bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA N6-methyladenosine demethylase FTO promotes pancreatic cancer progression by inducing the autocrine activity of PDGFC in an m6A-YTHDF2-dependent manner
Authors: Tan Zhen , Shi Si , Xu Jin , Liu Xiaomeng , Lei Yubin , Zhang Bo , Hua Jie , Meng Qingcai , Wang Wei , Yu Xianjun , Liang Chen 
Published: April 2022

AbstractRNA N6-methyladenosine (m6A) is an emerging regulator of mRNA modifications and represents a novel player in tumorigenesis. Although it has functional significance in both pathological and physiological processes, the role of m6A modification in pancreatic ductal cancer (PDAC) remains elusive. Here, we showed that high fat mass and obesity-associated gene (FTO) expression was associated with a poor prognosis in PDAC patients and that suppression of FTO expression inhibited cell proliferation. Here, m6A sequencing (m6A-seq) was performed to screen genes targeted by FTO. The effects of FTO stimulation on the biological characteristics of pancreatic cancer cells, including proliferation and colony formation, were investigated in vitro and in vivo. The results indicate that FTO directly targets platelet-derived growth factor C (PDGFC) and stabilizes its mRNA expression in an m6A-YTHDF2-dependent manner. m6A-methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), RNA immunoprecipitation (RIP), and luciferase reporter assays were employed to validate the specific binding of FTO to PDGFC. PDGFC upregulation led to reactivation of the Akt signaling pathway, promoting cell growth. Overall, our study reveals that FTO downregulation leads to increased m6A modifications in the 3ʹ UTR of PDGFC and then modulates the degradation of its transcriptional level in an m6A-YTHDF2-dependent manner, highlighting a potential therapeutic target for PDAC treatment and prognostic prediction.
MLKL deficiency in BrafV600EPten−/− melanoma model results in a modest delay of nevi development and reduced lymph node dissemination in male mice
Authors: Martens Sofie , Takahashi Nozomi , Blancke Gillian , Vandamme Niels , Verschuere Hanne , Divert Tatyana , Vuylsteke Marnik , Berx Geert , Vandenabeele Peter 
Published: April 2022

AbstractCancers acquire several capabilities to survive the multistep process in carcinogenesis. Resisting cell death is one of them. Silencing of the necroptosis initiator Ripk3 occurs in a wide variety of cancer types including melanoma. Little is known about the role of the necroptosis executioner MLKL in tumor development. Studies often indicate opposing roles for MLKL as a tumor-suppressing or a tumor-promoting protein. This study investigates the role of MLKL during melanoma initiation and progression using a tamoxifen-inducible melanoma mouse model driven by melanocyte-specific overexpression of mutated Braf and simultaneous deletion of Pten (BrafV600EPten−/−). In this model we observed a clear sex difference: melanoma initiation and progression were faster in females mice. Mlkl deficiency in male mice resulted in a modest but significant reduction of nevi growth rate compared to the littermate control. In these mice, infiltration and expansion of melanoma cells in the inguinal lymph node were also modestly decreased. This is likely to be a consequence of the delay in nevi development. No significant difference was observed in the Mlkl-deficient condition in female mice in which melanoma development was faster. Overall, our results indicate that in this genetic model MLKL has a minor role during melanoma initiation and progression.
Sex differences in global disability-adjusted life years due to ischemic stroke: findings from global burden of diseases study 2019
Authors: Cao Miaomiao , Li Bolin , Rong Jie , Li Qian , Sun Chaofeng 
Published: April 2022

AbstractTo investigate the sex differences in disability-adjusted life years (DALYs) due to ischemic stroke (IS) by year, location and age. We extracted sex-specific data on DALYs number, age-standardized DALYs rate (ASDR) and all-age DALYs rate of IS by year, location and age from the Global Burden of Diseases study 2019. The estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trend of ASDR. For both sexes, although the ASDR of IS slightly decreased from 1990 to 2019, there has been an 60.3% increase in DALYs number worldwide. Sex difference in DALYs number (men minus women) decreased from − 2.83 million in 1990 to 0.14 million in 2019, while the men to women’s ASDR ratio slightly increased from 1.10 in 1990 to 1.21 in 2019. The sex differences in IS DALYs showed remarkable regional variation. The largest sex differences in DALYs number and ASDR were in China and Vietnam. Middle-aged men had a higher IS DALYs than their age-matched counterparts. High systolic blood pressure accounted for the highest DALYs number in 2019, but the top three attributable risk factors that had the greatest sex differences were tobacco, dietary risk, and alcohol use. Sex differences in IS DALYs varied by year, location and age, mostly attributed to the disproportion of cardiovascular risk factors between sexes. Considering the population growth and aging, it is necessary to monitor the sex difference in IS DALYs in different populations and thus provide evidence for local administration to improve current preventive and management strategies of IS.
Nematic superconductivity in magic-angle twisted bilayer graphene from atomistic modeling
Authors: Löthman Tomas , Schmidt Johann , Parhizgar Fariborz , Black-Schaffer Annica M. 
Published: April 2022

AbstractTwisted bilayer graphene (TBG) develops large moiré patterns at small twist angles with flat energy bands hosting domes of superconductivity. The large system size and intricate band structure have however hampered investigations into the superconducting state. Here, using full-scale atomistic modelling with local electronic interactions, we find at and above experimentally relevant temperatures a highly inhomogeneous superconducting state with nematic ordering on both atomic and moiré length scales. The nematic state has a locally anisotropic real-valued d-wave pairing, with a nematic vector winding throughout the moiré pattern, and is three-fold degenerate. Although d-wave symmetric, the superconducting state has a full energy gap, which we tie to a π-phase interlayer coupling. The superconducting nematicity is further directly detectable in the local density of states. Our results show that atomistic modeling is essential and also that very similar local interactions produce very different superconducting states in TBG and the high-temperature cuprate superconductors.
Challenges and opportunities in the development of metal-based anticancer theranostic agents
Authors: Vaidya Shreyas P. , Gadre Shubhankar , Kamisetti Ravi Teja , Patra Malay 
Published: April 2022

AbstractAround 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach toward cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review, we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of its biological properties.
Beratung Angehöriger pathologischer
Glücksspieler/-innen: Status quo und
Unterstützungsbedarf
Authors: Härtl Sabine , Schröder Sonja , Gartner Corinna , Wodarz Norbert 
Published: April 2022

Zusammenfassung
Ziel Angehörige von Menschen mit Glücksspielproblemen sind
mit gesundheitlichen, sozialen und emotionalen Belastungen konfrontiert. Bis
dato existiert jedoch kein etabliertes Konzept zur Unterstützung
für diese Zielgruppe. Deshalb sollen in dieser Studie zum einen
relevante Rahmenbedingungen und inhaltliche Aspekte der Arbeit mit
Angehörigen von Menschen mit Glücksspielproblemen
geklärt und zum anderen die Grundlage für die Entwicklung einer
Kurzintervention geschaffen werden.
Methodik Onlinegestützte deutschlandweite Befragung von
Suchthilfe-Mitarbeitenden (n=102) sowie Gruppendiskussion mit
Angehörigen (n=4) im Herbst 2019.
Ergebnisse Die befragten Mitarbeitenden in der Suchthilfe nannten als die
wichtigsten Themen für die Beratung von Angehörigen von Menschen
mit Glücksspielproblemen das Verhalten Angehöriger
gegenüber Betroffenen, Geldmanagement, den Umgang mit Emotionen,
Beziehungsberatung und Psychoedukation. Die meisten Befragten gaben an, die
Angehörigen im Einzelsetting (68%) in durchschnittlich 3
Sitzungen (Median 2,5; Min=1; Max=15) zu beraten. Der Abstand
zwischen den Sitzungen beträgt durchschnittlich 3 Wochen (Median 2
Wochen). Für die zu entwickelnde Kurzintervention wurden
Verantwortungsrückgabe und Selbstfürsorge (69%),
Problem-/Belastungsexploration (42%) und Tipps zur finanziellen
Existenzsicherung (28%) als die drei wichtigsten Themen
ausgewählt. Sowohl als Erfolgsfaktor für eine gelingende
Angehörigenberatung als auch für die Adhärenz der
Angehörigen wurde eine positive bzw. wertschätzende
Beziehungsgestaltung am häufigsten genannt. Die Ergebnisse aus der
Gruppendiskussion mit Angehörigen deuten in eine ähnliche
Richtung: Die Themen Verhalten als Angehörige gegenüber
Betroffenen, Abgrenzung/Verantwortlichkeiten und konkrete
Verhaltenstipps wurden als wichtig erachtet; jedoch ging es den
Angehörigen eher darum, sich „richtig“ zu verhalten,
während der Fokus der Suchthilfe auf der Abgrenzung und
Selbstfürsorge lag.
Schlussfolgerungen Die Studie liefert wichtige Hinweise auf relevante
Themen und Inhalte für die Beratung Angehöriger von Menschen mit
Glücksspielproblemen. Auf Basis dieser Ergebnisse soll im
nächsten Schritt eine Kurzintervention entwickelt werden. Hinsichtlich
der Beratungsmethoden herrscht jedoch weiterer Forschungsbedarf. Zum anderen
sollte untersucht werden, wie der Zugang der Angehörigen zum Hilfesystem
und dessen Bekanntheit optimiert sowie bestehende Barrieren vermindert werden
können.
Newly proposed quantitative criteria can assess chronic atrophic gastritis via probe-based confocal laser endomicroscopy (pCLE): a pilot study
Authors: Robles-Medranda Carlos , Puga-Tejada Miguel , Oleas Roberto , Baquerizo-Burgos Jorge , Alcívar-Vásquez Juan , Del Valle Raquel , Cifuentes-Gordillo Carlos , Alvarado-Escobar Haydee , Ponce-Velez Daniel , Ospina-Arboleda Jesenia , Pitanga-Lukashok Hannah 
Published: April 2022

Abstract
Background and study aims Probe-based confocal laser endomicroscopy (pCLE) can provide high magnification to evaluate chronic atrophic gastritis (CAG), but the current pCLE criteria are qualitative and prone to variability. We aimed to propose a quantitative CAG criterion based on pCLE to distinguish non-atrophic gastritis (NAG) from CAG.
Patients and methods This observational, exploratory pilot study included patients with NAG and CAG evaluated via esophagogastroduodenoscopy, pCLE, and histology. We measured the gastric glands density, gastric gland area, and inter-glandular distance during pCLE.
Results Thirty-nine patients (30/39 with CAG) were included. In total, 194 glands were measured by pCLE, and 18301 were measured by histology, with a median of five glands per NAG patient and 4.5 per CAG patient; pCLE moderately correlate with histology (rho = 0.307; P = 0.087). A gland area of 1890–9105 µm2 and an inter-glandular distance of 12 to 72 µm based on the values observed in the NAG patients were considered normal. The proposed pCLE-based CAG criteria were as follows: a) glands density < 5; b) gland area < 1/16 the pCLE field area (< 1890 µm2) or > 1/4 the pCLE field area (> 9105 µm2); or c) inter-glandular distance < 12 or > 72 µm; CAG was diagnosed by the presence of at least one criterion. The proposed criteria discriminated CAG with a ranged sensitivity of 76.9 % to 92.3 %, a negative predictive value of 66.6 % to 80.0 %, and 69.6 % to 73.9% accuracy.
Conclusions The proposed pCLE criteria offer an accurate quantitative measurement of CAG with high sensitivity and excellent interobserver agreement. Larger studies are needed to validate the proposed criteria.
Hospital compound-level endoscopy training quality performance: scoping the spectrum
Authors: Eley Catherine , Brown Chris , Hawkes Neil D. , Egan Richard J. , Lewis Wyn G. 
Published: April 2022

Abstract
Background and study aims This study aimed to assess the quality of endoscopy training in a UK Statutory Educational Body compared with Joint Advisory Group on Gastrointestinal Endoscopy Training standards (JETS).
Methods A total of 28,298 training procedures recorded by 211 consecutive cross-specialty trainee endoscopists registered with JETS in 18 hospitals during 2019 were analyzed. Data included trainer and trainee numbers, training list frequency, procedures, direct observation of procedural skills (DOPS) completion, and key performance indicators.
Results Annual median training procedures per hospital were 1395 (interquartile range (IQR) 465–2365). Median trainers and trainees per unit were 11 (6–18) and 12 (7–16), respectively, (ratio 0.8 [0.7–1.3]). Annual training list frequency per trainee was 13 (10–17), 35.0 % short of Joint Advisory Group (JAG) standard (n = 20, P = 0.001, effect size –0.56). Median points per adjusted training list were 11 (5–18). Median DOPS per trainee and trainer were three (1–6) and four (1–7) respectively; completing 0.2 DOPS (0.1–0.4) per list and amounting to six (2–12) per 200 procedures: fewer than half of the JAG standard (20 per 200) (P < 0.001, –0.61). Esophagogastroduodenoscopy median KPI: J maneuver 94 % (90–96), D2 intubation 93 % (91–96); Colonoscopy KPI: cecal intubation 82 % (72–90), polyp detection rate 25 % (18–34). Compound hospital score ranged from nine to 26 (median 17 [14–20]).
Conclusions Important performance disparity emerged with three-fold variation in compound hospital training quality and most units underperforming compared with JAG standards. Trainees and training program directors should be aware of such metrics to improve quality endoscopy educational programs and consider formal adjuncts to optimize training.
Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions
Authors: Schutz Hannah M. , Quispel Rutger , Veldt Bart J. , Smedts Frank M.M. , Anten Marie-Paule G.F. , Hoogduin Klaas J. , Honkoop Pieter , van Nederveen Francien H. , Hol Lieke , Kliffen Mike , Fitzpatrick Claire E. , Erler Nicole S. , Bruno Marco J. , van Driel Lydi M.J.W. ,   on behalf of QUEST
Published: April 2022

AbstractBackground and study aims In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool.Patients and methods All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018. CUSUM learning curves were plotted for overall performance and for performance per center. The American Society of Gastrointestinal Endoscopy-defined key performance indicators, rate of adequate sample (RAS), and diagnostic yield of malignancy (DYM) were used for this purpose. Feedback regarding performance was provided on multiple occasions at regional interest group meetings during the study period.Results A total of 431 EUS-guided TA procedures in 403 patients were included in this study. The overall and per center CUSUM curves for RAS improved over time. CUSUM curves for DYM revealed gradual improvement, reaching the predefined performance target (70 %) overall, and in three of five contributing centers in 2018. Analysis of a sudden downslope development in the CUSUM curve of DYM in one center revealed temporary absence of a senior cytopathologist to have had a temporary negative impact on performance.Conclusions CUSUM-derived learning curves allow for assessment of best practices by comparison among peers in a multidisciplinary multicenter quality improvement initiative and proved to be a valuable and easy-to-interpret means to evaluate EUS performance over time.
Preservation of terminal branches of the palmar cutaneous branch of the median nerve in open carpal tunnel release
Authors: Montanari Sara , Corzani Marco , Luchetti Riccardo , Atzei Andrea 
Published: April 2022

Abstract
Purpose Post-operative pain in the palm and scar area is the most common complication after carpal tunnel release and injury to the terminal branches of the palmar cutaneous nerve is generally considered one of the causes for this complication. The Authors performed an intraoperative study preserving the terminal branches of the palmar cutaneous branch of the median nerve and verifying the frequency, location and direction of the branches that cross an interthenar incision.
Method and Material Eighty-five consecutive patients (57 F – 28 M, mean age 66 y) underwent carpal tunnel release between February and June 2021. The cutaneous branches crossing the incision were identified and preserved by careful dissection. Subsequently they were counted and classified by their direction and distance from the proximal border of the transverse carpal ligament.
Results Sensory branches were found in 40 % of cases (34/85) and their origin was observed at an average of 1.05 cm (0–1.8 cm) distal from the proximal border of the carpal tunnel. A total of 44 branches were observed of which 23 branches crossed the incision with a transverse course and 21 with an oblique, generally proximal-distal radio-ulnar course. The subcutaneous layer overlying the distal third of the transverse carpal ligament was found to be devoid of sensory branches, therefore it can be considered a relatively safe area.
Conclusion Isolation and protection of palmar sensory branches is important for improving carpal tunnel release results. This goal can be more easily achieved by locating the skin incision on the distal third of the transverse carpal ligament, where the sensory branches have a lower frequency, possibly associated with a second proximal incision (biportal technique) to better visualize the proximal portion of the ligament and antebrachial fascia.
Durchführung und Befundung der 123I-mIBG-Szintigraphie bei Kindern und Jugendlichen mit Neuroblastom (Version 3) – DGN-Handlungsempfehlung (S1-Leitlinie), Stand: 2/2020 – AWMF-Registernummer: 031-040
Authors: Schmidt Matthias , Decarolis Boris , Franzius Christiane , Hero Barbara , Pfluger Thomas , Rogasch Julian Manuel Michael , Simon Thorsten 
Published: April 2022

ZusammenfasssungDie aktualisierte 3. Fassung der 123I-mIBG-Szintigrafie bei Kindern und Jugendlichen berücksichtigt folgende aktuelle Entwicklungen: Die Leitlinie fokussiert auf die diagnostische Anwendung von 123I-mIBG beim Neuroblastom. 131I-mIBG kommt bei der Radionuklidtherapie zum Einsatz. An wenigen Stellen wird auf Besonderheiten des 131I-mIBG bei der Befundung von Posttherapie-Szintigrammen eingegangen. Es werden aktuelle Entwicklungen in der Patientenvorbereitung bei den Medikamenteninterferenzen und Empfehlungen zur Schilddrüsenblockade berücksichtigt. Neue Empfehlungen der zu applizierenden Aktivität werden genannt und die damit assoziierten Probleme diskutiert. Die Bildakquisition unter Berücksichtigung von SPECT bzw. SPECT/CT des Körperstammes inkl. des Kopfes wird berücksichtigt. Die Befundung unter Verwendung des SIOPEN-Scores wird neu aufgenommen. Auf PET bzw. PET/CT mit 18F-DOPA bzw. 68Ga-DotaTATE wird verwiesen.
Endoscopic ultrasound-guided gastroenterostomy versus surgical gastrojejunostomy in treatment of malignant gastric outlet obstruction: Systematic review and meta-analysis
Authors: Bomman Shivanand , Ghafoor Adil , Sanders David J. , Jayaraj Mahendran , Chandra Shruti , Krishnamoorthi Rajesh 
Published: April 2022

Abstract
Background and study aims Palliative treatment of malignant gastric outlet obstruction (GOO) has conventionally been with surgical gastrojejunostomy (SGJ). Advent of devices like lumen apposing metal stents has made endoscopic ultrasound-guided gastroenterostomy (EUS-GE) a potential alternative to SGJ for these patients. We performed a systematic review and meta-analysis of studies that compared outcomes of EUS-GE versus SGJ.
Methods We performed a comprehensive systematic search of multiple electronic databases and conference proceedings through January 2021 and identified six studies that compared outcomes of EUS-GE versus SGJ in the management of malignant GOO. The rates of technical success, clinical success, and AEs were analyzed, and pooled odds ratios were calculated using random effects model.
Results Six studies were included in our analysis with a total of 484 patients, of which 291 underwent EUS-GE and 193 underwent SGJ. The technical success rate of SGJ was superior to EUS-GE (OR = 0.195; 95 %CI:0.054–0.702; P = 0.012; I2 = 0). The clinical success of EUS-GE was statistically similar to SGJ (OR = 1.566; 95 %CI:0.585–4.197; P = 0.372; I2 = 46.68 %). EUS-GE had significantly fewer AEs compared to SGJ (OR = 0.295; 95 %CI:0.172–0.506; P < 0.005; I2 = 0). Among studies which reported reintervention rates, EUS-GE was statistically similar to SGJ (OR = 0.587; 95 %CI:0.174–1.979; P = 0.390, I2 = 54.91). Minimal to moderate heterogeneity was noted in the analyses.
Conclusions EUS-GE has equivalent clinical success and reintervention rates, but significantly lower adverse events compared to SGJ. When feasible, EUS-GE appears to be an effective and safe alternative to SGJ for palliative management of malignant GOO.