bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundLaboratory 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.ObjectivesThe 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.MethodsA 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.ResultsThe 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.ConclusionsBIA-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

AbstractIn 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

Abstract
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 &gt;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.
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

AbstractSpinal 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

Abstract
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

AbstractRett 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

Abstract

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

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

Abstract
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

AbstractAimsPost-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 resultsSingle-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.ConclusionOur 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

AbstractBackgroundTo 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.MethodsConsecutive 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.ResultsA 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 &lt; 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.ConclusionsReduction 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

Abstract

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 &lt; 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 &lt; 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 &lt; 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

Abstract

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.