Pre-Golgi Intermediate Compartment

The pre-Golgi intermediate compartment (IC), also referred to as the endoplasmic reticulum (ER)-Golgi IC (ERGIC), functions in molecular sorting and two-way trafficking in the early biosynthetic-secretory pathway. It receives newly synthesized proteins and lipids from the ER, associates with cytoskeletal filaments and binds COPI protein coats, thereby generating saccular, tubular and vesicular carriers that mediate antero- and retrograde transport at the ER-Golgi interface. Although the dynamic IC elements have traditionally been considered as transient transport intermediates, recent results showing their persistence during cell division, multifunctionality, and operation at the crossroads of Golgi-dependent and -independent transport routes provide evidence that they constitute a permanent organelle. © 2023 Elsevier Inc. All rights reserved.

Lessons from SENCOVAC: A prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

Characteristics and risk factors of COVID-19 mortality in Tamaulipas, one year after the pandemic / Características y factores de riesgo de mortalidad por COVID-19 en Tamaulipas, a un año de pandemia

Resumen Coronavirus 19 (COVID-19), es una enfermedad viral prevalente y diseminada a nivel mundial, considerada una pandemia con alta tasa de mortalidad. A la fecha no existen estudios que describan la influencia de las variables asociadas a la enfermedad en el estado fronterizo de Tamaulipas, México. El objetivo del presente estudio fue evaluar y analizar las características, complicaciones, tasas de letalidad y factores de riesgo asociados a mortalidad en paciente positivos a COVID-19 en el estado de Tamaulipas, a un año de la emergencia local. Se utilizó la frecuencia de casos observados en relación a características, complicaciones y comorbilidades para estimar prevalencias y tasas de letalidad. Se ajustó un modelo de regresión logística multivariada para estimar los factores de riesgo significativos y se utilizaron curvas de supervivencia de Kaplan-Meier para describir las comorbilidades más importantes. Los análisis indicaron una mayor infección en pacientes en edad productiva, con una probabilidad significativa de muerte a partir de los 40 años, más evidente en pacientes masculinos. Los riesgos asociados a la hospitalización, como intubación endotraqueal y neumonía, son factores muy importantes. Las comorbilidades con alta prevalencia (diabetes, hipertensión y obesidad) y enfermedad renal crónica (ERC) están asociados significativamente (P < 0.01) a mayor mortalidad por COVID-19 en pacientes positivos. El presente estudio demostró algunos patrones generales de prevalencia y tasas de letalidad por COVID-19, por lo que se sugieren particularidades en los factores asociados a mortalidad en la población de Tamaulipas que requieren atención en sus grupos vulnerables, sobre todo en posibles casos de rebrotes de la enfermedad.

Abstract Coronavirus 19 (COVID-19) is a prevalent and globally disseminated viral disease that has become a pandemic associated with a high case fatality rate. To date, there are no published studies that describe the influence of the variables associated with the disease, specifically in the border state of Tamaulipas, Mexico. The objective of the present study was to assess the characteristics, complications, fatality rates and risk factors associated to mortality in patients positive to COVID-19 in Tamaulipas, one year after the local emergency. Descriptive frequency of characteristics, complications for prevalence and case fatality rates were used. A multivariate logistic regression model was adjusted to estimate the meaningful risk factors, and Kaplan-Meier survival curves were used to describe the most important comorbidities. The analysis indicated higher infection rates in patients of productive age, with a significant death probability in male patients from the age of 40. The risks associated with hospitalization, such as endotracheal intubation and the presence of pneumonia are important risk factors. Comorbidities with high prevalence; diabetes, hypertension, obesity, and chronic kidney disease (CKD) were significantly associated (P < 0.01) with higher COVID-19 mortality risk in the assessed population. The present study demonstrated some COVID-19 general patterns on frequency and mortality rates. It also suggested particularities in factors associated to mortality in the Tamaulipas population, which require proper attention in vulnerable groups, especially in future outbreaks of the disease.

Determinant of earnings response coefficient on the Indonesian and Singaporean stock exchanges during the COVID-19 pandemic

Earnings response coefficient (ERC) is one of the important things for companies and investors, as it reflects a company's good value. The COVID-19 pandemic, which is happening globally, has greatly affected capital market conditions and companies in general. It is necessary to examine what factors affect ERC significantly to provide an overview to the company while maintaining the good name of the company. This study aims to analyze the effect of firm growth, leverage, information asymmetry, and systematic risk on ERC with dividend payout ratios as moderating on the Indonesia Stock Exchange and Singapore Stock Exchange. The study uses a quantitative approach with secondary data in the form of companies' annual reports. Population was made up of food and beverage and tobacco manufacturing companies in 2018-2020. It consists of 38 JASICA index companies on IDX, and 33 SGX index companies on SGX. The results showed that, firstly, leverage and systematic risk had a significant negative effect on ERC. Second, firm growth and information asymmetry have no effect on ERC. Third, dividend payout ratio can weaken a positive influence of information asymmetry on ERC. Fourth, dividend payout ratio failed to moderate a positive effect of firm growth and a negative effect of leverage and systematic risk on ERC. All variables have no significant statistical difference between the two stock exchanges. These results indicate that a company must improve the performance and quality of information;pay attention to obligations, mitigate and manage risk to obtain optimal ERC. © Niswah Baroroh, Heri Yanto, Muhammad Khafid, Kuat Waluyo Jati, Dinda Ayu Setyowati, 2022.

Multidisciplinary nutritional consensus on assessment and nutritional dietary treatment in patients with chronic kidney disease and SARS-CoV-2 infection.

The presence of malnutrition in patients with Chronic Kidney Disease (CKD) is high, it can be made worse by SARS-CoV2 infection. The nutritional assessment should be adapted to minimize the infection, recommending monitoring: weight loss percentage, body mass index (BMI), loss of appetite, analytical parameters and functional capacity using the dynamometer. As well as the sarcopenia assessment using the SCARF scale, and the possibility of using the GLIM criteria in those patients who have been tested positive by MUST. It is important to adapt the nutritional recommendations in the caloric and protein intake, to the CKD stage and to the SARS-CoV2 infection stage. In patients with hypercatabolism, to prioritize preserving the nutritional status (35 kcal/kg weight/day, proteins up to 1.5 g/kg/day). The rest of the nutrients will be adapted to CKD stage and the analytical values. In the post-infection stage, a complete nutritional assessment is recommended, including sarcopenia. The energy and protein requirements in this phase will be adapted to the nutritional status, with special attention to the loss of muscle mass. Dietary recommendations need to be tailored to side effects of SARS-CoV-2 infection: anorexia, dysphagia, dysgeusia, and diarrhea. Anorexia and hypercatabolism makes it difficult to meet the requirements through diet, therefore the use of oral nutritional supplements is recommended as well as the enteral or parenteral nutrition in severe phases.

A blockchain-based infection tracing and notification system by non-fungible tokens.

SARS-CoV2 pandemic is heavily affecting our lives. Many actions have been undertaken to slow down its expansion and, among the others, contact tracing applications are the less invasive to monitor the spread of the virus. The idea behind contact tracing is to track contacts between people by the exchange of identifiers, not linked to individuals, exploiting the use of Bluetooth Low Energy (BLE) technology to estimate the duration and proximity of contacts. The data collected in this way is used for the sole purpose of notifying a potential contact with an infected person without revealing their identity and location. This paper presents a contact tracing protocol based on blockchain technology that exploits smart contracts for reporting contacts at risk of contagion. The novelty of the proposed solution is the use of Non Fungible Tokens (NFT) to guarantee user privacy through a decentralized approach, equipped with a reliable non-proprietary notification mechanism that allows public access to anonymous infections data.

Evidence for the role of Rab11-positive recycling endosomes as intermediates in coronavirus egress from epithelial cells.

After their assembly by budding into the lumen of the intermediate compartment (IC) at the endoplasmic reticulum (ER)-Golgi interface, coronaviruses (CoVs) are released from their host cells following a pathway that remains poorly understood. The traditional view that CoV exit occurs via the constitutive secretory route has recently been questioned by studies suggesting that this process involves unconventional secretion. Here, using the avian infectious bronchitis virus (IBV) as a well-established model virus, we have applied confocal microscopy to investigate the pathway of CoV egress from epithelial Vero cells. We report a novel effect of IBV infection on cellular endomembranes, namely, the compaction of the pericentrosomal endocytic recycling compartment (ERC) defined by the GTPase Rab11, which coincides with the previously described Golgi fragmentation, as well as virus release. Despite Golgi disassembly, the IC elements containing the major IBV membrane protein (M)-which mostly associates with newly formed virus particles-maintain their close spatial connection with the Rab11-positive endocytic recycling system. Moreover, partial colocalization of the M protein with Rab11 was observed, whereas M displayed negligible overlap with LAMP-1, indicating that IBV egress does not occur via late endosomes or lysosomes. Synchronization of virus release using temperature-shift protocols was accompanied by increased colocalization of M and Rab11 in vesicular and vacuolar structures in the pericentrosomal region and at the cell periphery, most likely representing IBV-containing transport carriers. In conclusion, these results add CoVs to the growing list of viruses exploiting the endocytic recycling apparatus defined by Rab11 for their assembly and/or release.

Distributed Ledger Framework for an Adaptive University Management System

The true power and the state of any technology are best known during difficult times. The yet-to-over COVID-19 lockdown has unleashed the power of online and remote modes of learning, evaluation, and working. The universities and educational institutions worldwide faced their big-time challenge in delivering, managing, evaluating their student’s learning progress. The need for an online-virtual-remote learning platform has become inevitable, which comes with a multitude of challenges, including usability, security, privacy, and real-time adoption. In this paper, we propose an Adaptive University Management System Framework (UMS) based on Distributed Ledger Technology (DLT) like Ethereum Blockchain where we record the schedules, the delivered classes, the materials and track the student’s learning progress with the use of ERC-721 standard to tokenize the submissions & evaluations. To provide efficient and effective utilization, the learning materials and submissions made onto the system are stored in Distributed File Storage system - InterPlanetary File System (IPFS) and hosted in InterPlanetary Name System (IPNS) with files securely split using a secret sharing algorithm. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Novel fusion sarcomas including targetable NTRK and ALK.

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.

Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic.

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, EASL and ESCMID published a position paper to provide guidance for physicians involved in the care of patients with chronic liver disease. While some healthcare systems are returning to a more normal routine, many countries and healthcare systems have been, or still are, overwhelmed by the pandemic, which is significantly impacting on the care of these patients. In addition, many studies have been published focusing on how COVID-19 may affect the liver and how pre-existing liver diseases might influence the clinical course of COVID-19. While many aspects remain poorly understood, it has become increasingly evident that pre-existing liver diseases and liver injury during the disease course must be kept in mind when caring for patients with COVID-19. This review should serve as an update on the previous position paper, summarising the evidence for liver disease involvement during COVID-19 and providing recommendations on how to return to routine care wherever possible.

Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper.

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous challenge to healthcare systems in affected communities. Older patients and those with pre-existing medical conditions have been identified as populations at risk of a severe disease course. It remains unclear at this point to what extent chronic liver diseases should be considered as risk factors, due to a shortage of appropriate studies. However, patients with advanced liver disease and those after liver transplantation represent vulnerable patient cohorts with an increased risk of infection and/or a severe course of COVID-19. In addition, the current pandemic requires unusual allocation of healthcare resources which may negatively impact the care of patients with chronic liver disease that continue to require medical attention. Thus, the challenge hepatologists are facing is to promote telemedicine in the outpatient setting, prioritise outpatient contacts, avoid nosocomial dissemination of the virus to patients and healthcare providers, and at the same time maintain standard care for patients who require immediate medical attention.