Surf4 collaborates with derlin-2 and derlin-1 to mediate cyclooxygenase-2 translocation to the cytosol for degradation.

Derlin family members participate in the retrotranslocation of endoplasmic reticulum (ER) lumen proteins to the cytosol for ER-associated degradation (ERAD); however, the proteins facilitating this retrotranslocation remain to be explored. Using CRISPR library screening, we have found that derlin-2 and surfeit locus protein 4 (Surf4) are candidates to facilitate degradation of cyclooxygenase-2 (COX-2, also known as PTGS2). Our results show that derlin-2 acts upstream of derlin-1 and that Surf4 acts downstream of derlin-2 and derlin-1 to facilitate COX-2 degradation. Knockdown of derlin-2 or Surf4 impedes the ubiquitylation of COX-2 and the interaction of COX-2 with caveolin-1 (Cav-1) and p97 (also known as VCP) in the cytosol. Additionally, COX-2 degradation is N-glycosylation dependent. Although derlin-2 facilitates degradation of N-glycosylated COX-2, the interaction between derlin-2 and COX-2 is independent of COX-2 N-glycosylation. Derlin-1, Surf4 and p97 preferentially interact with non-glycosylated COX-2, whereas Cav-1 preferentially interacts with N-glycosylated COX-2, regardless of the N-glycosylation pattern. Collectively, our results reveal that Surf4 collaborates with derlin-2 and derlin-1 to mediate COX-2 translocation from the ER lumen to the cytosol. The derlin-2-derlin-1-Surf4-Cav-1 machinery might represent a unique pathway to accelerate COX-2 degradation in ERAD.

Fatal Case of Naegleria fowleri Primary Amebic Meningoencephalitis from Indoor Surfing Center, Taiwan, 2023.

We investigated a fatal case of primary amoebic meningoencephalitis from an indoor surfing center in Taiwan. The case was detected through encephalitis syndromic surveillance. Of 56 environmental specimens, 1 was positive for Naegleria fowleri ameba. This report emphasizes the risk for N. fowleri infection from inadequately disinfected recreational waters, even indoors.

Speech- and language-linked FOXP2 mutation targets protein motors in striatal neurons.

Human speech and language are among the most complex motor and cognitive abilities. The discovery of a mutation in the transcription factor FOXP2 in KE family members with speech disturbances has been a landmark example of the genetic control of vocal communication in humans. Cellular mechanisms underlying this control have remained unclear. By leveraging FOXP2 mutation/deletion mouse models, we found that the KE family FOXP2R553H mutation directly disables intracellular dynein-dynactin 'protein motors' in the striatum by induction of a disruptive high level of dynactin1 that impairs TrkB endosome trafficking, microtubule dynamics, dendritic outgrowth and electrophysiological activity in striatal neurons alongside vocalization deficits. Dynactin1 knockdown in mice carrying FOXP2R553H mutations rescued these cellular abnormalities and improved vocalization. We suggest that FOXP2 controls vocal circuit formation by regulating protein motor homeostasis in striatal neurons, and that its disruption could contribute to the pathophysiology of FOXP2 mutation/deletion-associated speech disorders.

Evaluating Cryo-TEM Reconstruction Accuracy of Self-Assembled Polymer Nanostructures.

Cryogenic transmission electron microscopy (cryo-TEM) combined with single particle analysis (SPA) is an emerging imaging approach for soft materials. However, the accuracy of SPA-reconstructed nanostructures, particularly those formed by synthetic polymers, remains uncertain due to potential packing heterogeneity of the nanostructures. In this study, the combination of molecular dynamics (MD) simulations and image simulations is utilized to validate the accuracy of cryo-TEM 3D reconstructions of self-assembled polypeptoid fibril nanostructures. Using CryoSPARC software, image simulations, 2D classifications, ab initio reconstructions, and homogenous refinements are performed. By comparing the results with atomic models, the recovery of molecular details is assessed, heterogeneous structures are identified, and the influence of extraction location on the reconstructions is evaluated. These findings confirm the fidelity of single particle analysis in accurately resolving complex structural characteristics and heterogeneous structures, exhibiting its potential as a valuable tool for detailed structural analysis of synthetic polymers and soft materials.

Implementation of a novel computer assisted telephone follow-up model for older patients after emergency department discharge in an Asian population.

BACKGROUND: While the impact of telephone follow-up (TFU) for older emergency department (ED) patients is controversial, its effects on the Asian population remain uncertain. In this study, we evaluated the effectiveness of a novel computer assisted TFU model specifically for this demographic. METHODS: At a Taiwanese tertiary medical center, we developed a TFU protocol that included a referral and case management system within the ED hospital information system. We provided TFU to older discharged patients between April 1, 2021, and May 31, 2021. We compared this cohort with a non-TFU cohort of older ED patients and analyzed demographic characteristics and post-ED discharge outcomes. RESULTS: The TFU model was successfully implemented, with 395 patients receiving TFU and 191 without TFU. TFU patients (median age: 76 years, male proportion: 48.9%) differed from non-TFU patients (median age: 74 years, male proportion: 43.5%). Compared with the non-TFU cohort, the multivariate logistic regression analysis revealed that the TFU cohort had a lower total medical expenditure < 1 month (adjusted odds ratio [AOR]: 0.32; 95% CI: 0.21 - 0.47 for amounts exceeding 5,000 New Taiwan Dollars), and higher satisfaction (AOR: 2.80; 95% CI: 1.46 - 5.36 for scores > 3 on a five-point Likert Scale). However, the TFU cohort also had a higher risk of hospitalization < 1 month (AOR: 2.50; 95% CI: 1.31 - 4.77) compared to the non-TFU cohort. CONCLUSION: Computer-assisted TFU appears promising. Further research involving a larger number of patients and validation in other hospitals is necessary to bolster the evidence and extend the findings to a broader context.

Examining the Association between Medical Marijuana Legalization and Criminal Behaviors: Evidence from a U.S. Representative Sample.

Background: Medical marijuana legalization (MML) has been widely implemented in the past decade. However, the debates regarding the consequences of MML persist, especially criminal behaviors. Objectives: We examined the association between MML and criminal behaviors among adults in the United States. The criminal behaviors measured three past-year offenses: whether the adult (1) have sold illegal drugs, (2) have stolen anything worth > $50 USD, or (3) have attacked someone. Methods: Using the 2015-2020 National Survey of Drug Use and Health, we included 214,505 adults in our primary analysis for 2015-2019 and 27,170 adults in 2020 for supplemental analysis (age > = 18). Weighted multivariable logistic regression models were used to examine the association between MML and three criminal behaviors. Results: In our primary analysis, we observed no statistically significant association between MML and the three outcomes of criminal behavior. Nevertheless, our supplemental analysis of the 2020 data showed MML was associated with increasing odds of the three criminal behaviors (have sold illegal drugs: AOR [adjusted odds ratio] = 1.7; have stolen anything worth > $50 USD: AOR = 1.9; have attacked someone: AOR = 1.8; all p < 0.05). Conclusion: Surveys from 2015 to 2019 did not suggest MML as a risk factor for higher incidence of criminal behaviors. However, 2020 data showed statistically significant association between MML and selected criminal behaviors. Issues related to the COVID-19 pandemic, such as the U.S. economic downturn, could potentially explain this discrepancy. Further research efforts may be warranted.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

Modified screening and management strategies for chronic rhinosinusitis in hematologic patients receiving hematopoietic stem cell transplantation.

OBJECTIVES: Given the lack of consensus on the screening and treatment for chronic rhinosinusitis (CRS) in the patients undergoing hematopoietic stem cell transplantation (HSCT), we reviewed the risk factors for CRS to improve the efficiency of sinonasal screening and analyzed the effect of treating CRS in search of guidance for modifying current management strategies for rhinosinusitis in HSCT patients. METHODS: We conducted a nested case-control study in a retrospective cohort of hematologic patients receiving HSCT from April 2011 to April 2021 and collected data on demographics, smoking/atopic status, hematological diseases, and features of rhinosinusitis for analysis. The associated factors for control of rhinosinusitis and survival were analyzed. RESULTS: Fifty-eight CRS patients were identified, and another 116 age- and sex-matched controls were selected from HSCT patients without CRS. Allergy and smoking were risk factors for CRS in HSCT patients. The multivariable logistic analysis indicated that endoscopic sinus surgery (ESS) was an independent factor for better control of CRS. However, survival was not associated with rhinosinusitis-related factors, but only with hematologic-related factors, including allogenic HSCT, reduced-intensity conditioning, and remission. CONCLUSIONS: Sinonasal evaluation should be targeted to the high-risk group. ESS is effective in managing CRS, while control of CRS is not determinant of overall survival in patients receiving HSCT.

Genome-wide characterization of microsatellites in cobia Rachycentron canadum (Linnaeus, 1766): Survey and analysis of their abundance and diversity.

The cobia Rachycentron canadum, mainly distributed in the warm waters of tropical and subtropical regions around the world, remains a fish of considerable economic importance. Detailed diversity and the number of microsatellite sequences in the cobia genome are still unintelligible. The primary aim of this work was to identify and quantify the miscellaneous SSR sequences in the cobia genome. More than 280,000 sequences were sequenced and screened using next-generation sequencing technology and microsatellite identification. Perfect mononucleotide repeats, dinucleotide microsatellites, and trinucleotide microsatellites contain (A)10 /(T)10 , (AC)6 /(TG)6 , and (AAT)5-32 as the largest number of motifs in each type of microsatellite, respectively. The tetranucleotide and pentanucleotide microsatellites (TTM and PTM) consist of the largest number of motifs of both (ATCT)5-32 and (TCAT)5-31 in TTMs, and (CTCTC)5-9 in PTMs, whereas the hexanucleotide microsatellites are rarely observed in the cobia genome. All c. 38000 sequences of composite microsatellites are extremely diverse, including compound (11.71%), interrupted compound (71.77%), complex (0.45%), and interrupted complex (16.07%). In this study, we developed a convenient and useful recording system for writing down and categorizing diverse composite microsatellite types. This system will provide great support for exploring repeat origins, evolutionary mechanisms, and the application of polymorphic microsatellites.

Unlocking Catalytic Potential: Exploring the Impact of Thermal Treatment on Enhanced Electrocatalysis of Nanomaterials.

In the evolving field of electrocatalysis, thermal treatment of nano-electrocatalysts has become an essential strategy for performance enhancement. This review systematically investigates the impact of various thermal treatments on the catalytic potential of nano-electrocatalysts. The focus encompasses an in-depth analysis of the changes induced in structural, morphological, and compositional properties, as well as alterations in electro-active surface area, surface chemistry, and crystal defects. By providing a comprehensive comparison of commonly used thermal techniques, such as annealing, calcination, sintering, pyrolysis, hydrothermal, and solvothermal methods, this review serves as a scientific guide for selecting the right thermal technique and favorable temperature to tailor the nano-electrocatalysts for optimal electrocatalysis. The resultant modifications in catalytic activity are explored across key electrochemical reactions such as electrochemical (bio)sensing, catalytic degradation, oxygen reduction reaction, hydrogen evolution reaction, overall water splitting, fuel cells, and carbon dioxide reduction reaction. Through a detailed examination of the underlying mechanisms and synergistic effects, this review contributes to a fundamental understanding of the role of thermal treatments in enhancing electrocatalytic properties. The insights provided offer a roadmap for future research aimed at optimizing the electrocatalytic performance of nanomaterials, fostering the development of next-generation sensors and energy conversion technologies.

Deep Learning-Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma.

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P = 0.025), low skewness of nuclear irregularity (P = 0.020), and high mean of nuclear irregularity (P = 0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P = 0.0038) was an independent prognostic factor in addition to bMIPI risk group (P = 0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P = 0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)-ATCUN Complexes.

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.

Practice effect and test-retest reliability of the Wechsler Memory Scale-Fourth Edition in people with dementia.

BACKGROUND: The Wechsler Memory Scale-Fourth Edition (WMS-IV) has been widely used to assess memory function in people with dementia. The older adult battery of the WMS-IV includes four indices and seven subtests. The aims of this study were to examine the practice effect and test-retest reliability and calculate the reliable change index modified for practice (RCIp) for the indices and subtests of the older adult battery of the WMS-IV for people with dementia. METHODS: Fifty-six participants completed the WMS-IV twice, two weeks apart. The practice effect was investigated using effect size (Cohen's d) and bootstrapping mixed design analysis of variance while considering the severity of dementia. The test-retest reliability was estimated using intraclass correlation coefficient (ICC). RESULTS: The results showed non-significant practice effects with Cohen's d < 0.20 in different severities of dementia on two indices and five subtests. The ICC values of these indices and subtests were 0.82-0.85 and 0.57-1.00, respectively. The other two indices (i.e., auditory memory and immediate memory) and two subtests (i.e., logical memory delayed recall and visual reproduction immediate recall) demonstrated small to moderate practice effect (d = 0.46-0.74) for people with mild severity of dementia. CONCLUSION: On the whole, the WMS-IV has no to moderate practice effects and moderate to excellent test-retest reliability in people with dementia. The values of the RCIp with 95% confidence interval for the indices and subtests were provided in this study, which are useful to clinicians and researchers for interpreting the real score change in persons with dementia. The two indices (i.e., auditory memory and immediate memory) and two subtests (i.e., logical memory delayed recall and visual reproduction immediate recall) with noticeable practice effect should be used with caution when assessing memory function repeatedly in people with mild severity of dementia.

Cognitive appraisals and coping strategies of registered nurses in the emergency department combating COVID-19: A scoping review.

OBJECTIVE: Explore the relevant evidence about stress-related cognitive appraisal and coping strategies among registered nurses in the emergency department (EDRNs) coping with the COVID-19 pandemic. METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus electronic databases for related studies from inception through February 2, 2022. This review further conducted study selection based on the PRISMA flow diagram and applied Lazarus and Folkman's Psychological Stress and Coping Theory to systematically organize, summarize, and report the findings. FINDINGS: Sixteen studies were included for synthesis. Most of the studies showed that the majority of EDRNs were overwhelmed by the COVID-19 pandemic. Depression, triaging distress, physical exhaustion, and intention to leave ED nursing were cited as major threats to their wellness. Additionally, comprehensive training, a modified triage system, a safe workplace, psychological support, promotion of resilience, and accepting responsibility may help EDRNs cope with pandemic-related challenges effectively. CONCLUSION: The long-lasting pandemic has affected the physical and mental health of EDRNs because they have increased their effort to respond to the outbreak with dynamically adjusted strategies. Future research should address a modified triage system, prolonged psychological issues, emergency healthcare quality, and solutions facing EDRNs during the COVID-19 or related future pandemics. CLINICAL RELEVANCE: EDRNs have experienced physical and psychological challenges during the pandemic. The ED administrators need to take action to ensure EDRNs' safety in the workplace, an up-to-date triage system, and mental health of frontline nurses to provide high-quality emergency care for combating COVID-19.

The role of serum osmolality in Meniere's disease with acute sensorineural hearing loss.

OBJECTIVE: This study investigated the role of serum osmolality in Meniere's disease (MD) patients with acute sensorineural hearing loss (SNHL). DESIGN: Retrospective study. STUDY SAMPLES: Twenty definite MD patients with acute unilateral SNHL were treated with an osmotic diuretic (Isosorbide, 100 mL daily) and assigned to Group A. Another 20 age- and sex-matched definite MD patients with acute SNHL were not given Isosorbide and assigned to Group B. Both groups underwent audiometry and blood examination for serum osmolality before and after treatment. RESULTS: Group A revealed a significant increase in serum osmolality after treatment. The optimal cut-off values for increased serum osmolality in Group A were +1.5 mOSM/L for predicting hearing improvement at frequencies of 250-1000 Hz, and +2.5 mOSM/L at 2000-4000 Hz. Comparing increased levels of serum osmolality (> +2.0 vs. ≤ +2.0 mOSM/L), Isosorbide dosing at 3.0 L vs. 1.0 L, significantly differed in the odds ratio (OR). Isosorbide at a total dosage of 3.0 L thus improves the hearing threshold by >10 dB at frequencies of 250-2000 Hz. CONCLUSION: The Isosorbide at a total dosage of 3.0 L may increase serum osmolality by > +2.0 mOSM/L, and improve the hearing threshold for hydropic ears at least >10 dB at low- and mid-frequencies.

Taiwan's National Health Insurance at the Emergency Department following the COVID-19 outbreak.

Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.

Harnessing the power of collective intelligence in dentistry: a pilot study in Victoria, Australia.

BACKGROUND: In many dental settings, diagnosis and treatment planning is the responsibility of a single clinician, and this process is inevitably influenced by the clinician's own heuristics and biases. Our aim was to test whether collective intelligence increases the accuracy of individual diagnoses and treatment plans, and whether such systems have potential to improve patient outcomes in a dental setting. METHODS: This pilot project was carried out to assess the feasibility of the protocol and appropriateness of the study design. We used a questionnaire survey and pre-post study design in which dental practitioners were involved in the diagnosis and treatment planning of two simulated cases. Participants were provided the opportunity to amend their original diagnosis/treatment decisions after viewing a consensus report made to simulate a collaborative setting. RESULTS: Around half (55%, n = 17) of the respondents worked in group private practices, however most practitioners (74%, n = 23) did not collaborate when planning treatment. Overall, the average practitioners' self-confidence score in managing different dental disciplines was 7.22 (s.d. 2.20) on a 1-10 scale. Practitioners tended to change their mind after viewing the consensus response, particularly for the complex case compared to the simple case (61.5% vs 38.5%, respectively). Practitioners' confidence ratings were also significantly higher (p < 0.05) after viewing the consensus for complex case. CONCLUSION: Our pilot study shows that collective intelligence in the form of peers' opinion can lead to modifications in diagnosis and treatment planning by dentists. Our results lay the foundations for larger scale investigations on whether peer collaboration can improve diagnostic accuracy, treatment planning and, ultimately, oral health outcomes.

Participation in mahjong and the associated smoking and alcohol consumption behaviors among Chinese older adults.

This study examined the relationship of playing mahjong with smoking and alcohol consumption behaviors among Chinese older adults. We used a large and nationally representative dataset, the 8th wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Older adults who were 65 years old or above were included in the final analysis sample (n = 10,954). Multivariable logistic regressions were used to examine the associations of playing mahjong with current and former smoking/alcohol consumption status. Additionally, we used negative binomial and multiple linear regressions to investigate the number of cigarettes smoked per day and the amount of alcohol consumed per day. Compared with older adults who did not play mahjong, those who played mahjong at least once per month were more likely to report both current and prior smoking/alcohol consumption habits (all p < 0.05). The sub-analysis revealed that older adults who played mahjong at least once per week tended to smoke more cigarettes per day (all p < 0.05) than those who did not play mahjong at all. When public health practitioners advocate for the health benefits of playing mahjong, they should also consider its associations with smoking/alcohol consumption behaviors among Chinese older adults.

SNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network.

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

Underdiagnosis of iron deficiency anemia among patients with colorectal cancer: an examination of electronic medical records.

BACKGROUND: Timely diagnosis and management of iron deficiency anemia (IDA) in colorectal cancer (CRC) patients improves overall quality of life and survival. This study assessed the proportion of CRC patients who were formally diagnosed with IDA and factors that predict a formal diagnosis of IDA and receiving iron therapy. METHODS: We retrieved electronic medical records (EMRs) of CRC patients from a large comprehensive cancer center in the Northeastern part of the United States (n = 499). We abstracted sociodemographic characteristics, relevant laboratory results, IDA diagnosis, and iron supplementation from the EMRs. We assessed relationships between participant characteristics, a diagnosis of IDA and receiving iron therapy through adjusted logistic regressions. RESULTS: IDA was formally diagnosed in 26 (5.2%) individuals judged by EMR documentation. Only 153 (30.7%) participants had iron laboratory results available. Among the 153 patients with iron panel data available, 113 (73.9%) had iron deficiency. Seventy-six had absolute iron deficiency as shown by ferritin levels below 100 ng/mL and iron saturation less than 20% and 37 had functional iron deficiency as shown by ferritin levels between 100 and 500 ng/mL and iron saturation less than 20%. 12% of all patients had documentation of iron therapy receipt. A formal diagnosis of IDA was not associated with any of the covariates. CONCLUSIONS: Iron deficiency anemia is under-diagnosed among CRC patients and most likely under-documented in clinical notes. Rates of iron repletion are low, suggesting that many patients with IDA are untreated. Future research should explore provider-level and other strategies for improving assessment and diagnosis of IDA among CRC patients.