bluuebunny/crossref_metadata_2025 huggingface dataset:
Blanking of Stainless Steel
Authors: Pätzold I , Tröber P , Welm M , Volk W
Published: May 2022

Slug pulling, adhesion formation and edge fracture are major challenges in the sheet metal processing industry. They lead to a strong reduction in part quality, process stability as well as profitability. In this study, investigations are carried out on stainless steel X5CrNi18-10 to address the previous mentioned challenges. While slug pulling and edge fracture strongly depend on the geometric characteristics of active elements as well as the selection of process parameters, adhesion formation is mainly determined by temperature and thermoelectric currents. In this publication, the influence of the die channel geometry on the slug pulling effect and the part quality is investigated. Furthermore, the temperature profile over the shear cutting process as well as the resulting thermoelectric currents are determined for the test material. The relationship between edge crack sensitivity, shear cutting parameters and strategies is examined. These investigations thus form the basis for an improved understanding of the shear cutting of stainless steel.
Optimisation of deep drawn corners subject to hot stamping constraints using a novel deep-learning-based platform
Authors: Attar H R , Li N
Published: May 2022

State-of-the-art hot stamping processes offer improved material formability and therefore have potential to successfully form challenging components. The feasibility of components to be formed through these processes is dependent on their geometric design and its complex interactions with the hot stamping environment. In industrial practice, trial-and-error approaches are currently used to update non-feasible designs where simulation runs are needed each time a design change is made. These approaches make the design process resource intensive and require considerable numerical and process expertise. To demonstrate a superior approach, this study presents a novel application of a deep-learning-based optimisation platform which adopts a non-parametric geometric modelling strategy. Here, deep drawn corner geometries from different geometry subclasses were optimised to minimise wasted volume due to radii while avoiding excessive post-stamping thinning. A neural network was trained to generate families of deep drawn corner geometries where each geometry was conditioned on an input latent vector. Another neural network was trained to predict the thinning distributions obtained from forming these geometries through a hot stamping process. Guided by these distributions, the latent vector, and therefore geometry, was iteratively updated by a new gradient-based optimisation technique. Overall, it is demonstrated that the platform is capable of optimising geometries, irrespective of complexity, subject to imposed post-stamped thinning constraints.
From effective-index model to phase-plate model
Authors: van Exter M P , Hissink E S , Koks C
Published: May 2022

In 1995, Hadley formulated an elegant effective-index model to describe the formation of transverse modes in optical cavities (Hadley 1995 Opt. Lett.
20 1483–5). We apply this model to Fabry–Perot cavities and discuss its limitations, using the well-known paraxial solutions of these cavities as reference. We also introduce a new model, which we call the phase-plate model, that has less limitations and yields the correct first-order correction to the resonance frequencies for longer cavities. The analysis uses scalar optical fields in the paraxial limit.
Cross-focusing of two chirped Gaussian laser beams and THz wave generation in plasmas of multi-ion species under a weakly relativistic and ponderomotive regime
Authors: JAFARI MILANI M R , REZAEI S , JAFARI M J
Published: May 2022

The generation of terahertz (THz) waves via the beating of two high-intensity chirped Gaussian lasers in a multi-ion-species plasma is numerically studied by taking into account the weak relativistic and ponderomotive regime of interaction. The coupled differential equations for beamwidth parameters are extracted by introducing the dielectric function of such plasma and using WKB and paraxial ray approximations. The amplitude of THz radiation at beat frequency resulting from the nonlinear current density induced by the beat ponderomotive force of the cross-focusing of beams was obtained. The impacts of the chirp frequency parameter, initial laser intensity and initial ionic species density (specifically, the presence of singly and doubly charged ions) in the plasma on THz generation were discussed. Our numerical results reveal that THz radiation generation strongly depends on the chirp frequency parameter. A specific range of chirp frequencies exists for self-focusing as well as THz generation with a ‘turning point’, where the THz emission reaches its maximum value. The results show that the strength of self-focusing and consequently the generated THz radiation are reduced by increasing the density of doubly charged ionic species in the plasma due to the suppression of the nonlinear effects.
Do Side Effects to the Primary COVID-19 Vaccine Reduce Intentions for a COVID-19 Vaccine Booster?
Authors: Geers Andrew L , Clemens Kelly S , Colagiuri Ben , Jason Emily , Colloca Luana , Webster Rebecca , Vase Lene , Seig Mette , Faasse Kate
Published: May 2022

Background

Vaccines are being administered worldwide to combat the COVID-19 pandemic. Vaccine boosters are essential for maintaining immunity and protecting against virus variants. The side effects of the primary COVID-19 vaccine (e.g., headache, nausea), however, could reduce intentions to repeat the vaccination experience, thereby hindering global inoculation efforts.

Purpose

The aim of this research was to test whether side effects of a primary COVID-19 vaccine relate to reduced intentions to receive a COVID-19 booster. The secondary aim was to test whether psychological and demographic factors predict booster intentions.

Methods

Secondary data analyses were conducted on a U.S. national sample of 551 individuals recruited through the online platform Prolific. Key measures in the dataset were side effects reported from a primary COVID-19 vaccination and subsequent intentions to receive a booster vaccine. Psychological and demographic variables that predicted primary vaccination intentions in prior studies were also measured.

Results

Booster intentions were high. COVID-19 booster vaccine intentions were uncorrelated with the number of side effects, intensity of side effects, or occurrence of an intense side effect from the primary COVID-19 vaccine. Correlational and regression analyses indicated intentions for a booster vaccination increased with positive vaccination attitudes, trust in vaccine development, worry about the COVID-19 pandemic, low concern over vaccine side effects, and democratic political party affiliation.

Conclusions

Side effects of a primary COVID-19 vaccine were not directly associated with lower intentions to receive a booster of the COVID-19 vaccine early in the pandemic. However, many variables that predict primary vaccination intentions also predict booster intentions.
The Role of Physical Activity in Long-term Weight Loss: 36-month Results From a Randomized Controlled Trial
Authors: Butryn Meghan L , Crane Nicole T , Lufburrow Emily , Hagerman Charlotte J , Forman Evan M , Zhang Fengqing
Published: May 2022

Background

Physical activity (PA) may promote long-term weight loss, but facilitating high levels of PA in behavioral weight loss programs is challenging.

Purpose

This study reports the 36-month follow-up of a behavioral weight loss trial that tested the efficacy of increasing the emphasis on PA during treatment and using traditional or acceptance-based therapy (ABT) for this purpose. We also examined the extent to which long-term weight loss differed by PA pattern and tested if individual differences in eating behavior moderated this relationship.

Methods

Participants (N = 320) were randomized to (1) standard behavioral weight loss treatment (BT), (2) BT with a focus on PA, or (3) ABT with a focus on PA. Weight loss and PA were measured at 24- and 36-month follow-up.

Results

There were no differences between conditions in weight loss or PA at 24 or 36 months. Participants consistently engaging in high PA experienced the greatest weight losses. The positive impact of PA on weight loss was more pronounced among those with low emotional eating and those who believed that exercise did not affect their appetite.

Conclusions

Findings emphasize the difficulty of improving long-term PA among adults with overweight/obesity beyond what standard behavioral weight loss treatment achieves. This study highlights the need to develop new PA treatment strategies, and suggests that ABT for weight loss may be more effective when applied to eating behavior versus PA. Results also demonstrate the importance of addressing problematic eating behavior and cognitions to fully realize the benefits of PA for weight loss.

Clinical Trial information

ClinicalTrials.gov identifier: NCT02363010
Age-Related Changes in the Submandibular Gland: An Imaging Study of Gland Ptosis Versus Volume
Authors: McCleary Sean P , Moghadam Shahrzad , Le Christina , Perez Kevin , Sim Myung-Shin , Roostaeian Jason
Published: May 2022

Background

Debate surrounding the morphological evolution of the submandibular gland (SMG) with aging, and the uncertain influence of patient demographics, has led to hesitancy about incorporating targeted interventions of the SMG into clinical practice.

Objectives

The aim of this study was to determine whether SMG ptosis, hypertrophy, or both is the primary etiology behind the increase in submandibular volume with age.

Methods

MRI segmentation was used to calculate the total and inframandibular (IM) volume and height of the SMG. Adult subjects with previous MRIs of the head and neck were used for analysis. Those with pathology or artifact compromising the SMG were excluded. Subjects were divided into 4 age-defined cohorts, for clinical applicability.

Results

The study included 129 patients (65 females; 64 males) with a mean age of 52.3 years (range, 20-85 years). No significant change in total SMG volume was observed between the reference group and all cohorts. The IM-SMG volume of the reference cohort was 5.77 cm3. All 3 cohorts had a greater IM-SMG volume than the reference group. The 45- to 54-year cohort had a mean volume of 6.7 cm3 (P = 0.4), the 55- to 64-year cohort, 7.5 cm3 (P = 0.01), and the ≥65-year cohort, 7.2 cm3 (P = 0.01). Male sex and overweight or obese BMI were associated with significantly larger total and IM-SMG volumes.

Conclusions

The novel finding of a significantly larger IM-SMG volume with no change in total volume provides evidence for SMG ptosis rather than hypertrophy as a significant contributor to age-related submandibular fullness. The lack of any significant difference in total volume or height with aging emphasizes the role of glandular descent.
2022 Practice Recommendation Updates From the World Consensus Conference on BIA-ALCL
Authors: Santanelli di Pompeo Fabio , Clemens Mark W , Atlan Michael , Botti Giovanni , Cordeiro Peter G , De Jong Daphne , Di Napoli Arianna , Hammond Dennis , Haymaker Cara L , Horwitz Steven M , Hunt Kelly , Lennox Peter , Mallucci Patrick , Miranda Roberto N , Munhoz Alexandre M , Swanson Eric , Turner Suzanne D , Firmani Guido , Sorotos Michail
Published: May 2022

Background

Laboratory and clinical research on breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

Objectives

The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

Methods

A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing conditions separate from BIA-ALCL were excluded. The study was conducted employing the Delphi process, gathering 18 experts panelists and utilizing email-based questionnaires to record the level of agreement with each statement by applying a 5-point Likert Scale. Median response, interquartile range, and comments were employed to accept, reject, or revise each statement.

Results

The literature search initially yielded 764 manuscripts, of which 405 were discarded. From the remaining 359, only 218 were included in the review and utilized to prepare 36 statements subdivided into 5 sections. After 1 round, panelists agreed on all criteria.

Conclusions

BIA-ALCL is uncommon and still largely underreported. Mandatory implant registries and actions by regulatory authorities are needed to better understand disease epidemiology and address initial lymphomagenesis and progression. Deviation from current diagnosis and treatment protocols can lead to disease recurrence, and research on breast implant risk factors provide insight to etiology.

Level of Evidence: 4
Mettl3 downregulation in germinal vesicle oocytes inhibits mRNA decay and the first polar body extrusion during maturation
Authors: Zhu Yan , Wu Wenjiao , Chen Shaoqing , Zhang Zhen , Zhang Guangli , Li Jie , Jiang Manxi
Published: May 2022

In oocytes, mRNA decay is essential for maturation and subsequent events, such as maternal-zygotic transition, zygotic genomic activation, and embryo development. Reversible N6-methyladenosine RNA methylation directly regulates transcription, pre-mRNA splicing, mRNA export, mRNA stability, and translation. Here, we identified that downregulation of N6-methyladenosine modification by microinjecting a methyltransferase-like 3 (Mettl3)-specific small interfering RNA into mouse germinal vesicle oocytes led to defects in meiotic spindles and the first polar body extrusion during maturation in vitro. By further quantitative real-time polymerase chain reaction and Poly(A)-tail assay analysis, we found that N6-methyladenosine methylation mainly acts by reducing deadenylation of mRNAs mediated by the carbon catabolite repression 4-negative on TATA less system, thereby causing mRNA accumulation in oocytes. Meanwhile, transcriptome analysis of germinal vesicle oocytes revealed the downregulation of transcripts of several genes encoding ribosomal subunits proteins in the Mettl3 small interfering RNA-treated group, suggesting that N6-methyladenosine modification might affect translation. Together, our results indicate that RNA methylation accelerates mRNA decay, confirming the critical role of RNA clearance in oocyte maturation.
Broadening the educational pipeline: the global landscape of master of science programs in reproductive science and medicine
Authors: Ataman-Millhouse Lauren M , Monahan Pamela , Willingham Rebecca , Vigone Giulia , Soulakis Mao , Gadea Joaquín , Jiménez-Movilla Maria , Romar Raquel , Cánovas Sebastián , Woodruff Teresa K , Duncan Francesca E
Published: May 2022

Reproductive health underpins overall health, and thus, research in reproductive science and medicine is essential. This requires a pipeline of trained scientists and clinicians, which is challenging given the relatively small size of the field. Educational programs outside the traditional doctorate or medical degrees are needed to generate and maintain a well-trained reproductive science and medicine workforce. Master’s programs have gained traction as a viable way for students to receive educational value relative to their career goals. Our hypothesis is master’s degree programs in the fundamental, applied, and allied health reproductive fields broadens the workforce and increases impact. An internet web search identified 73 programs that conferred an MS degree in the areas of animal science, clinical/embryology, and reproductive health/biology. These programs are spread across the globe in Europe (47%), North America (23%), Asia (14%), South America (7%), Oceania (5%), and Africa (4%). To evaluate global exemplars, we profiled the mission and structure, curriculum, and program impact of two established master’s degree programs: the Master of Science in Reproductive Science and Medicine at Northwestern University in the United States and the Biology and Technology of Reproduction in Mammals at the University of Murcia in Spain. Elements of infrastructure and support, program connectivity, and alumni networks were analyzed for their role in the success of the programs. These two programs have formally trained >375 individuals, demonstrating master’s degree programs in reproductive science are an important educational mechanism. The educational best practices shared here serve as templates for expanding training programs worldwide.
Catatonia: looking back and moving forward
Authors: Hirjak Dusan , Wolf Robert Christian , Landwehrmeyer G Bernhard , Northoff Georg
Published: May 2022

Catatonia is a complex neuropsychiatric syndrome with motor, cognitive-behavioural and affective manifestations. Hirjak et al. look back at the history of catatonia, but also provide a modern perspective on what the condition can tell us both clinically and scientifically, and how we can best understand it.
Characteristics of spinal and bulbar muscular atrophy in South Korea: a cross-sectional study of 157 patients
Authors: Cho Hee-Jin , Shin Jin-Hong , Park Young-Eun , Sohn Eunhee , Nam Tai-Seung , Kang Min-Gu , Park Jin-Mo , Park Donghwi , Park Jin-Sung
Published: May 2022

Spinal and bulbar muscular atrophy, namely Kennedy disease, is a rare progressive neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the androgen receptor gene on the X chromosome.

We assessed the clinical history, laboratory findings, functional scales and electrophysiological data, as well as the levels of luteinizing hormone, follicle-stimulating hormone and testosterone, in 157 Korean patients with genetically confirmed spinal and bulbar muscular atrophy (mean age at data collection = 56.9 years; range = 33–83 years).

Hand tremor was the first symptom noticed by patients at a median age of 35 years, followed by gynaecomastia, orofacial fasciculation, cramps and fatigability in ascending order. Clinical symptoms such as paraesthesia and dysphagia appeared during the later stages of the disease. Cane use during ambulation began at a median age of 62 years. There were statistically significant differences between patients and controls in the results of sensory nerve studies, motor conduction velocity, and distal latencies. Furthermore, among the hormone markers analysed, the level of luteinizing hormone exhibited a negative correlation with the spinal and bulbar muscular atrophy functional rating scale, Korean version. However, among the patients with a disease duration of ≤5 years, the levels of luteinizing hormone showed a significant correlation with assessments using the amyotrophic lateral sclerosis functional rating scale-revised, spinal and bulbar muscular atrophy functional rating scale, Korean version and the 6-minute walk test. In conclusion, our findings provide clinical information from a substantial number of patients with spinal and bulbar muscular atrophy in Korea that accorded with that of patients with this disease worldwide but with updated clinical features.
A methylation-driven genes prognostic signature and the immune microenvironment in epithelial ovarian cancer
Authors: Tan Mingzi , Wang Shengtan , Li Feifei , Xu Haoya , Gao Jian , Zhu Liancheng
Published: May 2022

Aberrant gene methylation has been implicated in the development and progression of tumors. In this study, we aimed to identity methylation-driven genes involved in epithelial ovarian cancer (EOC) to establish a prognostic signature for patients with EOC. We identified and verified 6 MDGs that are closely related to the prognosis of ovarian cancer. A prognostic risk score model and nomogram for predicting the prognosis of ovarian cancer were constructed based on the six MDGs. It can also effectively reflect the immune environment and immunotherapy response of ovarian cancer. These MDGs have great significance to the implementation of individualized treatment and disease monitoring of ovarian cancer patients.
A circuit-level biomarker of Rett syndrome based on ectopic phase-amplitude coupling during slow-wave-sleep
Authors: Davis Patrick , Takach Kyle , Maski Kiran , Levin April
Published: May 2022

Rett syndrome (RTT) is a neurodevelopmental disorder characterized by loss of purposeful hand use and spoken language following an initial period of normal development. Although much is known about the genetic and molecular underpinnings of RTT, less is known about the circuit-level etiopathology. Coupling of oscillations during slow-wave-sleep (SWS) underlies important neurocognitive processes in adulthood, yet its emergence has yet to be described in early typical development (TD) or in RTT. We therefore addressed these unknowns by describing SWS cross-frequency coupling in both RTT and early TD using a retrospective study design. We found that in TD, phase-amplitude coupling (PAC) during SWS was dominated by coupling of slow-wave (0.5–2 Hz) phase to theta amplitude (5–8 Hz, “SW:T”) as well as slow-wave to spindle-range (12–15 Hz, “SW:S”). Coupling exhibited characteristic vertex-prominent spatial topography, which emerged during an early developmental window. This topography failed to develop in patients with RTT due to persistent ectopic coupling. Furthermore, we found that subtypes of RTT exhibit distinct PAC topographic profiles, and that ectopic PAC correlates with clinical severity. These findings suggest that altered PAC dynamics and spatial organization during SWS may underlie the circuit-level pathophysiology of RTT and suggest that ectopic coupling may contribute to RTT pathogenesis.
Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate
Authors: Patel Sanjay S , Rauscher Martina , Kudela Maria , Pang Hang
Published: May 2022

Background

An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals.

Methods

Safety findings are presented herein from an integrated analysis of data for healthy 4–60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender.

Results

The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1–3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively).

Conclusions

No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4–60 years.
Severe Acute Respiratory Syndrome Coronavirus 2 Incidence and Risk Factors in a National, Community-Based Prospective Cohort of US Adults
Authors: Nash Denis , Rane Madhura S , Robertson McKaylee M , Chang Mindy , Kulkarni Sarah Gorrell , Zimba Rebecca , You William , Berry Amanda , Mirzayi Chloe , Kochhar Shivani , Maroko Andrew , Westmoreland Drew A , Parcesepe Angela M , Waldron Levi , Grov Christian
Published: May 2022

Background

Prospective cohort studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence complement case-based surveillance and cross-sectional seroprevalence surveys.

Methods

We estimated the incidence of SARS-CoV-2 infection in a national cohort of 6738 US adults, enrolled in March–August 2020. Using Poisson models, we examined the association of social distancing and a composite epidemiologic risk score with seroconversion. The risk score was created using least absolute shrinkage selection operator (LASSO) regression to identify factors predictive of seroconversion. The selected factors were household crowding, confirmed case in household, indoor dining, gathering with groups of ≥10, and no masking in gyms or salons.

Results

Among 4510 individuals with ≥1 serologic test, 323 (7.3% [95% confidence interval (CI), 6.5%–8.1%]) seroconverted by January 2021. Among 3422 participants seronegative in May–September 2020 and retested from November 2020 to January 2021, 161 seroconverted over 1646 person-years of follow-up (9.8 per 100 person-years [95% CI, 8.3–11.5]). The seroincidence rate was lower among women compared with men (incidence rate ratio [IRR], 0.69 [95% CI, .50–.94]) and higher among Hispanic (2.09 [1.41–3.05]) than white non-Hispanic participants. In adjusted models, participants who reported social distancing with people they did not know (IRR for always vs never social distancing, 0.42 [95% CI, .20–1.0]) and with people they knew (IRR for always vs never, 0.64 [.39–1.06]; IRR for sometimes vs never, 0.60 [.38–.96]) had lower seroconversion risk. Seroconversion risk increased with epidemiologic risk score (IRR for medium vs low score, 1.68 [95% CI, 1.03–2.81]; IRR for high vs low score, 3.49 [2.26–5.58]). Only 29% of those who seroconverted reported isolating, and only 19% were asked about contacts.

Conclusions

Modifiable risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the United States.
Willed Ignorance: Reflections on academic free speech, occasioned by the David Miller case
Authors: Julius Anthony
Published: May 2022

The David Miller case raises the question, does liberal free speech doctrine require academics to defend the antisemitic conspiracy-talk of a sociology professor? The article opens with a discussion of Louise Glück's poem ‘A Myth of Innocence’, and then proceeds towards an answer to this question, pausing to address details of the Miller case itself when the general argument requires it to do so.
AP-1 activation mediates post-natal cardiomyocyte maturation
Authors: Zhang Hongjie , Pei Lijuan , Ouyang Zhaohui , Wang Haocun , Chen Xin , Jiang Kai , Huang Shiqi , Jiang Rui , Xiang Yaozu , Wei Ke
Published: May 2022

Aims

Post-natal maturation of mammalian cardiomyocytes proceeds rapidly after birth, with most of the myocytes exiting cell cycle, becoming binucleated, and adopting oxidative phosphorylation as the primary metabolic route. The triggers and transcriptional programmes regulating cardiomyocyte maturation have not been fully understood yet. We performed single-cell RNA-Seq in post-natal rat hearts in order to identify the important factors for this process.

Methods and results

Single-cell RNA-Seq profiling was performed of post-natal Day 1 and Day 7 rat hearts, and we found that members of the activating protein 1 (AP-1) transcription factors showed a transient up-regulation in the maturing cardiomyocytes, suggesting their functional involvement in the process. Activating members of the AP-1 family by palmitate or adrenergic stimulation inhibited cardiomyocyte cytokinesis and promoted cardiomyocyte maturation. In contrast, knocking down AP-1 members Atf3 and Jun promoted cardiomyocyte cytokinesis, reduced polyploidy, and inhibited maturation. Mechanistically, RNA-Seq results and rescue experiments indicated that AP-1 members activate the expression of fatty acid metabolic genes to promote cardiomyocyte maturation. Finally, intraperitoneal injection of AP-1 inhibitor T-5224 in neonatal mice inhibits cardiomyocyte maturation in vivo.

Conclusion

Our results are the first evidence implicating AP-1 transcription factors in post-natal cardiomyocyte maturation both in vitro and in vivo, which expand our understanding of the molecular mechanism of cardiomyocyte maturation, and may lead to novel therapies to treat congenital heart diseases.
Intestinal Ultrasound Early on in Treatment Follow-up Predicts Endoscopic Response to Anti-TNFα Treatment in Crohn’s Disease
Authors: de Voogd F , Bots S , Gecse K , Gilja O H , D’Haens G , Nylund K
Published: May 2022

Background

To assess treatment response, objective measures are superior to clinical improvement in Crohn’s disease [CD]. Intestinal ultrasound [IUS] is an attractive, non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment initiation. Therefore, we investigated IUS and contrast-enhanced ultrasound [CEUS] to predict [early] endoscopic treatment response.

Methods

Consecutive patients with endoscopically active CD, starting anti-TNFα therapy, were included. Clinical, biochemical, IUS, and CEUS parameters at baseline [T0], after 4–8 weeks [T1] and 12–34 weeks [T2] were collected. The most severely inflamed segment at endoscopy (highest segmental Simplified Endoscopic Score for Crohn’s Disease [SES-CD]) and IUS (highest segmental bowel wall thickness [BWT]) was identified. At T2, endoscopic response [decrease in SES-CD ≥ 50%] and remission [SES-CD = 0] were scored.

Results

A total of 40 patients were included: 14 reached endoscopic remission and 17 endoscopic response. At T1 (3.1 mm [1.9–4.2] vs 5.3 mm [3.8–6.9], p = 0.005) and T2 (2.0 mm [1.8–3.1] vs 5.1 [3.0–6.3] mm, p = 0.002) BWT was lower in patients with endoscopic remission. At T1 and T2, 18% (area under the receiver operating curve [AUROC]: 0.77; odds ratio [OR]: 10.80, p = 0.012) and 29% [AUROC: 0.833; OR: 37.50, p = 0.006] BWT decrease predicted endoscopic response, respectively. To determine endoscopic remission, BWT 3.2 mm was most accurate [AUROC: 0.94; OR: 39.42, p < 0.0001] at T2. In addition, absence of colour Doppler signal [OR: 13.76, p = 0.03] and the CEUS parameter wash-out rate [OR: 0.76, p = 0.019] improved the prediction model.

Conclusions

Reduction in BWT, already after 4–8 weeks of follow-up, predicted endoscopic response and remission. CEUS parameters were of limited value. Furthermore, we have provided accurate cut-offs for BWT reflecting endoscopic response and remission at different time points.
Early superior cavopulmonary connection with preoperative computer tomography shows comparable outcomes for infants following Norwood palliation
Authors: Bellsham-Revell Hannah R , Tarmahomed Abdulla , Chou Catie , Wong James , Mathur Sujeev , Vigneswaran Trisha , Salih Caner
Published: May 2022

OBJECTIVES

There is increasing evidence that performing superior cavopulmonary connection (SCPC) at 3 months reduces mortality: reducing the risky ‘interstage’ period, volume off-loading the ventricle and reducing coronary steal, hopefully preserving ventricular function. Our objective was to describe our experience of early SCPC with preoperative computer tomography (CT) assessment compared to later connection at 6 months.

METHODS

Patients undergoing Norwood procedure from 2005 to 2020 were divided into 2 eras were described and compared. Era 1 from 2005 to 2016 when SCPC was undertaken at 6 months: and era 2 (2017–2020) when an earlier operation was performed. Demographics, mortality (interstage, early and late following SCPC) and data on postoperative course and complications were recorded.

RESULTS

In era 1, 191 patients underwent Norwood (120 survivors to SCPC) and 28 patients (23 survivors) in era 2. There were no significant differences in the demographics. Interstage mortality was 17.8% in era 1 and 8.0% in era 2 but not significantly significant (P = 0.22). The median (interquartile range) age at pre-imaging and SCPC was significantly lower: 99 (81–120) vs 77 (47–102) days and 175 (117–208) vs 106 (102–122) days in era 1 vs era 2 (P < 0.005). Weight was lower at SCPC in era 2 [mean (standard deviation) 6.2 kg (1.2) vs 5.1 kg (0.8), P < 0.05]. Intubation time and total length of stay were not statistically different. Median intensive care unit stay was statistically significantly longer, but not clinically significant: 2.5 (2–4) vs 3 (3–5) days, respectively (P < 0.05). There was no significant difference in early or late mortality, rates of diagnostic or interventional catheter, postoperative magnetic resonance imaging/CT or stroke. Logistic regression analysis demonstrates increasing age at SCPC was associated with increased chance of stroke or early death (P = 0.043).

CONCLUSIONS

Early SCPC with CT assessment is feasible and although intensive care unit length of stay was slightly longer there was no change in the overall length of stay and no change in postoperative mortality or complications.
Health care patterns and policies in 18 European countries during the first wave of the COVID-19 pandemic: an observational study
Authors: Panteli Dimitra , Reichebner Christoph , Rombey Tanja , Berger Elke , Winkelmann Juliane , Eckhardt Helene , Nimptsch Ulrike , Busse Reinhard
Published: May 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has developed into an unprecedented global challenge. Differences between countries in testing strategies, hospitalization protocols as well as ensuring and managing ICU capacities can illustrate initial responses to a major health system shock, and steer future preparedness activities.

Methods

Publicly available daily data for 18 European countries were retrieved manually from official sources and documented in an Excel table (March–July 2020). The ratio of tests to cases, the share of hospitalizations out of all cases and the share of ICU admissions out of all hospitalizations were computed using 7-day rolling averages per 100 000 population. Information on country policies was collected from the COVID-19 Health System Response Monitor of the European Observatory on Health Systems and Policies. Information on health care capacities, expenditure and utilization was extracted from the Eurostat health database.

Results

There was substantial variation across countries for all studied variables. In all countries, the ratio of tests to cases increased over time, albeit to varying degrees, while the shares of hospitalizations and ICU admissions stabilized, reflecting the evolution of testing strategies and the adaptation of COVID-19 health care delivery pathways, respectively. Health care patterns for COVID-19 at the outset of the pandemic did not necessarily follow the usual health service delivery pattern of each health system.

Conclusions

This study enables a general understanding of how the early evolution of the pandemic influenced and was influenced by country responses and clearly demonstrates the immense potential for cross-country learning.
Systemic exertion intolerance disease associated to neuroendocrine dysfunction and cortical atrophy: a case report
Authors: López-Amador Noé
Published: May 2022

Background

Scarce evidence about the organic and functional abnormalities of systemic exertion intolerance disease (SEID) is found in literature and the pathophysiology is still unclear.

Methods

Following the CARE Guidelines, this case report describes a patient with a 5-year history of nonspecific symptoms, lately recognized as SEID.

Results

Low serum thyroid- and adrenocorticotropic stimulating hormone levels, and 24-h urinary cortisol excretion almost twice the upper limit were detected. Computed tomography scan found significant cortical atrophy. Low-dose modafinil improved the clinical outcome, added to nonpharmacologic approach.

Conclusion

To ascertain an accurate SEID diagnosis and treatment are a challenge in daily clinical practice, that must be engaged based in clear methods and good practice recommendations. Thus, family practitioners should be aware of this diagnosis.
Three-dimensional seismic anisotropy in the Pacific upper mantle from inversion of a surface-wave dispersion data set
Authors: Eddy Celia L , Ekström Göran , Nettles Meredith
Published: May 2022

We present a new, 3-D model of seismic velocity and anisotropy in the Pacific upper mantle, PAC13E. We invert a data set of single-station surface-wave phase-anomaly measurements sensitive only to Pacific structure for the full set of 13 anisotropic parameters that describe surface-wave anisotropy. Realistic scaling relationships for surface-wave azimuthal anisotropy are calculated from petrological information about the oceanic upper mantle and are used to help constrain the model. The strong age dependence in the oceanic velocities associated with plate cooling is also used as a priori information to constrain the model. We find strong radial anisotropy with vSH > vSV in the upper mantle; the signal peaks at depths of 100–160 km. We observe an age dependence in the depth of peak anisotropy and the thickness of the anisotropic layer, which both increase with seafloor age, but see little age dependence in the depth to the top of the radially anisotropic layer. We also find strong azimuthal anisotropy, which typically peaks in the asthenosphere. The azimuthal anisotropy at asthenospheric depths aligns better with absolute-plate-motion directions while the anisotropy within the lithosphere aligns better with palaeospreading directions. The relative strengths of radial and azimuthal anisotropy are consistent with A-type olivine fabric. Our findings are generally consistent with an explanation in which corner flow at the ridge leads to the development and freezing-in of anisotropy in the lithosphere, and shear between the lithosphere and underlying asthenosphere leads to anisotropy beneath the plate. We also observe large regions within the Pacific basin where the orientation of anisotropy and the absolute-plate-motion direction differ; this disagreement suggests the presence of shear in the asthenosphere that is not aligned with absolute-plate-motion directions. Azimuthal-anisotropy orientation rotates with depth; the depth of the maximum vertical gradient in the fast-axis orientation tends to be age dependent and agrees well with a thermally controlled lithosphere–asthenosphere boundary. We observe that azimuthal-anisotropy strength at shallow depths depends on half-spreading rate, with higher spreading rates associated with stronger anisotropy. Our model implies that corner flow is more efficient at aligning olivine to form lattice-preferred orientation anisotropy fabrics in the asthenosphere when the spreading rate at the ridge is higher.
Identifying candidate genes and drug targets for Alzheimer’s disease by an integrative network approach using genetic and brain region-specific proteomic data
Authors: Liu Andi , Manuel Astrid M , Dai Yulin , Fernandes Brisa S , Enduru Nitesh , Jia Peilin , Zhao Zhongming
Published: May 2022

Genome-wide association studies (GWAS) have identified more than 75 genetic variants associated with Alzheimer’s disease (ad). However, how these variants function and impact protein expression in brain regions remain elusive. Large-scale proteomic datasets of ad postmortem brain tissues have become available recently. In this study, we used these datasets to investigate brain region-specific molecular pathways underlying ad pathogenesis and explore their potential drug targets. We applied our new network-based tool, Edge-Weighted Dense Module Search of GWAS (EW_dmGWAS), to integrate ad GWAS statistics of 472 868 individuals with proteomic profiles from two brain regions from two large-scale ad cohorts [parahippocampal gyrus (PHG), sample size n = 190; dorsolateral prefrontal cortex (DLPFC), n = 192]. The resulting network modules were evaluated using a scale-free network index, followed by a cross-region consistency evaluation. Our EW_dmGWAS analyses prioritized 52 top module genes (TMGs) specific in PHG and 58 TMGs in DLPFC, of which four genes (CLU, PICALM, PRRC2A and NDUFS3) overlapped. Those four genes were significantly associated with ad (GWAS gene-level false discovery rate < 0.05). To explore the impact of these genetic components on TMGs, we further examined their differentially co-expressed genes at the proteomic level and compared them with investigational drug targets. We pinpointed three potential drug target genes, APP, SNCA and VCAM1, specifically in PHG. Gene set enrichment analyses of TMGs in PHG and DLPFC revealed region-specific biological processes, tissue-cell type signatures and enriched drug signatures, suggesting potential region-specific drug repurposing targets for ad.
Bidirectional Correlations Between Health Confidence and Inflammatory Bowel Disease Activity: A Nationwide Longitudinal Cohort Study
Authors: Tse Chung Sang , Melmed Gil Y , Siegel Corey A , Weng Chien-Hsiang , Shah Samir A , Weaver S Alandra , Oliver Brant J , Elwyn Glyn , van Deen Welmoed K
Published: May 2022

Lay Summary

Health confidence—an individual’s belief in their ability and agency to affect disease outcomes—has bidirectional temporal correlations with inflammatory bowel disease activity. Low health confidence is associated with higher risks for future disease activity, and inflammatory bowel disease flares erode confidence.
Endoscopic vein harvesting: a guide for approaching difficult cases and assessing patients preoperatively
Authors: Siddiqui Sadiq , Whooley Jack , Miceli Antonio , Bartolozzi Fabio , Soo Alan
Published: May 2022

Coronary artery bypass grafting remains the most commonly performed cardiac surgical procedure worldwide. The long saphenous vein still presides as the first choice conduit as a second graft in multivessel coronary artery bypass grafting surgery. Traditionally, the long saphenous vein has been harvested with an open approach which can potentially result in significant wound complications in certain circumstances. Endoscopic vein harvesting is a minimally invasive vein harvesting technique, which requires a single 2–3 cm incision and is associated with a quicker return to normal daily activities, decreased wound complications and better quality of life in the longer term. There is a learning curve associated with endoscopic vein harvesting adoption and there are certain patient factors that can prove to be challenging when adopting an endoscopic approach. This commentary aims to provide a concise guide of certain challenging patient factors that operators may encounter during endoscopic vein harvesting, and how to approach these patients in both the preoperative and intraoperative settings. We suggest that with appropriate planning and awareness of the challenging patient factors and problematic venous anatomy that exists, the operator can consistently formulate a strategy for ensuring a successful endoscopic harvest.
Ruxolitinib withdrawal complicating emergency aortic root replacement
Authors: Szpytma Malgorzata (Maggie) , Gimpel Damian , Crouch Gareth , Bennetts Jayme S
Published: May 2022

Ruxolitinib, a Janus kinase inhibitor, is associated with severe withdrawal phenomena. Adequate tapering is often underemphasized in surgical emergencies and can complicate the postoperative course. We present a case of acute ruxolitinib withdrawal in a gentleman undergoing emergency cardiac surgery
Three-dimensional transesophageal echocardiographic morphological evaluation of the tricuspid valve
Authors: Kawase Takumi , Takahashi Yosuke , Ito Asahiro , Yoshida Hisako , Sumii Yosuke , Nishiya Kenta , Kishimoto Noriaki , Yamane Kokoro , Sakon Yoshito , Morisaki Akimasa , Fujii Hiromichi , Shibata Toshihiko
Published: May 2022

OBJECTIVES

The morphology of the tricuspid valve (TV), particularly valves with two posterior leaflets, is attracting attention. The present study was performed to investigate the usefulness of three-dimensional transoesophageal echocardiographic data for morphological evaluation of the TV .

METHODS

Sixty patients underwent morphological evaluation of the TV by preoperative transoesophageal echocardiography followed by TV repair with median sternotomy, and each leaflet was measured intraoperatively. We analysed the TV morphology in 51 patients whose preoperative echocardiographic findings were consistent with intraoperative findings.

RESULTS

The mid-systolic echo data, which included the annulus diameter of each leaflet, were correlated with the intraoperative evaluation findings compared with those in the mid-diastole. The annulus and area of the posterior leaflet were larger in patients with two than one posterior leaflet valve (42.4 ± 13.5 vs 30.7 ± 9.1 mm, P < 0.001 and 327 ± 185 vs 208 ± 77 mm2, P = 0.006, respectively). In the severe tricuspid regurgitation patients, the annulus of the posterior leaflet was larger and the annulus of the anterior leaflet was smaller in patients with two than one posterior leaflet valve [posterior: 48 mm [95% confidence interval (CI), 41–54 mm] vs 36 mm (95% CI, 27–45 mm), respectively; P = 0.043 and anterior: 38 mm (95% CI, 33–42 mm) vs 46 mm (95% CI, 40–52 mm), respectively; P = 0.025].

CONCLUSIONS

Patients who had a TV with two posterior leaflets had a larger annulus and area of the posterior leaflets. Preoperative three-dimensional transoesophageal echocardiography is useful for the morphological evaluation of the TV.
Very-long-term outcomes of mechanical valves in mitral position focusing on valve-related complications
Authors: Uchino Gaku , Murakami Hirohisa , Mukohara Nobuhiko , Tanaka Hiroshi , Nomura Yoshikatsu , Miyahara Shunsuke , Kawashima Motoharu , Fujisue Jun , Tonoki Shuto
Published: May 2022

OBJECTIVES

This study aimed to examine very-long-term outcomes of a mechanical valve at the mitral position.

METHODS

This study included all patients who underwent mitral valve replacement (MVR) using a mechanical valve including urgent operation at the Department of Cardiovascular Surgery, Hyogo Brain and Heart Center, Himeji, from January 1987 to December 2015.

RESULTS

Five hundred and eighty-three patients (277 men [47.51%]; age, 61 [54–67] years) were included in this study. The implanted valve models were as follows: SJM, 221 (37.91%); ATS, 35 (6.00%); On-X, 68 (11.66%); and Carbomedics 194, (33.28%).The median clinical follow-up duration was 13.3 (7.4–19.6) years. The survival rates at 10, 15, 20 and 25 years were 81.42%, 69.27%, 56.34% and 45.03%, respectively. Thromboembolism was observed in 38 patients, and the linearized ratio for each event was 0.626%/patient-year [95% confidence interval (CI), 0.443–0.859%]. Intracranial haemorrhage and gastrointestinal bleeding were observed in 26 and 9 patients, and the linearized ratio for each event was 0.425%/patient-year (95% CI, 0.277–0.006%) and 0.145%/patient-year (95% CI, 0.067–0.276%), respectively. Major paravalvular leak was observed in 32 patients, and the linearized ratio was 0.532%/patient-year (95% CI, 0.364%–0.751%). The cumulative incidence rate of major paravalvular leak at 10, 15, 20 and 25 years was 3.7%, 5.6%, 6.4% and 10.4%, respectively. Multivariable Cox regression analysis revealed that repeated MVR and male gender were associated with major paravalvular leak.

CONCLUSIONS

Male gender and repeated MVR were risk factors for paravalvular leak after mechanical MVR. Paravalvular leak could have occurred regardless of postoperative period even at 25 years after implantation. Lifelong clinical follow-up is considered necessary.