Search

Low iron (Fe) bioavailability can limit the biosynthesis of Fe-containing proteins, which are especially abundant in photosynthetic organisms, thus negatively affecting global primary productivity. Understanding cellular coping mechanisms under Fe limitation is therefore of great interest. We surveyed the temporal responses of Chlamydomonas (Chlamydomonas reinhardtii) cells transitioning from an Fe-rich to an Fe-free medium to document their short and long-term adjustments. While slower growth, chlorosis and lower photosynthetic parameters are evident only after one or more days in Fe-free medium, the abundance of some transcripts, such as those for genes encoding transporters and enzymes involved in Fe assimilation, change within minutes, before changes in intracellular Fe content are noticeable, suggestive of a sensitive mechanism for sensing Fe. Promoter reporter constructs indicate a transcriptional component to this immediate primary response. With acetate provided as a source of reduced carbon, transcripts encoding respiratory components are maintained relative to transcripts encoding components of photosynthesis and tetrapyrrole biosynthesis, indicating metabolic prioritization of respiration over photosynthesis. In contrast to the loss of chlorophyll, carotenoid content is maintained under Fe limitation despite a decrease in the transcripts for carotenoid biosynthesis genes, indicating carotenoid stability. These changes occur more slowly, only after the intracellular Fe quota responds, indicating a phased response in Chlamydomonas, involving both primary and secondary responses during acclimation to poor Fe nutrition.

A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle (http://data.myoanalytics.com) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape. Synopsis: A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in healthy untrained human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. Global protein-coding gene expression changes peak at 8 h after an acute hypertrophic stimulus in human skeletal muscle, and early DNA methylation responses predict later gene expression changes. MYC is a key transcription factor regulating gene expression after resistance exercise, specifically during late recovery (8–24 h). Genetically controlled pulses of Myc in skeletal muscle of mice are sufficient for hypertrophy. A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. [ABSTRACT FROM AUTHOR]

In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P <.001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Previous studies have identified structurally diverse N-acyl amino acid methyl esters (NAMEs) in culture extracts of Roseovarius tolerans EL-164 (Roseobacteraceae). NAMEs are structural analogues of the common signaling compounds N-acyl homoserine lactones (AHLs), but do not participate in AHL-mediated signaling. NAMEs show minor antialgal and antimicrobial activity, but whether this activity serves as the primary ecological role remains unclear. Results: To enable dose-dependent bioactivity-testing, we have established a chromatographic method for quantification of NAMEs in bacterial culture extracts. The concentrations determined for the two major NAMEs produced by EL-164, C16:1-NAME and C17:1-NAME, ranged between 0.685 and 5.731 mg L− 1 (2.0-16.9 µM) and 5.3–86.4 µg L− 1 (15.0-244.3 nM), respectively. Co-quantification of the C14:1-AHL showed concentrations ranging between 17.5 and 58.7 mg L− 1 (56.6-189.7 µM). We observed distinct production patterns for NAMEs and AHLs, with a continuous NAME production during the entire incubation period. We conducted a spike-in experiment, using the determined metabolite concentrations. By comparing the transcriptomes of pre- and post-metabolite-spikes, we identified three clusters of differentially expressed genes with distinct temporal expression patterns. Expression levels of stress response genes differed between NAME- and AHL-spiked EL-164 cultures in the stationary phase. Conclusions: Our findings support previous studies suggesting an ecological role for C16:1-NAME as antibiotic, by proving that NAME concentrations in batch cultures were higher than the minimal inhibitory concentrations against Maribacter sp. 62 − 1 (Flavobacteriia) and Skeletonema costatum CCMP 1332 (Coscinodiscophyceae) reported in the literature. Our study further exemplified the broad application range of dose-dependent testing and highlighted the different biological activities of NAMEs and AHLs. [ABSTRACT FROM AUTHOR]

Cisplatin is one of the most commonly used chemotherapy drugs for treating solid tumors. As a genotoxic agent, cisplatin binds to DNA and forms platinum-DNA adducts that cause DNA damage and activate a series of signaling pathways mediated by various DNA-binding proteins (DBPs), ultimately leading to cell death. Therefore, DBPs play crucial roles in the cellular response to cisplatin and in determining cell fate. However, systematic studies of DBPs responding to cisplatin damage and their temporal dynamics are still lacking. To address this, we developed a novel and user-friendly stand-alone software, DEWNA, designed for dynamic entropy weight network analysis to reveal the dynamic changes of DBPs and their functions. DEWNA utilizes the entropy weight method, multiscale embedded gene co-expression network analysis and generalized reporter score-based analysis to process time-course proteome expression data, helping scientists identify protein hubs and pathway entropy profiles during disease progression. We applied DEWNA to a dataset of DBPs from A549 cells responding to cisplatin-induced damage across 8 time points, with data generated by data-independent acquisition mass spectrometry (DIA-MS). The results demonstrate that DEWNA can effectively identify protein hubs and associated pathways that are significantly altered in response to cisplatin-induced DNA damage, and offer a comprehensive view of how different pathways interact and respond dynamically over time to cisplatin treatment. Notably, we observed the dynamic activation of distinct DNA repair pathways and cell death mechanisms during the drug treatment time course, providing new insights into the molecular mechanisms underlying the cellular response to DNA damage. [ABSTRACT FROM AUTHOR]

SUMMARY: Canker disease caused by the bacterium Lonsdalea populi is one of the most destructive diseases affecting poplar stems. However, the detailed stress response mechanisms of poplar have not been widely characterized. To explore the diverse regulatory RNA landscape and the function of key regulators in poplar subjected to L. populi stress, we integrated time‐course experiment with mock‐inoculation (CK) and inoculation (IN) with L. populi at the first, third, and sixth day (IN1, IN3, IN6) on Populus × euramericana cv. '74/76' (107), small RNA‐seq, whole transcriptome‐wide analysis, degradome analysis and transgenic experiments. A total of 98 differentially expressed (DE) miRNA, 17 974 DEmRNA, and 807 DElncRNA were identified in poplar infected by L. populi, presenting dynamic changes over the infection course. Regulatory networks among RNAs were further constructed. Notably, a network centered on ptc‐miR482a in CK‐vs‐IN3 contained most DEGs. We show that miR482a and miR1448 are located in one transcript as a polycistron. Overexpression of pre‐miR482a‐miR1448 (OX482‐1448) and pre‐miR482a (OX482) increased poplar susceptibility to canker pathogen with reduced accumulation of reactive oxygen species, while the suppression of miR482a (STTM482) conferred poplar disease resistance. PHA7 was validated as the target of miR482a with degradome sequencing and tobacco transient co‐transformation, its expression being downregulated in OX482‐1448 and OX482 lines. Additionally, a series of phasiRNAs were triggered by miR482a targeting PHA7, forming regulatory cascades with more RLP, NBS‐LRR, and PK genes, further verifying the defense function of miR482a. These findings provide insights for understanding the roles of ncRNAs and regulatory networks involved in poplar immunity. Significance Statement: This study integrated whole transcriptome‐wide analysis of time‐course inoculation on poplar and identified a center ptc‐miR482a, which is located in one transcript with miR1448 as a polycistron. MiR482a overexpression increased poplar susceptibility to canker pathogen and a series of phasiRNAs were triggered by miR482a targeting PHA7. This work provides insights for understanding the regulatory roles of ncRNAs involved in poplar immunity. [ABSTRACT FROM AUTHOR]

Attachment orientation has been reported to influence visual attention and cognitive decisions regarding facial expressions. However, previous studies have reported mixed results regarding the effects of attachment orientation. This study aims to examine how attachment anxiety and avoidance affect judgment and attention allocation during free viewing of dynamic facial expressions. Although we did not find any association between attachment orientation and the reaction time to judge the timings of changes in facial expressions, the relationship between attachment orientation and attention was found. When viewing the appearance of anger, attachment avoidance had a positive relationship and attachment anxiety had a negative relationship with looking time to the eye area. When the eye‐tracking data were divided into 12 consecutive intervals of 1 s each, the attachment orientation had different relationships with visual attention based on the type of emotion presented. We discuss possible explanations for these results and directions for further research in cross‐cultural contexts. [ABSTRACT FROM AUTHOR]

Purpose: Spontaneous closure of idiopathic full-thickness macular holes (iFTMH) has been reported regularly. However, little is known about its probability and timeline. Methods: In this retrospective study all consecutive patients who presented between August 2008 and August 2019 were screened for the presence of a macular hole and only iFTMHs were included. The primary outcome measure was the spontaneous closure of the iFTMH. Results: Of 1256 eyes with macular holes, 338 fulfilled the inclusion criteria. Spontaneous closure of the iFTMH was detected in 31 eyes (9.2%) with a median time of 44 days after diagnosis. Eyes exhibiting spontaneous closure demonstrated a higher baseline best-corrected visual-acuity (BCVA) and smaller iFTMH diameter (p < 0.0001 and p < 0.0001, respectively). The mean BCVA improved from 0.4 logMAR (SD ± 0.21) to 0.29 logMAR (SD ± 0.20) after spontaneous closure (p = 0.031). The iFTMH diameter was positively correlated with the time to spontaneous closure (Pearson-r = 0.37, p = 0.0377). Spontaneously closed iFTMHs reopened in 16% (n = 5) of cases, with a median of 136 days after closure. A logistic regression model showed the hole diameter was associated with spontaneous closure (odds-Ratio 0.97, 95%CI [0.96, 0.98]). The Kaplan–Meier-Curve revealed that approximately 25% of small-iFTMH (n = 124) and 55% of iFTMH with a diameter < 150µm (n = 48) closed spontaneously within two months. Conclusion: The established gold-standard for the treatment of iFTMHs is macular surgery. However, the potential for spontaneous closure of small iFTMHs must be acknowledged. Therefore, if surgical treatment is delayed in individual cases, close observation is recommended. [ABSTRACT FROM AUTHOR]

This study examined the immediate and sustained effects of acute exercise modalities and durations on inhibitory control including response inhibition and interference control. Fifty-nine young adults participated in three exercise interventions and a reading intervention. Three exercise interventions consisted of a 20-min moderate intensity continuous exercise (MICE), a 20-min high intensity interval exercise (HIIE) and a 10-min HIIE. Using a colour-word Stroop task and a Go/no-go task, interference control and response inhibition were assessed before the intervention (t0), immediately after the intervention (t1), and then at 30 min (t2) and 60 min (t3) after the intervention. During the Stroop task, the response time (RT) was significantly shorter for both congruent and incongruent trials immediately after 20-min HIIE compared to that before exercise, and this reduction lasted for 60 min. The improvement in the Stroop task can be maintained for 30 min after 20-min MICE. In addition, the 10-min HIIE intervention immediately reduced the RT of the incongruent trials. However, the Go/no-go results showed no significant change in task performance after the four interventions. The above findings suggest that when compared to MICE for the same exercise time, improvements in interference control were sustained longer and better following 20-min HIIE. In addition, HIIE for 20-min rather than shorter duration was best for both basic information processing and interference control performance. A duration of 20-min HIIE may be a more effective way to improve interference control. Neither HIIE nor MICE had any effect on response inhibition. [ABSTRACT FROM AUTHOR]

In many meta-analyses and literature reviews on fish microbiota, the provenance of the animals (farmed vs. wild) is often overlooked. Given the well-established role of diet as a key factor in shaping gut microbiota, this study investigates the impact of dietary nature by comparing the microbiota of gilthead seabream (Sparus aurata) fed a commercial diet versus a wild-type diet, all reared within a recirculating aquaculture system. Over a 60-day period, we tracked changes in gut bacterial diversity, structure, and composition following a shift from a commercial feed to a diet exclusively based on pink shrimp (Parapenaeus longirostris). Gut bacterial communities were assessed using 16S rRNA gene sequencing (Illumina MiSeq platform) with primers targeting the V3-V4 hypervariable regions. Twenty days after the dietary change, microbial diversity (Shannon index) increased in fish fed the shrimp diet compared to those fed the commercial diet, while Dominance index values decreased. Additionally, inter-individual (beta-) diversity based on Bray-Curtis distances also differed between dietary treatments. These results support further that microbiota comparisons between farmed/captive and wild fish are challenging due to the unpredictable feeding regimes and dietary variations in wild fish. However, the diet impact on microbiota diminished over time, with the differences in intra- and inter-individual diversity being reduced after 40 days, which suggests an adaptation of microbial communities to dietary changes. At this point, gut microbial communities also showed a similar taxonomical composition. Moreover, a core microbiota consisting of species belonging to the genera Ralstonia, Paraburkholderia, Fulvimonas, Pseudomonas, and Cutibacterium was maintained in all sampling times under both dietary treatments. Overall, this study serves as a conceptual approach that shows a long-term adaptation of the gut microbiota after a radical dietary change, probably driven by host-inherent factors. Furthermore, these results may be a valuable insight for feed manufacturers aiming to develop sustainable and cost-effective ingredients since they suggest that some alternative feeds and ingredients do not have adverse long-term effects on fish gut microbiota.

IntroductionNumerous studies have explored the linguistic and executive processes underlying verbal fluency using association designs, which provide limited evidence. To assess the validity of our model, we aimed to refine the cognitive architecture of verbal fluency using an interference design.MethodsA total of 487 healthy participants performed letter and semantic fluency tests under the single condition and dual conditions while concurrently performing a secondary task that interferes with speed, semantics, phonology, or flexibility. We examined the effect of such interference on fluency indices including correct responses, clustering, switching, and time course.Results(1) All secondary tasks decreased fluency (p

Abstract Background Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. Methods This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2–4 months, 4–6 months, and 6–8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. Results In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. Conclusions The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing.

Listeria monocytogenes, which causes human listeriosis after consumption of contaminated food, can adapt and survive under a wide range of physiological and chemical stresses. In this study, the overall proteomic response of the L. monocytogenes strain F2365—a strain with mutations limiting its ability to tolerate acidic conditions—to progressive non-thermal acidic inactivation was investigated. The challenge process was investigated in the early stationary growth phase where F2365 cultures were acidified (pH 3.0, HCl) at 5 min, 1 h, and 2 h, generating pH 4.8, pH 4.1, and pH 3.5, respectively, with protein abundance measured using iTRAQ. Approximately 73 proteins increased in abundance and 8 declined when acidic stress became non-growth-permissive (pH < 4.1) and inactivation accelerated to approximately 2 log units/h. The functional categories of responding proteins were broad but the proteins involved were specific in nature and did not include whole pathways. Many responses likely accentuate energy conservation and compensate vital metabolic processes. For example, further repression of FlaA, normally repressed under acidic stress, occurs accompanied by an increase in quinol oxidase subunit QoxA and glycerol kinase GlpK. Proteins maintaining cell wall integrity, such as Iap and CwlO, manifested the overall largest abundance increase trend. Virulence proteins were also induced, including InlA, InlC, Hyl, Mpl, PlcA, and PlcB, suggesting that acidification may have mimicked conditions inducing some host survival traits. The overall suite of proteins affected appears to be the "last ditch" responses to non-thermal inactivation above and beyond the standard protections afforded in the stationary-growth phase. The array of proteins found here may provide a deeper understanding of the physiological responses of this pathogen during non-thermal inactivation.

BackgroundAfter ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post-IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy.MethodsThe transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNA-seq as a function of time and etiology after stroke. Differential expression analyses were performed at 0-24 h, 24-48 h, and >48 h following stroke.ResultsUnique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils, and whole blood with enrichment of interleukin signaling pathways for different time points and stroke etiologies. Compared to control subjects, gene expression was generally upregulated in neutrophils and generally downregulated in monocytes over all times for cardioembolic, large vessel, and small vessel strokes. Self-organizing maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co-expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood.ConclusionsAltogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.

Background: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. Methods: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2–4 months, 4–6 months, and 6–8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. Results: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. Conclusions: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group. [ABSTRACT FROM AUTHOR]

Background/Objectives: In the absence of an effective antiviral treatment for BK polyomavirus (BKPyV), a better understanding of the epidemiology and time course of BKPyV replication after kidney transplantation is needed to limit the virus's impact on the graft outcome. Methods: In a 7-year study, we screened more than 430 kidney transplant recipients and analyzed the time course and virological characteristics of BKPyV replication. Results: Urinary viral replication was observed in 116 (27%) of the 430 patients, and 90 of the 116 (78%) had viral DNAemia. Thirty-eight patients (8.8%) were presumed to have nephropathy (DNAemia > 4 log10 copies/mL). Of the patients with BKPyV replication, 48%, 60%, 71%, and 80% were first found to be positive one, two, three, and four months post-transplantation. The initial viral load in the urine was below 7 log10 copies/mL in 100% of the patients with viral replication first detected before the first month, and this proportion was 57% when viral replication was first detected after the first month. When the BKPyV replication was first detected in a urine sample at month 3 or later, 81.5% of patients had concomitant BKPyV DNAemia. The predominant viral subtype was Ib2 (60%), and there was no apparent relationship between the subtype and the time course of BKPyV replication. Conclusions: Urinary BKPyV replication occurs early after renal transplantation and in most patients will increase to a level requiring therapeutic intervention. Close monitoring for BKPyV in the early post-transplantation period would enable the pre-emptive adjustment of the immunosuppression regimen. [ABSTRACT FROM AUTHOR]

Abstract Background The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis. Methods This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated. Results In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674–0.823), and 0.601 (95% CI: 0.524–0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025–6.891) was an independent risk factor for 28-day mortality. Conclusions The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.

Lung inflammation and fibrogenesis are the two main characteristics during the development of pulmonary fibrosis (PF), which are particularly associated with pulmonary macrophages. In this context, whether cryptotanshinone (CTS) could alleviate PF through regulating macrophage polarization were preliminarily demonstrated in vitro. Then the time course of PF and its relationship with macrophage polarization was determined in BLM-induced mice based on cytokine levels in bronchoalveolar lavage fluid (BALF), lung histopathology, flow cytometric analysis, mRNA and protein expression. CTS was loaded into macrophage-targeted and responsively released mannose-modified liposomes (Man-lipo), and the liposomes were then embedded into mannitol microparticles (M-MPs) using spray drying to achieve efficient pulmonary delivery. Afterwards, how CTS regulates macrophage polarization in vivo during different time courses of PF was probed. Furthermore, the molecular mechanisms of CTS against PF by regulating macrophage polarization were elucidated in vivo and in vitro. The full-course therapy group could achieve comparable therapeutic effects compared with the positive control drug PFD group. CTS can alleviate PF through regulating macrophage polarization, mainly by inhibiting NLRP3/TGF-β1 pathway during the inflammation course and modulating MMP-9/TIMP-1 balance during the fibrosis development course, providing new insights into chronic PF treatment. [Display omitted] • l The time course of PF development was established using BLM-induced mice, and its relationship with macrophage polarization was determined using a flow cytometer. • l Cryptotanshinone (CTS) was loaded into macrophage targeting and responsive released liposomes, and then the liposomes were incorporated into microparticles using spray drying for efficient pulmonary delivery. • l CTS could reverse LPS-induced polarization of M1 macrophages toward M2, and meanwhile, limit IL-4-triggered polarization of M2, which was consistent with animal results. • l The anti-PF efficacy of CTS through regulating macrophage polarization was confirmed in vitro and in vivo. The full-course therapy group could achieve comparable therapeutic effects with positive control drug PFD group. • l CTS could effectively alleviate PF by regulating macrophage polarization, including inhibiting NLRP3/TGF-β1 pathway during the inflammation course and modulating MMP-9/TIMP-1 balance during the fibrosis development course. [ABSTRACT FROM AUTHOR]

Copyright of Journal for Sociology of Education & Socialization / Zeitschrift für Soziologie der Erziehung & Sozialisation is the property of Julius Beltz GmbH & Co. KG Beltz Juventa and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ObjectiveThis study aimed to investigate the time course of cardiac rupture (CR) after acute myocardial infarction (AMI) and the differences among different rupture types.MethodWe retrospectively analyzed 145 patients with CR after AMI at Shanxi Cardiovascular Hospital from June 2016 to September 2022. Firstly, according to the time from onset of chest pain to CR, the patients were divided into early CR (≤24 h) (n = 61 patients) and late CR (>24 h) (n = 75 patients) to explore the difference between early CR and late CR. Secondly, according to the type of CR, the patients were divided into free wall rupture (FWR) (n = 55) and ventricular septal rupture (VSR) (n = 90) to explore the difference between FWR and VSR.ResultsMultivariate logistic regression analysis showed that high white blood cell count (OR = 1.134, 95% CI: 1.019–1.260, P = 0.021), low creatinine (OR = 0.991, 95% CI: 0.982–0.999, P = 0.026) were independently associated with early CR. In addition, rapid heart rate (OR = 1.035, 95% CI: 1.009–1.061, P = 0.009), low systolic blood pressure (OR = 0.981, 95% CI: 0.962–1.000, P = 0.048), and anterior myocardial infarction (OR = 5.989, 95% CI: 1.978–18.136, P = 0.002) were independently associated with VSR.ConclusionIn patients with CR, high white blood cell count and low creatinine were independently associated with early CR, rapid heart rate, low systolic blood pressure, and anterior myocardial infarction were independently associated with VSR.

Background Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long‐term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. Methods and Results Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%–14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8–10 days group, 2.0% [95% CI, −4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14–16 days group, 7.4% [95% CI, −5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, −14.4% [95% CI, −27.8% to 0.0%]; P=0.05). Conclusions Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

BackgroundData on the stability of whole blood electrolytes is limited to small sample sizes. We sought to determine the stability of whole blood electrolytes under room temperature and slushed iced conditions in human patients at a major hospital center.MethodsWhole blood samples were obtained from 203 patients hospitalized for various pathophysiological conditions. Electrolyte concentrations of sodium, potassium [K+], ionized calcium, and chloride were measured at 5 different timepoints spanning 3 h. Samples were stored at room temperature (22-24 °C) or under slushed ice conditions (0.1-0.2 °C) before analysis.ResultsUnder both conditions, sodium, ionized calcium, and chloride did not show a measurable change up to 109 min compared to baseline; however, the mean increase in [K+] over 138 min of storage in slushed ice was 0.0032 (0.0021 [5th percentile] to 0.0047 [95th percentile]) mmol/L/min (adjusted R2 = 0.62, P

Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48?h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12?h post-CCI compared to mitochondria from injured males at 24?h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12?h post-CCI, whereas mitochondria from injured females showed impairment at 24?h post-CCI. Based on bioenergetic impairments at 24?h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24?h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.

Abstract Background Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI. Methods A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP

Abstract Background The time required for PCR detection of DNA in human blood meals in vector mosquitoes may vary, depending on the molecular markers used, based on the size and copy number of the amplicons. Detailed knowledge of the blood-feeding behavior of mosquito populations in nature is an essential component for evaluating their vectorial capacity and for assessing the roles of individual vertebrates as potential hosts involved in the transmission of vector-borne diseases. Methods Laboratory experiments were conducted to compare the time course of PCR detection of DNA in human blood meals from individual blood-fed Anopheles stephensi mosquitoes, using loci with different characteristics, including two mitochondrial DNA (mtDNA) genes, cytB (228 bp) and 16S ribosomal RNA (rRNA) (157 bp) and nuclear Alu-repeat elements (226 bp) at different time points after the blood meal. Results Human DNA was detectable up to 84–120 h post-blood-feeding, depending on the length and copy number of the loci. Our results suggest that 16S rRNA and Alu-repeat markers can be successfully recovered from human DNA up to 5 days post-blood-meal. The 16S rDNA and Alu-repeat loci have a significantly (P = 0.008) slower decline rate than the cytB locus. Median detection periods (T50) for the amplicons were 117, 113 and 86.4 h for Alu-repeat, 16S rDNA and cytB, respectively, suggesting an inverse linear relationship between amplicon size/copy number and digestion time. Conclusion This comparative study shows that the Alu-repeat locus is the most efficient marker for time-course identification of human DNA from blood meals in female mosquitoes. It is also a promising tool for determining the anthropophilic index (AI) or human blood index (HBI), i.e. the proportion of blood meals from humans, which is often reported as a relative measure of anthropophagy of different mosquito vectors, and hence a measure of the vector competence of mosquito species collected in the field. Graphical Abstract

Abstract Background The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. Methods This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006–2007, 2010–2011, and 2014–2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 − 10) and late (cumCVAI10 − 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. Results During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13–1.61) in the highest quartile of cumCVAI, 1.35 (1.14–1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12–1.43) in those with a cumulative burden > 0, and 1.43 (1.14–1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11–1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03–1.46) for cumCVAI ≥ median with a positive slope. Conclusions In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.

Introduction: Postoperative nausea and vomiting (PONV) and pain are common and distressing complications in patients undergoing surgery. However, it remains uncertain whether timing of the postoperative course or the diel rhythm influences the occurrence of PONV or severe pain. Therefore, we aimed to explore the temporal distribution of PONV and severe pain. Material and methods: In this prospective observational study, we enrolled patients aged 18–65 years with American Society of Anesthesiologists classifications I–III, who were scheduled for surgery under general anesthesia. Patients were visited postoperatively at regular intervals (every 6 h over a 24-h period). Incidence of PONV was recorded and categorized based on real-time divisions: before dawn (00:00–05:59), morning (06:00–11:59), afternoon (12:00–17:59), and evening (18:00–23:59) and as sequential periods (i.e., 0–6, 6–12, 12–18, and 18–24 h). Severe pain and use of additional remedies were also recorded. Results: A total of 724 patients were included in the final analysis. Of these, 14.92 % experienced PONV within the first 6 h, and 8.29 % received antiemetic therapy. Occurrence of PONV and administration of remedies declined over the 24-h postoperative period. The lowest rate of PONV was observed during the pre-dawn hours (5.66 %). There was no statistically significant difference in the incidence of PONV 24-h postoperatively between surgeries with different end times. Patients underwent orthopedic surgeries had the highest incidence of PONV during 18:00–23:59, gynecological surgery patients had the highest incidence at 12:00–17:59, and 6:00–11:59 for other surgery patients. All patients had the lowest incidence during 0:00–5:59. During the initial 6-h postoperative period, 24.59 % of patients experienced severe pain, which declined in the remaining episodes. Patients who underwent orthopedic and gynecological surgeries exhibited similar temporal patterns and distribution characteristics of PONV and severe pain. Discussion: Both PONV and severe pain declined within the 24-h postoperative period, particularly within the first 6 h. Additionally, the onset patterns of PONV vary among patients undergoing different types of surgeries, all patients demonstrated decreased susceptibility to PONV between 00:00–05:59. Our findings enhance prevention and treatment strategies within an optimized timeframe during the postoperative course.

Empirical evidence and theoretical models suggest that phonetic category perception involves two stages of auditory and phonetic processing. However, few studies examined the time course of these two processing stages. With brief stop consonant segments as context stimuli, this study examined the temporal dynamics of stop consonant perception by varying the inter-stimulus interval between context and target stimuli. The results suggest that phonetic category activation of stop consonants may appear before 100 ms of processing time. Furthermore, the activation of phonetic categories resulted in contrast context effects on identifying the target stop continuum; the auditory processing of stop consonants resulted in a different context effect from those caused by phonetic category activation. The findings provide further evidence for the two-stage model of speech perception and reveal the time course of auditory and phonetic processing. [ABSTRACT FROM AUTHOR]

Background: The time required for PCR detection of DNA in human blood meals in vector mosquitoes may vary, depending on the molecular markers used, based on the size and copy number of the amplicons. Detailed knowledge of the blood-feeding behavior of mosquito populations in nature is an essential component for evaluating their vectorial capacity and for assessing the roles of individual vertebrates as potential hosts involved in the transmission of vector-borne diseases. Methods: Laboratory experiments were conducted to compare the time course of PCR detection of DNA in human blood meals from individual blood-fed Anopheles stephensi mosquitoes, using loci with different characteristics, including two mitochondrial DNA (mtDNA) genes, cytB (228 bp) and 16S ribosomal RNA (rRNA) (157 bp) and nuclear Alu-repeat elements (226 bp) at different time points after the blood meal. Results: Human DNA was detectable up to 84–120 h post-blood-feeding, depending on the length and copy number of the loci. Our results suggest that 16S rRNA and Alu-repeat markers can be successfully recovered from human DNA up to 5 days post-blood-meal. The 16S rDNA and Alu-repeat loci have a significantly (P = 0.008) slower decline rate than the cytB locus. Median detection periods (T50) for the amplicons were 117, 113 and 86.4 h for Alu-repeat, 16S rDNA and cytB, respectively, suggesting an inverse linear relationship between amplicon size/copy number and digestion time. Conclusion: This comparative study shows that the Alu-repeat locus is the most efficient marker for time-course identification of human DNA from blood meals in female mosquitoes. It is also a promising tool for determining the anthropophilic index (AI) or human blood index (HBI), i.e. the proportion of blood meals from humans, which is often reported as a relative measure of anthropophagy of different mosquito vectors, and hence a measure of the vector competence of mosquito species collected in the field. [ABSTRACT FROM AUTHOR]

Chromatin accessibility sequencing has been widely used for uncovering genetic regulatory mechanisms and inferring gene regulatory networks. However, effectively integrating large‐scale chromatin accessibility datasets has posed a significant challenge. This is due to the lack of a comprehensive end‐to‐end solution, as many existing tools primarily emphasize data preprocessing and overlook downstream analyses. To bridge this gap, we have introduced cisDynet, a holistic solution that combines streamlined data preprocessing using Snakemake and R functions with advanced downstream analysis capabilities. cisDynet excels in conventional data analyses, encompassing peak statistics, peak annotation, differential analysis, motif enrichment analysis, and more. Additionally, it allows to perform sophisticated data exploration, such as tissue‐specific peak identification, time course data modeling, integration of RNA‐seq data to establish peak‐to‐gene associations, constructing regulatory networks, and conducting enrichment analysis of genome‐wide association study (GWAS) variants. As a proof of concept, we applied cisDynet to reanalyze comprehensive ATAC‐seq datasets across various tissues from the Encyclopedia of DNA Elements (ENCODE) project. The analysis successfully delineated tissue‐specific open chromatin regions (OCRs), established connections between OCRs and target genes, and effectively linked these discoveries with 1861 GWAS variants. Furthermore, cisDynet was instrumental in dissecting the time course open chromatin data of mouse embryonic development, revealing the dynamic behavior of OCRs over developmental stages and identifying key transcription factors governing differentiation trajectories. In summary, cisDynet offers researchers a user‐friendly solution that minimizes the need for extensive coding, ensures the reproducibility of results, and greatly simplifies the exploration of epigenomic data. Highlights: cisDynet enables comprehensive and efficient processing of chromatin accessibility data, including preprocessing, advanced downstream data analysis, and visualization.cisDynet provides a range of analytical features, such as processing of time course data, co‐accessibility analysis, linking open chromatin regions (OCRs) to genes, building cis‐regulatory networks, and genome‐wide association study variant enrichment analysis.cisDynet simplifies the identification of tissue/cell type‐specific OCRs or dynamic OCR changes over time and facilitates the integration of RNA‐seq data to depict temporal trajectories. [ABSTRACT FROM AUTHOR]

Background: The death of a child is a highly traumatic event for parents and often leads to posttraumatic stress disorder (PTSD). Attentional bias has been demonstrated in the onset and maintenance of PTSD symptoms. Objective: This study aimed to investigate the time course of attentional bias among bereaved Chinese parents who have lost their only child (Shidu parents), and to examine its relationship with PTSD symptoms and symptom clusters. Methods: Shidu parents (n = 38; 50–72 years of age) completed a dot-probe task with negative (trauma-related), positive, and neutral images at four stimulus presentation times (250, 500, 750, and 1250 ms). PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5). Results: We observed difficulty in disengaging from both negative and positive stimuli at 750 ms and attentional bias away from negative stimuli at 1250 ms. At 1250 ms, attentional avoidance of trauma-related stimuli was positively correlated with PCL-5 total and intrusion scores. Difficulty in disengaging from positive stimuli was negatively correlated with PCL-5 total and intrusion scores as well as negative alterations in cogniti and mood scores. Conclusions: These findings enhance our understanding of attentional bias and cognitive–affective processing in PTSD. This study provides evidence that attentional bias (difficulty in disengaging from positive stimuli and bias away from negative stimuli) are correlated with PTSD symptoms and certain symptom clusters. The current study examined the time course of attentional bias among bereaved Chinese parents who have lost their only child through a dot-probe task and investigated its relationship with PTSD symptoms and symptom clusters. Participants exhibited difficulty in disengaging from both trauma-related and positive stimuli at 750 ms and exhibited attentional avoidance of trauma-related stimuli at 1250 ms. Attentional avoidance of trauma-related stimuli was positively correlated with PCL-5 total and intrusion scores. Difficulty in disengaging from positive stimuli was negatively correlated with PCL-5 total and intrusion scores as well as negative alterations in cognition and mood scores. [ABSTRACT FROM AUTHOR]

The reverse transcription polymerase chain reaction (RT-PCR) is considered the gold standard method for the detection of viruses in a clinic. The aim of this study was to compare the ability of conventional RT-PCR test (FTDTM SARSCoV- 2 Test) and laboratory-developed ultra-fast PCR test (NextGenPCRTM SARS-CoV-2 RT-PCR Reagent Kit) to detect the coronavirus SARS-CoV- 2 causing COVID-19. A total of 318 nasopharyngeal swab specimens were collected from people under investigation for COVID-19. Despite the collection of two swab specimens from each patient and their different processing, the analysis showed an overall agreement of 95.9% between the conventional and laboratory-developed tests. The positive percentage agreement was 90.5% (114/126) and the negative percentage agreement was 99.5% (191/192). The ultra-fast NextGenPCR method does not require the isolation of RNA, provides a result of 20--96 specimens within 57--82 min after sampling, and offers a simple procedure of sample processing, analysis, and evaluation. Our results indicate that this method can be considered a potential diagnostic method for the detection of SARS-CoV-2 virus in hospitals, healthcare facilities, and research laboratories. [ABSTRACT FROM AUTHOR]

Phenoloxidase (PO) is a significant biomolecule involved in humoral defence mechanism of invertebrates. Spontaneous melanization of insect haemolymph is the major hinderance for studying PO activity, as haemolymph was collected devoid of phenylthiourea. In the study, no visible melanization was observed in crude serum from the grub of Oryctes rhinoceros up to 30 min of incubation amongst crude haemolymph, diluted haemolymph, crude serum and diluted serum that were subjected to visual observation for spontaneous melanization reaction. Accordingly, crude serum was taken for evaluating PO activity. At the same time, as PO substrates tend to auto-oxidize and provide false optical density value, tris-buffered saline devoid of any substrates were used as blank for PO assays. The ideal wavelength at which maximum PO activity occurred for each substrate, namely, tyrosine, tyramine, dopamine, L-dopa, DL-dopa, catechol, protocatechuic acid and pyrogallol was determined as 407, 410, 429, 465, 403, 466, 428 and 400 nm, respectively. Additionally, time course of oxidation for each phenolic substrate by the serum PO were examined and DL-dopa was identified as the specific substrate for serum PO in the grub of O. rhinoceros. Furthermore, maximum PO activity was observed at 5 min of incubation for 10 mM of DL-dopa that was considered as optimum concentration. The ideal pH and temperature for serum PO activity was observed as 7.5 and 20°C, respectively. These results suggested that standardizing a suitable substrate is an essential prerequisite to evaluate the real PO activity of serum which might significantly fluctuate in each insect model. [ABSTRACT FROM AUTHOR]

Background/Objectives: In the absence of an effective antiviral treatment for BK polyomavirus (BKPyV), a better understanding of the epidemiology and time course of BKPyV replication after kidney transplantation is needed to limit the virus’s impact on the graft outcome. Methods: In a 7-year study, we screened more than 430 kidney transplant recipients and analyzed the time course and virological characteristics of BKPyV replication. Results: Urinary viral replication was observed in 116 (27%) of the 430 patients, and 90 of the 116 (78%) had viral DNAemia. Thirty-eight patients (8.8%) were presumed to have nephropathy (DNAemia > 4 log10 copies/mL). Of the patients with BKPyV replication, 48%, 60%, 71%, and 80% were first found to be positive one, two, three, and four months post-transplantation. The initial viral load in the urine was below 7 log10 copies/mL in 100% of the patients with viral replication first detected before the first month, and this proportion was 57% when viral replication was first detected after the first month. When the BKPyV replication was first detected in a urine sample at month 3 or later, 81.5% of patients had concomitant BKPyV DNAemia. The predominant viral subtype was Ib2 (60%), and there was no apparent relationship between the subtype and the time course of BKPyV replication. Conclusions: Urinary BKPyV replication occurs early after renal transplantation and in most patients will increase to a level requiring therapeutic intervention. Close monitoring for BKPyV in the early post-transplantation period would enable the pre-emptive adjustment of the immunosuppression regimen.

This study was designed to assess the effects of acute exercise on performance of a paired associate learning (PAL) test, an operationalization of hippocampal-dependent associative memory. Participants performed a PAL test and then ran on a treadmill (exercise group, n = 52) or solved Sudoku puzzles (control group, n = 54). Participants returned 2, 5, or 8 hr later to perform a second, different, PAL test. PAL scores for the control group did not change over time. Similarly, scores on tests taken 2 and 5 hr after exercise were not different from baseline or control data. Scores on tests taken 8 hr after exercise, however, fell significantly below baseline (by 8.6%) and control (by 9.8%) scores. These data demonstrate that acute exercise can negatively affect the encoding and retrieval of new information even hours after the exercise bout, which should be a consideration when designing exercise programs to enhance, and not hinder, learning. [ABSTRACT FROM AUTHOR]

Abstract Chromatin accessibility sequencing has been widely used for uncovering genetic regulatory mechanisms and inferring gene regulatory networks. However, effectively integrating large‐scale chromatin accessibility datasets has posed a significant challenge. This is due to the lack of a comprehensive end‐to‐end solution, as many existing tools primarily emphasize data preprocessing and overlook downstream analyses. To bridge this gap, we have introduced cisDynet, a holistic solution that combines streamlined data preprocessing using Snakemake and R functions with advanced downstream analysis capabilities. cisDynet excels in conventional data analyses, encompassing peak statistics, peak annotation, differential analysis, motif enrichment analysis, and more. Additionally, it allows to perform sophisticated data exploration, such as tissue‐specific peak identification, time course data modeling, integration of RNA‐seq data to establish peak‐to‐gene associations, constructing regulatory networks, and conducting enrichment analysis of genome‐wide association study (GWAS) variants. As a proof of concept, we applied cisDynet to reanalyze comprehensive ATAC‐seq datasets across various tissues from the Encyclopedia of DNA Elements (ENCODE) project. The analysis successfully delineated tissue‐specific open chromatin regions (OCRs), established connections between OCRs and target genes, and effectively linked these discoveries with 1861 GWAS variants. Furthermore, cisDynet was instrumental in dissecting the time course open chromatin data of mouse embryonic development, revealing the dynamic behavior of OCRs over developmental stages and identifying key transcription factors governing differentiation trajectories. In summary, cisDynet offers researchers a user‐friendly solution that minimizes the need for extensive coding, ensures the reproducibility of results, and greatly simplifies the exploration of epigenomic data.

Background: The death of a child is a highly traumatic event for parents and often leads to posttraumatic stress disorder (PTSD). Attentional bias has been demonstrated in the onset and maintenance of PTSD symptoms. Objective: This study aimed to investigate the time course of attentional bias among bereaved Chinese parents who have lost their only child (Shidu parents), and to examine its relationship with PTSD symptoms and symptom clusters. Methods: Shidu parents (n = 38; 50–72 years of age) completed a dot-probe task with negative (trauma-related), positive, and neutral images at four stimulus presentation times (250, 500, 750, and 1250 ms). PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5). Results: We observed difficulty in disengaging from both negative and positive stimuli at 750 ms and attentional bias away from negative stimuli at 1250 ms. At 1250 ms, attentional avoidance of trauma-related stimuli was positively correlated with PCL-5 total and intrusion scores. Difficulty in disengaging from positive stimuli was negatively correlated with PCL-5 total and intrusion scores as well as negative alterations in cogniti and mood scores. Conclusions: These findings enhance our understanding of attentional bias and cognitive–affective processing in PTSD. This study provides evidence that attentional bias (difficulty in disengaging from positive stimuli and bias away from negative stimuli) are correlated with PTSD symptoms and certain symptom clusters.

Background: Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI. Methods: A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP < or ≥ median (− 0.12) and AIP slope. Results: After 11.05 years of follow-up, 766 incident MI cases were documented. After adjustment for potential confounders, higher risk of MI was observed in participants with the highest time-weighted cumulative AIP quartile (HR, 1.89; 95% CI 1.47–2.43), the longest exposure duration of high AIP (HR, 1.52; 95% CI 1.18–1.95), and those with high time-weighted cumulative AIP and negative slope (HR, 1.42; 95% CI 1.13–1.79). Conclusions: Long-term cumulative exposure to AIP and the time course of AIP accumulation increased the risk of MI. High AIP earlier resulted in a greater risk increase than later in life with the same time-weighted cumulative AIP, emphasizing the importance of controlling atherogenic dyslipidemia early in life. [ABSTRACT FROM AUTHOR]

Background: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. Methods: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006–2007, 2010–2011, and 2014–2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 − 10) and late (cumCVAI10 − 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. Results: During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13–1.61) in the highest quartile of cumCVAI, 1.35 (1.14–1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12–1.43) in those with a cumulative burden > 0, and 1.43 (1.14–1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11–1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03–1.46) for cumCVAI ≥ median with a positive slope. Conclusions: In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life. [ABSTRACT FROM AUTHOR]

Listeners spontaneously form impressions of a person from their voice: Is someone old or young? Trustworthy or untrustworthy? Some studies suggest that these impressions emerge rapidly (e.g., < 400 ms for traits), but it is unclear just how rapidly different impressions can emerge and whether the time courses differ across characteristics. I presented 618 adult listeners with voice recordings ranging from 25 ms to 800 ms in duration and asked them to rate physical (age, sex, health), trait (trustworthiness, dominance, attractiveness), and social (educatedness, poshness, professionalism) characteristics. I then used interrater agreement as an index for impression formation. Impressions of physical characteristics and dominance emerged fastest, showing high agreement after only 25 ms of exposure. In contrast, agreement for trait and social characteristics was initially low to moderate and gradually increased. Such a staggered time course suggests that there could be a temporo-perceptual hierarchy for person perception in which faster impressions could influence later ones. [ABSTRACT FROM AUTHOR]

The mental health of children and adolescents with autism spectrum disorder (ASD) is a concern of recent years. However, a large-scale longitudinal study investigating the risk and the time course of subsequent psychiatric comorbidities is still lacking. Using the Taiwan National Health Insurance Research Database, 13,382 children and adolescents with ASD, and 53,528 age- and sex-matched non-ASD controls were enrolled between 2001 and 2009, and followed to the end of 2011. The adjusted hazard ratio (HR) with a corresponding 95 % confidence interval for psychiatric comorbidities among children and adolescents with ASD vs matched controls was estimated. The subjects who developed schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and obsessive-compulsive disorder (OCD) were identified during the follow-up. Children and adolescents with ASD compared with controls were more likely to be diagnosed with schizophrenia (19.21; 13.74, 26.88), bipolar disorder (17.59; 12.66, 24.44), depressive disorder (5.56; 4.72, 6.56), anxiety disorder (5.01; 4.49, 5.59), and OCD (16.12; 11.66, 22.30) later in life. The time course of subsequent psychiatric comorbidity showed that anxiety disorder occurred first, usually in late childhood, with psychotic and affective disorders proceeding in adolescence. Those with ASD and anxiety disorder had an additionally increased likelihood of developing subsequent psychiatric comorbidity compared with those with ASD only. In claims data analysis, clinical parameters or possible confounders may not be fully captured. Patients with ASD are predisposed to the development of anxiety disorder in late childhood, as well as schizophrenia, bipolar disorder, depressive disorder, and OCD in adolescence. • ASD predisposes the development of anxiety disorder, schizophrenia, bipolar disorder, depressive disorder, and OCD. • Anxiety disorder typically develops earlier than other psychiatric comorbidities. • Co-occurring anxiety disorder can independently increase risks of other psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

When seeing a face or hearing a voice, perceivers readily form first impressions of a person's characteristics--are they trustworthy, do they seem aggressive? One of the key claims about trait impressions from faces and voices alike is that these impressions are formed rapidly. For faces, studies have systematically mapped this rapid time course of trait impressions, finding that they are well formed and stable after approximately 100 ms of exposure. For voices, however, no systematic investigation of the time course of trait perception exists. In the current study, listeners provided trait judgments (attractiveness, dominance, trustworthiness) based on recordings of 100 voices that lasted either 50, 100, 200, 400, or 800 ms. Based on measures of intra- and interrater agreement as well as correlations of mean ratings for different exposure conditions, we find that trait perception from voices is indeed rapid. Unlike faces, however, trait impressions from voices require longer exposure to develop and stabilize although they are still formed by 400 ms. Furthermore, differences in the time course of trait perception from voices emerge across traits and voice gender: The formation of impressions of attractiveness and dominance required less exposure when based on male voices, whereas impressions of trustworthiness evolved over a more gradual time course for male and female voices alike. These findings not only provide the first estimate of the time course of the formation of voice trait impressions, but they also have implications for voice perception models where voices are regarded as "auditory faces.". [ABSTRACT FROM AUTHOR]

The present meta-analysis examined the effects of resistance training on increasing the rate of force development (RFD), followed by exploring the changes in RFD occurring during training cessation. Five databases were searched to find eligible studies. Their methodological quality was evaluated using the Downs and Black checklist. The data were pooled in a random-effects meta-analysis. Seven studies with 11 training groups were included in the meta-analysis. All studies were classified as being of good or moderate quality. Resistance training increased RFD (d : 0.24; 95% confidence interval [CI]: 0.09–0.38). There was no significant difference in RFD between the postintervention and postdetraining periods (d : −0.02; 95% CI: −0.10–0.06). In subgroup meta-analyses, there was no significant difference (all p > 0.05) between the postintervention and postdetraining RFD when categorized according to detraining duration (up to 4 weeks versus 7–16 weeks) or participants' training status (untrained versus trained). This meta-analysis demonstrated that resistance training effectively increases RFD. More importantly, the results also indicated that gains in RFD are maintained after detraining. Thus, unlike a few other resistance training–induced adaptations (e.g., increases in muscular strength and muscular endurance), it seems that gains in RFD are preserved during a detraining phase. [ABSTRACT FROM AUTHOR]