Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactivation of herpesviruses during COVID‐19: A systematic review and meta‐analysis

To provide a comprehensive systematic review and meta‐analysis regarding the cumulative incidence (incidence proportion) of human herpesvirus (HHV) reactivation among patients with coronavirus disease 2019 (COVID‐19), we searched PubMed/MEDLINE, Web of Science, and EMBASE up to 25 September 2022, with no language restrictions. All interventional and observational studies enrolling patients with confirmed COVID‐19 and providing data regarding HHV reactivation were included. The random‐effects model was used in the meta‐analyses. We included information from 32 studies. HHV reactivation was considered a positive polymerase chain reaction result taken at the time of COVID‐19 infection. Most of the included patients were severe COVID‐19 cases. The pooled cumulative incidence estimate was 38% (95% Confidence Intervals [CI], 28%–50%, I2 = 86%) for herpes simplex virus (HSV), 19% (95% CI, 13%–28%, I2 = 87%) for cytomegalovirus (CMV), 45% (95% CI, 28%–63%, I2 = 96%) for Epstein‐Barr virus (EBV), 18% (95% CI, 8%–35%) for human herpesvirus 6 (HHV‐6), 44% (95% CI, 32%–56%) for human herpesvirus 7 (HHV‐7), and 19% (95% CI, 14%–26%) for human herpesvirus 8 (HHV‐8). There was no evidence of funnel plot asymmetry based on visual inspection and Egger's regression test for the results of HSV (p = 0.84), CMV (p = 0.82), and EBV (p = 0.27) reactivation. In conclusion, the identification of HHV reactivation in severe COVID‐19 patients is helpful in the management of patients as well as the prevention of complications. Further research is required to elucidate the interaction between HHVs and COVID‐19. Systematic review registration: PROSPERO CRD42022321973.
Regressive changes in sizes of somatosensory cuneate nucleus after sensory loss in primates

Significance Sensory loss from the hand and arm has consequences throughout the somatosensory-motor system. In the cuneate nucleus of the lower brainstem, an initial station of processing, a histological consequence is a reduction in the area size, which depends on the extent of the sensory loss and recovery time. The loss appears to result from decreases in neuron size and the surrounding neuropil, with little or no neuron loss. Thus, even years after an injury, the potential exists to restore the lost sensation from the hand and arm by reactivating cuneate nucleus neurons. The results indicate that the relative size of the cuneate nucleus can serve as a measure of sensory loss (and potential for recovery) across different primates.
Risk and Protective Factors for Cancer Mortality among United States Service Members and Veterans (2001–2018)

Abstract Background: Prior research linking military factors with cancer-specific mortality has shown inconsistent findings, with few studies examining these associations among U.S. service members and veterans who served in Operation Iraqi Freedom/Operation Enduring Freedom conflicts. Methods: Cancer mortality between 2001 and 2018 was ascertained from the Department of Defense Medical Mortality Registry and National Death Index for 194,689 Millennium Cohort Study participants. Cause-specific Cox proportional hazard models were used to examine links between military characteristics and cancer mortality [overall, early (<45 years), and lung]. Results: Compared with individuals who deployed with no combat experiences, non-deployers had a greater risk of overall [HR = 1.34; 95% confidence interval (CI) = 1.01–1.77] and early cancer mortality (HR = 1.80; 95% CI = 1.06–3.04). Enlisted individuals had a greater risk of lung cancer mortality compared with officers (HR = 2.65; 95% CI = 1.27–5.53). No associations by service component, branch, or military occupation and cancer mortality were observed. Higher education was associated with reduced overall, early and lung cancer mortality risk and smoking and life stressors were associated with elevated overall and lung cancer mortality risk. Conclusions: These findings are consistent with the healthy deployer effect in which military personnel who were deployed tend to be healthier than those who did not deploy. Further, these findings highlight the importance of considering socioeconomic factors, such as military rank, that may have long-term implications for health. Impact: These findings highlight military occupational factors that may predict long-term health outcomes. Additional work is necessary to investigate more nuanced environmental and occupational military exposures and cancer mortality.
Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the REVEAL‐HBV and REVEAL‐HCV cohort studies

Gut barrier dysfunction can result in the liver being exposed to an elevated level of gut‐derived bacterial products via portal circulation. Growing evidence suggests that systemic exposure to these bacterial products promotes liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, prospective studies have not examined the association between biomarkers of gut barrier dysfunction and HCC risk in a population of hepatitis B or C viral (HBV/HCV) carriers. We investigated whether prediagnostic, circulating biomarkers of gut barrier dysfunction were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)‐HBV and REVEAL‐HCV cohorts from Taiwan. REVEAL‐HBV included 185 cases and 161 matched controls, and REVEAL‐HCV 96 cases and 96 matched controls. The biomarkers quantitated were immunoglobulin A (IgA), IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and LPS‐binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable‐adjusted logistic regression. A doubling of the circulating levels of antiflagellin IgA or LBP was associated with a 76% to 93% increased risk of HBV‐related HCC (OR per one unit change in log2 antiflagellin IgA = 1.76, 95% CI: 1.06‐2.93; OR for LBP = 1.93, 95% CI: 1.10‐3.38). None of the other markers were associated with an increased risk of HBV‐related or HCV‐related HCC. Results were similar when cases diagnosed in the first 5 years of follow‐up were excluded. Our findings contribute to understanding the interplay of gut barrier dysfunction and primary liver cancer etiology.
A note on the degeneration of systems under pencil equivalence

The authors continue their study of orbit closure problems for generalized state space systems initiated previously (see Proc. 29th IEEE Conf. on Dec. and Cont., p.55-60, 1990). A theorem concerning the degeneration of these systems under pencil equivalence is reported, and some system-theoretic consequences are discussed. <<ETX>>
The role of immune activation and antigen persistence in acute and long COVID

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%–20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4+ and CD8+ T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.
Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study

Background: Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC). Aims: The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound. Methods: We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1 cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively. Results: Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7 cm (interquartile range: 0.5–0.8 cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3–6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2–47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10 ng/mL (HR: 4.01, 95% CI, 1.85–8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95–12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27–5.08). Conclusions: Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3–6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.
Effect of feedback on the capacity of discrete additive channels with memory

We consider discrete channels with arbitrary additive noise. Note that such channels need not be memoryless; in general, they have memory. We show that feedback does not increase the capacity of such channels. The same result is also shown for a larger class of channels to which additive channels belong, the class of discrete symmetric channels with memory. These channels have the property that their infinite-information rate is maximized for equally likely iid input processes. Finally, we impose cost constraints on the input of the additive channels, rendering them non-symmetric. In this case, we show that feedback can increase their capacity-cost function. <<ETX>>
Morphology-guided transcriptomic analysis of human pancreatic cancer organoids reveals microenvironmental signals that enhance invasion.

Pancreatic ductal adenocarcinoma (PDAC) frequently presents with metastasis, but the molecular programs in human PDAC cells that drive invasion are not well understood. Using an experimental pipeline enabling PDAC organoid isolation and collection based on invasive phenotype, we assessed the transcriptomic programs associated with invasion in our organoid model. We identified differentially expressed genes in invasive organoids compared to matched non-invasive organoids from the same patients, and we confirmed that the encoded proteins were enhanced in organoid invasive protrusions. We identified three distinct transcriptomic groups in invasive organoids, two of which correlated directly with the morphological invasion patterns and were characterized by distinct upregulated pathways. Leveraging publicly available single-cell RNA-sequencing data, we mapped our transcriptomic groups onto human PDAC tissue samples, highlighting differences in the tumor microenvironment between transcriptomic groups and suggesting that non-neoplastic cells in the tumor microenvironment can modulate tumor cell invasion. To further address this possibility, we performed computational ligand-receptor analysis and validated the impact of multiple ligands (TGFB1, IL6, CXCL12, MMP9) on invasion and gene expression in an independent cohort of fresh human PDAC organoids. Our results identify unique molecular programs driving morphologically defined invasion patterns and highlight the tumor microenvironment as a potential modulator of these programs.
Tissue iron distribution in patients with anemia of inflammation: Results of a pilot study

Anemia of inflammation (AI) is frequently present in subjects with inflammatory disorders, primarily caused by inflammation‐driven iron retention in macrophages. So far, only limited data on qualitative and quantitative estimates of tissue iron retention in AI patients exist. We performed a prospective cohort study analyzing splenic, hepatic, pancreatic, and cardiac iron content with MRI‐based R2*‐relaxometry in AI patients, including subjects with concomitant true iron deficiency (AI+IDA) hospitalized between 05/2020–01/2022. Control groups were individuals without inflammation. Spleen R2* values in AI patients with ferritin ≤200 μg/L (AI+IDA) were comparable with those found in controls. In AI patients with ferritin >200 μg/L, spleen (47.6 s−1 vs. 19.3 s−1, p < .001) and pancreatic R2* values (32.5 s−1 vs. 24.9 s−1, p = .011) were significantly higher compared with controls, while liver and heart R2*‐values did not differ. Higher spleen R2* values were associated with higher ferritin, hepcidin, CRP, and IL‐6 concentrations. Spleen R2* values normalized in AI patients after recovery (23.6 s−1 vs. 47.6 s−1, p = .008), while no changes were found in patients with baseline AI+IDA. This is the first study investigating tissue iron distribution in patients with inflammatory anemia and AI with concomitant true iron deficiency. The results support the findings in animal models demonstrating iron retention in macrophages, which are primarily accumulating in the spleen under inflammatory conditions. MRI‐related iron measurement may help to better characterize actual iron needs and to define better biomarker thresholds in the diagnosis of true ID in patients with AI. It may qualify as a useful diagnostic method to estimate the need for iron supplementation and to guide therapy.
Strain-dependent assessment of dough’s polymer structure and functionality during the baking process

During the baking process, the functionality of the heterogeneous dough matrix changes as the composing polymers experience conformational transition processes. The thermally induced structural changes affect the involvement and functionality of the polymers in the dough matrix. With the main hypothesis being that different types and magnitudes of strain exerted during the measurement would provide information on different structural levels and interactions, SAOS rheology in multiwave mode and large deformation extensional rheometry were applied to two microstructurally different systems. The functionality of the two systems, a highly connected standard wheat dough (φ ≈ 1.1) and an aerated, yeasted wheat dough (φ ≈ 2.3), depicting limited connectivity and strength of interactions, was accessed under different deformations and types of strains. Applying SAOS rheology, starch functionality prevailed on the behavior of the dough matrix. In contrast, gluten functionality prevailed the large deformation behavior. Using an inline fermentation and baking LSF technique, the heat-induced gluten polymerization was shown to increase strain hardening behavior above 70°C. In the aerated system, the strain hardening effect became already evident under small deformation testing, as the expansion of gas cells caused a pre-expansion of the gluten strands. The expanded dough matrix of yeasted dough was further shown to be substantially subjected to degradation once the network reached beyond its maximal gas holding capacity. Using this approach, the combined impact of yeast fermentation and thermal treatment on the strain hardening behavior of wheat dough was revealed for the first time by LSF. Furthermore, the rheological properties were successfully linked to oven rise behavior: a decreasing connectivity combined with the initiation of strain hardening by fast extension processes occurring in the yeasted dough matrix during the final baking phase was linked to limited oven rise functionality prematurely around 60°C.
Two-Year Outcomes of Cochlear Implant Use for Children With Unilateral Hearing Loss: Benefits and Comparison to Children With Normal Hearing

Objectives: Children with severe-to-profound unilateral hearing loss, including cases of single-sided deafness (SSD), lack access to binaural cues that support spatial hearing, such as recognizing speech in complex multisource environments and sound source localization. Listening in a monaural condition negatively impacts communication, learning, and quality of life for children with SSD. Cochlear implant (CI) use may restore binaural hearing abilities and improve outcomes as compared to alternative treatments or no treatment. This study investigated performance over 24 months of CI use in young children with SSD as compared to the better hearing ear alone and to children with bilateral normal hearing (NH). Design: Eighteen children with SSD who received a CI between the ages of 3.5 and 6.5 years as part of a prospective clinical trial completed assessments of word recognition in quiet, masked sentence recognition, and sound source localization at regular intervals out to 24-month postactivation. Eighteen peers with bilateral NH, matched by age at the group level, completed the same test battery. Performance at 24-month postactivation for the SSD group was compared to the performance of the NH group. Results: Children with SSD have significantly poorer speech recognition in quiet, masked sentence recognition, and localization both with and without the use of the CI than their peers with NH. The SSD group experienced significant benefits with the CI+NH versus the NH ear alone on measures of isolated word recognition, masked sentence recognition, and localization. These benefits were realized within the first 3 months of use and were maintained through the 24-month postactivation interval. Conclusions: Young children with SSD who use a CI experience significant isolated word recognition and bilateral spatial hearing benefits, although their performance remains poorer than their peers with NH.
Effects of early-life environment and adulthood SES on cognitive change in a multiethnic cohort

Abstract Objectives: Early-life socioeconomic status (SES) and adversity are associated with late-life cognition and risk of dementia. We examined the association between early-life SES and adversity and late-life cross-sectional cognitive outcomes as well as global cognitive decline, hypothesizing that adulthood SES would mediate these associations. Methods: Our sample (N = 837) was a racially and ethnically diverse cohort of non-Hispanic/Latino White (48%), Black (27%), and Hispanic/Latino (19%) participants from Northern California. Participant addresses were geocoded to the level of the census tract, and US Census Tract 2010 variables (e.g., percent with high school diploma) were extracted and combined to create a neighborhood SES composite. We used multilevel latent variable models to estimate early-life (e.g., parental education, whether participant ever went hungry) and adult (participant’s education, main occupation) SES factors and their associations with cross-sectional and longitudinal cognitive outcomes of episodic memory, semantic memory, executive function, and spatial ability. Results: Child and adult factors were strongly related to domain-specific cognitive intercepts (0.20–0.48 SD per SD of SES factor); in contrast, SES factors were not related to global cognitive change (0.001–0.01 SD per year per SD of SES factor). Adulthood SES mediated a large percentage (68–75%) of the total early-life effect on cognition. Conclusions: Early-life sociocontextual factors are more strongly associated with cross-sectional late-life cognitive performance compared to cognitive change; this effect is largely mediated through associations with adulthood SES.
Association of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease and retinopathy in type 2 diabetes

Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D).
Dissolved gases in the deep North Atlantic track ocean ventilation processes

Significance The physicochemical transfer of gases between the atmosphere and the vast ocean interior occurs at a small number of high-latitude locations during winter months, often under extreme weather. As a result, few direct observations exist. Dissolved noble gases and their isotopes, which are chemically and biologically unreactive, are useful tools to quantify air-sea gas exchange. Here, we present high-precision dissolved noble gas data from the deep North Atlantic to evaluate gas exchange using an ocean circulation model. Our findings suggest a large role for bubble mediated-gas exchange, and our model allows us to isolate biological from physical sources of N2 in the deep ocean, with relevance to the marine nitrogen cycle and its role in ocean carbon storage.
Reduced graphene oxide/ionic liquid composites with tunable interlayer spacing for improved charge/discharge kinetics in supercapacitors

The large specific surface area and high conductivity of reduced graphene oxide (RGO) make it a promising material for supercapacitors. However, aggregation of graphene sheets into graphitic domains upon drying hampers supercapacitor performance by drastically impeding ion transport inside electrodes. Here, we present a facile approach to optimize charge storage performance in RGO-based supercapacitors by systematically tuning their micropore structure. To this end, we combine RGOs with room temperature ionic liquids during electrode processing to impede stacking of sheets into graphitic structures with small interlayer distance. In this process, RGO sheets function as the active electrode material while ionic liquid serves both as a charge carrier and a spacer to control interlayer spacing inside electrodes and form ion transport channels. We show that composite RGO/ionic liquid electrodes with larger interlayer spacing and more ordered structure exhibit improved capacitance and charging kinetics.
Discordant growth of nasal cartilage and bone contributes to phenotypic variability of the skull in a mouse model

We previously determined a nonlinear relationship between connexin 43 (Cx43) function and craniofacial phenotypic variation in the mutant mouse model G60S/+, and that this variation was driven by nasal bone deviation. While nonlinearities in the genotype‐phenotype map appear to be common, few studies have looked at the developmental processes that underlie this nonlinearity. Here, we investigated the potential tissue‐level developmental determinants of the variation in nasal bone phenotype in G60S/+ mice through postnatal development.