Two-dimensional heavy fermions in the van der Waals metal CeSiI.

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions1-6. A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases7-11, which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions. Owing to its vdW nature, CeSiI has a quasi-2D electronic structure, and we can control its physical dimension through exfoliation. The emergence of coherent hybridization of f and conduction electrons at low temperature is supported by the temperature evolution of angle-resolved photoemission and scanning tunnelling spectra near the Fermi level and by heat capacity measurements. Electrical transport measurements on few-layer flakes reveal heavy-fermion behaviour and magnetic order down to the ultra-thin regime. Our work establishes CeSiI and related materials as a unique platform for studying dimensionally confined heavy fermions in bulk crystals and employing 2D device fabrication techniques and vdW heterostructures12 to manipulate the interplay between Kondo screening, magnetic order and proximity effects.

Exposome in ischaemic heart disease: beyond traditional risk factors.

Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the 'exposome' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.

An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome".

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.

Lymphocyte recovery after bendamustine therapy in patients with mantle cell lymphoma. Results of a retrospective analysis and prognostic impact in the CAR-T era.

Bendamustine in combination with rituximab (BR) or with rituximab and cytarabine (R-BAC) is the standard first-line immunochemotherapy in mantle cell lymphoma (MCL) for elderly patients and patients ineligible for intensive regimens or autologous transplantation. As bendamustine causes prolonged lymphopenia and the literature lacks evidence of its persistence in patients with MCL, this retrospective analysis aims to estimate the lymphocyte recovery time, also in view of potential immunotherapy with CAR-T cells. Data were collected from 44 consecutive MCL patients who received bendamustine (BR or R-BAC) as first-line therapy at the Hematology Unit of Sapienza University Hospital between May 2011 and April 2022. Twenty patients (45%) were treated with R-BAC and 24 (55%) with BR. At baseline, the median lymphocyte count was 1795/µl (range: 370-11730/µL). One month after the end of therapy, it was 450/µl (range: 50-3300/µl) and 3 months after 768/µl (range: 260-1650/µl). After 6 and 9 months, we observed a gradual increase in median lymphocyte count of 900/µl (range: 370-2560/µl and 130-2770/µl, respectively). After 12 months median lymphocyte count was 1256/µl (range: 240-4140/µl). Median lymphocyte count at 1, 3, 6, and 9 months post-treatment was significantly lower than baseline but showed recovery by the 12 months. This finding is crucial for MCL patients considering CAR-T cell therapy, suggesting a minimum 9-month interval between bendamustine administration and leukapheresis.

The impact of a community-based music program during infancy on the quality of parent-child language interactions.

The early language environment, especially high-quality, contingent parent-child language interactions, is crucial for a child's language development and later academic success. In this secondary analysis study, 89 parent-child dyads were randomly assigned to either the Music Together® (music) or play date (control) classes. Children were 9- to 15-month old at baseline, primarily white (86.7%) and female (52%). Measures of conversational turns (CTs) and parental verbal quality were coded from parent-child free play episodes at baseline, mid-intervention (month 6), and post-intervention (month 12). Results show that participants in the music group had a significantly greater increase in CT measures and quality of parent verbalization post-intervention. Music enrichment programs may be a strategy to enhance parent-child language interactions during early childhood.

Comparison between different referral strategies for acute ischemic stroke patients in a hub-spoke emergency stroke network: a real-world experience in south-east Lazio.

AIM: To describe different referral strategies for acute ischemic stroke (AIS) patients in a Hub-Spoke emergency stroke network with their incidence, time metrics and related outcomes. METHODS: Referral paradigms were defined as follows: primary transfer to the comprehensive stroke center (CSC) from a remote region, called mothership (MS); secondary transfer to the CSC from a primary stroke center where intravenous thrombolysis was available, called drip and ship (DS); secondary transfer to the CSC from a community hospital where no reperfusion therapy was available, called ship and drip (SD); primary transfer to the CSC from its catchment area, called direct CSC (dCSC). RESULTS: Among 517 anterior circulation AIS patients treated with mechanical thrombectomy between 2015 and 2020, 16.6% of them were SD, in addition to the well-known referral paradigms of MS (21.8%) and DS (18.1%). This rate grew to 30% when only patients whose place of onset was outside the CSC catchment area were considered. In the SD group, onset to CSC and onset to groin were significantly longer (178±80 min vs. 102±60 min, p<0.001, and 277±77 min vs. 211±61 min, p<0.001, respectively), and the risk of any intracranial hemorrhage (ICH) was significantly higher (OR: 2.514; 95%CI: 1.18-5.35, p=0.017) compared to MS. CONCLUSION: In this hub-spoke stroke network, a high proportion of SD paradigm was found, which was associated with longer times to treatment and higher rates of any ICH. A closer cooperation between hospital stroke physicians, national health system staff, and paramedics is warranted to identify the most appropriate referral strategy for each patient.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

AIMS: Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS: This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1ß. Circulating plasma levels of interleukin-1ß decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION: This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

Quenched Excitons in WSe2/α-RuCl3 Heterostructures Revealed by Multimessenger Nanoscopy.

We investigate heterostructures composed of monolayer WSe2 stacked on α-RuCl3 using a combination of Terahertz (THz) and infrared (IR) nanospectroscopy and imaging, scanning tunneling spectroscopy (STS), and photoluminescence (PL). Our observations reveal itinerant carriers in the heterostructure prompted by charge transfer across the WSe2/α-RuCl3 interface. Local STS measurements show the Fermi level is shifted to the valence band edge of WSe2 which is consistent with p-type doping and verified by density functional theory (DFT) calculations. We observe prominent resonances in near-IR nano-optical and PL spectra, which are associated with the A-exciton of WSe2. We identify a concomitant, near total, quenching of the A-exciton resonance in the WSe2/α-RuCl3 heterostructure. Our nano-optical measurements show that the charge-transfer doping vanishes while excitonic resonances exhibit near-total recovery in "nanobubbles", where WSe2 and α-RuCl3 are separated by nanometer distances. Our broadband nanoinfrared inquiry elucidates local electrodynamics of excitons and an electron-hole plasma in the WSe2/α-RuCl3 system.

Microvascular Dysfunction across the Spectrum of Heart Failure Pathology: Pathophysiology, Clinical Features and Therapeutic Implications.

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

Insulin Resistance and Glycated Hemoglobin in Obesity Are Associated With Preference for Sugar-Sweetened Yogurt: A Pilot Study.

OBJECTIVE: Insulin resistance is associated with elevated activation of food reward, which should be associated with an increased reinforcing value of food. Research has also shown that sugar is a macronutrient strongly associated with reward and reinforcing value of food. This research is designed to assess whether insulin resistance is associated with a stronger preference for sugar-sweetened, thus elevating blood glucose responses in obese people with varying degrees of insulin resistance. METHODS: Thirteen people with obesity (body mass index, 39.1 kg/m 2 ; range, 30.0-45.1 kg/m 2 ) with varying degrees of insulin resistance (Homeostatic Model Assessment of Insulin Resistance, 5.2; range, 0.7-11.6) consumed novel flavored-colored yogurts that were sweetened with either sugar or monkfruit daily for 6 days to assess whether when given the choice of sugar-sweetened versus monkfruit-sweetened yogurts to consume, participants preferred sugar-sweetened yogurts. RESULTS: Participants consumed a greater amount ( p = .009) and percentage ( p = .04) of sugar-sweetened yogurt earned than monkfruit-sweetened yogurt. The percent of sugar-sweetened versus monkfruit-sweetened yogurt consumed in relationship to amount earned was related to insulin resistance ( r = 0.64, p = .019), glycated hemoglobin ( r = 0.61, p = .027), insulin ( r = 0.58, p = .007), and glucose ( r = 0.56, p = .048). CONCLUSIONS: Insulin resistance is associated with preference for sugar-sweetened foods in participants with obesity, which may make it hard to make dietary changes. Research is needed to assess whether treatments that improve insulin resistance also change the preference for sugar-sweetened or high-glycemic-index foods.

Parents, but not their children, demonstrate greater delay discounting with resource scarcity.

BACKGROUND: Individuals with obesity tend to discount the future (delay discounting), focusing on immediate gratification. Delay discounting is reliably related to indicators of economic scarcity (i.e., insufficient resources), including lower income and decreased educational attainment in adults. It is unclear whether the impact of these factors experienced by parents also influence child delay discounting between the ages of 8 and 12-years in families with obesity. METHODS: The relationship between indices of family income and delay discounting was studied in 452 families with parents and 6-12-year-old children with obesity. Differences in the relationships between parent economic, educational and Medicaid status, and parent and child delay discounting were tested. RESULTS: Results showed lower parent income (p = 0.019) and Medicaid status (p = 0.021) were differentially related to greater parent but not child delay discounting among systematic responders. CONCLUSIONS: These data suggest differences in how indicators of scarcity influence delay discounting for parents and children, indicating that adults with scarce resources may be shaped to focus on immediate needs instead of long-term goals. It is possible that parents can reduce the impact of economic scarcity on their children during preadolescent years. These findings suggest a need for policy change to alleviate the burden of scarce conditions and intervention to modify delay discounting rate and to improve health-related choices and to address weight disparities.

Cardiac patterns for differentiation of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage versus acute ischemic stroke.

AIMS: Neurogenic stunned myocardium (NSM) has heterogeneous presentations for acute ischemic stroke (AIS) and aneurysmal subarachnoid hemorrhage (SAH). We sought to better define NSM and differences between AIS and SAH by evaluating individual left ventricular (LV) functional patterns by speckle tracking echocardiography (STE). METHODS: We evaluated consecutive patients with SAH and AIS. Via STE, LV longitudinal strain (LS) values of basal, mid, and apical segments were averaged and compared. Different multivariable logistic regression models were created by defining stroke subtype (SAH or AIS) and functional outcome as dependent variables. RESULTS: One hundred thirty-four patients with SAH and AIS were identified. Univariable analyses using the chi-squared test and independent samples t-test identified demographic variables and global and regional LS segments with significant differences. In multivariable logistic regression analysis, when comparing AIS to SAH, AIS was associated with older age (OR 1.07, 95% CI 1.02-1.13, p = 0.01), poor clinical condition on admission (OR 7.74, 95% CI 2.33-25.71, p < 0.001), decreased likelihood of elevated admission serum troponin (OR .09, 95% CI .02-.35, p < 0.001), and worse LS basal segments (OR 1.18, 95% CI 1.02-1.37, p = 0.03). CONCLUSION: In patients with neurogenic stunned myocardium, significantly impaired LV contraction by LS basal segments was found in patients with AIS but not with SAH. Individual LV segments in our combined SAH and AIS population were also not associated with clinical outcomes. Our findings suggest that strain echocardiography may identify subtle forms of NSM and help differentiate the NSM pathophysiology in SAH and AIS.

The effects of a music enrichment program on parent-infant interactions during mealtime: A randomized controlled trial.

BACKGROUND: Parent-child interactions are linked to childhood obesity. Music enrichment programs enhance parent-child interactions and may be a strategy for early childhood obesity prevention. OBJECTIVE: We implemented a 2-year randomized, controlled trial to assess the effects of a music enrichment program (music, n = 45) vs. active play date control (control, n = 45) on parent-child interactional quality and infant weight status. METHODS: Typically developing infants aged 9-to 15-months were enrolled with a primary caregiver in the Music Together ® or a play date program. Participants attended once per week group meetings for 12 months and once per month group meetings for an additional 12 months. Parent-child interaction was measured using the Parent Child Early Relational Assessment (PCERA) at baseline, month 6, 12, and 24. We used a modified intent-to-treat mixed model regression to test group differences in parent-child interactions and Weight for length z-score (zWFL) growth trajectories were modeled. RESULTS: There were significant differential group changes across time for negative affect during feeding (group*month; p = 0.02) in that those parents in the music group significantly decreased their negative affect score compared with the control group from baseline to month 12 (music change = -0.279 ± 0.129; control change = +0.254 ± 0.131.; p = 0.00). Additionally, we also observed significant differential group changes across time for parent intrusiveness during feeding (group*month; p = 0.04) in that those parents in the music group significantly decreased their intrusiveness score compared with the control group from month 6 to month 12 (music change = -0.209 ± 0.121; control change = 0.326 ± 0.141; p = 0.01). We did not find a significant association between any of the changes in parental negative affect and intrusiveness with child zWFL trajectories. CONCLUSION: Participating in a music enrichment program from an early age may promote positive parent-child interactions during feeding, although this improvement in the quality of parent-child interactions during feeding was not associated with weight gain trajectories.

Posterior communicating artery infundibulum with oculomotor nerve palsy treated with microvascular decompression: a case report and 2-dimensional technical operative video.

Oculomotor nerve palsies are typically associated with posterior communicating artery (PcommA) aneurysms. We report a rare case of an oculomotor nerve palsy caused by a PcommA infundibular dilatation. Although there are cases of infundibular dilatations causing cranial nerve palsies, only reports of three involving the PcommA exists. We review these reported cases in the literature and discuss their treatments as well as other non-aneurysmal compressive etiologies that may cause oculomotor nerve palsies. We present the case of a 53-year-old female with transient oculomotor nerve palsy that was initially diagnosed with a PcommA aneurysm. She underwent a craniotomy with plans of microsurgical clipping; however, the dilatation was identified correctly as an infundibulum intraoperatively. The operation was completed as a microvascular decompression and her oculomotor nerve palsy has not returned at the 1-year follow-up. We provide a detailed microsurgical report and video detailing the operative technique and relevant anatomy for this operation. Although rare and not as life-threatening as aneurysms, infundibular dilatations as a cause of oculomotor nerve palsy should remain as a differential diagnosis. Given the difference in natural history and treatment of these two entities, it is important to diagnose and treat them appropriately. Multimodal imaging such as thin-sliced computed tomography angiogram (CTA) and 3-dimensional (3D) rotational angiography can aid in diagnosis.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

Nanoscale Femtosecond Dynamics of Mott Insulator (Ca0.99Sr0.01)2RuO4.

Ca2RuO4 is a transition-metal oxide that exhibits a Mott insulator-metal transition (IMT) concurrent with a symmetry-preserving Jahn-Teller distortion (JT) at 350 K. The coincidence of these two transitions demonstrates a high level of coupling between the electronic and structural degrees of freedom in Ca2RuO4. Using spectroscopic measurements with nanoscale spatial resolution, we interrogate the interplay of the JT and IMT through the temperature-driven transition. Then, we introduce photoexcitation with subpicosecond temporal resolution to explore the coupling of the JT and IMT via electron-hole injection under ambient conditions. Through the temperature-driven IMT, we observe phase coexistence in the form of a stripe phase existing at the domain wall between macroscopic insulating and metallic domains. Through ultrafast carrier injection, we observe the formation of midgap states via enhanced optical absorption. We propose that these midgap states become trapped by lattice polarons originating from the local perturbation of the JT.

Microvascular complications identify a specific coronary atherosclerotic phenotype in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. METHODS: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. RESULTS: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). CONCLUSIONS: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.

Invasive Functional Coronary Assessment in Myocardial Ischemia with Non-Obstructive Coronary Arteries: from Pathophysiological Mechanisms to Clinical Implications.

Despite ischemic heart disease (IHD) has been commonly identified as the consequence of obstructive coronary artery disease (OCAD), a significant percentage of patients undergoing coronary angiography because of signs and/or symptoms of myocardial ischemia do not have any significant coronary artery stenosis. Several mechanisms other than coronary atherosclerosis, including coronary microvascular dysfunction (CMD), coronary endothelial dysfunction and epicardial coronary vasospasm, can determine myocardial ischemia or even myocardial infarction in the absence of flow-limiting epicardial coronary stenosis, highlighting the need of performing adjunctive diagnostic tests at the time of coronary angiography to achieve a correct diagnosis. This review provides updated evidence of the pathophysiologic mechanisms of myocardial ischemia with non-obstructive coronary arteries, focusing on the diagnostic and therapeutic implications of performing a comprehensive invasive functional evaluation consisting of the assessment of both vasodilation and vasoconstriction disorders. Moreover, performing a comprehensive invasive functional assessment may have important prognostic and therapeutic implications both in patients presenting with myocardial ischemia with non-obstructive coronary arteries (INOCA) or myocardial infarction with non-obstructive coronary arteries (MINOCA), as the implementation of a tailored patient management demonstrated to improve patient's symptoms and prognosis. However, given the limited knowledge of myocardial ischaemia with non-obstructive coronary arteries, there are no specific therapeutic interventions for these patients, and further research is warranted aiming to elucidate the underlying mechanisms and risk factors and to develop personalized forms of treatment.

The Perils of Being Unhinged: On the Accuracy of Classifiers Minimizing a Noise-Robust Convex Loss.

van Rooyen, Menon, and Williamson (2015) introduced a notion of convex loss functions being robust to random classification noise and established that the "unhinged" loss function is robust in this sense. In this letter, we study the accuracy of binary classifiers obtained by minimizing the unhinged loss and observe that even for simple linearly separable data distributions, minimizing the unhinged loss may only yield a binary classifier with accuracy no better than random guessing.

Pathophysiology of Coronary Microvascular Dysfunction.

Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD ("primary" microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.