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University and college leaders are tasked with enhancing student outcomes with fewer resources. Student retention is one such key outcome of interest for many policy makers as well as for university administrators. Over the years, administrators have turned to High Impact Practices (HIPs) such as Learning Communities (LCs) to aid in retention. This quantitative study explores the impact LCs have on student retention at a large R1 university in the Midwest. Additionally, the financial return on investment in LCs at this institution is measured via tuition dollars generated from students who are retained as a result of their participation in a LC at the institution. Two key findings of this study are that LCs are positively associated with increased odds of student retention, and that investing in LCs makes good financial sense. Our research contributes to the scholarship on retention attributable to LCs and provides researchers and practitioners with a "template" to evaluate the efficacy of specific retention initiatives in relation to their financial return on investments.

Abstract Medullary carcinoma of the breast (MedBC) is a rare histological type that accounts for less than 5% of all invasive breast cancers. Here, we performed an exploratory study aimed to determine whether imaging mass cytometry (IMC) can be used to characterize the immune infiltration and the spatial distribution heterogeneity in the rare subtype of MedBC compared to atypical MedBC and TNBC-TILS+ tumors. In both MedBC and TNBC-TILs+, there was a notable enrichment of immune cells in the peripheral regions of the tumors, whereas in atypical MedBC, the immune cells exhibited a central enrichment pattern. This distribution of infiltrated cells reflects an active immune recruitment correlated to more favorable prognosis. In MedBC, spatial analysis shows that immune cells are localized at a greater distance from the tumor cells. IMC highlights the heterogeneity of immune microenvironment across three main subtypes of breast tumors and could help to define distinct immune patterns.

Abstract Understanding breast cancer survivors’ perspectives is critical to personalizing endocrine therapy (ET) in the adjuvant setting. A nationwide survey among breast cancer survivors was proposed in France, in collaboration with patient advocacy organizations, to assess their perspectives on personalizing ET and developing dedicated informative tools. This survey explored patients’ preferences regarding ET intake schedule, formulation, presentation (color, taste, shape, size, design, and packaging), combination with agents targeting ET-related adverse events, and a mobile application to support them during ET. Of the 1103 individuals who started the survey, 939 (85.1%) were eligible for enrollment and completed the survey. The majority of the participants considered that a personalized ET should take into consideration the intake schedule (n = 974, 90.7%) and swallowable tablet formulation (n = 606, 64.5%), without a preference for ET presentation (n = 619; 65.9%). The majority of the participants expressed a willingness to participate in a potential clinical trial evaluating the combination of ET with agents targeting ET-related adverse events at the start of ET (n = 752, 80.1%) or in the case of major ET-related adverse events (n = 778, 82.8%). The primary considerations were to have an uncompromised ET efficacy and a guaranteed reduction of adverse events. Last, a dedicated mobile application was considered helpful by 665 participants (70.8%). Informative tools should focus on the recommendations for dealing with adverse events (n = 593, 63.2%), the impact on the patient’s daily life (n = 515, 54.9%), benefits (n = 504, 53.7%), and adverse events (n = 494, 52.6%) of ET. This survey paves the way for multimodal strategies that can include a personalized ET (e.g., ET in combination with agents targeting ET-related adverse events) and dedicated mobile applications to ultimately improve adherence.

Objective: Breast Cancer (BC) is the primary oncological diagnosis in women, with the annual incidence expected to exceed 3 million new cases by 2040 due to population growth and ageing. During the COVID-19 pandemic, novel methods were adopted to provide continuous care to patients, including the introduction of telehealth. This technique allows for improved access to care, reduced emissions with environmental impact, better resource utilization, and ultimately improved continuity of care. A current issue is the environmental impact of hospitals, particularly operating rooms, as it has been analyzed that 25-30% of hospital waste comes from these areas. In this regard, there has been a consideration to introduce the ERAS protocol, already active in colorectal surgery, into breast surgery, aiming to optimize resources, reduce hospital waste, and expedite waiting lists. Materials and Methods: With the introduction of the Breast Green Surgery (BuGS) protocol, the focus is not only on creating a more environmentally sustainable operating room by reducing waste, but also on minimizing the anesthetic impact on the patient and the environment. It is known that volatile anesthetics significantly contribute to pollution. Results: Our goal is to reduce their use by favoring awake surgery, using local anesthetics along with sedatives to maintain patient comfort during the procedure. Conclusions: Therefore, our multidisciplinary BuGS protocol aims at evaluating for the synergistic effect of different procedure for the first time on Clinical Outcome, Patients’ Reported Outcome Measure (PROM), and Environment Related Outcome Measure (EROM) in BC surgery.

Precoce creato cistercense di Chiaravalle Milanese, l’abbazia cistercense di Fiastra è testimone dei profondi mutamenti sofferti dal Piceno a metà del XII secolo, quando era ancora dominato dalla declinante signoria farfense. Per suo conto, il nascente cenobio veicola un modello claustrale in corso di codificazione, a monte concepito per l’azione colonizzatrice della casa-madre Clairvaux al tempo dell’abate Bernardo. Fenomeno monastico di respiro europeo volto a replicare un comune standard insediativo, obiettivo del presente contributo è mettere a fuoco la genetica progettuale dell’abbaziale di Fiastra, una tessera “incompiuta” tra le filiazioni dirette e indirette di Clairvaux fondate dopo il 1140. Dotata di un coro più agile a fronte dei dilatati chevet di prima generazione, al pari delle Tre Fontane a Roma, il cantiere di Fiastra deroga pure su altri fronti, perché è finalmente indotto a misurarsi anche con l’eredità romana del territorio, ben prima di un effettivo reimpiego dell’antico. A precocious Cistercian creation of Chiaravalle Milanese, Fiastra Abbey witnessed the profound transformations of the Piceno territory in the mid-12th century, when it was dominated by the declining Farfense seignory. For its part, the coenoby transmits a cloistered typology still in the process of codification, conceived upstream through the colonizing action of the house-mother Clairvaux at the time of Abbot Bernard. A monastic phenomenon of European scope aimed at replicating a common settlement standard, this paper focuses attention on the genetics of the abbey project at Fiastra, an “unfinished” building among the Clairvaux filiations founded after 1140. Equipped with a smaller chorus than the dilated first-generation chevets, such as the Tre Fontane, the Bernardine abbey of Fiastra also derogates to something else, because it is finally induced to measure itself with the Roman heritage of the territory, even before the actual reuse of the ancient.

Breast cancer (BC) is the second most diagnosed cancer in 2018 with around 2.3 million cases globally in 2020. In March 2020 and after its worldwide spread, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak, a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, a pandemic. During this time, cancer patients were heavily impacted and their treatment plans were changed due to measures to fight the disease and solutions had to be found to maintain their follow-up and management from a distance. Some cancer groups worldwide have recommended then the use of telemedicine for oncology patients to ensure the continuity of medical care during the pandemic. This method was considered effective and clinicians worldwide continued using telehealth even after the cessation of worldwide restrictions. To this end, current up-to-date data on the use of telemedicine in BC patient after the COVID-19 outbreak are summarized in this narrative review.

Abstract Purpose This study assessed sustainable return to work (SRTW) of breast cancer survivors (BCS). Methods We used data from the prospective French cohort, CANTO. We included 1811 stage I–III BCS who were 50 (OR = 0.59; 95%CI = 0.43–0.82), stage III (2.56; 1.70–3.85), tumour subtype HR+/HER2+ (0.61; 0.39–0.95), severe fatigue (1.45; 1.06–1.98), workplace accommodations (1.63; 1.14–2.33) and life priorities (0.71; 0.53–0.95). Unemployment was associated with age > 50 (0.45; 0.29–0.72), working in the public sector (0.31; 0.19–0.51), for a small company (3.00; 1.74–5.20) and having a fixed‐term contract (7.50; 4.74–11.86). Conclusions A high number of BCS have periods of sick leave or unemployment after RTW. The determinants differ between sick leave and unemployment. Implications for cancer survivors BCS need to be supported even after RTW, which should be regarded as a process.

Artificial Intelligence (AI) is not a recent development. However, with increasing computational capabilities, AI has developed into Natural Language Processing and Machine Learning, technologies particularly good at detecting correlations and patterns, and categorising, predicting, or extracting information. Within archaeology, AI can process big data accumulated over decades of research and deposited in archives. By combining these capabilities, AI offers new insights and exciting opportunities to create knowledge from archaeological archives for contemporary and future research. However, the ethical implications and human costs are not yet fully understood. Therefore, we question whether AI in archaeology is a blessing or a curse.

Objective Protein–energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly.Methods and analysis In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the ‘Joint Programming Initiative A healthy diet for a healthy life’. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9–1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics.Ethics and dissemination All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects’ regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals.Trial registration number NCT05343611.

In this work we report the characterization of thin metallic coatings of interest for nuclear fusion technology through the ns double-pulse LIBS technique. The coatings, composed of a tungsten (W) or tungsten-tantalum (W-Ta) mixture were enriched with deuterium (D), to simulate plasma-facing materials (PFMs) or components (PFCs) of the next generation devices contaminated with nuclear fuel in the divertor area of the vacuum vessel (VV), with special attention to ITER, whose divertor will be made of W. The double pulse LIBS technique allowed for the detection of D and Ta at low concentrations, with a single laser shot and an average ablation rate of about 110 nm. The calibration free (CF-LIBS) procedure provided a semi-quantitative estimation of the retained deuterium in the coatings, without the need of reference samples. The presented results demonstrate that LIBS is an eligible diagnostic tool to characterize PFCs with high sensitivity and accuracy, being minimally destructive on the samples, without PFCs manipulation. The CF-LIBS procedure can be used for the search for any other materials in the VV without any preliminary reference samples.

Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies. Methods: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L. Results: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed. Conclusions: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective. ClinicalTrials.gov registration number: NCT02400476.

Deep neural networks for graphs have emerged as a powerful tool for learning on complex non-euclidean data, which is becoming increasingly common for a variety of different applications. Yet, although their potential has been widely recognised in the machine learning community, graph learning is largely unexplored for downstream tasks such as robotics applications. To fully unlock their potential, hence, we propose a review of graph neural architectures from a robotics perspective. The paper covers the fundamentals of graph-based models, including their architecture, training procedures, and applications. It also discusses recent advancements and challenges that arise in applied settings, related for example to the integration of perception, decision-making, and control. Finally, the paper provides an extensive review of various robotic applications that benefit from learning on graph structures, such as bodies and contacts modelling, robotic manipulation, action recognition, fleet motion planning, and many more. This survey aims to provide readers with a thorough understanding of the capabilities and limitations of graph neural architectures in robotics, and to highlight potential avenues for future research.

Abstract Background The need for whole mandibular bone reconstruction and bilateral joint replacement is fortunately rare, but it is an extremely challenging topic in maxillofacial surgery, due to its functional implications. CAD-CAM techniques development has opened new broad horizons in the surgical planning of complex maxillofacial reconstructions, in terms of accuracy, predictability, and functional cosmetic results. The review of the literature has revealed a small number of scientific reports on total mandibulectomy including the condyles, with only eleven cases from 1980. Most of the works describe reconstructions secondary to dysplastic or inflammatory diseases affecting the lower jaw. The aim of this work, reporting a rare case of massive fibrous dysplasia of the whole mandible, is to share our experience in the management of extended mandibular and bilateral joint reconstruction, using porous titanium patient-specific implants. Case presentation The authors present a 20-year-old male patient suffering from massive bone fibrous dysplasia of the mandible. The mandibular body and both the rami and the condylar processes had been involved, causing severe functional impairment, tooth loss, and facial deformation. The young patient, after repeated ineffective conservative surgical treatments, has required a biarticular mandibular replacement. Using virtual surgical planning (VSP) software, the authors, in collaboration with medical engineers, have created a custom-made original titanium porous mandibular implant, suspended from a bilateral artificial temporomandibular joint. The mandibular titanium implant body has been specifically designed to support soft tissues and to fix, in the alveolar region, a free fibular bone graft, for delayed dental implant prosthetic rehabilitation. Conclusion The surgical and technical details, as well as the new trends in mandibular reconstructions using porous titanium implants, are reported, and discussed, reviewing literature reports on this topic. Satisfactory functional and cosmetic restorative results have been obtained, and no major complications have occurred. The patient, currently in the 18th month clinical and radiological follow-up, has recently completed the functional restoration program by an implant-supported full-arch dental prosthesis.

The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward developing antibody-conjugation methods have led to the development of a new class of compelling compounds, the antibody-drug conjugates (ADCs) targeting HER2 which have profoundly transformed the treatment landscape of breast cancer. HER2-targeting ADCs, trastuzumab-emtansine and trastuzumab-deruxtecan, have improved the overall survival in the second and third-line settings with manageable adverse events. Other HER2-targeting ADCs using novel technological advances in the antibody, linker and/or payload conception have shown promising activity in preclinical and clinical studies and some of them are now being evaluated in larger clinical trials. Multiple challenges still impede the success of ADCs in breast cancer namely the lack of a comprehensive understanding of resistance mechanisms as well as the mechanisms of action of ADCs in special subgroups of patients such as those with low or ultra-low HER2 expression and patients with brain or leptomeningeal metastases (BM). In this framework, we review the approved indications and ongoing trials for HER2-targeting ADCs, across patient subgroups, including those with BM and discuss the associated potential mechanisms of action and resistance. Last, we provide an overview of the future perspectives involving HER2-targeting ADCs in breast cancer.

Objective Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).Methods and analysis We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.Results The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.Conclusions We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.Trial registration number NCT00116090.

IntroductionOral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral malignancies and has a 5-year mortality rate close to 50%. A consistent part (70%) of all oral cancers is diagnosed at an advanced stage since available screening techniques are ineffective. Therefore, it would be urgent to improve them. The diagnostic gold standard is tissue biopsy with histological and immunohistochemical assessment. This method presents some limitations. Biopsy is invasive and the histopathological evaluation is semi-quantitative, and the absolute abundance of the target cannot be reliably determined. In addition, tissue is highly processed and may lead to loss of information of the natural state. The search for classical and new clinical biomarkers on fragments of tissue/cells collected with a cytobrush is a highly hopeful technique for early detection and diagnosis of OSCC, because of its non-invasive sampling and easy collection method.MethodsHere we analyzed cytobrush biopsies samples collected from the oral cavity of 15 patients with already diagnosed OSCC by applying an innovative high-sensitivity ELISA technique, in order to verify if this approach may provide useful information for detection, diagnosis, and prognosis of OSCC. To this end, we selected six biomarkers, already used in clinical practice for the diagnosis of OSCC (EGFR, Ki67, p53) or selected based on recent scientific and clinical data which indicate their presence or over-expression in cells undergoing transformation and their role as possible molecular targets in immunecheckpoints blockade therapies (PD-L1, HLA-E, B7-H6).ResultsThe selected tumor biomarkers were highly expressed in the tumor core, while were virtually negative in healthy tissue collected from the same patients. These differences were highly statistically significant and consistent with those obtained using the gold standard test clearly indicating that the proposed approach, i.e. analysis of biomarkers by a custom ELISA technique, is strongly reliable.DiscussionThese preliminary data suggest that this non-invasive rapid phenotyping technique could be useful as a screening tool for phenotyping oral lesions and support clinical practice by precise indications on the characteristics of the lesion, also with a view to the application of new anti-tumor treatments, such as immunotherapy, aimed at OSCC patients.

In this work, we present a compact LIBS sensor developed for characterization of samples on a crime scene following requirements of law enforcement agencies involved in the project. The sensor operates both in a tabletop mode, for aside measurements of swabbed materials or taken fragments, and in handheld mode where the sensor head is pointed directly on targets at the scene. The sensor head is connected via an umbilical to an instrument box that could be battery-powered and contains also a color camera for sample visualization, illumination LEDs, and pointing system for placing the target in focus. Here we describe the sensor’s architecture and functionalities, the optimization of the acquisition parameters, and the results of some LIBS measurements. On nano-plotted traces at silica wafer and in optimized conditions, for most of the elements the detection limits, in term of the absolute element masses, were found to be below 10 picograms. We also show results obtained on some representative materials, like fingerprints, swabbed soil and gunshot residue, varnishes on metal, and coated plastics. The last, solid samples were used to evaluate the depth profiling capabilities of the instrument, where the recognition of all four car paint layers was achieved.

An overview is presented of the progress since 2021 in the construction and scientific programme preparation of the Divertor Tokamak Test (DTT) facility. Licensing for building construction has been granted at the end of 2021. Licensing for Cat. A radiologic source has been also granted in 2022. The construction of the toroidal field magnet system is progressing. The prototype of the 170 GHz gyrotron has been produced and it is now under test on the FALCON facility. The design of the vacuum vessel, the poloidal field coils and the civil infrastructures has been completed. The shape of the first DTT divertor has been agreed with EUROfusion to test different plasma and exhaust scenarios: single null, double null, X-divertor and negative triangularity plasmas. A detailed research plan is being elaborated with the involvement of the EUROfusion laboratories.

Nerve growth factor (NGF) signalling affects spermatogenesis and mature sperm traits. In this paper, we aimed to evaluate the distribution and the role of NGF and its receptors (p75NTR and TrKA) on the reproductive apparatus (testis and epididymis) and sperm of fertile men (F) and men with different pathologies, namely varicocele (V) and urogenital infections (UGIs). We collected semen samples from 21 individuals (31–40 years old) subdivided as follows: V (n = 7), UGIs (n = 7), and F (n = 7). We submitted the semen samples to bacteriological analysis, leucocyte identification, and analysis of sperm parameters (concentration, motility, morphology, and viability). We determined the seminal plasma levels of NGF, interleukin 1β (IL-1β), and F2-isoprostanes (F2-IsoPs), and the gene and protein expression of NGF receptors on sperm. We also used immunofluorescence to examine NGF receptors on ejaculated sperm, testis, and epididymis. As expected, fertile men showed better sperm parameters as well as lower levels of NGF, F2-IsoPs, and IL-1β compared with men with infertility. Notably, in normal sperm, p75NTR and TrKA were localised throughout the entire tail. TrKA was also found in the post-acrosomal sheath. This localisation appeared different in patients with infertility: in particular, there was a strong p75NTR signal in the midpiece and the cytoplasmic residue or coiled tails of altered ejaculated sperm. In line with these findings, NGF receptors were intensely expressed in the epididymis and interstitial tissue of the testis. These data suggest the distinctive involvement of NGF and its receptors in the physiology of sperm from fertile men and men with infertility, indicating a possible role for new targeted treatment strategies.

Abstract Background Fatigue is common in patents with breast cancer (BC), and can occur in patients with early stage disease and in the absence of muscle wasting (i.e. cachexia). We have reported transcriptional and proteomic alterations in muscles from BC patients, which are associated with fatigue. Mice implanted with human BC xenografts recapitulate the muscle molecular composition changes seen in patients, coupled with a greater rate of contraction‐induced fatigue. Multiple bioinformatics platforms in both human and mouse muscles have identified peroxisome proliferator activated receptor gamma (PPARG) as central to this phenotype, with several PPARG target genes downregulated in muscle in response to tumour growth. The current study tested the hypothesis that the PPARG agonist pioglitazone (pio), a commonly prescribed diabetes drug, would rescue the transcriptional alterations observed in muscles of tumour‐bearing mice. Methods Sixteen female NSG mice were implanted with breast cancer patient‐derived orthotopic xenografts (BC‐PDOX) via transplantation of Her2/neu+ human tumour fragments. BC‐PDOX mice were randomly assigned to a treatment group that received daily oral pio at 30 mg/kg (n = 8), or a control group that received a similar volume of vehicle (n = 8). Treatment was initiated when tumours reached a volume of 600 mm3, and lasted for 2 weeks. Hindlimb muscles were isolated from BC‐PDOX and non‐tumour bearing mice for RNA‐sequencing, gene expression validation, and ATP quantification. Differentially expressed genes (DEGs) in muscles from BC‐PDOX mice relative to non‐tumour bearing controls were identified using DESeq2, and multiple bioinformatics platforms were employed to contextualize the DEGs. Results We found that the administration of pio restored the muscle gene expression patterns of BC‐PDOX mice to a profile resembling muscles of non‐tumour bearing NSG control mice. Validation of skeletal muscle gene expression by qPCR confirmed pio increased the expression of PPARG target genes (P

We report the case of a patient with metastatic breast cancer who presented with an orthostatic headache. After a comprehensive diagnostic workup including MRI and lumbar puncture, we maintained the diagnosis of intracranial hypotension (IH). The patient was therefore treated with two consecutive non targeted epidural blood patches, resulting in the remission of IH symptoms for 6 months. IH in cancer patients is a rarer cause of headache than carcinomatous meningitis. As the diagnosis can be made by standard examination and the treatment is relatively simple and effective, IH deserves to be better known by oncologists.

Abstract Background Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology. Methods Patients (N = 220) with stage I–III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500–1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225–300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40. Discussion MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care. Trial registration ClinicalTrials.gov NCT04304924

Anatomic studies have traditionally relied on macroscopic, microscopic, and histological techniques to investigate the structure of tissues and organs. Anatomic studies are essential in many fields, including medicine, biology, and veterinary science. Advances in technology, such as imaging techniques and molecular biology, continue to provide new insights into the anatomy of living organisms. Therefore, anatomy remains an active and important area in the scientific field. The consolidation in recent years of some omics technologies such as genomics, transcriptomics, proteomics, and metabolomics allows for a more complete and detailed understanding of the structure and function of cells, tissues, and organs. These have been joined more recently by “omics” such as radiomics, pathomics, and connectomics, supported by computer-assisted technologies such as neural networks, 3D bioprinting, and artificial intelligence. All these new tools, although some are still in the early stages of development, have the potential to strongly contribute to the macroscopic and microscopic characterization in medicine. For anatomists, it is time to hitch a ride and get on board omics technologies to sail to new frontiers and to explore novel scenarios in anatomy.

Abstract Radiocarbon dating of the carbonate binder of historical mortars is a strategic research topic not lacking in complexities. The critical step is the separation of anthropogenic CaCO3-binder from other carbonate sources that could severely affect the resulting dates. Here we present a complete procedure for the processing and characterization of difficult mortars and of the separated binder fractions in order to assess a priori the chances of positively dating the mortar, and produce a binder fraction yielding the most reliable radiocarbon dates possible. Two complex architectural case studies from Northern Italy are presented and discussed in detail: the churches of Santa Maria Maggiore (Lomello, Pavia) and Santa Maria (Torba, Varese). The results support that both the reliability assessment and the successful radiocarbon dating are possible through a multi-analytical approach encompassing mineralogical and petrographic characterization, X-ray powder diffraction, scanning electron microscopy, measurement of carbon and oxygen stable isotopes, and optical cathodoluminescence.

IntroductionAmong substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl2 could counteract the toxic effects induced by Cd in an in vitro model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl2 for 48 h.Materials and MethodsApoptosis, cell cycle, and cell functionality were assessed. The gene expression of Nrf2 and its downstream antioxidant enzymes, ERK1/2, and AKT kinase signaling pathways were evaluated.Materials and ResultsWe found that Zn, in co-treatment with subtoxic and toxic Cd concentration, increased the number of metabolically active SCs compared to Cd exposure alone but restored SC functionality only in co-treatment with subtoxic Cd concentration with respect to subtoxic Cd alone. Exposure of Cd disrupted cell cycle in SCs, and Zn co-treatment was not able to counteract this effect. Cd alone induced SC death through apoptosis and necrosis in a dose-dependent manner, and co-treatment with Zn increased the pro-apoptotic effect of Cd. Subtoxic and toxic Cd exposures activated the Nrf2 signaling pathway by increasing gene expression of Nrf2 and its downstream genes (SOD, HO-1, and GSHPx). Zn co-treatment with subtoxic Cd attenuated upregulation on the Nrf2 system, while with toxic Cd, the effect was more erratic. Studying ERK1/2 and AKT pathways as a target, we found that the phosphorylation ratio of p-ERK1/2 and p-AKT was upregulated by both subtoxic and toxic Cd exposure alone and in co-treatment with Zn.DiscussionOur results suggest that Zn could counteract Cd effects by increasing the number of metabolically active SCs, fully or partially restoring their functionality by modulating Nrf2, ERK1/2, and AKT pathways. Our SC model could be useful to study the effects of early Cd exposure on immature testis, evaluating the possible protective effects of Zn.

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498).Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and −1.01 [-1.98 to −0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.

Purpose: Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy. Methods: The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified. Results: Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively. Conclusion: The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.