bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: a case control study
Authors: Said Khalid N. , Al-Momani Ahmed M. , Almaseeh Jassim A. , Marouf Nadya , Shatta Amer , Al-Abdulla Jassim , Alaji Sahar , Daas Hanin , Tharupeedikayil Shailaja S. , Chinta Venkateswara Rao , Hssain Ali Ait , Abusamak Mohammad , Salih Shiraz , Barhom Noha , Cai Wenji , Sanz Mariano , Tamimi Faleh 
Published: July 2022

Abstract

Background
In previous studies, COVID-19 complications were reported to be associated with periodontitis. Accordingly, this study was designed to test the hypothesis that a history of periodontal therapy could be associated with lower risk of COVID-19 complications.

Methods
A case–control study was performed using the medical health records of COVID-19 patients in the State of Qatar between March 2020 and February 2021 and dental records between January 2017 and December 2021. Cases were defined as COVID-19 patients who suffered complications (death, ICU admissions and/or mechanical ventilation); controls were COVID-19 patients who recovered without major complications. Associations between a history of periodontal therapy and COVID-19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood parameters were compared using Kruskal–Wallis test.

Results
In total, 1,325 patients were included. Adjusted odds ratio (AOR) analysis revealed that non-treated periodontitis was associated with significant risk of need for mechanical ventilation (AOR = 3.91, 95% CI 1.21–12.57, p = 0.022) compared to periodontally healthy patients, while treated periodontitis was not (AOR = 1.28, 95% CI 0.25–6.58, p = 0.768). Blood analyses revealed that periodontitis patients with a history of periodontal therapy had significantly lower levels of D-dimer and Ferritin than non-treated periodontitis patients.

Conclusion
Among COVID-19 patients with periodontal bone loss, only those that have not received periodontal therapy had higher risk of need for assisted ventilation. COVID-19 patients with a history of periodontal therapy were associated with significantly lower D-dimer levels than those without recent records of periodontal therapy.

Clinical relevance
The fact that patients with treated periodontitis were less likely to suffer COVID-19 complications than non-treated ones further strengthen the hypothesis linking periodontitis to COVID-19 complications and suggests that managing periodontitis could help reduce the risk for COVID-19 complications, although future research is needed to verify this.
The role of threat anticipation in the development of psychopathology in adolescence: findings from the SIGMA Study
Authors: Paetzold Isabell , Gugel Jessica , Schick Anita , Kirtley Olivia J. , Achterhof Robin , Hagemann Noemi , Hermans Karlijn S. F. M. , Hiekkaranta Anu P. , Lecei Aleksandra , Myin-Germeys Inez , Reininghaus Ulrich 
Published: July 2022

AbstractChildhood adversity is associated with psychopathology. First evidence in adults suggests that threat anticipation, i.e., an enhanced anticipation of unpleasant events creating an enduring sense of threat, may be a putative mechanism linking childhood adversity to psychopathology. This study aimed to test the indirect effect of childhood adversity on psychopathology via threat anticipation in a large community sample of adolescents. We measured childhood trauma and bullying victimization (as indicators of childhood adversity), threat anticipation, general psychopathology and prodromal psychotic symptoms in adolescents aged 12–16 years (full sample size N = 1682; minimum sample size in the complete case sample N = 449) in wave I of the SIGMA study. We found strong evidence that childhood adversity (e.g. childhood trauma, adj. β (aβ) = 0.54, p < .001) and threat anticipation (e.g. aβ = 0.36, p < .001) were associated with general psychopathology and prodromal psychotic symptoms. Moreover, there was evidence that the association between childhood adversity, general psychopathology and prodromal psychotic symptoms is mediated via pathways through threat anticipation (e.g. childhood trauma, aβindirect effect = 0.13, p < .001). Threat anticipation may be a potential mechanism linking childhood adversity and psychopathology in adolescents.
The enigma of mixed connective tissue disease—challenges in routine care
Authors: Wanzenried Adrian , Garaiman Alexandru , Jordan Suzana , Distler Oliver , Maurer Britta 
Published: July 2022

Abstract

Objectives
As a rare and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge. Herein, we aimed to unravel potential pitfalls including correct referral diagnosis, distinction from other connective tissue diseases (CTD) and treatment modalities.

Methods
We characterised the MCTD cohort at our tertiary referral centre. All patients were evaluated for fulfilment of classification criteria of various CTDs. SLEDAI-2 K and EUSTAR-AI were used in accordance with previous research to evaluate disease activity and treatment response.

Results
Out of 85 patients initially referred as MCTD, only one-third (33/85, 39%) fulfilled the diagnostic MCTD criteria and the other patients had undifferentiated CTD (16/85, 19%), non-MCTD overlap syndromes (11/85, 13%) and other rheumatic diseases. In our final cohort of 33 MCTD patients, 16 (48%) also met the diagnostic criteria of systemic sclerosis, 13 (39%) these of systemic lupus erythematosus, 6 (18%) these of rheumatoid arthritis and 3 (9%) these of primary myositis. Management of MCTD required immunomodulating combination therapy in most cases (15/28, 54%), whereas monotherapy was less frequent (10/28, 36%), and only a few (3/28, 11%) remained without immune modulators until the end of the follow-up period. Treatment led to a significant decline in disease activity.

Conclusions
Our study showed a high risk for misdiagnosis for patients with MCTD. As a multi-organ disease, MCTD required prolonged immunomodulating therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.

Key Points• This cohort study aimed to identify challenges in the highly complex management of MCTD.• Clinical presentation of MCTD significantly overlaps with that of other CTDs, leading to a high risk of misdiagnosis.• Manifestations of MCTD are highly variable and potentially life-threatening, requiring continued immunomodulating treatment in most cases.• A composite score based on SLEDAI-2 K and EUSTAR-AI measures could represent an easy applicable tool to monitor disease activity and treatment response.
The role of amyloid β in the pathological mechanism of GNE myopathy
Authors: Zhang Tongtong , Shang Ren , Miao Jing 
Published: July 2022

Abstract
GNE myopathy is a hereditary muscle disorder characterized by muscle atrophy and weakness initially involving the lower distal extremities. The treatment of GNE myopathy mainly focuses on a sialic acid deficiency caused by a mutation in the GNE gene, but it has not achieved the expected effect. The main pathological features of GNE myopathy are myofiber atrophy and rimmed vacuoles, including accumulation of amyloid β, which is mainly found in atrophic muscle fibers. Although the role of amyloid β and other misfolded proteins on the nervous system has been widely recognized, the cause and process of the formation of amyloid β in the pathological process of GNE myopathy are unclear. In addition, amyloid β has been reported to be linked to quality control mechanisms of proteins, such as molecular chaperones, the ubiquitin–proteasome system, and the autophagy-lysosome system. Herein, we summarize the possible reasons for amyloid β deposition and illustrate amyloid β-mediated events in the cells and their role in muscle atrophy in GNE myopathy. This review represents an overview of amyloid β and GNE myopathy that could help identify a potential mechanism and thereby a plausible therapeutic for the disease.
Semi-streaming algorithms for submodular matroid intersection
Authors: Garg Paritosh , Jordan Linus , Svensson Ola 
Published: July 2022

AbstractWhile the basic greedy algorithm gives a semi-streaming algorithm with an approximation guarantee of 2 for the unweighted matching problem, it was only recently that Paz and Schwartzman obtained an analogous result for weighted instances. Their approach is based on the versatile local ratio technique and also applies to generalizations such as weighted hypergraph matchings. However, the framework for the analysis fails for the related problem of weighted matroid intersection and as a result the approximation guarantee for weighted instances did not match the factor 2 achieved by the greedy algorithm for unweighted instances.Our main result closes this gap by developing a semi-streaming algorithm with an approximation guarantee of $$2+\varepsilon $$

2
+
ε

for weighted matroid intersection, improving upon the previous best guarantee of $$4+\varepsilon $$

4
+
ε

. Our techniques also allow us to generalize recent results by Levin and Wajc on submodular maximization subject to matching constraints to that of matroid-intersection constraints. While our algorithm is an adaptation of the local ratio technique used in previous works, the analysis deviates significantly and relies on structural properties of matroid intersection, called kernels. Finally, we also conjecture that our algorithm gives a $$(k+\varepsilon )$$

(
k
+
ε
)

approximation for the intersection of k matroids but prove that new tools are needed in the analysis as the structural properties we use fail for $$k\ge 3$$

k
≥
3

.
State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain
Authors: Steiger Hans-Jakob , Vollmer Kathrin , Rogers Susanne , Schwyzer Lucia 
Published: July 2022

AbstractIn 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term “personalized medicine,” that is to say, the targeting of drugs to each unique genetic profile. From today’s perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)–positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.
Phase II study of BKM120 in patients with advanced esophageal squamous cell carcinoma (EPOC1303)
Authors: Kojima Takashi , Kato Ken , Hara Hiroki , Takahashi Shunji , Muro Kei , Nishina Tomohiro , Wakabayashi Masashi , Nomura Shogo , Sato Akihiro , Ohtsu Atsushi , Doi Toshihiko 
Published: July 2022

Abstract
Background
PI3K/AKT/mTOR pathway is frequently overactive in esophageal squamous cell carcinoma (ESCC), making it an attractive treatment target. BKM120 is an oral pan-class I PI3K inhibitor with promising activity in several cancers. We prospectively investigated efficacy, safety, and biomarkers of BKM120 in advanced ESCC. We conducted a multicenter phase II study of BKM120 monotherapy in patients with pretreated advanced ESCC.

Methods
BKM120 (100 mg/day) was administered orally in a 28-day cycle. The primary end point was disease control rate (DCR). Tumor samples for all patients were collected for gene alteration analysis in a comprehensive genomic profiling assay.

Results
Of 42 patients enrolled, 20 had stable disease and two had confirmed partial response. One ineligible patient was excluded from the primary analysis, which met the primary end point (DCR 51.2%; 95% confidence interval [CI], 35.1–67.1). In the 42 patients, median progression-free survival and overall survival were 2.3 (95% CI 1.8–3.2) and 9.0 (95% CI 6.5–11.4) months, respectively. Common grade 3 or 4 adverse events were rash, anorexia, hyponatremia, and abnormal hepatic function; profiles of these events in this study were similar to those in previous studies of BKM120 monotherapy. No treatment-related deaths occurred. PI3K pathway activation was observed in patients with good clinical response.

Conclusions
BKM120 monotherapy showed promising efficacy and a manageable toxicity profile even in patients with pretreated advanced ESCC. This study showed the potential target PI3K for ESCC, and further confirmatory trial will be necessary to confirm it. Unique ID issued by UMIN: UMIN 000011217.
On the quality of emission reductions: observed effects of carbon pricing on investments, innovation, and operational shifts. A response to van den Bergh and Savin (2021)
Authors: Lilliestam Johan , Patt Anthony , Bersalli Germán 
Published: July 2022

AbstractTo meet the Paris Agreement targets, carbon emissions from the energy system must be eliminated by mid-century, implying vast investment and systemic change challenges ahead. In an article in WIREs Climate Change, we reviewed the empirical evidence for effects of carbon pricing systems on technological change towards full decarbonisation, finding weak or no effects. In response, van den Bergh and Savin (2021) criticised our review in an article in this journal, claiming that it is “unfair”, incomplete and flawed in various ways. Here, we respond to this critique by elaborating on the conceptual roots of our argumentation based on the importance of short-term emission reductions and longer-term technological change, and by expanding the review. This verifies our original findings: existing carbon pricing schemes have sometimes reduced emissions, mainly through switching to lower-carbon fossil fuels and efficiency increases, and have triggered weak innovation increases. There is no evidence that carbon pricing systems have triggered zero-carbon investments, and scarce but consistent evidence that they have not. Our findings highlight the importance of adapting and improving climate policy assessment metrics beyond short-term emissions by also assessing thequalityof emission reductions and the progress of underlying technological change.
Topographic effects on buoyancy driven flows along the slope
Authors: Berntsen Jarle , Darelius Elin , Avlesen Helge 
Published: July 2022

AbstractThe flow and descent of dense water masses formed in shallow regions of the ocean is an important leg in the global overturning circulation. The dense overflow waters tend to flow along the continental slopes as geostrophically balanced gravity plumes, but may be steered downslope by canyons and ridges cross-cutting the slopes. In that process, entrainment and mixing will be greatly enhanced. Ilicak et al. (Ocean Model 38:71–84, 2011) propose a parameterization to include the effects of corrugations in large scale models by increasing the vertical mixing locally. We re-visit the problem using the terrain-following Bergen Ocean Model and a DOME-inspired idealized topography. It is shown that the applied corrugations can move the core of the plume 800 m down the slope, while enhanced mixing raises the center of gravity by only 1–200 m. The overall effect of a corrugation is hence to lower the center of gravity, suggesting that the parameterization proposed by Ilicak et al. (Ocean Model 38:71–84) will act in the wrong vertical direction, if used on its own. A comparison of two bottom drag parameterizations, show that a parameterization consistent with a no-slip boundary condition is needed to correctly represent Ekman drainage, and that the Ekman drainage contribution to plume descent is comparable to that of the corrugation. Ridges are more effective in steering dense water downward than canyons, and we compare the dynamics between the two settings to explain the difference.
Sea level variability along the Japanese coast forced by the Kuroshio and its extension
Authors: Usui Norihisa , Ogawa Koji 
Published: July 2022

AbstractSea level variability along the Japanese coast and its relation to the Kuroshio-Kuroshio Extension (KE) are investigated using ocean reanalysis data. The first mode of an empirical-orthogonal-function for the coastal sea-level represents a simultaneous sea-level change along the whole Japanese coast, which is synchronized with sea levels in the KE region , the Japan Sea and the East China Sea. The second mode is characterized by an east–west dipole pattern at the south coast. The first mode is correlated with the Kuroshio variations around the Izu–Ogasawara Ridge (IOR) and tends to be in a positive phase when the Kuroshio takes a nearshore path around IOR. The Kuroshio’s position around IOR is closely related to the KE dynamic state. When the KE jet is in a stable (unstable) state, a nearshore (meandering) Kuroshio path is formed around IOR. A composite analysis suggests that the sea level along the Japanese coast becomes high due to propagation of coastal trapped waves when the Kuroshio takes a nearshore path around IOR. That is why the first mode is synchronized with the KE decadal variability. The second mode has a close relation with the Kuroshio Large Meander (LM). The eastern positive anomaly at the coast between the Izu and Kii Peninsulas is formed by warm Kuroshio water brought by a westward branch flow along the coast. The western negative anomaly is attributed to a southward shift in the Kuroshio south of the Kii Peninsula associated with the LM.
P2Y1R and P2Y2R: potential molecular triggers in muscle regeneration
Authors: Wang Min-Jia , Yang Bi-Ru , Jing Xin-Yu , Wang Yao-Zheng , Kang Lu , Ren Kai , Kang Liang 
Published: July 2022

AbstractMuscle regeneration is indispensable for skeletal muscle health and daily life when injury, muscular disease, and aging occur. Among the muscle regeneration, muscle stem cells’ (MuSCs) activation, proliferation, and differentiation play a key role in muscle regeneration. Purines bind to its specific receptors during muscle development, which transmit environmental stimuli and play a crucial role of modulator of muscle regeneration. Evidences proved P2R expression during development and regeneration of skeletal muscle, both in human and mouse. In contrast to P2XR, which have been extensively investigated in skeletal muscles, the knowledge of P2YR in this tissue is less comprehensive. This review summarized muscle regeneration via P2Y1R and P2Y2R and speculated that P2Y1R and P2Y2R might be potential molecular triggers for MuSCs’ activation and proliferation via the p-ERK1/2 and PLC pathways, explored their cascade effects on skeletal muscle, and proposed P2Y1/2 receptors as potential pharmacological targets in muscle regeneration, to advance the purinergic signaling within muscle and provide promising strategies for alleviating muscular disease.
Emulierung von „target trials“ mit Real-world-Daten
Authors: Braitmaier Malte , Didelez Vanessa 
Published: July 2022

Zusammenfassung
Hintergrund
Die „real world data“ (RWD), z. B. Krankenkassendaten, bieten reichhaltige Informationen zu gesundheitsrelevanten Faktoren und können die Basis für Studien zur Arzneimittelsicherheit, Wirksamkeit medizinischer Interventionen u. v. m. darstellen. Ein besonderer Vorteil ist die je nach Datenquelle größere Verallgemeinerbarkeit, wenn z. B. Informationen zu bestimmten Subgruppen der Population vorliegen und ein Volunteer-Bias ausgeschlossen werden kann. Gerade in Fällen, in denen randomisierte kontrollierte Studien („randomized controlled trials“, RCT) nicht durchgeführt werden können, sind Beobachtungsstudien basierend auf RWD eine wichtige Informationsquelle. Die valide Analyse von RWD stellt allerdings einige Herausforderung dar, wobei insbesondere mögliche Verzerrungen, die durch ein sorgfältiges Studiendesign vermeidbar wären, Beachtung finden sollen. Hier setzt das Prinzip der Target-trial-Emulierung (TTE) an.

Ziel der Arbeit
In diesem Artikel soll aufgezeigt werden, wie die TTE den Herausforderungen bei der Analyse von RWD begegnet.

Material und Methoden
Die TTE wird allgemein verständlich vorgestellt. Prinzipien, Vorteile, Annahmen und spezifische statistische Aspekte werden anhand relevanter Literatur und praktischer Beispiele erläutert.

Ergebnisse
Damit die Analyse von RWD valide, kausal interpretierbare Ergebnisse liefern kann, müssen einige Bedingungen erfüllt sein. Neben einem ausreichenden Informationsgehalt der Daten sind auch eine klare Fragestellung und ein geeignetes Studiendesign, das u. a. Selektionseffekte vermeidet, von zentraler Bedeutung. Das Target-trial-Prinzip besteht darin, dass zunächst das Auswertungskonzept für einen RCT erarbeitet wird, welches in einem zweiten Schritt mit Beobachtungsdaten „emuliert“ wird. Somit liefert die TTE quasi eine Anleitung, um die Fragestellung zu definieren und ein geeignetes Studiendesign zu entwerfen. TTE kann mit unterschiedlichen statistischen Methoden kombiniert werden, wobei statistische Effizienz durch sequenzielle Trials und das sog. Klonen gewonnen werden kann.

Schlussfolgerung
Die TTE ist ein allgemeines und übergreifendes Prinzip, das zentralen Herausforderungen bei der Analyse von Beobachtungsdaten, also auch RWD, systematisch begegnet.