anterior mini‐thoracotomy in multivessel coronary revascularization by Cyn I read with interest the article, routine minimally invasive approach via left ak and colleagues1. The main problem of mini anterior thoracotomy coronary revascularization is the limited or even bad exposure to the right coronary and posterior obtuse marginal branches which may affect the quality of the distal anastomosis. This is the most important technical point of a successful revascularization.

Myeloid cell leukemia-1 (MCL1), an anti-apoptotic BCL-2 family protein plays a major role in the control of apoptosis as the regulator of mitochondrial permeability which is deregulated in various solid and hematological malignancies. Interaction of the executioner proteins Bak/Bax with anti-apoptotic MCL1 and its cellular composition determines the apoptotic or survival pathway. This study highlighted the deleterious MCL1-Bax stabilizing effect of the mutation V220F on MCL1 structure through computational protein-protein interaction predictions and molecular dynamics simulations. The single point mutation at V220F was selected as it is residing at the hydrophobic core region of BH3 conserved domain, the site of Bax binding. The molecular dynamics simulation studies showed increase in stability of the mutated MCL1 before and after Bax binding comparable with the native MCL1. The clusters from free energy landscape found out structural variation in folding pattern with additional helix near the BH3 domain in the mutated structure. This loop to helix structural change in the mutated complex favored stable interaction of the complex and also induced Bax conformational change. Moreover, molecular mechanics based binding free energy calculations confirmed increased affinity of Bax towards mutated MCL1. Residue-wise interaction network analysis showed the individual residues in Bax binding responsible for the change in stability and interaction due to the protein mutation. In conclusion, the overall findings from the study reveal that the presence of V220F mutation on MCL1 is responsible for the structural confirmational change leading to disruption of its biological functions which might be responsible for tumorigenesis. The mutation could possibly be used as future diagnostic markers in treating cancers.

Host cell proteins (HCPs) are a significant class of process-related impurities commonly associated with the manufacturing of biopharmaceuticals. However, due to the increased use of crude enzymes as biocatalysts for modern organic synthesis, HCPs can also be introduced as a new class of impurities in chemical drugs. In both cases, residual HCPs need to be adequately removed to ensure product purity, quality, and patient safety. Although a lot of attentions have been focused on defining a universally acceptable limit for such impurities, the risks associated with residual HCPs on product quality, safety, and efficacy often need to be determined on a case-by-case basis taken into consideration of residual HCP profile in the product, the dose, dosage form, and administration route etc. Here we describe the unique challenges for residual HCP control presented by the biocatalytic synthesis of a Merck investigational stimulator of interferon genes protein (STING) agonist, MK-1454, which is a cyclic dinucleotide synthesized using E. coli cell lysate overexpressing cyclic GMP-AMP synthase (cGAS) as a biocatalyst. In this study, a holistic characterization of residual protein impurities using a variety of analytical tools, together with in silico immunogenicity prediction of identified proteins, facilitated risk assessment and guided process development to achieve adequate removal of residual protein impurities in MK-1454 API.

Retinal arterial macroaneurysm shows rapid vision loss when rupture occurs; therefore, preventive photocoagulation should be considered, if necessary.

A 22-year male presented with complaints of dyspnea. Multimodality imaging revealed a polypoidal right atrial mass with sub-massive pulmonary embolism. The patient underwent urgent surgery. The pathological examination confirmed it as cardiac myxoma. Cardiac myxoma, a most common primary cardiac tumor, is commonly found in the left atrium. The right atrium is an uncommon site and the usual mode of presentation is the tumor or thrombus embolisation to the pulmonary circulation.

Patients with relapsed follicular lymphoma who do not respond to CAR-T have a poor outcome. We present a case of refractory follicular lymphoma who relapsed after two CAR-T infusions and achieved a complete remission after treatment with obinutuzumab and lenalidomide. This represents a promising treatment option in the post-CAR-T setting.

A 73-year-old man underwent a stage Ⅱ sigmoid colon cancer resection. Careful monitoring was undertaken, and no evidence of metastasis or anastomotic recurrence was noted until 51 months later. Anal examination revealed a pink, firm perianal tumor histologically identified as a metastasis of the colon adenocarcinoma.

Error-in-variables model (EVM) methods require information about input and output measurement variances when estimating model parameters. In EVM, using replicate experiments for estimating output measurement variances is complicated, because true values of inputs may be different when multiple attempts are made to repeat an experiment. To address this issue, we categorize attempted replicate experiments as: i) true replicates (TRs) when uncertain inputs are the same in replicated runs and ii) pseudo-replicates (PRs) when measured inputs are the same, but unknown true values of inputs are different. We propose methodologies to obtain output measurement variance estimates and associated parameter estimates for both situations. We also propose bootstrap methods for obtaining joint-confidence information for the resulting parameter estimates. A copolymerization case study is used to illustrate the proposed techniques. We show that different assumptions noticeably affect the uncertainties in the resulting reactivity-ratio estimates.

Primary invasive breast carcinoma with neuroendocrine differentiation is an uncommon presentation. We hereby report a case diagnosed as invasive ductal carcinoma with neuroendocrine differentiation in a 52-year-old female who presented with a painless right breast lump.

A document by Hanshe Lim. Click on the document to view its contents.

A maturing body of evidence suggests that anthropogenic impacts on river-wetland corridors may be greater and more widespread than previously recognized. We applied the Geomorphic Grade Line (GGL) method to define pre-Anthropocene valley surfaces within segments of the 42-kilometer Entiat River Valley (ERV) of the North Cascade Mountains, USA. We developed GGL-relative elevation models (GGL-REMs) by subtracting, from high-resolution digital elevation data, a detrending surface based on relic fluvial features of the valley floor. We validated the GGL-REMs using surficial geologic maps, C 14-dated soil profiles, and the identifiable remnants of historic dams. We interpreted these data in the context of settlement land use practices including channelization, large wood removal, and beaver ( Castor canadensis) trapping. Our analysis indicates that since the early 20 th century, the river has incised more than two meters in many areas. This triggered a rapid state and process change, wherein unconfined and partially-confined valleys transitioned from net deposition to erosion and transport environments. The distribution of river types shifted from ecologically rich river-wetland corridors towards simpler, single-threaded channels common in confined valleys. The effects of this state change on salmon productivity were profound. Results from the Entiat and other locales indicate that GGL-REMs can be used to help define the fluvial process-form domains, including the vertical dimension needed to guide valley floor restoration. These tools can be used to envisage pre-degradation riverscapes, especially when used in concert with other datasets. Once the pre-Anthropogenic conditions of rivers like Entiatqua have been recognized, the case for restoring lost river-wetland corridors to unlock their ecological potential becomes compelling.

Anthropogenic activities are leading to changes in the environment at global scales, and understanding these changes requires rapid, high-throughput methods of assessment. Pollen DNA metabarcoding and related methods provide advantages in throughput and efficiency over traditional methods, such as microscopic identification of pollen and visual observation of plant-pollinator interactions. Pollen DNA metabarcoding is currently being applied to assessments of plant-pollinator interactions and their responses to land-use change such as increased agricultural intensity and urbanisation, surveillance of ecosystem change, and monitoring of spatiotemporal distribution of allergenic pollen. In combination with historical specimens, pollen DNA metabarcoding can compare contemporary and past ecosystems. Current technical challenges with pollen DNA metabarcoding include the need to understand the relationship between sequence read and species abundance, develop methods for determining confidence limits for detection and taxonomic classification, increase method standardisation, and improve of gaps in reference databases. Future research expanding the method to intraspecific identification, analysis of DNA in ancient pollen samples, and increased use of museum and herbarium specimens could open further avenues for research. Ongoing developments in sequencing technologies can accelerate progress towards these goals. Global ecological change is happening rapidly, and we anticipate that high-throughput methods such as pollen DNA metabarcoding are critical for assessing these changes and providing timely management recommendations to preserve biodiversity and the evolutionary and ecological processes that support it.

Dissimilatory sulfite reductase is an ancient enzyme that has linked the global sulfur and carbon biogeochemical cycles since at least 3.47 Gya. While much has been learned about the phylogenetic distribution and diversity of DsrAB across environmental gradients, far less is known about the structural changes that occurred to maintain DsrAB function as the enzyme accompanied diversification of sulfate/sulfite reducing organisms (SRO) into new environments. Analyses of available crystal structures of DsrAB from Archaeoglobus fulgidus and Desulfovibrio vulgaris, representing early and late evolving lineages, respectively, show that certain features of DsrAB are structurally conserved, including active siro-heme binding motifs. Whether such structural features are conserved among DsrAB recovered from varied environments, including hot spring environments that host representatives of the earliest evolving SRO lineage (e.g., MV2-Eury), is not known. To begin to overcome these gaps in our understanding of the evolution of DsrAB, structural models from MV2.Eury were generated and evolutionary sequence co-variance analyses were conducted on a curated DsrAB database. Phylogenetically diverse DsrAB harbor many conserved functional residues including those that ligate active siro-heme(s). However, evolutionary co-variance analysis of monomeric DsrAB subunits revealed several False Positive Evolutionary Couplings (FPEC) that correspond to residues that have co-evolved despite being too spatially distant in the monomeric structure to allow for direct contact. One set of FPECs corresponds to residues that form a structural path between the two active siro-heme moieties across the interface between heterodimers, suggesting the potential for allostery or electron transfer within the enzyme complex. Other FPECs correspond to structural loops and gaps that may have been selected to stabilize enzyme function in different environments. These structural bioinformatics results suggest that DsrAB has maintained allosteric communication pathways between subunits as SRO diversified into new environments. The observations outlined here provide a framework for future biochemical and structural analyses of DsrAB to examine potential allosteric control of this enzyme.

Both in medicine and in psychiatry, it’s essential to thoroughly identify the cases in which it is necessary to intervene therapeutically, and justify a sick leave or make forensic interpretations, among others. Therefore, it is important to find a general concept and definition for medical and psychiatric disorders. Boorse, develops one of the most widespread models of medical disorder that aspired to be value-free and that was based in medical dysfunction. But values appear implicitly or explicitly with a deeper analysis of this concept. On the other hand, there is the overtly value laden (harm) component that has been used in the definition of disorder, defended as essential by several authors over the time, once symptoms and their consequences (disability, distress) have been considered as a priority in medicine. In this article, we intend to review, through a conceptual analysis, the proximity between the concepts of mental and physical disorders regarding the presence of values, and to propose a way to deal with the different kinds of values that might be present. It is concluded that values are present in the main concepts that have been used to define medical or psychiatric disorder. What is essential is to understand what is descriptive and what is value and to try to avoid moral values.

1. Prairie dogs (Cynomys sp.) are considered keystone species and ecosystem engineers for their grazing and burrowing activities (summarized here as disturbances). As climate changes and its variability increases, the mechanisms underlying organisms’ interactions with their habitat will likely shift. Understanding the mediating role of prairie dog disturbance on vegetation structure, and its interaction with environmental conditions through time, will increase knowledge on the risks and vulnerability of grasslands. 2. Here, we compared how plant taxonomic and functional diversity metrics, along with community-weighted trait means (CWM), respond to prairie dog disturbance across grassland types and seasons in a conservation priority, semiarid grassland of Northeast Mexico. 3. Our findings suggest that functional metrics and CWM analyses responded to interactions between prairie dog disturbance, grassland type and season, whilst species diversity and cover measures were less sensitive to the role of prairie dog disturbance. Contrary to previous studies, we found weak evidence that prairie dog disturbance has a negative effect on vegetation structure, except for minimal effects on C4 and graminoid cover, which depend mainly on season. Grassland type and season explained most of the effects on plant functional and taxonomic diversity as well as CWM traits. Furthermore, we found that leaf area as well as forb and annual cover increased during the wet season, independent of prairie dog disturbance. 4. Our results provide evidence that prairie dog disturbance is less important than grassland type and that environmental effects have a stronger role than grazing and animal disturbances on vegetation. We argue that a focus on disturbance and grazing effects is misleading, and instead attention is needed on the relationships between vegetation and environmental conditions which will be critical to understand semi-arid grassland dynamics in the region. In addition, explicit management strategies to mitigate climate change would need to consider these relationships

Coronavirus disease 2019 (COVID-19) vaccination is reportedly safe and effective. The histologic features of post-COVID-19 vaccination myocarditis are unknown. We present a 77-year-old Japanese woman who was diagnosed with eosinophilic myocarditis using endomyocardial biopsy, 7 days after receiving the second dose of BNT162b2 COVID-19 vaccine. Methylprednisolone pulse therapy was effective.

Summary: The unusual genetic diversity of the Omicron strain has led to speculation about its origin. The mathematical modeling platform developed for the Stockholm Paradigm (SP) indicates strongly that it has retro-colonized humans from an unidentified animal reservoir originally infected by humans. The relationship between Omicron and all other SARS-CoV-2 variants indicates oscillations among hosts, a core part of the SP. Such oscillations result from the emergence of novel variants following colonization of new hosts, replenishing and expanding the risk space for disease emergence. The SP predicts that pathogens colonize new hosts using pre-existing capacities. Those events are thus predictable to a certain extent. Novel variants emerge after a colonization and are not predictable. This makes it imperative to take proactive measures for anticipating emerging infectious diseases (EID) and mitigating their impact. The SP suggests a policy protocol to accomplish this goal. This is the DAMA Protocol: comprising DOCUMENT to detect pathogens before they emerge in new places or colonize new hosts; ASSESS to determine risk; MONITOR to detect changes in pathogen populations that increase the risk of outbreaks; and ACT to prevent outbreaks when possible and minimize their impact when they occur.

The ongoing COVID-19 pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. Four cross-sectional surveys were electronically distributed among pediatric onco-hematologist in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. 453 pediatric onco-hematologists from 20 countries responded the first survey with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active on-going patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (OR:1.84, 95%C:1.19;2.8), surgeries (OR:3, 95%CI:1.9;4.6) and radiotherapy (OR:6, 95%CI:3.5;10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR:3, 95%CI:1.4;6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR:3.48, 95%CI:1.6;7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.