Large Subset Research Articles

The Role of the Immune Response to Helicobacter pylori Antigens and Its Relevance in Gastric Disorders

Helicobacter pylori (H.p.) is a Gram-negative bacterium endowed with gastric tropism. H.p. infection is widely spread throughout the world, accounting for various pathologies, such as peptic ulcer, gastric cancer, mucosa-associated lymphoid tissue lymphoma, and extra-gastric manifestations. This bacterium possesses several virulence factors, e.g., lipopolysaccharides (LPS), the toxins CagA and VacA, and adhesins, which elicit a robust immune response during the initial phase of the infection. Of note, the lipid A moiety of the LPS exhibits a lower endotoxic potency than that of other LPSs, thus facilitating infection through a mechanism of immune escape. H.p. colonization of the gastric mucosa induces an initial protective immune response with innate immune cells, e.g., neutrophils, monocytes, and macrophages, which engulf and kill bacteria. Moreover, the same cells, along with gastric epithelial cells, secrete cytokines and chemokines, which recruit T cells [T helper (h)1 and Th17 cells] to the site of infection, thus leading to H.p. eradication. In a large subset of individuals, the perturbation of such an immune equilibrium leads to a harmful response, with an expansion of T regulatory (TREG) cells, which suppress the protective immune response. In fact, TREG cells, via the production of interleukin (IL)-10, downregulate Th1- and Th17-related cytokines, thus allowing H.p. survival and the perpetuation of inflammation. As far as the humoral immune response is concerned, B cells, upon H.p. stimulation, produce autoreactive antibodies, and IgG anti-Lex antibodies are harmful to the gastric mucosa. In this review, the structure and function of H.p. antigenic components and immune mechanisms elicited by this bacterium will be described in relation to gastric damage.

Brachial Plexus Birth Injury: Treatment and Interventions.

Introduction: Brachial plexus birth injury (BPBI) is a condition affecting newborns and involves damage to the nerve fibers compromising the brachial plexus during birth. Although most newborns recover spontaneously, a large subset require surgery to regain function, and others will have permanent disability despite intervention. Deciding when to pursue surgical intervention remains a challenge for clinicians treating BPBI. Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and MEDLINE databases. A total of 24 primary and secondary sources were chosen for inclusion following full-text assessments. All sources were analyzed to provide a comprehensive review on the development of BPBI treatments and interventions over time. Results: Spontaneous recovery can be achieved in many cases of BPBI, but most patients require physical therapy and other forms of treatment to avoid muscle imbalance and prevent contracture formation. In addition to physical therapy, the most common non-surgical interventions include botulinum toxin injections and splinting. In cases requiring surgery, clinicians may use several tests and diagnostic imaging to aid in decision making. Common surgical interventions for BPBI include nerve grafting, nerve transfers, and muscle and tendon transfers. Conclusion: Most newborns recover from BPBI within the first 3 months of life. However, some require treatment to restore optimal function. In general, non-surgical interventions should be the primary course of treatment, and surgery should be avoided unless the patient is deemed unable to recover with any other treatment.

Self-Sufficient Electrochromic Solar Cells: Photovoltaic and Color Modulating Smart Windows.

Electronic devices cover a large subset of daily life gadgets which use power to run, hence increasing the load of the energy needs and indirectly impacting greenhouse gas emissions. Smart electrochromic windows provide a solution to this through remarkable energy saving by adjusting optical behavior depending on the environmental conditions. Since the electrochromic windows also need power to run, a self-powered electrochromic panel will be a better solution. Electrochromic solar cell (ECSC) technology stands out among the available technologies by offering multifunctional functionalities. Utilizing ECSCs, energy efficiency may be greatly increased by harvesting solar energy and using it to generate and store electricity while dynamically adjusting thermal and optical properties. Looking at this emerging trend, material selection and device architecture that can store and utilize solar energy in their performance mechanism are the need of the hour. The ECSCs hold substantial potential for energy savings in heating, cooling, and lighting, making them crucial for the development of energy-efficient buildings. The present spotlight provides information on the necessary materials, device designs that have emerged so far, and their impact on optical modulation and energy harvesting and sheds light on future perspectives.

Finding product sets in some classes of amenable groups

Abstract In [15], using methods from ergodic theory, a longstanding conjecture of Erdős (see [5, Page 305]) about sumsets in large subsets of the natural numbers was resolved. In this paper, we extend this result to several important classes of amenable groups, including all finitely generated virtually nilpotent groups and all abelian groups $(G,+)$ with the property that the subgroup $2G := \{g+g : g\in G\}$ has finite index. We prove that in any group G from the above classes, any $A\subset G$ with positive upper Banach density contains a shifted product set of the form $\{tb_ib_j\colon i<j\}$ , for some infinite sequence $(b_n)_{n\in \mathbb {N}}$ and some $t\in G$ . In fact, we show this result for all amenable groups that posses a property which we call square absolute continuity. Our results provide answers to several questions and conjectures posed in [13].

Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis.

Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease. A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses. We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4%; disease control rate [DCR], 94.4%; and clinical benefit rate [CBR], 79.3%) and a 12-month PFS of 64.7% and OS of 82.7%. Intracranial ORR, DCR, and CBR were seen in 62.2%, 88.6%, and 68.6% of patients, respectively, and 67.4% achieved intracranial PFS at 12months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95% confidence interval 1.3-10.8, p=0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4% and 94.1% of patients, respectively. This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.

W mass and muon g−2 in an inert 2HDM extended by a singlet complex scalar

The deviations of the recent measurements of the muon magnetic moment and the W-boson mass from their SM predictions hint to new physics beyond the SM. In this article, we address the observed discrepancies in the W-boson mass and muon anomalous magnetic moment in the Inert Two Higgs Doublet Model extended by a complex scalar field singlet under the SM gauge group. The model is constrained from the existing Large Electron Positron Collider (LEP) data and the measurements of partial decay widths to gauge bosons at LHC. It is shown that a large subset of the constrained parameter space of the model can accommodate both the experimentally measured as well as SM global fit value of W-boson mass while simultaneously explaining the observed muon g−2 anomaly. Published by the American Physical Society 2024

RNA profiles differ between small and large extracellular vesicle subsets isolated from porcine seminal plasma

BackgroundExtracellular vesicles (EVs) are essential for cell-to-cell communication because they transport functionally active molecules, including proteins, RNA, and lipids, from secretory cells to nearby or distant target cells. Seminal plasma contains a large number of EVs (sEVs) that are phenotypically heterogeneous. The aim of the present study was to identify the RNA species contained in two subsets of porcine sEVs of different sizes, namely small sEVs (S-sEVs) and large sEVs (L-sEVs). The two subsets of sEVs were isolated from 54 seminal plasma samples by a method combining serial centrifugations, size exclusion chromatography, and ultrafiltration. The sEVs were characterized using an orthogonal approach. Analysis of RNA content and quantification were performed using RNA-seq analysis.ResultsThe two subsets of sEVs had different size distributions (P < 0.001). They also showed differences in concentration, morphology, and specific protein markers (P < 0.05). A total of 735 RNAs were identified and quantified, which included: (1) mRNAs, rRNAs, snoRNAs, snRNAs, tRNAs, other ncRNAs (termed as “all RNAs”), (2) miRNAs and (3) piRNAs. The distribution pattern of these RNA classes differed between S-sEVs and L-sEVs (P < 0.05). More than half of “all RNAs”, miRNAs and piRNAs were found to be differentially abundant between S- and L-sEVs (FDR < 0.1%). Among the differentially abundant RNAs, “all RNAs” were more abundant in L- than in S-sEVs, whereas the most of the miRNAs were more abundant in S- than in L-sEVs. Differentially abundant piRNAs were equally distributed between S- and L-sEVs. Some of the all RNAs and miRNAs found to be differentially abundant between S- and L-sEVs were associated with sperm quality and functionality and male fertility success.ConclusionsSmall and large sEVs isolated from porcine seminal plasma show quantitative differences in RNA content. These differences would suggest that each sEV subtype exerts different functional activities in the targeted cells, namely spermatozoa and functional cells of the female reproductive tract.

Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.

The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.

ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory T Cells in Intrarenal Inflammation.

The P2X7 ion channel, a key sensor of sterile inflammation, has been implicated as a therapeutic target in glomerulonephritis, and P2X7-antagonistic nanobodies can attenuate experimental glomerulonephritis. However, little is known about the expression of P2X7 on renal immune cells. We used conventional immunofluorescence of kidney sections as well as intraperitoneal injection of nanobodies in mice followed by flow cytometry analysis of parenchymal T cells and RNA-sequencing to elucidate the expression and function of P2X7 on parenchymal and vascular immune cells in the mouse kidney. Our study showed that parenchymal T cells, including a large subset of natural killer T cells and CD69+ tissue-resident memory T cells, display much higher cell surface levels of P2X7 than vascular T cells. After a single intraperitoneal injection of P2X7-blocking nanobodies, P2X7 on parenchymal T cells was fully occupied by the injected nanobodies within 30 min. This resulted in an effective protection of these cells from NAD-induced cell death during cell preparation. Conversely, systemic injection of NAD that mimics sterile inflammation results in the selective depletion of P2X7hiCD69hi T cells from the kidney parenchyma. Our study uncovered a novel purinergic regulatory mechanism affecting kidney-resident T cell populations.

Abnormal Upper Gastrointestinal Motility Reduces the Efficacy of Colectomy for Colonic Inertia: A Systematic Review and Meta-analysis.

This systematic review aimed to assess the effects of upper gastrointestinal (UGI) dysmotility on outcomes of surgical treatment of colonic inertia (CI). This PRISMA-compliant systematic review and meta-analysis searched PubMed, Scopus, Google Scholar, and clinicaltrials.gov through October 2023 for studies that assessed outcomes of CI patients who underwent colectomy while putting data on UGI motility in context. The primary outcome was postoperative persistence or recurrence of constipation. Secondary outcomes were postoperative complications, continence, and quality of life (QoL) improvements. The revised tool to assess the risk of bias in nonrandomized studies of interventions was used to assess the risk of bias, and the certainty of evidence was graded using the GRADE approach. Eight studies (1991 to 2013) included data on UGI evaluation of CI patients; 12.8 to 24.3% were tested for concomitant GI dysmotility. High rates of motility abnormalities were in the small bowel (31.4%), stomach (34.1%), and esophagus (48.5%). Patients with UGI dysmotility and CI were more likely to experience constipation recurrence (OR: 10.71, 95% CI: 2.17; 52.87, P=0.004) and less likely to have postoperative QoL improvements (OR: 0.16, 95% CI: 0.04; 0.65, P=0.010) compared with patients with CI and no abnormal UGI testing. There were no differences in postoperative complications (OR: 1.59, 95% CI: 0.64; 4.267, P=0.542) or continence (OR: 0.29, 95% CI: 0.06; 1.47, P=0.0136) rates. Large subsets of CI patients with concomitant UGI dysmotility may be preoperatively underdiagnosed. UGI dysmotility may be associated with a higher risk of postoperative recurrence of constipation and suboptimal improvements in QoL. We recommend routine UGI evaluation before surgery for CI.

Serial Clinical and Biomarker Monitoring during Graft-Versus-Host Disease Treatment Identifies Distinct Risk Strata Including an Ultra-Low Risk Group.

The standard treatment for acute graft-vs-host disease (GVHD), a common complication following allogeneic hematopoietic cell transplant, remains prolonged courses of high dose corticosteroids. Previous attempts to decrease corticosteroid exposure during GVHD therapy failed because physicians lack the tools necessary to safely reduce and shorten therapy and fear loss of GVHD control in responding patients. Prior studies have shown that a serum biomarker risk score, the MAGIC algorithm probability (MAP), provided prognostic value within groups with similar clinical severity and that patients with GVHD that is Minnesota standard risk by clinical symptoms and who have a low MAP at the start of corticosteroid treatment represent a low risk group with good outcomes. This study tested the hypothesis that serial monitoring of GVHD symptoms and the MAP score in patients with low risk GVHD could provide further risk stratification, and would identify a subset with exceptionally low rates of failure with standard treatment, which we term ultra-low risk (ULR) GVHD who might benefit from reduced corticosteroid treatment. Weekly monitoring of clinical symptoms and MAPs from initiation to day 14 of treatment was used to further divide 450 patients with low risk GVHD into groups with different outcomes, such as overall response rates at day 28 and non-relapse mortality at six-months. 310/450 low risk patients (69%) who achieved clinical response by day 14 and had low MAPs at days 7 and 14 constituted an ultra-low risk (ULR) group. that experienced a significantly higher overall response rate at day 28 (93% vs 50%, p<0.001) that was sustained to day 56 (84% vs 45%, p<0.001) and significantly lower six-month NRM (4% vs 13%, p<0.001) compared to the non-ULR patients. Patients who achieved clinical response by day 14 but who developed a high MAP during monitoring (n=20) experienced six-fold higher six-month NRM than the ULR group (25% vs 4%, p<0.001). Among 120 patients who did not achieve a clinical response by day 14, the overwhelming majority (n=112) who maintained low MAPs at both days 7 and 14 of treatment experienced six-fold lower NRM at six months compared to patients with a high MAP at either time point (8% vs 50%, p<0.001). The majority of deaths within the ULR group were due to infections in patients with complete and sustained control of GVHD symptoms while the majority of deaths in the non-ULR group were due to poorly controlled GVHD. Serial monitoring during treatment can identify a large subset of patients by day 14 who achieve excellent GVHD control but remain at risk for treatment complications with standard treatment and who might be suitable candidates for testing abbreviated corticosteroid courses.

An Evaluation of a Trauma-Informed Intervention in Secure Juvenile Detention: The Impact on Youth-Level Incidents of Violence

Few studies have examined the impact of trauma-specific interventions in juvenile justice settings, and juvenile justice-related outcomes are infrequently assessed. This study examined the impact of implementing youth skills groups ( Skills Training in Affective and Interpersonal Regulation [STAIR]) and trauma training for staff (Think Trauma) on individual-level assaults in two secure detention facilities. The impact of the intervention was primarily evidenced in one facility among Black youth. In the same facility, the staff training (pre-skills groups) cohort and skills group cohort (post-staff training) evidenced a significantly greater reduction in violent incident rates as compared to the pre-intervention cohort. These findings highlight the importance of trauma-focused training for staff as a promising step toward reducing violence and improving staff members’ responses to a large subset of vulnerable youth.

G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target ATRX-deficient malignant glioma.

Inactivation of α-thalassaemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models. Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the latter a central element of current treatment standards. CX-5461 promoted dose-sensitive lethality in ATRX-deficient GSCs relative to ATRX-intact controls. Mechanistic studies revealed that CX-5461 disrupted histone variant H3.3 deposition, enhanced replication stress and DNA damage, activated p53-independent apoptosis, and induced G2/M arrest to a greater extent in ATRX-deficient GSCs than in ATRX-intact counterparts. These data were corroborated in vivo, where CX-5461/IR treatment profoundly delayed tumor growth and prolonged survival in mice bearing ATRX-deficient flank xenografts. Histopathological analyses revealed decreased proliferation, increased apoptosis, and significant G4 induction, replication stress, and DNA damage in CX-5461-treated tumors, both alone and in combination with IR. Finally, despite suboptimal blood-brain-barrier penetration, systemic CX-5461 treatment induced tangible pharmacodynamic effects in ATRX-deficient intracranial GSC models. In totality, our work substantively demonstrates efficacy and defines mechanisms of action for G4 stabilization as a novel therapeutic strategy targeting ATRX-deficient malignant glioma, laying the groundwork for clinical translation.

BIOM-46. REAL-WORLD EXPERIENCE WITH CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID IN PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS

Abstract Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) offers a minimally invasive approach to identify somatic alterations for individuals with central nervous system (CNS) cancers. Here, we review our ‘real world’ experience using a clinically validated, FDA-authorized platform, MSK-IMPACTTM, to comprehensively profile ctDNA from CSF samples with and without clinically documented CNS involvement by cancer (1007 samples, 711 patients). The patient cohort included patients with over 90 distinct tumor types of primary CNS and metastatic origin, with lung cancer (n = 188), breast cancer (n = 150), and glioma (n = 148) representing the most common broad categories. We identified genetic alterations (ctDNA-positive) in 489/922 (53.0%) CSF samples from patients with clinically documented CNS cancer. Over half of these ctDNA-positive samples (248, 50.7%) possessed a biomarker that was predictive of response to an FDA-approved drug (OncoKB level 1). Furthermore, the distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Of patients without clinical documentation of CNS cancer, none of these 85 CSF samples were ctDNA-positive (specificity = 100%). Successive CSF sequencing over time identified clonal evolution and the emergence of resistance mechanisms to therapies. ctDNA positivity corresponded with shortened overall survival after CSF collection (HR: 3.23, 95% CI: 2.58-4.05, P &amp;lt; 0.001). NGS of CSF cfDNA can detect clinically actionable somatic alterations in a large subset of CNS cancer patients and allows tracking of tumor evolution. Detection of somatic alterations in CSF may be a useful prognostic biomarker for survival in cancer patients.

TMET-37. TARGETING LIPID MEDIATED NON-CANONICAL CELL DEATH IN MALIGNANT GLIOMA

Abstract Resistance to canonical cell death mechanisms (e.g. apoptosis) is a hallmark of glioma and consequently driving the dismal outcomes of patients with glioma. Recent work has demonstrated gliomas are susceptible to non-apoptotic forms of cell death mediated by rewired lipid metabolism. Here we explored whether gliomas are vulnerable to other lipid-dependent forms of cell death. Our investigation revealed a large subset of patient-derived glioma cells that are exquisitely sensitive to a novel cell death pathway dependent on palmitate. Intriguingly, sensitivity to this type of cell death was linked to glioma tumor cells having a proneural identity and a specific enrichment in sphingolipid metabolic features. The catabolism of glioma sphingolipids established palmitate pools for protein S-palmitoylation, a necessary requirement to trigger palmitate mediated cell death in glioma, which was coupled to the exclusive expression of palmitoyl acyltransferases unique to proneural glioma tumors. Ongoing efforts aim to explore the mechanistic link between glioma identity, lipotype and susceptibility to palmitate dependent lethality. Taken together, these results identify a new approach to drive glioma cell death by targeting non-canonical cell death mediated by rewired glioma lipid metabolism.

An Architecture for Transformation in Child Mental Health

This Viewpoint describes efforts to provide timely, comprehensive, and high-quality mental health care to a large population-representative subset of children within a single health system and demonstrate its potential impact and true cost.

Two Decades of High-Resolution Peripheral Quantitative Computed Tomography: Present and Future Clinical Perspectives.

Twenty years have passed since the introduction of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess human bone microarchitecture. During that time, the technique has emerged as an important research tool used by clinicians and scientists to learn about the pathophysiology of bone adaptation in the context of osteoporosis and many other bone-affected conditions. Its rich three-dimensional data is well suited for precise longitudinal monitoring of bone microarchitecture and associated patient-specific estimated bone strength.However, uptake of HR-pQCT as a clinical diagnostic tool has been limited, in part due to challenges such as availability, regulatory approvals, and demonstrated cost effectiveness. New research suggests fracture risk assessment using HR-pQCT is comparable with current standards based on traditional bone densitometry, but its contribution to clinical care is best suited to two areas: (1) leveraging microarchitectural information to assist in treatment decisions for the large subset of patients who lie in the so-called gray zone by current fracture risk assessment, and (2) longitudinal monitoring that establishes highly refined trajectories of bone adaptation and can inform decisions to initiate treatment, monitor treatment effects, and inform cessation.

Profiling Astroturfers on Facebook: A Complete Framework for Labeling, Feature Extraction, and Classification

The practice of online astroturfing has become increasingly pervasive in recent years, with the growth in popularity of social media. Astroturfing consists of promoting social, political, or other agendas in a non-transparent or deceitful way, where the promoters masquerade as normative users while acting behind a mask that conceals their true identity, and at times that they are not human. In politics, astroturfing is currently considered one of the most severe online threats to democracy. The ability to automatically identify astroturfers thus constitutes a first step in eradicating this threat. We present a complete framework for handling a dataset of profiles, from data collection and efficient labeling, through feature extraction, and finally, to the identification of astroturfers lurking in the dataset. The data were collected over a period of 15 months, during which three consecutive elections were held in Israel. These raw data are unique in scope and size, consisting of several million public comments and reactions to posts on political candidates’ pages. For the manual labeling stage, we present a technique that can zoom in on a sufficiently large subset of astroturfer profiles, thus making the procedure highly efficient. The feature extraction stage consists of a temporal layer of features, which proves useful for identifying astroturfers. We then applied and compared several algorithms in the classification stage, and achieved improved results, with an F1 score of 77% and accuracy of 92%.

The Evolution of Sustainable Accounting and Carbon monitoring: A Decade on Decade Analysis

The aim of this essay is to define sustainable accounting and how it has evolved over the years, highlighting the need and the formation, and the changes implemented on a decade-by-decade basis. The initial trend is thought to be inexistent when climate change was relatively not as big an issue as it is today, slightly existent when developed nations started waking up to changes in the climate and lastly, strongly existent, when sustainable accounting and carbon monitoring is not an option, but mandatory for a large subset of countries, multinational firms, and organizations all over the world.

Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.

LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking. The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care. In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction. 21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients. ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.