bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion
Authors: Patarrão Rita S. , Duarte Nádia , Coelho Inês , Ward Joey , Ribeiro Rogério T. , Meneses Maria João , Andrade Rita , Costa João , Correia Isabel , Boavida José Manuel , Duarte Rui , Gardete-Correia Luís , Medina José Luís , Pell Jill , Petrie John , Raposo João F. , Macedo Maria Paula , Penha-Gonçalves Carlos 
Published: February 2022

Abstract
Aims/hypothesis
Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.

Methods
We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.

Results
In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10−7) and C-peptide release responses (rs2300757, p=6.86x10−5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states.

Conclusions/interpretation
These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Graphical abstract
Colorectal cancer chemotherapy: can sex-specific disparities impact on drug toxicities?
Authors: De Francia Silvia , Berchialla Paola , Armando Tiziana , Storto Silvana , Allegra Sarah , Sciannameo Veronica , Soave Giulia , Sprio Andrea Elio , Racca Silvia , Caiaffa Maria Rosaria , Ciuffreda Libero , Mussa Maria Valentina 
Published: February 2022

Abstract
Purpose
Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy.

Methods
We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity.

Results
According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005).

Conclusion
According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients’ biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.
Revidierte Fassung der S3-Leitlinie Zervixkarzinom 2021 – Anforderungen an die Pathologie
Authors: Horn Lars-Christian , Beckmann Matthias W. , Follmann Markus , Koch Martin C. , Nothacker Monika , Pöschel Birgit , Stübs Frederik , Schmidt Dietmar , Höhn Anne Kathrin ,   Kommission zur Erstellung der S3-Leitlinie Zervixkarzinom
Published: February 2022

ZusammenfassungIm Jahr 2015 wurde die S3-Leitlinie für Diagnostik und Therapie des Zervixkarzinoms erstellt, die 2021 in ihrer revidierten Fassung vorliegt. Neu für die Pathologie sind die Aufnahme der International Endocervical Adenocarcinoma Classification (IECC), die zwischen HPV-assoziierten und non-HPV-assoziierten Karzinomen unterschiedet, sowie des prognostisch relevanten morphologischen Wachstumsmusters bei (HPV-assoziierten) Adenokarzinomen (sog. Silva-Pattern). Die Multifokalität beim mikroinvasiven Zervixkarzinom ist nun definiert als der Nachweis voneinander histologisch klar separierter invasiver Foci mit einem minimalen Abstand von 0,2 cm. Aufgrund einer möglichen intratumoralen Heterogenität sollen Zervixkarzinome ≤ 2 cm vollständig und Tumoren > 2 cm mit einem Block pro Zentimeter größter Ausdehnung eingebettet werden. Bei der (radikalen) Trachelektomie/Hysterektomie sollen der vaginale Resektionsrand und das parametrane Gewebe vollständig eingebettet werden. Neu ist die Empfehlung zur Aufarbeitung von Sentinellymphknoten. Diese sollen entlang ihrer Längsachse in 0,2 cm Abstand lamelliert, vollständig eingebettet und mittels Ultrastaging aufgearbeitet werden. Die FIGO-Klassifikation von 2009 bzw. TNM-Kategorisierung von 2017 wird beibehalten, die Angabe der FIGO-Klassifikation 2018/19 ist optional. Molekulare Marker spielen derzeit noch keine relevante Rolle in der Prognose und zum Therapieentscheid.
A regional (land–ocean) comparison of the seasonal to decadal variability of the Northern Hemisphere jet stream 1871–2011
Authors: Hallam Samantha , Josey Simon A. , McCarthy Gerard D. , Hirschi Joël J.-M. 
Published: February 2022

AbstractSeasonal to decadal variations in Northern Hemisphere jet stream latitude and speed over land (Eurasia, North America) and oceanic (North Atlantic, North Pacific) regions are presented for the period 1871–2011 from the Twentieth Century Reanalysis dataset. Significant regional differences are seen on seasonal to decadal timescales. Seasonally, the jet latitude range is lower over the oceans compared to land, reduced from 20° over Eurasia to 10° over the North Atlantic where the ocean meridional heat transport is greatest. The mean jet latitude range is at a minimum in winter (DJF), particularly along the western boundary of the North Pacific and North Atlantic, where the land-sea contrast and SST gradients are strongest. The 141-year trends in jet latitude and speed show differences on a regional basis. The North Atlantic has significant increasing jet latitude trends in all seasons, up to 3° in winter. Eurasia has significant increasing trends in winter and summer, however, no increase is seen across the North Pacific or North America. Jet speed shows significant increases evident in winter (up to 4.7 ms−1), spring and autumn over the North Atlantic, Eurasia and North America however, over the North Pacific no increase is observed. Long term trends are generally overlaid by multidecadal variability, particularly evident in the North Pacific, where 20-year variability in jet latitude and jet speed are seen, associated with the Pacific Decadal Oscillation which explains 50% of the winter variance in jet latitude since 1940. The results highlight that northern hemisphere jet variability and trends differ on a regional basis (North Atlantic, North Pacific, Eurasia and North America) on seasonal to decadal timescales, suggesting that different mechanisms are influencing the jet latitude and speed. This is important from a climate modelling perspective and for climate predictions in the near and longer term.
Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Authors: Wang Zijun , Zhao Siya , Tang Yuyi , Wang Zhili , Shi Qianling , Dang Xiangyang , Gan Lidan , Peng Shuai , Li Weiguo , Zhou Qi , Li Qinyuan , Mafiana Joy James , Cortés Rafael González , Luo Zhengxiu , Liu Enmei , Chen Yaolong 
Published: February 2022

AbstractThe purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

What is Known:• The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear.

What is New:• Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C.• We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
Weniger Operationen und Kosten wegen Rückenschmerzen in einem Versorgungsprogramm mit interdisziplinärem Zweitmeinungsverfahren
Authors: Wagner Christoph J. , Lindena Gabriele , Ayyad Grit , Otzdorff Andrea , Marnitz Ulf , Bienek Karen , von Pickardt Björn , Sehlen Stephanie , Wyrwich Werner 
Published: February 2022

Zusammenfassung
Hintergrund
Für interdisziplinäre Zweitmeinungsverfahren (IZMV) bei empfohlenen Rückenoperationen (ROP) fehlen Wirksamkeitsbelege. Die AOK Nordost bietet seit 2015 das Versorgungsprogramm RückenSPEZIAL an. Es enthält Vorbefundprüfung, IZMV und optional eine interdisziplinär-multimodale Schmerztherapie (IMST). Ziel dieser Studie ist die Ermittlung der Wirksamkeit von RückenSPEZIAL für ROP und rückenschmerzbezogene Kosten (RBK) im Vergleich zu Patienten mit ROP-Empfehlung ohne RückenSPEZIAL.

Methoden
Versicherte der AOK Nordost legten im AOK-Servicecenter einen ROP-Krankenhauseinweisungsschein vor und erhielten eine dokumentierte Beratung zur RückenSPEZIAL-Teilnahme. Nach einer 1:1-Matched-pairs-Ziehung wurden Patienten, die nach dieser Beratung (= Stichtag) an RückenSPEZIAL teilnahmen (Interventionsgruppe [IG]), mit Patienten verglichen, die nach der Beratung nicht teilnahmen (Vergleichsgruppe [VG]). Patientenmerkmale, ROP und RBK wurden aus Daten der AOK Nordost operationalisiert.

Ergebnisse
Von 108 IG-Patienten und 108 VG-Patienten hatten 34 (42 %) weniger IG-Patienten eine oder mehr ROP in 365 Folgetagen (relatives Risiko [RR] 0,58; p < 0,001). Die Subgruppenanalyse zeigte für 21 IG-Patienten mit IZMV und IMST ein RR von 0,13 (p < 0,001) und für 67 IG-Patienten mit alleinigem IZMV ohne IMST ein RR von 0,59 (p < 0,001). Die Veränderung der RBK von Vorjahr auf Folgejahr war für die IG um 50,2 %-Punkte geringer als für die VG (p = 0,088).

Diskussion
Die ROP-Unterschiede zugunsten des Selektivvertrags RückenSPEZIAL waren signifikant (p < 0,05). Für die spezifische Population ist eine Refinanzierung der Interventionskosten von RückenSPEZIAL tendenziell erwartbar (näherungsweise signifikant, geringe Fallzahl). Es ist eine Verzerrung aufgrund von Selbstselektion anzunehmen.
Numerical 3D modeling of burial and temperature history, source rock maturity, and hydrocarbon generation in the onshore northeastern Netherlands
Authors: Amberg Sebastian , Back Stefan , Sachse Victoria , Littke Ralf 
Published: February 2022

AbstractNumerical 3D basin modeling is used to reconstruct the burial and temperature histories in onshore northeastern Netherlands, incorporating the four main geological structural elements Groningen Platform, Lauwerszee Trough, Friesland Platform, and Lower Saxony Basin. The structural framework is based on recently published open access depth surface data; public temperature and vitrinite reflectance data from 28 wells are used to evaluate burial and temperature histories. Four modeled burial histories and the maturity evolution of the structural elements are presented. The hydrocarbon generation in major source rock intervals in the Carboniferous, Jurassic, and Cretaceous is simulated using recently published kinetic and literature data. Modeling results indicate highest present-day temperatures and maturities of the Paleozoic sedimentary succession in the Lauwerszee Trough and the Lower Saxony Basin, where the deepest burial occurred. Two major phases of deep burial and subsequent uplift occurred in Carboniferous to Permian times and from the Triassic to the Jurassic. Both intervals strongly influenced the maturation and transformation of kerogen from Paleozoic source rocks. The highest modeled maturities of the Mesozoic groups are observed in depressions between salt diapirs in the Lower Saxony Basin. Out of the two major source rock intervals within the Mesozoic, the Cretaceous Wealden Shale generated hydrocarbons from Late Cretaceous times.
Classification of synoptic and local-scale wind patterns using k-means clustering in a Tyrrhenian coastal area (Italy)
Authors: Di Bernardino Annalisa , Iannarelli Anna Maria , Casadio Stefano , Pisacane Giovanna , Mevi Gabriele , Cacciani Marco 
Published: February 2022

AbstractIn coastal regions, the complex interaction of synoptic-scale dynamics and breeze regimes influence the local atmospheric circulation, permitting to distinguish typical yet alternative patterns. In this paper, the k-means clustering algorithm is applied to the hourly time series of wind intensity and direction collected by in-situ weather stations at seven locations within 30 km from the western coastline of central Italy, in the proximity of Rome, over the period 2014–2020. The selection of both wind-integral quantities and ad hoc objective parameters allows for the identification of three characteristic clusters, two of which are closely related to the synoptic circulation and governed by persistent winds, blowing from either the northeast or the southeast direction throughout the day. In the latter case, synoptic and mesoscale contributions add up, giving rise to a complex circulation at the ground level. On the contrary, the third cluster is closely related to the sea breeze regime. The results allow the identification of some general information about the low-level circulation, showing that the synoptic circulation dominates in winter and, partly, in spring and autumn, when high ventilation and low recirculation conditions occur. Conversely, during summer the sea breeze regime is more frequent and stronger, generating intense air recirculation. Our analysis permits to discern rigorously and objectively the typical coastal meteorological patterns, only requiring anemological in-situ data.
Strategic bidding in freight transport using deep reinforcement learning
Authors: van Heeswijk W. J. A. 
Published: February 2022

AbstractThis paper presents a multi-agent reinforcement learning algorithm to represent strategic bidding behavior by carriers and shippers in freight transport markets. We investigate whether feasible market equilibriums arise without central control or communication between agents. Observed behavior in such environments serves as a stepping stone towards self-organizing logistics systems like the Physical Internet, while also offering valuable insights for the design of contemporary transport brokerage platforms. We model an agent-based environment in which shipper and carrier actively learn bidding strategies using policy gradient methods, posing bid- and ask prices at the individual container level. Both agents aim to learn the best response given the expected behavior of the opposing agent. Inspired by financial markets, a neutral broker allocates jobs based on bid-ask spreads. Our game-theoretical analysis and numerical experiments focus on behavioral insights. To evaluate system performance, we measure adherence to Nash equilibria, fairness of reward division and utilization of transport capacity. We observe good performance both in predictable, deterministic settings ($$\sim $$
∼
95% adherence to Nash equilibria) and highly stochastic environments ($$\sim $$
∼
85% adherence). Risk-seeking behavior may increase an agent’s reward share, yet overly aggressive strategies destabilize the system. The results suggest a potential for full automation and decentralization of freight transport markets. These insights ease the design of real-world market platforms, suggesting an innate tendency of markets to reach equilibria without behavioral models, information sharing or explicit incentives.
Business group affiliation and entrepreneurial orientation: Contingent effect of level of internationalization and firm’s performance
Authors: Purkayastha Anish , Gupta Vishal K. 
Published: February 2022

AbstractThis paper explores effect of business group affiliation on entrepreneurial orientation of the affiliated firms. Building on the argument that organizational and governance structure influence entrepreneurship, we argue that despite some potential advantage that business group affiliation has on a firm through intermediate market filling roles, the entrenchment behavior of business groups discourages entrepreneurial orientation of affiliated firms. Taking a firm-specific contingent perspective we also posit that the level of internationalization of a firm and its performance helps to alleviate- even counter–the negative influence of business group affiliation on the firm’s entrepreneurial orientation. We find support for our predictions in a longitudinal data set of 419 Indian firms for the period from 2006 to 2019. The implications and directions for future research are discussed in the context of business group affiliation in emerging economies.
Sex Under the Influence of Drugs Among People Who Use Drugs in Cambodia: Findings From a National Survey
Authors: Saing Chan Hang , Chhoun Pheak , Chann Navy , Uk Ponha , Mun Phalkun , Tuot Sovannary , Yi Siyan 
Published: February 2022

AbstractStudies in drug use settings rarely use sex under the influence of drugs as an indicator of sexual risk behaviors. This study explored the prevalence of sex under the influence of drugs and its correlates among people who use drugs (PWUD) in Cambodia. We included 1147 PWUD from 12 provinces in this study. A multiple logistic regression analysis was conducted to identify factors associated with sex under the influence of drugs. Of the total, 39.7% reported having had sex under the influence of drugs in the past three months. After adjustment, sex under the influence of drugs was significantly associated with living in urban areas (AOR 2.97, 95% CI 1.68–5.27), having two to three (AOR 2.48, 95% CI 1.76–3.49) and four or more sexual partners (AOR 6.46, 95% CI 4.24–9.85), engaging in transactional sex (AOR 1.69, 95% CI 1.19–2.39), using methamphetamine (AOR 2.97, 95% CI 2.06–4.31), using drugs for three years or longer (AOR 1.67, 95% CI 1.15–2.41), having been to a drug rehabilitation center (AOR 1.77, 95% CI 1.18–2.41), having a network of ten or more PWUD (AOR 1.82, 95% CI 1.25–2.66), and having high psychological distress (AOR 1.66, 95% CI 1.25–2.22). This study documents the high prevalence of sex under the influence of drugs and its risk factors among male and female PWUD in Cambodia. These findings point to the need for integrating HIV and harm-reduction programs using innovative approaches to address the overlapping risks in this key population.
Real-world clinical outcomes of patients with BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer: a CancerLinQ® study
Authors: Miller Robert S. , Mokiou Stella , Taylor Aliki , Sun Ping , Baria Katherine 
Published: February 2022

Abstract
Purpose
To investigate real-world clinical outcomes in patients with BRCA-mutated (BRCAm), HER2-negative metastatic breast cancer (mBC) according to BRCA and hormone receptor (HR) status.

Methods
Patients diagnosed with HER2-negative mBC between 01 January 2010 and 31 December 2018 were retrospectively identified from the American Society of Clinical Oncology’s CancerLinQ Discovery® database. Time to first subsequent therapy or death (TFST) from date of mBC diagnosis and start of first-line treatment for mBC and overall survival (OS) from date of mBC diagnosis were investigated according to BRCA status (BRCAm, BRCA wild type [BRCAwt] or unknown BRCA [BRCAu]) and HR status (positive/triple negative breast cancer [TNBC]). Follow-up continued until 31 August 2019 (i.e. minimum of 8 months).

Results
3744 patients with HER2-negative mBC were identified (BRCAwt, n = 460; BRCAm, n = 83; BRCAu, n = 3201) (HR-positive, n = 2738). Median (Q1, Q3) age was 63.0 (54.0, 73.0) years. Median (95% confidence interval [CI]) TFST (months) from mBC diagnosis was as follows: HR-positive, 7.7 (5.0, 11.2), 8.3 (6.6, 10.2) and 9.4 (8.7, 10.1); TNBC, 5.4 (3.9, 12.4), 5.6 (4.7, 6.6) and 5.4 (5.0, 6.2) for BRCAm, BRCAwt and BRCAu, respectively. Median (95% CI) OS (months) was as follows: HR-positive, 41.1 (31.5, not calculable), 55.1 (43.5, 65.5) and 33.0 (31.3, 34.8); TNBC, 13.7 (11.1, not calculable), 14.4 (10.7, 17.0) and 11.7 (10.3, 12.8) for BRCAm, BRCAwt and BRCAu, respectively.

Conclusion
When stratified by HR status, TFST and OS were broadly similar for patients with HER2-negative mBC, irrespective of BRCA status. Further global real-world studies are needed to study outcomes of this patient population.