bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraining $$ \mathcal{CP} $$-violation in the Higgs-top-quark interaction using machine-learning-based inference
Authors: Bahl Henning , Brass Simon 
Published: March 2022

AbstractWhile$$ \mathcal{CP} $$CPviolation in the Higgs interactions with massive vector boson is already tightly constrained, the$$ \mathcal{CP} $$CPnature of the Higgs interactions with fermions is far less constrained. In this work, we assess the potential of machine-learning-based inference methods to constrain$$ \mathcal{CP} $$CPviolation in the Higgs top-Yukawa coupling. This approach enables the use of the full available kinematic information. Concentrating on top-associated Higgs production with the Higgs decaying to two photons, we derive expected exclusion bounds for the LHC and the high-luminosity phase of the LHC. We also study the dependence of these bounds on the Higgs interaction with massive vector bosons and their robustness against theoretical uncertainties. In addition to deriving expected exclusion bounds, we discuss at which level a non-zero$$ \mathcal{CP} $$CP-violating top-Yukawa coupling can be distinguished from the SM. Moreover, we analyze which kinematic distributions are most sensitive to a$$ \mathcal{CP} $$CP-violating top-Yukawa coupling.
Upstream open reading frames regulate translation of cancer-associated transcripts and encode HLA-presented immunogenic tumor antigens
Authors: Nelde Annika , Flötotto Lea , Jürgens Lara , Szymik Laura , Hubert Elvira , Bauer Jens , Schliemann Christoph , Kessler Torsten , Lenz Georg , Rammensee Hans-Georg , Walz Juliane S. , Wethmar Klaus 
Published: March 2022

Abstract
Background
Upstream open reading frames (uORFs) represent translational control elements within eukaryotic transcript leader sequences. Recent data showed that uORFs can encode for biologically active proteins and human leukocyte antigen (HLA)-presented peptides in malignant and benign cells suggesting their potential role in cancer cell development and survival. However, the role of uORFs in translational regulation of cancer-associated transcripts as well as in cancer immune surveillance is still incompletely understood.

Methods
We examined the translational regulatory effect of 29 uORFs in 13 cancer-associated genes by dual-luciferase assays. Cellular expression and localization of uORF-encoded peptides (uPeptides) were investigated by immunoblotting and immunofluorescence-based microscopy. Furthermore, we utilized mass spectrometry-based immunopeptidome analyses in an extensive dataset of primary malignant and benign tissue samples for the identification of naturally presented uORF-derived HLA-presented peptides screening for more than 2000 uORFs.

Results
We provide experimental evidence for similarly effective translational regulation of cancer-associated transcripts through uORFs initiated by either canonical AUG codons or by alternative translation initiation sites (aTISs). We further demonstrate frequent cellular expression and reveal occasional specific cellular localization of uORF-derived peptides, suggesting uPeptide-specific biological implications. Immunopeptidome analyses delineated a set of 125 naturally presented uORF-derived HLA-presented peptides. Comparative immunopeptidome profiling of malignant and benign tissue-derived immunopeptidomes identified several tumor-associated uORF-derived HLA ligands capable to induce multifunctional T cell responses.

Conclusion
Our data provide direct evidence for the frequent expression of uPeptides in benign and malignant human tissues, suggesting a potentially widespread function of uPeptides in cancer biology. These findings may inspire novel approaches in direct molecular as well as immunotherapeutic targeting of cancer-associated uORFs and uPeptides.
Therapeutische Injektion und Manuelle Medizin beim tiefen Rückenschmerz
Authors: Schütz Uwe H. W. 
Published: March 2022

Zusammenfassung
Hintergrund
Angelehnt an die zielorientierte Therapieplanung und -führung in der Versorgung chronisch Rheumakranker, plädiert der Autor bei Patienten mit (chronischem) degenerativem tiefem Rückenschmerz (TRS), orientiert an den differenzialtherapeutischen Grundsätzen der Manuellen Medizin (MM), und unter Kenntnis von Techniken und Evidenzen therapeutischer Lokalinfiltrationen (TLI), für die Etablierung eines strukturierten mechanismenbasierten Therapiekonzeptes im Sinne des „treat to target“ (T2T) im ambulanten schmerztherapeutischen Versorgungsbereich.

Diagnostik
Dies setzt eine konsequente (Primär‑)Diagnostik mit Schmerzanalyse unter der Prämisse, dass TRS, wenn strukturell-funktionell bedingt, immer spezifisch ist, voraus. Eine breite biopsychosoziale Anamnese und strukturbezogene klinisch-bildgebende (Ausschluss‑)Diagnostik mit funktioneller Differenzierung nach MM-Grundsätzen und ggf. interventionelle Blocks, sollten am Ende zur Formulierung einer 3‑Ebenen-Diagnose als Voraussetzung zu einer mechanismenbasiert-zielorientiert-hierarchischen Stufentherapie bei TRS führen. Diese wird in diesem Artikel pragmatisch fallorientiert, unter Implementierung von Techniken und Evidenzen der TLI und MM, vorgestellt.
Effects of elevated temperature on the performance and survival of pacific crown-of-thorns starfish (Acanthaster cf. solaris)
Authors: Lang Bethan J. , Donelson Jennifer M. , Caballes Ciemon F. , Uthicke Sven , Doll Peter C. , Pratchett Morgan S. 
Published: March 2022

AbstractPopulation irruptions of Pacific crown-of-thorns starfish (Acanthaster cf. solaris) have caused substantial damage to coral reefs, but it is largely unknown how this asteroid will fare in a warmer ocean. We exposed these starfish to one of four thermal treatments, with final temperatures of 26 °C (control, annual average), 28 °C (summer average), 30 °C (summer maximum) and 32 °C (predicted summer maximum by 2100). We measured the righting time, movement rate, standard metabolic rate and probability of survival of the crown-of-thorns starfish at various timepoints over ~ 60 days. We found that while temperature did not affect righting time, it did significantly affect movement rate. The movement rate of starfish increased across the 26 to 30 °C range, with those at 28 °C and 30 °C moving 18 and 27% faster than those at the control temperature. Similarly, the standard metabolic rate of starfish increased from 26 to 30 °C, with metabolism 100% and 260% faster at 28 °C and 30 °C compared to those at the 26 °C control. At 32 °C, individual starfish exhibited a 14% slower movement rate, a 33% slower metabolic rate, and also exhibited a fourfold lower probability of survival than those at 30 °C. These results indicate that 32 °C is above the thermal optimum of crown-of-thorns starfish, suggesting that prolonged exposure to temperatures that are expected to be regularly exceeded under near-future climate change may be detrimental to this species.
Clinical comparative study assessing the effect of ivabradine on neopterin and NT-Pro BNP against standard treatment in chronic heart failure patients
Authors: Dogheim Gaidaa M. , Khairat Ibtsam , Omran Gamal A. , El-Haggar Sahar M. , Amrawy Ahmed M. El , Werida Rehab H. 
Published: March 2022

Abstract
Purpose
Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers.

Methods
Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups.

Results
There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002).

Conclusion
Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF.
Trial registration
Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure—Full Text View—ClinicalTrials.gov.
Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy
Authors: Sato Yosuke , Casson Cierra N. , Matsuda Atsushi , Kim James I. , Shi Judy Qiuju , Iwasaki Shinji , Chen Susan , Modrell Brett , Chan Chingkit , Tavares Daniel , Austen Douglas , Ida Koh , Tayber Olga , Hein Pyae , Comeau Robert , Lin Yafang , Shaw Michael H. 
Published: March 2022

AbstractIpilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed that Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through the depletion of intratumoral regulatory T cells (Tregs). However, the contribution of the Fc-independent functions of anti-CTLA-4 antibodies to the observed efficacy is not fully understood. H11, a non-Fc-containing single-domain antibody (VHH) against CTLA-4, has previously been demonstrated to block CTLA-4-ligand interaction. However, in vivo studies demonstrated lack of anti-tumor efficacy with H11 treatment. Here, we show that a half-life extended H11 (H11-HLE), despite the lack of Fc effector functions, induced potent anti-tumor efficacy in mouse syngeneic tumor models. In addition, a non-Fc receptor binding version of ipilimumab (Ipi-LALAPG) also demonstrated anti-tumor activity in the absence of Treg depletion. Thus, we demonstrate that Fc-independent functions of anti-CTLA-4 antibodies contributed to anti-tumor efficacy, which may indicate that non-Treg depleting activity of anti-CTLA-4 therapy could benefit cancer patients in the clinic.
Esophageal Achalasia: Pros and Cons of the Treatment Options
Authors: Costantini Mario , Salvador Renato , Costantini Andrea 
Published: March 2022

AbstractAchalasia is a primary esophageal motility disorder of unknown origin. The goal of treatment is to reduce the resistance caused by a lower esophageal sphincter that fails to relax and is frequently hypertensive. Many treatment options are available to achieve this goal. In this review, we discuss the pros and cons of each therapeutic approach.
Influence of oral contrast type and volume on patient experience and quality of luminal distension at MR Enterography in Crohn’s disease: an observational study of patients recruited to the METRIC trial
Authors: Bhatnagar Gauraang , Mallett Sue , Quinn Laura , Ilangovan Rajapandian , Patel Uday , Jaffer Asif , Pawley Christopher , Gupta Arun , Higginson Anthony , Slater Andrew , Tolan Damian , Zealley Ian , Halligan Steve , Taylor Stuart A ,   on behalf of the METRIC study investigators
Published: March 2022

Abstract
Objectives
To compare the distention quality and patient experience of oral mannitol and polyethylene glycol (PEG) for MRE.

Methods
This study is a retrospective, observational study of a subset of patients enrolled in a multicentre, prospective trial evaluating the diagnostic accuracy of MRE for small bowel Crohn’s. Overall and segmental MRE small bowel distention, from 105 patients (64 F, mean age 37) was scored from 0 = poor to 4 = excellent by two experienced observers (68 [65%] mannitol and 37 [35%] PEG). Additionally, 130 patients (77 F, mean age 34) completed a questionnaire rating tolerability of various symptoms immediately and 2 days after MRE (85 [65%] receiving mannitol 45 [35%] receiving PEG). Distension was compared between agents and between those ingesting ≤ 1 L or > 1 L of mannitol using the test of proportions. Tolerability grades were collapsed into “very tolerable,” “moderately tolerable,” and “not tolerable.”

Results
Per patient distension quality was similar between agents (“excellent” or “good” in 54% [37/68] versus 46% [17/37]) with mannitol and PEG respectively. Jejunal distension was significantly better with mannitol compared to PEG (40% [27/68] versus 14% [5/37] rated as excellent or good respectively). There was no significant difference according to the volume of mannitol ingested. Symptom tolerability was comparable between agents, although fullness following MRE was graded as “very tolerable” in 27% (12/45) of patients ingesting PEG, verses 44% (37/84) ingesting mannitol, difference 17% (95% CI 0.6 to 34%).

Conclusion
Mannitol-based solutions and PEG generally achieve comparable distension quality and side effect profiles, although jejunal distension is better quality with mannitol. Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.

Key Points
• Mannitol-based and PEG-based oral preparation agents generally achieve comparable distension quality for MRE with the exception of the jejunum which is better distended with mannitol.
• Mannitol-based and PEG-based oral preparation agents used for MRE have similar side effect profiles.
• Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol.
Vitreous cytokine levels following the administration of a single 0.19 mg fluocinolone acetonide (ILUVIEN®) implant in patients with refractory diabetic macular edema (DME)—results from the ILUVIT study
Authors: Deuchler Svenja K. , Schubert Ralf , Singh Pankaj , Chedid Adonis , Kenikstul Ninel , Scott Julia , Kohnen Thomas , Ackermann Hanns , Koch Frank 
Published: March 2022

Abstract
Purpose
To investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema.

Methods
A single-center phase IV study involving 12 patients’ eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined.

Results
There were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout.

Conclusion
This study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture.
A co-alteration parceling of the cingulate cortex
Authors: Manuello Jordi , Mancuso Lorenzo , Liloia Donato , Cauda Franco , Duca Sergio , Costa Tommaso 
Published: March 2022

AbstractThe cingulate cortex is known to be a complex structure, involved in several cognitive and emotional functions, as well as being altered by a variety of brain disorders. This heterogeneity is reflected in the multiple parceling models proposed in the literature. At the present, sub-regions of the cingulate cortex had been identified taking into account functional and structural connectivity, as well as cytological and electrochemical properties. In the present work, we propose an innovative node-wise parceling approach based on meta-analytic Bayesian co-alteration. To this aim, 193 case–control voxel-based morphometry experiments were analyzed, and the Patel’sκindex was used to assess probability of morphometric co-alteration between nodes placed in the cingulate cortex and in the rest of the brain. Hierarchical clustering was then applied to identify nodes in the cingulate cortex exhibiting a similar pattern of whole-brain co-alteration. The obtained dendrogram highlighted a robust fronto-parietal cluster compatible with the default mode network, and being supported by the interplay between the retrosplenial cortex and the anterior and posterior cingulate cortex, rarely described in the literature. This ensemble was further confirmed by the analysis of functional patterns. Leveraging on co-alteration to investigate cortical organization could, therefore, allow to combine multimodal information, resolving conflicting results sometimes coming from the separate use of singular modalities. Crucially, this provides a valuable way to understand the pathological brain using data driven, whole-brain informed and context-specific evidence in a way not yet explored in the field.
Cognitive and academic outcomes in children with chronic kidney disease
Authors: Kim Siah , Van Zwieten Anita , Lorenzo Jennifer , Khalid Rabia , Lah Suncica , Chen Kerry , Didsbury Madeleine , Francis Anna , Mctaggart Steven , Walker Amanda , Mackie Fiona E. , Prestidge Chanel , Teixeira-Pinto Armando , Tong Allison , Blazek Katrina , Barton Belinda , Craig Jonathan C. , Wong Germaine 
Published: March 2022

Abstract
Background
Few data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time.

Methods
We included 53 participants (aged 6–18 years) with CKD stages 1–5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status.

Results
At baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1–5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (− 25.3, − 3.3), 11 (− 18.5, − 3.6), 8.5 (− 17.6, 0.76), and 10 (− 18.6, − 1.3) points lower than children with CKD Stages 1–5. Spelling and numerical operations scores declined by 0.7 (− 1.4, − 0.1) and 1.0 (− 2.0, 0.2) units per year increase in age, regardless of CKD stage.

Conclusions
Children treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1–5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD.

Graphical abstract
A higher resolution version of the Graphical abstract is available as Supplementary information.
Health-related quality of life in long-term survivors of childhood brain tumors: a population-based cohort study
Authors: Ljungman Lisa , Remes Tiina , Westin Elisabeth , Huittinen Alina , Lönnqvist Tuula , Sirkiä Kirsti , Rantala Heikki , Ojaniemi Marja , Harila Marika , Lähteenmäki Päivi , Arikoski Pekka , Wikman Anna , Harila-Saari Arja 
Published: March 2022

Abstract
Purpose
Survivors of childhood brain tumors (BT) are at high risk for long-term physical and psychological sequelae. Still, knowledge about health-related quality of life (HRQL) and associated factors in this population is sparse. This study investigated HRQL and its predictors in long-term survivors of childhood BT.

Methods
Survivors of childhood BT (mean age = 28.1 years, SD = 6.8, n = 60) underwent clinical examination and neurocognitive examination, and completed self-rating questionnaires assessing HRQL (RAND-36) and depressive symptoms (Beck Depression Inventory-II). Socio-demographic information was gathered via a questionnaire. Tumor- and treatment-related information was collected from medical records. Control group data were collected from age-matched controls (n = 146) without a history of cancer, randomly selected from the local population registry. Multiple linear regression models were used to investigate predictors of HRQL; separate models were fitted for each domain of the RAND-36.

Results
Male survivors (mean age = 27.0, SD = 6.0, n = 39) reported significantly lower HRQL than male controls in the domains of physical functioning, general health, vitality, social functioning, and role limitations-emotional. Female survivors (mean age = 30.2 years, SD = 7.6, n = 21) reported comparable levels as female controls in all domains except physical functioning. A higher burden of late effects, not working/studying, being diagnosed with BT during adolescence, and reporting current depressive symptoms were significant predictors of lower HRQL.

Conclusion
Our results highlight that male survivors of childhood BT are at particular risk of impaired HRQL. Also, results point to the close relation between symptoms of depression and impaired HRQL in survivors of childhood BT which should be acknowledged by long-term follow-up care.
Effect of intraoperative needle biopsy on the survival of nonsmall cell lung cancer patients: a propensity score matching analysis
Authors: Morota Mizuki , Nagano Masaaki , Ijiri Naohiro , Yoshiyasu Nobuyuki , Shinohara Yoshikazu , Nobori Yuya , Yamaguchi Hirokazu , Kawashima Shun , Yanagiya Masahiro , Konoeda Chihiro , Kitano Kentaro , Sato Masaaki , Nakajima Jun 
Published: March 2022

Abstract
Purpose
It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC).

Methods
The subjects of this retrospective study were 953 patients with pathological stage I–III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups.

Results
After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05).

Conclusions
The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.