meaningful symptomatology. RESULTS: Most participants (N = 140; Mage = 60.8 years, SD = 10.4) had ovarian cancer (49%) and Stage III disease (55%). Participants reported worse fatigue, depressive symptoms, sleep disturbance, and sleep efficiency from pre- to posttreatment at each cycle (ps < .001). With each successive cycle, participants reported worse pretreatment fatigue (p < .001) and depressive symptoms (p < .01) but better sleep efficiency (p = .02). Fatigue increases attenuated across cycles (p = .04). There were no changes in physical activity. Across time points, at least half of participants met clinical thresholds for fatigue, sleep disturbance, and low sleep efficiency and were minimally physically active. Postchemotherapy cycle 6, 23% of participants reported clinically meaningful depressive symptoms. CONCLUSIONS: Patients with gynecologic malignancies have high rates of clinically meaningful symptomatology during chemotherapy. Patients may experience a cumulative burden of symptomatology as treatment progresses, which could have therapeutic implications. Early implementation of supportive interventions should be considered to prevent or mitigate cumulative treatment burden. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Off-label use of paclitaxel and pembrolizumab in a case of platinum refractory epithelial ovarian cancer and extensive thromboembolism.

•Management of platinum refractory ovarian cancer is challenging.•Extensive venous thromboembolism precludes anti-angiogenic combination chemotherapy.•Weekly paclitaxel and immune-checkpoint inhibitor combination provides a durable tumor control option.

The impact of distance to closest negative margin on survival after pelvic exenteration.

OBJECTIVE: To determine the effect of distance to closest negative margin on survival after pelvic exenteration (PE). METHODS: In this retrospective analysis of PE at Moffitt Cancer Center from 2000 to 2019, baseline characteristics, clinical details, and outcomes were ascertained. Distance to closest negative margin was measured. Close and distant negative margins were defined as <3 mm and ≥3 mm from malignancy to nearest surgical margin, respectively. Overall survival (OS) and progression-free survival (PFS) were determined, and Kaplan-Meier curves were compared. Cox proportional hazards regression was used to examine the association of margin status with OS and PFS. RESULTS: Of 124 PEs with malignancy, 80 (64.5%) had negative margins. Median survival was 62 (95% confidence interval [CI] 27-70) months for negative and 21 (95% CI 15-29) months for positive margins. Of 76 with negative margins and documented margin length, 26 had close and 50 had distant margins. Median survival was 32 (95% CI 14-62) months for close and 111 (95% CI 42-166) months for distant margins. Distant margins were associated with improved OS (p = 0.0054) and PFS (p = 0.0099) compared to close margins. After adjusting for other prognostic factors, patients with distant margins had significantly decreased risk of all-cause mortality (HR 0.39, 95% CI 0.19-0.78; p = 0.008) and progression (HR 0.48, 95% CI 0.23-0.99; p = 0.04) compared to positive margins. No significant differences in OS or PFS were observed between close and positive margins. This survival benefit remained among those with cervical cancer. Median survival in this cohort was 34.1 (95% CI 2.0-69.8) months for close and 165.7 (95% CI 24.5-165.7) for distant margins. CONCLUSIONS: Distant margins following PE are associated with improved OS and PFS compared to close margins.

Intraoperative tumor spill during minimally invasive hysterectomy for endometrial cancer: A survey study on experience and practice.

OBJECTIVE: Tumor spill during surgical treatment is associated with adverse oncologic outcomes in many solid tumors. However, in minimally invasive hysterectomy for endometrial cancer, intraoperative tumor spill has not been well studied. This study examined surgeon experiences and practices related to intraoperative tumor spill during minimally invasive hysterectomy for endometrial cancer. METHODS: A cross-sectional survey was conducted to the Society of Gynecologic Oncology. Participants were 220 U.S. gynecologic oncologists practicing minimally invasive hysterectomy for endometrial cancer. Interventions were 20 questions regarding surgeon demographics, surgical practice patterns (fallopian tubal ablation/ligation, intra-uterine manipulator use, and colpotomy approach), and tumor spill experience (uterine perforation with intra-uterine manipulator and tumor exposure during colpotomy). RESULTS: Nearly half of the responding surgeons completed subspeciality training >10 years ago (50.5%), and 74.1% had annual surgical volume of >40 cases. The majority of surgeons used an intra-uterine manipulator during minimally invasive hysterectomies for endometrial cancer (90.1%), and 87.2% of the users have experienced uterine perforation with an intra-uterine manipulator. Almost all surgeons performed colpotomy laparoscopically (95.9%), and nearly 60% had experienced tumor spill while making colpotomy (59.8%). Nearly 10-15% of surgeons have changed their postoperative therapy as a result of intraoperative uterine perforation (11.8%) or tumor spill (14.5%). Surgeons infrequently ablated or ligated fallopian tubes prior to performing the hysterectomy (14.1%). CONCLUSION: Our survey study suggests that many surgeons experienced intraoperative tumor spillage during minimally invasive hysterectomy for endometrial cancer. These findings warrant further studies examining its incidence and impact on clinical outcomes.

Trends in ureteral surgery on an academic gynecologic oncology service.

OBJECTIVE: To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. METHODS: We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005-2020) was compared to our prior series (1997-2004). RESULTS: Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997-2004) to 2.63 (2005-2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. CONCLUSIONS: Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.