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In February of 2024, the Society of Gynecologic Oncology (SGO) hosted a journal club focused on new treatment options for the management of advanced and metastatic endometrial cancer. This clinical commentary is intended to provide a summary report of that presentation. The session described the importance of molecular characterization shown in the work of The Cancer Genome Atlas (TCGA). The updated 2023 FIGO staging of endometrial cancer was reviewed. The panel then described the role of upfront immunotherapy for the treatment of advanced or recurrent endometrial cancer as demonstrated in four recent trials (RUBY, NRG-GY018, AtTEnd, and DUO-E studies). The DUO-E study uniquely examined the combination immunotherapy with a PARP inhibitor. The trials had unique differences in inclusion criteria, primary outcomes, and length of maintenance therapy, but all boasted similarly promising results particularly in mismatch repair deficient (dMMR) endometrial cancer. This era of rapid innovation in advanced and recurrent endometrial cancer will hopefully enhance individualized treatment approaches and improved outcomes for patients with endometrial cancer.

This article describes a three-year qualitative study on how youth of color in one community-based organization, Durham Community Youth, used the mentor text, Dr. Martin Luther King Jr.'s "What's your life's blueprint?" speech, as a reflective tool to transform themselves and their community. Using a critical literacy framework, the authors situate the study within the rich history of the Black community in Durham, North Carolina and examine how students' writing advocated for their communities by speaking out against oppressive forces. The article offers implications on how educators can reimagine the implementation and intentionality of mentor texts for youth.

INTRODUCTION: Across specialties, surgeons over-prescribe opioids to patients after surgery. We aimed to develop and implement an evidence-based calculator to inform post-discharge opioid prescription size for gynecologic oncology patients after laparotomy. METHODS: In 2021, open surgical gynecologic oncology patients were called 2-4 weeks after surgery to ask about their home opioid use. This data was used to develop a calculator for post-discharge opioid prescription size using two factors: 1) age of the patient, 2) oral morphine equivalents (OME) used by patients the day before hospital discharge. The calculator was implemented on the inpatient service from 8/21/22 and patients were contacted 2-4 weeks after surgery to again assess their opioid use at home. RESULTS: Data from 95 surveys were used to develop the opioid prescription size calculator and are compared to 95 post-intervention surveys. There was no difference pre- to post-intervention in demographic data, surgical procedure, or immediate postoperative recovery. The median opioid prescription size decreased from 150 to 37.5 OME (p

BackgroundIntervention with a mobile Health (mHealth) app can improve the efficacy of early detection of oral cancer and the outcomes for patients taking oral anticancer medications. The quality of life of oral cancer patients is significantly reduced within three months after surgery; also, their needs for nursing care and health information increase, mainly due to side effects and associated psychological problems. ObjectiveThis study aimed to evaluate changes in the care needs and quality of life of patients with oral cancer after receiving the intervention of a newly developed mHealth app. MethodsAfter surgery, oral cancer patients were divided into an experimental group (n=50) who received the mHealth app intervention and a control group (n=50) who received routine health care and instruction. After 3 months of intervention, survey questionnaires were used to assess the patients’ quality of life, nursing care needs, and acceptance of the mHealth app. ResultsThe physiological care needs were significantly decreased in the experimental group compared with the control group (P

BACKGROUND: Racial and ethnic disparities in pain management are well documented. Differences in pain assessment and management by language have not been studied in the postoperative setting in gynecologic surgery. OBJECTIVE: This study aimed to investigate the association between language and immediate postoperative pain management by comparing pain assessments and perioperative opioid use in non-English speakers and English speakers. STUDY DESIGN: This was a retrospective cohort study comparing perioperative outcomes between non-English-speaking patients and English-speaking patients who had undergone a gynecologic oncology open surgery between July 2012 and December 2020. The primary language was extracted from the electronic medical record. Opioid use is expressed in oral morphine equivalents. Proportions are compared using chi-square tests, and mean values are compared using 2-sample t tests. Although interpreter services are widely available in our institution, the use of interpreters for any given inpatient-provider interaction is not documented. RESULTS: Between 2012 and 2020, 1203 gynecologic oncology patients underwent open surgery, of whom 181 (15.1%) were non-English speakers and 1018 (84.9%) were English speakers. There was no difference between the 2 cohorts concerning body mass index, surgical risk score, or preoperative opioid use. Compared with the English-speaking group, the non-English-speaking group was younger (57 vs 54 years old, respectively; P

OBJECTIVE: To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS). METHODS: This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review. Intraoperatively, the MAPS protocol includes placement of ureteral stents, possible placental mapping with ultrasound, and uterine artery embolization by interventional radiology. Patients suspected to have PAS on prenatal imaging who underwent c-hyst were included in the analysis. Primary outcomes were intraoperative complications and postoperative complications. Secondary outcomes were blood loss, need for ICU, and length of stay. Proportions were compared using Fishers exact test, and continuous variables were compared used t-tests and Moods Median test. RESULTS: There were no differences in baseline demographics between the pre- (n = 38) and post-MAPS (n = 34) groups. The pre-MAPS group had more placenta previa (95% pre- vs. 74% post-MAPS, p = 0.013) and prior cesarean sections (2 prior pre- vs. 1 prior post-MAPS, p = 0.012). The post-MAPS group had more severe pathology (PAS Grade 3 8% pre- vs. 47% post-MAPS, p = 0.001). There were fewer intraoperative complications (39% pre- vs.3% post-MAPS, p 1l (95% pre- vs.65% post-MAPS, p = 0.001), ICU admissions (59% pre- vs.35% post-MAPS, p = 0.04) and shorter hospital stays (10 days pre- vs.7 days post-MAPS, p = 0.02) in the post-MAPS compared to pre-MAPS patients. Neonatal length of stay was 8 days longer in the post-MAPS group (9 days pre- vs. 17 days post-MAPS, p = 0.03). Subgroup analyses demonstrated that ureteral stent placement and uterine artery embolization (UAE) may be important steps to reduce complications and ICU admissions. When comparing just those who underwent UAE, patients in the post-MAPS group experienced fewer hemorrhages greater five liters (EBL >5l 43% pre- vs.4% post-MAPS, p = 0.007). CONCLUSION: An evidence-informed approach to management of PAS was associated with decreased complication rate, EBL >1l, ICU admission and length of hospitalization, particularly for patients with severe pathology.

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

BACKGROUND: Literature evaluating the management of abnormal uterine bleeding in premenopausal patients prior to endometrial malignancy diagnosis is lacking. OBJECTIVE: To evaluate predictors and consequences of inadequate evaluation and management of abnormal uterine bleeding and time to endometrial sampling in premenopausal patients prior to endometrial malignancy diagnosis.Study Design.This was a retrospective cohort study of premenopausal individuals with endometrioid endometrial cancer or atypical hyperplasia at a single institution from 2015 to 2020.. Complete noninvasive management encompassed pelvic exam, ultrasound, and progestin treatment before or in conjunction with the endometrial sampling of diagnosis. Multivariable logistic and ordinal odds models were used to evaluate predictors and outcomes. RESULTS: 152 subjects were included, 80.3 % with cancer and 19.7 % with atypical hyperplasia. The majority of patients had anovulatory bleeding, obesityand recent health care. Only 20.4 % had complete nonvinvasive management, and only 12.5 % had complete noninvasive management or endometrial sampling within 2 months of presentation with abnormal bleeding. Class III obesity reduced the likelihood of complete assessment and increased time to sampling, while age 45 and up and parity reduced time to sampling. Most patients had partial workup but no progestin treatment and long intervals before endometrial sampling after presentation to a provider with abnormal bleeding. Incomplete workup correlated to worse cancer grade and stage. CONCLUSION: Despite high clinical risk and health care contact, most patients had insufficient gynecologic management preceding a diagnosis of endometrial malignancy. Inadequate care correlated to worse oncologic outcomes and demonstrates missed opportunities for early detection and prevention of endometrial cancer.

The emergence of targeted therapies has transformed ovarian cancer treatment. However, biomarker profiling for precision medicine is limited by access to quality, tumour‐enriched tissue samples. The use of cell‐free DNA (cfDNA) in ascites presents a potential solution to this challenge. In this study, next‐generation sequencing was performed on ascites‐derived cfDNA samples (26 samples from 15 human participants with ovarian cancer), with matched DNA from ascites‐derived tumour cells (n = 5) and archived formalin‐fixed paraffin‐embedded (FFPE) tissue (n = 5). Similar tumour purity and variant detection were achieved with cfDNA compared to FFPE and ascites cell DNA. Analysis of large‐scale genomic alterations, loss of heterozygosity and tumour mutation burden identified six cases of high genomic instability (including four with pathogenic BRCA1 and BRCA2 mutations). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Ascites cfDNA identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. This advocates for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy.

Objective: Identify risk factors for development of preeclampsia refractory to aspirin prophylaxis in women at high-risk of preeclampsia. Material and methods: A retrospective cohort study analyzed 206 women identified as high-risk for preeclampsia through first-trimester screening and prescribed aspirin prophylaxis. We compared maternal characteristics, medical history, biochemical markers, and uterine artery Doppler indices between those with and without preeclampsia. Results: Women with preeclampsia had significantly higher rates of chronic hypertension (54.3% vs. 8.2%), higher first-trimester mean arterial pressure (MAP, 109.6 vs. 95.4 mmHg), and higher body mass index (BMI, 27.6 vs. 24.9) compared to controls. Second-trimester MAP and mean uterine artery pulsatility index (UtA-PI) were also significantly elevated in the preeclampsia group (103.3 mmHg and 1.39, respectively) compared to controls (89.7 mmHg and 1.05). ROC curve analysis identified an optimal second trimester UtA-PI cut-off of 1.36 for predicting preeclampsia, with sensitivity of 49% and specificity of 87.1%. When using a cut-off value of 0.77 for the second-to-first trimester UtA-PI ratio, the sensitivity and specificity were 60% and 90.6%, respectively. Conclusion: Chronic hypertension, high first and second trimester MAP, higher BMI, and elevated second trimester UtA-PI are associated with preeclampsia despite aspirin prophylaxis. Evaluating second trimester UtA-PI or the ratio of second to first trimester UtA-PI may be a promising tool for identifying women who do not respond to aspirin.

Abstract Background Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co‐chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo. Methods We generated mouse strain with Dnaja3 heterozygosity (HSA‐Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA‐Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA‐Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short‐term and long‐term GMI treatment were administrated intraperitoneally to the HSA‐Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively. Results Muscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P

BACKGROUND: The impact of albumin use during major surgery is unknown, and a dearth of evidence governing its use in major noncardiac surgery has long precluded its standardization in clinical guidelines. OBJECTIVE: In this study, we investigate institutional variation in albumin use among medical centers in the United States during major noncardiac surgery and explore the association of intraoperative albumin administration with important postoperative outcomes. METHODS: The study is an observational retrospective cohort analysis performed among 54 U.S. hospitals in the Multicenter Perioperative Outcomes Group and includes adult patients who underwent major noncardiac surgery under general anesthesia between January 2014 and June 2020. The primary endpoint was the incidence of albumin administration. Secondary endpoints are acute kidney injury (AKI), net-positive fluid balance, pulmonary complications, and 30-day mortality. Albumin-exposed and albumin-unexposed cases were compared within a propensity score-matched cohort to evaluate associations of albumin use with outcomes. RESULTS: Among 614,215 major surgeries, predominantly iso-oncotic albumin was administered in 15.3% of cases and featured significant inter-institutional variability in use patterns. Cases receiving intraoperative albumin involved patients of higher American Society of Anesthesiologists physical status and featured larger infused crystalloid volumes, greater blood loss, and vasopressor use. Overall, albumin was most often administered at high-volume surgery centers with academic affiliation, and within a propensity score-matched cohort (n=153,218), the use of albumin was associated with AKI (aOR 1.24, 95% CI 1.20-1.28, P

ObjectiveTo describe the evolution of perioperative opioid management in gynecologic oncology patients after open surgeries and determine current opioid over-prescription rates.MethodsPart one of this two-part study was a retrospective chart review of adult patients who underwent laparotomy by a gynecologic oncologist from July 1, 2012 to June 30, 2021, comparing changes in clinical characteristics, pain management and discharge opioid prescription sizes between fiscal year 2012 (FY2012) and 2020 (FY2020). In part two, we prospectively surveyed patients after laparotomy in 2021 to determine opioid use after hospital discharge.Results1187 patients were included in the chart review. Demographic and surgical characteristics remained stable from FY2012 to FY2020 with differences notable for increased rates of interval cytoreductive surgeries for advanced ovarian cancer and decreased rates of full lymph node dissection. Median inpatient opioid use decreased by 62 % from FY2012 to FY2020. Median discharge opioid prescription size was 675 oral morphine equivalents (OME) per patient in FY2012 and decreased by 77.7 % to 150 OME in FY2020. Of 95 surveyed patients in 2021, median self-reported opioid use after discharge was 22.5 OME. Patients had an excess of opioids equivalent to 1331 doses of 5-milligram oxycodone tablets per 100 patients.ConclusionInpatient opioid use in our gynecologic oncology open surgical patients and post-discharge opioid prescription size significantly decreased over the last decade. Despite this progress, our current prescribing patterns continue to significantly overestimate patients' actual opioid use after hospital discharge. Individualized point of care tools are needed to determine an appropriate opioid prescription size.

Abstract Background Klebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk. Case presentation A 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection. Conclusion Concomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue.

Abstract As medical treatment increasingly focuses on improving health-related quality of life, patient-reported outcome measures (PROMs) are an essential component of clinical research. The National Gynae-Oncology Registry (NGOR) is an Australian clinical quality registry. A suitable PROM was required for the NGOR ovarian cancer module to complement clinical outcomes and provide insights into outcomes important to patients. Our narrative review aimed to identify existing ovarian cancer-specific PROMs and ascertain which tool would be most appropriate for implementation into the NGOR ovarian cancer module. A literature review of Cochrane Library, Embase, MEDLINE and PubMed databases was performed to identify existing ovarian cancer-specific PROM tools. A steering committee was convened to (1) determine the purpose of, and criteria for our required PROM; and (2) to review the available tools against the criteria and recommend the most appropriate one for implementation within the NGOR. The literature review yielded five tools: MOST, EORTC QLQ-OV28, FACIT-O, NFOSI-18 and QOL-OVCA. All were developed and validated for use in clinical trials, but none had been validated for use in clinical quality registry. Our expert steering committee pre-determined purpose of a PROM tool for use within the NGOR was to enable cross-service comparison and benchmarking to drive quality improvements. They identified that while there was no ideal, pre-existing, ovarian cancer-specific PROM tool for implementation into the NGOR, on the basis of its psychometric properties, its available translations, its length and its ability to be adapted, the EORTC tool is most fit-for-purpose for integration into the NGOR. This process enabled identification of the tool most appropriate to provide insights into how ovarian cancer treatments impact patients’ quality of life and permit benchmarking across health services.

Abstract Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting angiogenesis, are promising candidates in cancer treatment. We propose AAPL, a sequence-based predictor to identify AAPs with machine learning models of improved prediction accuracy. Each peptide sequence was transformed to a vector of 4335 numeric values according to 58 different feature types, followed by a heuristic algorithm for feature selection. Next, the hyperparameters of six machine learning models were optimized with respect to the feature subset. We considered two datasets, one with entire peptide sequences and the other with 15 amino acids from peptide N-termini. AAPL achieved Matthew’s correlation coefficients of 0.671 and 0.756 for independent tests based on the two datasets, respectively, outperforming existing predictors by a range of 5.3% to 24.6%. Further analyses show that AAPL yields higher prediction accuracy for peptides with more hydrophobic residues, and fewer hydrophilic and charged residues. The source code of AAPL is available at https://github.com/yunzheng2002/Anti-angiogenic .

BackgroundGlaucoma is a chronic progressive optic neuropathy that necessitates lifelong treatment to reduce the decline of the optic nerve. Due to the extended and continuous treatments required for patients, complementary therapies are often considered alongside conventional treatments to enhance the effectiveness of the treatment. Acupuncture has demonstrated the potential to lower intraocular pressure in previous clinical trials, making it a promising glaucoma intervention. ObjectiveThe primary objective of this study is to conduct a single-center randomized control trial involving patients with glaucoma. Acupuncture will be evaluated as an adjunctive therapy. The trial aims to explore its effectiveness for glaucoma. MethodsIn this single-center randomized controlled trial, participants (N=50) with primary open-angle glaucoma will be randomly assigned to the treatment group, receiving ophthalmic acupuncture with “De Qi” sensation, or the control group, receiving minimum acupuncture stimulation on nonophthalmic acupoints. The intervention will consist of weekly acupuncture treatments for a total of 6 sessions. Participants will be assessed at 8 time points, which are baseline, during the intervention (6 times), and at a 3-month follow-up. The primary outcome measure is a change in the intraocular pressure before and after each acupuncture treatment. Secondary outcomes will include measurements of heart rate and blood pressure before and after acupuncture, best-corrected visual acuity, visual field, optical coherence tomography, optical coherence tomography angiography, the Glaucoma Symptom Scale, and the Glaucoma Quality of Life-15 questionnaire. ResultsRecruitment of participants for the trial commenced on June 28, 2023. A total of 10 participants have been enrolled to test the feasibility of the experiment. We anticipate that the preliminary data from this trial will be completed by December 2025. ConclusionsThis trial uses rigorous methodology and comprehensive outcome measurements to assess the clinical efficacy of acupuncture as an adjunctive therapy for glaucoma, providing valuable insights for future clinical treatment guidelines. Trial RegistrationClinicalTrials.gov NCT05753137; https://clinicaltrials.gov/study/NCT05753137 International Registered Report Identifier (IRRID)DERR1-10.2196/57888

Abstract Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan–Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression‐free survival, cancer‐specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K‐AKT‐mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT‐mTOR pathway. Furthermore, the overexpression of NTRK3 in UM‐UC‐14 cells promoted AKT‐mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT‐mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Abstract Multiple mating by avian females may increase hatching and overall brood success; however, reproductive effort and parental investment are costly, and females may be gradually depleted, with lowered outputs over time. Thus, males in social polyandry systems may differ greatly in their reproductive gains. In the present study, we investigated the reproductive outputs of social polyandrous and sex-role-reversed pheasant-tailed jacanas, Hydrophasianus chirurgus, to assess the effects of polyandry, seasonality, and male mating order on breeding success. Female jacanas produced multiple clutches, either by leaving two or more clutches with an individual male (22%), or by mating with two or more males (78%). The polyandrous females laid both the first and second clutches earlier and showed a breeding period more than twice as long as that of monandrous females. Both polyandry and seasonality affected the fate of a clutch, where clutches from polyandrous females and the early season had higher hatching and brood success rates, but the number of polyandrous females declined over the season. Polyandrous females not only laid more clutches and eggs, and gained more hatchlings and fledglings, but also achieved higher per-clutch outputs and hatching rates than monandrous females. In polyandry groups, males gained higher total hatchlings and fledglings, although not total clutches or eggs, than males in monandry or bi-andry groups. Moreover, males in polyandry groups achieved higher hatchlings and fledglings per clutch and higher hatching and brood success rates. In polyandry groups, the first-mating males obtained more clutches, eggs, and hatchlings; however, they did not have higher success rates, nor total fledglings and per-clutch outputs, than males who mated later. Overall, the results indicate a selective advantage of polyandry for the jacanas studied, particularly in the early breeding season. This advantage, however, differs both between the sexes and intra-sexually, suggesting strong connections with certain ecological/environmental conditions in addition to the jacanas’ own quality.

Abstract Background Most sepsis patients could potentially experience advantageous outcomes from targeted medical intervention, such as fluid resuscitation, antibiotic administration, respiratory support, and nursing care, promptly upon arrival at the emergency department (ED). Several scoring systems have been devised to predict hospital outcomes in sepsis patients, including the Sequential Organ Failure Assessment (SOFA) score. In contrast to prior research, our study introduces the novel approach of utilizing the National Early Warning Score 2 (NEWS2) as a means of assessing treatment efficacy and disease progression during an ED stay for sepsis. Objectives To evaluate the sepsis prognosis and effectiveness of treatment administered during ED admission in reducing overall hospital mortality rates resulting from sepsis, as measured by the NEWS2. Methods The present investigation was conducted at a medical center from 1997 to 2020. The NEWS2 was calculated for patients with sepsis who were admitted to the ED in a consecutive manner. The computation was based on the initial and final parameters that were obtained during their stay in the ED. The alteration in the NEWS2 from the initial to the final measurements was utilized to evaluate the benefit of ED management to the hospital outcome of sepsis. Univariate and multivariate Cox regression analyses were performed, encompassing all clinically significant variables, to evaluate the adjusted hazard ratio (HR) for total hospital mortality in sepsis patients with reduced severity, measured by NEWS2 score difference, with a 95% confidence interval (adjusted HR with 95% CI). The study employed Kaplan-Meier analysis with a Log-rank test to assess variations in overall hospital mortality rates between two groups: the “improvement (reduced NEWS2)” and “non-improvement (no change or increased NEWS2)” groups. Results The present investigation recruited a cohort of 11,011 individuals who experienced the first occurrence of sepsis as the primary diagnosis while hospitalized. The mean age of the improvement and non-improvement groups were 69.57 (± 16.19) and 68.82 (± 16.63) years, respectively. The mean SOFA score of the improvement and non-improvement groups were of no remarkable difference, 9.7 (± 3.39) and 9.8 (± 3.38) years, respectively. The total hospital mortality for sepsis was 42.92% (4,727/11,011). Following treatment by the prevailing guidelines at that time, a total of 5,598 out of 11,011 patients (50.88%) demonstrated improvement in the NEWS2, while the remaining 5,403 patients (49.12%) did not. The improvement group had a total hospital mortality rate of 38.51%, while the non-improvement group had a higher rate of 47.58%. The non-improvement group exhibited a lower prevalence of comorbidities such as congestive heart failure, cerebral vascular disease, and renal disease. The non-improvement group exhibited a lower Charlson comorbidity index score [4.73 (± 3.34)] compared to the improvement group [4.82 (± 3.38)] The group that underwent improvement exhibited a comparatively lower incidence of septic shock development in contrast to the non-improvement group (51.13% versus 54.34%, P

The jigsaw method which utilises peer-teaching in small-group settings permits a facilitator to incorporate active learning strategies into their educational toolbox. In November 2022, we evaluated the impact of the jigsaw method with groups stratified by post-graduate year (PGY) level. We assessed pre and post learner confidence and medical knowledge during a facilitator-led workshop. Participants were stratified into three groups who presented on the following subtopics about osteoporosis in men: (1) history and physical examination (PGY1s), (2) lab work and imaging studies (PGY2s) and (3) management and interventions (PGY3s). We evaluated if stratifying by PGY level impacted learner medical knowledge and confidence in November 2022. We had an 80% response rate from 16 actual participants from a total of 20 possible participants. Authors found a statistically significant increases in residents’ confidence and medical knowledge after the training for all questions, but broad application across a variety of learners is still needed. The jigsaw method showed improvement in learner confidence about osteoporosis in men and may be implemented in teams distributed by PGY levels. Distribution by PGY level allows each team to building on their current training level to educate their peers.

This study explores the design of a cost-effective climate policy mix for transition toward net-zero emissions in the mid-term (by 2035). Its novelty lies in the methodological advancements through the development of a soft-linking procedure that integrates a top-down computable general equilibrium model with a bottom-up energy system model. The integrated assessment focuses on the climate policy mix under the framework of Taiwan’s Climate Change Response Act passed in 2023. The analysis shows that a policy mix combining investments in energy transition with user-pay hybrid pricing measures can facilitate cost-effective mitigation and enhance public acceptance. The proposed hybrid pricing includes cost-based electricity pricing and a two-step carbon pricing strategy that encourages early action (before 2030) for larger emitters. Finally, we demonstrate that accelerating the transition is crucial, as it reduces the economic costs of meeting emission targets by inducing further investments in energy efficiency improvement and lowering the carbon pricing levels required to close the abatement gap.

BACKGROUND: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B. METHODS: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1. RESULTS: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (

BackgroundTERT promoter mutations are observed in 80% of wild-type IDH glioblastoma (GBM). Moreover, the upstream TERT transcription factor GABPB1 was recently identified as a cancer-specific therapeutic target for tumors harboring a TERT promoter mutation. In that context, noninvasive imaging biomarkers are needed for the detection of TERT modulation.MethodsMultiple GBM models were investigated as cells and in vivo tumors and the impact of TERT silencing, either directly or by targeting GABPB1, was determined using 1H and hyperpolarized 13C magnetic resonance spectroscopy (MRS). Changes in associated metabolic enzymes were also investigated.Results1H-MRS revealed that lactate and glutathione (GSH) were the most significantly altered metabolites when either TERT or GABPB1 was silenced, and lactate and GSH levels were correlated with cellular TERT expression. Consistent with the drop in lactate, 13C-MRS showed that hyperpolarized [1-13C]lactate production from [1-13C]pyruvate was also reduced when TERT was silenced. Mechanistically, the reduction in GSH was associated with a reduction in pentose phosphate pathway flux, reduced activity of glucose-6-phosphate dehydrogenase, and reduced NADPH. The drop in lactate and hyperpolarized lactate were associated with reductions in glycolytic flux, NADH, and expression/activity of GLUT1, monocarboxylate transporters, and lactate dehydrogenase A.ConclusionsOur study indicates that MRS-detectable GSH, lactate, and lactate production could serve as metabolic biomarkers of response to emerging TERT-targeted therapies for GBM with activating TERT promoter mutations. Importantly these biomarkers are readily translatable to the clinic, and thus could ultimately improve GBM patient management.

This study proposes a hybrid approach to predict customer churn by combining statistic approaches and machine learning models. Unlike traditional methods, where churn is defined by a fixed period of time, the proposed algorithm uses the probability of customer alive derived from the statistical model to dynamically determine the churn line. After observing customer churn through clustering over time, the proposed method segmented customers into four behaviors: new, short-term, high-value, and churn, and selected machine learning models to predict the churned customers. This combination reduces the risk to be misjudged as churn for customers with longer consumption cycles. Two public datasets were used to evaluate the hybrid approach, an online retail of U.K. gift sellers and the largest E-Commerce of Pakistan. Based on the top three learning models, the recall ranged from 0.56 to 0.72 in the former while that ranged from 0.91 to 0.95 in the latter. Results show that the proposed approach enables companies to retain important customers earlier by predicting customer churn. The proposed hybrid method requires less data than existing methods.

This paper demonstrates the effectiveness and superiority of Empirical Mode Decomposition (EMD) in projecting non-stationary hydrological data. The study focuses on daily Sea Surface Temperature (SST) sequences in the Niño 3.4 region and uses EMD to forecast the probability of El Niño events. Applying the Mann–Kendall test at the 5% significance level reveals a significant increasing trend in SST changes in this region, particularly noticeable after 1980. This trend is associated with the occurrence of El Niño and La Niña events, which have a recurrence interval of approximately 8.4 years and persist for over a year. The modified Oceanic Niño Index (ONI) proposed in this study demonstrates high forecast accuracy, with 97.56% accuracy for El Niño and 89.80% for La Niña events. Additionally, the EMD of SST data results in 13 Intrinsic Mode Functions (IMFs) and a residual component. The oscillation period increases with each IMF level, with IMF7 exhibiting the largest amplitude, fluctuating between ±1 °C. The residual component shows a significant upward trend, with an average annual increase of 0.0107 °C. These findings reveal that the EMD-based data generation method overcomes the limitations of traditional hydrological models in managing non-stationary sequences, representing a notable advancement in data-driven hydrological time series modeling. Practically, the EMD-based 5-year moving process can generate daily sea temperature sequences for the coming year in this region, offering valuable insights for assessing El Niño probabilities and facilitating annual updates.

BackgroundPatients with gynecologic cancer undergoing chemotherapy experience multiple co-occurring symptoms. Understanding how symptom clusters change over time is essential to the development of interventions that target multiple co-occurring symptoms.ObjectiveThe aim of this study was to assess the relative stability of symptom clusters across a chemotherapy cycle in patients with gynecologic cancer.MethodsThis is a longitudinal, descriptive study. Eligible patients (n = 232) were English-speaking adults (≥18 years old) with gynecologic cancer. Data were collected in the week before patients' second or third cycle of chemotherapy (T1) and at 1 (T2) and 2 (T3) weeks after chemotherapy. Three dimensions of the symptom experience (occurrence, severity, and distress) were assessed using a modified version of the Memorial Symptom Assessment Scale. Symptom clusters for each dimension and time point were identified through exploratory factor analysis.ResultsA 5-factor solution was selected for each exploratory factor analysis. Hormonal, respiratory, and weight change clusters were identified across all dimensions and time points. A psychological symptom cluster was identified at T1 for occurrence and severity and at T2 and T3 for all 3 dimensions. A gastrointestinal symptom cluster was identified at T1 for occurrence and at T2 and T3 for all 3 dimensions. The hormonal, respiratory, psychological, and weight change symptom clusters exhibited common symptoms across dimensions and time points.ConclusionsHormonal, respiratory, weight change, and psychological symptom clusters are relatively stable across a cycle of chemotherapy in patients with gynecologic cancer.Implications for practiceClinicians need to assess patients for multiple co-occurring symptoms and initiate multimodal interventions.

Abstract Background The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. Methods To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. Results Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. Conclusion CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

Abstract Background Taiwan’s unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors. Methods A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses. Results Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor’s degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p