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This article explores the persistent challenges in addressing police brutality through civil rights litigation, focusing on the limitations imposed by federal jurisdiction and justiciability doctrines post-Lyons. It argues that the Supreme Court's approach, which conflates jurisdictional inquiries with procedural or remedial ones, has significantly hindered access to justice for plaintiffs seeking to vindicate their constitutional rights under §1983. By examining the foundational jurisdictional and procedural principles at stake, the article reveals the Court's missteps and suggests ways to disentangle these concepts, aiming to restore §1983's essential role in defending constitutional rights and ensuring that victims of police misconduct can obtain full redress in federal courts. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of this study is to emphasize the importance of genetic testing for healthy individuals with a strong family history of hereditary malignancies. A total of 103 healthy subjects with at least two relatives with cancer were enrolled. By NGS analysis of 27 genes, 5% were found to carry a pathogenic variant in a hereditary cancer susceptibility gene. In the era of personalized medicine, genetic testing of healthy subjects in the absence of a living affected collateral is crucially important for early diagnosis, clinical surveillance and surgical choice. Hereditary cancer syndromes caused by germline mutations account for 5–10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network's (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first- or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found, while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status. [ABSTRACT FROM AUTHOR]

Breast cancer treatments can elicit negative kinesiological side effects concerning both the posture and functional status of breast cancer survivors. As our body is functionally organized in myofascial meridians, physical exercise practice should favor a whole-body approach rather than a local one. The aim of the study was to investigate and compare the effects of two whole-body disciplines, i.e., adapted Nordic Walking and myofascial exercise, on the flexibility and strength performances in BCS. One hundred and sixty breast cancer survivors were trained three times per week for 12 weeks through adapted Nordic Walking or myofascial exercise. Handgrip, sit and reach, back scratch, and single leg back bridge tests and body composition were assessed at the beginning and completion of the training period. Linear mixed models showed no significant changes in body composition, whereas flexibility (p < 0.001), strength (p < 0.001), and muscle quality index (p = 0.003) changed independently from the treatment. When data modification has been analyzed according to sub-sample membership, no significant differences have been observed. Age, radiation therapy, and chemotherapy seem to have independent effects on several investigated variables. Twelve weeks of adapted myofascial exercise and Nordic Walking led to significant changes in flexibility, strength, and muscle quality in breast cancer survivors, with no apparent superiority of one approach over the other. [ABSTRACT FROM AUTHOR]

Simple Summary: During the last few decades, the basis for a genetic predisposition for several cancer syndromes has been clarified, and the highly penetrant/high-risk genes mutated in familial cases are currently subjected to genetic diagnostic screening programs. Mutation testing in these genes has a major impact on genetic counseling, defines the prognosis of carriers, identifies the most appropriate and personalized prophylactic measures, and increases the chance of survival. We aim to underline the effectiveness of the multigene panel in increasing the detection rate of germline mutations in cancer patients and consequently improve the healthy carriers' identification. Background: Several hereditary–familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5–10% of all tumors. Advances in genetic technology and the implementation of Next-Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing for the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multigene panel to a group of oncological patients subsequently leads to improvement in the identification of carriers of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) and prevention of the disease in these cases. Methods: Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected via a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members via Sanger sequencing. Results: A total of 131 out of the 250 cases (52%) were not carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs on BRCA1/2 (33%), 35/250 harbored PVs/LPVs on other genes beyond BRCA1 and BRCA2 (14%), and 3/250 (1%) were PVs/LPVs carriers both on BRCA1/2 and on another susceptibility gene. Conclusion: Our results show that the analysis of BRCA1/2 genes would have only resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%). [ABSTRACT FROM AUTHOR]

This Article delves into the nuanced meaning of substantive due process by tracing its historical and contemporary contexts. Beginning with the exploration of pre-ratification state constitutions, the debates surrounding ratification, and early Court views on the Constitution's nature (perceived not as a code but an enduring collection of principles), the study then addresses the role and meaning of stare decisis as positive of history and tradition, and the role of judicial decision-making in our system starting from Marbury v. Madison. The Article concludes by linking substantive due process to universally recognized fundamental rights, emphasizing that our Constitution's true intent is to safeguard these inalienable rights in service of our system and "We the People". [ABSTRACT FROM AUTHOR]

Purpose. Integrative treatments are growing among breast cancer survivors (BCS), and both acupuncture and Nordic walking (NW) are found particularly useful for them. Their positive effect on BCS health is partially due to their impact on bodily fluid balance. The study of bodily resistance and reactance is a practical method to monitor bodily fluid balance. The aims of our study were to investigate (a) the acute effects of acupuncture treatment on resistance and reactance in BCS who never had received acupuncture treatment before; (b) if BCS practising NW had better resistance and reactance than non-exercising BCS; and (c) if BCS practising NW presented a better response after acupuncture treatment than other conditions. Methods. A total of 80 BCS (53.24 ± 5.50 years), including 38 women not practising physical exercise and 42 Nordic walkers, were recruited and investigated for bodily resistance and reactance immediately before and after (a) acupuncture treatment; (b) supine rest without acupuncture. Results. Acupuncture seems to positively influence bodily resistance and reactance variation compared with supine rest. NW practice seems able to assure the best resistance and reactance basal values, and their best positive variation after supine rest and acupuncture alone. The observed results are amplified when NW and acupuncture are coupled. Conclusions. Both acupuncture and NW could be used to positively influence bodily fluids distribution, also considering that, when coupled, their positive effects are amplified. Therefore, NW should be prescribed to maintain the positive effect of acupuncture or to prepare the body for it. [ABSTRACT FROM AUTHOR]

Aim of the study: The study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies. Methods: Patients' data were provided by the Senonetwork data warehouse Senonet. In order to examine changes in the surgical and oncological management of BC patients during different phases of COVID-19 pandemic, we took advantage of a selection quality indicators (QIs). We performed the analyses in two time-frames, from July to September (Jul-Sep) (2019 versus 2020) and from October to December (Oct-Dec) (2019 versus 2020). Results: Our analysis did not show any statistically significant difference in terms of diagnosis, surgical, oncological and radiation therapy procedures between the two trimesters 2019 and 2020. Nevertheless, we observed statistically significant differences, favoring 2020, when analyzing time-to surgery and time-to radiotherapy. On the other hand, we observed a significant reduction of neoadjuvant chemotherapy and we did not recollect any data on a major use of neoadjuvant endocrine therapy. Conclusions: In Italian Breast Centers, partners of Senonetwork, we could not observe any treatment delay or change in standard clinical practice for BC care during the 2020 pandemic year, compared to 2019 pre-pandemic year. This finding is in contrast with the globally reported decrease in the performance of the Italian Breast Centers due to the COVID-19 pandemic, and has to be linked to the sharp selection of Senonetwork Breast Centers. [ABSTRACT FROM AUTHOR]

In breast cancer survivors (BCS), the contemporaneous increase of sedentary time and reduction of physical activity (PA) requires early attention because it has negative consequences for their health. Aims of the study were to investigate: a) the correlations between PA, sedentarism, and health-related measures; b) the association between different patterns of daily activity and health-related outcomes. Two hundred and nineteen BCS (50.98 ± 6.28) were selected for this study. Psychological, anthropometric, endocrine, sleeping, and both daily sedentary time and PA variables were considered. Sedentarism and PA have opposite correlations with anthropometric variables, anxiety, depression, morning salivary cortisol, and sleeping characteristics. The first favors pathological values and the latter favors normal values. Regression tree analysis showed the impact of different daily sedentary time and PA combinations on the investigated variables and allowed the individualization of their optimal combination for health. Our results could be useful to healthcare providers and BCS. [ABSTRACT FROM AUTHOR]

Purpose: Axillary management remains unclear when sentinel lymph node (SLN) results are positive in cN0 patients with breast cancer (BC). The trial ACOSOG Z0011 represented a revolution with axillary lymph node dissection (ALND) omission in SLN+ patients, despite critiques regarding non-uniformity of radiation fields. We conducted an observational study (LISEN) where whole breast radiotherapy (WBRT) was planned with tangential fields without nodal irradiation in patients eligible for the Z0011 trial. Methods: Inclusion criteria were female patients with histologically proven BC, cT1-2cN0, planned conservative surgery, no neoadjuvant therapy. Patients were stratified into two groups: micrometastatic (pN1mic, group 1) and macrometastatic (pN1a, group 2) lymph nodes. Tangential field WBRT was mandatory. Clinical outcomes were analysed, measured from surgery until the first event. Results: In all, 199 patients underwent conservative surgery and SLN biopsy; 133 patients meeting criteria were analysed: 41 patients (30.8%) pN1mic and 92 (69.2%) pN1a. The 5‑year disease-free survival (DFS) was 95.0% (85.9–100%) in group 1 and 93.0% (86.3–100.0%) in group 2 (p = 0.78). Overall survival (OS) was 100% (100–100%) in group 1 and 97.4% (92.4–100%) in group 2 (p = 0.74). For the whole cohort DFS and OS were 93.6% (88.2–99.4%) and 96.9% (91.5–100.0%), respectively. For groups 1 and 2, the 5‑year outcomes were 5.0% (0.0–14.4%) and 2.3% (0.0–6.1%) for local recurrence (p = 0.51), and 6.2% (0.0–17.4%) and 7.0% (0.0–13.7%) for distant metastasis (p = 0.61), respectively. In group 1, regional recurrence (RR) and local regional recurrence (LRR) were 5.0% (0.0–14.1%; p = 0.13). In group 2, RR and LRR were 0.0% (0.0–0.0%). Conclusion: Our results showed good regional control in patients who met the Z0011 trial criteria. WBRT, without nodal surgery or RT, avoiding axillary morbidity, seems to be a good choice. [ABSTRACT FROM AUTHOR]

Background: Distress and adrenal balance of breast cancer survivors (BCS) are key elements of their psychophysical health, and increasing evidence has shown both physical exercise and the natural environment are effective for their modulation. The aim of the study was to evaluate the acute effects of the environment and type of light intensity workouts, on distress, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) in BCS. Methods: Twenty-four BCS participated in six different workouts, each with the same duration and intensity. Three of them were conducted in natural environments - walking (Wnature), canoeing with assistance (Cnature) and a mix of myofascial and yoga exercises (MYnature). The others were conducted in an urban environment, namely walking (Wurban), or an indoor environment, namely mobilisation and light upper body exercises (MCgym) and a mix of myofascial and yoga exercises (MYgym). Before and after each workout, the Distress Thermometer was completed and saliva was collected. Results: Workouts practised in natural environments elicited a higher reduction in cortisol and the cortisol to DHEA-S ratio and a greater DHEA-S increase compared with workouts practised in urban and indoor environments. Overall, Cnature and MYnature were the best activities; among those practised in urban and indoor environments, MYgym elicited the best results. Distress was not acutely reduced after Wurban and MCgym. Conclusion: Natural environments seem to provide the best management of distress, cortisol, DHEA-S and their balance when working out at light intensities. The simultaneous presence of forests and rivers seems to be the key element of the observed results. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the effects of weekly personal feedback, based on objectively measured physical activity, on daily sleep in breast cancer survivors (BCS) with those of an intervention that also included online supervised physical exercise sessions (OSPES). BCS benefiting from both personal feedback and OSPES (n = 24), from pre-lockdown (T0) to the first month (T1) of the national lockdown, experienced an increase in both total (p ≤ 0.001) and restorative (p ≤ 0.001) sleep time, inverting their trend from the first month of lockdown to its end (total sleeping time T1 vs. T2 0.01 ≤ p <.001, T1 vs. T3 p ≤ 0.001; restorative sleeping time T1 vs. T2 0.05 ≤ p <.01, T1 vs. T3 p ≤ 0.001). Supportive technology, together with the reception of weekly tailored advice and OSPES seems to improve both quality and quantity of sleep. [ABSTRACT FROM AUTHOR]

Background: To prevent and fight the increase of daily sedentary time and to promote and stimulate the positive effects of physical activity and exercise on health, both traditional interventions and new strategies are important for breast cancer survivors (BCS). The research goal was to compare the effects of weekly personal feedback, based on objectively measured physical activity, on the trends of both daily sedentary time and on the physical activity of BCS (E− group) with those of an intervention also including online supervised physical exercise sessions (E+ group), during the Italy COVID-19 lockdown. Methods: The Italian COVID-19 emergency allowed the possibility to also observe the effects of social and personal limitations. A total of 51 BCS were studied over an 18-week period and had an objective registration of day-to-day sedentary time, physical activity, and sleep. Both subsamples received weekly or fortnight personal feedback. Data were analysed considering four key periods, according to the COVID-19 emergency steps. Results: Statistical analysis showed an additive effect for sedentary time and a multiplicative effect both for light-to vigorous and light-intensity physical activities. The E− group had a high overall sedentary time and a different trend of light-to vigorous and light-intensity physical activities, with a reduction from the 1st to the 2nd periods (national and personal restrictions), showing a significant rise just at the end of the national restrictions. Conclusions: The use of an activity tracker and its accompanying app, with the reception of weekly tailored advice and supervised online physical exercise sessions, can elicit proper physical activity recomposition in BCS in the COVID-19 era. [ABSTRACT FROM AUTHOR]

The article examines the modern law of class actions and due process in the U.S. Topics discussed include fundamental principles of due process and how it permeated the civil justice system and the Federal Rules of Civil Procedure, original form and current iteration of Federal Rule of Civil Procedure 23 governing adequate legal representation by a counsel and dismissal or compromise of a class action, as well as Supreme Court decisions interpreting Rule 23 from the perspective of due process.

Background: Aromatase inhibitors (AIs) are more effective than tamoxifen as neoadjuvant endocrine therapy (NET) for hormone receptor (HR)-positive breast cancer. Here we report the surgical and long-term outcome of elderly postmenopausal patients with locally advanced, HR-positive breast cancer treated with preoperative AIs. Methods: Between January 2003 and December 2012, 144 postmenopausal patients inoperable with breast conservative surgery (BCS) received letrozole, anastrozole, or exemestane as NET. Patients underwent breast surgery and received adjuvant AIs. Adjuvant systemic therapy, chemotherapy and/or trastuzumab, and adjuvant radiotherapy were administered as appropriate, but limited to high-risk patients with few or no comorbidities. Results: After a median follow-up of 49 months, 4 (3.0 %) patients had local relapse, 18 (12.5 %) had distant metastases, and 24 (17.0 %) died. BCS was performed in 121 (84.0 %) patients. A tumor size <3 cm and human epidermal growth factor receptor 2 (HER2) negativity were predictors of BCS. The achievement of BCS and grade G1 were significantly associated with longer disease-free survival (DFS) ( p = 0.009 and p = 0.01, respectively) and overall survival ( p = 0.002 and p = 0.005, respectively). Residual tumor ≤2 cm (yT0-yT1) in the longest diameter after NET was also statistically associated with longer DFS ( p = 0.005). Conclusions: The results of this retrospective study indicate that elderly breast cancer patients with a tumor size <3 cm at diagnosis and HER2 negativity have a higher probability of achieving BCS after NET. Moreover, patients treated with BCS and with grade G1 tumor have a reduced risk of recurrence and death in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice. Methods: Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate. Results: At Kaplan-Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer ( p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS ( p < 0.0049) and OS ( p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity ( p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS. Conclusions: HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period. [ABSTRACT FROM AUTHOR]

FANCM binds and remodels replication fork structures in vitro. We report that in vivo, FANCM controls DNA chain elongation in an ATPase-dependent manner. In the presence of replication inhibitors that do not damage DNA, FANCM counteracts fork movement, possibly by remodelling fork structures. Conversely, through damaged DNA, FANCM promotes replication and recovers stalled forks. Hence, the impact of FANCM on fork progression depends on the underlying hindrance. We further report that signalling through the checkpoint effector kinase Chk1 prevents FANCM from degradation by the proteasome after exposure to DNA damage. FANCM also acts in a feedback loop to stabilize Chk1. We propose that FANCM is a ringmaster in the response to replication stress by physically altering replication fork structures and by providing a tight link to S-phase checkpoint signalling. [ABSTRACT FROM AUTHOR]

Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. It was reported earlier that FANCD2 co-localizes with NBS1. However, the functional connection between FANCD2 and MRE11 is poorly understood. In this study, we show that inhibition of MRE11, NBS1 or RAD50 leads to a destabilization of FANCD2. FANCD2 accumulated from mid-S to G2 phase within sites containing single-stranded DNA (ssDNA) intermediates, or at sites of DNA damage, such as those created by restriction endonucleases and laser irradiation. Purified FANCD2, a ring-like particle by electron microscopy, preferentially bound ssDNA over various DNA substrates. Inhibition of MRE11 nuclease activity by Mirin decreased the number of FANCD2 foci formed in vivo. We propose that FANCD2 binds to ssDNA arising from MRE11-processed DNA double-strand breaks. Our data establish MRN as a crucial regulator of FANCD2 stability and function in the DNA damage response. [ABSTRACT FROM AUTHOR]