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Abstract Clinical success with poly (ADP-ribose) polymerase inhibitors (PARPi) is impeded by inevitable resistance and associated cytotoxicity. Depletion of Amplified in Liver Cancer 1 (ALC1), a chromatin-remodeling enzyme, can overcome these limitations by hypersensitizing BReast CAncer genes 1/2 (BRCA1/2) mutant cells to PARPi. Here, we demonstrate that PARPi hypersensitivity upon ALC1 loss is reliant on its role in promoting the repair of chromatin buried abasic sites. We show that ALC1 enhances the ability of the abasic site processing enzyme, Apurinic/Apyrimidinic endonuclease 1 (APE1) to cleave nucleosome-occluded abasic sites. However, unrepaired abasic sites in ALC1-deficient cells are readily accessed by APE1 at the nucleosome-free replication forks. APE1 cleavage leads to fork breakage and trapping of PARP1/2 upon PARPi treatment, resulting in hypersensitivity. Collectively, our studies reveal how cells overcome the chromatin barrier to repair abasic lesions and uncover cleavage of abasic sites as a mechanism to overcome limitations of PARPi.

Ferromagnetism is typically discussed in terms of the exchange interaction and magnetic anisotropies. Yet real samples are inevitably affected by the magnetostatic dipole-dipole interaction. Because of this interaction, a theorem [R.B. Griffiths, Free Energy of interacting magnetic dipoles, Phys. Rev. 176, 655 (1968)] forbids a spontaneous magnetization in, nota bene, three-dimensional bodies. Here we discuss perpendicularly and in-plane magnetized ferromagnetic bodies in the shape of a slab of finite thickness. In perpendicularly magnetized slabs, magnetic domains are energetically favored when the lateral size is sufficiently large, i.e., there is no spontaneous magnetization. For in-plane magnetization, instead, spontaneous magnetization is possible below a critical thickness which, in very thin films, could be as small as few monolayers. At this critical thickness, we predict a genuine phase transition to a multi-domain state. These results have implications for two-dimensional ferromagnetism.

BackgroundThe forehead flap is probably the most used method for nose reconstruction after cancer resection. During the past century, this technique has been continuously refined to achieve better functional and aesthetic outcomes. Different variations have been described, with the original technique being modified based on tissue loss, the layer to be replaced, and the management of the donor area.MethodsWe propose a new and innovative version of the forehead flap in which both the forehead skin and the frontal muscle are harvested simultaneously using the same vascular pedicle. Partially separating the two layers allows muscle tissue to replace the inner layer and cover the nasal septum framework, while the skin will replace the outer layer. The nostrils are reconstructed simultaneously using bilateral hinge-over lining skin flaps harvested from the nasal folds.ResultsStep by step, a schematic illustration of the technique is given, followed by a complete report on a successful total nose reconstruction case.ConclusionsDespite the increasing number of techniques which have been introduced to achieve full reconstruction of the nose, including microsurgical tissue transfer, the simultaneous replacement of both the inner and outer layers continues to be an issue for the plastic surgeon. In this article, we suggest a solution for total nose reconstruction in a single-stage procedure.

Enabling technologies (KETs) offer transformative potential for agriculture by addressing major challenges such as climate change, resource efficiency, and sustainable development across economic, social, and environmental dimensions. However, KET adoption is often limited by high R&D requirements, rapid innovation cycles, investment costs, and cultural or training barriers, especially among small agricultural businesses. Sicily’s agricultural sector, already strained by pandemic-related economic setbacks and inflationary pressures, faces additional barriers in adopting these technologies. To investigate these adoption challenges and develop viable solutions, the ARIA Living Lab (Agritech Research Innovation Environment) was established within the PNRR framework. A qualitative approach was used, involving documentary analysis and data from stakeholders across Sicilian agriculture. This approach enabled an in-depth exploration of sector-specific needs, infrastructure, and socio-economic factors influencing KET adoption. The analysis highlighted that adoption barriers differ significantly across sectors (citrus, olive, and wine), with public incentives and digital infrastructure playing key roles. However, a persistent lack of technical skills among farmers reduces the effectiveness of these innovations. The findings suggest that an integrated approach—combining targeted incentives, training, and enhanced infrastructure—is essential for a sustainable transition to KETs. Future research should examine collaborative efforts between farms and tech providers and evaluate the impact of public policies in promoting the widespread, informed adoption of enabling technologies.

Background:. Currently, the evaluation of pigmented skin lesions relies on dermoscopy, which has become the standard of care. As melanoma is one of the principal areas of expertise in plastic surgery, it is essential that diagnostic skills be acquired during the course of specialization. This study aimed to assess the impact and effectiveness of a brief and intensive dermoscopy training program for plastic surgery residents. Methods:. This study was carried out on a group of 41 doctors, who were divided into three categories based on their experience in dermoscopy (none, intermediate, and advanced). A preliminary assessment of each participant’s baseline knowledge was conducted by using a 15-query test. Subsequently, the participants attended a 90-minute lecture on diagnostic techniques and the process of differentiating between various skin lesions. To determine the effectiveness of the lecture in improving diagnostic skills, the participants were tested immediately after the lecture and again after a 3-month period. Results:. At the conclusion of the final examination, all three groups achieved an accuracy rate of at least 80% for dermatoscopic diagnosis. However, none of the groups was completely successful. The variations in diagnostic accuracy among the three groups are presented, and P values were calculated for each group. Conclusion:. The short, intensive course of dermoscopy has proven to have a significant positive impact on plastic surgeons in their postdegree training program.

Obesity is defined as a complex, systemic disease characterized by excessive and dysfunctional adipose tissue, leading to adverse health effects. This condition is marked by low-grade inflammation, oxidative stress, and metabolic abnormalities, including mitochondrial dysfunction. These factors promote energy dysregulation and impact body composition not only by increasing body fat but also by promoting skeletal muscle mass atrophy. The decline in muscle mass is associated with an increased risk of all-cause mortality in individuals with this disease. The European Food Safety Authority approved pyrroloquinoline quinone (PQQ), a natural compound, as a dietary supplement in 2018. This narrative review aims to provide a comprehensive overview of the potential role of PQQ, based on its anti-inflammatory and antioxidant properties, in addressing dysfunctional adipose tissue metabolism and related disorders.

Background:. This study presents a case of thumb replantation performed despite several risk factors: age, comorbidities, and trauma mechanism are major adverse prognostic factors directly impacting thumb replantation. Most of the literature backs up this claim that a thumb that works, even partially, is a better outcome for the patient than amputation. Methods:. We performed thumb replantation on a 94-year-old patient with type 2 diabetes mellitus who arrived at the emergency department with a thumb avulsion due to a dog bite. The intraoperative indocyanine green fluorescence angiography method aided us in carrying out the operation. Results:. We successfully used indocyanine green angiography intraoperatively to guide surgical debridement and evaluate the efficacy of anastomosis and reperfusion of the replanted segment during surgery. Two months after the operation, the patient had regained satisfactory hand function. Conclusions:. Although indocyanine green angiography is not a technology created for revascularization procedures, it is instrumental in assessing vascular function and predicting a successful outcome. Given its undeniable potential, more research is needed on the possibility of widespread use in hand surgery and its indications.

Angelo Di Vincenzo,1 Marnie Granzotto,1 Marika Crescenzi,1 Camilla Costa,1 Stefano Piaserico,2 Vincenzo Vindigni,3 Roberto Vettor,1 Marco Rossato1 1Department of Medicine – DIMED, Clinica Medica 3, University - Hospital of Padova, Padova, Italy; 2Department of Medicine - DIMED, Section of Dermatology, University - Hospital of Padova, Padova, Italy; 3Department of Neurosciences, Clinic of Plastic Reconstructive and Aesthetic Surgery, University – Hospital of Padova, Padova, ItalyCorrespondence: Marco Rossato, Department of Medicine – DIMED, Clinica Medica 3, University Hospital of Padova, Via Giustiniani 2, Padova, 35128, Italy, Tel +39 49 8218746, Fax +39 49 8213332, Email marco.rossato@unipd.itPurpose: Psoriasis is a chronic systemic inflammatory disease involving the production of many pro-inflammatory cytokines derived from immune cells and interacting with different tissues leading to the typical skin lesions. Psoriasis shows a higher prevalence and a worse progression in obese than in lean subjects. The IL-23/IL-17 immune axis has a pivotal role in the pathogenesis of psoriasis and anti-IL-23 monoclonal antibodies are highly effective in its treatment. Since obesity in frequently associated with elevated insulin plasma levels, we have investigated the ability of in vitro differentiated human adipocytes to produce IL-23 at basal conditions and after insulin stimulation.Material and Methods: In vitro differentiated human adipocytes were incubated in the absence and presence of different insulin concentrations and the expression of IL-23 was analyzed by real-time PCR and Western blotting.Results: The results of this study show that in vitro differentiated human adipocytes spontaneously express IL-23 mRNA and protein being stimulated by insulin in a dose-dependent manner. The stimulatory effects of insulin on IL-23 expression were specific since it did not stimulate the expression of other well-known cytokines involved in psoriasis pathogenesis such as Il-22 nor LL-37. Furthermore, lipopolysaccharide did not stimulate IL-23 expression in human adipocytes, thus highlightening the specific effects of insulin in the stimulation of IL-23 expression in human adipocytes.Conclusion: Here we show that human adipocytes spontaneously express IL-23 and that insulin stimulates IL-23 production by these cells in a specific manner as other stimuli, known to be involved in psoriasis pathophysiology, are ineffective. These observations could explain the association between psoriasis and obesity, a condition frequently characterized by a state of insulin hypersecretion.Keywords: adipocyte, human, IL-23, insulin, obesity, psoriasis

Summary:. This case report addresses the discovery, surgical management, histology, and postoperative outcomes of an incidentaloma during the preoperative evaluation of a 58-year-old woman planning to undergo abdominoplasty and hernia correction after bariatric surgery. The patient’s computed tomography scan revealed a large pelvic mass in addition to an enlarged uterus and an umbilical hernia. Subsequent surgical intervention included umbilical hernia repair, subtotal omental excision, and en-bloc removal of the uterine and ovarian structures. Histological analysis confirmed the mass as a high-grade utero-ovarian leiomyosarcoma. The patient received adjuvant chemotherapy and demonstrated a positive response in follow-up imaging at 6 months, with reduced mass size and no significant lymphadenopathy. Both aesthetic and morpho-functional outcomes were satisfactory. The report highlights the challenges of diagnosing and treating incidentalomas, emphasizing the need for individualized management. It discusses the rarity of primary ovarian leiomyosarcoma and the surgical approach used. The case ultimately emphasizes the importance of multidisciplinary clinical evaluations in ensuring comprehensive care for patients with unexpected radiological findings, such as utero-ovarian leiomyosarcoma.

ABSTRACTColorectal cancer (CRC) is a leading cancer worldwide; incidence varies greatly by country and racial group. We compared 2018 American Indian/Alaska Native (AI/AN) CRC incidence rates in Alaska to other Tribal, racial, and international population rates. AI/AN persons in Alaska had the highest CRC incidence rate among US Tribal and racial groups (61.9/100,000 in 2018). AI/AN persons in Alaska also had higher rates than those reported for any other country in the world in 2018 except for Hungary, where males had a higher CRC incidence rate than AI/AN males in Alaska (70.6/100,000 and 63.6/100,000 respectively). This review of CRC incidence rates from populations in the United States and worldwide showed that AI/AN persons in Alaska had the highest documented incidence rate of CRC in the world in 2018. It is important to inform health systems serving AI/AN persons in Alaska about policies and interventions that can support CRC screening to reduce the burden of this disease.

Subcellular localization plays an important yet underappreciated role in protein functions. Here the authors defined novel and context-dependent nuclear functions of the actin-binding factor profilin-1 in DNA replication fork dynamics and stability.

Historically, both governmental and private sectors have significantly underinvested in the agriculture industry. Increasing agricultural and food system investments is necessary to enhance food security and nutrition, reduce poverty, and adapt to climate change. To achieve long-term benefits, it is crucial to ensure not only that more investments are made, but also that these investments are responsible. The purpose of this paper is to conduct a literature review of financial sustainability and ethical investing in the agriculture industry. The findings indicate that the academic community has begun to focus on these concerns in recent years. Specifically, issues concerning finance in developing nations and the management of irrigation systems are attracting attention. This paper’s goal is to encourage more financial institutions, financial services managers, policymakers, and universities to participate in sustainable development projects in the financial services sector.

Abstract Background Chiropractic is a mostly privatised health profession within Australia, with people experiencing disadvantage typically having limited access due to financial barriers. However, some universities within Australia offer community outreach clinics where students provide chiropractic care to people living with disadvantage. This demographic experiences higher rates of chronic conditions including musculoskeletal complaints and requires subsidisation to access privatised care. This need also offers opportunity for the chiropractic profession to work within community healthcare teams. A mixed-methods observational study was used to investigate how the unique setting of a student chiropractic community clinic may influence the experience and outcomes of those who attend. Methods Three patient-reported outcome measures (PROMs) investigated client outcomes: Measure Yourself Medical Outcome Profile (MYMOP); European Five Domain Five Level Quality of Life Questionnaire (EQ-5D-5L); and the Patient Enablement Instrument. The PROMs data were analysed descriptively and inferentially. Interviews were conducted with clients who had received chiropractic care, chiropractic students, clinical supervisors and staff of the centre. Interview data were coded using thematic analysis, and themes were formed using Bronfenbrenner’s socio-ecological systems framework and non-participant observations. Results Thirty-seven participants completed baseline PROMs and 17 completed follow-ups after four treatments. Seventy-two percent of participants nominated their primary complaint as chronic. Significant change was noted in general health and wellbeing for the MYMOP, pain and disability for the EQ-5D-5L and index scores for the EQ-5D-5L suggested improved health and wellbeing. Most clients experienced higher levels of enablement post treatment. Twelve participants were interviewed (four were clients), with five themes emerging from the interview data. Clients reported their lived experiences impacted their health problems and attending the clinic offered benefits beyond improvement of pain and disability. Conclusions Interview data suggested that these benefits were due to a combination of therapy, the setting and the relationships formed within that setting. Complementing this, PROM data suggested clients experienced better levels of health and wellbeing and decreased levels of pain and disability. Findings indicated that people who experienced disadvantage may receive broader benefits from attending community centres offering chiropractic care. Services such as chiropractic may be complementary in meeting the healthcare needs of those experiencing disadvantage.

Background Massive weight loss (MWL) is a very common presentation that you may face as a plastic surgeon. Each patient has his own individual criteria, so, you should work according to a well-organized plan, especially when such cases have concerns about their gluteal area contour that were neglected before by many surgeons. A decision-making strategy was used to give a personalized treatment for targeting gluteal region reshaping of MWL patients. Methods This study considered all patients with MWL subjected to buttock reshaping. There was no randomization in treatment; there was a case-by-case assessment. We analyzed the features of the buttocks, the type of surgery performed, the outcomes, and the complications. Results Fifty two patients were included (41 females and 11 males), ages ranged between 21 and 66 years. Demographic data, preoperative body mass index (BMI), duration of surgery, type of surgery, and postoperative complications were collected. Statistically significant improvements were observed in gluteal ptosis and patient satisfaction grades. Conclusion Aesthetic improvement of the buttocks involves either augmentation or contouring that may be obtained by liposculpture, surgical lifting, or combination. Patients with MWL have high expectations and are often treated with multiple procedures. Thus, an easy strategic approach personalized on each patient to treat multiple adjacent areas in one operation is necessary. Adipose tissue distribution, gluteal skin status, and BMI were the main factors that can forcefully affect our plan to guarantee reduction of unpleasant results and complications and improve patient satisfaction.

Enabling technologies (KETs) offer transformative potential for agriculture by addressing major challenges such as climate change, resource efficiency, and sustainable development across economic, social, and environmental dimensions. However, KET adoption is often limited by high R&D requirements, rapid innovation cycles, investment costs, and cultural or training barriers, especially among small agricultural businesses. Sicily's agricultural sector, already strained by pandemic-related economic setbacks and inflationary pressures, faces additional barriers in adopting these technologies. To investigate these adoption challenges and develop viable solutions, the ARIA Living Lab (Agritech Research Innovation Environment) was established within the PNRR framework. A qualitative approach was used, involving documentary analysis and data from stakeholders across Sicilian agriculture. This approach enabled an in-depth exploration of sector-specific needs, infrastructure, and socio-economic factors influencing KET adoption. The analysis highlighted that adoption barriers differ significantly across sectors (citrus, olive, and wine), with public incentives and digital infrastructure playing key roles. However, a persistent lack of technical skills among farmers reduces the effectiveness of these innovations. The findings suggest that an integrated approach—combining targeted incentives, training, and enhanced infrastructure—is essential for a sustainable transition to KETs. Future research should examine collaborative efforts between farms and tech providers and evaluate the impact of public policies in promoting the widespread, informed adoption of enabling technologies. [ABSTRACT FROM AUTHOR]

Background: Breast reconstruction with implants is now the preferred procedure following mastectomies. For successful reconstruction, accurate evaluation of the patient and skin flap viability is essential. This study aimed to analyze the impact of risk factors on mastectomy skin flap necrosis (MSFN) and the effectiveness of indocyanine green angiography (ICGA) in preventing complications. Methods: Fifty consecutive patients undergoing mastectomy were divided into two groups (arms A and B) based on the method of skin flap evaluation (ICGA vs. clinical assessment, respectively). Demographic details and the risk factor incidence were collected, and complication rates were compared between the two groups. Univariate analysis was conducted to identify correlations between mastectomy skin flap necrosis and the aforementioned risk factors. Results: The two groups showed comparable demographics and incidences of risk factors. Patients in arm A exhibited a lower rate of complications and reinterventions, although no significant differences were observed. Statistical analysis revealed a significant association between BMI, implant volume, and MSFN. Conclusions: ICGA proves to be an effective diagnostic tool for assessing skin flap viability. When coupled with meticulous patient selection, it aids in preventing complications. [ABSTRACT FROM AUTHOR]

Composite graft is a useful tool for the reconstruction of specific facial aesthetic subunits with a single surgical stage. This technique, when successful, gives optimal results in the reconstruction of small defects of nose, ear, eyelid and lips. The aim of this work is to optimize the attachment of composite grafts in the reconstruction of small complex facial defects by combining it with Fluorescent Light Energy (FLE) during the healing process of the graft. The beneficial effects of photobiomodulation (PBM) on wound healing might be attributed to anti-inflammatory signaling, cell proliferation, protein synthesis, and decreased bacterial infection. We previously experienced rewarding achievements using Photonic energy in the treatment of burns, non-healing wounds and pathological scars. Therefore, we chose to exploit the potential of bioluminescent energy to maximize aesthetical and functional results, enhancing the formation of new vascular connections and modulating both inflammatory and scarring processes. From the 2nd postoperative day, the patients were locally treated with 5 FLE sessions every (48/72 h) 2 or 3 days. We evaluated results in terms of time for engraftment, quality of the scarring, infective complications and morbidity of the donor site. Graft survival is subject to many factors, both local and systemic. To overcome these issues, various methods have been studied and described. We here report the successful reconstruction of full-thickness defects of the free margin of the nasal alar rim and the central portion of the inferior lip with a composite graft. These results were highly encouraging if compared with the literature. By analyzing our small cohort, we demonstrated how new technologies may push this traditional reconstructive procedure beyond their old boundaries: overcoming an increased size demand or a potential infective wound environment. [ABSTRACT FROM AUTHOR]