bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum scEMC10 Levels are Negatively Associated With Resting Metabolic Rate and age in Humans
Authors: Chen Kuangyang , Dai Jiarong , Klöting Nora , Cao Xinyi , Jin Shuoshuo , Chen Lijiao , Wang Yahao , Liu Shan , Hu Yao , Jiang Lin , Liew Chong Wee , Blüher Matthias , Wang Xuanchun 
Published: April 2023

Abstract

Context
We have recently shown that the secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is upregulated in human obesity and that overexpression of scEMC10 promotes, whereas antibody neutralization of circulating scEMC10 prevents diet-induced obesity in mice.

Objective
To explore associations of serum scEMC10 with body mass index (BMI), resting metabolism rate (RMR), and age in humans.

Design
A cross-sectional study.

Setting and Patients
A total of 833 participants from a Chinese physical examination cohort and 191 participants from the Leipzig Obesity Biobank cohort.

Main Outcome Measures
Serum scEMC10 concentrations are measured using chemiluminescent immunoassay. RMR is calculated based on measurements from indirect calorimetry with an open-circuit ventilated-hood system.

Results
In the Chinese physical examination cohort, a J-shaped nonlinear correlation between BMI and serum scEMC10 was identified in participants where underweight, overweight, and obese people all presented higher serum scEMC10 levels than normal weight people. Participants younger than age 30 years old exhibited significantly higher serum scEMC10 levels than those older than 50 years of age. In addition, participants aged 30 to 40 years also had significantly higher serum scEMC10 levels than those aged 50 to 60 years. In the Leipzig Obesity Biobank cohort, we observed a significantly negative correlation between serum scEMC10 and resting energy expenditure after adjusting for BMI. Participants in the highest quartile of serum scEMC10 levels had significantly lower RMR than those in the first quartile. RMR had an independently inverse association with serum scEMC10.

Conclusions
Serum scEMC10 levels are negatively associated with age and RMR in humans.
Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management
Authors: Chiosea Simion , Hodak Steven P , Yip Linwah , Abraham Devaprabu , Baldwin Chelsey , Baloch Zubair , Gulec Seza A , Hannoush Zeina C , Haugen Bryan R , Joseph Lija , Kargi Atil Y , Khanafshar Elham , Livhits Masha J , McIver Bryan , Patel Kepal , Patel Snehal G , Randolph Gregory W , Shaha Ashok R , Sharma Jyotirmay , Stathatos Nikolaos , van Zante Annemieke , Carty Sally E , Nikiforov Yuri E , Nikiforova Marina N 
Published: April 2023

Abstract

Context
Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported.

Objective
To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules.

Methods
This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients.

Results
Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases.

Conclusion
In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.
Critical Approach to Hypothyroid Patients With Persistent Symptoms
Authors: Biondi Bernadette , Celi Francesco S , McAninch Elizabeth A 
Published: April 2023

Abstract
Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms. Some population-based studies and international population-based surveys have confirmed dissatisfaction with LT4 treatment in some hypothyroid patients. It is well established that hypothyroid patients treated with LT4 exhibit higher serum thyroxine:triiodothyronine ratios and can have a persistent increase in cardiovascular risk factors. Moreover, variants in deiodinases and thyroid hormone transporter genes have been associated with subnormal T3 concentrations, persistent symptoms in LT4-treated patients, and improvement in response to the addition of liothyronine to LT4 therapy.
The American (ATA) and European Thyroid Association (ETA) guidelines have recently evolved in their recognition of the potential limitations of LT4. This shift is reflected in prescribing patterns: Physicians’ use of combination therapy is prevalent and possibly increasing. Randomized clinical trials have recently been published and, while they have found no improvement in treating hypothyroid patients, a number of important limitations did not allow generalizability. Meta-analyses have reported a preference rate for combination therapy in 46.2% hypothyroid patients treated with LT4. To promote discussions about an optimal study design, the ATA, ETA, and British Thyroid Association have recently published a consensus document.
Our study provides a useful counterpoint on the controversial benefits of treating hypothyroid patients with combination therapy.
Actin filaments accumulated in the nucleus remain in the vicinity of condensing chromosomes in the zebrafish early embryo
Authors: Oda Haruka , Sato Yuko , Kawashima Shigehiro A. , Fujiwara Yusuke , Pálfy Máté , Wu Edlyn , Vastenhouw Nadine L. , Kanai Motomu , Kimura Hiroshi 
Published: April 2023

ABSTRACT
In the cytoplasm, filamentous actin (F-actin) plays a critical role in cell regulation, including cell migration, stress fiber formation, and cytokinesis. Recent studies have shown that actin filaments that form in the nucleus are associated with diverse functions. Here, using live imaging of an F-actin-specific probe, superfolder GFP-tagged utrophin (UtrCH-sfGFP), we demonstrated the dynamics of nuclear actin in zebrafish (Danio rerio) embryos. In early zebrafish embryos up to around the high stage, UtrCH-sfGFP increasingly accumulated in nuclei during the interphase and reached a peak during the prophase. After nuclear envelope breakdown (NEBD), patches of UtrCH-sfGFP remained in the vicinity of condensing chromosomes during the prometaphase to metaphase. When zygotic transcription was inhibited by injecting α-amanitin, the nuclear accumulation of UtrCH-sfGFP was still observed at the sphere and dome stages, suggesting that zygotic transcription may induce a decrease in nuclear F-actin. The accumulation of F-actin in nuclei may contribute to proper mitotic progression of large cells with rapid cell cycles in zebrafish early embryos, by assisting in NEBD, chromosome congression, and/or spindle assembly.
New horizons of microphysiological systems: India forging its path in human-relevant research
Authors: Parvatam Surat , Mahadik Kasturi , Banerjee Anushka , Patil Kadambari , Radha V. , Rao Madhusudhana 
Published: April 2023

ABSTRACT
The past decade has seen expeditious developments in our ability to grow and maintain a variety of human cells and tissues, with properties closely mimicking those in the human body. Prominent researchers and entrepreneurs from all over the world assembled in Hyderabad, India to discuss developments in this field that have not only aided fundamental understanding of organ development and disease processes but have served as good physiological models for toxicity testing and drug development. The speakers presented ingenious, cutting-edge technology and forward-thinking ideas. This report presents the salient aspects of their discussions, highlights the importance of identifying unmet needs, and discusses setting of standards that will help regulatory approvals as we move into a new era, with nominal animal use in research and effective drug discovery.
Transplanted human intestinal organoids: a resource for modeling human intestinal development
Authors: Singh Akaljot , Poling Holly M. , Chaturvedi Praneet , Thorner Konrad , Sundaram Nambirajan , Kechele Daniel O. , Childs Charlie J. , McCauley Heather A. , Fisher Garrett W. , Brown Nicole E. , Spence Jason R. , Wells James M. , Helmrath Michael A. 
Published: April 2023

ABSTRACT
The in vitro differentiation of pluripotent stem cells into human intestinal organoids (HIOs) has served as a powerful means for creating complex three-dimensional intestinal structures. Owing to their diverse cell populations, transplantation into an animal host is supported with this system and allows the temporal formation of fully laminated structures, including crypt-villus architecture and smooth muscle layers that resemble native human intestine. Although the endpoint of HIO engraftment has been well described, here we aim to elucidate the developmental stages of HIO engraftment and establish whether it parallels fetal human intestinal development. We analyzed a time course of transplanted HIOs histologically at 2, 4, 6 and 8 weeks post-transplantation, and demonstrated that HIO maturation closely resembles key stages of fetal human intestinal development. We also utilized single-nuclear RNA sequencing to determine and track the emergence of distinct cell populations over time, and validated our transcriptomic data through in situ protein expression. These observations suggest that transplanted HIOs do indeed recapitulate early intestinal development, solidifying their value as a human intestinal model system.
The in vivo functional significance of PUF hub partnerships in C. elegans germline stem cells
Authors: Ferdous Ahlan S. , Costa Dos Santos Stephany J. , Kanzler Charlotte R. , Shin Heaji , Carrick Brian H. , Crittenden Sarah L. , Wickens Marvin , Kimble Judith 
Published: April 2023

ABSTRACT
PUF RNA-binding proteins are conserved stem cell regulators. Four PUF proteins govern self-renewal of Caenorhabditis elegans germline stem cells together with two intrinsically disordered proteins, LST-1 and SYGL-1. Based on yeast two-hybrid results, we previously proposed a composite self-renewal hub in the stem cell regulatory network, with eight PUF partnerships and extensive redundancy. Here, we investigate LST-1–PUF and SYGL-1–PUF partnerships and their molecular activities in their natural context – nematode stem cells. We confirm LST-1–PUF partnerships and their specificity to self-renewal PUFs by co-immunoprecipitation and show that an LST-1(AmBm) mutant defective for PUF-interacting motifs does not complex with PUFs in nematodes. LST-1(AmBm) is used to explore the in vivo functional significance of the LST-1–PUF partnership. Tethered LST-1 requires this partnership to repress expression of a reporter RNA, and LST-1 requires the partnership to co-immunoprecipitate with NTL-1/Not1 of the CCR4-NOT complex. We suggest that the partnership provides multiple molecular interactions that work together to form an effector complex on PUF target RNAs in vivo. Comparison of LST-1–PUF and Nanos–Pumilio reveals fundamental molecular differences, making LST-1–PUF a distinct paradigm for PUF partnerships.
A Planner-Trader Decomposition for Multimarket Hydro Scheduling
Authors: Schindler Kilian , Rujeerapaiboon Napat , Kuhn Daniel , Wiesemann Wolfram 
Published: April 2023

Multimarket Multireservoir Hydro Scheduling Peak/off-peak spreads on European electricity forward and spot markets are eroding due to the ongoing nuclear phaseout in Germany and the steady growth in photovoltaic capacity. The reduced profitability of peak/off-peak arbitrage forces hydropower producers to recover part of their original profitability on the reserve markets. In their paper titled “A Planner-Trader Decomposition for Multimarket Hydro Scheduling” Schindler, Rujeerapaiboon, Kuhn, and Wiesemann propose a bi-layer stochastic programming framework that jointly optimizes the trading strategies on the spot and reserve markets. The model faithfully accounts for uncertainty in electricity prices, water inflows, and reserve activations, and it ensures that the hydropower producers can fulfill their market commitments under any circumstances. The model is numerically challenging due to the various sources of uncertainty that are revealed at different time scales and that affect the problem's objective function and constraints, and the authors propose a new planner-trader decomposition and an information restriction for its solution. A case study based on real data from Austria reveals significant benefits of simultaneously participating in the spot and the reserve markets.
Dermatitis artefacta in the orofacial region: a case report with literature review
Authors: Patel Nutan , Mumtaz Shadaab , Deroide Florence , Amini Ali 
Published: April 2023

In spite of wide prevalence, deliberate self-injury in the oro-facial region is rarely reported in literature. It is also associated with misinterpretation related to ‘attention seeking’ or ‘mental health crises’ leading to deficient understanding of this phenomenon. A literature review was performed using online search databases looking at dermatitis artefacta in the head and neck region. A case of a patient who was seen in our unit is also presented to give important insights into this condition. In total, 54 cases from 15 publications were included in this observational study. Female gender predilection was notable (4:1) with an average presenting age of 30 years. The face itself was more frequently injured, along with the neck and scalp. Only one-third (34%) of the patients were known to have psychiatric conditions, such as depressive and personality disorders. Dermatitis artefacta is a well-known skin condition caused by deliberate self-injury. It is a complex entity that is frequently unrecognized and underdiagnosed. CPD/Clinical Relevance: Understanding dermatitis artefacta will facilitate correct diagnosis and improve patient care.
Case report of an Afro-Caribbean adolescent with moderate hypodontia managed with a partial flexible denture
Authors: Ramlogan Shaun , Raman Vidya 
Published: April 2023

A 14-year-old male of Afro-Caribbean descent presented with moderate hypodontia, missing some of the permanent mandibular premolars and the lower central incisors, which was a rare finding. There were no apparent associated systemic or syndromic relationships. The main dental concerns were aesthetics, function and space maintenance until adolescent craniofacial bone growth had ceased. Thus, an initial intervention entailed provision of a unilateral removable partial flexible denture that was acceptable to the patient and provided a suitable aesthetic result for the young person. This approach was preferred to a ‘band and loop’ appliance proposed in the literature because the removable partial denture supported function and aesthetics. CPD/Clinical Relevance: Unilateral removable partial flexible dentures may be useful in mid-adolescent cases of hypodontia.
An overzealous use of zinc oxide: zinc toxicity from temporary dental cement
Authors: George Ifan , Friend Thomas , McNally Lisa 
Published: April 2023

A 52-year-old male attended a dental hospital following a referral from a royal infirmary regarding hyperzincaemia (zinc toxicity) and hypocupraemia (low copper levels). The patient had been using an excessive amount of over-the-counter zinc oxide temporary dental material for the previous 18 months owing to a phobia of dentists and misconception about amalgam fillings as caries. This resulted in acquired peripheral neuropathy, muscle weakness and the inability to walk without wheelchair aid. We present the reasons clear warnings should be in place and education is required for the general public when self-prescribing with ‘at-home’ dental kits. CPD/Clinical Relevance: It is important to break down patient barriers to accessing dental care.
Complications and maintenance in prosthodontic care: removable partial dentures
Authors: Khalid Taimur 
Published: April 2023

The number of partially dentate adults is increasing, and many patients will require replacement of missing teeth. Oral rehabilitation with removable partial dentures (RPD) is a less time-consuming and a low-cost, conservative treatment alternative that meets the functional and aesthetics needs for many partially dentate patients. Given the high prevalence of RPD usage, it is pertinent to question its impact on general and oral health. However, there is limited evidence on the maintenance and recall regimens for patients with RPDs. Therefore, this article reviews and evaluates the available scientific evidence on complications, and patient recall and maintenance regimens.CPD/Clinical Relevance: An understanding of the complications associated with removable partial dentures will help us strategize patient maintenance regimens.
Ideation Patterns für ressourcenzentrierte digitale Innovation
Authors: Lindenthal Anna-Katharina , Oberländer Anna Maria , Rosemann Michael , Röglinger Maximilian 
Published: April 2023

ZusammenfassungDigitale Transformation ist für Unternehmen in allen Branchen ein Muss und erfordert sowohl die Weiterentwicklung von bestehenden Geschäftsmodellen, als auch gleichzeitig die Entwicklung neuer digitaler Geschäftsmodelle. Die Digitalisierung bietet Unternehmen hierbei zahlreiche Möglichkeiten für die systematische Wiederverwendung und Rekombination vorhandener Ressourcen (Mittel und Fähigkeiten), um innovative Lösungen zu finden und neue Wertangebote zu schaffen. Dies erfolgt durch die Nutzung interner Ressourcen, den Zugang zu geteilten Ressourcen, bspw. über Plattformen und die Einbeziehung von externen Ressourcen, bspw. von Kund*innen. Trotz der vielfältigen digitalen Möglichkeiten stellt die Generierung von Ideen für digitale Innovationen für Unternehmen eine komplexe Herausforderung dar. Dabei fällt es oft schwer, digitale Innovationen systematisch zu identifizieren, die auf der einen Seite die Verbesserung bestehender Angebote (Exploitation) berücksichtigen und auf der anderen Seite die Exploration neuer Angebote fördern (Ambidextrie) und entsprechende Anleitungen fehlen. Um Unternehmen bei der Entwicklung von Innovationsideen aus einer Ambidextrie-Perspektive zu unterstützen, stellt dieser Beitrag die relevanten Innovationstypen für etablierte Unternehmen aus einer Ressourcenperspektive vor. Der Beitrag zeigt auf, wie Unternehmen systematisch und ressourcenzentriert digitale Innovationsideen entwickeln können. Anhand von 136 digitalen Initiativen haben wir praxisrelevante Erkenntnisse für die Entwicklung von Innovationsideen abgeleitet. Abschließend sprechen wir Handlungsempfehlungen für Unternehmen aus, die vor ähnlichen (Innovations‑)Herausforderungen stehen und eine gezielte Entwicklung von digitalen Innovationen ergänzend zum bestehenden Produkt- und Service-Portfolio anstreben. Dies bietet Unternehmen Ansatzpunkte für die Anbindung an digitale Märkte und Ökosysteme sowie für die Stärkung ihre Wettbewerbsfähigkeit.
Changes in eligibility for a subcutaneous cardioverter-defibrillator after implantation of a left ventricular assist device–A prospective analysis
Authors: Zormpas Christos , Mueller-Leisse Johanna , Hohmann Stephan , Eiringhaus Jörg , Hillmann Henrike Aenne Katrin , Schmitto Jan D. , Veltmann Christian , Duncker David 
Published: April 2023

Background
The number of left ventricular assist devices (LVADs) implanted in patients with end-stage heart failure is increasing. In this patient cohort, subcutaneous implantable cardioverter defibrillators (S-ICDs) could be a promising alternative to transvenous ICDs due to lower infection rates and avoidance of venous access. However, eligibility for the S-ICD depends on ECG features that may be influenced by an LVAD. The aim of the present study was a prospective evaluation of S-ICD eligibility before and after LVAD implantation.

Methods
The study recruited all patients presenting at Hannover Medical School for LVAD implantation between 2016 and 2020. S-ICD eligibility was evaluated using the ECG-based and the device-based S-ICD screening test before and after LVAD implantation.

Results
Twenty-two patients (57.3 ± 8.7 years of age, 95.5% male) were included in the analysis. The most common underlying diseases were dilated cardiomyopathy (n = 16, 72.7%) and ischemic cardiomyopathy (n = 5, 22.7%). Before LVAD implantation 16 patients were found eligible for the S-ICD according to both screening tests (72.7%), but only 7 patients were eligible after LVAD, 31.8%; p = 0.05). Oversensing due to electromagnetic interference was observed in 6 patients (66.6%) found ineligible for S-ICD after LVAD implantation. A lower S wave amplitude in leads I (p = 0.009), II (p = 0.006) and aVF (p = 0.006) before LVAD implantation was associated with higher rate of S-ICD ineligibility after LVAD implantation.

Conclusion
LVAD implantation can impair S-ICD eligibility. Patients with lower S wave amplitude in leads I, II and aVF were more likely to be ineligible for S-ICD implantation after LVAD implantation. Thus, S-ICD therapy should be carefully considered in patients who are candidates for LVAD therapy.
Systematic review and meta-analysis of anti-thymocyte globulin dosage as a component of graft-versus-host disease prophylaxis
Authors: Zuckermann Joice , Castro Bruno Mateus de , Cunha Thiago Almirante , Paz Alessandra , Moreira Leila Beltrami 
Published: April 2023

Rabbit anti-thymocyte globulin (ATG) has been used in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for graft-versus-host disease (GvHD) prophylaxis. Since the best dose has not been defined yet, this study aimed to determine the efficacy and safety of different doses of ATG in Allo-HSCT. Data sources were MEDLINE/PUBMED, EMBASE, Cochrane Library, Web of Science, LILACS, and SciELO. Studies were eligible when comparing doses of ATG. The higher dose was in the intervention group. A total of 22 articles (2002–2022) were included. Higher doses (4–12 mg/kg) of ATG-T reduced the incidence of grade III-IV acute GvHD (RR 0.60; 95%CI 0.42–0.84) and limited chronic GvHD (RR 0.64 95%CI 0.45–0.92) compared with lower doses (2–7.5 mg/kg). Higher doses increased the Epstein-Barr virus (RR 1.90 95% CI 1.49–2.42) and Cytomegalovirus reactivation (RR, 1.30; 95% CI 1.03–1.64). Relapse rates were higher in the higher dose group (RR 1.34, 95% CI 1.07–167). The ATG-T dose ≥7mg/kg versus the lower dose showed a number needed to treat 7.4 for acute GvHD III-IV, with a number to harm of 7.7 for relapse at one year in the higher dose group. A dose lower than 7 mg/kg suggests a better risk-benefit ratio than a higher one. Well-designed RCT is needed to define the best risk-benefit doses.
Trial registration: Trial registration number: PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173449.