Beginning in the 2023-2024 application cycle, specialties began to try out different approaches to program signaling. This study explores the effects of program signals in deciding whom to interview across small number signal (SNS), large number signal (LNS) and two-tier signal (2TS) approaches. Of the 22 specialties that used signaling in the Electronic Residency Application Service (ERAS) in the 2023-2024 cycle, dermatology, emergency medicine, general surgery, neurological surgery, obstetrics and gynecology, and orthopaedic surgery were analyzed as representative of the signaling approaches being studied. Data on signals, applicant type, passing USMLE Step 1, USMLE Step 2 CK score, school and program state were collected from the MyERAS application; interview data was collected from ERAS PDWS and/or Thalamus. Multilevel logistic regression was used to assess the relationship between signals, other application data, and interview invitation. The presence of a signal increased interview likelihood regardless of approach. Applicants who signaled in SNS specialties observed a 4.7 to 7.4 times the odds of receiving interview offers compared to 8.4 to 18.5 times the odds in LNS, and up to 55 to 218 times the odds for gold signals in the 2TS approach. In-state status, applicant type, never failing Step 1, and Step 2 CK scores contributed to interview selection, though the effects were not as great as the signal contribution. The effect of signaling was stronger for out-of-state applicants. The authors report a strong association between signaling and the likelihood of an interview regardless of signaling method, though the effect was greatest with two-tier and large signal approaches. There was variation in the use of signals and the weight a program allocates to signals. Never having failed the Step 1 exam, state alignment, applicant type, and Step 2 CK scores were also associated with interview invitation.
Training in gynecologic oncology requires mastery of complex decision making and technically demanding procedures, yet opportunities for repetitive practice are often limited by case volume, patient-safety considerations, and unequal access to expert supervision. Artificial intelligence (AI) has therefore attracted attention as a potential adjunct to simulation-based and feedback-intensive surgical education. This qualitative study explored how educators and learners perceive the role of AI in gynecologic oncology training. Semi-structured interviews were conducted with five gynecologic oncology faculty members and ten postgraduate obstetrics and gynecology trainees at a university-affiliated teaching hospital. Interview data were analyzed using inductive thematic analysis. Three themes were identified: AI as a tool for expanding deliberate practice and structured feedback, barriers that limit acceptable adoption, and conditions required for responsible implementation. Participants described AI-enhanced simulation as valuable for risk-free rehearsal, exposure to uncommon cases, and more objective assessment, while also emphasizing concerns about realism, cost, access, and data governance. Both groups supported a hybrid educational model in which AI supplements rather than replaces human mentorship. These findings suggest that AI can strengthen gynecologic oncology education when it is integrated into competency-based curricula, accompanied by faculty oversight, and supported by appropriate ethical and infrastructural safeguards.
Recurrent hemorrhagic pleural effusion presents as a challenge for both the clinician and the patient, with common causes being tuberculosis, malignancy, and collagen vascular diseases. Among uncommon causes of recurrent hemorrhagic effusion is catamenial hemothorax, which is a part of thoracic endometriosis syndrome (TES). Endometriosis is the extrauterine growth of endometrial glands and stroma. It is relatively common among women of reproductive age-group, with reported incidence of around 11%. Although rare, the thorax is the most common extraabdominal site for endometriosis. Here we present a rare case of recurrent hemorrhagic pleural effusion due to thoracic endometriosis in a young female with infertility. A 33-year-old female housewife presented with dyspnea on exertion modified Medical Research Council (mMRC) grade 2 and dry cough occasionally for 6 months. She had a history of tubercular cervical lymphadenopathy for which she was on treatment. Therapeutic thoracocentesis was performed thrice in 4 months. Routine microscopy showed predominantly lymphocytes, mesothelial cells, and numerous foamy histiocytes, some pigment laden. There were no malignant cells or acid-fast bacilli (AFB) detected in the fluid. Pleural fluid amylase and lipase were normal. Contrast-enhanced computed tomography (CT) thorax showed moderate right-sided pleural effusion without any evident parenchymal lesions, pleural lesions, or mediastinal lymphadenopathy. Ultrasonography (USG) abdomen and pelvis showed mild ascites which was nontappable. As we had not reached a definitive diagnosis, medical thoracoscopy was performed. It showed moderate hemorrhagic pleural fluid in the pleural cavity and a small raised erythematous glandular tissue on the parietal pleural surface from which biopsy was taken. Histopathology showed an island of endometrial stroma with a single gland. Immunohistochemistry was performed on this section, which was PAX8 and CD10 positive, confirming the diagnosis of thoracic endometriosis. Pleurodesis with talc slurry was done to prevent further refilling of the effusion. Gynecology opinion was sought, and patient was started on monthly subcutaneous injections of gonadotropin-releasing hormone (GnRH) analogue for 3 months. Chest X-ray after 3 months showed no refilling of pleural effusion. Catamenial hemothorax is the second commonest manifestation of TES, occurring in approximately 14% of cases. It affects the right side in about 80% of the cases. Diagnosis is based on high degree of suspicion and is often delayed. Video-assisted thoracic surgery (VATS) remains the gold standard for diagnosis and management of TES. Medical thoracoscopy is a viable alternative in resource-poor settings or when diagnosis is not confirmed. On histology, diagnosis is confirmed by the presence of endometriotic glands or stroma, which may also show stromal arterioles, erythrocytes, and pigmented histiocytes. In difficult-to-diagnose cases, CD10 immunohistochemical staining can help in diagnosis of endometrial tissue. There are various treatment modalities considered in the management of catamenial hemothorax, like surgical resection, medical management along with pleurodesis, combination therapy, or in some cases, simple observation. Currently, VATS with GnRH analogue therapy is considered the gold standard of management.
Patients with advanced ovarian cancer receiving neoadjuvant chemotherapy are at increased risk of venous thromboembolism, although the reported incidence, risk factors, and its impact on the timing of interval debulking surgery remain heterogeneous. This study evaluates the rate and predictors of venous thromboembolism during neoadjuvant chemotherapy, its effect on surgical timing, and contextualizes the findings through a targeted narrative review of the literature. We conducted a retrospective cohort study of patients with International Federation of Gynecology and Obstetrics stage III-IV epithelial ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery at the European Institute of Oncology between January 2014 and December 2023. Routine thromboprophylaxis was not administered. Clinicopathologic data were collected, and logistic regression analyses were performed to identify predictors of venous thromboembolism and delayed surgery, defined as receiving ≥5 cycles of neoadjuvant chemotherapy prior to surgery. A targeted narrative review of PubMed (2012-2025) summarized venous thromboembolism rates and associated risk factors. Among 694 patients, 32 (4.6%) developed venous thromboembolism during neoadjuvant chemotherapy, including 23 deep vein thromboses (71.9%) and 9 pulmonary embolisms (28.1%). No baseline clinical or pathological factors predicted thromboembolism. However, it was independently associated with surgical delay; affected patients were more than twice as likely to undergo surgery after ≥5 cycles of chemotherapy (adjusted odds ratio 2.15, 95% confidence interval 1.04 to 4.43, p =.04). Venous thromboembolism during neoadjuvant chemotherapy is relatively uncommon but clinically relevant, as it delays surgery. Early detection and preventive strategies may mitigate its impact in this high-risk population.
The primary objective was to compare endostatin levels between patients with preeclampsia and those with normal pregnancies. The secondary objectives comprised comparing endostatin levels in early-onset preeclampsia, late-onset preeclampsia, and normal pregnancies, as well as comparing pregnancy and neonatal outcomes between preeclampsia and normal pregnancies. This cross-sectional analytic study included 68 patients with preeclampsia and 68 normal pregnancies. The groups were matched for gestational age. The study was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, from July 2024 to July 2025. Blood samples were collected in non-heparinized tubes and stored at -80 °C until assayed. Maternal endostatin levels were measured using enzyme-linked immunosorbent assays (ELISA). Maternal and neonatal outcomes were recorded. The median serum endostatin level in patients with preeclampsia was not significantly different from that in normal pregnancies (3.45 vs. 4.32 ng/ml, p = 0.304). The median endostatin levels in early-onset preeclampsia and late-onset preeclampsia did not differ from those in normal pregnancies at the same gestational age (2.84 vs. 7.09 ng/ml, p = 0.05, and 3.86 vs. 4.26 ng/ml, p = 0.845, respectively). Patients with preeclampsia had a higher rate of cesarean delivery (63.2% vs. 41.2%, p = 0.01) and a higher rate of composite maternal complications (16.2% vs. 1.5%, p = 0.004) compared to normal pregnancies. Preeclampsia patients had lower neonatal birth weight (2,419 ± 655 vs. 2,903 ± 507 g, p < 0.001) and longer neonatal lengths of stay (median 5 vs. 4 days, p = 0.01) than those in normal pregnancy. The endostatin level in patients with preeclampsia was not statistically different from that in normal pregnancies. These research findings refute the hypothesis that serum endostatin levels are higher in preeclampsia. Therefore, serum endostatin levels may not be a reliable biomarker for predicting preeclampsia in this population. Preeclampsia is associated with adverse maternal and neonatal outcomes.
New Accreditation Council for Graduate Medical Education and American Board of Family Medicine guidelines encourage training family medicine residents in point-of-care ultrasound (POCUS). Prior studies have focused on the perceived needs of learners but did not assess patient or community need. We performed a triangulated learner- and patient-oriented needs assessment to inform POCUS curriculum development within a family medicine residency. Our learner assessment consisted of a Likert scale survey of the perceived skill and importance of 36 POCUS modalities discussed in the 2016 American Academy of Family Physicians POCUS curriculum guidelines. Our patient-oriented needs assessment was collected through analysis of all family medicine practice (FMP) site imaging orders placed in 2023. The learner survey demonstrated the highest skill gaps in POCUS training to be evaluation for hemothorax and evaluation for pleural effusion. FMP site imaging order analysis demonstrated that hepatobiliary and obstetrics/gynecology concerns were the most frequently answered by POCUS for patients seen at the FMP site. POCUS is an important and underutilized diagnostic tool in family medicine. POCUS curricula in graduate medical education are vital to successful implementation of POCUS in primary care; however, needs assessment techniques used in prior studies differ from the patient and community needs in our study. We recommend the use of both needs assessment strategies for optimal POCUS training outcomes. Further research replicating this modality is necessary to determine the optimal needs assessment approach for POCUS in family medicine.
Multiple mitochondrial dysfunction syndrome type 3 (MMDS3; OMIM #615330) is a rare autosomal recessive disorder caused by mutations in IBA57. Its complex clinical presentation and molecular pathogenesis remain incompletely understood. The study included comprehensive clinical evaluation, IBA57 genetic testing, Western Blotting for protein expression, and transcriptomic and metabolomic analyses of amniotic fluid cells. The proband presented with typical MMDS3 features, and both affected siblings carried compound heterozygous IBA57 missense mutations (c.310G>T and c.826C>T) leading to reduced IBA57 protein expression. RNA-seq revealed transcriptional dysregulation of the PI3K-Akt signaling pathway, and metabolomics demonstrated TCA cycle disturbances in amniocytes. Respiratory chain enzyme assays showed a selective deficiency of complex II activity in fetal liver. The compound heterozygous IBA57 mutations c.310G>T and c.826C>T lead to reduced IBA57 protein expression, selective impairment of respiratory chain complex II, and transcriptional dysregulation of the PI3K-Akt pathway, together contributing to the MMDS3 phenotype in the proband and the affected fetus.
Neonatal mortality remains high in low‑ and middle‑income countries, where early postnatal care (PNC) within 48 hours can avert many deaths. Yet neither the national coverage of newborn PNC nor the factors associated with its receipt have been assessed. We assessed the coverage of newborn PNC components and the factors associated with their receipt in Afghanistan. We conducted a cross‑sectional analysis of 11,965 mother-infant dyads from the 2022-2023 Afghanistan Multiple Indicator Cluster Survey. The outcome was coded 'yes' if the infant received at least two of the following six newborn PNC components within 2 days of birth: temperature measurement, weighing, cord examination, breastfeeding counseling, observation of breastfeeding, and counseling on danger signs. We fitted a multivariable logistic regression model to identify factors associated with the outcome. Only 41.0% of infants received ≥2 components; merely 1.9% received all six components of PNC. The odds of receiving ≥2 components of PNC were higher among infants whose households had an educated head, whose mothers attended 1-3 or ≥4 antenatal care (ANC) visits, those born in private and public health facilities, and those delivered by cesarean section. Infants in higher wealth quintiles also had progressively greater odds. Conversely, infants perceived as small at birth had lower odds of receiving ≥2 PNC components. Four out of ten newborns received ≥2 components of PNC, with marked inequities by head of household education, ANC use, delivery setting, and wealth status. Targeted interventions addressing these inequalities are urgently needed to strengthen early newborn PNC. Main findings: Four out of ten newborns in Afghanistan received at least two components of early postnatal care, with substantial inequalities by head of household education, antenatal care use, place of birth, birth size, and household wealth.Added knowledge: This study provides nationally representative evidence on the receipt and associated factors of early newborn postnatal care in Afghanistan, moving beyond previous work that mainly examined individual newborn care components or maternal postnatal care.Global health impact for policy and action: Strengthening antenatal care, facility-based delivery, postnatal care quality, and targeted support for small and disadvantaged newborns can help improve newborn survival and reduce inequities in fragile health systems.
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Nigeria continues to face persistent circulation of circulating vaccine-derived poliovirus type 2 (cVDPV2), driven by sustained transmission of dominant viral lineages and intermittent emergence of new strains. Since 2020, the NIE-ZAS-1 lineage has remained the most epidemiologically significant strain, with ongoing spread across multiple states. This study describes the temporal, spatial, and lineage-specific transmission dynamics of NIE-ZAS-1 and emerging related lineages between 2020 and 2025. We conducted a descriptive epidemiological and spatial analysis of poliovirus lineage surveillance data across Nigeria from 2020 to 2025. Genetic lineage classifications (NIE-ZAS-1, NIE-YBS-1, NIE-YBS-2, NIE-BOS-1, NIE-KTS-1) were analyzed by state, year, and quarter. Geographic diffusion patterns were reconstructed using state-level detection timelines, frequency counts, and directional spread from presumed origin states. NIE-ZAS-1 originated in Zamfara State in 2020 and expanded to at least 21 states by 2025, accounting for the majority of detections throughout the study period. Transmission showed marked seasonality, with consistent Q3 peaks. In contrast, newer lineages such as NIE-YBS-1, NIE-YBS-2, NIE-BOS-1, and NIE-KTS-1 demonstrated limited spatial spread and short-lived circulation, largely confined to Borno, Yobe, and Kano states. Despite reductions in case counts in some quarters, no lineage showed sustained interruption of transmission by 2025. Persistent cVDPV2 transmission in Nigeria is driven predominantly by the long-standing NIE-ZAS-1 lineage, with emerging strains failing to replace but adding complexity to the transmission landscape. These findings underscore the need for geographically targeted, lineage-informed vaccination strategies, enhanced surveillance in origin and amplifier states, and intensified efforts during high-risk seasonal periods.
Twin pregnancy is traditionally high risk, and with rising incidence, there is a need for evaluating the outcomes as a marker of the quality of care offered. There is some evidence to suggest that the second twin is at higher risk of adverse fetal outcomes, though several studies, especially in more advanced healthcare settings, have debunked this. There is a need for robust evidence on second twin outcomes in low-resource settings like ours to enable standardization and improved quality of care, which will lead to improved fetal outcomes. The objective of this study is to compare the delivery outcomes of first and second twins in terms of Apgar scores and stillbirth rates. The records of women who presented with twin gestation to the delivery suite, from January 2016 to December 2022, were retrieved using a structured proforma. Delivery outcomes were the Apgar scores at one and five minutes, and stillbirth rates. The most common presentation of the second twin was cephalic, and the mode of delivery was via CS. There was no statistically significant difference in Apgar score and stillbirth rate between the first and second twins. However, in those that had vaginal deliveries, the first- and fifth-minute Apgar scores were significantly lower in the second twin than the first twin. There were no significant differences in adverse fetal outcomes between the first and second twins in the general population. However, the second twin may be at higher risk of birth asphyxia in twins delivered vaginally.
Laparoscopic surgery is widely preferred for benign ovarian tumors because it is associated with less postoperative pain, fewer complications, and shorter recovery time compared with laparotomy. However, laparoscopic surgery for giant cystic ovarian tumors occupying the entire abdominal cavity poses substantial challenges, including difficult trocar insertion and the risk of intraperitoneal spillage, particularly when the cyst contains highly viscous mucinous material that is difficult to aspirate with standard suction devices. We report a case of a 72-year-old woman with a 37.7 × 32.0 × 15.5 cm multilocular ovarian tumor extending from the pouch of Douglas to the upper abdomen. Ultrasonography suggested highly viscous contents, and magnetic resonance imaging showed no findings of malignancy. Given that the tumor markedly bulged into the pouch of Douglas, a transvaginal approach was selected to achieve safe decompression prior to trocar placement. Through a posterior colpotomy, the cyst wall was exposed extraperitoneally, enabling controlled extracorporeal incision and drainage of 9,782 mL of highly viscous fluid facilitated by manual abdominal compression. Tumor decompression enabled safe trocar insertion, pneumoperitoneum establishment, and laparoscopic adhesiolysis of dense adhesions to the abdominal wall and omentum. The adnexa were subsequently ligated and removed transvaginally without macroscopically evident intraperitoneal spillage of the tumor contents. Histopathology examination confirmed mucinous cystadenoma arising in a mature cystic teratoma. The patient experienced an uneventful recovery and was discharged on postoperative day 3. This case highlights that transvaginal drainage via posterior colpotomy is an effective strategy for giant ovarian cystic tumors with highly viscous contents, particularly when the tumor protrudes into the pouch of Douglas. Tailoring the surgical approach to the tumor's anatomical characteristics can facilitate safe, minimally invasive management even in cases traditionally managed by laparotomy.
Cannabis use is rising among adults with type 2 diabetes mellitus (T2DM). Whether cannabis use modifies the cardio-renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is unknown. Retrospective propensity score-matched cohort study in the TriNetX Research Network (January 2017-December 2025). Adults with T2DM initiating GLP-1 RA therapy were classified as people who use cannabis (≥2 ICD-10-CM F12.x codes within 2 years before index) or as people who did not (the comparison cohort). 1:1 matching was performed on more than 40 baseline covariates. The primary outcome was all-cause mortality; secondary outcomes were 4-point major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE). Cox models estimated hazard ratios (HRs); E-values assessed robustness to unmeasured confounding. Among 614,333 eligible patients, 4117 people who use cannabis were matched to 4117 comparison patients (median follow-up 2.6 years). Cannabis use was associated with increased all-cause mortality (HR 1.64, 95% CI 1.38-1.96), MACE (HR 1.42, 1.26-1.59), and MAKE (HR 1.55, 1.34-1.79). A dose-response was observed: cannabis use disorder (HR 2.20) conferred greater mortality risk than non-disordered use (HR 1.73). Associations persisted across sensitivity and subgroup analyses; E-values were 2.21-2.63. In an exploratory analysis, concomitant sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy was associated with lower mortality (HR 0.62, 0.45-0.85) and MAKE (HR 0.70, 0.54-0.92) in this group. Cannabis use was associated with substantially higher mortality, cardiovascular, and renal risk among patients with T2DM initiating GLP-1 RAs, with a dose-response pattern. Clinicians should inquire about cannabis use when prescribing GLP-1 RAs.
Congenital cytomegalovirus (cCMV) infection is a major cause of neurodevelopmental impairment and sensorineural hearing loss worldwide, particularly in low- and middle-income countries where standardized molecular screening programs are not routinely implemented. Early laboratory confirmation within the first 21 days of life is essential to differentiate congenital from postnatal infection. This study evaluated the diagnostic agreement between the Simplexa cCMV Direct real-time PCR assay and conventional nested PCR for detecting CMV DNA in neonatal urine specimens in Indonesia. A cross-sectional diagnostic agreement study was conducted between September and December 2023 at a tertiary referral hospital. Urine samples from 87 neonates aged <= 21 days with clinical suspicion of congenital infection were tested using both assays. The Simplexa assay detected 29 positive and 58 negative samples, while conventional nested PCR identified 28 positive and 59 negative samples. Agreement was assessed using Cohen's kappa coefficient, McNemar's test, and positive and negative agreement rates. The assays demonstrated near-perfect agreement (k = 0.87; 95% CI: 0.75-0.98; p < 0.001). Positive and negative agreement were 91.2% and 95.7%, respectively, with no statistically significant difference between methods (McNemar p = 1.00). Simplexa Direct real-time PCR showed high agreement with conventional nested PCR while offering operational advantages including simplified workflow and reduced contamination risk. These findings support the implementation of automated direct molecular platforms for neonatal cCMV diagnosis in tropical and resource-limited healthcare settings.
Tuberculosis (TB) is an important global health problem, especially for pregnant women, a vulnerable group. This systematic review and meta-analysis was conducted in this group to obtain cumulative results in a collective effort toward the World Health Organization (WHO) End TB Strategy. The databases Ovid MEDLINE, Embase, PubMed, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials were searched for the last 10 years till 14th January 2025. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this analysis. Pregnancy outcomes in terms of maternal complications and perinatal complications, including observed mortality, were considered for analysis. A total of 9,873 records were identified through database searching, and 15 studies, including 3,045 pregnant women with TB, were selected for final analysis. The pooled mean maternal age was 27.6 years, and more than half of TB cases were diagnosed antenatally. Among pregnancy-related complications, fetal growth restriction, pregnancy-induced hypertension, oligohydramnios, and gestational diabetes were seen in 19, 15, 11, and 10% of cases, respectively. Low birth weight, preterm birth, small for age, and low Apgar score (<7) had pooled prevalences of 30, 22, 20, and 13%, respectively. Maternal mortality and neonatal mortality showed pooled prevalences of 0.05 [95% confidence interval (CI): 0.03-0.08] and 5% (95% CI: 3-8%), respectively. Low to moderate heterogeneity was found among observations. This systematic review and meta-analysis showed continued maternal and perinatal adverse outcomes in pregnant women with TB even in the current era, highlighting the need to optimize healthcare.
Since 2021, a Dutch guideline recommends offering induction of labor (IOL) from 41 + 0 weeks, alongside the option of expectant management (EM), through shared decision-making (SDM). We examined care providers' opinions and use of the guidelines' SDM tools, self-reported adherence to SDM content recommendations, perspectives on SDM conversations, and its association with birth beliefs. For this cross-sectional survey, including 575 maternity care providers, an online questionnaire was developed. Most questions used a 5-point Likert scale. Birth beliefs (medical vs. natural) were assessed using the Birth Beliefs Scale. Uni- and multivariable regression analyses were used to assess the association between a medical and natural view and SDM content and perspectives. Among participants aware of the tools, usage rates were 63% for Tool 1 (steps of SDM), 72% for Tool 2 (choice card IOL/EM), and 51% for Tool 3 (choice card alternatives). Helpfulness scores exceeded the neutral midpoint (3.7, 3.8, and 3.7). The majority of participants reported addressing most of the items of SDM that were recommended in the guideline, though lower rates were seen for addressing outcome percentages (37%), parity differences (33%), and EM beyond 42 weeks (37%). Birth beliefs influenced SDM content, emphasis on advantages of options, and perspectives; those with stronger natural views paid more attention to women's preferences and alternatives. Care providers are generally positive about the tools in the late-term management guideline, though not all use them. Key elements for SDM are often omitted, and birth beliefs influence how SDM is conducted.
Resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) in high-grade serous ovarian cancer (HGSOC) is increasingly driven by non-genetic drug-tolerant dormant cell populations, yet the adaptive programs sustaining these cells remain poorly understood. Here, we established a longitudinal model of PARPi-induced dormancy and proliferative recovery using authenticated HGSOC cell lines spanning low, intermediate, and high homologous recombination deficiency (HRD) contexts. PARPi treatment generated a reversible reservoir enriched in polyploid giant cancer cells (PGCCs), with distinct recovery trajectories across HRD contexts. Despite heterogeneous metabolic, mesenchymal, and stress-adaptive remodeling, integrated transcriptomic and proteomic analyses identified a conserved dependence on redox homeostasis during dormancy. Transcriptomics-guided functional screening identified disulfiram as a candidate therapeutic strategy targeting this shared vulnerability. Disulfiram synergized with PARPi to disrupt ALDH-associated redox buffering, increase reactive oxygen species, enhance DNA damage, and deplete the PGCC-enriched dormant reservoir. Antioxidant rescue experiments supported oxidative stress as a key mediator of this effect. Live-cell time-lapse imaging further demonstrated that a subset of PGCCs generated mononuclear progeny following PARPi withdrawal, supporting their contribution to post-treatment repopulation. Importantly, the disulfiram-PARPi combination durably suppressed clonogenic recovery after drug withdrawal while exhibiting preferential cytotoxicity toward HGSOC cells relative to the non-malignant epithelial models tested. Together, these findings demonstrate that, despite heterogeneous adaptive responses across HRD contexts, PARPi-induced dormant HGSOC cells converge on a shared redox-dependent vulnerability. Targeting ALDH-associated redox homeostasis with disulfiram represents a mechanistically supported strategy to eliminate recovery-competent dormant cells and potentially delay PARPi resistance and disease recurrence.
Noninvasive detection of ultra-weak biomagnetic signals is crucial for modern biosensing, but conventional magnetic sensors are fundamentally limited by intrinsic noise. Orthogonal fluxgates (OFGs) enable high signal-to-noise-ratio detection of weak magnetic fields, yet their performance is still constrained by intrinsic 1/f noise and Barkhausen-related magnetic fluctuations. This study reports a low-noise orthogonal fluxgate in which a newly designed magnetic core and circuit mitigate existing noise limitations. The CoP/Ag composite core, featuring an amorphous-nanocrystalline dual phase, is associated with reduced low-frequency magnetic loss and improved noise performance. When integrated with a closed-loop feedback, the sensor achieves a noise floor of 8 pT/√Hz at 1 Hz. The sensor enables reliable detection of ultralow-concentration magnetic-bead signals. Alpha-fetoprotein (AFP) was used as a model biomarker in an immunomagnetic bead assay, yielding a linear response from 50 fg mL-1 to 100 ng mL-1 and a detection limit of 50 fg mL-1, which compares favorably with representative reported AFP magnetic biosensors. OFGs demonstrate strong prospects in biosensing, geomagnetic measurements, and weak field detection.
The involvement of oxidative stress (OS) in pre-eclampsia (PE) has been reported, and the present study probed into the OS-related feature genes in PE. The dataset GSE60438 was used to identify the OS-related features in PE, and corresponding feature genes were identified using machine learning algorithms including weighted gene co-expression network analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and support vector machine-recursive feature elimination (SVM-RFE). The diagnostic value of the feature genes and their correlation with immune infiltration were explored. Gene set enrichment analysis (GSEA) was performed to identify enriched pathways of these genes. Furthermore, regulatory networks involving the feature genes were constructed. The role of these genes in hypoxia/reoxygenation (H/R)-induced trophoblasts was investigated. Two WGCNA-identified modules (MEpurple and MEturquoise) were intersected with OS-related genes, yielding 359 common genes. Through machine learning algorithms and expression validation, three genes (CPT1A, CYGB and MRPL3) were identified and used to establish a diagnostic model, which reached an AUC of 0.930. The transcription factor (TF) SPI1 and multiple miRNAs formed a potential regulatory network for CPT1A, CYGB and MRPL3, and the expression of these three genes was closely associated with the infiltration of various immune cells (such as monocytes and macrophages M1) in PE. Cellular experiments confirmed that CPT1A silencing alleviated trophoblast dysfunction, reduced reactive oxygen species (ROS) levels, and decreased apoptosis under H/R conditions. The present study examined the OS features in PE, hoping to contribute to the management of PE.
Female genital mutilation/cutting (FGM/C) remains widespread in Nigeria. With an estimated 19.9 million survivors, Nigeria accounts for the third highest number of women and girls who have undergone FGM worldwide. This study, therefore, aimed at identifying the factors that sustain the practice despite its illegality. Primary healthcare providers' experience and their perspectives on the elimination of FGM/C. This study used a descriptive qualitative design based on grounded theory. We used purposive sampling to identify and recruit primary health care providers. In-depth interviews and focus group discussions were conducted, and qualitative analysis was undertaken to develop a conceptual framework for understanding both the roots and the drivers of FGM. Historical traditions and religious rites preserve FGM and ensure its continuity, and older women and peers are a source of support for the practice through the pressure they exert. The easy movement of circumcisers across communities helps to perpetuate the practice, as does the belief that FGM will reduce promiscuity. Data collected between October and December 2023 were transcribed verbatim and thematically analyzed. Three themes exploring healthcare providers' perspectives on elimination of FGM/C were identified, namely understanding laws against FGM/C; perspectives on culturally sensitive education; and exploring public awareness raising activities in Nigeria. Female Genital Mutilation continues to persist despite its illegality because of social pressure on women/girls to conform to social norms, peer acceptance, fear of criticism, and religious reasons. Implementing interventions targeting schools, religious leaders, older men, women, and strengthening Violence Against Persons (Prohibition) Act (VAPP) will help eradicate the practice.