Tag: pubmed

Methods. 2024 May 18:S1046-2023(24)00125-7. doi: 10.1016/j.ymeth.2024.05.009. Online ahead of print.

ABSTRACT

With the recent advanced direct RNA sequencing technique that proposed by the Oxford Nanopore Technologies, RNA modifications can be detected and profiled in a simple and straightforward manner. Majority nanopore-based modification studies were devoted to those popular types such as m6A and pseudouridine. To address current limitations on studying the crucial regulator, m1A modification, we conceived this study. We have developed an integrated computational workflow designed for the detection of m1A modifications from direct RNA sequencing data. This workflow comprises a feature extractor responsible for capturing signal characteristics (such as mean, standard deviations, and length of electric signals), a single molecule-level m1A predictor trained with features extracted from the IVT dataset using classical machine learning algorithms, a confident m1A site selector employing the binomial test to identify statistically significant m1A sites, and an m1A modification rate estimator. Our model achieved accurate molecule-level prediction (Average AUC = 0.9689) and reliable m1A site detection and quantification. To show the feasibility of our workflow, we conducted a study on in vivo transcribed human HEK293 cell line, and the results were carefully annotated and compared with other techniques (i.e., Illumina sequencing-based techniques). We believed that this tool will enabling a comprehensive understanding of the m1A modification and its functional mechanisms within cells and organisms.

PMID:38768930 | DOI:10.1016/j.ymeth.2024.05.009

Am J Obstet Gynecol MFM. 2024 May 18:101385. doi: 10.1016/j.ajogmf.2024.101385. Online ahead of print.

ABSTRACT

BACKGROUND: Few recent studies have examined the rate of severe maternal morbidity (SMM) occurring during the antenatal and/or the postpartum period through 42 days postpartum. However, little is known about the rate of SMM occurring beyond 42 days postpartum.

OBJECTIVE: To examine the distribution of SMM and its indicators during antenatal, delivery, and postpartum hospitalizations through 365 days postpartum, and to estimate the increase in SMM rate and its indicators after accounting for antenatal and postpartum SMM through 365 days postpartum.

STUDY DESIGN: We conducted a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from Michigan, Oregon, and South Carolina from 2008-2020. We examined the distribution of SMM, non-transfusion SMM, and SMM indicators during antenatal, delivery, and postpartum hospitalizations through 365 days postpartum. We subsequently examined “SMM cases added,” which represent cases among unique individuals that are included by considering the antenatal and postpartum periods but that would be missed if only the delivery hospitalization cases were included.

RESULTS: A total of 64,661 (2.5%) individuals experienced SMM while 37,112 (1.4%) individuals experienced non-transfusion SMM during antenatal, delivery, and/or postpartum hospitalization. A total of 31% of SMM cases were added after accounting for SMM occurring during the antenatal or postpartum hospitalization through 365 days postpartum while 49% of non-transfusion SMM cases were added after accounting for non-transfusion SMM occurring during the antenatal or postpartum periods. SMM occurring between 43 and 365 days postpartum contributed to 12% of all SMM cases while non-transfusion SMM occurring between 43 and 365 days postpartum contributed to 19% of all non-transfusion SMM cases.

CONCLUSION: We showed that a total of 31% of SMM and 49% of non-transfusion SMM cases were added after accounting for SMM occurring during the antenatal or postpartum hospitalization through 365 days postpartum. Our findings highlight the importance of expanding the SMM definition beyond the delivery hospitalization to better capture the full period of increased risk, identify contributing factors, and design strategies to mitigate this risk. Only then, can we improve outcomes for mothers and subsequently the quality of life of their infants.

PMID:38768903 | DOI:10.1016/j.ajogmf.2024.101385

Environ Res. 2024 May 18:119178. doi: 10.1016/j.envres.2024.119178. Online ahead of print.

ABSTRACT

BACKGROUND: Reported associations between particulate matter with aerodynamic diameter < 2.5μm (PM_2.5) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity.

OBJECTIVES: To assess agreement between PM_2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM_2.5 and cognitive or MRI outcomes.

METHODS: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM_2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM_2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM_2.5 exposure estimates with cognitive scores (n=4,678) and MRI outcomes (n=1,518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors.

RESULTS: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM_2.5-cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors.

DISCUSSION: PM_2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health.

PMID:38768885 | DOI:10.1016/j.envres.2024.119178

Diabetes Res Clin Pract. 2024 May 18:111709. doi: 10.1016/j.diabres.2024.111709. Online ahead of print.

ABSTRACT

Previous studies have assessed how supplementing with policosanol affects blood sugar levels. The outcomes, nevertheless, were not constant. Multiple electronic databases were searched including ISI Web of Science, Cochrane Library, PubMed, Google Scholar, and Scopus until February 9, 2023. To assess the effects of policosanol on glucose, we employed a random-effects or fixed-effects meta-analysis approach to examine the weighted mean differences (WMDs) and associated 95 % confidence intervals (CI) before and after policosanol and placebo administration. The final analysis comprised a total of 25 trials with 2680 participants. Compared to the control group, policosanol supplementation significantly reduced blood glucose levels (WMD: -2.24 mg/dl; 95 % CI: -4.05, -0.42, P = 0.01). Findings from subgroup analysis revealed a significant reduction of policosanol supplementation on glucose levels in period of less than 24 weeks, and in individuals below 50 years of age. Additionally, the reduction was statistically significant in dosage of 10 mg/day. Our dose-response analysis indicates no evidence of a non-linear relationship between policosanol dose and duration and changes in glucose levels (P-nonlinearity = 0.52, and P-nonlinearity = 0.52, respectively). Policosanol supplementation might improve blood glucose. Further trials with more complex designs are required to confirm the findings.

PMID:38768866 | DOI:10.1016/j.diabres.2024.111709

J Vasc Surg. 2024 May 18:S0741-5214(24)01211-4. doi: 10.1016/j.jvs.2024.05.032. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to identify trends in hospital (HLOS) and ICU (ICULOS) lengths of stay, and the relationship with cerebrospinal fluid drainage (CSFD) protocols in patients undergoing fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms (TAAAs).

METHODS: A retrospective review of patients who underwent elective FB-EVAR for extent I-IV TAAAs between 2008-2023 at a single aortic center of excellence was conducted. Patient demographics, cardiovascular comorbidities, surgical risk, technical details, CSFD strategy (prophylactic or therapeutic), procedural success, and perioperative outcomes were collected. Patients were divided into two groups based on CSFD protocol. Group 1 included patients treated before 2020 when prophylactic CSFD was performed widely, and Group 2 consisted of patients treated since 2020 with therapeutic CSFD. Primary endpoints were HLOS, ICULOS, major adverse events (MAE), and perioperative mortality.

RESULTS: FB-EVAR was performed in 702 patients; 412 underwent elective TAAA repair and were included in the analysis. Mean age was 73 years (SD±8) and 68% were males. Patient-specific manufactured devices were used in 252 patients (61%), physician-modified endografts in 110 (27%), and 50 patients (12%) were treated with off-the-shelf devices. Demographics, aneurysm extent, MAE (including spinal cord ischemia), and mortality were similar in both groups. A significant reduction in mean HLOS between the groups (9±9. vs 6±5 days, p = .02) coincided with decreased use of prophylactic CSFD (70% vs 1.2%, p < .001), with similar rates of SCI (7.6% vs 4.9%, p = .627) and ICULOS (3±3 vs 2.5±3, p = .19). Patients in the therapeutic drainage cohort (group 2) had a higher incidence of congestive heart failure (24% vs 11%, p = .003), hypercholesterolemia (91% vs 80%, p = .015), COPD (55% vs 37%, p = .004), and peripheral artery disease (39% vs 19%, p < .001) compared to group 1, suggesting treatment of a more complex patient cohort. On adjusted multivariable analysis accounting for ASA score, comorbidities, and device type, the difference in HLOS remained statistically significant (p = .01).

CONCLUSION: HLOS decreased over time in patients undergoing FB-EVAR for TAAA following transition from prophylactic to therapeutic CSFD protocol. This transition was the only modifiable, independent risk factor for shorter HLOS, without an increase in SCI, albeit with similar ICULOS.

PMID:38768834 | DOI:10.1016/j.jvs.2024.05.032

J Vasc Surg. 2024 May 18:S0741-5214(24)01106-6. doi: 10.1016/j.jvs.2024.04.073. Online ahead of print.

ABSTRACT

INTRODUCTION: Length of stay (LOS) is a major driver of cost and resource utilization following lower extremity bypass (LEB). However, the variable comorbidity burden and mobility status of LEB patients makes implementing enhanced recovery after surgery (ERAS) pathways challenging. The aim of this study was to utilize a large national database to identify patient factors associated with ultrashort LOS among patients undergoing LEB for peripheral artery disease (PAD).

METHODS: All patients undergoing LEB for PAD in the National Surgical Quality Improvement Project database from 2011-2018 were included. Patients were divided into two groups based on the length of postoperative stay: ultrashort (<=2 days) and standard (>2 days). Thirty-day outcomes were compared using descriptive statistics, and multivariable logistic regression was used to identify patient factors associated with ultrashort LOS.

RESULTS: Overall, 17,510 patients were identified who underwent LEB, of which 2,678 (15.3%) patients had an ultrashort postoperative LOS (mean 1.8 days) and 14,832 (84.7%) patients had a standard LOS (mean 7.1 days). When compared to patients with standard LOS, patients with an ultrashort LOS were more likely to be admitted from home (95.9% vs 88.0%, p<0.001), undergo elective surgery (86.1% vs. 59.1%, p<0.001) and to be active smokers (52.1% vs. 40.4%, p<0.001). Ultrashort LOS patients were also more likely to have claudication as the indication for LEB (53.1% vs. 22.5%, p<0.001), have a popliteal revascularization target rather than a tibial/pedal target (76.7% vs 55.3%, p<0.001) and had a prosthetic conduit (40.0% vs. 29.9%, p<0.001). There was no significant difference in mortality between the two groups (1.4% vs 1.8%, p=0.21); however ultrashort LOS patients had a lower frequency of unplanned readmission (10.7% vs. 18.8%, p<0.001) and need for major reintervention (1.9% vs. 5.6%, p<0.001). On multivariable analysis, elective status (OR:2.66, 95%CI:2.33-3.04), active smoking (OR:1.18, 95%CI:1.07-1.30) and lack of vein harvest (OR:1.55, 95%CI:1.41-1.70) were associated with ultrashort LOS. Presence of rest pain (OR:0.57, 95%CI:0.51-0.63), tissue loss (OR:0.30, 95%CI:0.27-0.34) and totally dependent functional status (OR:0.54, 95%CI:0.35-0.84) were negatively associated with ultrashort LOS. When examining the subgroup of patients who underwent vein harvest, totally dependent (OR:0.38 95%CI:0.19-0.75) and partially dependent (OR:0.53, 95%CI:0.32-0.88) functional status were persistently negatively associated with ultrashort LOS.

CONCLUSIONS: Ultrashort LOS (<= 2 days) following LEB is uncommon but feasible in select patients. Preoperative functional status and mobility are important factors to consider when identifying LEB patients who may be candidates for early discharge.

PMID:38768833 | DOI:10.1016/j.jvs.2024.04.073

J Affect Disord. 2024 May 18:S0165-0327(24)00821-8. doi: 10.1016/j.jad.2024.05.085. Online ahead of print.

ABSTRACT

BACKGROUND: Depression tends to develop in correlation with hypothyroidism, however it’s unclear how testosterone traits contribute to this association. We examined the causal association between depression, testosterone traits, and hypothyroidism using Mendelian randomization (MR).

METHOD: We conducted univariable and multivariable MR studies using summary-level statistics from genome-wide association studies (GWAS) of Hypothyroidism (n = 213,990), broad depression (n = 322,580), probable major depressive disorder (probable MDD) (n = 174,519), and International Classification of Diseases (ICD)-9 or ICD-10-coded MDD (n = 217,584) from European ancestry. The inverse variance weighted (IVW) method was used as the main MR analysis.

RESULTS: In univariate MR analysis, there is a positive causal relationship between hypothyroidism and broad depression (P = 0.0074; OR = 1.0066; 95%CI: 1.0018-1.0114) and probable MDD (P = 0.0242; OR = 1.0056; 95%CI: 1.0007-1.0105). In females, there is a causal relationship between hypothyroidism and decreased total testosterone (P < 0.001; OR = 0.9747; 95%CI: 0.9612-0.9885) and sex hormone binding globulin (SHBG) levels (P = 0.0418; OR = 0.9858; 95%CI: 0.9723-0.9995). In females, there is an inverse causal relationship between total testosterone and broad depression (P = 0.0349; OR = 0.9898; 95%CI: 0.9804-0.9993). Furthermore, in multivariate MR analysis, after adjusting for total testosterone in females, hypothyroidism only has a positive causal relationship with probable MDD, and the relationship with broad depression is no longer significant. Most notably, after adjusting for hypothyroidism, the inverse causal effect of female total testosterone levels on broad depression becomes more significant (P = 0.0154; OR = 0.9878; 95%CI: 0.9780-0.9977).

CONCLUSION: Hypothyroidism increases the risk of broad depression and probable MDD development. Total Testosterone appears to play an important role in the relationship between hypothyroidism and broad depression in female.

PMID:38768827 | DOI:10.1016/j.jad.2024.05.085

J Chin Med Assoc. 2024 May 17. doi: 10.1097/JCMA.0000000000001109. Online ahead of print.

ABSTRACT

BACKGROUND: PSA remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the Body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or BMI, instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy.

METHODS: We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results.

RESULTS: A total of 174 patients diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N=165) were considered to have localized disease on preoperative multi-parameter magnetic resoanace imaging. After prostatectomy, 73% (N=127) of the patients remained in the localized disease group (group A) and 27%(N=47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in Group B (16.9 vs 11.2 ng/dL; p= 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA x body weight and PSA x BMI, a statistically significant difference emerged between the two groups (p= 0.0198 in PSA × BW; p=0.0110 in PSA × BMI).

CONCLUSION: The Body mass weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.

PMID:38768317 | DOI:10.1097/JCMA.0000000000001109

Vet Ophthalmol. 2024 May 20. doi: 10.1111/vop.13224. Online ahead of print.

ABSTRACT

OBJECTIVE: Identify microorganisms present in canine eyes affected by ulcerative keratitis and assess its resistance profile to available antimicrobial drugs.

METHODS: Samples were collected from 88 canine eyes that exhibited ulcerative keratitis. They were identified using MALDI-TOF and subjected to antimicrobial susceptibility testing by disk diffusion.

RESULTS: Among the assessed subjects, brachycephalic dogs accounted for 74.48% (50/83) of the evaluated canines. Among the 88 evaluated eyes, 90.9% (80/88) showed positive cultures, with 11.33% (10/88) of the samples isolating more than one species of bacteria. Of all bacterial isolates identified (90), Gram-positive bacteria accounted for 63.33% (57/90), while Gram-negative bacteria constituted 36.66% (33/90), with predominance of Staphylococcus spp. at 35.55% (32/90) being, Staphylococcus pseudintermedius at 68.75% (22/32), and Pseudomonas aeruginosa at 15.55% (14/90), respectively. Staphylococcus spp. exhibited resistance to penicillin (89.29%), sulfadiazine and trimethoprim (60.71%), and tetracycline (67.86%), while doxycycline (88.89%), cefotaxime (85.71%), chloramphenicol (82.14%), gentamicin, and moxifloxacin (78.57%) showed the highest sensitivity rates. Pseudomonas aeruginosa displayed sensitivity (100%) to gentamicin and imipenem, and resistance (8.33%) to norfloxacin, ciprofloxacin, and cefepime. Similarly, the Enterobacteriaceae family showed higher sensitivity to amikacin and gentamicin (88.89%), imipenem (88.24%), and levofloxacin (87.5%), with pronounced resistance to amoxicillin-clavulanate (50%) and cefazolin (47.06%). This highlights multiresistance in 23.33% (21/90) of the isolates.

CONCLUSIONS: The most isolated species in canine ulcerative keratitis are S. pseudintermedius and P. aeruginosa. However, other species were also isolated, demonstrating diversity in ocular microbiota infection. There is a high-rate multidrug resistance associated with canine ulcerative keratitis. Nevertheless, these strains exhibited sensitivity to antimicrobials commonly used in veterinary ophthalmology.

PMID:38768284 | DOI:10.1111/vop.13224

BJS Open. 2024 May 8;8(3):zrae047. doi: 10.1093/bjsopen/zrae047.

ABSTRACT

BACKGROUND: Extended aortic repair is considered a key issue for the long-term durability of surgery for DeBakey type 1 aortic dissection. The risk of aortic degeneration may be higher in young patients due to their long life expectancy. The early outcome and durability of aortic surgery in these patients were investigated in the present study.

METHODS: The subjects of the present analysis were patients under 60 years old who underwent surgical repair for acute DeBakey type 1 aortic dissection at 18 cardiac surgery centres across Europe between 2005 and 2021. Patients underwent ascending aortic repair or total aortic arch repair using the conventional technique or the frozen elephant trunk technique. The primary outcome was 5-year cumulative incidence of reoperation on the distal aorta.

RESULTS: Overall, 915 patients underwent surgical ascending aortic repair and 284 patients underwent surgical total aortic arch repair. The frozen elephant trunk procedure was performed in 128 patients. Among 245 propensity score-matched pairs, total aortic arch repair did not decrease the rate of distal aortic reoperation compared to ascending aortic repair (5-year cumulative incidence, 6.7% versus 6.7%, subdistributional hazard ratio 1.127, 95% c.i. 0.523 to 2.427). Total aortic arch repair increased the incidence of postoperative stroke/global brain ischaemia (25.7% versus 18.4%, P = 0.050) and dialysis (19.6% versus 12.7%, P = 0.003). Five-year mortality was comparable after ascending aortic repair and total aortic arch repair (22.8% versus 27.3%, P = 0.172).

CONCLUSIONS: In patients under 60 years old with DeBakey type 1 aortic dissection, total aortic arch replacement compared with ascending aortic repair did not reduce the incidence of distal aortic operations at 5 years. When feasible, ascending aortic repair for DeBakey type 1 aortic dissection is associated with satisfactory early and mid-term outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

PMID:38768283 | DOI:10.1093/bjsopen/zrae047