bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular events following coronavirus disease 2019 vaccination in adults: a nationwide Swedish study
Authors: Xu Yiyi , Li Huiqi , Santosa Ailiana , Wettermark Björn , Fall Tove , Björk Jonas , Börjesson Mats , Gisslén Magnus , Nyberg Fredrik
Published: September 2024

Background and Aims

While the rationale for coronavirus disease 2019 (COVID-19) vaccination is to reduce complications and overall mortality, some cardiovascular complications from the vaccine itself have been demonstrated. Myocarditis and pericarditis are recognized as rare acute adverse events after mRNA vaccines in young males, while evidence regarding other cardiovascular events remains limited and inconsistent. This study assessed the risks of several cardiovascular and cerebrovascular events in a Swedish nationwide register-based cohort.

Methods

Post-vaccination risk of myocarditis/pericarditis, dysrhythmias, heart failure, myocardial infarction, and cerebrovascular events (transient ischaemic attack and stroke) in several risk windows after each vaccine dose were assessed among all Swedish adults (n = 8 070 674). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) compared with unvaccinated were estimated from Cox regression models adjusted for potential confounders.

Results

For most studied outcomes, decreased risks of cardiovascular events post-vaccination were observed, especially after dose three (HRs for dose three ranging from .69 to .81), while replicating the increased risk of myocarditis and pericarditis 1–2 weeks after COVID-19 mRNA vaccination. Slightly increased risks, similar across vaccines, were observed for extrasystoles [HR 1.17 (95% CI 1.06–1.28) for dose one and HR 1.22 (95% CI 1.10–1.36) for dose two, stronger in elderly and males] but not for arrhythmias and for transient ischaemic attack [HR 1.13 (95% CI 1.05–1.23), mainly in elderly] but not for stroke.

Conclusions

Risk of myopericarditis (mRNA vaccines only), extrasystoles, and transient ischaemic attack was transiently increased after COVID-19 vaccination, but full vaccination substantially reduced the risk of several more severe COVID-19-associated cardiovascular outcomes, underscoring the protective benefits of complete vaccination.
Is dabigatran a good alternative to warfarin in patients with atrial fibrillation accompanied by valvular and nonvalvular heart diseases? A systematic review and meta-analysis
Authors: Youssef Eman , Daher Mohanad , Milad Abanoub , Gamal Aliaa , Elmezayen Rafeek Walid
Published: September 2024

Background

There is ongoing discussion regarding the terminology used when atrial fibrillation (AF) is present alongside either valvular heart disease (VHD) or non-valvular heart disease (NVHD). Warfarin has been used for decades for stroke (S) and systemic embolism (SE) prophylaxis in atrial fibrillation (AF) patients. However, due to its drug and food interactions, pharmacogenetic approach via VKORC1, narrow therapeutic window, frequent monitoring, and high risk of intracranial hemorrhage (ICH), it is not preferred as a first-line anticoagulant for AF patients. Is it time to retire warfarin and replace it with dabigatran?

Aim and objectives

We conducted this meta-analysis to assess the effectiveness and safety of dabigatran compared to warfarin and find out how likely it could be used instead of warfarin in AF patients with VHD and NVHD.

Methods

PubMed, SCOPUS, Web of Science, and Cochrane CENTRAL were searched online from inception till June 2023, and eligible randomized controlled trials (RCTs) were selected. The outcomes were analyzed and calculated using the risk ratio (RR), and its confidence interval (CI) using STATA software. The Cochrane Risk of Bias 2.0 tool (ROB2) was used to assess the included studies.

Results

In the NVHD subgroup, dabigatran 150 mg showed a significantly low risk of S and SE (RR 0.74, 95% CI: [0.62,0.88]), ICH (RR 0.38, 95% CI: [0.26,0.56]), death (RR 0.85, 95% CI: [0.74,0.99]), and high risk of gastrointestinal bleeding (GIB) (RR 1.47, 95% CI: [1.17,1.85]) compared to Warfarin. Dabigatran 110 mg showed a low risk of ICH (RR 0.31, 95% CI: [0.21,0.47]), and no significant differences in S/SE (RR 1.02, 95% CI: [0.87,1.19]) and death (RR 0.94, 95% CI: [0.82,1.09]) compared to warfarin. In the VHD subgroup, dabigatran showed no significant differences in S/SE (RR 2.57, 95% CI: [0.57,11.56]), major bleeding (RR 1.14, 95% CI: [0.35,3.68]), and death (RR 0.35, 95% CI: [0.07,1.81]) compared to warfarin. In the catheter ablation subgroup, dabigatran showed a significant reduction only in groin hematoma (RR 0.19, 95% CI: [0.05,0.73]), compared to warfarin.

Conclusion

Dabigatran 150 mg was superior to warfarin in AF patients with NVHD; except with GIB; otherwise, Dabigatran 110 mg was superior only to warfarin in reducing ICH. In catheter ablation, dabigatran only reduced the groin hematoma. In AF patients with VHD, dabigatran did not show either superiority or inferiority to warfarin, further studies are needed. “Non-valvular AF” term is outdated and should be replaced with “type II VHD” to differentiate it from other valvular heart diseases that are accompanied by AF.
Is LVH a must in an amyloid heart?
Authors: Elganainy Mohammed N , Kazim Hameedullah M , Daood Muhammad S , Abdallah Amr , Elsaban Khaled , Althomali Muteb , Almalki Mazen M , Embaby Ahmed , Elsheikh Haitham , Elheet Ahmed A
Published: September 2024

Background

Transthyretin amyloidosis (ATTR), an infiltrative cardiomyopathy, is characterized by the infiltration of transthyretin-derived amyloid fibrils into the cardiac extracellular space, which causes morphological and functional heart damage. Because of the vast range of symptoms that can accompany ATTR cardiac amyloidosis, the illness remains unknown. However, misdiagnosis or delayed diagnosis due to inconsistencies between clinical findings and the severity of the underlying disease hampers treatment methods.

Aim and objectives

This article investigates the intricate relationship between ATTR amyloidosis pathogenesis and clinical signs to understand better the challenges and advancements in early discovery, treatment, and prognosis of this concealed sickness.

Methods & Results

Between November 2022 and April 2024, we conducted a prospective analysis on a cohort of 71 patients diagnosed with ATTR cardiac amyloidosis utilizing PYP imaging at our institution (Al Hada Armed Force Hospital, Taif, Saudi Arabia). The Medical Ethics Review Committee of the hospital accepted this project (2023-720). During our study, we faced two cases without LVH and both cases have grade II-III cardiac uptake.

1st case

A 66-year-old male patient who is a known case of ischemic cardiomyopathy with EF 35% since 2018, he underwent PCI in 2018. The patient is following the cardio clinic since 2018 and on every visit he was asymptomatic, The Patient in 2021 experienced new shortness of breath within six minutes’ walk distance less than 400 meters. The patient experienced erectile dysfunction and underwent intervention for his carpal tunnel syndrome. ECG showed old Q in anterior leads. Echo showed the same EF 35% and old wall motion abnormalities. Diagnostic coronary angiography showed patent stents and no residual ischemia. When we revised his old echo study that was done in 2017, we found EF 55%, concentric LVH. PYP bone scintigraphy was decided and showed grade II-III cardiac uptake.

2nd case

A 53-year-old hypothyroid female patient and she has metastatic left breast cancer. During her workup bone scan, grade III cardiac uptake was accidentally discovered using an HMDP isotope. The patient was referred to the cardio clinic where the patient denied any cardiac or non-cardiac symptoms. All her labs, ECG and Echo were within normal range. CMR showed diffuse subendocardial LGE suggestive of infiltrative disease.

Conclusion

Based on unique pathological features of CA that would present as morphological LVH with /without ECG evidence of LVH. We hypothesized that LVH would occur in the later stages of the disease or may be decreased due to other pathology as coronary artery disease. Clinical suspicion remains the cornerstone for early diagnosis and workup.
Atypical fractures at non-classical sites associated with anti-resorptive therapy: a systematic review
Authors: Collins Lucy , Ronan Alec , Hutcheon Evelyn , Ebeling Peter R , Grill Vivian , Nguyen Hanh H
Published: September 2024

Osteoporosis is common, affecting more than 20% of women and 6% of men globally over the age of 50. Anti-resorptive drugs, bisphosphonates and denosumab, have been effective treatments for osteoporosis for more than 30 years. Rare complications of anti-resorptive therapy include medication-related osteonecrosis of the jaw and atypical femur fractures (AFF). The American Society for Bone and Mineral Research (ASBMR) proposed a case definition for these atypical femoral fractures in 2010, which was updated in 2013. However, atypical fractures at non-classical sites have been increasingly described. We aimed to systematically identify atypical fracture cases excluded from the ASBMR AFF case definition in patients receiving anti-resorptive medication for longer than 3 yr. A structured search of electronic databases, including PubMed, Medline (Ovid), Embase (Ovid), Cochrane, and Web of Sciences, and hand-searching of conference abstracts were undertaken. All full-text articles written in English describing an atypical fracture in patients (aged >18 yr) and receiving anti-resorptive medication for >3 yr were included, with data extracted and analyzed by two independent reviewers. Sixty-six articles were identified, describing 151 cases of atypical fractures in 114 individuals. The most frequent fracture site was the ulna, followed by the tibia. All patients were taking anti-resorptive treatment prior to or at the time of fracture, most frequently alendronate monotherapy (44%). Most commonly, fractures were transverse in nature (95%), following minimal or no trauma (96%), and non-comminuted (98%) with cortical thickening of the surrounding bone (69%). Anti-resorptive treatment was ceased following an atypical fracture in the majority (89%). Atypical fractures are rare and should not deter physicians from appropriate anti-resorptive therapy for osteoporosis. However, clinicians should be alert to their presence at additional sites to the femur. An update of the current ASBMR AFF case definition to include other skeletal sites could be timely.
Genotype–phenotype correlations in 294 pediatric patients with osteogenesis imperfecta
Authors: Byrd Jay J , White Andrew C , Nissen Claire G , Schissel Makayla , Van Ormer Matthew , Velasco Danita , Wallace Maegen
Published: September 2024

Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility with extraskeletal manifestations mostly due to COL1A1 and COL1A2 variants. Currently, 23 genes have been implicated in the pathogenesis of OI; however, literature on genotype–phenotype correlation and incidence of non-skeletal clinical features are limited. This study aims to identify genotype–phenotype correlations in patients with OI, allowing clinicians to better inform families of prognosis, optimize patient care, and facilitate evidence-based clinical decision-making. We retrospectively reviewed 294 patients with OI to collect demographic data, clinical characteristics, and genotypic information. Patients were stratified by COL1A1/1A2 vs non-COL1A1/1A2 variants to evaluate differences in phenotype. The majority of OI was due to variants in COL1A1/1A2 (91%), with the remaining 9% due to non-COL1A1/1A2 variants. Most patients in the COL1A1/2 group were White compared to the non-COL1A1/2 group (78% vs 50%; p = 0.004). COL1A/1A2 patients had higher incidence of blue sclerae (83% vs 58%, p = 0.002), dentinogenesis imperfecta (49% vs 15%, p < 0.001), and family history of OI (34% vs 12%, p = 0.03). Those in the non-COL1A1/1A2 group have higher rates of scoliosis compared to those in the COL1A1/1A2 group (62% vs 40%, p = 0.04), as well as higher rates of expressive language disorder/delay (15% vs 0.4% in non-COL1A1/1A2 and COL1A1/1A2 patients, respectively; p < 0.001). Identifying the underlying molecular etiology early is imperative for optimal clinical care, allowing for appropriate risk counseling, identification of affected relatives, and improved anticipatory care and management. These data support that rare subtypes of OI occur more frequently in non-White individuals and demonstrated genetic associations with incidence of blue sclera, dentinogenesis imperfecta, scoliosis, and expressive language disorders.
Characterizing reproductive development in female white shrimp Penaeus setiferus (Decapoda: Dendrobranchiata: Penaeidae) in South Carolina, USA
Authors: Mitchell Alexandra C , Wagner Graham A , Kingsley-Smith Peter R , Brunson Jeff F , Kendrick Michael R
Published: September 2024

Accurate assessments of female reproductive development are an important component to the sustainable management of the fishery of the white shrimp Penaeus setiferus (Linnaeus, 1767) in the southeastern U.S. Reproductive development has been commonly assessed macroscopically based on ovarian color; however, distinguishing females that have never spawned from those that have previously spawned using this approach can be challenging due to their similarity in appearance. Histological approaches allow for higher resolution in quantifying microscopic phases of reproductive development and may reveal evidence of prior spawning events. Our objective was to characterize reproductive development and spawning activity in female P. setiferus through histology by: 1) defining major phases of reproductive development; 2) investigating and distinguishing the characteristics of oocyte atresia; and 3) using a standardized framework to describe the phenology of ovarian development in P. setiferus. Weekly samples of female P. setiferus were collected from March to June 2022 and ovarian tissues from 520 individuals were processed histologically. A detailed framework for distinguishing microscopically-observed ovarian development phases based on defining oocyte characteristics is provided. Oocyte atresia was observed in the ovarian tissue of 51% (N = 264) of individuals examined, with further examination differentiating between non-spawning atresia (N = 205) and post-spawning atresia (N = 59). Individuals with no atresia and non-spawning atresia were present from all sampling events, whereas individuals with post-spawning atresia first appeared on 22 April 2022. Our descriptions of ovarian development and oocyte atresia contribute to a growing framework of standardized microscopic assessments that should be tested more broadly for applicability to other commercially important crustaceans.
Delimiting species, revealing cryptic diversity in Molytinae (Coleoptera: Curculionidae) weevil through DNA barcoding
Authors: Ren Jinliang , Zhang Runzhi
Published: September 2024

The subfamily Molytinae (Coleoptera: Curculionidae), being the second largest group within the family Curculionidae, exhibits a diverse range of hosts and poses a serious threat to agricultural and forestry industries. We used 1,290 cytochrome c oxidase subunit I (COI) barcodes to assess the efficiency of COI barcodes in species differentiation and uncover cryptic species diversity within weevils of Molytinae. The average Kimura 2-parameter distances within species, genus, and subfamily were 2.90%, 11.0%, and 22.26%, respectively, indicating significant genetic differentiation at both levels. Moreover, there exists a considerable degree of overlap between intraspecific (0%–27.50%) and interspecific genetic distances (GDs; 0%–39.30%). The application of Automatic barcode gap discovery, Assemble Species by Automatic Partitioning, Barcode Index Number, Poisson Tree Processes (PTP), Bayesian Poisson Tree Processes (bPTP), and jMOTU resulted in the identification of 279, 275, 494, 322, 320, and 279 molecular operational taxonomic units, respectively. The integration of 6 methods successfully delimited species of Molytinae in 86.6% of all examined morphospecies, surpassing a threshold value of 3% GD (73.0%). A total of 28 morphospecies exhibiting significant intraspecific divergences were assigned to multiple MOTUs, respectively, suggesting the presence of cryptic diversity or population divergence. The identification of cryptic species within certain morphological species in this study necessitates further investigation through comprehensive taxonomic practices in the future.
Anatomy of a pest control failure: introgression of cytochrome P450 337B3 alleles from invasive old-world bollworm into native corn earworm (Lepidoptera: Noctuidae)
Authors: Nufer Marissa I , Coates Brad S , Abel Craig A , O’Neill Patrick , McCracken Morgan , Jain Devendra , Pierce Calvin A , Glover James , Towles Tyler , Reddy Gadi V P , Perera Omaththage P
Published: September 2024

The establishment of invasive species populations can threaten the ecological balance in naïve habitats and impact agricultural production practices. Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) (old-world bollworm, OWBW) and Helicoverpa zea (corn earworm, CEW) were geographically separated prior to the 2013 report of OWBW invasion into South America. Introgression of OWBW-specific cytochrome P450 337B3 (CYP337B3) gene into CEW was repeatedly detected across South America and the Caribbean. Two hybrids were documented from Texas in 2019. In this study, screening insects collected in Olathe, CO, USA, where a failure of pyrethroids to control CEW damage to conventional sweetcorn in 2023 detected 28.6% of insects with the OWBW-specific CYP337B3 marker. Nucleotide sequencing of the CYP337B3 gene identified 73.1% and 26.9% of insects carried CYP337B3v2 and CYP337B3v6 alleles, respectively, and 0.15 overall frequency of CYP337B3 alleles. Based on prior data for distinct phylogeographic origins of CYP337B3v2 and v6 alleles, our results indicate Olathe samples were derived from 2 different introductions: An uncertain source of the v6 allele that was initially reported in West Africa and possibly South American or Caribbean origin of the globally distributed v2 allele. One of the 1618 individuals screened also carried a ribosomal RNA internal transcribed spacer 1 derived from OWBW. Local selection pressures at the Olathe location imposed by repeated pyrethroid exposures are likely attributed to the prevalence of CYP337B3, where control practices hasten the accumulation of phenotypic resistance by adaptive introgression. Pyrethroid and other resistance factors carried by invasive OWBW may continue to impact CEW management tactics across the Americas.
The influence of self-generated song during aggression on brain serotonin levels in male crickets
Authors: Itoh Masanori T
Published: September 2024

Pairs of adult male crickets, Gryllus bimaculatus, fight and immediately determine winner and loser statuses. The winner male repeatedly produces an aggressive (rival) song by rubbing his forewings together. In this study, I removed the plectrum, a sound-producing structure in the forewing, from male crickets and measured their brain serotonin (5-hydroxytryptamine: 5-HT) levels immediately after a 10-min aggressive interaction. Pairs of plectrum-removed males fought and established clear winner–loser relationships, like the case of intact males. The plectrum-removed winner males frequently rubbed their forewings together, but were unable to produce song. Aggressive interaction reduced significantly brain 5-HT levels in the plectrum-removed males, regardless of their winner and loser statuses. Furthermore, the reduction of brain 5-HT was detected primarily in the central body, a group of neuropils spanning the midline of the brain. In contrast, in pairs of intact males, aggressive interaction reduced brain 5-HT levels in the loser males, but not in the winner males. Plectrum removal alone did not affect the brain’s 5-HT levels. These results suggest that aggressive song emitted by the winner male cricket prevents the reduction of 5-HT levels in his own brain, especially in the central body.
Peroxisomal import stress activates integrated stress response and inhibits ribosome biogenesis
Authors: Kim Jinoh , Huang Kerui , Vo Pham Thuy Tien , Miao Ting , Correia Jacinta , Kumar Ankur , Simons Mirre J P , Bai Hua
Published: September 2024

Impaired organelle-specific protein import triggers a variety of cellular stress responses, including adaptive pathways to balance protein homeostasis. Most of the previous studies focus on the cellular stress response triggered by misfolded proteins or defective protein import in the endoplasmic reticulum or mitochondria. However, little is known about the cellular stress response to impaired protein import in the peroxisome, an understudied organelle that has recently emerged as a key signaling hub for cellular and metabolic homeostasis. To uncover evolutionarily conserved cellular responses upon defective peroxisomal import, we carried out a comparative transcriptomic analysis on fruit flies with tissue-specific peroxin knockdown and human HEK293 cells expressing dominant-negative PEX5C11A. Our RNA-seq results reveal that defective peroxisomal import upregulates integrated stress response (ISR) and downregulates ribosome biogenesis in both flies and human cells. Functional analyses confirm that impaired peroxisomal import induces eIF2α phosphorylation and ATF4 expression. Loss of ATF4 exaggerates cellular damage upon peroxisomal import defects, suggesting that ATF4 activation serves as a cellular cytoprotective mechanism upon peroxisomal import stress. Intriguingly, we show that peroxisomal import stress decreases the expression of rRNA processing genes and inhibits early pre-rRNA processing, which leads to the accumulation of 47S precursor rRNA and reduction of downstream rRNA intermediates. Taken together, we identify ISR activation and ribosome biogenesis inhibition as conserved adaptive stress responses to defective peroxisomal import and uncover a novel link between peroxisomal dysfunction and rRNA processing.
Systemic inflammation in asymptomatic hyperuricaemia with sonographic crystal deposits, including a comparison with normouricaemia and gout
Authors: Peral-Garrido María-Luisa , Gómez-Sabater Silvia , Caño Rocío , Bermúdez-García Alejandra , Boix Paula , Lozano Teresa , Sánchez-Ortiga Ruth , Perdiguero Miguel , Caro-Martínez Elena , Ruiz-García Carolina , Francés Rubén , Pascual Eliseo , Andrés Mariano
Published: September 2024

Objective

To describe the inflammatory profile of asymptomatic hyperuricaemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout and normouricaemia.

Methods

Based on serum urate levels, musculoskeletal ultrasound and history of flares, we divided 122 participants into four groups: normouricaemia, AH-MSUneg, AH-MSUpos and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2–3 (G2–3) double contour and/or tophi, G1–3 double contour and/or tophi, G1–3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint) and G2–3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricaemics.

Results

Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-β and galectin-3 were higher in hyperuricaemics vs normouricaemics. Sex, obesity and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUpos  vs AH-MSUneg groups, except for higher calprotectin using G1–3 sonographic definitions and higher CRP and TGF-β when restricted to women and obese participants.

Conclusions

Hyperuricaemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-β. Sex, obesity, and comorbidities influenced some inflammatory responses.
The appointment of trustees, disclaimer of gifts and legal personality: fundamental principles and conceptual limits
Authors: Walsh Xavier P , Cordeschi Daniel B
Published: September 2024

What happens when an executor of a Will is gifted property under that Will in its capacity as trustee of an existing trust but later disclaims the gift in that capacity? What purpose is served by the executor then seeking to be appointed by the Court as trustee over the same property? These questions were presented by the unique facts in Perpetual Trustee Company Ltd v University of New South Wales [2023] NSWSC 1061. This article uses the facts and decision in Perpetual to explore fundamental principles and conceptual limits concerning: the Court’s jurisdiction(s) to appoint trustees; the proposition that a trustee can(not) hold property on trust for itself; and the disclaimer of gifts.
Efficacy of Sentinel Cerebral Embolic Protection Device in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials and Propensity Score-Matched Studies
Authors: Jain Hritvik , Pervez Neha , Dey Debankur , Odat Ramez M. , Jain Jyoti , Goyal Aman , Saggar Anmol , Hussein Ayham Mohammad , Mathur Aniket , Khanna Sukul , Ahmed Raheel , Shahid Farhan
Published: September 2024

Transcatheter aortic valve replacement (TAVR) is frequently associated with stroke due to debris embolization. Although the risk of stroke with newer-generation devices is lower, stroke still represents a significant cause of mortality and morbidity post-TAVR. The Sentinel cerebral embolic protection device (CEPD) is a dual-embolic filter device designed to capture debris dislodged during TAVR. A systematic literature search was performed on the major bibliographic databases to retrieve studies that compared TAVR with and without Sentinel CEPD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian–Laird random-effects model, with a P value of <0.05 considered statistically significant. This meta-analysis included 6 studies with 25,130 patients undergoing TAVR (12,608: Sentinel CEPD; 12,522: without Sentinel CEPD). The use of the Sentinel CEPD in TAVR was associated with a statistically significant lower risk of acute kidney injury (OR: 0.89; 95% CI: 0.81–0.97; P = 0.01]. The use of Sentinel CEPD in TAVR was associated with a statistically insignificant trend toward a reduction in stroke (OR: 0.80; 95% CI: 0.58–1.10; P = 0.18), all-cause mortality (OR: 0.74; 95% CI: 0.51–1.07; P = 0.11), and major vascular complications (OR: 0.74; 95% CI: 0.46–1.19; P = 0.21). The use of Sentinel CEPD in patients undergoing TAVR does not lead to a statistically significant reduction in stroke, all-cause mortality, or major vascular complications; however, the risk of acute kidney injury is lower. Further randomized studies are warranted to confirm these findings.
Outcomes of Xenograft with Platelet-rich Fibrin versus Autogenous Bone in Alveolar Cleft Grafting
Authors: Bedeer Hager Montaser , Asklany Awny , Ali Wagdi M. , Elyounsi Mohamed , Mohammed Mohamed Nahed Attia , Youssef Mostafa Mahmoud , El-shazly Mohamed
Published: September 2024

Background:

The use of a suitable graft material helps with sufficient osseointegration. The aim of this study was to compare the clinical and radiographic outcomes of two types of alveolar bone graft materials, xenografts with platelet-rich fibrin (PRF) and autogenous grafts, in patients with alveolar clefts.

Methods:

Thirty-six patients with alveolar clefts were enrolled in this study. Those patients were randomly divided into two groups: group A, where the autogenous iliac bone graft was used to fill the alveolar defect, and group B, where the xenograft with PRF was used to fill the alveolar defect. After 6 months of grafting, patients were assessed in terms of pain, duration of hospital stay, and donor site morbidity associated with iliac crest harvesting, while bone formation was evaluated radiographically using cone beam computed tomography.

Results:

The results showed no statistical differences as regards baseline and perioperative data. Operative duration was significantly lower among xenograft with PRF patients. Both groups had comparable postoperative success scores, and total failure was reported in a total of three patients (one patient in group A and two patients in group B).

Conclusions:

With no potential donor site morbidities, xenograft with PRF is an equivalent bone transplant replacement to the autologous iliac bone graft. Additionally, it is associated with a significant success rate, and a significant decrease in operative time and hospital stay. Many future studies are warranted to draw firm conclusions.
Transplantation for immune dysregulatory disorders: current themes and future expectations
Authors: McClory Susan E. , Oved Joseph H.
Published: September 2024

Purpose of review

Primary immune regulatory disorders (PIRDs) are an increasing indication for hematopoietic stem cell transplant (HCT) in pediatric patients. Here, we provide an updated overview of HCT for PIRDs, and discuss future avenues for improvement in outcomes.

Recent findings

There are now more than 50 described monogenic PIRDs, which impact all aspects of immune tolerance, regulation, and suppression. Disease characteristics are highly variable, and HCT remains the only option for cure. We review advances in targeted therapies for individual PIRDs, which have significantly improved outcomes and the ability to safely bridge to transplant. Additionally, advances in GVHD prevention, graft manipulation, personalized conditioning regimens, and supportive care have all increased survival after HCT. The high inflammatory state increases the risk of nonengraftment, rejection, and autologous reconstitution. Therapy to reduce the inflammatory state may further improve outcomes. In addition, although younger patients with fewer comorbidities have better outcomes, the clinical courses of these diseases may be extremely variable thereby complicating the decision to proceed to HCT.

HCT for PIRDs is a growing consideration in cell therapy. Yet, there remain significant gaps in our understanding of which patients this curative therapy could benefit the most. Here, we review the current data supporting HCT for PIRDs as well as areas for future improvement.
Causal relationships between leukocyte telomere length and female reproductive system diseases: A bidirectional Mendelian randomization study
Authors: She Jun-Sen , Liu Rui , Mao Su-Qing , Wu Xiao-Jing , Ding Meng-Zhen , Wang Ling-Xiang , Cao Yi-Ning , Wu Hai-Yan , Long Yu-Hang , Guo Fei , Zhou Bo-Kang , Gao Ling , Huang He-Feng
Published: September 2024

Objective:

Although numerous observational studies have revealed a correlation between leukocyte telomere length (LTL) and female reproductive system diseases (RSDs), the findings of these studies have tended to be consistent. In this study, we accordingly sought to clarify the causal relationships between LTL and RSDs.

Methods:

We performed a bidirectional two-sample Mendelian randomization (MR) analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs. The final results were analyzed using five MR methods, with the inverse variance weighted (IVW) method used as the primary outcome. We applied MR-PRESSO to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.

Results:

In the forward MR analysis, a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis (IVW: OR = 1.25, 95%CI: 1.06–1.46, P = 0.008), leiomyoma of the uterus (IVW: OR = 1.73, 95%: 1.52–1.98, P = 4.9E-16) and ovarian cysts (IVW: OR = 1.31, 95%:1.19–1.45, P = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all P-values > 0.05). Sensitivity analysis confirmed the robustness of these results.

Conclusions:

Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis, leiomyoma of the uterus, and ovarian cysts, with no influence of RSDs on LTL. These findings contribute to establishing a causal link between LTL and RSDs, overcoming the constraints of earlier observational studies. They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis, leiomyoma of the uterus, and ovarian cysts.
Perioperative Fully Closed-loop versus Usual Care Glucose Management in Adults Undergoing Major Abdominal Surgery – A Two-centre Randomised Controlled Trial
Authors: Krutkyte Gabija , Goerg Arna M C , Grob Christian A , Piazza Camillo D , Rolfes Eva-Dorothea , Gloor Beat , Wenning Anna S , Beldi Guido , Kollmar Otto , Hovorka Roman , Wilinska Malgorzata E , Herzig David , Vogt Andreas P , Girard Thierry , Bally Lia
Published: September 2024

Objective:

To assess the efficacy and safety of fully closed-loop (FCL) compared with usual care (UC) glucose control in patients experiencing major abdominal surgery-related stress hyperglycaemia.

Summary Background Data:

Major abdominal surgery-related stress and periprocedural interventions predispose to perioperative hyperglycaemia, both in diabetes and non-diabetes patients. Insulin corrects hyperglycaemia effectively, but its safe use remains challenging.

Methods:

In this two-centre randomised controlled trial, we contrasted subcutaneous FCL with UC glucose management in patients undergoing major abdominal surgery anticipated to experience prolonged hyperglycaemia. FCL (CamAPS HX, Dexcom G6, mylife YpsoPump 1.5x) or UC treatment was used from hospital admission to discharge (max 20 d). Glucose control was assessed using continuous glucose monitoring (masked in the UC group). The primary outcome was the proportion of time with sensor glucose values in target range 5.6-10.0 mmol/L.

Results:

Thirty-seven surgical patients (54% pancreas, 22% liver, 19% upper gastrointestinal, 5% lower gastrointestinal), of whom 18 received FCL and 19 UC glucose management, were included in the analysis. Mean±SD percentage time with sensor glucose in target range was 80.1±10.0% in the FCL and 53.7±19.7% in the UC group (P<0.001). Mean±SD glucose was 7.5±0.5 mmol/L in the FCL and 9.1±2.4 mmol/L in the UC group (P=0.015). Time in hypoglycaemia (<3.0 mmol/L) was low in either group. No study-related serious adverse events occurred.

Conclusions:

The FCL approach resulted in significantly better glycaemic control compared to UC management, without increasing the risk of hypoglycaemia. Automated glucose-responsive insulin delivery is a safe and effective strategy to minimise hyperglycaemia in complex surgical populations.
Corporal aspiration and sympathomimetic injection for priapism: “Preprocedure preparation” and “procedural considerations”
Authors: Huang I-Shen , Bennett Nelson E. , Huang William J.
Published: September 2024

Priapism is a prolonged and persistent erection that lasts more than 4 hours and is unrelated to sexual stimulation. Although uncommon, it requires expeditious treatment to prevent erectile function compromise. Corporal aspiration is the first-line treatment for patients with ischemic priapism. This article focuses on contemporary corporal aspiration techniques for the management of priapism. After obtaining informed consent and administering local anesthesia, corporal aspiration was initiated by inserting 2 large-bore butterfly needles into the penile shaft. Aspiration is then performed using 10-mL syringes to decompress the corporeal pressure, flush out clots, and restore the pH balance of the penis. Diluted phenylephrine (100–1000 μg/mL) is injected in 1 mL aliquots every 5 to 10 minutes until complete detumescence is achieved. The results show that the overall resolution rate using corporal aspiration followed by phenylephrine injection is 65% to 72%. Ninety percent of men experience detumescence success if aspiration and phenylephrine injection are performed within 12 hours. Conversely, 85% of patients with priapism may require penile shunt surgery if the priapism exceeds 24 hours, and in the majority of these patients, health care providers will consider placing a penile prosthesis if the priapism exceeds 36 hours. Corporal aspiration is the first-line treatment for priapism. When properly performed expeditiously, patients experience a high rate of detumescence. Ischemic priapism is a true urological emergency that requires prompt diagnosis and treatment. The advantages of using corporal aspiration as a first-line treatment include pain relief and the prompt restoration of circulation.
Risk factors for urinary retention requiring catheterization after ischemic middle cerebral artery stroke
Authors: Chiu Tai-Hua , Chen Yu-Chen , Wu Meng-Ni , Juan Yung-Shun , Lin Yi-Hui , Chen Hao-Wei
Published: September 2024

Purpose:

Urinary retention is common in patients with ischemic stroke. Therefore, we aimed to identify the risk factors for urinary retention requiring indwelling urinary catheters (IUCs) in patients with acute middle cerebral artery (MCA) ischemic stroke.

Materials and methods:

We retrospectively reviewed the medical records of all patients with acute MCA infarction who required admission to the neurological intensive care unit between January 2009 and December 2019 at our tertiary hospital. Patients who did not need IUCs before the stroke but required them after the stroke were included. Multivariate logistic regression analysis was used to identify the risk factors associated with urinary retention requiring IUCs after 7, 14, 21, and 28 days of stroke.

Results:

A total of 104 patients were included in this study. Among them, 75 (72.2%), 65 (62.5%), 52 (50.0%), and 44 (42.3%) patients required IUCs 7, 14, 21, and 28 days after stroke, respectively. Multivariate logistic regression analysis showed that hypertension was associated significantly with the requirement of IUCs 7 days (odds ratio [OR] = 2.987; P = 0.026) and 14 days (OR = 3.047; P = 0.021) after acute stroke. Furthermore, a higher National Institutes of Health Stroke Scale score was associated significantly with the requirement for IUCs 14 days (OR = 1.096; P = 0.030) and 21 days (OR = 1.091; P = 0.027) after stroke.

Conclusion:

Hypertension and higher National Institutes of Health Stroke Scale scores are associated significantly with urinary retention requiring IUCs after acute ischemic MCA stroke and could serve as risk factors for voiding dysfunction in this population.
The association of 5-alpha reductase inhibitors treatment with prostate cancer in benign prostate hyperplasia patients: A population-based case-control study
Authors: Lee Sz-En , Chiu Kun-Yuan , Wang Shian-Shiang , Cheng Chen-Li , Lin Ching-Heng , Li Jian-Ri
Published: September 2024

Purpose:

Benign prostatic hyperplasia (BPH) is the most common cause of difficult voiding in elderly men. Alpha-blockers and 5-alpha reductase inhibitors (5ARIs) are evidence-based standards of care in treating BPH according to current guidelines. We have conducted a nationwide population-based study to evaluate the association of 5ARIs treatment with prostate cancer in patients with benign prostate hyperplasia.

Materials and methods:

Between 2005 and 2010, patient data from the National Health Insurance Research Database were obtained. Newly diagnosed patients with BPH were divided into 2 groups: prostate cancer group and BPH group. We conducted a retrospective study on their history of medication usage with 5ARIs. Results were compared with a matched noncancerous control group. The outcome measurements were the incidence and the prostate cancer diagnosis-free survival rate after the BPH index date. Statistical analyses included t test, chi-square test, multivariable logistic regression analysis, and Kaplan-Meier curves with log-rank tests.

Results:

A total of 18,620 newly diagnosed patients with BPH were selected. After eliminating patients according to the exclusion criteria, a total of 17,716 patients were enrolled as the study subjects. Among them, 530 patients (2.99%) developed prostate cancer and 17,186 (97.01%) did not. The mean age of the total case-control study was 69.1 years. The odds ratio of prostate cancer in patients with BPH with 5ARIs usage was 1.14 with a P value of 0.539, indicating that the use of 5ARIs was not associated with a higher risk of developing prostate cancer. Multivariate analysis showed no significant intergroup difference in the risk of developing prostate cancer (odds ratio = 1.14, 95% CI: 0.75–1.74, P = 0.539). A subgroup survival analysis, observing the time interval from BPH diagnosis to the development of prostate cancer based on 5ARIs usage, revealed a nonsignificant difference in the prostate cancer diagnosis-free survival rate, with a P value of 0.3592.

Conclusion:

The 5ARI usage in patients with BPH was not associated with increased risk of developing prostate cancer. Furthermore, the prostate cancer diagnosis-free survival rate, when stratified based on 5ARIs usage, showed no statistically significant difference. Under our health insurance regulation and clinical practice, 5ARIs are consider safe in treating BPH.
Experimental study into the effects of pitch and coning angles on the flight performance of the natural samara
Authors: Jung Byung Kwon , Rezgui Djamel
Published: September 2024

Using their light wing and through the use of a leading-edge vortex (LEV), autorotating samaras can generate high lift while descending at extremely low speeds. But the flight performance of the samara, with respect to the wide design envelope, is still not well understood. Therefore, this paper aims to experimentally assess how the flight performance of three natural samara wings varies with differing wind speeds and flight conditions. The tests were conducted within a vertical wind tunnel and a novel rig was devised to effectively measure the vertical thrust and rotational rate of the autorotating samara at near frictionless conditions. Furthermore, a bespoke hub was implemented to control the coning and pitch angles of the samara wing. The tests generated a novel and comprehensive set of experimental data of autorotating samaras with changing wind speed, coning and pitch angles. The results also revealed that coning angles between 5 and 15 degrees can increase the vertical thrust produced by the samara by up to a maximum of

9.6
%

. Additionally, it was found that samaras operate at extremely low pitch angles between −0.7 and −2.6 degrees to maximise their thrust, even though the conditions are close to the autorotational stability boundary.
The nuclear lamin network passively responds to both active or passive cell movement through confinements
Authors: Amiri Sirine , Bos Inge , Reyssat Etienne , Sykes Cécile
Published: September 2024

Physical models of cell motility rely mostly on cytoskeletal dynamical assembly. However, when cells move through the complex 3D environment of living tissues, they have to squeeze their nucleus that is stiffer than the rest of the cell. The lamin network, organised as a shell right underneath the nuclear membrane, contributes to the nuclear integrity and stiffness. Yet, its response during squeezed cell motility has never been fully characterised. As a result, up to now, the interpretations on the lamin response mechanism are mainly speculative. Here, we quantitatively map the lamin A/C distribution in both a microfluidic migration device and a microfluidic aspiration device. In the first case, the cell is actively involved in translocating the nucleus through the constriction, while in the second case, the cell behaves as a passive object that is pushed through the constriction by an external pressure. Using a quantitative description of the lamin shell response based on mass conservation arguments applied on the fluorescence signal of lamin, we show that in both cases of migration and aspiration, the response of the lamin network is passive. In this way, our results not only further elucidate the lamin response mechanism, but also allow to distinguish this passive deformation response from other active responses that may occur when the nucleus is squeezed through constrictions.
Generation of synthetic TSPO PET maps from structural MRI images
Authors: Ferrante Matteo , Inglese Marianna , Brusaferri Ludovica , Toschi Nicola , Loggia Marco L
Published: September 2024

Background

Neuroinflammation, a pathophysiological process involved in numerous disorders, is typically imaged using [11C]PBR28 (or TSPO) PET. However, this technique is limited by high costs and ionizing radiation, restricting its widespread clinical use. MRI, a more accessible alternative, is commonly used for structural or functional imaging, but when used using traditional approaches has limited sensitivity to specific molecular processes. This study aims to develop a deep learning model to generate TSPO PET images from structural MRI data collected in human subjects.

Methods

A total of 204 scans, from participants with knee osteoarthritis (n = 15 scanned once, 15 scanned twice, 14 scanned three times), back pain (n = 40 scanned twice, 3 scanned three times), and healthy controls (n=28, scanned once), underwent simultaneous 3T MRI and [11C]PBR28 TSPO PET scans. A 3D U-Net model was trained on 80% of these PET-MRI pairs and validated using 5-fold cross-validation. The model’s accuracy in reconstructed PET from MRI only was assessed using various intensity and noise metrics.

Results

The model achieved a low voxel-wise mean squared error (0.0033 ± 0.0010) across all folds and a median contrast-to-noise ratio of 0.0640 ± 0.2500 when comparing true to reconstructed PET images. The synthesized PET images accurately replicated the spatial patterns observed in the original PET data. Additionally, the reconstruction accuracy was maintained even after spatial normalization.

Conclusion

This study demonstrates that deep learning can accurately synthesize TSPO PET images from conventional, T1-weighted MRI. This approach could enable low-cost, noninvasive neuroinflammation imaging, expanding the clinical applicability of this imaging method.
ACE1 Does Not Influence Cerebral Aβ Degradation or Amyloid Plaque Accumulation in 5XFAD Mice
Authors: Jeon Sohee , Alia Alia O. , Popovic Jelena , Vassar Robert J. , Cuddy Leah K.
Published: September 2024

Alzheimer’s disease (AD) is the most common form of dementia, and multiple lines of evidence support the relevance of Aβ deposition and amyloid plaque accumulation in the neurotoxicity and cognitive decline in AD. Rare mutations in angiotensin-converting-enzyme-1 (ACE1) have been highly associated with late onset AD patients; however, the mechanism for ACE1 mutation in AD pathogenesis is unknown. Given the relevance of ACE1 with AD and the strong association of Aβ to AD pathogenesis, we investigated whether ACE1 degrades Aβ and affects amyloid burden in 5XFAD micein vivo. To investigate this, we analyzed 6-month-old 5XFAD mice with ACE1 loss of function. ACE1 loss of function was mediated either by crossing 5XFAD mice to ACE1 conditional knockout mice or administering 5XFAD mice with the ACE1 inhibitor enalapril. Our analyses revealed that ACE1 loss of function through both genetic and pharmacological methods does not affect amyloid plaque load and neuroinflammation in the hippocampus and cortex of 5XFAD mice.