NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions.

NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.

A Unique Case of Mesenteric Gastrointestinal Stromal Tumor Presenting as an Acute Abdomen.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract and arise from the interstitial cells of Cajal in the mesenteric plexus. These tumors can originate in any part of the GI tract; however, a higher burden has been observed in the stomach and small intestines. Mesenteric GISTs are exceedingly rare, with unique clinicopathological features and a poorer prognosis. Herein, we describe a unique case of a 66-year-old female with a remote history of appendectomy who presented to the emergency room complaining of severe abdominal pain and vomiting. On imaging, the patient was found to have a large inflammatory mass associated with small bowel loops, and the pathology confirmed a mesenteric GIST. The tumor was resected, and the genomic test results confirmed the KIT (exon 11) mutation. Although the tumor had a low mitotic rate, the tumor was large enough to warrant the initiation of adjuvant imatinib mesylate for 36 months with regular bloodwork and imaging.

The Role of Physiotherapy in Peripheral Artery Disease in Patients With Diabetes Mellitus: A Narrative Review.

Diabetes mellitus (DM) comprises a spectrum of metabolic disorders distinguished by the persistent elevation of glucose levels in the bloodstream. It stands as a primary risk factor for peripheral arterial disease (PAD), denoted by atherosclerosis affecting the lower extremities. One clinical manifestation of symptomatic PAD is intermittent claudication alleviated by rest but also capable of presenting as atypical leg pain. Confirmatory diagnostic measures, including the ankle-brachial index (ABI), toe-brachial index (TBI), or Doppler waveform analysis, are imperative in the verification of PAD. For management, the recommendation is to incorporate physiotherapy alongside concurrent medical interventions, such as anticoagulants, antiplatelet agents, statins, or, in certain cases, surgical procedures. This narrative review seeks to elucidate the advantages of physiotherapy in diabetic patients with PAD, contributing to the deceleration of disease progression and improving symptoms. Although supervised exercise therapy is strongly supported by empirical evidence as more beneficial, the absence of supervised environments is a common issue. Consequently, the preference lies in the combination of supervised exercise with home-based regimens. The objective is that each patient exercises for more than three days per week, progressively extending their duration weekly. This approach has demonstrated a noteworthy enhancement in walking functionality, exercise tolerance, pain alleviation, and an overall improvement in the quality of life for patients.

Depolarization of echo chambers by random dynamical nudge.

In social networks, users often engage with like-minded peers. This selective exposure to opinions might result in echo chambers, i.e., political fragmentation and social polarization of user interactions. When echo chambers form, opinions have a bimodal distribution with two peaks on opposite sides. In certain issues, where either extreme positions contain a degree of misinformation, neutral consensus is preferable for promoting discourse. In this paper, we use an opinion dynamics model that naturally forms echo chambers in order to find a feedback mechanism that bridges these communities and leads to a neutral consensus. We introduce the random dynamical nudge (RDN), which presents each agent with input from a random selection of other agents' opinions and does not require surveillance of every person's opinions. Our computational results in two different models suggest that the RDN leads to a unimodal distribution of opinions centered around the neutral consensus. Furthermore, the RDN is effective both for preventing the formation of echo chambers and also for depolarizing existing echo chambers. Due to the simple and robust nature of the RDN, social media networks might be able to implement a version of this self-feedback mechanism, when appropriate, to prevent the segregation of online communities on complex social issues.

Will I die of coronavirus? Google Trends data reveal that politics determine virus fears.

Is Google Trends (GT) useful to survey populations? Extant work has shown that certain search queries reflect the attitudes of hard-to-survey populations, but we do not know if this extends to the general population. In this article, we leverage abundant data from the Covid-19 pandemic to assess whether people's worries about the pandemic match epidemiological trends as well as political preferences. We use the string 'will I die from coronavirus' on GT as the measure for people's level of distress regarding Covid-19. We also test whether concern for coronavirus is a partisan issue by contrasting GT data and 2016 election results. We find strong evidence that (1) GT search volume close matches epidemiological data and (2) significant differences exist between states that supported Clinton or Trump in 2016.

Doble lesión de la médula espinal por proyectil de arma de fuego con migración en el canal medular: reporte de un caso / Dual spinal cord injury caused by a firearm projectile migrated into the spinal canal: A case report

Introducción. El tratamiento quirúrgico de las lesiones por proyectil de arma de fuego en la columna es controversial; sin embargo, el déficit neurológico es uno de los criterios para su indicación. Presentación del caso. Hombre de 21 años que ingresó al servicio de urgencias de un hospital de tercer nivel en Bogotá, Colombia, por múltiples heridas de arma de fuego, paraplejía, hipoestesia en miembros inferiores y silla de montar, e incapacidad para moverse, por lo que se realizó toracotomía y laparotomía. Ante la ausencia de fuerza muscular y reflejos, se diagnosticó lesión de la médula espinal de grado A según la American Spinal Injury Association Impairment Scale (ASIA). A las 12 horas del ingreso, se llevó al paciente a extracción quirúrgica de un proyectil (laminectomía y durotomía longitudinal) sin lograr la extracción, por lo que se utilizó fluoroscopia, en la que se observó que la bala había migrado cefálicamente al espacio intervertebral L4-L5. Se realizó laminectomía de L4-L5, exposición del saco dural y durotomía longitudinal, logrando la extracción del proyectil. A los 20 días se observó mejoría de la función motora y la fuerza muscular, contracción voluntaria de cuádriceps y grado C en ASIA.Conclusión. La extracción del proyectil en lesiones de la médula espinal se recomienda cuando hay migración de este en el canal medular. Se sugiere usar fluoroscopia antes y después de la cirugía

Introduction: Surgical treatment of spinal gunshot wounds is controversial, however, neurological deficit is one of the criteria for its indication. Case presentation: A 21-year-old man was admitted to the emergency department of a tertiary care hospital in Bogotá, Colombia, due to multiple gunshot wounds, paraplegia, hypoesthesia in the lower limbs and saddle area, and inability to move, for which thoracotomy and laparotomy were performed. Given the absence of muscle strength and reflexes, a grade A spinal cord injury was diagnosed according to the American Spinal Injury Association Impairment Scale (ASIA). Twelve hours after admission, the patient was taken to surgery for the removal of a firearm projectile (laminectomy and longitudinal durotomy) without achieving the extraction, so a fluoroscopy was carried out, in which it was observed that the bullet had migrated cephalad to the L4-L5 intervertebral space. L4-L5 laminectomy, dural sac exposure, and longitudinal durotomy were performed, leading to the removal of the projectile. After 20 days, improvement of motor function and muscle strength, voluntary contraction of quadriceps, and grade C in ASIA were reported.Conclusion: Projectile removal in spinal cord injuries is recommended when the projectile migrates into the spinal canal. Fluoroscopy is recommended before and after surgery