Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its treatment remains a significant challenge. This study investigated the mechanism of Jujuboside A (JuA) in the treatment of PCOS through mitophagy. Granulosa cells (GCs) were collected from follicular fluid derived from PCOS women. The effects of JuA on PCOS were determined by measuring body weight, ovarian weight, estrous cycle, glucose level, insulin tolerance, and ovarian morphology in dehydroepiandrosterone-induced mice. SIRT3 expression levels were quantified in GCs, KGN cells, and mouse ovaries. The effects of JuA on SIRT3-related oxidative stress and mitochondrial damage were investigated in KGN cells and mice. Transmission electron microscopy was used to observe mitochondrial damage and mitophagy in GCs. The expression of mitophagy-related proteins (PINK1 and Parkin) was analyzed. JuA significantly improved body weight, estrous cycle, ovarian morphology, glucose tolerance, and insulin resistance, partially restoring ovarian function in PCOS mice. Moreover, JuA significantly activated SIRT3 expression and alleviated SIRT3-related oxidative stress and mitochondrial damage in mouse ovaries, GCs, and KGN cells. Mechanistically, JuA upregulated SIRT3 and inhibited excessive activation of the PINK1/Parkin pathway to reduce mitophagy. These findings demonstrated JuA protected GCs from mitochondrial damage by activating SIRT3 and inhibiting PINK1/Parkin-mediated mitophagy.

Thermoradiotherapy at 40-43 °C is an effective treatment for locoregional recurrent (LRR) breast cancer patients. During hyperthermia temperature monitoring is often limited to skin temperatures, but their predictive value for achieving locoregional tumor control (LRC) remains unclear for tumor depths ≥1cm. This study compared predictive value of skin versus invasive intratarget temperatures.

We reported earlier the thermal dose-effect relationship in 112 patients with LRR breast cancer treated in 2010-2017 with postoperative re-irradiation (8 × 4 Gy/23 × 2 Gy) and 4-5 weekly hyperthermia sessions with 434 MHz microwave applicators. Bolus cooling enabled semi-superficial target depths (1-4 cm), thermocouple thermometry monitored both skin and intratarget temperatures. The present study analyzes relationships between LRC and average skin and intratarget median temperature T₅₀ and best session with highest median thermal dose CEM43T50 (cumulative equivalent minutes at 43 °C). Pearson correlation coefficient analysis evaluated correlation between intratarget and skin temperature parameters.

Average median skin and invasive temperatures were T₅₀ = 40.6 °C (Interquartile Range IQR 40.3-40.8) and T₅₀ = 40.7 °C (IQR 40.0-41.3), respectively, without association between skin and intratarget temperatures. Median CEM43T50 for skin and intratarget were 2.8 (IQR 2.0-4.3) and 7.2 min (IQR 3.4-15.9) in the best hyperthermia session, respectively. Twenty-four patients developed infield recurrences; median time-to-recurrence was 3.4 years (IQR 2.7-4.6 years). Univariate and multivariate analysis showed significant association of intratarget temperature parameters with LRC (p = 0.015; p = 0.021, respectively), but not for skin temperature parameters and LRC (p = 0.131; p = 0.215, respectively).

Temperature monitoring using both skin and invasive intratarget measurements is key for ensuring good quality superficial hyperthermia delivery for tumor depths ≥1cm.

Fishermen are among the occupational groups with substantial sun exposure and are prone to dehydration, sunburn, photoaging, actinic cheilitis, and oral cancer. The objective of this study was to evaluate the dermatological condition of the lips of fishermen in the Guarujá/Santos port region, investigate whether they use preventive measures to avoid such lesions, and develop a suitable product for lip protection.

Thirty participants underwent an initial clinical examination and photo-graphic documentation. All 30 participants received the developed lip protector, which contained UV filters and moisturizing agents. At re-evaluation one month later, 17 participants returned, corresponding to a loss to follow-up of 43.40%.

All fishermen were male, with a minimum age of 23 and a maximum age of 74. When asked about lip balm use, only 1 of the 30 participants reported using it. At follow-up, among the 17 participants, only 1 reported using the provided lip balm and reapplying it during the day; this use was described as "sporadic."

The findings highlight the need for educational strategies to promote lip protection and prevent potentially malignant lesions among outdoor workers exposed to ultraviolet radiation.

Epidemiological and survival data on osteosarcoma of the jaws (OSJ) in Latin America remain scarce. We characterized the clinicopathological, radiographic, treatment-related, and survival features of OSJ in Latin America.

This multicenter case series involved 22 institutions from Brazil, Chile, Argentina, Colombia, Venezuela, Uruguay, and Mexico. Demographic, clinical, radiographic, histopathological, treatment, and survival data were analyzed using descriptive and inferential statistical methods. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models.

A total of 119 OSJ cases were included. The median age was 33 years, with a female predominance (58%), and the mandible was the most commonly affected site (68.9%). A mixed radiographic appearance predominated and was frequently accompanied by cortical perforation and a sunburst periosteal reaction. Histologically, the osteoblastic subtype accounted for 63.5% of cases. Surgical resection was the main treatment modality (71.2%). Increasing age (p = 0.034) and multimodal or nonsurgical management (p = 0.023) were independently associated with poorer survival. The estimated overall survival rates were 67.5% at 12 months and 37.5% at 60 months.

Data corroborate previous literature and demonstrate that OSJ in Latin America predominantly affects adults and exhibits aggressive patterns. Surgical management remains central to improving survival whenever it is technically feasible.

Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. Although PARP inhibitor sensitivity has traditionally been attributed to synthetic lethality in tumors with BRCA1/2 mutations or homologous recombination repair deficiency, emerging evidence indicates that clinical and preclinical activity may extend to selected tumors beyond those harboring germline BRCA1/2 mutations. This study investigated the mechanism underlying talazoparib efficacy in both BRCA1/2-mutant and BRCA1/2 wild-type breast cancer cells.

Twenty-one breast cancer cell lines, including both BRCA-1/2-mutant and wild-type cells, were treated with talazoparib, and the effects of the treatment on cell proliferation, cell cycle progression, DNA damage accumulation, and apoptosis were evaluated.

Talazoparib demonstrated antiproliferative effects in BRCA1/2-mutant and wild-type cells in a long-term culture system, as assessed by colony formation assays. Accumulation of single-stranded and double-stranded DNA damage was observed in talazoparib-sensitive cell lines, as indicated by phosphorylated RPA and γ-H2AX, respectively. This was accompanied by G2/M arrest and subsequent apoptosis, as evidenced by cleaved caspase-3 expression and Annexin V staining. Abnormal mitotic nuclei were observed in talazoparib-sensitive cell lines, which also exhibited potent and sustained PARP1 trapping on chromatin.

Talazoparib exerts anti-tumor effects in BRCA1/2-mutant and wild-type breast cancer cells by promoting the formation of abnormal mitotic nuclei and inducing apoptosis in sensitive cells. Our findings support the potential therapeutic application of talazoparib beyond its current indications for BRCA1/2-mutant tumors.

Antibody-drug conjugates (ADCs) have transformed second-line metastatic breast cancer (MBC) therapy, yet their multidimensional quality-of-life impact versus conventional intravenous chemotherapy in real-world practice, particularly on lifestyle and caregiver burden, remains poorly characterized.

This prospective cohort enrolled 122 consecutive patients with MBC starting second-line therapy: 51 received ADCs and 71 conventional intravenous chemotherapy, allocated by tumor biology and clinical factors. The DAMA (Digital Antibody drug conjugate Modulator in breAst cancer) framework collected electronic patient-reported outcome measures (ePROMs) on anthropometric, lifestyle, symptom, psychosocial, and caregiver-burden domains at baseline, 3 and 6 months, analyzed with linear mixed-effects models.

At baseline, measured lifestyle, symptom, psychosocial and caregiver variables were broadly similar between cohorts, although treatment-related characteristics differed. At 3 months, ADC patients had greater mean weight loss (-3.1 vs - 1.2 kg), a larger decline in weekly physical activity (-41 vs - 22 minutes/week), higher stress and caregiver burden, but lower pain scores (3.7 vs 5.3). By 6 months, several differences attenuated. In pooled descriptive analyses, weekly physical activity showed little association with pain (r = 0.03, p = 0.56), stress (r = -0.12, p = 0.03), anxiety (r = -0.02, p = 0.73), caregiver emotional wellbeing (r = 0.00, p = 0.97), or sleep duration (r = 0.04, p = 0.47).

In this prospective real-world cohort, ADC and conventional chemotherapy cohorts showed different longitudinal patterns of patient- and caregiver-reported burden. Because treatment allocation was biology- and clinically driven, these findings are exploratory and should not be interpreted as causal treatment effects. Systematic ePROM collection within the DAMA framework was feasible and may support identification of supportive-care needs.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. We report a case of CRC in a man in his late 70s with hereditary haemochromatosis (HH) who historically required venesection two to three times per year to maintain target ferritin levels. Despite the absence of gastrointestinal symptoms or anaemia, his requirement for maintenance venesection unexpectedly ceased and ferritin levels remained low without treatment. Two faecal immunochemical tests were negative. Colonoscopy subsequently revealed an adenocarcinoma in the caecum. Chronic occult blood loss from the tumour likely counterbalanced the increased intestinal iron absorption characteristic of HH. This case highlights that an unexplained reduction in venesection requirements in HH may represent an early marker of occult gastrointestinal blood loss and should prompt consideration of further investigation.

The sternalis muscle is an uncommon anatomical variant of the anterior thoracic wall. Although regarded as functionally insignificant, its presence may influence diagnostic interpretation, surgical dissection and reconstructive planning in breast surgery. We report bilateral sternalis muscles discovered during bilateral skin-sparing mastectomy and immediate autologous reconstruction in a woman in her late 40s. The sternalis muscles were identified intraoperatively, following which retrospective review of preoperative imaging confirmed their presence. Recognition of this variant aided orientation and safe exposure of the internal mammary vessels during reconstruction. Awareness of the sternalis muscle can prevent imaging misinterpretation, avoid intraoperative confusion and optimise reconstructive outcomes.

Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) for oestrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer can rarely cause severe liver injury. We report a fatal case of abemaciclib-induced mixed hepatocellular-cholestatic injury progressing to liver failure. A Hispanic woman in her mid-60s with metastatic ER+/HER2- breast cancer developed progressive hepatocellular-cholestatic injury 1 month after starting abemaciclib with letrozole. She presented with jaundice, pruritus and dark urine. Labs showed markedly elevated bilirubin, liver enzymes and alkaline phosphatase. Liver biopsy revealed portal inflammation, bile duct injury, cholestasis and steatosis. Extensive work-up excluded other causes. Despite initial fall in transaminases with drug withdrawal and high-dose steroids, her condition progressed with rising bilirubin and worsening coagulopathy signalling progressive loss of hepatic synthetic function suggestive of impending liver failure and death. In clinical trial, any-grade transaminase elevation occurs in 14%-15% of patients receiving abemaciclib, with grade 3 hepatotoxicity in 2.9%-4.8%. In a retrospective cohort of patients receiving abemaciclib plus endocrine therapy, 29% (15/52) developed abemaciclib-induced liver injury (AILI), with age ≥65 years, fatty liver disease and concomitant aromatase inhibitor use identified as risk factors. Educating patients to recognise early symptoms of liver injury is essential for prompt detection and management of AILI. This case highlights the need for patient education, close liver monitoring, early cessation of abemaciclib and consideration of genetic risk factors in high-risk patients.

Cellular plasticity is a central feature of malignant progression, allowing tumour cells to change identity during tumour evolution, therapeutic adaptation, and metastatic dissemination. This issue is especially acute in lung cancer, where the respiratory epithelium is intrinsically permissive to cell-state change. Genetic lesions, chromatin regulation, and metabolic adaptation are often framed as parallel determinants of lineage plasticity. Emerging evidence instead points to functional coupling across these layers. Oncogenic alterations can weaken lineage fidelity and open alternative trajectories, chromatin regulators can stabilise transitional states and enforce new transcriptional programmes, and metabolic rewiring can supply the biochemical conditions required for these states to emerge and persist. Microenvironmental cues further influence which trajectories are selected and maintained. Here, we discuss the genetic, epigenetic, and metabolic determinants of lineage plasticity in lung cancer, focusing on the points at which they intersect. We propose that plasticity is most usefully understood as a coupled regulatory state, arising from the interaction between oncogenic context, chromatin control, and metabolic support. Defining how these dependencies arise and become functionally coupled within high-plasticity transitional states should help identify points at which lineage switching can be intercepted before alternative lineage programmes are stabilised.